Commentary

I enjoyed Dr. Nasrallah’s recent editorial “We are physicians, not providers, and we treat patients, not clients!” (From the Editor, Current Psychiatry. February 2020, p. 5-7,29). In 1993, my colleagues and I incorporated under the name “Psychiatric Physicians” while managing the psychiatric unit of our local hospital. We did this in part to remind hospital administration and our medical colleagues of our identity and value. I personally coined this name in response to a casual remark my older brother made years ago. When I informed him that I was choosing a residency in psychiatry, he replied, “Why don’t you want to be a real doctor?”

A stethoscope, pressure cuff, and ophthalmoscope sit on the side table next to my psychotherapy chair, and I use them often. For years, I have administered electroconvulsive therapy and managed vagus nerve stimulation. I inject long-acting depot antipsychotics as well as depot buprenorphine and naltrexone, and I provide esketamine treatment. I spend significant parts of my patients’ visits explaining the treatments their other physicians have prescribed, in words they can understand. I still spend hours each week providing psychotherapy.

My psychiatric training afforded me the insight that my brother’s remark caused a lifelong change in my own behavior. Our capacity to blend psychology and medicine distinguishes us from our medical brethren and psychology colleagues.

I agree wholeheartedly that the medical bureaucracy/insurance industry degrades and demeans our profession, and we should do all in our power to resist this.

Jim Wiaduck, MD
Norton Shores, Michigan

I congratulate Dr. Nasrallah on his forceful and clear editorial aimed at demystifying labels that only blur our identity and the nature of the patient-physician covenant.

Carlos E. Sluzki, MD
Washington, DC

Continue to: I absolutely...

I absolutely agree with Dr. Nasrallah’s position that we are physicians, not “providers,” and that the people we care for are patients, not “clients.” Given the enthusiasm with which insurance companies have embraced the term provider (under the notion that we are indistinguishable from other types of trained professionals providing care), perhaps we should stop referring to them as “payors” because this does not seem to be their primary function. Instead, we can refer to them as “withholders” to better indicate the difference between what clinicians do (provide care) and what insurance companies do (withhold payment and thus delay care, sometimes with disastrous consequences).

Douglas Berne, MD
Orefield, Pennsylvania

Regarding being called “providers,” I believe we have brought this on ourselves by allowing “management experts” to decide how we treat our patients.

Shyamala Vatsa, MBBS, DPM
Bengaluru, India

Being called a “provider” has been one of the most annoying and insulting things that we have had to endure in the last few years. Until Dr. Nasrallah’s editorial, I had never heard anyone raise this issue in a medical journal. The American Psychiatric Association (APA) and the American Medical Association (AMA) must help us with this. I have been saying for years that we are all going to be replaced by nurse practitioners (NPs)!

Rose Gomez, MD, DFAPA
Chicago, Illinois

Continue to: I thank...

I thank Dr. Nasrallah very much for his editorial about being called “providers,” which has always irritated me. We worked hard to get our MDs. I’ve told my residents for a long time that the term “provider” sounds more like a wholesale grocery company. A similar term also confounds me: behavioral medicine. What is that, an old-fashioned reform school? We don’t change patients’ behavior to conform; we treat their illnesses and symptoms so that they can do better for themselves.

Henry Kandler, MD
Bronx, New York

I commend Dr. Nasrallah’s recent editorial. Society must reconsider the concept that health care is a “product.” Patient education is key!

This editorial was translated into Portuguese by a colleague, and it has started a very interesting and fruitful debate.

Renato Ambrósio Jr., MD, PhD
Rio de Janeiro, Brasil

I was extremely impressed with the wisdom Dr. Nasrallah expressed in his editorial about how we should be referred to as physicians, not as “providers.” For many years, I have referred to my primary care colleagues as “PCPs,” which stands for primary care providers. I will do this no more and instead use the preferred and more accurate term primary care physicians. And yes, I do support his suggestion that the APA’s name be changed to the American Psychiatric Physicians Association, and hope that the plan to implement these improvements succeeds throughout the United States.

Donald Banzhaf, MD
Rochester, New York

Continue to: I absolutely...

I absolutely loved Dr. Nasrallah's editorial and completely agree with him. Perhaps we could begin a letter-writing campaign urging Congress to amend Public Law 93-641 by replacing “provider” with “physicians and/or other health specialists” or something to that effect. With enough persuasion, the AMA might even take the lead on this.

Deborah Young, MD
Encinitas, California

I found Dr. Nasrallah's editorial extremely interesting and on target. I agree with his concern about the trend towards “bottom line” medicine.

I understand that, justifiably, Dr. Nasrallah's basic interest is in the realm of psychiatry (both clinicians and patients); however, shouldn’t that concern be broadened by recognizing that in all medical relationships, the individual (ie, physician assistant [PA], NP, registered nurse, respiratory therapist, etc.) is a “clinician” who cares for a patient

Also, while more and more people are willing to admit to being a patient undergoing mental health care, there still are many people who prefer not to called a patient when—or if—they describe the experience of receiving mental health care.

I teach a class called “Legal & Ethical Issues In Medicine” in a PA program, and one of the major objectives is to get the students to recognize and feel that they are becoming professionals. They are becoming clinicians who will help manage the health care of a patient.

Again, I appreciate Dr. Nasrallah's points, and wish that they could have a broader exposure.

Robert C. Grosz, EdD
Ft. Lauderdale, Florida

Continue to: I love...

I found Dr. Nasrallah's editorial to be a breath of fresh air. I thank him for it!

Laura K. Kendall, MD
Los Angeles, California

I want to congratulate Dr. Nasrallah for addressing the "provider" issue in his editorial. It is right on the mark and has been a thorn in my side for many years (as is the “client” vs “patient” issue). He worded it very well! I thank Dr. Nasrallah for discussing this.

René S. Kahn, MD, PhD
New York, New York

Continue to: Dr. Nasrallah responds

I thank my colleagues, whose letters confirm that being called “providers” instead of “physicians” is something that all psychiatrists resent and oppose. I hope each psychiatric physician reader of current psychiatry vocally demands to be called a physician, not a provider. I also hope the APA will fight for this issue at the national level.

Henry A. Nasrallah, MD
Professor of Psychiatry, Neurology, and Neuroscience
Medical Director: Neuropsychiatry
Director, Schizophrenia and Neuropsychiatry Programs
University of Cincinnati College of Medicine
Cincinnati, Ohio
Professor Emeritus, Saint Louis University
St. Louis, Missouri

I enjoyed Dr. Nasrallah’s recent editorial “We are physicians, not providers, and we treat patients, not clients!” (From the Editor, Current Psychiatry. February 2020, p. 5-7,29). In 1993, my colleagues and I incorporated under the name “Psychiatric Physicians” while managing the psychiatric unit of our local hospital. We did this in part to remind hospital administration and our medical colleagues of our identity and value. I personally coined this name in response to a casual remark my older brother made years ago. When I informed him that I was choosing a residency in psychiatry, he replied, “Why don’t you want to be a real doctor?”

A stethoscope, pressure cuff, and ophthalmoscope sit on the side table next to my psychotherapy chair, and I use them often. For years, I have administered electroconvulsive therapy and managed vagus nerve stimulation. I inject long-acting depot antipsychotics as well as depot buprenorphine and naltrexone, and I provide esketamine treatment. I spend significant parts of my patients’ visits explaining the treatments their other physicians have prescribed, in words they can understand. I still spend hours each week providing psychotherapy.

My psychiatric training afforded me the insight that my brother’s remark caused a lifelong change in my own behavior. Our capacity to blend psychology and medicine distinguishes us from our medical brethren and psychology colleagues.

I agree wholeheartedly that the medical bureaucracy/insurance industry degrades and demeans our profession, and we should do all in our power to resist this.

Jim Wiaduck, MD
Norton Shores, Michigan

I congratulate Dr. Nasrallah on his forceful and clear editorial aimed at demystifying labels that only blur our identity and the nature of the patient-physician covenant.

Carlos E. Sluzki, MD
Washington, DC

Continue to: I absolutely...

I absolutely agree with Dr. Nasrallah’s position that we are physicians, not “providers,” and that the people we care for are patients, not “clients.” Given the enthusiasm with which insurance companies have embraced the term provider (under the notion that we are indistinguishable from other types of trained professionals providing care), perhaps we should stop referring to them as “payors” because this does not seem to be their primary function. Instead, we can refer to them as “withholders” to better indicate the difference between what clinicians do (provide care) and what insurance companies do (withhold payment and thus delay care, sometimes with disastrous consequences).

Douglas Berne, MD
Orefield, Pennsylvania

Regarding being called “providers,” I believe we have brought this on ourselves by allowing “management experts” to decide how we treat our patients.

Shyamala Vatsa, MBBS, DPM
Bengaluru, India

Being called a “provider” has been one of the most annoying and insulting things that we have had to endure in the last few years. Until Dr. Nasrallah’s editorial, I had never heard anyone raise this issue in a medical journal. The American Psychiatric Association (APA) and the American Medical Association (AMA) must help us with this. I have been saying for years that we are all going to be replaced by nurse practitioners (NPs)!

Rose Gomez, MD, DFAPA
Chicago, Illinois

Continue to: I thank...

I thank Dr. Nasrallah very much for his editorial about being called “providers,” which has always irritated me. We worked hard to get our MDs. I’ve told my residents for a long time that the term “provider” sounds more like a wholesale grocery company. A similar term also confounds me: behavioral medicine. What is that, an old-fashioned reform school? We don’t change patients’ behavior to conform; we treat their illnesses and symptoms so that they can do better for themselves.

Henry Kandler, MD
Bronx, New York

I commend Dr. Nasrallah’s recent editorial. Society must reconsider the concept that health care is a “product.” Patient education is key!

This editorial was translated into Portuguese by a colleague, and it has started a very interesting and fruitful debate.

Renato Ambrósio Jr., MD, PhD
Rio de Janeiro, Brasil

I was extremely impressed with the wisdom Dr. Nasrallah expressed in his editorial about how we should be referred to as physicians, not as “providers.” For many years, I have referred to my primary care colleagues as “PCPs,” which stands for primary care providers. I will do this no more and instead use the preferred and more accurate term primary care physicians. And yes, I do support his suggestion that the APA’s name be changed to the American Psychiatric Physicians Association, and hope that the plan to implement these improvements succeeds throughout the United States.

Donald Banzhaf, MD
Rochester, New York

Continue to: I absolutely...

I absolutely loved Dr. Nasrallah's editorial and completely agree with him. Perhaps we could begin a letter-writing campaign urging Congress to amend Public Law 93-641 by replacing “provider” with “physicians and/or other health specialists” or something to that effect. With enough persuasion, the AMA might even take the lead on this.

Deborah Young, MD
Encinitas, California

I found Dr. Nasrallah's editorial extremely interesting and on target. I agree with his concern about the trend towards “bottom line” medicine.

I understand that, justifiably, Dr. Nasrallah's basic interest is in the realm of psychiatry (both clinicians and patients); however, shouldn’t that concern be broadened by recognizing that in all medical relationships, the individual (ie, physician assistant [PA], NP, registered nurse, respiratory therapist, etc.) is a “clinician” who cares for a patient

Also, while more and more people are willing to admit to being a patient undergoing mental health care, there still are many people who prefer not to called a patient when—or if—they describe the experience of receiving mental health care.

I teach a class called “Legal & Ethical Issues In Medicine” in a PA program, and one of the major objectives is to get the students to recognize and feel that they are becoming professionals. They are becoming clinicians who will help manage the health care of a patient.

Again, I appreciate Dr. Nasrallah's points, and wish that they could have a broader exposure.

Robert C. Grosz, EdD
Ft. Lauderdale, Florida

Continue to: I love...

I found Dr. Nasrallah's editorial to be a breath of fresh air. I thank him for it!

Laura K. Kendall, MD
Los Angeles, California

I want to congratulate Dr. Nasrallah for addressing the "provider" issue in his editorial. It is right on the mark and has been a thorn in my side for many years (as is the “client” vs “patient” issue). He worded it very well! I thank Dr. Nasrallah for discussing this.

René S. Kahn, MD, PhD
New York, New York

Continue to: Dr. Nasrallah responds

I thank my colleagues, whose letters confirm that being called “providers” instead of “physicians” is something that all psychiatrists resent and oppose. I hope each psychiatric physician reader of current psychiatry vocally demands to be called a physician, not a provider. I also hope the APA will fight for this issue at the national level.

Henry A. Nasrallah, MD
Professor of Psychiatry, Neurology, and Neuroscience
Medical Director: Neuropsychiatry
Director, Schizophrenia and Neuropsychiatry Programs
University of Cincinnati College of Medicine
Cincinnati, Ohio
Professor Emeritus, Saint Louis University
St. Louis, Missouri

I enjoyed Dr. Nasrallah’s recent editorial “We are physicians, not providers, and we treat patients, not clients!” (From the Editor, Current Psychiatry. February 2020, p. 5-7,29). In 1993, my colleagues and I incorporated under the name “Psychiatric Physicians” while managing the psychiatric unit of our local hospital. We did this in part to remind hospital administration and our medical colleagues of our identity and value. I personally coined this name in response to a casual remark my older brother made years ago. When I informed him that I was choosing a residency in psychiatry, he replied, “Why don’t you want to be a real doctor?”

A stethoscope, pressure cuff, and ophthalmoscope sit on the side table next to my psychotherapy chair, and I use them often. For years, I have administered electroconvulsive therapy and managed vagus nerve stimulation. I inject long-acting depot antipsychotics as well as depot buprenorphine and naltrexone, and I provide esketamine treatment. I spend significant parts of my patients’ visits explaining the treatments their other physicians have prescribed, in words they can understand. I still spend hours each week providing psychotherapy.

My psychiatric training afforded me the insight that my brother’s remark caused a lifelong change in my own behavior. Our capacity to blend psychology and medicine distinguishes us from our medical brethren and psychology colleagues.

I agree wholeheartedly that the medical bureaucracy/insurance industry degrades and demeans our profession, and we should do all in our power to resist this.

Jim Wiaduck, MD
Norton Shores, Michigan

I congratulate Dr. Nasrallah on his forceful and clear editorial aimed at demystifying labels that only blur our identity and the nature of the patient-physician covenant.

Carlos E. Sluzki, MD
Washington, DC

Continue to: I absolutely...

I absolutely agree with Dr. Nasrallah’s position that we are physicians, not “providers,” and that the people we care for are patients, not “clients.” Given the enthusiasm with which insurance companies have embraced the term provider (under the notion that we are indistinguishable from other types of trained professionals providing care), perhaps we should stop referring to them as “payors” because this does not seem to be their primary function. Instead, we can refer to them as “withholders” to better indicate the difference between what clinicians do (provide care) and what insurance companies do (withhold payment and thus delay care, sometimes with disastrous consequences).

Douglas Berne, MD
Orefield, Pennsylvania

Regarding being called “providers,” I believe we have brought this on ourselves by allowing “management experts” to decide how we treat our patients.

Shyamala Vatsa, MBBS, DPM
Bengaluru, India

Being called a “provider” has been one of the most annoying and insulting things that we have had to endure in the last few years. Until Dr. Nasrallah’s editorial, I had never heard anyone raise this issue in a medical journal. The American Psychiatric Association (APA) and the American Medical Association (AMA) must help us with this. I have been saying for years that we are all going to be replaced by nurse practitioners (NPs)!

Rose Gomez, MD, DFAPA
Chicago, Illinois

Continue to: I thank...

I thank Dr. Nasrallah very much for his editorial about being called “providers,” which has always irritated me. We worked hard to get our MDs. I’ve told my residents for a long time that the term “provider” sounds more like a wholesale grocery company. A similar term also confounds me: behavioral medicine. What is that, an old-fashioned reform school? We don’t change patients’ behavior to conform; we treat their illnesses and symptoms so that they can do better for themselves.

Henry Kandler, MD
Bronx, New York

I commend Dr. Nasrallah’s recent editorial. Society must reconsider the concept that health care is a “product.” Patient education is key!

This editorial was translated into Portuguese by a colleague, and it has started a very interesting and fruitful debate.

Renato Ambrósio Jr., MD, PhD
Rio de Janeiro, Brasil

I was extremely impressed with the wisdom Dr. Nasrallah expressed in his editorial about how we should be referred to as physicians, not as “providers.” For many years, I have referred to my primary care colleagues as “PCPs,” which stands for primary care providers. I will do this no more and instead use the preferred and more accurate term primary care physicians. And yes, I do support his suggestion that the APA’s name be changed to the American Psychiatric Physicians Association, and hope that the plan to implement these improvements succeeds throughout the United States.

Donald Banzhaf, MD
Rochester, New York

Continue to: I absolutely...

I absolutely loved Dr. Nasrallah's editorial and completely agree with him. Perhaps we could begin a letter-writing campaign urging Congress to amend Public Law 93-641 by replacing “provider” with “physicians and/or other health specialists” or something to that effect. With enough persuasion, the AMA might even take the lead on this.

Deborah Young, MD
Encinitas, California

I found Dr. Nasrallah's editorial extremely interesting and on target. I agree with his concern about the trend towards “bottom line” medicine.

I understand that, justifiably, Dr. Nasrallah's basic interest is in the realm of psychiatry (both clinicians and patients); however, shouldn’t that concern be broadened by recognizing that in all medical relationships, the individual (ie, physician assistant [PA], NP, registered nurse, respiratory therapist, etc.) is a “clinician” who cares for a patient

Also, while more and more people are willing to admit to being a patient undergoing mental health care, there still are many people who prefer not to called a patient when—or if—they describe the experience of receiving mental health care.

I teach a class called “Legal & Ethical Issues In Medicine” in a PA program, and one of the major objectives is to get the students to recognize and feel that they are becoming professionals. They are becoming clinicians who will help manage the health care of a patient.

Again, I appreciate Dr. Nasrallah's points, and wish that they could have a broader exposure.

Robert C. Grosz, EdD
Ft. Lauderdale, Florida

Continue to: I love...

I found Dr. Nasrallah's editorial to be a breath of fresh air. I thank him for it!

Laura K. Kendall, MD
Los Angeles, California

I want to congratulate Dr. Nasrallah for addressing the "provider" issue in his editorial. It is right on the mark and has been a thorn in my side for many years (as is the “client” vs “patient” issue). He worded it very well! I thank Dr. Nasrallah for discussing this.

René S. Kahn, MD, PhD
New York, New York

Continue to: Dr. Nasrallah responds

I thank my colleagues, whose letters confirm that being called “providers” instead of “physicians” is something that all psychiatrists resent and oppose. I hope each psychiatric physician reader of current psychiatry vocally demands to be called a physician, not a provider. I also hope the APA will fight for this issue at the national level.

Henry A. Nasrallah, MD
Professor of Psychiatry, Neurology, and Neuroscience
Medical Director: Neuropsychiatry
Director, Schizophrenia and Neuropsychiatry Programs
University of Cincinnati College of Medicine
Cincinnati, Ohio
Professor Emeritus, Saint Louis University
St. Louis, Missouri

Pre-authorization is a despicable scam. It’s a national racket by avaricious insurance companies, and it must be stopped. Since it first reared its ugly head 2 decades ago, it has inflicted great harm to countless patients, demoralized their physicians, and needlessly imposed higher costs in clinical practice while simultaneously depriving patients of the treatment their physicians prescribed for them.

Pre-authorization has become the nemesis of medical care. It recklessly and arbitrarily vetoes the clinical decision-making of competent physicians doing their best to address their patients’ medical needs. Yet, despite its outrageous disruption of the clinical practice of hundreds of thousands of practitioners, it continues unabated, without a forceful pushback. It has become the “new normal,” but in fact, it is the “new abnormal.” This harassment of clinicians must be outlawed.

Think about it: Pre-authorization is essentially practicing medicine without a license, which is a felony. When a remote and invisible insurance company staff member either prevents a patient from receiving a medication prescribed by that patient’s personal physician following a full diagnostic evaluation or pressures the physician to prescribe a different medication, he/she is basically deciding what the treatment should be for a patient who that insurance company employee has never seen, let alone examined. How did for-profit insurance companies empower themselves to tyrannize clinical practice so that the treatment administered isn’t customized to the patient’s need but instead to fatten the profits of the insurance company? That is patently unethical, in addition to being a felonious practice of medicine by an absentee person unqualified to decide what a patient needs without a direct examination.

