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FDA Withdraws Melflufen Approval, but EMA Still Allows Its Use
But the European Medicines Agency (EMA) still authorizes the drug’s manufacturer Oncopeptides AB to market the drug, also called Pepaxti, in Europe, Iceland, Lichtenstein, Norway, and the United Kingdom.
Amol Akhade, MBBS, who describes himself as a senior consultant medical and hemato oncologist–bone marrow transplant physician on LinkedIn, raised questions about the inconsistencies between the FDA and EMA’s opinions about these drugs. Dr. Akhad, of Suyog Cancer Clinics in India, posted via the following handle @SuyogCancer on X (Twitter):
“How can one drug and one trial data [have] two diagonally different outcomes from two different drug approval agencies?
Melphalan Flufenamide is finally completely withdrawn by @US_FDA
But approval by @EMA_News stays.
How can be one drug be harmful across one side of Atlantic Ocean and becomes safe and useful on the other side of Atlantic Ocean?
Modern day miracle?”
EMA: Pepaxti’s Benefits Exceed Its Risks
The EMA, which could not be reached for comment regarding why the agency was still allowing patients to use the drug, said the following about Pepaxti on its website:
“The European Medicines Agency decided that Pepaxti’s benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted the unmet medical need for patients with multiple myeloma who no longer improve with the available therapies. Despite some limitations in the studies, the results were considered clinically relevant, with the exception of the subgroup of patients who had an autologous stem cell transplant and whose disease progressed within three years of transplantation.
Regarding safety, although side effects, including severe effects, were seen with treatment involving Pepaxti, these were considered acceptable and manageable,” the agency wrote.
“Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pepaxti have been included in the summary of product characteristics and the package leaflet.
As for all medicines, data on the use of Pepaxti are continuously monitored. Suspected side effects reported with Pepaxti are carefully evaluated and any necessary action taken to protect patients,” according to the EMA.
The FDA’s final decision, issued on February 23, 2024, follows its warning in 2021 that meflufen plus dexamethasone exposed patients with multiple myeloma to increased risk for death, and its call for withdrawal of the drug in 2022.
“The grounds for withdrawing approval have been met because: (1) the confirmatory study conducted as a condition of accelerated approval did not confirm Pepaxto’s clinical benefit and (2) the available evidence demonstrates that Pepaxto is not shown to be safe or effective under its conditions of use,” Peter Marks, MD, PhD, Director of the FDA Center for Biologics Evaluation and Research, wrote in the final decision document.
Oncopeptides AB: Drug ‘Caters to a Large Unmet Need’
David Augustsson, Director of Corporate Affairs, Oncopeptides AB, explained in an interview why he thinks the EMA and FDA’s actions regarding the drug differ from each other.
“The European Medicines Agency had the opinion that the OCEAN study met its primary endpoint by demonstrating superior progression-free survival and it agreed that the potential detriment of overall survival was limited to patients progressing less than 36 months after an autologous stem cell transplant,” he said.“The FDA was not willing to acknowledge the observed clinically relevant differences across patient subgroups in the OCEAN study as confirmed.”
Mr. Augustsson added that this decision will deprive US patients of access to “a drug we believe caters to a large unmet need among elderly multiple myeloma patients with few treatment options left.”
“While we remain confident that we have science on our side we are of course disappointed in the decision [to remove Pepaxto from the US market],” Oncopeptides AB CEO Sofia Heigis said in a statement. “At the same time this is no change to our plans and we will continue to focus all our attention on the commercialization in Europe, progression of our pipeline and rest of world opportunities.”
FDA 'Took Swift Action' to Ensure Users of Pepaxto Were Informed of Risks
In February 2021, the FDA used the Accelerated Approval Program to enable certain patients with multiple myeloma to be treated with the peptide conjugated alkylating drug melflufen plus dexamethasone. Under the program, Oncopeptides was required to conduct the phase III randomized, controlled OCEAN clinical trial.
OCEAN enrolled 495 patients with relapsed/refractory multiple myeloma who had 2 to 4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy. Participants in the multinational study received either melflufen plus dexamethasone or pomalidomide plus dexamethasone until disease progression, unacceptable toxicity, or lack of benefit.
In July 2021, the FDA issued an alert that the study results showed increased risk for death in participants treated with melflufen. In October that year, at FDA request, Oncopeptides removed the drug from the US market but continued to provide it to patients already receiving it. In December 2022, the FDA requested that the company withdraw melflufen’s US marketing authorization.
Responding to questions about the timing of the FDA’s most recent decision about Pepaxto and how the decision will affect patient care in the US, the FDA emailed the following statement to this news organization:
“Since the OCEAN trial results for Pepaxto in 2021, the FDA has responded to safety concerns about Pepaxto by issuing a CDER Alert, communicating concerns to Oncopeptides, holding an Oncologic Drugs Advisory Committee meeting in September 2022, and issuing a letter of notice to Oncopeptides in July 2023, proposing to withdraw Pepaxto (NDA 214383). After receiving the notice, Oncopeptides appealed the withdrawal in August 2023. A meeting was held with the Commissioner’s designee, Dr. Peter Marks, Oncopeptides, and others from FDA in October 2023. Dr. Marks reviewed the record and considered the arguments made on appeal and issued a final decision on February 23, 2024. Prior to reaching a decision, the FDA took swift action to ensure those receiving Pepaxto in the post-confirmatory clinical trial were informed of the risks and that no new patients were enrolled in the trial. We also note that it is our understanding that Pepaxto has not been marketed in the U.S. since October 22, 2021.”
“This is the first time FDA has used the amended procedures for withdrawal of accelerated approval that were enacted in 2023, as part of the Food and Drug Omnibus Report Act of 2022 (FDORA),” the agency wrote in a Feb 23 statement. The agency will also remove melflufen from the Approved Drug Products with Therapeutic Equivalence Evaluations, also called the Orange Book.
But the European Medicines Agency (EMA) still authorizes the drug’s manufacturer Oncopeptides AB to market the drug, also called Pepaxti, in Europe, Iceland, Lichtenstein, Norway, and the United Kingdom.
Amol Akhade, MBBS, who describes himself as a senior consultant medical and hemato oncologist–bone marrow transplant physician on LinkedIn, raised questions about the inconsistencies between the FDA and EMA’s opinions about these drugs. Dr. Akhad, of Suyog Cancer Clinics in India, posted via the following handle @SuyogCancer on X (Twitter):
“How can one drug and one trial data [have] two diagonally different outcomes from two different drug approval agencies?
Melphalan Flufenamide is finally completely withdrawn by @US_FDA
But approval by @EMA_News stays.
How can be one drug be harmful across one side of Atlantic Ocean and becomes safe and useful on the other side of Atlantic Ocean?
Modern day miracle?”
EMA: Pepaxti’s Benefits Exceed Its Risks
The EMA, which could not be reached for comment regarding why the agency was still allowing patients to use the drug, said the following about Pepaxti on its website:
“The European Medicines Agency decided that Pepaxti’s benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted the unmet medical need for patients with multiple myeloma who no longer improve with the available therapies. Despite some limitations in the studies, the results were considered clinically relevant, with the exception of the subgroup of patients who had an autologous stem cell transplant and whose disease progressed within three years of transplantation.
Regarding safety, although side effects, including severe effects, were seen with treatment involving Pepaxti, these were considered acceptable and manageable,” the agency wrote.
“Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pepaxti have been included in the summary of product characteristics and the package leaflet.
As for all medicines, data on the use of Pepaxti are continuously monitored. Suspected side effects reported with Pepaxti are carefully evaluated and any necessary action taken to protect patients,” according to the EMA.
The FDA’s final decision, issued on February 23, 2024, follows its warning in 2021 that meflufen plus dexamethasone exposed patients with multiple myeloma to increased risk for death, and its call for withdrawal of the drug in 2022.
“The grounds for withdrawing approval have been met because: (1) the confirmatory study conducted as a condition of accelerated approval did not confirm Pepaxto’s clinical benefit and (2) the available evidence demonstrates that Pepaxto is not shown to be safe or effective under its conditions of use,” Peter Marks, MD, PhD, Director of the FDA Center for Biologics Evaluation and Research, wrote in the final decision document.
Oncopeptides AB: Drug ‘Caters to a Large Unmet Need’
David Augustsson, Director of Corporate Affairs, Oncopeptides AB, explained in an interview why he thinks the EMA and FDA’s actions regarding the drug differ from each other.
“The European Medicines Agency had the opinion that the OCEAN study met its primary endpoint by demonstrating superior progression-free survival and it agreed that the potential detriment of overall survival was limited to patients progressing less than 36 months after an autologous stem cell transplant,” he said.“The FDA was not willing to acknowledge the observed clinically relevant differences across patient subgroups in the OCEAN study as confirmed.”
Mr. Augustsson added that this decision will deprive US patients of access to “a drug we believe caters to a large unmet need among elderly multiple myeloma patients with few treatment options left.”
“While we remain confident that we have science on our side we are of course disappointed in the decision [to remove Pepaxto from the US market],” Oncopeptides AB CEO Sofia Heigis said in a statement. “At the same time this is no change to our plans and we will continue to focus all our attention on the commercialization in Europe, progression of our pipeline and rest of world opportunities.”
FDA 'Took Swift Action' to Ensure Users of Pepaxto Were Informed of Risks
In February 2021, the FDA used the Accelerated Approval Program to enable certain patients with multiple myeloma to be treated with the peptide conjugated alkylating drug melflufen plus dexamethasone. Under the program, Oncopeptides was required to conduct the phase III randomized, controlled OCEAN clinical trial.
OCEAN enrolled 495 patients with relapsed/refractory multiple myeloma who had 2 to 4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy. Participants in the multinational study received either melflufen plus dexamethasone or pomalidomide plus dexamethasone until disease progression, unacceptable toxicity, or lack of benefit.
In July 2021, the FDA issued an alert that the study results showed increased risk for death in participants treated with melflufen. In October that year, at FDA request, Oncopeptides removed the drug from the US market but continued to provide it to patients already receiving it. In December 2022, the FDA requested that the company withdraw melflufen’s US marketing authorization.
Responding to questions about the timing of the FDA’s most recent decision about Pepaxto and how the decision will affect patient care in the US, the FDA emailed the following statement to this news organization:
“Since the OCEAN trial results for Pepaxto in 2021, the FDA has responded to safety concerns about Pepaxto by issuing a CDER Alert, communicating concerns to Oncopeptides, holding an Oncologic Drugs Advisory Committee meeting in September 2022, and issuing a letter of notice to Oncopeptides in July 2023, proposing to withdraw Pepaxto (NDA 214383). After receiving the notice, Oncopeptides appealed the withdrawal in August 2023. A meeting was held with the Commissioner’s designee, Dr. Peter Marks, Oncopeptides, and others from FDA in October 2023. Dr. Marks reviewed the record and considered the arguments made on appeal and issued a final decision on February 23, 2024. Prior to reaching a decision, the FDA took swift action to ensure those receiving Pepaxto in the post-confirmatory clinical trial were informed of the risks and that no new patients were enrolled in the trial. We also note that it is our understanding that Pepaxto has not been marketed in the U.S. since October 22, 2021.”
“This is the first time FDA has used the amended procedures for withdrawal of accelerated approval that were enacted in 2023, as part of the Food and Drug Omnibus Report Act of 2022 (FDORA),” the agency wrote in a Feb 23 statement. The agency will also remove melflufen from the Approved Drug Products with Therapeutic Equivalence Evaluations, also called the Orange Book.