Consider the multiple malignant consequences of such brazen and egregious restriction or distortion of medical care:

1. The physician’s clinical judgment is abrogated, even when it is clearly in the patient’s best interest.

2. Patients are deprived of receiving the medication that their personal physician deemed optimal.

3. The physician in private practice has to spend an inordinate amount of time going to web sites, such as CoverMyMeds.com, to fill out extensive forms containing numerous questions about the patient’s illness and diagnosis, and then selecting from a list of medications that the insurance company ironically labels as “smart choices.” These medications often are not necessarily what the physician considers a smart choice, but are the cheapest (regardless of whether their efficacy, safety, or tolerability are the best fit for the patient). After the physician completes the forms, there is a waiting period, followed by additional questions that consume more valuable time and take the physician away from seeing more patients. Some busy colleagues told me they often take the pre-authorization “homework” with them to do at home, consuming part of what should be their family time. For physicians who see patients in an institutional “clinic,” medical assistants or nurses must be hired at significant expense to work full-time on pre-authorizations, adding to the overhead of the clinic while increasing the profits of the third-party insurer.

4. Patients who have been stable on a medication for months, even years, are forced to switch to another medication if they change jobs and become covered by a different insurance company that does not have the patient’s current medication on their infamous list of “approved drugs,” an evil euphemism for “cheapest drugs.” Switching medications is known to be a possibly hazardous process with lower efficacy and/or tolerability, but that appears to be irrelevant to the insurance company. The welfare of the patient is not on the insurance company’s radar screen, perhaps because it is crowded out by dollar signs. We should all urge policymakers to pass legislation that goes beyond requiring insurance companies to cover “pre-existing conditions” and expands it to cover “pre-existing medications.”

Continue to: Often, frustrated physicians...

5. Often, frustrated physicians who do not want to see their patients receive a medication they do not believe is appropriate may spend valuable time writing letters of appeal, making phone calls, or printing and faxing scientific articles to the insurance company to convince them to authorize a medication that is not on the “approved list.” Based on my own clinical experience, that justification sometimes works and sometimes doesn’t.

6. Physicians are inevitably and understandably demoralized because their expertise and sound clinical judgment are arbitrarily dismissed and overruled by an invisible insurance employee whose knowledge about and compassion for the patient is miniscule at best.

7. New medication development has collided with the biased despotism of pre-authorization, which generally rejects any new medication (always costlier than generics) irrespective of whether the new medication was demonstrated in controlled clinical trials to have a measurably better profile than older generics. This has ominous implications for numerous medical disorders that do not have any approved medications (for psychiatry, a published study¹ found that 82% of DSM disorders do not have a FDA-approved medication).

The lack of utilizing newly introduced medications has discouraged the pharmaceutical industry from investing to develop innovative new mechanisms of action for a variety of complex neuropsychiatric medical conditions. Some companies have already abandoned psychiatric drug development, which is dire for clinical care because pharmaceutical companies are the only entities that develop new treatments for our patients (some health care professionals wish the government had a pharmaceutical agency that develops medications for various illness, but no such agency has ever existed).

8. Hospitalization for a seriously ill patient is either denied, delayed, or eventually approved for an absurdly short period (a few days), which is woefully inadequate, culminating in discharging patients with unresolved symptoms. This can lead to disastrous consequences, including suicide, homicide, or incarceration.

Continue to: I have been personally infuriated...

I have been personally infuriated many times because of the adverse impact pre-authorization had on my patients. One example that still haunts me is a 23-year-old college graduate with severe treatment-resistant depression who failed multiple antidepressant trials, including IV ketamine. She harbored daily thoughts of suicide (throwing herself in front of a train, which she saw daily as she drove to work). She admitted to frequently contemplating which dress she should wear in her coffin. Based on several published double-blind studies showing that modafinil improved bipolar depression,² I prescribed modafinil, 200 mg/d, as adjunctive treatment to venlafaxine, 300 mg/d, and she improved significantly for 10 months. Suddenly, the insurance company refused to renew her refill of modafinil, and it took 4 weeks of incessant communication (phone calls, faxes, letters, sending published articles) before it was finally approved. In the meantime, the patient deteriorated and began to have active suicidal urges. When she was restarted on modafinil, she never achieved the same level of improvement she had prior to discontinuing modafinil. The insurance company damaged this patient’s recovery with its refusal to authorize a medication that was “not approved” for depression despite the clear benefit it had provided this treatment-resistant patient for almost 1 year. Their motive was clearly to avoid covering the high cost of modafinil, regardless of this patient’s high risk of suicide.

Every physician can recite a litany of complaints about the evil of pre-authorizations. We must therefore unite and vigorously lobby legislators to pass laws that protect patients and uphold physicians’ authority to determine the right treatment for their patients. We must terminate the plague of pre-authorization that takes our patients hostage to the greed of insurance companies, who have no regard to the agony of patients who are prevented from receiving the medication that their personal physician prescribes. Physicians’ well-being would be greatly enhanced if they were not enslaved to the avarice of insurance companies.

The travesty of pre-authorization and its pervasive and deleterious effects on medical care, society, and citizens must be stopped. It’s a plague that sacrifices the practice of medicine on the altar of financial greed. Just because it has gone on for many years does not mean it should be accepted as the “new normal.” It must be condemned as the “new abnormal,” a cancerous lesion on health care delivery that must be excised and discarded.

Pre-authorization is a despicable scam. It’s a national racket by avaricious insurance companies, and it must be stopped. Since it first reared its ugly head 2 decades ago, it has inflicted great harm to countless patients, demoralized their physicians, and needlessly imposed higher costs in clinical practice while simultaneously depriving patients of the treatment their physicians prescribed for them.

Pre-authorization has become the nemesis of medical care. It recklessly and arbitrarily vetoes the clinical decision-making of competent physicians doing their best to address their patients’ medical needs. Yet, despite its outrageous disruption of the clinical practice of hundreds of thousands of practitioners, it continues unabated, without a forceful pushback. It has become the “new normal,” but in fact, it is the “new abnormal.” This harassment of clinicians must be outlawed.

Think about it: Pre-authorization is essentially practicing medicine without a license, which is a felony. When a remote and invisible insurance company staff member either prevents a patient from receiving a medication prescribed by that patient’s personal physician following a full diagnostic evaluation or pressures the physician to prescribe a different medication, he/she is basically deciding what the treatment should be for a patient who that insurance company employee has never seen, let alone examined. How did for-profit insurance companies empower themselves to tyrannize clinical practice so that the treatment administered isn’t customized to the patient’s need but instead to fatten the profits of the insurance company? That is patently unethical, in addition to being a felonious practice of medicine by an absentee person unqualified to decide what a patient needs without a direct examination.

Consider the multiple malignant consequences of such brazen and egregious restriction or distortion of medical care:

1. The physician’s clinical judgment is abrogated, even when it is clearly in the patient’s best interest.

2. Patients are deprived of receiving the medication that their personal physician deemed optimal.

3. The physician in private practice has to spend an inordinate amount of time going to web sites, such as CoverMyMeds.com, to fill out extensive forms containing numerous questions about the patient’s illness and diagnosis, and then selecting from a list of medications that the insurance company ironically labels as “smart choices.” These medications often are not necessarily what the physician considers a smart choice, but are the cheapest (regardless of whether their efficacy, safety, or tolerability are the best fit for the patient). After the physician completes the forms, there is a waiting period, followed by additional questions that consume more valuable time and take the physician away from seeing more patients. Some busy colleagues told me they often take the pre-authorization “homework” with them to do at home, consuming part of what should be their family time. For physicians who see patients in an institutional “clinic,” medical assistants or nurses must be hired at significant expense to work full-time on pre-authorizations, adding to the overhead of the clinic while increasing the profits of the third-party insurer.

4. Patients who have been stable on a medication for months, even years, are forced to switch to another medication if they change jobs and become covered by a different insurance company that does not have the patient’s current medication on their infamous list of “approved drugs,” an evil euphemism for “cheapest drugs.” Switching medications is known to be a possibly hazardous process with lower efficacy and/or tolerability, but that appears to be irrelevant to the insurance company. The welfare of the patient is not on the insurance company’s radar screen, perhaps because it is crowded out by dollar signs. We should all urge policymakers to pass legislation that goes beyond requiring insurance companies to cover “pre-existing conditions” and expands it to cover “pre-existing medications.”

Continue to: Often, frustrated physicians...

5. Often, frustrated physicians who do not want to see their patients receive a medication they do not believe is appropriate may spend valuable time writing letters of appeal, making phone calls, or printing and faxing scientific articles to the insurance company to convince them to authorize a medication that is not on the “approved list.” Based on my own clinical experience, that justification sometimes works and sometimes doesn’t.

6. Physicians are inevitably and understandably demoralized because their expertise and sound clinical judgment are arbitrarily dismissed and overruled by an invisible insurance employee whose knowledge about and compassion for the patient is miniscule at best.

7. New medication development has collided with the biased despotism of pre-authorization, which generally rejects any new medication (always costlier than generics) irrespective of whether the new medication was demonstrated in controlled clinical trials to have a measurably better profile than older generics. This has ominous implications for numerous medical disorders that do not have any approved medications (for psychiatry, a published study¹ found that 82% of DSM disorders do not have a FDA-approved medication).

The lack of utilizing newly introduced medications has discouraged the pharmaceutical industry from investing to develop innovative new mechanisms of action for a variety of complex neuropsychiatric medical conditions. Some companies have already abandoned psychiatric drug development, which is dire for clinical care because pharmaceutical companies are the only entities that develop new treatments for our patients (some health care professionals wish the government had a pharmaceutical agency that develops medications for various illness, but no such agency has ever existed).

8. Hospitalization for a seriously ill patient is either denied, delayed, or eventually approved for an absurdly short period (a few days), which is woefully inadequate, culminating in discharging patients with unresolved symptoms. This can lead to disastrous consequences, including suicide, homicide, or incarceration.

Continue to: I have been personally infuriated...

I have been personally infuriated many times because of the adverse impact pre-authorization had on my patients. One example that still haunts me is a 23-year-old college graduate with severe treatment-resistant depression who failed multiple antidepressant trials, including IV ketamine. She harbored daily thoughts of suicide (throwing herself in front of a train, which she saw daily as she drove to work). She admitted to frequently contemplating which dress she should wear in her coffin. Based on several published double-blind studies showing that modafinil improved bipolar depression,² I prescribed modafinil, 200 mg/d, as adjunctive treatment to venlafaxine, 300 mg/d, and she improved significantly for 10 months. Suddenly, the insurance company refused to renew her refill of modafinil, and it took 4 weeks of incessant communication (phone calls, faxes, letters, sending published articles) before it was finally approved. In the meantime, the patient deteriorated and began to have active suicidal urges. When she was restarted on modafinil, she never achieved the same level of improvement she had prior to discontinuing modafinil. The insurance company damaged this patient’s recovery with its refusal to authorize a medication that was “not approved” for depression despite the clear benefit it had provided this treatment-resistant patient for almost 1 year. Their motive was clearly to avoid covering the high cost of modafinil, regardless of this patient’s high risk of suicide.

Every physician can recite a litany of complaints about the evil of pre-authorizations. We must therefore unite and vigorously lobby legislators to pass laws that protect patients and uphold physicians’ authority to determine the right treatment for their patients. We must terminate the plague of pre-authorization that takes our patients hostage to the greed of insurance companies, who have no regard to the agony of patients who are prevented from receiving the medication that their personal physician prescribes. Physicians’ well-being would be greatly enhanced if they were not enslaved to the avarice of insurance companies.

The travesty of pre-authorization and its pervasive and deleterious effects on medical care, society, and citizens must be stopped. It’s a plague that sacrifices the practice of medicine on the altar of financial greed. Just because it has gone on for many years does not mean it should be accepted as the “new normal.” It must be condemned as the “new abnormal,” a cancerous lesion on health care delivery that must be excised and discarded.

Pre-authorization is a despicable scam. It’s a national racket by avaricious insurance companies, and it must be stopped. Since it first reared its ugly head 2 decades ago, it has inflicted great harm to countless patients, demoralized their physicians, and needlessly imposed higher costs in clinical practice while simultaneously depriving patients of the treatment their physicians prescribed for them.

Pre-authorization has become the nemesis of medical care. It recklessly and arbitrarily vetoes the clinical decision-making of competent physicians doing their best to address their patients’ medical needs. Yet, despite its outrageous disruption of the clinical practice of hundreds of thousands of practitioners, it continues unabated, without a forceful pushback. It has become the “new normal,” but in fact, it is the “new abnormal.” This harassment of clinicians must be outlawed.

Think about it: Pre-authorization is essentially practicing medicine without a license, which is a felony. When a remote and invisible insurance company staff member either prevents a patient from receiving a medication prescribed by that patient’s personal physician following a full diagnostic evaluation or pressures the physician to prescribe a different medication, he/she is basically deciding what the treatment should be for a patient who that insurance company employee has never seen, let alone examined. How did for-profit insurance companies empower themselves to tyrannize clinical practice so that the treatment administered isn’t customized to the patient’s need but instead to fatten the profits of the insurance company? That is patently unethical, in addition to being a felonious practice of medicine by an absentee person unqualified to decide what a patient needs without a direct examination.

Consider the multiple malignant consequences of such brazen and egregious restriction or distortion of medical care:

1. The physician’s clinical judgment is abrogated, even when it is clearly in the patient’s best interest.

2. Patients are deprived of receiving the medication that their personal physician deemed optimal.

3. The physician in private practice has to spend an inordinate amount of time going to web sites, such as CoverMyMeds.com, to fill out extensive forms containing numerous questions about the patient’s illness and diagnosis, and then selecting from a list of medications that the insurance company ironically labels as “smart choices.” These medications often are not necessarily what the physician considers a smart choice, but are the cheapest (regardless of whether their efficacy, safety, or tolerability are the best fit for the patient). After the physician completes the forms, there is a waiting period, followed by additional questions that consume more valuable time and take the physician away from seeing more patients. Some busy colleagues told me they often take the pre-authorization “homework” with them to do at home, consuming part of what should be their family time. For physicians who see patients in an institutional “clinic,” medical assistants or nurses must be hired at significant expense to work full-time on pre-authorizations, adding to the overhead of the clinic while increasing the profits of the third-party insurer.

4. Patients who have been stable on a medication for months, even years, are forced to switch to another medication if they change jobs and become covered by a different insurance company that does not have the patient’s current medication on their infamous list of “approved drugs,” an evil euphemism for “cheapest drugs.” Switching medications is known to be a possibly hazardous process with lower efficacy and/or tolerability, but that appears to be irrelevant to the insurance company. The welfare of the patient is not on the insurance company’s radar screen, perhaps because it is crowded out by dollar signs. We should all urge policymakers to pass legislation that goes beyond requiring insurance companies to cover “pre-existing conditions” and expands it to cover “pre-existing medications.”

Continue to: Often, frustrated physicians...

5. Often, frustrated physicians who do not want to see their patients receive a medication they do not believe is appropriate may spend valuable time writing letters of appeal, making phone calls, or printing and faxing scientific articles to the insurance company to convince them to authorize a medication that is not on the “approved list.” Based on my own clinical experience, that justification sometimes works and sometimes doesn’t.

6. Physicians are inevitably and understandably demoralized because their expertise and sound clinical judgment are arbitrarily dismissed and overruled by an invisible insurance employee whose knowledge about and compassion for the patient is miniscule at best.

7. New medication development has collided with the biased despotism of pre-authorization, which generally rejects any new medication (always costlier than generics) irrespective of whether the new medication was demonstrated in controlled clinical trials to have a measurably better profile than older generics. This has ominous implications for numerous medical disorders that do not have any approved medications (for psychiatry, a published study¹ found that 82% of DSM disorders do not have a FDA-approved medication).

The lack of utilizing newly introduced medications has discouraged the pharmaceutical industry from investing to develop innovative new mechanisms of action for a variety of complex neuropsychiatric medical conditions. Some companies have already abandoned psychiatric drug development, which is dire for clinical care because pharmaceutical companies are the only entities that develop new treatments for our patients (some health care professionals wish the government had a pharmaceutical agency that develops medications for various illness, but no such agency has ever existed).

8. Hospitalization for a seriously ill patient is either denied, delayed, or eventually approved for an absurdly short period (a few days), which is woefully inadequate, culminating in discharging patients with unresolved symptoms. This can lead to disastrous consequences, including suicide, homicide, or incarceration.

Continue to: I have been personally infuriated...

I have been personally infuriated many times because of the adverse impact pre-authorization had on my patients. One example that still haunts me is a 23-year-old college graduate with severe treatment-resistant depression who failed multiple antidepressant trials, including IV ketamine. She harbored daily thoughts of suicide (throwing herself in front of a train, which she saw daily as she drove to work). She admitted to frequently contemplating which dress she should wear in her coffin. Based on several published double-blind studies showing that modafinil improved bipolar depression,² I prescribed modafinil, 200 mg/d, as adjunctive treatment to venlafaxine, 300 mg/d, and she improved significantly for 10 months. Suddenly, the insurance company refused to renew her refill of modafinil, and it took 4 weeks of incessant communication (phone calls, faxes, letters, sending published articles) before it was finally approved. In the meantime, the patient deteriorated and began to have active suicidal urges. When she was restarted on modafinil, she never achieved the same level of improvement she had prior to discontinuing modafinil. The insurance company damaged this patient’s recovery with its refusal to authorize a medication that was “not approved” for depression despite the clear benefit it had provided this treatment-resistant patient for almost 1 year. Their motive was clearly to avoid covering the high cost of modafinil, regardless of this patient’s high risk of suicide.

Every physician can recite a litany of complaints about the evil of pre-authorizations. We must therefore unite and vigorously lobby legislators to pass laws that protect patients and uphold physicians’ authority to determine the right treatment for their patients. We must terminate the plague of pre-authorization that takes our patients hostage to the greed of insurance companies, who have no regard to the agony of patients who are prevented from receiving the medication that their personal physician prescribes. Physicians’ well-being would be greatly enhanced if they were not enslaved to the avarice of insurance companies.

The travesty of pre-authorization and its pervasive and deleterious effects on medical care, society, and citizens must be stopped. It’s a plague that sacrifices the practice of medicine on the altar of financial greed. Just because it has gone on for many years does not mean it should be accepted as the “new normal.” It must be condemned as the “new abnormal,” a cancerous lesion on health care delivery that must be excised and discarded.

Despite the tremendous advances in psychiatry in recent years, the current clinical practice of psychiatry continues to rely on data from intermittent assessments along with subjective and unquantifiable accounts from patients and caregivers. Furthermore, there continues to be significant diagnostic variations among practitioners. Fortunately, technology to address these issues appears to be on the horizon.

How might the psychiatric clinic of the future look? What changes could we envision? These 4 critical factors may soon bring about dynamic changes in the way we practice psychiatry:

• precision psychiatry
• digital psychiatry
• technology-enhanced psychotherapy
• electronic health record (EHR) reforms.

In this article, we review how advances in each of these areas might lead to improved care for our patients.

Precision psychiatry

Precision psychiatry takes into account each patient’s variability in genes, environment, and lifestyle to determine individualized treatment and prevention strategies. It relies on pharmacogenomic testing as the primary tool. Pharmacogenomics is the study of variability in drug response due to heredity.

Emerging data on the clinical utility and cost-effectiveness of pharmacogenomic testing are encouraging, but its routine use is not well supported by current evidence.² One limit to using pharmacogenomic testing is that many genes simultaneously exert an effect on the structure and function of neurons and associated pathophysiology. According to the International Society of Psychiatric Genetics, no single genetic variant is sufficient to cause psychiatric disorders such as depression, bipolar disorder, substance dependence, or schizophrenia. This limits the possibility of using genetic tests to establish a diagnosis.³

In the future, better algorithms could promote more accurate pharmacogenomics profiles for individual patients, which could influence treatment.

Precision psychiatry could lead to:

• identification of novel targets for new medications
• pharmacogenetic profiling of the patient to predict disease susceptibility and medication response
• personalized therapy: the right drug at the right dose for the right patient.
• improved efficacy and fewer adverse medication reactions.