But the European Medicines Agency (EMA) still authorizes the drug’s manufacturer Oncopeptides AB to market the drug, also called Pepaxti, in Europe, Iceland, Lichtenstein, Norway, and the United Kingdom.
Amol Akhade, MBBS, who describes himself as a senior consultant medical and hemato oncologist–bone marrow transplant physician on LinkedIn, raised questions about the inconsistencies between the FDA and EMA’s opinions about these drugs. Dr. Akhad, of Suyog Cancer Clinics in India, posted via the following handle @SuyogCancer on X (Twitter):
“How can one drug and one trial data [have] two diagonally different outcomes from two different drug approval agencies?
Melphalan Flufenamide is finally completely withdrawn by @US_FDA
But approval by @EMA_News stays.
How can be one drug be harmful across one side of Atlantic Ocean and becomes safe and useful on the other side of Atlantic Ocean?
Modern day miracle?”
EMA: Pepaxti’s Benefits Exceed Its Risks
The EMA, which could not be reached for comment regarding why the agency was still allowing patients to use the drug, said the following about Pepaxti on its website:
“The European Medicines Agency decided that Pepaxti’s benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted the unmet medical need for patients with multiple myeloma who no longer improve with the available therapies. Despite some limitations in the studies, the results were considered clinically relevant, with the exception of the subgroup of patients who had an autologous stem cell transplant and whose disease progressed within three years of transplantation.
Regarding safety, although side effects, including severe effects, were seen with treatment involving Pepaxti, these were considered acceptable and manageable,” the agency wrote.
“Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pepaxti have been included in the summary of product characteristics and the package leaflet.
As for all medicines, data on the use of Pepaxti are continuously monitored. Suspected side effects reported with Pepaxti are carefully evaluated and any necessary action taken to protect patients,” according to the EMA.
The FDA’s final decision, issued on February 23, 2024, follows its warning in 2021 that meflufen plus dexamethasone exposed patients with multiple myeloma to increased risk for death, and its call for withdrawal of the drug in 2022.
“The grounds for withdrawing approval have been met because: (1) the confirmatory study conducted as a condition of accelerated approval did not confirm Pepaxto’s clinical benefit and (2) the available evidence demonstrates that Pepaxto is not shown to be safe or effective under its conditions of use,” Peter Marks, MD, PhD, Director of the FDA Center for Biologics Evaluation and Research, wrote in the final decision document.
Oncopeptides AB: Drug ‘Caters to a Large Unmet Need’
David Augustsson, Director of Corporate Affairs, Oncopeptides AB, explained in an interview why he thinks the EMA and FDA’s actions regarding the drug differ from each other.
“The European Medicines Agency had the opinion that the OCEAN study met its primary endpoint by demonstrating superior progression-free survival and it agreed that the potential detriment of overall survival was limited to patients progressing less than 36 months after an autologous stem cell transplant,” he said.“The FDA was not willing to acknowledge the observed clinically relevant differences across patient subgroups in the OCEAN study as confirmed.”
Mr. Augustsson added that this decision will deprive US patients of access to “a drug we believe caters to a large unmet need among elderly multiple myeloma patients with few treatment options left.”
“While we remain confident that we have science on our side we are of course disappointed in the decision [to remove Pepaxto from the US market],” Oncopeptides AB CEO Sofia Heigis said in a statement. “At the same time this is no change to our plans and we will continue to focus all our attention on the commercialization in Europe, progression of our pipeline and rest of world opportunities.”
FDA 'Took Swift Action' to Ensure Users of Pepaxto Were Informed of Risks
In February 2021, the FDA used the Accelerated Approval Program to enable certain patients with multiple myeloma to be treated with the peptide conjugated alkylating drug melflufen plus dexamethasone. Under the program, Oncopeptides was required to conduct the phase III randomized, controlled OCEAN clinical trial.
OCEAN enrolled 495 patients with relapsed/refractory multiple myeloma who had 2 to 4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy. Participants in the multinational study received either melflufen plus dexamethasone or pomalidomide plus dexamethasone until disease progression, unacceptable toxicity, or lack of benefit.
In July 2021, the FDA issued an alert that the study results showed increased risk for death in participants treated with melflufen. In October that year, at FDA request, Oncopeptides removed the drug from the US market but continued to provide it to patients already receiving it. In December 2022, the FDA requested that the company withdraw melflufen’s US marketing authorization.
Responding to questions about the timing of the FDA’s most recent decision about Pepaxto and how the decision will affect patient care in the US, the FDA emailed the following statement to this news organization:
“Since the OCEAN trial results for Pepaxto in 2021, the FDA has responded to safety concerns about Pepaxto by issuing a CDER Alert, communicating concerns to Oncopeptides, holding an Oncologic Drugs Advisory Committee meeting in September 2022, and issuing a letter of notice to Oncopeptides in July 2023, proposing to withdraw Pepaxto (NDA 214383). After receiving the notice, Oncopeptides appealed the withdrawal in August 2023. A meeting was held with the Commissioner’s designee, Dr. Peter Marks, Oncopeptides, and others from FDA in October 2023. Dr. Marks reviewed the record and considered the arguments made on appeal and issued a final decision on February 23, 2024. Prior to reaching a decision, the FDA took swift action to ensure those receiving Pepaxto in the post-confirmatory clinical trial were informed of the risks and that no new patients were enrolled in the trial. We also note that it is our understanding that Pepaxto has not been marketed in the U.S. since October 22, 2021.”