Continue to: Digital psychiatry

Integrating computer-based technology into psychiatric practice has given birth to a new frontier that could be called digital psychiatry. This might encompass the following:

• telepsychiatry
• social media with a mental health focus
• web-based applications/devices
• artificial intelligence (AI).

Telepsychiatry. Videoconferencing is the most widely used form of telepsychiatry. It provides patients with easier access to mental health treatment.⁴ Telepsychiatry has the potential to match patients and clinicians with similar cultural backgrounds, thus minimizing cultural gaps and misunderstandings. Most importantly, it is comparable to face-to-face interviews in terms of the reliability of assessment and treatment outcomes.⁵

Telepsychiatry might be particularly helpful for patients with restricted mobility, such as those who live in remote areas, nursing homes, or correctional facilities. In correctional settings, transferring prisoners is expensive and carries the risk of escape. In a small study (N = 86) conducted in Hong Kong, Chen et al⁶ found that using videoconferencing to conduct clinical interviews of inmates was cost-efficient and scored high in terms of patient acceptability.

Social media. Social media could be a powerful platform for early detection of mental illness. Staying connected with patients on social media could allow psychiatrists to be more aware of their patient’s mood fluctuations, which might lead to more timely assessments. Physicians could be automatically notified about changes in their patients’ social media activity that indicate changes in mental state, which could solicit immediate intervention and treatment. On the other hand, such use of social media could blur professional boundaries. Psychiatrists also could use social media to promote awareness of mental health and educate the public on ways to improve or maintain their mental well-being.⁷

Web-based applications/devices. Real-time monitoring through applications or internet-based smart devices creates a new avenue for patients to receive personalized assessments, treatment, and intervention.⁸ Smartwatches with internet connectivity may offer a glimpse of the wearer’s sleep architecture and duration, thus providing real-time data on patients who have insomnia. We can now passively collect objective data from devices, such as smartphones and laptops, to phenotype an individual’s mood and mental state, a process called digital phenotyping. The Table⁹ lists examples of the types of mental health–related metrics that can be captured by smartphones, smartwatches, and similar technology. Information from these devices can be accumulated to create a database that can be used to predict symptoms.¹⁰ For example, the way people use a smartphone’s keyboard, including latency time between space and character types, can be used to generate variables for data. This type of information is being studied for use in screening depression and passively assessing mood in real time.¹¹

Continue to: Artificial intelligence

Artificial intelligence—the development of computer systems able to perform tasks that normally require human intelligence—is being increasingly used in psychiatry. Some studies have suggested AI can be used to identify patients’ risk of suicide^12-15 or psychosis.^16,17Kalanderian and Nasrallah¹⁸ reviewed several of these studies in Current Psychiatry, August 2019. This article is available at mdedge.com/psychiatry/article/205527/schizophrenia-other-psychotic-disorders/artificial-intelligence-psychiatry.

Other researchers have found clinical uses for machine learning, a subset of AI that uses methods to automatically detect patterns and make predictions based on those patterns. In one study, a machine learning analysis of functional MRI scans was able to identify 4 distinct subtypes of depression.¹⁹ In another study, a machine learning model was able to predict with 60% accuracy which patients with depression would respond to antidepressants.²⁰

In the future, AI might be used to change mental health classification systems. Because many mental health disorders share similar symptom clusters, machine learning can help to identify associations between symptoms, behavior, brain function, and real-world function across different diagnoses, potentially affecting how we will classify mental disorders.²¹

Technology-enhanced psychotherapy

In the future, it might be common for psychotherapy to be provided by a computer, or “virtual therapist.” Several studies have evaluated the use of technology-enhanced psychotherapy.

Lucas et al²² investigated patients’ interactions with a virtual therapist. Participants were interviewed by an avatar named Ellie, who they saw on a TV screen. Half of the participants were told Ellie was not human, and half were told Ellie was being controlled remotely by a human. Three psychologists who were blinded to group allocations analyzed transcripts of the interviews and video recordings of participants’ facial expressions to quantify the participants’ fear, sadness, and other emotional responses during the interviews, as well as their openness to the questions. Participants who believed Ellie was fully automated reported significantly lower fear of self-disclosure and impression management (attempts to control how others perceive them) than participants who were told that Ellie was operated by a human. Additionally, participants who believed they were interacting with a computer were more open during the interview.²²

Continue to: Researchers at the University of Southern California...

Researchers at the University of Southern California developed software that assessed 74 acoustic features, including pitch, volume, quality, shimmer, jitter, and prosody, to predict outcomes among patients receiving couples therapy. This software was able to predict marital discord at least as well as human therapists.²³

Many mental health apps purport to implement specific components of psychotherapy. Many of these apps focus on cognitive-behavioral therapy worksheets, mindfulness exercises, and/or mood tracking. The features provided by such apps emulate the tasks and intended outcomes of traditional psychotherapy, but in an entirely decentralized venue.²⁴

Some have expressed concern that an increased use of virtual therapists powered by AI might lead to a dehumanization of psychiatry (Box^25,26).

Box

Electronic health record reforms

Although many clinicians find EHRs to be onerous and time-consuming, EHR technology is constantly improving, and EHRs have revolutionized documentation and order implementation. Several potential advances could improve clinical practice. For example, EHRs could incorporate a clinical decision support system that uses AI-based algorithms to assist psychiatrists with diagnosis, monitoring, and treatment.²⁷ In the future, EHRs might have the ability to monitor and learn from errors and adverse events, and automatically design an algorithm to avoid them.²⁸ They should be designed to better manage analysis of pharmacogenetic test results, which is challenging due to the amount and complexity of the data.²⁹ Future EHRs should eliminate the non-intuitive and multi-click interfaces and cumbersome data searches of today’s EHRs.³⁰

Technology brings new ethical considerations

Mental health interventions based on AI typically work with algorithms, and algorithms bring ethical issues. Mental health devices or systems that use AI could contain biases that have the potential to harm in unintended ways, such as a data-driven sexist or racist bias.³¹ This may require investing additional time to explain to patients (and their families) what an algorithm is and how it works in relation to the therapy provided.

Continue to: Another concern is patient...

Another concern is patient autonomy.³² For example, it would be ethically problematic if a patient were to assume that there was a human physician “at the other end” of a virtual therapist or other technology who is communicating or reviewing his/her messages. Similarly, an older adult or a patient with intellectual disabilities may not be able to understand advanced technology or what it does when it is installed in their home to monitor the patient’s activities. This would increase the risk of privacy violations, manipulation, or even coercion if the requirements for informed consent are not satisfied.

A flowchart for the future

Although current research and innovations typically target specific areas of psychiatry, these advances can be integrated by devising algorithms and protocols that will change the current practice of psychiatry. The Figure provides a glimpse of how the psychiatry clinic of the future might work. A maxim of management is that “the best way to predict the future is to create it.” However, the mere conception of a vision is not enough—working towards it is essential.

Bottom Line

With advances in technology, psychiatric practice will soon be radically different from what it is today. The expanded use of telepsychiatry, social media, artificial intelligence, and web-based applications/devices holds great promise for psychiatric assessment, diagnosis, and treatment, although certain ethical and privacy concerns need to be adequately addressed.

Related Resources

• National Institute of Mental Health. Technology and the future of mental health treatment. www.nimh.nih.gov/health/topics/technology-and-the-future-of-mental-health-treatment/index.shtml. Revised September 2019.
• Hays R, Farrell HM, Touros J. Mobile apps and mental health: using technology to quantify real-time clinical risk. Current Psychiatry. 2019;18(6):37-41.
• Torous J, Luo J, Chan SR. Mental health apps: what to tell patients. Current Psychiatry. 2018;17(3):21-25.

Despite the tremendous advances in psychiatry in recent years, the current clinical practice of psychiatry continues to rely on data from intermittent assessments along with subjective and unquantifiable accounts from patients and caregivers. Furthermore, there continues to be significant diagnostic variations among practitioners. Fortunately, technology to address these issues appears to be on the horizon.

How might the psychiatric clinic of the future look? What changes could we envision? These 4 critical factors may soon bring about dynamic changes in the way we practice psychiatry:

• precision psychiatry
• digital psychiatry
• technology-enhanced psychotherapy
• electronic health record (EHR) reforms.

In this article, we review how advances in each of these areas might lead to improved care for our patients.

Precision psychiatry

Precision psychiatry takes into account each patient’s variability in genes, environment, and lifestyle to determine individualized treatment and prevention strategies. It relies on pharmacogenomic testing as the primary tool. Pharmacogenomics is the study of variability in drug response due to heredity.

Emerging data on the clinical utility and cost-effectiveness of pharmacogenomic testing are encouraging, but its routine use is not well supported by current evidence.² One limit to using pharmacogenomic testing is that many genes simultaneously exert an effect on the structure and function of neurons and associated pathophysiology. According to the International Society of Psychiatric Genetics, no single genetic variant is sufficient to cause psychiatric disorders such as depression, bipolar disorder, substance dependence, or schizophrenia. This limits the possibility of using genetic tests to establish a diagnosis.³

In the future, better algorithms could promote more accurate pharmacogenomics profiles for individual patients, which could influence treatment.

Precision psychiatry could lead to:

• identification of novel targets for new medications
• pharmacogenetic profiling of the patient to predict disease susceptibility and medication response
• personalized therapy: the right drug at the right dose for the right patient.
• improved efficacy and fewer adverse medication reactions.

Continue to: Digital psychiatry

Integrating computer-based technology into psychiatric practice has given birth to a new frontier that could be called digital psychiatry. This might encompass the following:

• telepsychiatry
• social media with a mental health focus
• web-based applications/devices
• artificial intelligence (AI).

Telepsychiatry. Videoconferencing is the most widely used form of telepsychiatry. It provides patients with easier access to mental health treatment.⁴ Telepsychiatry has the potential to match patients and clinicians with similar cultural backgrounds, thus minimizing cultural gaps and misunderstandings. Most importantly, it is comparable to face-to-face interviews in terms of the reliability of assessment and treatment outcomes.⁵

Telepsychiatry might be particularly helpful for patients with restricted mobility, such as those who live in remote areas, nursing homes, or correctional facilities. In correctional settings, transferring prisoners is expensive and carries the risk of escape. In a small study (N = 86) conducted in Hong Kong, Chen et al⁶ found that using videoconferencing to conduct clinical interviews of inmates was cost-efficient and scored high in terms of patient acceptability.

Social media. Social media could be a powerful platform for early detection of mental illness. Staying connected with patients on social media could allow psychiatrists to be more aware of their patient’s mood fluctuations, which might lead to more timely assessments. Physicians could be automatically notified about changes in their patients’ social media activity that indicate changes in mental state, which could solicit immediate intervention and treatment. On the other hand, such use of social media could blur professional boundaries. Psychiatrists also could use social media to promote awareness of mental health and educate the public on ways to improve or maintain their mental well-being.⁷

Web-based applications/devices. Real-time monitoring through applications or internet-based smart devices creates a new avenue for patients to receive personalized assessments, treatment, and intervention.⁸ Smartwatches with internet connectivity may offer a glimpse of the wearer’s sleep architecture and duration, thus providing real-time data on patients who have insomnia. We can now passively collect objective data from devices, such as smartphones and laptops, to phenotype an individual’s mood and mental state, a process called digital phenotyping. The Table⁹ lists examples of the types of mental health–related metrics that can be captured by smartphones, smartwatches, and similar technology. Information from these devices can be accumulated to create a database that can be used to predict symptoms.¹⁰ For example, the way people use a smartphone’s keyboard, including latency time between space and character types, can be used to generate variables for data. This type of information is being studied for use in screening depression and passively assessing mood in real time.¹¹

Continue to: Artificial intelligence

Artificial intelligence—the development of computer systems able to perform tasks that normally require human intelligence—is being increasingly used in psychiatry. Some studies have suggested AI can be used to identify patients’ risk of suicide^12-15 or psychosis.^16,17Kalanderian and Nasrallah¹⁸ reviewed several of these studies in Current Psychiatry, August 2019. This article is available at mdedge.com/psychiatry/article/205527/schizophrenia-other-psychotic-disorders/artificial-intelligence-psychiatry.

Other researchers have found clinical uses for machine learning, a subset of AI that uses methods to automatically detect patterns and make predictions based on those patterns. In one study, a machine learning analysis of functional MRI scans was able to identify 4 distinct subtypes of depression.¹⁹ In another study, a machine learning model was able to predict with 60% accuracy which patients with depression would respond to antidepressants.²⁰

In the future, AI might be used to change mental health classification systems. Because many mental health disorders share similar symptom clusters, machine learning can help to identify associations between symptoms, behavior, brain function, and real-world function across different diagnoses, potentially affecting how we will classify mental disorders.²¹

Technology-enhanced psychotherapy

In the future, it might be common for psychotherapy to be provided by a computer, or “virtual therapist.” Several studies have evaluated the use of technology-enhanced psychotherapy.

Lucas et al²² investigated patients’ interactions with a virtual therapist. Participants were interviewed by an avatar named Ellie, who they saw on a TV screen. Half of the participants were told Ellie was not human, and half were told Ellie was being controlled remotely by a human. Three psychologists who were blinded to group allocations analyzed transcripts of the interviews and video recordings of participants’ facial expressions to quantify the participants’ fear, sadness, and other emotional responses during the interviews, as well as their openness to the questions. Participants who believed Ellie was fully automated reported significantly lower fear of self-disclosure and impression management (attempts to control how others perceive them) than participants who were told that Ellie was operated by a human. Additionally, participants who believed they were interacting with a computer were more open during the interview.²²

Continue to: Researchers at the University of Southern California...

Researchers at the University of Southern California developed software that assessed 74 acoustic features, including pitch, volume, quality, shimmer, jitter, and prosody, to predict outcomes among patients receiving couples therapy. This software was able to predict marital discord at least as well as human therapists.²³

Many mental health apps purport to implement specific components of psychotherapy. Many of these apps focus on cognitive-behavioral therapy worksheets, mindfulness exercises, and/or mood tracking. The features provided by such apps emulate the tasks and intended outcomes of traditional psychotherapy, but in an entirely decentralized venue.²⁴

Some have expressed concern that an increased use of virtual therapists powered by AI might lead to a dehumanization of psychiatry (Box^25,26).

Box

Electronic health record reforms

Although many clinicians find EHRs to be onerous and time-consuming, EHR technology is constantly improving, and EHRs have revolutionized documentation and order implementation. Several potential advances could improve clinical practice. For example, EHRs could incorporate a clinical decision support system that uses AI-based algorithms to assist psychiatrists with diagnosis, monitoring, and treatment.²⁷ In the future, EHRs might have the ability to monitor and learn from errors and adverse events, and automatically design an algorithm to avoid them.²⁸ They should be designed to better manage analysis of pharmacogenetic test results, which is challenging due to the amount and complexity of the data.²⁹ Future EHRs should eliminate the non-intuitive and multi-click interfaces and cumbersome data searches of today’s EHRs.³⁰

Technology brings new ethical considerations

Mental health interventions based on AI typically work with algorithms, and algorithms bring ethical issues. Mental health devices or systems that use AI could contain biases that have the potential to harm in unintended ways, such as a data-driven sexist or racist bias.³¹ This may require investing additional time to explain to patients (and their families) what an algorithm is and how it works in relation to the therapy provided.

Continue to: Another concern is patient...

Another concern is patient autonomy.³² For example, it would be ethically problematic if a patient were to assume that there was a human physician “at the other end” of a virtual therapist or other technology who is communicating or reviewing his/her messages. Similarly, an older adult or a patient with intellectual disabilities may not be able to understand advanced technology or what it does when it is installed in their home to monitor the patient’s activities. This would increase the risk of privacy violations, manipulation, or even coercion if the requirements for informed consent are not satisfied.

A flowchart for the future

Although current research and innovations typically target specific areas of psychiatry, these advances can be integrated by devising algorithms and protocols that will change the current practice of psychiatry. The Figure provides a glimpse of how the psychiatry clinic of the future might work. A maxim of management is that “the best way to predict the future is to create it.” However, the mere conception of a vision is not enough—working towards it is essential.

Bottom Line

With advances in technology, psychiatric practice will soon be radically different from what it is today. The expanded use of telepsychiatry, social media, artificial intelligence, and web-based applications/devices holds great promise for psychiatric assessment, diagnosis, and treatment, although certain ethical and privacy concerns need to be adequately addressed.

Related Resources

• National Institute of Mental Health. Technology and the future of mental health treatment. www.nimh.nih.gov/health/topics/technology-and-the-future-of-mental-health-treatment/index.shtml. Revised September 2019.
• Hays R, Farrell HM, Touros J. Mobile apps and mental health: using technology to quantify real-time clinical risk. Current Psychiatry. 2019;18(6):37-41.
• Torous J, Luo J, Chan SR. Mental health apps: what to tell patients. Current Psychiatry. 2018;17(3):21-25.

Despite the tremendous advances in psychiatry in recent years, the current clinical practice of psychiatry continues to rely on data from intermittent assessments along with subjective and unquantifiable accounts from patients and caregivers. Furthermore, there continues to be significant diagnostic variations among practitioners. Fortunately, technology to address these issues appears to be on the horizon.

How might the psychiatric clinic of the future look? What changes could we envision? These 4 critical factors may soon bring about dynamic changes in the way we practice psychiatry:

• precision psychiatry
• digital psychiatry
• technology-enhanced psychotherapy
• electronic health record (EHR) reforms.

In this article, we review how advances in each of these areas might lead to improved care for our patients.

Precision psychiatry

Precision psychiatry takes into account each patient’s variability in genes, environment, and lifestyle to determine individualized treatment and prevention strategies. It relies on pharmacogenomic testing as the primary tool. Pharmacogenomics is the study of variability in drug response due to heredity.

Emerging data on the clinical utility and cost-effectiveness of pharmacogenomic testing are encouraging, but its routine use is not well supported by current evidence.² One limit to using pharmacogenomic testing is that many genes simultaneously exert an effect on the structure and function of neurons and associated pathophysiology. According to the International Society of Psychiatric Genetics, no single genetic variant is sufficient to cause psychiatric disorders such as depression, bipolar disorder, substance dependence, or schizophrenia. This limits the possibility of using genetic tests to establish a diagnosis.³

In the future, better algorithms could promote more accurate pharmacogenomics profiles for individual patients, which could influence treatment.

Precision psychiatry could lead to:

• identification of novel targets for new medications
• pharmacogenetic profiling of the patient to predict disease susceptibility and medication response
• personalized therapy: the right drug at the right dose for the right patient.
• improved efficacy and fewer adverse medication reactions.

Continue to: Digital psychiatry

Integrating computer-based technology into psychiatric practice has given birth to a new frontier that could be called digital psychiatry. This might encompass the following:

• telepsychiatry
• social media with a mental health focus
• web-based applications/devices
• artificial intelligence (AI).

Telepsychiatry. Videoconferencing is the most widely used form of telepsychiatry. It provides patients with easier access to mental health treatment.⁴ Telepsychiatry has the potential to match patients and clinicians with similar cultural backgrounds, thus minimizing cultural gaps and misunderstandings. Most importantly, it is comparable to face-to-face interviews in terms of the reliability of assessment and treatment outcomes.⁵

Telepsychiatry might be particularly helpful for patients with restricted mobility, such as those who live in remote areas, nursing homes, or correctional facilities. In correctional settings, transferring prisoners is expensive and carries the risk of escape. In a small study (N = 86) conducted in Hong Kong, Chen et al⁶ found that using videoconferencing to conduct clinical interviews of inmates was cost-efficient and scored high in terms of patient acceptability.

Social media. Social media could be a powerful platform for early detection of mental illness. Staying connected with patients on social media could allow psychiatrists to be more aware of their patient’s mood fluctuations, which might lead to more timely assessments. Physicians could be automatically notified about changes in their patients’ social media activity that indicate changes in mental state, which could solicit immediate intervention and treatment. On the other hand, such use of social media could blur professional boundaries. Psychiatrists also could use social media to promote awareness of mental health and educate the public on ways to improve or maintain their mental well-being.⁷

Web-based applications/devices. Real-time monitoring through applications or internet-based smart devices creates a new avenue for patients to receive personalized assessments, treatment, and intervention.⁸ Smartwatches with internet connectivity may offer a glimpse of the wearer’s sleep architecture and duration, thus providing real-time data on patients who have insomnia. We can now passively collect objective data from devices, such as smartphones and laptops, to phenotype an individual’s mood and mental state, a process called digital phenotyping. The Table⁹ lists examples of the types of mental health–related metrics that can be captured by smartphones, smartwatches, and similar technology. Information from these devices can be accumulated to create a database that can be used to predict symptoms.¹⁰ For example, the way people use a smartphone’s keyboard, including latency time between space and character types, can be used to generate variables for data. This type of information is being studied for use in screening depression and passively assessing mood in real time.¹¹

Continue to: Artificial intelligence

Artificial intelligence—the development of computer systems able to perform tasks that normally require human intelligence—is being increasingly used in psychiatry. Some studies have suggested AI can be used to identify patients’ risk of suicide^12-15 or psychosis.^16,17Kalanderian and Nasrallah¹⁸ reviewed several of these studies in Current Psychiatry, August 2019. This article is available at mdedge.com/psychiatry/article/205527/schizophrenia-other-psychotic-disorders/artificial-intelligence-psychiatry.

Other researchers have found clinical uses for machine learning, a subset of AI that uses methods to automatically detect patterns and make predictions based on those patterns. In one study, a machine learning analysis of functional MRI scans was able to identify 4 distinct subtypes of depression.¹⁹ In another study, a machine learning model was able to predict with 60% accuracy which patients with depression would respond to antidepressants.²⁰

In the future, AI might be used to change mental health classification systems. Because many mental health disorders share similar symptom clusters, machine learning can help to identify associations between symptoms, behavior, brain function, and real-world function across different diagnoses, potentially affecting how we will classify mental disorders.²¹

Technology-enhanced psychotherapy

In the future, it might be common for psychotherapy to be provided by a computer, or “virtual therapist.” Several studies have evaluated the use of technology-enhanced psychotherapy.

Lucas et al²² investigated patients’ interactions with a virtual therapist. Participants were interviewed by an avatar named Ellie, who they saw on a TV screen. Half of the participants were told Ellie was not human, and half were told Ellie was being controlled remotely by a human. Three psychologists who were blinded to group allocations analyzed transcripts of the interviews and video recordings of participants’ facial expressions to quantify the participants’ fear, sadness, and other emotional responses during the interviews, as well as their openness to the questions. Participants who believed Ellie was fully automated reported significantly lower fear of self-disclosure and impression management (attempts to control how others perceive them) than participants who were told that Ellie was operated by a human. Additionally, participants who believed they were interacting with a computer were more open during the interview.²²

Continue to: Researchers at the University of Southern California...

Researchers at the University of Southern California developed software that assessed 74 acoustic features, including pitch, volume, quality, shimmer, jitter, and prosody, to predict outcomes among patients receiving couples therapy. This software was able to predict marital discord at least as well as human therapists.²³

Many mental health apps purport to implement specific components of psychotherapy. Many of these apps focus on cognitive-behavioral therapy worksheets, mindfulness exercises, and/or mood tracking. The features provided by such apps emulate the tasks and intended outcomes of traditional psychotherapy, but in an entirely decentralized venue.²⁴

Some have expressed concern that an increased use of virtual therapists powered by AI might lead to a dehumanization of psychiatry (Box^25,26).

Box

Electronic health record reforms

Although many clinicians find EHRs to be onerous and time-consuming, EHR technology is constantly improving, and EHRs have revolutionized documentation and order implementation. Several potential advances could improve clinical practice. For example, EHRs could incorporate a clinical decision support system that uses AI-based algorithms to assist psychiatrists with diagnosis, monitoring, and treatment.²⁷ In the future, EHRs might have the ability to monitor and learn from errors and adverse events, and automatically design an algorithm to avoid them.²⁸ They should be designed to better manage analysis of pharmacogenetic test results, which is challenging due to the amount and complexity of the data.²⁹ Future EHRs should eliminate the non-intuitive and multi-click interfaces and cumbersome data searches of today’s EHRs.³⁰

Technology brings new ethical considerations

Mental health interventions based on AI typically work with algorithms, and algorithms bring ethical issues. Mental health devices or systems that use AI could contain biases that have the potential to harm in unintended ways, such as a data-driven sexist or racist bias.³¹ This may require investing additional time to explain to patients (and their families) what an algorithm is and how it works in relation to the therapy provided.

Continue to: Another concern is patient...

Another concern is patient autonomy.³² For example, it would be ethically problematic if a patient were to assume that there was a human physician “at the other end” of a virtual therapist or other technology who is communicating or reviewing his/her messages. Similarly, an older adult or a patient with intellectual disabilities may not be able to understand advanced technology or what it does when it is installed in their home to monitor the patient’s activities. This would increase the risk of privacy violations, manipulation, or even coercion if the requirements for informed consent are not satisfied.

A flowchart for the future

Although current research and innovations typically target specific areas of psychiatry, these advances can be integrated by devising algorithms and protocols that will change the current practice of psychiatry. The Figure provides a glimpse of how the psychiatry clinic of the future might work. A maxim of management is that “the best way to predict the future is to create it.” However, the mere conception of a vision is not enough—working towards it is essential.

Bottom Line

With advances in technology, psychiatric practice will soon be radically different from what it is today. The expanded use of telepsychiatry, social media, artificial intelligence, and web-based applications/devices holds great promise for psychiatric assessment, diagnosis, and treatment, although certain ethical and privacy concerns need to be adequately addressed.

Related Resources

• National Institute of Mental Health. Technology and the future of mental health treatment. www.nimh.nih.gov/health/topics/technology-and-the-future-of-mental-health-treatment/index.shtml. Revised September 2019.
• Hays R, Farrell HM, Touros J. Mobile apps and mental health: using technology to quantify real-time clinical risk. Current Psychiatry. 2019;18(6):37-41.
• Torous J, Luo J, Chan SR. Mental health apps: what to tell patients. Current Psychiatry. 2018;17(3):21-25.

“There is no sound save the throb of the blowers and the vibration of the hard-driven engines. There is little motion as the gun crews man their guns and the fire-control details stand with heads bent and their hands clapped over their headphones. Somewhere out there are the enemy planes.”

That’s from one of my favorite WW2 histories, “Torpedo Junction,” by Robert J. Casey. He was a reporter stationed on board the cruiser USS Salt Lake City. The entry is from a day in February 1942 when the ship was part of a force that bombarded the Japanese encampment on Wake Island. The excerpt describes the scene later that afternoon, as they awaited a counterattack from Japanese planes.

For some reason that paragraph kept going through my mind this past Sunday afternoon, in the comparatively mundane situation of sitting in the hospital library signing off on my dictations and reviewing test results. I certainly was in no danger of being bombed or strafed, yet ...

Around me, the hospital was preparing for battle. As I rounded, most of the beds were empty and many of the floors above me were shut down and darkened. Waiting rooms were empty. If you hadn’t read the news you’d think there was a sudden lull in the health care world.

But the real truth is that it’s the calm before an anticipated storm. The elective procedures have all been canceled. Nonurgent outpatient tests are on hold. Only the sickest are being admitted, and they’re being sent out as soon as possible. Every bed possible is being kept open for the feared onslaught of coronavirus patients in the coming weeks. Protective equipment, already in short supply, is being stockpiled as it becomes available. Plans have been made to erect triage tents in the parking lots. 

I sit in the library and think of this. It’s quiet except for the soft hum of the air conditioning blowers as Phoenix starts to warm up for another summer. The muted purr of the computer’s hard drive as I click away on the keys. On the floors above me the nurses and respiratory techs and doctors go about their daily business of patient care, wondering when the real battle will begin (probably 2-3 weeks from the time of this writing, if not sooner).

These are scary times. I’d be lying if I said I wasn’t frightened about what might happen to me, my family, my friends, my coworkers, my patients.

The people working in the hospital above me are in the same boat, all nervous about what’s going to happen. None of them is any more immune to coronavirus than the people they’ll be treating.

But, like the crew of the USS Salt Lake City, they’re ready to do their jobs. Because it’s part of what drove each of us into our own part of this field. Because we care and want to help. And health care doesn’t work unless the whole team does.

I respect them all for it. I always have and always will, and now more than ever.

Good luck.

Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.

“There is no sound save the throb of the blowers and the vibration of the hard-driven engines. There is little motion as the gun crews man their guns and the fire-control details stand with heads bent and their hands clapped over their headphones. Somewhere out there are the enemy planes.”

That’s from one of my favorite WW2 histories, “Torpedo Junction,” by Robert J. Casey. He was a reporter stationed on board the cruiser USS Salt Lake City. The entry is from a day in February 1942 when the ship was part of a force that bombarded the Japanese encampment on Wake Island. The excerpt describes the scene later that afternoon, as they awaited a counterattack from Japanese planes.

For some reason that paragraph kept going through my mind this past Sunday afternoon, in the comparatively mundane situation of sitting in the hospital library signing off on my dictations and reviewing test results. I certainly was in no danger of being bombed or strafed, yet ...

Around me, the hospital was preparing for battle. As I rounded, most of the beds were empty and many of the floors above me were shut down and darkened. Waiting rooms were empty. If you hadn’t read the news you’d think there was a sudden lull in the health care world.

But the real truth is that it’s the calm before an anticipated storm. The elective procedures have all been canceled. Nonurgent outpatient tests are on hold. Only the sickest are being admitted, and they’re being sent out as soon as possible. Every bed possible is being kept open for the feared onslaught of coronavirus patients in the coming weeks. Protective equipment, already in short supply, is being stockpiled as it becomes available. Plans have been made to erect triage tents in the parking lots. 

I sit in the library and think of this. It’s quiet except for the soft hum of the air conditioning blowers as Phoenix starts to warm up for another summer. The muted purr of the computer’s hard drive as I click away on the keys. On the floors above me the nurses and respiratory techs and doctors go about their daily business of patient care, wondering when the real battle will begin (probably 2-3 weeks from the time of this writing, if not sooner).

These are scary times. I’d be lying if I said I wasn’t frightened about what might happen to me, my family, my friends, my coworkers, my patients.

The people working in the hospital above me are in the same boat, all nervous about what’s going to happen. None of them is any more immune to coronavirus than the people they’ll be treating.

But, like the crew of the USS Salt Lake City, they’re ready to do their jobs. Because it’s part of what drove each of us into our own part of this field. Because we care and want to help. And health care doesn’t work unless the whole team does.

I respect them all for it. I always have and always will, and now more than ever.

Good luck.

Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.

“There is no sound save the throb of the blowers and the vibration of the hard-driven engines. There is little motion as the gun crews man their guns and the fire-control details stand with heads bent and their hands clapped over their headphones. Somewhere out there are the enemy planes.”

That’s from one of my favorite WW2 histories, “Torpedo Junction,” by Robert J. Casey. He was a reporter stationed on board the cruiser USS Salt Lake City. The entry is from a day in February 1942 when the ship was part of a force that bombarded the Japanese encampment on Wake Island. The excerpt describes the scene later that afternoon, as they awaited a counterattack from Japanese planes.

For some reason that paragraph kept going through my mind this past Sunday afternoon, in the comparatively mundane situation of sitting in the hospital library signing off on my dictations and reviewing test results. I certainly was in no danger of being bombed or strafed, yet ...

Around me, the hospital was preparing for battle. As I rounded, most of the beds were empty and many of the floors above me were shut down and darkened. Waiting rooms were empty. If you hadn’t read the news you’d think there was a sudden lull in the health care world.

But the real truth is that it’s the calm before an anticipated storm. The elective procedures have all been canceled. Nonurgent outpatient tests are on hold. Only the sickest are being admitted, and they’re being sent out as soon as possible. Every bed possible is being kept open for the feared onslaught of coronavirus patients in the coming weeks. Protective equipment, already in short supply, is being stockpiled as it becomes available. Plans have been made to erect triage tents in the parking lots. 

I sit in the library and think of this. It’s quiet except for the soft hum of the air conditioning blowers as Phoenix starts to warm up for another summer. The muted purr of the computer’s hard drive as I click away on the keys. On the floors above me the nurses and respiratory techs and doctors go about their daily business of patient care, wondering when the real battle will begin (probably 2-3 weeks from the time of this writing, if not sooner).

These are scary times. I’d be lying if I said I wasn’t frightened about what might happen to me, my family, my friends, my coworkers, my patients.

The people working in the hospital above me are in the same boat, all nervous about what’s going to happen. None of them is any more immune to coronavirus than the people they’ll be treating.

But, like the crew of the USS Salt Lake City, they’re ready to do their jobs. Because it’s part of what drove each of us into our own part of this field. Because we care and want to help. And health care doesn’t work unless the whole team does.

I respect them all for it. I always have and always will, and now more than ever.

Good luck.

Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.

In this edition of “Applying research to practice,” I highlight a study suggesting olaparib is helpful in patients BRCA mutations experiencing multiple relapses of ovarian cancer.

SOLO3 was the first phase 3 trial comparing the oral PARP inhibitor olaparib (OLA; 300 mg twice daily) with physician’s choice of intravenous single-agent chemotherapy (TPC) in relapsed high-grade serous or endometroid ovarian, fallopian tube, or primary peritoneal cancer (J Clin Oncol. 2020 Feb 19. doi: 10.1200/JCO.19.02745).

The trial involved 266 BRCA-mutated patients who had received two (approximately 50%) or more lines of platinum-based TPC. All patients were required to be completely platinum sensitive (progression beyond 12 months from last platinum exposure) or partially platinum sensitive (progression within 6-12 months).

Women were randomized to receive either OLA or nonplatinum TPC (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). After an amendment to the study in 2017, the primary endpoint was objective response rate, determined by blinded independent central review, with a variety of secondary endpoints.

Among 223 patients with measurable disease, the objective response rate was 72.2% with OLA and 51.4% with TPC (odds ratio, 2.53; P = .002). Across all patients, the median progression-free survival was significantly better with OLA (13.4 months) than with TPC (9.2 months; P = .013). Overall survival data were immature.

The superiority of OLA for the primary endpoint was maintained in multiple subgroups of patients, including those who had received only two prior lines of therapy (OR, 3.44) and those who had three or more prior lines (OR, 2.21). Time to first subsequent therapy (HR, 0.48) and time to treatment discontinuation or death (HR, 0.17) were significantly longer for OLA than for TPC.

Adverse events were consistent with the established safety profiles of OLA and chemotherapy. The most common grade 3 or higher adverse events were anemia (21.3%) with OLA and neutropenia (15.8%) and hand-foot syndrome (11.8%) with TPC.

However, median treatment durations were substantially and consistently longer for OLA than for TPC, and there were fewer treatment discontinuations because of toxicity for OLA than for TPC. At the time of data cutoff, 43 patients in the OLA group and 1 patient in the TPC cohort remained on treatment.
 

How these results influence practice

The results of the SOLO3 trial are clear: Treatment with OLA is a reasonable alternative to nonplatinum-containing chemotherapy for women with BRCA mutations and platinum-sensitive ovarian cancer. OLA is a “chemotherapy-free” option for these patients in the second- and later-line settings.

Less clear are the following:

• How many patients with BRCA mutations will not have already received a PARP inhibitor in the frontline maintenance setting in the future? SOLO3 required modification in the accrual target and endpoint because of challenges in patient recruitment from the entry of PARP inhibitors into routine clinical practice.
• Would OLA be superior to a carboplatin doublet rather than a nonplatinum single agent in patients with two prior relapses of platinum-sensitive ovarian cancer? Standard practice would be for patients in the second-line setting to receive a platinum doublet.
• Is extending the platinum-free interval a worthwhile objective, or would some patients prefer a finite interval of a platinum doublet over an indefinite period of treatment with OLA?

All phase 3 clinical trials have limitations since they require years to complete and the applicability of the results are challenged by intercurrent advances in treatment options and diagnostic tests.

However, overall, the results of SOLO3 are impressive and should influence clinical practice for the subset of relapsed ovarian cancer patients who would have qualified to participate in it. OLA represents an important treatment advance for a group of patients who are trying to string together remission after remission, with limited negative impact on quality of life.



Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

In this edition of “Applying research to practice,” I highlight a study suggesting olaparib is helpful in patients BRCA mutations experiencing multiple relapses of ovarian cancer.

SOLO3 was the first phase 3 trial comparing the oral PARP inhibitor olaparib (OLA; 300 mg twice daily) with physician’s choice of intravenous single-agent chemotherapy (TPC) in relapsed high-grade serous or endometroid ovarian, fallopian tube, or primary peritoneal cancer (J Clin Oncol. 2020 Feb 19. doi: 10.1200/JCO.19.02745).

The trial involved 266 BRCA-mutated patients who had received two (approximately 50%) or more lines of platinum-based TPC. All patients were required to be completely platinum sensitive (progression beyond 12 months from last platinum exposure) or partially platinum sensitive (progression within 6-12 months).

Women were randomized to receive either OLA or nonplatinum TPC (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). After an amendment to the study in 2017, the primary endpoint was objective response rate, determined by blinded independent central review, with a variety of secondary endpoints.

Among 223 patients with measurable disease, the objective response rate was 72.2% with OLA and 51.4% with TPC (odds ratio, 2.53; P = .002). Across all patients, the median progression-free survival was significantly better with OLA (13.4 months) than with TPC (9.2 months; P = .013). Overall survival data were immature.

The superiority of OLA for the primary endpoint was maintained in multiple subgroups of patients, including those who had received only two prior lines of therapy (OR, 3.44) and those who had three or more prior lines (OR, 2.21). Time to first subsequent therapy (HR, 0.48) and time to treatment discontinuation or death (HR, 0.17) were significantly longer for OLA than for TPC.

Adverse events were consistent with the established safety profiles of OLA and chemotherapy. The most common grade 3 or higher adverse events were anemia (21.3%) with OLA and neutropenia (15.8%) and hand-foot syndrome (11.8%) with TPC.

However, median treatment durations were substantially and consistently longer for OLA than for TPC, and there were fewer treatment discontinuations because of toxicity for OLA than for TPC. At the time of data cutoff, 43 patients in the OLA group and 1 patient in the TPC cohort remained on treatment.
 

How these results influence practice

The results of the SOLO3 trial are clear: Treatment with OLA is a reasonable alternative to nonplatinum-containing chemotherapy for women with BRCA mutations and platinum-sensitive ovarian cancer. OLA is a “chemotherapy-free” option for these patients in the second- and later-line settings.

Less clear are the following:

• How many patients with BRCA mutations will not have already received a PARP inhibitor in the frontline maintenance setting in the future? SOLO3 required modification in the accrual target and endpoint because of challenges in patient recruitment from the entry of PARP inhibitors into routine clinical practice.
• Would OLA be superior to a carboplatin doublet rather than a nonplatinum single agent in patients with two prior relapses of platinum-sensitive ovarian cancer? Standard practice would be for patients in the second-line setting to receive a platinum doublet.
• Is extending the platinum-free interval a worthwhile objective, or would some patients prefer a finite interval of a platinum doublet over an indefinite period of treatment with OLA?

All phase 3 clinical trials have limitations since they require years to complete and the applicability of the results are challenged by intercurrent advances in treatment options and diagnostic tests.

However, overall, the results of SOLO3 are impressive and should influence clinical practice for the subset of relapsed ovarian cancer patients who would have qualified to participate in it. OLA represents an important treatment advance for a group of patients who are trying to string together remission after remission, with limited negative impact on quality of life.



Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

In this edition of “Applying research to practice,” I highlight a study suggesting olaparib is helpful in patients BRCA mutations experiencing multiple relapses of ovarian cancer.

SOLO3 was the first phase 3 trial comparing the oral PARP inhibitor olaparib (OLA; 300 mg twice daily) with physician’s choice of intravenous single-agent chemotherapy (TPC) in relapsed high-grade serous or endometroid ovarian, fallopian tube, or primary peritoneal cancer (J Clin Oncol. 2020 Feb 19. doi: 10.1200/JCO.19.02745).

The trial involved 266 BRCA-mutated patients who had received two (approximately 50%) or more lines of platinum-based TPC. All patients were required to be completely platinum sensitive (progression beyond 12 months from last platinum exposure) or partially platinum sensitive (progression within 6-12 months).

Women were randomized to receive either OLA or nonplatinum TPC (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). After an amendment to the study in 2017, the primary endpoint was objective response rate, determined by blinded independent central review, with a variety of secondary endpoints.