“This is the first time FDA has used the amended procedures for withdrawal of accelerated approval that were enacted in 2023, as part of the Food and Drug Omnibus Report Act of 2022 (FDORA),” the agency wrote in a Feb 23 statement. The agency will also remove melflufen from the Approved Drug Products with Therapeutic Equivalence Evaluations, also called the Orange Book.
Judge Won’t Overturn Invalidated USMLE Scores
(USMLE).
In a February 23 order, Judge Christopher R. Cooper, of the US District Court for the District of Columbia, denied Latika Giri’s emergency motion to block the National Board of Medical Examiners (NBME) from invalidating the scores, ruling the public interest plainly weighs against granting the request.
“First and foremost, is the overriding interest in public safety,” Cooper wrote in his 32-page order. “This is a case about the credentials of doctors applying to medical residency programs…Granting the preliminary injunction would create an unacceptable risk that individuals who lack the requisite knowledge and skills they purport to possess because they achieved their exam scores fraudulently will be administering medical care to unsuspecting patients across the nation.”
Attorneys for Giri did not return messages seeking comment about the order.
The NBME also did not return messages seeking comment. The board previously said it does not comment on pending litigation.
The decision is the latest development in a widespread cheating scandal. Giri, an international medical graduate (IMG) from Kathmandu, sued NBME earlier this month claiming the board discriminated against Nepali medical graduates when it invalidated hundreds of exam scores linked to the country.
Giri also accused NBME of violating its own procedures when it voided the scores before giving examinees a chance to argue and appeal. She asked the district court to block NBME from invalidating her exam scores while the lawsuit continues and restore her original results.
In court documents, NBME argued that it did not invalidate the scores because the examinees were Nepali but because staff concluded that there was “a good faith basis for questioning the validity of the scores.”
The invalidations were based on concerns that the results reflected prior access to secure exam content rather than knowledge and understanding of the medical principles and skills the exams are intended to assess, according to the NBME’s legal response.
“The USMLE program took reasonable and appropriate actions to prevent the significant harm and disruption that would result from allowing potentially unqualified individuals to participate in the 2024 residency Match,” the NBME stated in court documents. “If granted, the requested injunction would cause enormous harm not only to NBME… but also to state licensing authorities, which rely upon USMLE results to help ensure that physicians have the minimum competencies needed to provide safe and effective health care.”
In his order, Cooper wrote that Giri has not proven the board’s actions were discriminatory against Nepali doctors.
“Nothing in the present record suggests that NBME went looking for a problem in Nepal out of ethnicity-or national-origin based [sic] suspicion,” Cooper wrote. “[It] followed the trail of evidence, including tips about organized cheating taking place in medical schools and at a testing center located in Nepal, and on an online forum for which a ‘nexus to Nepal’ was a ticket to admission.”
NBME: Nepal Outperformed All Other Countries on USMLE
Court documents shed more light on NBME’s investigation into the suspected cheating and on the anomalous patterns the board allegedly discovered from Nepal medical graduates.
In response to anonymous tips, the USMLE program in early 2023 asked the NBME Psychometrics and Data Analysis (PADA) unit to analyze examinee performance data for test centers in Jordan, Nepal, and Pakistan, according to court records. Within the initial data analysis, the data involving the single test center in Nepal was “the most extreme,” the unit found.
Out of more than 400 test centers across the world, including those in the United States, the test center in Nepal produced the highest test scores in the world for Step 1 in 2021 and 2022 and the highest test scores in the world for Step 2 CK in 2022, according to court documents. For the 2022 Step 1 exam for example, the average score of examinees testing in the Nepal test center was 240. No other test center in the world had an average examinee score above 227, according to the NBME’s legal response.
The median item response time for examinees who tested at the Nepal test center in 2022 was also among the fastest of all international test centers for Step 1 and Step 2 CK, investigators found.
In addition, the volume of examinees taking the USMLE Step 1 and Step 2 CK at the Nepal test center in Nepal had sharply increased. Step 1 volume more than doubled in the Nepal test center from 281 examinees in 2019 to 662 examinees in 2022, according to court documents.
The rapid increase continued in 2023, when examinee volume was nearly three-and-a-half times higher than the 2019 volume. The data were consistent with anonymous tips received by the USMLE program office, suggesting there may be wide-scale collection and sharing of live USMLE exam content within Nepal.
Investigation Finds Similar Correct and Incorrect Answers
Agreement similarity among the exams analyzed also raised red flags. Investigators ran an “agreement analysis” for all examinees who tested at centers in Jordan, Nepal, and Pakistan as well as two centers in India, according to court documents.
For the 2022 Step 1 exam and the 2021 and 2022 Step 2 CK exam, the analysis showed a substantially higher percentage of examinees with a statistically significant level of agreement matches in the examine group that tested at centers in Jordan, Nepal, Pakistan, and India compared with the baseline group, according to legal records.
The vast majority of examinees with a statistically significant number of matching incorrect answers tested at the Nepal test center, data showed.
Further analysis found that examinee volumes increased considerably at the Nepal test center in the months prior to the USMLE program releasing new test items, “suggesting that candidates who had prior access to disclosed exam questions wanted to test before new questions came into the item pool.”
Investigators also identified posts on social medial and in online chat rooms suggesting groups were collecting and sharing large amounts of secure exam material in private groups. Some posts advised examinees to use the full examination time when taking the USMLE “to avoid raising suspicion about having had prior access to secure exam materials,” according to court documents.
From its investigation and analysis, the USMLE program identified 832 examinees who had passing level exam results whose validity the USMLE program had a significant and good faith basis for questioning, according to court records.
Of the total, 618 examinees had one Step score flagged as being of questioned validity, 202 examinees had two Step exam scores flagged, and 12 examinees had scores flagged on all three Step exams.