Among 223 patients with measurable disease, the objective response rate was 72.2% with OLA and 51.4% with TPC (odds ratio, 2.53; P = .002). Across all patients, the median progression-free survival was significantly better with OLA (13.4 months) than with TPC (9.2 months; P = .013). Overall survival data were immature.

The superiority of OLA for the primary endpoint was maintained in multiple subgroups of patients, including those who had received only two prior lines of therapy (OR, 3.44) and those who had three or more prior lines (OR, 2.21). Time to first subsequent therapy (HR, 0.48) and time to treatment discontinuation or death (HR, 0.17) were significantly longer for OLA than for TPC.

Adverse events were consistent with the established safety profiles of OLA and chemotherapy. The most common grade 3 or higher adverse events were anemia (21.3%) with OLA and neutropenia (15.8%) and hand-foot syndrome (11.8%) with TPC.

However, median treatment durations were substantially and consistently longer for OLA than for TPC, and there were fewer treatment discontinuations because of toxicity for OLA than for TPC. At the time of data cutoff, 43 patients in the OLA group and 1 patient in the TPC cohort remained on treatment.
 

How these results influence practice

The results of the SOLO3 trial are clear: Treatment with OLA is a reasonable alternative to nonplatinum-containing chemotherapy for women with BRCA mutations and platinum-sensitive ovarian cancer. OLA is a “chemotherapy-free” option for these patients in the second- and later-line settings.

Less clear are the following:

• How many patients with BRCA mutations will not have already received a PARP inhibitor in the frontline maintenance setting in the future? SOLO3 required modification in the accrual target and endpoint because of challenges in patient recruitment from the entry of PARP inhibitors into routine clinical practice.
• Would OLA be superior to a carboplatin doublet rather than a nonplatinum single agent in patients with two prior relapses of platinum-sensitive ovarian cancer? Standard practice would be for patients in the second-line setting to receive a platinum doublet.
• Is extending the platinum-free interval a worthwhile objective, or would some patients prefer a finite interval of a platinum doublet over an indefinite period of treatment with OLA?

All phase 3 clinical trials have limitations since they require years to complete and the applicability of the results are challenged by intercurrent advances in treatment options and diagnostic tests.

However, overall, the results of SOLO3 are impressive and should influence clinical practice for the subset of relapsed ovarian cancer patients who would have qualified to participate in it. OLA represents an important treatment advance for a group of patients who are trying to string together remission after remission, with limited negative impact on quality of life.



Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

In Part I of our discussion we introduced the concept of person-generated health data (PGHD), defined as wellness and/or health-related data created, recorded, or gathered by individuals. The ubiquity and remarkable technological progress of personal computing devices, including wearables, smartphones, and tablets, along with the multitude of sensor modalities embedded within these devices, enables a continuous connection with individuals wanting to share information about their behavior and daily life.

Such rich, longitudinal information is now being used in combination with traditional clinical information to predict, diagnose, and formulate treatment plans for diseases, as well as understand the safety and effectiveness of medical interventions.
 

Identifying a disease early

One novel example of digital technologies being used for early identification of disease was a promising 2019 study by Eli Lilly (in collaboration with Apple and Evidation Health) called the Lilly Exploratory Digital Assessment Study.

In this study, the feasibility of using PGHD for identifying physiological and behavioral signatures of cognitive impairment was examined for the purpose of seeking new methods to detect mild cognitive impairment (MCI) in a timely and cost-effective manner. The study enrolled 31 study participants with cognitive impairment and 82 without cognitive impairment. It used consumer-grade sensor technologies (the iPhone, Apple Watch, iPad, and Beddit sleep monitor) to continuously and unobtrusively collect data. Among the information the researchers collected were interaction with the phone keyboard, accelerometer data from the Apple Watch, volume of messages sent/received, and sleep cycles.¹

Courtesy of Evidation Health, Inc.

A total of 16 terabytes of data were collected over the course of 12 weeks. Data were organized into a behaviorgram (See Figure 1) that gives a holistic picture of a day in a patient’s life. A machine learning model was used to distinguish between behaviorgrams of symptomatic versus healthy controls, identifying typing speed, circadian rhythm shifts, and reliance on helper apps, among other things, as differentiating cognitively impaired from healthy controls. These behaviorgrams may someday serve as “fingerprints” of different diseases, with specific diseases displaying predictable patterns. In the near future, digital measures like the ones investigated in this study are likely to be used to help clinicians predict and diagnose disease, as well as to better understand disease progression and treatment response.
 

Leading to better health outcomes

The potential of PGHD to detect diseases early and lead to better health outcomes is being investigated in the Heartline study, a collaboration between Johnson & Johnson and Apple, which is supported by Evidation.²

This study aims to enroll 150,000 adults age 65 years and over to analyze the impact of Apple Watch–based early detection of irregular heart rhythms consistent with atrial fibrillation (AFib). The researchers’ hypothesis is that jointly detecting atrial fibrillation early and providing cardiovascular health programs to new AFib patients, will lead to patients being treated by a medical provider for AFib that otherwise would not have been detected. This, in turn, would lead to these AFib patients decreasing their risks of stroke and other serious cardiovascular events, including death, the study authors speculated.

Presenting new challenges

While PGHD has the potential to help people, it also presents new challenges. It is highly sensitive and personal – it can be as identifying as DNA.³

Cortesy of Evidation Health

The vast amount of data that PGHD can collect from interaction with consumer wearable devices poses serious privacy risks if done improperly. To address those risks, companies like Evidation have built in protections. Evidation has an app, Achievement, that has enlisted a connected population of more than 3.5 million members who earn rewards for performing health-related actions, as tracked by wearables devices and apps. Through the Achievement app (See Figure 2.), members are provided opportunities to join research studies. As part of these studies, data collected from sensors and apps is used by permission of the member so that it is clear how their data are contributing to specific research questions or use cases.

This is a collaborative model of data collection built upon trust and permission and is substantially different than the collection of data from electronic health records (EHRs) – which is typically aggregated, deidentified, and commercialized, often without the patients’ knowledge or consent. Stringent protections, explicit permission, and transparency are absolutely imperative until privacy frameworks for data outside of HIPAA regulation catches up and protects patients from discrimination and unintended uses of their data.

Large connected cohorts can help advance our understanding of public health. In one study run on Achievement during the 2017-2018 flu season, a survey was sent to the Achievement population every week asking about symptoms of influenza-like illness and requesting permission to access historical data from their wearable around the influenza-like illness event.⁴ With the data, it was possible to analyze patterns of activity, sleep, and resting heart rate change around flu events.  Resting heart rate, in particular, is shown to increase during fever and at the population level. In fact, through the use of PGHD, it is possible to use the fraction of people with resting heart rate above their usual baseline as a proxy to quantify the number of infected people in a region.⁵ This resting heart rate–informed flu surveillance method, if refined to increased accuracy, can work in near real time. This means it may be able detect influenza outbreaks days earlier than current epidemiological methods.

Health data generated by connected populations are in the early stages of development. It is clear that it will yield novel insights into health and disease. Only time will tell if it will be able to help clinicians and patients better predict, diagnose, and formulate treatment plans for disease.

Neil Skolnik, M.D. is a professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, and associate director of the Family Medicine Residency Program at Abington Jefferson Health. Luca Foschini PhD, is co-founder & chief data scientist at Evidation Health. Bray Patrick-Lake, MFS, is a patient thought leader and director of strategic partnerships at Evidation Health.

References

1. Chen R et al. Developing measures of cognitive impairment in the real world from consumer-grade multimodal sensor streams. KDD ’19. August 4–8, 2019 Aug 4-8.

2. The Heartline Study. https://www.heartline.com.

3. Foschini L. Privacy of Wearable and Sensors Data (or, the Lack Thereof?). Data Driven Investor, Medium. 2019.

4. Bradshaw B et al. Influenza surveillance using wearable mobile health devices. Online J Public Health Inform. 2019;11(1):e249.

5. Radin JM et al. Harnessing wearable device data to improve state-level real-time surveillance of influenza-like illness in the USA: a population-based study. Lancet Digital Health. 2020. doi: 10.1016/S2589-7500(19)30222-5.

In Part I of our discussion we introduced the concept of person-generated health data (PGHD), defined as wellness and/or health-related data created, recorded, or gathered by individuals. The ubiquity and remarkable technological progress of personal computing devices, including wearables, smartphones, and tablets, along with the multitude of sensor modalities embedded within these devices, enables a continuous connection with individuals wanting to share information about their behavior and daily life.

Such rich, longitudinal information is now being used in combination with traditional clinical information to predict, diagnose, and formulate treatment plans for diseases, as well as understand the safety and effectiveness of medical interventions.
 

Identifying a disease early

One novel example of digital technologies being used for early identification of disease was a promising 2019 study by Eli Lilly (in collaboration with Apple and Evidation Health) called the Lilly Exploratory Digital Assessment Study.

In this study, the feasibility of using PGHD for identifying physiological and behavioral signatures of cognitive impairment was examined for the purpose of seeking new methods to detect mild cognitive impairment (MCI) in a timely and cost-effective manner. The study enrolled 31 study participants with cognitive impairment and 82 without cognitive impairment. It used consumer-grade sensor technologies (the iPhone, Apple Watch, iPad, and Beddit sleep monitor) to continuously and unobtrusively collect data. Among the information the researchers collected were interaction with the phone keyboard, accelerometer data from the Apple Watch, volume of messages sent/received, and sleep cycles.¹

Courtesy of Evidation Health, Inc.

A total of 16 terabytes of data were collected over the course of 12 weeks. Data were organized into a behaviorgram (See Figure 1) that gives a holistic picture of a day in a patient’s life. A machine learning model was used to distinguish between behaviorgrams of symptomatic versus healthy controls, identifying typing speed, circadian rhythm shifts, and reliance on helper apps, among other things, as differentiating cognitively impaired from healthy controls. These behaviorgrams may someday serve as “fingerprints” of different diseases, with specific diseases displaying predictable patterns. In the near future, digital measures like the ones investigated in this study are likely to be used to help clinicians predict and diagnose disease, as well as to better understand disease progression and treatment response.
 

Leading to better health outcomes

The potential of PGHD to detect diseases early and lead to better health outcomes is being investigated in the Heartline study, a collaboration between Johnson & Johnson and Apple, which is supported by Evidation.²

This study aims to enroll 150,000 adults age 65 years and over to analyze the impact of Apple Watch–based early detection of irregular heart rhythms consistent with atrial fibrillation (AFib). The researchers’ hypothesis is that jointly detecting atrial fibrillation early and providing cardiovascular health programs to new AFib patients, will lead to patients being treated by a medical provider for AFib that otherwise would not have been detected. This, in turn, would lead to these AFib patients decreasing their risks of stroke and other serious cardiovascular events, including death, the study authors speculated.

Presenting new challenges

While PGHD has the potential to help people, it also presents new challenges. It is highly sensitive and personal – it can be as identifying as DNA.³

Cortesy of Evidation Health

The vast amount of data that PGHD can collect from interaction with consumer wearable devices poses serious privacy risks if done improperly. To address those risks, companies like Evidation have built in protections. Evidation has an app, Achievement, that has enlisted a connected population of more than 3.5 million members who earn rewards for performing health-related actions, as tracked by wearables devices and apps. Through the Achievement app (See Figure 2.), members are provided opportunities to join research studies. As part of these studies, data collected from sensors and apps is used by permission of the member so that it is clear how their data are contributing to specific research questions or use cases.

This is a collaborative model of data collection built upon trust and permission and is substantially different than the collection of data from electronic health records (EHRs) – which is typically aggregated, deidentified, and commercialized, often without the patients’ knowledge or consent. Stringent protections, explicit permission, and transparency are absolutely imperative until privacy frameworks for data outside of HIPAA regulation catches up and protects patients from discrimination and unintended uses of their data.

Large connected cohorts can help advance our understanding of public health. In one study run on Achievement during the 2017-2018 flu season, a survey was sent to the Achievement population every week asking about symptoms of influenza-like illness and requesting permission to access historical data from their wearable around the influenza-like illness event.⁴ With the data, it was possible to analyze patterns of activity, sleep, and resting heart rate change around flu events.  Resting heart rate, in particular, is shown to increase during fever and at the population level. In fact, through the use of PGHD, it is possible to use the fraction of people with resting heart rate above their usual baseline as a proxy to quantify the number of infected people in a region.⁵ This resting heart rate–informed flu surveillance method, if refined to increased accuracy, can work in near real time. This means it may be able detect influenza outbreaks days earlier than current epidemiological methods.

Health data generated by connected populations are in the early stages of development. It is clear that it will yield novel insights into health and disease. Only time will tell if it will be able to help clinicians and patients better predict, diagnose, and formulate treatment plans for disease.

Neil Skolnik, M.D. is a professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, and associate director of the Family Medicine Residency Program at Abington Jefferson Health. Luca Foschini PhD, is co-founder & chief data scientist at Evidation Health. Bray Patrick-Lake, MFS, is a patient thought leader and director of strategic partnerships at Evidation Health.

References

1. Chen R et al. Developing measures of cognitive impairment in the real world from consumer-grade multimodal sensor streams. KDD ’19. August 4–8, 2019 Aug 4-8.

2. The Heartline Study. https://www.heartline.com.

3. Foschini L. Privacy of Wearable and Sensors Data (or, the Lack Thereof?). Data Driven Investor, Medium. 2019.

4. Bradshaw B et al. Influenza surveillance using wearable mobile health devices. Online J Public Health Inform. 2019;11(1):e249.

5. Radin JM et al. Harnessing wearable device data to improve state-level real-time surveillance of influenza-like illness in the USA: a population-based study. Lancet Digital Health. 2020. doi: 10.1016/S2589-7500(19)30222-5.

In Part I of our discussion we introduced the concept of person-generated health data (PGHD), defined as wellness and/or health-related data created, recorded, or gathered by individuals. The ubiquity and remarkable technological progress of personal computing devices, including wearables, smartphones, and tablets, along with the multitude of sensor modalities embedded within these devices, enables a continuous connection with individuals wanting to share information about their behavior and daily life.

Such rich, longitudinal information is now being used in combination with traditional clinical information to predict, diagnose, and formulate treatment plans for diseases, as well as understand the safety and effectiveness of medical interventions.
 

Identifying a disease early

One novel example of digital technologies being used for early identification of disease was a promising 2019 study by Eli Lilly (in collaboration with Apple and Evidation Health) called the Lilly Exploratory Digital Assessment Study.

In this study, the feasibility of using PGHD for identifying physiological and behavioral signatures of cognitive impairment was examined for the purpose of seeking new methods to detect mild cognitive impairment (MCI) in a timely and cost-effective manner. The study enrolled 31 study participants with cognitive impairment and 82 without cognitive impairment. It used consumer-grade sensor technologies (the iPhone, Apple Watch, iPad, and Beddit sleep monitor) to continuously and unobtrusively collect data. Among the information the researchers collected were interaction with the phone keyboard, accelerometer data from the Apple Watch, volume of messages sent/received, and sleep cycles.¹

Courtesy of Evidation Health, Inc.

A total of 16 terabytes of data were collected over the course of 12 weeks. Data were organized into a behaviorgram (See Figure 1) that gives a holistic picture of a day in a patient’s life. A machine learning model was used to distinguish between behaviorgrams of symptomatic versus healthy controls, identifying typing speed, circadian rhythm shifts, and reliance on helper apps, among other things, as differentiating cognitively impaired from healthy controls. These behaviorgrams may someday serve as “fingerprints” of different diseases, with specific diseases displaying predictable patterns. In the near future, digital measures like the ones investigated in this study are likely to be used to help clinicians predict and diagnose disease, as well as to better understand disease progression and treatment response.
 

Leading to better health outcomes

The potential of PGHD to detect diseases early and lead to better health outcomes is being investigated in the Heartline study, a collaboration between Johnson & Johnson and Apple, which is supported by Evidation.²

This study aims to enroll 150,000 adults age 65 years and over to analyze the impact of Apple Watch–based early detection of irregular heart rhythms consistent with atrial fibrillation (AFib). The researchers’ hypothesis is that jointly detecting atrial fibrillation early and providing cardiovascular health programs to new AFib patients, will lead to patients being treated by a medical provider for AFib that otherwise would not have been detected. This, in turn, would lead to these AFib patients decreasing their risks of stroke and other serious cardiovascular events, including death, the study authors speculated.

Presenting new challenges

While PGHD has the potential to help people, it also presents new challenges. It is highly sensitive and personal – it can be as identifying as DNA.³

Cortesy of Evidation Health

The vast amount of data that PGHD can collect from interaction with consumer wearable devices poses serious privacy risks if done improperly. To address those risks, companies like Evidation have built in protections. Evidation has an app, Achievement, that has enlisted a connected population of more than 3.5 million members who earn rewards for performing health-related actions, as tracked by wearables devices and apps. Through the Achievement app (See Figure 2.), members are provided opportunities to join research studies. As part of these studies, data collected from sensors and apps is used by permission of the member so that it is clear how their data are contributing to specific research questions or use cases.

This is a collaborative model of data collection built upon trust and permission and is substantially different than the collection of data from electronic health records (EHRs) – which is typically aggregated, deidentified, and commercialized, often without the patients’ knowledge or consent. Stringent protections, explicit permission, and transparency are absolutely imperative until privacy frameworks for data outside of HIPAA regulation catches up and protects patients from discrimination and unintended uses of their data.

Large connected cohorts can help advance our understanding of public health. In one study run on Achievement during the 2017-2018 flu season, a survey was sent to the Achievement population every week asking about symptoms of influenza-like illness and requesting permission to access historical data from their wearable around the influenza-like illness event.⁴ With the data, it was possible to analyze patterns of activity, sleep, and resting heart rate change around flu events.  Resting heart rate, in particular, is shown to increase during fever and at the population level. In fact, through the use of PGHD, it is possible to use the fraction of people with resting heart rate above their usual baseline as a proxy to quantify the number of infected people in a region.⁵ This resting heart rate–informed flu surveillance method, if refined to increased accuracy, can work in near real time. This means it may be able detect influenza outbreaks days earlier than current epidemiological methods.

Health data generated by connected populations are in the early stages of development. It is clear that it will yield novel insights into health and disease. Only time will tell if it will be able to help clinicians and patients better predict, diagnose, and formulate treatment plans for disease.

Neil Skolnik, M.D. is a professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, and associate director of the Family Medicine Residency Program at Abington Jefferson Health. Luca Foschini PhD, is co-founder & chief data scientist at Evidation Health. Bray Patrick-Lake, MFS, is a patient thought leader and director of strategic partnerships at Evidation Health.

References

1. Chen R et al. Developing measures of cognitive impairment in the real world from consumer-grade multimodal sensor streams. KDD ’19. August 4–8, 2019 Aug 4-8.

2. The Heartline Study. https://www.heartline.com.

3. Foschini L. Privacy of Wearable and Sensors Data (or, the Lack Thereof?). Data Driven Investor, Medium. 2019.

4. Bradshaw B et al. Influenza surveillance using wearable mobile health devices. Online J Public Health Inform. 2019;11(1):e249.

5. Radin JM et al. Harnessing wearable device data to improve state-level real-time surveillance of influenza-like illness in the USA: a population-based study. Lancet Digital Health. 2020. doi: 10.1016/S2589-7500(19)30222-5.

In 2019, the Food and Drug Administration approved 42 drugs, 6 of which will not be discussed here because of space limitations: recarbrio, a three-drug combination, containing imipenem, cilastatin, and relebactam; polatuzumab (Polivy) combined with bendamustine and a rituximab product; pretomanid combined with bedaquiline and linezolid; romosozumab (Evenity) for postmenopausal women; and alpelisib (Piqray) for postmenopausal women. In addition, darolutamide (Nubeqa) will not be included because it is indicated for the treatment of patients with prostate cancer. The remaining 36 agents are listed alphabetically below with the trade names in parentheses.

PhotoDisk

The molecular weights (if available), rounded to the nearest whole number, are shown in parentheses. As with nearly all drugs, avoiding these agents in pregnancy is the best choice.

Air polymer-type a intrauterine foam (ExEm Foam), an ultrasound contrast agent, is indicated for sonohysterosalpingography to assess fallopian tube patency in women with known or suspected infertility. Animal studies have not been conducted, and the agent is contraindicated in pregnancy.