NBME Defends Departure From Traditional Procedures
In court documents, NBME disputed claims that it violated its own procedures by invalidating the exam scores. Giri’s report contends that examinees suspected of cheating are typically first advised of the matter, given an opportunity to share relevant information, and provided the right to appeal — during which time, their scores are treated as valid.
But the NBME said the USMLE program is authorized to take any actions it deems appropriate in response to concerns regarding score validity if the USMLE Committee for Individualized Review or the USMLE Composite Committee concludes that alternative or supplemental procedures are warranted in response to a given set of facts or circumstances.
“Following the month-long investigation and analysis…the USMLE program concluded that alternative procedures were warranted to address the score invalidity concerns identified in the interest of providing a process that is timely, efficient, effective, and fair, and given the large number of examinees involved in the investigation,” the board stated in its legal response.
In his order, Cooper wrote the current scenario, which implicates that more than 800 test-takers, is “clearly a situation calling for a procedure geared toward efficiency.” No evidence shows the board would not have taken similarly swift action if confronted with evidence of cheating on a comparable scale elsewhere, he wrote.
The judge also denied Giri’s motion to certify the lawsuit as a class action. The motion was denied without prejudice, meaning the plaintiff has the option to renew the motion should the case proceed.
A version of this article appeared on Medscape.com.
(USMLE).
In a February 23 order, Judge Christopher R. Cooper, of the US District Court for the District of Columbia, denied Latika Giri’s emergency motion to block the National Board of Medical Examiners (NBME) from invalidating the scores, ruling the public interest plainly weighs against granting the request.
“First and foremost, is the overriding interest in public safety,” Cooper wrote in his 32-page order. “This is a case about the credentials of doctors applying to medical residency programs…Granting the preliminary injunction would create an unacceptable risk that individuals who lack the requisite knowledge and skills they purport to possess because they achieved their exam scores fraudulently will be administering medical care to unsuspecting patients across the nation.”
Attorneys for Giri did not return messages seeking comment about the order.
The NBME also did not return messages seeking comment. The board previously said it does not comment on pending litigation.
The decision is the latest development in a widespread cheating scandal. Giri, an international medical graduate (IMG) from Kathmandu, sued NBME earlier this month claiming the board discriminated against Nepali medical graduates when it invalidated hundreds of exam scores linked to the country.
Giri also accused NBME of violating its own procedures when it voided the scores before giving examinees a chance to argue and appeal. She asked the district court to block NBME from invalidating her exam scores while the lawsuit continues and restore her original results.
In court documents, NBME argued that it did not invalidate the scores because the examinees were Nepali but because staff concluded that there was “a good faith basis for questioning the validity of the scores.”
The invalidations were based on concerns that the results reflected prior access to secure exam content rather than knowledge and understanding of the medical principles and skills the exams are intended to assess, according to the NBME’s legal response.
“The USMLE program took reasonable and appropriate actions to prevent the significant harm and disruption that would result from allowing potentially unqualified individuals to participate in the 2024 residency Match,” the NBME stated in court documents. “If granted, the requested injunction would cause enormous harm not only to NBME… but also to state licensing authorities, which rely upon USMLE results to help ensure that physicians have the minimum competencies needed to provide safe and effective health care.”
In his order, Cooper wrote that Giri has not proven the board’s actions were discriminatory against Nepali doctors.
“Nothing in the present record suggests that NBME went looking for a problem in Nepal out of ethnicity-or national-origin based [sic] suspicion,” Cooper wrote. “[It] followed the trail of evidence, including tips about organized cheating taking place in medical schools and at a testing center located in Nepal, and on an online forum for which a ‘nexus to Nepal’ was a ticket to admission.”
NBME: Nepal Outperformed All Other Countries on USMLE
Court documents shed more light on NBME’s investigation into the suspected cheating and on the anomalous patterns the board allegedly discovered from Nepal medical graduates.
In response to anonymous tips, the USMLE program in early 2023 asked the NBME Psychometrics and Data Analysis (PADA) unit to analyze examinee performance data for test centers in Jordan, Nepal, and Pakistan, according to court records. Within the initial data analysis, the data involving the single test center in Nepal was “the most extreme,” the unit found.
Out of more than 400 test centers across the world, including those in the United States, the test center in Nepal produced the highest test scores in the world for Step 1 in 2021 and 2022 and the highest test scores in the world for Step 2 CK in 2022, according to court documents. For the 2022 Step 1 exam for example, the average score of examinees testing in the Nepal test center was 240. No other test center in the world had an average examinee score above 227, according to the NBME’s legal response.
The median item response time for examinees who tested at the Nepal test center in 2022 was also among the fastest of all international test centers for Step 1 and Step 2 CK, investigators found.
In addition, the volume of examinees taking the USMLE Step 1 and Step 2 CK at the Nepal test center in Nepal had sharply increased. Step 1 volume more than doubled in the Nepal test center from 281 examinees in 2019 to 662 examinees in 2022, according to court documents.
The rapid increase continued in 2023, when examinee volume was nearly three-and-a-half times higher than the 2019 volume. The data were consistent with anonymous tips received by the USMLE program office, suggesting there may be wide-scale collection and sharing of live USMLE exam content within Nepal.
Investigation Finds Similar Correct and Incorrect Answers
Agreement similarity among the exams analyzed also raised red flags. Investigators ran an “agreement analysis” for all examinees who tested at centers in Jordan, Nepal, and Pakistan as well as two centers in India, according to court documents.
For the 2022 Step 1 exam and the 2021 and 2022 Step 2 CK exam, the analysis showed a substantially higher percentage of examinees with a statistically significant level of agreement matches in the examine group that tested at centers in Jordan, Nepal, Pakistan, and India compared with the baseline group, according to legal records.
The vast majority of examinees with a statistically significant number of matching incorrect answers tested at the Nepal test center, data showed.