Afamelanotide implant (Scenesse) (1,647) is a melanocortin 1 receptor agonist that is indicated to increase pain-free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria. The drug caused no embryofetal toxicity in two species of rats. The molecular weight suggests that it will not cross the placenta, at least early in pregnancy.

Alpelisib (Piqray) (441) is a kinase inhibitor that is combined with fulvestrant for the treatment of advanced breast cancer in women and men. The molecular weight suggests that it can cross the human placenta. It is contraindicated in pregnancy because it can cause embryofetal toxicity.

Bremelanotide (Vyleesi) (1,025) is indicated for the treatment of premenopausal women with hypoactive sexual disorder. The drug caused fetal harm in dogs and mice. If a pregnant woman is exposed to the drug, health care providers are encouraged to call the VYLEESI Pregnancy Exposure Registry at 877-411-2510.

Brolucizumab (Beovu) (26,000) is a human vascular endothelial growth factor that is indicated for the treatment of neovascular age-related macular degeneration. In animals, it caused malformations, embryofetal resorption, and decreased fetal weight. Other adverse effects were follicular development, corpus luteum function, and fertility.

Caplacizumab (Cablivi) (28,000) is indicated for the treatment of adult patients with acquired thrombotic thrombocytopenia purpura, in combination with plasma exchange and immunosuppressive therapy. If used in pregnancy, there is a risk of hemorrhage in the mother and fetus. In guinea pigs given intramuscular doses of the drug, there was no evidence of adverse developmental outcomes.

Cefiderocol (Fetroja) (3,044) is an IV cephalosporin antibiotic indicated for the treatment of urinary tract infections, including pyelonephritis. The manufacturer states that it should be used in patients 18 years of age or older who have limited or no alternative treatment options. Consistent with other cephalosporins, no developmental adverse effects were observed in rats and mice.

Cenobamate (Xcopri) (268) is indicated for the treatment of partial-onset seizures in adults. In pregnant animals given the drug, there was increased embryo-fetal mortality, decreased fetal and offspring body weight, and neurobehavioral and reproductive impairment in offspring. If a pregnant woman receives this drug, encourage her to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling the toll-free number 1-888-233-2334.

Crizanlizumab (Adakveo) (146,000) is indicated to reduce the frequency of vaso-occlusive crises in patients with sickle cell disease. In monkeys given doses slightly higher than those given to humans, there was increased fetal loss (abortions/stillbirths).

Entrectinib (Rozlytrek) (561) is a kinase inhibitor indicated for the treatment of cancer. The drug was teratogenic in rats. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.

Erdafitinib (Balversa) (447), a kinase inhibitor, is indicated for the treatment of locally advanced or metastatic urothelial carcinoma. In rats given doses during organogenesis with maternal exposures less than human exposures, the drug was teratogenic and caused embryofetal death. The manufacturer states that women of reproductive potential should use effective contraception during treatment and for 1 month after the last dose. The same advice was provided for male patients with female partners of reproductive potential. It is contraindicated in pregnancy because it can cause embryofetal toxicity.

Fedratinib (Inrebic) (616), a kinase inhibitor, is indicated for patients with intermediate-2 or high-risk primary or secondary myelofibrosis. The drug was teratogenic in rats when doses that were about 0.1 times the human exposure based on AUC (area under the curve) at the recommended daily dose during organogenesis. It is contraindicated in pregnancy because it can cause embryofetal toxicity.

Fluorodopa f18 (214) is a radioactive diagnostic agent. It is indicated for use in positron emission tomography to visualize dopaminergic nerve terminals in the striatum for evaluation of adult patients with suspected parkinsonian syndromes. The potential for adverse pregnant outcomes is based on the radiation dose and the gestational timing of exposure.

Givosiran sodium (Givlaari) (17,2460) is an aminolevulinate synthase 1-directed small interfering RNA given subcutaneously. It is indicated for the treatment of adults with acute hepatic porphyria. Doses less than 10 times the human dose in rats and rabbits produced maternal toxicity. In rats there was increased postimplantation loss, and in rats there was skeletal variation (incomplete ossification of pubes).

Golodirsen (Vyondys 53) (8,647) is indicated for the treatment of Duchenne muscular dystrophy given intravenously. There are no human or animal data available to assess the use of this drug during pregnancy.

Istradefylline (Nourianz) (384) is an adenosine receptor antagonist given orally. It is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. In pregnant rats and rabbits, the drug was related to teratogenicity, embryo-fetal and offspring mortality, and growth deficits at clinically relevant exposures.

Lasmiditan (Reyvow) (436), a serotonin receptor agonist, is indicated for acute treatment of migraine with or without aura. In animals, the drug caused increased incidences of fetal defects, increased embryo-fetal and offspring mortality, and decreased fetal body weight at maternal exposures less than (rabbits) or greater than (rat) those observed clinically.

Lefamulin (Xenleta) (568) is an antibacterial agent available for oral and IV administration. They are indicated for the treatment of community-acquired bacterial pneumonia. The drug was teratogenic in rats at systemic exposures lower than those in humans, an increased incidence of post-implantation fetal loss and stillbirths, and decreased fetal body weights and ossification. There was also an apparent delay in sexual maturation in rats.

Luspatercept (Reblozyl) (76,000) is given subcutaneously for the treatment of anemia in patients with beta thalassemia who require regular red blood cell transfusions. In rats and rabbits, the drug cause increased embryo-fetal mortality, alteration to growth, and structural defects at exposures (based on AUC) that were about 13 times (rats) and 18 times (rabbits) the maximum recommended human dose.

Pexidartinib (Turalio) (454) is an oral kinase inhibitor that is indicated for the treatment of symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations and not amenable with surgery. In rats and rabbits, the drug caused malformations, increased post-implantation loss, and abortion at exposures nearly equal to the human exposure. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.

Pitolisant HCl (Wakix) (296) is an histamine-3 receptor antagonist/inverse agonist indicated for the treatment of excessive daytime sleepiness in patients with narcolepsy. The drug has caused maternal and embryofetal toxicity in rats and rabbits at doses greater than and equal to 13 times and greater than 4 times the maximum human dose, respectively. The manufacturer has a pregnancy exposure registry that patients can contact at 1-800-833-7460.

Prabotulinum toxin A (Jeuveau) (900,000) is an acetylcholine release inhibitor and a neuromuscular blocking agent indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity. The drug caused no adverse embryo-fetal in rats with doses up to 12 times the human dose.

Risankizumab-rzaa (Skyrizi) (molecular weight unknown), an interleukin-23 antagonist, is used for the treatment of moderate-to-severe plaque psoriasis. In pregnant monkeys, doses that were 20 times the maximum human dose increased fetal/infant loss.

Selinexor (Xpovio) (443) is an oral nuclear export inhibitor given in combination with dexamethasone for the treatment of relapsed or refractory myeloma. At doses lower than those used clinically, the drug caused structural abnormalities and alterations to growth in fetal rats.

Siponimod (Mayzent) (1,149) is an oral sphingosine 1-phosphate receptor modulator. It is indicated for the treatment of relapsing forms of multiple sclerosis. At low doses, the drug caused embryotoxicity and fetotoxicity in rats and rabbits including embryofetal deaths and abortions. The drug was teratogenic in both species.

Solriamfetol (Sunosi) (231) is an oral dopamine and norepinephrine reuptake inhibitor that is indicated to improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea. The drug caused maternal and fetal toxicities in rats and rabbits and was teratogenic. The manufacturer has a pregnancy exposure registry to monitor pregnancy outcomes. Health care providers or patients can enroll in the program by calling 1-877-283-6220 or contacting the company.

Tafamidis meglumine (Vyndaqel) (503) and tafamidis (Vyndamax) (308) are indicated for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis to reduce cardiovascular mortality and cardiovascular-related hospitalization. In rabbits and rats, use of the drugs during pregnancy caused birth defects, embryo-fetal mortality, and fetal body weight reduction. Limited available data with Vyndaqel use in human pregnancy at a dose of 20 mg/day have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see package insert).

Tenapanor (Ibsrela) (1,218) is indicated for the treatment of irritable bowel syndrome with constipation. The drug is minimally absorbed systemically, with plasma concentrations below the limit of quantification. No adverse maternal or fetal outcomes in rats or rabbits were observed. As reported by the manufacturer, in a small number of pregnant women, no drug-induced adverse maternal or fetal outcomes were identified.

Triclabendazole (Egaten) (360), an oral anthelmintic, is indicated for the treatment of fascioliasis. The drug was not teratogenic in mice and rabbits.

Trifarotene (Aklief) (460) cream is a retinoid that is indicated for the topical treatment of acne vulgaris. Animal data was related to oral retinoids and it not applicable to this agent. The manufacturer reported that available data from the use of the cream in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Upadacitinib (Rinvoq) (389) is an oral Janus inhibitor. It is indicated for the treatment of moderate to severe active rheumatoid arthritis in patients who have had an inadequate response or intolerance to methotrexate. The drug caused increases in fetal malformations when given to rats and rabbits during organogenesis.

Voxelotor (Oxbryta) (337) is an oral hemoglobin S polymerization inhibitor indicated for the treatment of sickle cell disease. In rats and rabbits, there was no evidence of adverse developmental outcomes.

Zanubrutinib (Brukinsa) (472), an oral kinase inhibitor, is indicated for the treatment of mantle cell lymphoma. The drug caused embryofetal toxicity in pregnant rats, including malformations. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.

Breastfeeding

Brexanolone (Zulresso) (319) is indicated for the treatment of postpartum depression. It is given as a continuous IV infusion over 60 hours. The drug, at exposures close to those seen in humans, did not cause structural defects in rabbits and rats, but did cause fetal toxicity. Because patients are at risk of excessive sedation or sudden loss of consciousness when receiving the drug, it is only available through a restricted program called the ZULRESSO REMS. Health care providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 844-405-6185. To obtain a list of health care facilities enrolled in the program call 844-472-4379.

Nearly all of the above drugs will cross into a woman’s colostrum during the first 48 hours post partum. These amounts should be very small, but not breastfeeding is the best choice.
 

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

In 2019, the Food and Drug Administration approved 42 drugs, 6 of which will not be discussed here because of space limitations: recarbrio, a three-drug combination, containing imipenem, cilastatin, and relebactam; polatuzumab (Polivy) combined with bendamustine and a rituximab product; pretomanid combined with bedaquiline and linezolid; romosozumab (Evenity) for postmenopausal women; and alpelisib (Piqray) for postmenopausal women. In addition, darolutamide (Nubeqa) will not be included because it is indicated for the treatment of patients with prostate cancer. The remaining 36 agents are listed alphabetically below with the trade names in parentheses.

PhotoDisk

The molecular weights (if available), rounded to the nearest whole number, are shown in parentheses. As with nearly all drugs, avoiding these agents in pregnancy is the best choice.

Air polymer-type a intrauterine foam (ExEm Foam), an ultrasound contrast agent, is indicated for sonohysterosalpingography to assess fallopian tube patency in women with known or suspected infertility. Animal studies have not been conducted, and the agent is contraindicated in pregnancy.

Afamelanotide implant (Scenesse) (1,647) is a melanocortin 1 receptor agonist that is indicated to increase pain-free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria. The drug caused no embryofetal toxicity in two species of rats. The molecular weight suggests that it will not cross the placenta, at least early in pregnancy.

Alpelisib (Piqray) (441) is a kinase inhibitor that is combined with fulvestrant for the treatment of advanced breast cancer in women and men. The molecular weight suggests that it can cross the human placenta. It is contraindicated in pregnancy because it can cause embryofetal toxicity.

Bremelanotide (Vyleesi) (1,025) is indicated for the treatment of premenopausal women with hypoactive sexual disorder. The drug caused fetal harm in dogs and mice. If a pregnant woman is exposed to the drug, health care providers are encouraged to call the VYLEESI Pregnancy Exposure Registry at 877-411-2510.

Brolucizumab (Beovu) (26,000) is a human vascular endothelial growth factor that is indicated for the treatment of neovascular age-related macular degeneration. In animals, it caused malformations, embryofetal resorption, and decreased fetal weight. Other adverse effects were follicular development, corpus luteum function, and fertility.

Caplacizumab (Cablivi) (28,000) is indicated for the treatment of adult patients with acquired thrombotic thrombocytopenia purpura, in combination with plasma exchange and immunosuppressive therapy. If used in pregnancy, there is a risk of hemorrhage in the mother and fetus. In guinea pigs given intramuscular doses of the drug, there was no evidence of adverse developmental outcomes.

Cefiderocol (Fetroja) (3,044) is an IV cephalosporin antibiotic indicated for the treatment of urinary tract infections, including pyelonephritis. The manufacturer states that it should be used in patients 18 years of age or older who have limited or no alternative treatment options. Consistent with other cephalosporins, no developmental adverse effects were observed in rats and mice.

Cenobamate (Xcopri) (268) is indicated for the treatment of partial-onset seizures in adults. In pregnant animals given the drug, there was increased embryo-fetal mortality, decreased fetal and offspring body weight, and neurobehavioral and reproductive impairment in offspring. If a pregnant woman receives this drug, encourage her to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling the toll-free number 1-888-233-2334.

Crizanlizumab (Adakveo) (146,000) is indicated to reduce the frequency of vaso-occlusive crises in patients with sickle cell disease. In monkeys given doses slightly higher than those given to humans, there was increased fetal loss (abortions/stillbirths).

Entrectinib (Rozlytrek) (561) is a kinase inhibitor indicated for the treatment of cancer. The drug was teratogenic in rats. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.

Erdafitinib (Balversa) (447), a kinase inhibitor, is indicated for the treatment of locally advanced or metastatic urothelial carcinoma. In rats given doses during organogenesis with maternal exposures less than human exposures, the drug was teratogenic and caused embryofetal death. The manufacturer states that women of reproductive potential should use effective contraception during treatment and for 1 month after the last dose. The same advice was provided for male patients with female partners of reproductive potential. It is contraindicated in pregnancy because it can cause embryofetal toxicity.

Fedratinib (Inrebic) (616), a kinase inhibitor, is indicated for patients with intermediate-2 or high-risk primary or secondary myelofibrosis. The drug was teratogenic in rats when doses that were about 0.1 times the human exposure based on AUC (area under the curve) at the recommended daily dose during organogenesis. It is contraindicated in pregnancy because it can cause embryofetal toxicity.

Fluorodopa f18 (214) is a radioactive diagnostic agent. It is indicated for use in positron emission tomography to visualize dopaminergic nerve terminals in the striatum for evaluation of adult patients with suspected parkinsonian syndromes. The potential for adverse pregnant outcomes is based on the radiation dose and the gestational timing of exposure.

Givosiran sodium (Givlaari) (17,2460) is an aminolevulinate synthase 1-directed small interfering RNA given subcutaneously. It is indicated for the treatment of adults with acute hepatic porphyria. Doses less than 10 times the human dose in rats and rabbits produced maternal toxicity. In rats there was increased postimplantation loss, and in rats there was skeletal variation (incomplete ossification of pubes).

Golodirsen (Vyondys 53) (8,647) is indicated for the treatment of Duchenne muscular dystrophy given intravenously. There are no human or animal data available to assess the use of this drug during pregnancy.

Istradefylline (Nourianz) (384) is an adenosine receptor antagonist given orally. It is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. In pregnant rats and rabbits, the drug was related to teratogenicity, embryo-fetal and offspring mortality, and growth deficits at clinically relevant exposures.

Lasmiditan (Reyvow) (436), a serotonin receptor agonist, is indicated for acute treatment of migraine with or without aura. In animals, the drug caused increased incidences of fetal defects, increased embryo-fetal and offspring mortality, and decreased fetal body weight at maternal exposures less than (rabbits) or greater than (rat) those observed clinically.

Lefamulin (Xenleta) (568) is an antibacterial agent available for oral and IV administration. They are indicated for the treatment of community-acquired bacterial pneumonia. The drug was teratogenic in rats at systemic exposures lower than those in humans, an increased incidence of post-implantation fetal loss and stillbirths, and decreased fetal body weights and ossification. There was also an apparent delay in sexual maturation in rats.

Luspatercept (Reblozyl) (76,000) is given subcutaneously for the treatment of anemia in patients with beta thalassemia who require regular red blood cell transfusions. In rats and rabbits, the drug cause increased embryo-fetal mortality, alteration to growth, and structural defects at exposures (based on AUC) that were about 13 times (rats) and 18 times (rabbits) the maximum recommended human dose.

Pexidartinib (Turalio) (454) is an oral kinase inhibitor that is indicated for the treatment of symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations and not amenable with surgery. In rats and rabbits, the drug caused malformations, increased post-implantation loss, and abortion at exposures nearly equal to the human exposure. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.

Pitolisant HCl (Wakix) (296) is an histamine-3 receptor antagonist/inverse agonist indicated for the treatment of excessive daytime sleepiness in patients with narcolepsy. The drug has caused maternal and embryofetal toxicity in rats and rabbits at doses greater than and equal to 13 times and greater than 4 times the maximum human dose, respectively. The manufacturer has a pregnancy exposure registry that patients can contact at 1-800-833-7460.

Prabotulinum toxin A (Jeuveau) (900,000) is an acetylcholine release inhibitor and a neuromuscular blocking agent indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity. The drug caused no adverse embryo-fetal in rats with doses up to 12 times the human dose.

Risankizumab-rzaa (Skyrizi) (molecular weight unknown), an interleukin-23 antagonist, is used for the treatment of moderate-to-severe plaque psoriasis. In pregnant monkeys, doses that were 20 times the maximum human dose increased fetal/infant loss.

Selinexor (Xpovio) (443) is an oral nuclear export inhibitor given in combination with dexamethasone for the treatment of relapsed or refractory myeloma. At doses lower than those used clinically, the drug caused structural abnormalities and alterations to growth in fetal rats.

Siponimod (Mayzent) (1,149) is an oral sphingosine 1-phosphate receptor modulator. It is indicated for the treatment of relapsing forms of multiple sclerosis. At low doses, the drug caused embryotoxicity and fetotoxicity in rats and rabbits including embryofetal deaths and abortions. The drug was teratogenic in both species.

Solriamfetol (Sunosi) (231) is an oral dopamine and norepinephrine reuptake inhibitor that is indicated to improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea. The drug caused maternal and fetal toxicities in rats and rabbits and was teratogenic. The manufacturer has a pregnancy exposure registry to monitor pregnancy outcomes. Health care providers or patients can enroll in the program by calling 1-877-283-6220 or contacting the company.

Tafamidis meglumine (Vyndaqel) (503) and tafamidis (Vyndamax) (308) are indicated for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis to reduce cardiovascular mortality and cardiovascular-related hospitalization. In rabbits and rats, use of the drugs during pregnancy caused birth defects, embryo-fetal mortality, and fetal body weight reduction. Limited available data with Vyndaqel use in human pregnancy at a dose of 20 mg/day have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see package insert).

Tenapanor (Ibsrela) (1,218) is indicated for the treatment of irritable bowel syndrome with constipation. The drug is minimally absorbed systemically, with plasma concentrations below the limit of quantification. No adverse maternal or fetal outcomes in rats or rabbits were observed. As reported by the manufacturer, in a small number of pregnant women, no drug-induced adverse maternal or fetal outcomes were identified.

Triclabendazole (Egaten) (360), an oral anthelmintic, is indicated for the treatment of fascioliasis. The drug was not teratogenic in mice and rabbits.

Trifarotene (Aklief) (460) cream is a retinoid that is indicated for the topical treatment of acne vulgaris. Animal data was related to oral retinoids and it not applicable to this agent. The manufacturer reported that available data from the use of the cream in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Upadacitinib (Rinvoq) (389) is an oral Janus inhibitor. It is indicated for the treatment of moderate to severe active rheumatoid arthritis in patients who have had an inadequate response or intolerance to methotrexate. The drug caused increases in fetal malformations when given to rats and rabbits during organogenesis.

Voxelotor (Oxbryta) (337) is an oral hemoglobin S polymerization inhibitor indicated for the treatment of sickle cell disease. In rats and rabbits, there was no evidence of adverse developmental outcomes.

Zanubrutinib (Brukinsa) (472), an oral kinase inhibitor, is indicated for the treatment of mantle cell lymphoma. The drug caused embryofetal toxicity in pregnant rats, including malformations. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.