Further analysis found that examinee volumes increased considerably at the Nepal test center in the months prior to the USMLE program releasing new test items, “suggesting that candidates who had prior access to disclosed exam questions wanted to test before new questions came into the item pool.”
Investigators also identified posts on social medial and in online chat rooms suggesting groups were collecting and sharing large amounts of secure exam material in private groups. Some posts advised examinees to use the full examination time when taking the USMLE “to avoid raising suspicion about having had prior access to secure exam materials,” according to court documents.
From its investigation and analysis, the USMLE program identified 832 examinees who had passing level exam results whose validity the USMLE program had a significant and good faith basis for questioning, according to court records.
Of the total, 618 examinees had one Step score flagged as being of questioned validity, 202 examinees had two Step exam scores flagged, and 12 examinees had scores flagged on all three Step exams.
NBME Defends Departure From Traditional Procedures
In court documents, NBME disputed claims that it violated its own procedures by invalidating the exam scores. Giri’s report contends that examinees suspected of cheating are typically first advised of the matter, given an opportunity to share relevant information, and provided the right to appeal — during which time, their scores are treated as valid.
But the NBME said the USMLE program is authorized to take any actions it deems appropriate in response to concerns regarding score validity if the USMLE Committee for Individualized Review or the USMLE Composite Committee concludes that alternative or supplemental procedures are warranted in response to a given set of facts or circumstances.
“Following the month-long investigation and analysis…the USMLE program concluded that alternative procedures were warranted to address the score invalidity concerns identified in the interest of providing a process that is timely, efficient, effective, and fair, and given the large number of examinees involved in the investigation,” the board stated in its legal response.
In his order, Cooper wrote the current scenario, which implicates that more than 800 test-takers, is “clearly a situation calling for a procedure geared toward efficiency.” No evidence shows the board would not have taken similarly swift action if confronted with evidence of cheating on a comparable scale elsewhere, he wrote.
The judge also denied Giri’s motion to certify the lawsuit as a class action. The motion was denied without prejudice, meaning the plaintiff has the option to renew the motion should the case proceed.
A version of this article appeared on Medscape.com.
(USMLE).
In a February 23 order, Judge Christopher R. Cooper, of the US District Court for the District of Columbia, denied Latika Giri’s emergency motion to block the National Board of Medical Examiners (NBME) from invalidating the scores, ruling the public interest plainly weighs against granting the request.
“First and foremost, is the overriding interest in public safety,” Cooper wrote in his 32-page order. “This is a case about the credentials of doctors applying to medical residency programs…Granting the preliminary injunction would create an unacceptable risk that individuals who lack the requisite knowledge and skills they purport to possess because they achieved their exam scores fraudulently will be administering medical care to unsuspecting patients across the nation.”
Attorneys for Giri did not return messages seeking comment about the order.
The NBME also did not return messages seeking comment. The board previously said it does not comment on pending litigation.
The decision is the latest development in a widespread cheating scandal. Giri, an international medical graduate (IMG) from Kathmandu, sued NBME earlier this month claiming the board discriminated against Nepali medical graduates when it invalidated hundreds of exam scores linked to the country.
Giri also accused NBME of violating its own procedures when it voided the scores before giving examinees a chance to argue and appeal. She asked the district court to block NBME from invalidating her exam scores while the lawsuit continues and restore her original results.
In court documents, NBME argued that it did not invalidate the scores because the examinees were Nepali but because staff concluded that there was “a good faith basis for questioning the validity of the scores.”
The invalidations were based on concerns that the results reflected prior access to secure exam content rather than knowledge and understanding of the medical principles and skills the exams are intended to assess, according to the NBME’s legal response.
“The USMLE program took reasonable and appropriate actions to prevent the significant harm and disruption that would result from allowing potentially unqualified individuals to participate in the 2024 residency Match,” the NBME stated in court documents. “If granted, the requested injunction would cause enormous harm not only to NBME… but also to state licensing authorities, which rely upon USMLE results to help ensure that physicians have the minimum competencies needed to provide safe and effective health care.”
In his order, Cooper wrote that Giri has not proven the board’s actions were discriminatory against Nepali doctors.
“Nothing in the present record suggests that NBME went looking for a problem in Nepal out of ethnicity-or national-origin based [sic] suspicion,” Cooper wrote. “[It] followed the trail of evidence, including tips about organized cheating taking place in medical schools and at a testing center located in Nepal, and on an online forum for which a ‘nexus to Nepal’ was a ticket to admission.”
NBME: Nepal Outperformed All Other Countries on USMLE
Court documents shed more light on NBME’s investigation into the suspected cheating and on the anomalous patterns the board allegedly discovered from Nepal medical graduates.
In response to anonymous tips, the USMLE program in early 2023 asked the NBME Psychometrics and Data Analysis (PADA) unit to analyze examinee performance data for test centers in Jordan, Nepal, and Pakistan, according to court records. Within the initial data analysis, the data involving the single test center in Nepal was “the most extreme,” the unit found.
Out of more than 400 test centers across the world, including those in the United States, the test center in Nepal produced the highest test scores in the world for Step 1 in 2021 and 2022 and the highest test scores in the world for Step 2 CK in 2022, according to court documents. For the 2022 Step 1 exam for example, the average score of examinees testing in the Nepal test center was 240. No other test center in the world had an average examinee score above 227, according to the NBME’s legal response.
The median item response time for examinees who tested at the Nepal test center in 2022 was also among the fastest of all international test centers for Step 1 and Step 2 CK, investigators found.
In addition, the volume of examinees taking the USMLE Step 1 and Step 2 CK at the Nepal test center in Nepal had sharply increased. Step 1 volume more than doubled in the Nepal test center from 281 examinees in 2019 to 662 examinees in 2022, according to court documents.