Breastfeeding

Brexanolone (Zulresso) (319) is indicated for the treatment of postpartum depression. It is given as a continuous IV infusion over 60 hours. The drug, at exposures close to those seen in humans, did not cause structural defects in rabbits and rats, but did cause fetal toxicity. Because patients are at risk of excessive sedation or sudden loss of consciousness when receiving the drug, it is only available through a restricted program called the ZULRESSO REMS. Health care providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 844-405-6185. To obtain a list of health care facilities enrolled in the program call 844-472-4379.

Nearly all of the above drugs will cross into a woman’s colostrum during the first 48 hours post partum. These amounts should be very small, but not breastfeeding is the best choice.
 

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

In 2019, the Food and Drug Administration approved 42 drugs, 6 of which will not be discussed here because of space limitations: recarbrio, a three-drug combination, containing imipenem, cilastatin, and relebactam; polatuzumab (Polivy) combined with bendamustine and a rituximab product; pretomanid combined with bedaquiline and linezolid; romosozumab (Evenity) for postmenopausal women; and alpelisib (Piqray) for postmenopausal women. In addition, darolutamide (Nubeqa) will not be included because it is indicated for the treatment of patients with prostate cancer. The remaining 36 agents are listed alphabetically below with the trade names in parentheses.

PhotoDisk

The molecular weights (if available), rounded to the nearest whole number, are shown in parentheses. As with nearly all drugs, avoiding these agents in pregnancy is the best choice.

Air polymer-type a intrauterine foam (ExEm Foam), an ultrasound contrast agent, is indicated for sonohysterosalpingography to assess fallopian tube patency in women with known or suspected infertility. Animal studies have not been conducted, and the agent is contraindicated in pregnancy.

Afamelanotide implant (Scenesse) (1,647) is a melanocortin 1 receptor agonist that is indicated to increase pain-free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria. The drug caused no embryofetal toxicity in two species of rats. The molecular weight suggests that it will not cross the placenta, at least early in pregnancy.

Alpelisib (Piqray) (441) is a kinase inhibitor that is combined with fulvestrant for the treatment of advanced breast cancer in women and men. The molecular weight suggests that it can cross the human placenta. It is contraindicated in pregnancy because it can cause embryofetal toxicity.

Bremelanotide (Vyleesi) (1,025) is indicated for the treatment of premenopausal women with hypoactive sexual disorder. The drug caused fetal harm in dogs and mice. If a pregnant woman is exposed to the drug, health care providers are encouraged to call the VYLEESI Pregnancy Exposure Registry at 877-411-2510.

Brolucizumab (Beovu) (26,000) is a human vascular endothelial growth factor that is indicated for the treatment of neovascular age-related macular degeneration. In animals, it caused malformations, embryofetal resorption, and decreased fetal weight. Other adverse effects were follicular development, corpus luteum function, and fertility.

Caplacizumab (Cablivi) (28,000) is indicated for the treatment of adult patients with acquired thrombotic thrombocytopenia purpura, in combination with plasma exchange and immunosuppressive therapy. If used in pregnancy, there is a risk of hemorrhage in the mother and fetus. In guinea pigs given intramuscular doses of the drug, there was no evidence of adverse developmental outcomes.

Cefiderocol (Fetroja) (3,044) is an IV cephalosporin antibiotic indicated for the treatment of urinary tract infections, including pyelonephritis. The manufacturer states that it should be used in patients 18 years of age or older who have limited or no alternative treatment options. Consistent with other cephalosporins, no developmental adverse effects were observed in rats and mice.

Cenobamate (Xcopri) (268) is indicated for the treatment of partial-onset seizures in adults. In pregnant animals given the drug, there was increased embryo-fetal mortality, decreased fetal and offspring body weight, and neurobehavioral and reproductive impairment in offspring. If a pregnant woman receives this drug, encourage her to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling the toll-free number 1-888-233-2334.

Crizanlizumab (Adakveo) (146,000) is indicated to reduce the frequency of vaso-occlusive crises in patients with sickle cell disease. In monkeys given doses slightly higher than those given to humans, there was increased fetal loss (abortions/stillbirths).

Entrectinib (Rozlytrek) (561) is a kinase inhibitor indicated for the treatment of cancer. The drug was teratogenic in rats. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.

Erdafitinib (Balversa) (447), a kinase inhibitor, is indicated for the treatment of locally advanced or metastatic urothelial carcinoma. In rats given doses during organogenesis with maternal exposures less than human exposures, the drug was teratogenic and caused embryofetal death. The manufacturer states that women of reproductive potential should use effective contraception during treatment and for 1 month after the last dose. The same advice was provided for male patients with female partners of reproductive potential. It is contraindicated in pregnancy because it can cause embryofetal toxicity.

Fedratinib (Inrebic) (616), a kinase inhibitor, is indicated for patients with intermediate-2 or high-risk primary or secondary myelofibrosis. The drug was teratogenic in rats when doses that were about 0.1 times the human exposure based on AUC (area under the curve) at the recommended daily dose during organogenesis. It is contraindicated in pregnancy because it can cause embryofetal toxicity.

Fluorodopa f18 (214) is a radioactive diagnostic agent. It is indicated for use in positron emission tomography to visualize dopaminergic nerve terminals in the striatum for evaluation of adult patients with suspected parkinsonian syndromes. The potential for adverse pregnant outcomes is based on the radiation dose and the gestational timing of exposure.

Givosiran sodium (Givlaari) (17,2460) is an aminolevulinate synthase 1-directed small interfering RNA given subcutaneously. It is indicated for the treatment of adults with acute hepatic porphyria. Doses less than 10 times the human dose in rats and rabbits produced maternal toxicity. In rats there was increased postimplantation loss, and in rats there was skeletal variation (incomplete ossification of pubes).

Golodirsen (Vyondys 53) (8,647) is indicated for the treatment of Duchenne muscular dystrophy given intravenously. There are no human or animal data available to assess the use of this drug during pregnancy.

Istradefylline (Nourianz) (384) is an adenosine receptor antagonist given orally. It is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. In pregnant rats and rabbits, the drug was related to teratogenicity, embryo-fetal and offspring mortality, and growth deficits at clinically relevant exposures.

Lasmiditan (Reyvow) (436), a serotonin receptor agonist, is indicated for acute treatment of migraine with or without aura. In animals, the drug caused increased incidences of fetal defects, increased embryo-fetal and offspring mortality, and decreased fetal body weight at maternal exposures less than (rabbits) or greater than (rat) those observed clinically.

Lefamulin (Xenleta) (568) is an antibacterial agent available for oral and IV administration. They are indicated for the treatment of community-acquired bacterial pneumonia. The drug was teratogenic in rats at systemic exposures lower than those in humans, an increased incidence of post-implantation fetal loss and stillbirths, and decreased fetal body weights and ossification. There was also an apparent delay in sexual maturation in rats.

Luspatercept (Reblozyl) (76,000) is given subcutaneously for the treatment of anemia in patients with beta thalassemia who require regular red blood cell transfusions. In rats and rabbits, the drug cause increased embryo-fetal mortality, alteration to growth, and structural defects at exposures (based on AUC) that were about 13 times (rats) and 18 times (rabbits) the maximum recommended human dose.

Pexidartinib (Turalio) (454) is an oral kinase inhibitor that is indicated for the treatment of symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations and not amenable with surgery. In rats and rabbits, the drug caused malformations, increased post-implantation loss, and abortion at exposures nearly equal to the human exposure. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.

Pitolisant HCl (Wakix) (296) is an histamine-3 receptor antagonist/inverse agonist indicated for the treatment of excessive daytime sleepiness in patients with narcolepsy. The drug has caused maternal and embryofetal toxicity in rats and rabbits at doses greater than and equal to 13 times and greater than 4 times the maximum human dose, respectively. The manufacturer has a pregnancy exposure registry that patients can contact at 1-800-833-7460.

Prabotulinum toxin A (Jeuveau) (900,000) is an acetylcholine release inhibitor and a neuromuscular blocking agent indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity. The drug caused no adverse embryo-fetal in rats with doses up to 12 times the human dose.

Risankizumab-rzaa (Skyrizi) (molecular weight unknown), an interleukin-23 antagonist, is used for the treatment of moderate-to-severe plaque psoriasis. In pregnant monkeys, doses that were 20 times the maximum human dose increased fetal/infant loss.

Selinexor (Xpovio) (443) is an oral nuclear export inhibitor given in combination with dexamethasone for the treatment of relapsed or refractory myeloma. At doses lower than those used clinically, the drug caused structural abnormalities and alterations to growth in fetal rats.

Siponimod (Mayzent) (1,149) is an oral sphingosine 1-phosphate receptor modulator. It is indicated for the treatment of relapsing forms of multiple sclerosis. At low doses, the drug caused embryotoxicity and fetotoxicity in rats and rabbits including embryofetal deaths and abortions. The drug was teratogenic in both species.

Solriamfetol (Sunosi) (231) is an oral dopamine and norepinephrine reuptake inhibitor that is indicated to improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea. The drug caused maternal and fetal toxicities in rats and rabbits and was teratogenic. The manufacturer has a pregnancy exposure registry to monitor pregnancy outcomes. Health care providers or patients can enroll in the program by calling 1-877-283-6220 or contacting the company.

Tafamidis meglumine (Vyndaqel) (503) and tafamidis (Vyndamax) (308) are indicated for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis to reduce cardiovascular mortality and cardiovascular-related hospitalization. In rabbits and rats, use of the drugs during pregnancy caused birth defects, embryo-fetal mortality, and fetal body weight reduction. Limited available data with Vyndaqel use in human pregnancy at a dose of 20 mg/day have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see package insert).

Tenapanor (Ibsrela) (1,218) is indicated for the treatment of irritable bowel syndrome with constipation. The drug is minimally absorbed systemically, with plasma concentrations below the limit of quantification. No adverse maternal or fetal outcomes in rats or rabbits were observed. As reported by the manufacturer, in a small number of pregnant women, no drug-induced adverse maternal or fetal outcomes were identified.

Triclabendazole (Egaten) (360), an oral anthelmintic, is indicated for the treatment of fascioliasis. The drug was not teratogenic in mice and rabbits.

Trifarotene (Aklief) (460) cream is a retinoid that is indicated for the topical treatment of acne vulgaris. Animal data was related to oral retinoids and it not applicable to this agent. The manufacturer reported that available data from the use of the cream in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Upadacitinib (Rinvoq) (389) is an oral Janus inhibitor. It is indicated for the treatment of moderate to severe active rheumatoid arthritis in patients who have had an inadequate response or intolerance to methotrexate. The drug caused increases in fetal malformations when given to rats and rabbits during organogenesis.

Voxelotor (Oxbryta) (337) is an oral hemoglobin S polymerization inhibitor indicated for the treatment of sickle cell disease. In rats and rabbits, there was no evidence of adverse developmental outcomes.

Zanubrutinib (Brukinsa) (472), an oral kinase inhibitor, is indicated for the treatment of mantle cell lymphoma. The drug caused embryofetal toxicity in pregnant rats, including malformations. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.

Breastfeeding

Brexanolone (Zulresso) (319) is indicated for the treatment of postpartum depression. It is given as a continuous IV infusion over 60 hours. The drug, at exposures close to those seen in humans, did not cause structural defects in rabbits and rats, but did cause fetal toxicity. Because patients are at risk of excessive sedation or sudden loss of consciousness when receiving the drug, it is only available through a restricted program called the ZULRESSO REMS. Health care providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 844-405-6185. To obtain a list of health care facilities enrolled in the program call 844-472-4379.

Nearly all of the above drugs will cross into a woman’s colostrum during the first 48 hours post partum. These amounts should be very small, but not breastfeeding is the best choice.
 

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at [email protected].

On January 30, 2020, the World Health Organization declared the outbreak of coronavirus disease 2019 (COVID-19) a public health emergency of international concern.¹ Severe acute respiratory syndrome–associated coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is an enveloped, single-stranded RNA virus. It is the seventh known coronavirus to infect humans and third zoonotic Coronaviridae to cause fatal respiratory illness, along with SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV).² There has been a rapid shift in the geographic center of the outbreak as well as the numbers of confirmed cases and deaths. Although the first cases in late 2019 and early 2020 were in China, by mid-March Italy became the center of the pandemic, with a steep increase in the number of cases in other European countries and the United States.³ Although COVID-19 does not have known dermatologic manifestations, it has the potential for wide-reaching impact on our field.

Strained Resources

In the United States, COVID-19 initially was associated with international travel but is now rapidly spreading throughout the community. I am currently a dermatology resident at New York-Presbyterian, Columbia campus, in New York, New York, a city that unfortunately finds itself underprepared to handle this unprecedented crisis. As of Monday, March 16, 2020, New York-Presbyterian made the decision to postpone all elective procedures, including Mohs micrographic surgery, to preserve hospital resources, including trained personnel, personal protective equipment, ventilators, and hospital beds. There have not been clear-cut guidelines regarding how to approach other dermatologic care for our patients, including routine clinic visits and inpatient dermatology consultations, leaving decisions up to individual departments and providers.

It would be prudent to learn from our colleagues in China who report steps that have been successful in preventing nosocomial spread of COVID-19 in the dermatologic setting. Tao et al⁴ described their protocols in both the outpatient and inpatient dermatologic setting, beginning with strict triage before patients can even enter a clinic building for their outpatient appointment. Those who screen positive are sent to a fever clinic for further evaluation, which may include a rapid computed tomography scan (using a machine that may perform 200 chest computed tomography scans per day) and SARS-CoV-2 polymerase chain reaction.⁵ For inpatient dermatologic consultation of patients with known COVID-19, telehealth and multidisciplinary meetings are first and second line, respectively, with bedside dermatologic consultation as a last resort.⁴ Chen et al⁶ described similarly strict triage protocols as well as physician use of full-body personal protective equipment during all patient encounters. These measures are taken in light of the well-documented phenomenon of asymptomatic carriage and transmission, as all patients entering their dermatologic clinics have screened negative for symptomatic SARS-CoV-2 infection.⁶

Conferences and Education

Coronavirus is impacting the education of millions of individuals worldwide, including that of dermatology residents. The Annual Meeting of the American Academy of Dermatology, which was scheduled to take place in March 2020, was canceled due to COVID-19.⁷ The American Board of Dermatology has released a statement indicating that for all dermatology residents, time spent in COVID-19–mandated quarantine will count as clinical education if residents are able to work with their program to complete independent structured academic activity during that time.⁸ We also must consider the possibility that dermatology residents are reassigned to work outside of our specialty, resulting in less time and experience caring for patients with dermatologic conditions. Dermatologists in other countries have been called upon to care for COVID-19 patients, even reported to be working in intensive care units in Italy.⁹ Virtual technologies may be used in novel ways to support dermatology resident education throughout this process.

Final Thoughts

As physicians, dermatologists are in the position to educate their patients regarding prevention strategies, especially given that the lay press disseminates confusing and inaccurate information. The World Health Organization provides specific guidance, focusing on handwashing, respiratory hygiene, social distancing, and encouraging symptomatic patients to seek remote care whenever possible.¹⁰ Many of our patients are at high risk of complications due to COVID-19, whether due to their age or because they are immunocompromised. As the situation unfolds, the impact on and role of dermatology in this crisis will continue to evolve.

On January 30, 2020, the World Health Organization declared the outbreak of coronavirus disease 2019 (COVID-19) a public health emergency of international concern.¹ Severe acute respiratory syndrome–associated coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is an enveloped, single-stranded RNA virus. It is the seventh known coronavirus to infect humans and third zoonotic Coronaviridae to cause fatal respiratory illness, along with SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV).² There has been a rapid shift in the geographic center of the outbreak as well as the numbers of confirmed cases and deaths. Although the first cases in late 2019 and early 2020 were in China, by mid-March Italy became the center of the pandemic, with a steep increase in the number of cases in other European countries and the United States.³ Although COVID-19 does not have known dermatologic manifestations, it has the potential for wide-reaching impact on our field.

Strained Resources

In the United States, COVID-19 initially was associated with international travel but is now rapidly spreading throughout the community. I am currently a dermatology resident at New York-Presbyterian, Columbia campus, in New York, New York, a city that unfortunately finds itself underprepared to handle this unprecedented crisis. As of Monday, March 16, 2020, New York-Presbyterian made the decision to postpone all elective procedures, including Mohs micrographic surgery, to preserve hospital resources, including trained personnel, personal protective equipment, ventilators, and hospital beds. There have not been clear-cut guidelines regarding how to approach other dermatologic care for our patients, including routine clinic visits and inpatient dermatology consultations, leaving decisions up to individual departments and providers.

It would be prudent to learn from our colleagues in China who report steps that have been successful in preventing nosocomial spread of COVID-19 in the dermatologic setting. Tao et al⁴ described their protocols in both the outpatient and inpatient dermatologic setting, beginning with strict triage before patients can even enter a clinic building for their outpatient appointment. Those who screen positive are sent to a fever clinic for further evaluation, which may include a rapid computed tomography scan (using a machine that may perform 200 chest computed tomography scans per day) and SARS-CoV-2 polymerase chain reaction.⁵ For inpatient dermatologic consultation of patients with known COVID-19, telehealth and multidisciplinary meetings are first and second line, respectively, with bedside dermatologic consultation as a last resort.⁴ Chen et al⁶ described similarly strict triage protocols as well as physician use of full-body personal protective equipment during all patient encounters. These measures are taken in light of the well-documented phenomenon of asymptomatic carriage and transmission, as all patients entering their dermatologic clinics have screened negative for symptomatic SARS-CoV-2 infection.⁶

Conferences and Education

Coronavirus is impacting the education of millions of individuals worldwide, including that of dermatology residents. The Annual Meeting of the American Academy of Dermatology, which was scheduled to take place in March 2020, was canceled due to COVID-19.⁷ The American Board of Dermatology has released a statement indicating that for all dermatology residents, time spent in COVID-19–mandated quarantine will count as clinical education if residents are able to work with their program to complete independent structured academic activity during that time.⁸ We also must consider the possibility that dermatology residents are reassigned to work outside of our specialty, resulting in less time and experience caring for patients with dermatologic conditions. Dermatologists in other countries have been called upon to care for COVID-19 patients, even reported to be working in intensive care units in Italy.⁹ Virtual technologies may be used in novel ways to support dermatology resident education throughout this process.

Final Thoughts

As physicians, dermatologists are in the position to educate their patients regarding prevention strategies, especially given that the lay press disseminates confusing and inaccurate information. The World Health Organization provides specific guidance, focusing on handwashing, respiratory hygiene, social distancing, and encouraging symptomatic patients to seek remote care whenever possible.¹⁰ Many of our patients are at high risk of complications due to COVID-19, whether due to their age or because they are immunocompromised. As the situation unfolds, the impact on and role of dermatology in this crisis will continue to evolve.

On January 30, 2020, the World Health Organization declared the outbreak of coronavirus disease 2019 (COVID-19) a public health emergency of international concern.¹ Severe acute respiratory syndrome–associated coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is an enveloped, single-stranded RNA virus. It is the seventh known coronavirus to infect humans and third zoonotic Coronaviridae to cause fatal respiratory illness, along with SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV).² There has been a rapid shift in the geographic center of the outbreak as well as the numbers of confirmed cases and deaths. Although the first cases in late 2019 and early 2020 were in China, by mid-March Italy became the center of the pandemic, with a steep increase in the number of cases in other European countries and the United States.³ Although COVID-19 does not have known dermatologic manifestations, it has the potential for wide-reaching impact on our field.

Strained Resources

In the United States, COVID-19 initially was associated with international travel but is now rapidly spreading throughout the community. I am currently a dermatology resident at New York-Presbyterian, Columbia campus, in New York, New York, a city that unfortunately finds itself underprepared to handle this unprecedented crisis. As of Monday, March 16, 2020, New York-Presbyterian made the decision to postpone all elective procedures, including Mohs micrographic surgery, to preserve hospital resources, including trained personnel, personal protective equipment, ventilators, and hospital beds. There have not been clear-cut guidelines regarding how to approach other dermatologic care for our patients, including routine clinic visits and inpatient dermatology consultations, leaving decisions up to individual departments and providers.