The rapid increase continued in 2023, when examinee volume was nearly three-and-a-half times higher than the 2019 volume. The data were consistent with anonymous tips received by the USMLE program office, suggesting there may be wide-scale collection and sharing of live USMLE exam content within Nepal.
Investigation Finds Similar Correct and Incorrect Answers
Agreement similarity among the exams analyzed also raised red flags. Investigators ran an “agreement analysis” for all examinees who tested at centers in Jordan, Nepal, and Pakistan as well as two centers in India, according to court documents.
For the 2022 Step 1 exam and the 2021 and 2022 Step 2 CK exam, the analysis showed a substantially higher percentage of examinees with a statistically significant level of agreement matches in the examine group that tested at centers in Jordan, Nepal, Pakistan, and India compared with the baseline group, according to legal records.
The vast majority of examinees with a statistically significant number of matching incorrect answers tested at the Nepal test center, data showed.
Further analysis found that examinee volumes increased considerably at the Nepal test center in the months prior to the USMLE program releasing new test items, “suggesting that candidates who had prior access to disclosed exam questions wanted to test before new questions came into the item pool.”
Investigators also identified posts on social medial and in online chat rooms suggesting groups were collecting and sharing large amounts of secure exam material in private groups. Some posts advised examinees to use the full examination time when taking the USMLE “to avoid raising suspicion about having had prior access to secure exam materials,” according to court documents.
From its investigation and analysis, the USMLE program identified 832 examinees who had passing level exam results whose validity the USMLE program had a significant and good faith basis for questioning, according to court records.
Of the total, 618 examinees had one Step score flagged as being of questioned validity, 202 examinees had two Step exam scores flagged, and 12 examinees had scores flagged on all three Step exams.
NBME Defends Departure From Traditional Procedures
In court documents, NBME disputed claims that it violated its own procedures by invalidating the exam scores. Giri’s report contends that examinees suspected of cheating are typically first advised of the matter, given an opportunity to share relevant information, and provided the right to appeal — during which time, their scores are treated as valid.
But the NBME said the USMLE program is authorized to take any actions it deems appropriate in response to concerns regarding score validity if the USMLE Committee for Individualized Review or the USMLE Composite Committee concludes that alternative or supplemental procedures are warranted in response to a given set of facts or circumstances.
“Following the month-long investigation and analysis…the USMLE program concluded that alternative procedures were warranted to address the score invalidity concerns identified in the interest of providing a process that is timely, efficient, effective, and fair, and given the large number of examinees involved in the investigation,” the board stated in its legal response.
In his order, Cooper wrote the current scenario, which implicates that more than 800 test-takers, is “clearly a situation calling for a procedure geared toward efficiency.” No evidence shows the board would not have taken similarly swift action if confronted with evidence of cheating on a comparable scale elsewhere, he wrote.
The judge also denied Giri’s motion to certify the lawsuit as a class action. The motion was denied without prejudice, meaning the plaintiff has the option to renew the motion should the case proceed.
A version of this article appeared on Medscape.com.
MOC Woes? This System Might Be the Solution
, and what he hopes will prove less stressful approach to maintaining his credentials: The Longitudinal Knowledge Assessment (LKA).
Dr. Ali, assistant professor at the Icahn School of Medicine at Mount Sinai in New York City, is far from alone. Since the American Board of Internal Medicine (ABIM) launched the new method in 2022, approximately 80% of internists have chosen the LKA to maintain their board certification over the 10-year Maintenance of Certification (MOC) exam coupled with continuing education requirements.
“You have to keep learning. I think the LKA is good in that regard, as long as the questions are relevantly updated,” said Dr. Ali, who was first board-certified in 2018 and obtained his geriatrics certification in 2020.
Many other internists contend the MOC is too time-consuming and expensive and have taken action.
Some specialists, including a group of oncologists, argue the exam contains too much information that has become irrelevant to clinical practice. Members of the American College of Cardiology have even left ABIM over the certification process, as this news organization previously reported. After receiving criticism, the ABIM introduced longitudinal assessment as a less onerous means to maintain certification — although the group denies it succumbed to negative feedback.
One and Done, or More Flexibility?
Both the traditional 10-year exam and the LKA have their advantages and disadvantages, according to Helen Chen, MD, the chair of the Geriatric Medicine Board Exam–Writing Committee at ABIM.
The LKA is arguably easier to access and available for most internal medicine disciplines. It requires no preparation for studying, and internists can complete exam questions on their phone, computer, or tablet.
Participants receive 30 questions per quarter for 5 years. Feedback is immediate and includes links to references for further learning. Once the process is completed and a physician meets the performance standard, the next 5-year cycle begins.
Still, some physicians still prefer the traditional 10-year, long-form exam. Studying for the test can be intense and take months. Physicians also must travel to an exam center on a designated date. However, once the test is over, the certification test does not roll around for another decade.
“It’s really about choice. Some doctors want to sit down and do it all at once and get it over with; others prefer to do a few questions at a time and never feel rushed,” said Dr. Chen, who is triple-boarded in geriatrics, internal medicine, and hospice and palliative medicine.
In 2022, Dr. Chen opted to begin the LKA cycle; a cross-country move and new job would not have allowed her enough time to prepare for the long-form exam, she said.
The new exam challenged her knowledge in smaller bites, provided immediate feedback, and allowed her to satisfy her curiosity through additional reading, she said, even if some questions were not relevant to her clinical practice.
The LKA is not yet as specialized, and ABIM is working to refine questions to be more relevant for some subspecialties.
Questions for both the LKA and long-form exam are developed from physician input, according to Dr. Chen. They are regularly assessed for relevance, accuracy, and changes to practice guidelines.
She acknowledged that questions can sometimes become outdated in a relatively short time, particularly for those taking the 10-year exam. But feedback from physicians helps committees analyze the relevancy of questions and how intensely an area should be tested. Committee members will even throw out questions if the literature changes significantly.