It would be prudent to learn from our colleagues in China who report steps that have been successful in preventing nosocomial spread of COVID-19 in the dermatologic setting. Tao et al⁴ described their protocols in both the outpatient and inpatient dermatologic setting, beginning with strict triage before patients can even enter a clinic building for their outpatient appointment. Those who screen positive are sent to a fever clinic for further evaluation, which may include a rapid computed tomography scan (using a machine that may perform 200 chest computed tomography scans per day) and SARS-CoV-2 polymerase chain reaction.⁵ For inpatient dermatologic consultation of patients with known COVID-19, telehealth and multidisciplinary meetings are first and second line, respectively, with bedside dermatologic consultation as a last resort.⁴ Chen et al⁶ described similarly strict triage protocols as well as physician use of full-body personal protective equipment during all patient encounters. These measures are taken in light of the well-documented phenomenon of asymptomatic carriage and transmission, as all patients entering their dermatologic clinics have screened negative for symptomatic SARS-CoV-2 infection.⁶

Conferences and Education

Coronavirus is impacting the education of millions of individuals worldwide, including that of dermatology residents. The Annual Meeting of the American Academy of Dermatology, which was scheduled to take place in March 2020, was canceled due to COVID-19.⁷ The American Board of Dermatology has released a statement indicating that for all dermatology residents, time spent in COVID-19–mandated quarantine will count as clinical education if residents are able to work with their program to complete independent structured academic activity during that time.⁸ We also must consider the possibility that dermatology residents are reassigned to work outside of our specialty, resulting in less time and experience caring for patients with dermatologic conditions. Dermatologists in other countries have been called upon to care for COVID-19 patients, even reported to be working in intensive care units in Italy.⁹ Virtual technologies may be used in novel ways to support dermatology resident education throughout this process.

Final Thoughts

As physicians, dermatologists are in the position to educate their patients regarding prevention strategies, especially given that the lay press disseminates confusing and inaccurate information. The World Health Organization provides specific guidance, focusing on handwashing, respiratory hygiene, social distancing, and encouraging symptomatic patients to seek remote care whenever possible.¹⁰ Many of our patients are at high risk of complications due to COVID-19, whether due to their age or because they are immunocompromised. As the situation unfolds, the impact on and role of dermatology in this crisis will continue to evolve.

I have no knowledge of, or experience with, managing a cancer patient during a pandemic. However, from the published and otherwise shared experience of others, we should not allow ourselves to underestimate the voracity of the coronavirus pandemic on our patients, communities, and health care systems.

Data from China suggest cancer patients infected with SARS-CoV-2 face a 3.5 times higher risk of mechanical ventilation, intensive care unit admission, or death, compared with infected patients without cancer (Lancet Oncol 2020;21:335-7).

Health care workers in Seattle have also shared their experiences battling coronavirus infections in cancer patients (J Natl Compr Canc Netw. 2020 Mar 20. doi: 10.6004/jnccn.2020.7560). Masumi Ueda, MD, of Seattle Cancer Care Alliance, and colleagues reviewed their decisions in multiple domains over a 7-week period, during which the state of Washington went from a single case of SARS-CoV-2 infection to nearly 650 cases and 40 deaths.
 

Making tough treatment decisions

Dr. Ueda and colleagues contrasted their customary resource-rich, innovation-oriented, cancer-combatting environment with their current circumstance, in which they must prioritize treatment for patients for whom the risk-reward balance has tilted substantially toward “risk.”

The authors noted that their most difficult decisions were those regarding delay of cancer treatment. They suggested that plans for potentially curative adjuvant therapy should likely proceed, but, for patients with metastatic disease, the equation is more nuanced.

In some cases, treatment should be delayed or interrupted with recognition of how that could result in worsening performance status and admission for symptom palliation, further stressing inpatient resources.

The authors suggested scenarios for prioritizing cancer surgery. For example, several months of systemic therapy (ideally, low-risk systemic therapy such as hormone therapy for breast or prostate cancer) and surgical delay may be worthwhile, without compromising patient care.

Patients with aggressive hematologic malignancy requiring urgent systemic treatment (potentially stem cell transplantation and cellular immunotherapies) should be treated promptly. However, even in those cases, opportunities should be sought to lessen immunosuppression and transition care as quickly as possible to the outpatient clinic, according to guidelines from the American Society of Transplantation and Cellular Therapy.
 

See one, do one, teach one

Rendering patient care during a pandemic would be unique for me. However, I, like all physicians, am familiar with feelings of inadequacy at times of professional challenge. On countless occasions, I have started my day or walked into a patient’s room wondering whether I will have the fortitude, knowledge, creativity, or help I need to get through that day or make that patient “better” by any definition of that word.

We all know the formula: “Work hard. Make evidence-based, personalized decisions for those who have entrusted their care to us. Learn from those encounters. Teach from our knowledge and experience – that is, ‘See one, do one, teach one.’ ”

The Seattle oncologists are living the lives of first responders and deserve our admiration for putting pen to paper so we can learn from their considerable, relevant experience.

Similar admiration is due to Giuseppe Curigliano, MD, of the European Institute of Oncology in Milan. In the ASCO Daily News, Dr. Curigliano described an epidemic that, within 3 weeks, overloaded the health care system across northern Italy.

Hospitalization was needed for over 60% of infected patients, and nearly 15% of those patients needed intensive care unit services for respiratory distress. The Italians centralized oncology care in specialized hubs, with spokes of institutions working in parallel to provide cancer-specific care in a COVID-free environment.

To build upon cancer-specific information from Italy and other areas hard-hit by COVID-19, more than 30 cancer centers have joined together to form the COVID-19 and Cancer Consortium. The consortium’s website hosts a survey designed to “capture details related to cancer patients presumed to have COVID-19.”
 

Calculating deaths and long-term consequences for cancer care delivery

It is proper that the authors from China, Italy, and Seattle did not focus attention on the case fatality rate from the COVID-19 pandemic among cancer patients. To say the least, it would be complicated to tally the direct mortality – either overall or in clinically important subsets of patients, including country-specific cohorts.

What we know from published reports is that, in Italy, cancer patients account for about 20% of deaths from coronavirus. In China, the case-fatality rate for patients with cancer was 5.6% (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).

However, we know nothing about the indirect death toll from malignancy (without coronavirus infection) that was untreated or managed less than optimally because of personnel and physical resources that were diverted to COVID-19–associated cases.

Similarly, we cannot begin to estimate indirect consequences of the pandemic to oncology practices, such as accelerated burnout and posttraumatic stress disorder, as well as the long-range effects of economic turmoil on patients, health care workers, and provider organizations.
 

What happens to cancer trials?

From China, Italy, and Seattle, thus far, there is little information about how the pandemic will affect the vital clinical research endeavor. The Seattle physicians did say they plan to enroll patients on clinical trials only when the trial offers a high chance of benefiting the patient over standard therapy alone.

Fortunately, the National Institutes of Health and Food and Drug Administration have released guidance documents related to clinical trials.

The National Cancer Institute (NCI) has also released guidance documents (March 13 guidance; March 23 guidance) for patients on clinical trials supported by the NCI Cancer Therapy Evaluation Program (CTEP) and the NCI Community Oncology Research Program (NCORP).

CTEP and NCORP are making reasonable accommodations to suspend monitoring visits and audits, allow tele–follow-up visits for patients, and permit local physicians to provide care for patients on study. In addition, with appropriate procedural adherence and documentation, CTEP and NCORP will allow oral investigational medicines to be mailed directly to patients’ homes.

Planned NCI National Clinical Trials Network meetings will be conducted via remote access webinars, conference calls, and similar technology. These adjustments – and probably many more to come – are geared toward facilitating ongoing care to proceed safely and with minimal risk for patients currently receiving investigational therapies and for the sites and investigators engaged in those studies.

Each of us has probably faced a personal “defining professional moment,” when we had to utilize every skill in our arsenal and examine the motivations that led us to a career in oncology. However, it is clear from the forgoing clinical and research processes and guidelines that the COVID-19 pandemic is such a defining professional moment for each of us, in every community we serve.

Critical junctures like this cause more rapid behavior change and innovation than the slow-moving pace that characterizes our idealized preferences. As oncologists who embrace new data and behavioral change, we stand to learn processes that will facilitate more perfected systems of care than the one that preceded this unprecedented crisis, promote more efficient sharing of high-quality information, and improve the outcome for our future patients.


Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

I have no knowledge of, or experience with, managing a cancer patient during a pandemic. However, from the published and otherwise shared experience of others, we should not allow ourselves to underestimate the voracity of the coronavirus pandemic on our patients, communities, and health care systems.

Data from China suggest cancer patients infected with SARS-CoV-2 face a 3.5 times higher risk of mechanical ventilation, intensive care unit admission, or death, compared with infected patients without cancer (Lancet Oncol 2020;21:335-7).

Health care workers in Seattle have also shared their experiences battling coronavirus infections in cancer patients (J Natl Compr Canc Netw. 2020 Mar 20. doi: 10.6004/jnccn.2020.7560). Masumi Ueda, MD, of Seattle Cancer Care Alliance, and colleagues reviewed their decisions in multiple domains over a 7-week period, during which the state of Washington went from a single case of SARS-CoV-2 infection to nearly 650 cases and 40 deaths.
 

Making tough treatment decisions

Dr. Ueda and colleagues contrasted their customary resource-rich, innovation-oriented, cancer-combatting environment with their current circumstance, in which they must prioritize treatment for patients for whom the risk-reward balance has tilted substantially toward “risk.”

The authors noted that their most difficult decisions were those regarding delay of cancer treatment. They suggested that plans for potentially curative adjuvant therapy should likely proceed, but, for patients with metastatic disease, the equation is more nuanced.

In some cases, treatment should be delayed or interrupted with recognition of how that could result in worsening performance status and admission for symptom palliation, further stressing inpatient resources.

The authors suggested scenarios for prioritizing cancer surgery. For example, several months of systemic therapy (ideally, low-risk systemic therapy such as hormone therapy for breast or prostate cancer) and surgical delay may be worthwhile, without compromising patient care.

Patients with aggressive hematologic malignancy requiring urgent systemic treatment (potentially stem cell transplantation and cellular immunotherapies) should be treated promptly. However, even in those cases, opportunities should be sought to lessen immunosuppression and transition care as quickly as possible to the outpatient clinic, according to guidelines from the American Society of Transplantation and Cellular Therapy.
 

See one, do one, teach one

Rendering patient care during a pandemic would be unique for me. However, I, like all physicians, am familiar with feelings of inadequacy at times of professional challenge. On countless occasions, I have started my day or walked into a patient’s room wondering whether I will have the fortitude, knowledge, creativity, or help I need to get through that day or make that patient “better” by any definition of that word.

We all know the formula: “Work hard. Make evidence-based, personalized decisions for those who have entrusted their care to us. Learn from those encounters. Teach from our knowledge and experience – that is, ‘See one, do one, teach one.’ ”

The Seattle oncologists are living the lives of first responders and deserve our admiration for putting pen to paper so we can learn from their considerable, relevant experience.

Similar admiration is due to Giuseppe Curigliano, MD, of the European Institute of Oncology in Milan. In the ASCO Daily News, Dr. Curigliano described an epidemic that, within 3 weeks, overloaded the health care system across northern Italy.

Hospitalization was needed for over 60% of infected patients, and nearly 15% of those patients needed intensive care unit services for respiratory distress. The Italians centralized oncology care in specialized hubs, with spokes of institutions working in parallel to provide cancer-specific care in a COVID-free environment.

To build upon cancer-specific information from Italy and other areas hard-hit by COVID-19, more than 30 cancer centers have joined together to form the COVID-19 and Cancer Consortium. The consortium’s website hosts a survey designed to “capture details related to cancer patients presumed to have COVID-19.”
 

Calculating deaths and long-term consequences for cancer care delivery

It is proper that the authors from China, Italy, and Seattle did not focus attention on the case fatality rate from the COVID-19 pandemic among cancer patients. To say the least, it would be complicated to tally the direct mortality – either overall or in clinically important subsets of patients, including country-specific cohorts.

What we know from published reports is that, in Italy, cancer patients account for about 20% of deaths from coronavirus. In China, the case-fatality rate for patients with cancer was 5.6% (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).

However, we know nothing about the indirect death toll from malignancy (without coronavirus infection) that was untreated or managed less than optimally because of personnel and physical resources that were diverted to COVID-19–associated cases.

Similarly, we cannot begin to estimate indirect consequences of the pandemic to oncology practices, such as accelerated burnout and posttraumatic stress disorder, as well as the long-range effects of economic turmoil on patients, health care workers, and provider organizations.
 

What happens to cancer trials?

From China, Italy, and Seattle, thus far, there is little information about how the pandemic will affect the vital clinical research endeavor. The Seattle physicians did say they plan to enroll patients on clinical trials only when the trial offers a high chance of benefiting the patient over standard therapy alone.

Fortunately, the National Institutes of Health and Food and Drug Administration have released guidance documents related to clinical trials.

The National Cancer Institute (NCI) has also released guidance documents (March 13 guidance; March 23 guidance) for patients on clinical trials supported by the NCI Cancer Therapy Evaluation Program (CTEP) and the NCI Community Oncology Research Program (NCORP).

CTEP and NCORP are making reasonable accommodations to suspend monitoring visits and audits, allow tele–follow-up visits for patients, and permit local physicians to provide care for patients on study. In addition, with appropriate procedural adherence and documentation, CTEP and NCORP will allow oral investigational medicines to be mailed directly to patients’ homes.

Planned NCI National Clinical Trials Network meetings will be conducted via remote access webinars, conference calls, and similar technology. These adjustments – and probably many more to come – are geared toward facilitating ongoing care to proceed safely and with minimal risk for patients currently receiving investigational therapies and for the sites and investigators engaged in those studies.

Each of us has probably faced a personal “defining professional moment,” when we had to utilize every skill in our arsenal and examine the motivations that led us to a career in oncology. However, it is clear from the forgoing clinical and research processes and guidelines that the COVID-19 pandemic is such a defining professional moment for each of us, in every community we serve.

Critical junctures like this cause more rapid behavior change and innovation than the slow-moving pace that characterizes our idealized preferences. As oncologists who embrace new data and behavioral change, we stand to learn processes that will facilitate more perfected systems of care than the one that preceded this unprecedented crisis, promote more efficient sharing of high-quality information, and improve the outcome for our future patients.


Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

I have no knowledge of, or experience with, managing a cancer patient during a pandemic. However, from the published and otherwise shared experience of others, we should not allow ourselves to underestimate the voracity of the coronavirus pandemic on our patients, communities, and health care systems.

Data from China suggest cancer patients infected with SARS-CoV-2 face a 3.5 times higher risk of mechanical ventilation, intensive care unit admission, or death, compared with infected patients without cancer (Lancet Oncol 2020;21:335-7).

Health care workers in Seattle have also shared their experiences battling coronavirus infections in cancer patients (J Natl Compr Canc Netw. 2020 Mar 20. doi: 10.6004/jnccn.2020.7560). Masumi Ueda, MD, of Seattle Cancer Care Alliance, and colleagues reviewed their decisions in multiple domains over a 7-week period, during which the state of Washington went from a single case of SARS-CoV-2 infection to nearly 650 cases and 40 deaths.
 

Making tough treatment decisions

Dr. Ueda and colleagues contrasted their customary resource-rich, innovation-oriented, cancer-combatting environment with their current circumstance, in which they must prioritize treatment for patients for whom the risk-reward balance has tilted substantially toward “risk.”

The authors noted that their most difficult decisions were those regarding delay of cancer treatment. They suggested that plans for potentially curative adjuvant therapy should likely proceed, but, for patients with metastatic disease, the equation is more nuanced.

In some cases, treatment should be delayed or interrupted with recognition of how that could result in worsening performance status and admission for symptom palliation, further stressing inpatient resources.

The authors suggested scenarios for prioritizing cancer surgery. For example, several months of systemic therapy (ideally, low-risk systemic therapy such as hormone therapy for breast or prostate cancer) and surgical delay may be worthwhile, without compromising patient care.

Patients with aggressive hematologic malignancy requiring urgent systemic treatment (potentially stem cell transplantation and cellular immunotherapies) should be treated promptly. However, even in those cases, opportunities should be sought to lessen immunosuppression and transition care as quickly as possible to the outpatient clinic, according to guidelines from the American Society of Transplantation and Cellular Therapy.
 

See one, do one, teach one

Rendering patient care during a pandemic would be unique for me. However, I, like all physicians, am familiar with feelings of inadequacy at times of professional challenge. On countless occasions, I have started my day or walked into a patient’s room wondering whether I will have the fortitude, knowledge, creativity, or help I need to get through that day or make that patient “better” by any definition of that word.

We all know the formula: “Work hard. Make evidence-based, personalized decisions for those who have entrusted their care to us. Learn from those encounters. Teach from our knowledge and experience – that is, ‘See one, do one, teach one.’ ”

The Seattle oncologists are living the lives of first responders and deserve our admiration for putting pen to paper so we can learn from their considerable, relevant experience.

Similar admiration is due to Giuseppe Curigliano, MD, of the European Institute of Oncology in Milan. In the ASCO Daily News, Dr. Curigliano described an epidemic that, within 3 weeks, overloaded the health care system across northern Italy.

Hospitalization was needed for over 60% of infected patients, and nearly 15% of those patients needed intensive care unit services for respiratory distress. The Italians centralized oncology care in specialized hubs, with spokes of institutions working in parallel to provide cancer-specific care in a COVID-free environment.

To build upon cancer-specific information from Italy and other areas hard-hit by COVID-19, more than 30 cancer centers have joined together to form the COVID-19 and Cancer Consortium. The consortium’s website hosts a survey designed to “capture details related to cancer patients presumed to have COVID-19.”
 

Calculating deaths and long-term consequences for cancer care delivery

It is proper that the authors from China, Italy, and Seattle did not focus attention on the case fatality rate from the COVID-19 pandemic among cancer patients. To say the least, it would be complicated to tally the direct mortality – either overall or in clinically important subsets of patients, including country-specific cohorts.

What we know from published reports is that, in Italy, cancer patients account for about 20% of deaths from coronavirus. In China, the case-fatality rate for patients with cancer was 5.6% (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).

However, we know nothing about the indirect death toll from malignancy (without coronavirus infection) that was untreated or managed less than optimally because of personnel and physical resources that were diverted to COVID-19–associated cases.

Similarly, we cannot begin to estimate indirect consequences of the pandemic to oncology practices, such as accelerated burnout and posttraumatic stress disorder, as well as the long-range effects of economic turmoil on patients, health care workers, and provider organizations.
 

What happens to cancer trials?

From China, Italy, and Seattle, thus far, there is little information about how the pandemic will affect the vital clinical research endeavor. The Seattle physicians did say they plan to enroll patients on clinical trials only when the trial offers a high chance of benefiting the patient over standard therapy alone.

Fortunately, the National Institutes of Health and Food and Drug Administration have released guidance documents related to clinical trials.

The National Cancer Institute (NCI) has also released guidance documents (March 13 guidance; March 23 guidance) for patients on clinical trials supported by the NCI Cancer Therapy Evaluation Program (CTEP) and the NCI Community Oncology Research Program (NCORP).

CTEP and NCORP are making reasonable accommodations to suspend monitoring visits and audits, allow tele–follow-up visits for patients, and permit local physicians to provide care for patients on study. In addition, with appropriate procedural adherence and documentation, CTEP and NCORP will allow oral investigational medicines to be mailed directly to patients’ homes.

Planned NCI National Clinical Trials Network meetings will be conducted via remote access webinars, conference calls, and similar technology. These adjustments – and probably many more to come – are geared toward facilitating ongoing care to proceed safely and with minimal risk for patients currently receiving investigational therapies and for the sites and investigators engaged in those studies.

Each of us has probably faced a personal “defining professional moment,” when we had to utilize every skill in our arsenal and examine the motivations that led us to a career in oncology. However, it is clear from the forgoing clinical and research processes and guidelines that the COVID-19 pandemic is such a defining professional moment for each of us, in every community we serve.

Critical junctures like this cause more rapid behavior change and innovation than the slow-moving pace that characterizes our idealized preferences. As oncologists who embrace new data and behavioral change, we stand to learn processes that will facilitate more perfected systems of care than the one that preceded this unprecedented crisis, promote more efficient sharing of high-quality information, and improve the outcome for our future patients.


Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.