An Unnecessary Exercise
As criticism has mounted over the MOC, physicians have questioned whether recertification is necessary.
According to a survey of 1700 members of the American Society of Clinical Oncology (ASCO), most (64%) backed initial ABIM certification, but three quarters said the recertification process did not benefit their knowledge of clinical practice. More than 80% reported that Continuing Medical Education (CME) credits should suffice for ongoing learning, without having to be supplemented by the MOC exam. ASCO is considering alternative pathways to the current process based on their member feedback and plans to release a proposal to members in the first half of 2024.
Meanwhile, some cardiologists have called the MOC process “an onerous and unnecessary addition to continuing medical education requirements they already must meet at the state and hospital levels.”
The ABIM responded in part in a recent JAMA Viewpoint written by several members of the ABIM board of directors. They said board-certified physicians save the health system about $5 billion annually, compared with those who are not.
“Patients who are cared for by physicians who demonstrate more medical knowledge through certification and MOC have a better prognosis for a host of important outcomes including lower mortality from cardiovascular disease, fewer emergency department visits, and fewer unplanned hospitalizations,” the group wrote.
Certification provides a significant benefit, according to Dr. Ali. Some of his patients do ask about his credentials. He said he also finds keeping up with the latest information essential. Ongoing learning shows patients he is committed to providing the best care, he said. “It benefits me, and I’ve benefited my patients. When they come in with questions, I can speak knowledgeably,” he said.
Maintaining board certification is also not unique to internal medicine physicians or subspecialists. Other physician specialties mandate more frequent exams, include both oral and written portions, or administer exams totally online. The American Academy of Family Physicians (AAFP) has a longitudinal option, similar to the LKA, as an alternative to their 1-day exam.
Margo Savoy, MD, MPH, senior vice president of education, inclusiveness, and physician well-being at AAFP, said physicians should make the best choice for them.
“The AAFP welcomes the opportunity for family physicians to have options for how to demonstrate their competence and strongly encourages a balanced approach that avoids undue administrative burdens and fosters a culture of physician well-being and high-quality care,” Dr. Savoy said.
The ABIM has also been criticized for the fee structure for MOC, which some physicians consider excessive: $220 per year for the first certification and $120 for each additional certification. Physicians choosing to take the 10-year exam are charged an additional $700 testing center fee. Those charges do not include the cost of attending CME-related activities. One analysis estimated the cost of maintaining certification could reach into the tens of thousands of dollars, primarily from the time physicians must spend preparing for the long-form exam.
Dr. Chen pushed back on the contention that the ABIM is making a huge profit off of the 10-year exam. She called MOC fees reasonable when amortized over a 10-year cycle and noted the costs for longitudinal assessment are included in those charges.
Meanwhile, she encouraged physicians who were on the fence about maintaining board certification at all to consider both the benefit to their practice and to their patients, especially since the LKA has already demonstrated such popularity.
“There’s nothing like continuous learning to keep you humble,” Dr. Chen said. “You just don’t know everything.”
A version of this article appeared on Medscape.com.
, and what he hopes will prove less stressful approach to maintaining his credentials: The Longitudinal Knowledge Assessment (LKA).
Dr. Ali, assistant professor at the Icahn School of Medicine at Mount Sinai in New York City, is far from alone. Since the American Board of Internal Medicine (ABIM) launched the new method in 2022, approximately 80% of internists have chosen the LKA to maintain their board certification over the 10-year Maintenance of Certification (MOC) exam coupled with continuing education requirements.
“You have to keep learning. I think the LKA is good in that regard, as long as the questions are relevantly updated,” said Dr. Ali, who was first board-certified in 2018 and obtained his geriatrics certification in 2020.
Many other internists contend the MOC is too time-consuming and expensive and have taken action.
Some specialists, including a group of oncologists, argue the exam contains too much information that has become irrelevant to clinical practice. Members of the American College of Cardiology have even left ABIM over the certification process, as this news organization previously reported. After receiving criticism, the ABIM introduced longitudinal assessment as a less onerous means to maintain certification — although the group denies it succumbed to negative feedback.
One and Done, or More Flexibility?
Both the traditional 10-year exam and the LKA have their advantages and disadvantages, according to Helen Chen, MD, the chair of the Geriatric Medicine Board Exam–Writing Committee at ABIM.
The LKA is arguably easier to access and available for most internal medicine disciplines. It requires no preparation for studying, and internists can complete exam questions on their phone, computer, or tablet.
Participants receive 30 questions per quarter for 5 years. Feedback is immediate and includes links to references for further learning. Once the process is completed and a physician meets the performance standard, the next 5-year cycle begins.
Still, some physicians still prefer the traditional 10-year, long-form exam. Studying for the test can be intense and take months. Physicians also must travel to an exam center on a designated date. However, once the test is over, the certification test does not roll around for another decade.
“It’s really about choice. Some doctors want to sit down and do it all at once and get it over with; others prefer to do a few questions at a time and never feel rushed,” said Dr. Chen, who is triple-boarded in geriatrics, internal medicine, and hospice and palliative medicine.
In 2022, Dr. Chen opted to begin the LKA cycle; a cross-country move and new job would not have allowed her enough time to prepare for the long-form exam, she said.
The new exam challenged her knowledge in smaller bites, provided immediate feedback, and allowed her to satisfy her curiosity through additional reading, she said, even if some questions were not relevant to her clinical practice.
The LKA is not yet as specialized, and ABIM is working to refine questions to be more relevant for some subspecialties.
Questions for both the LKA and long-form exam are developed from physician input, according to Dr. Chen. They are regularly assessed for relevance, accuracy, and changes to practice guidelines.
She acknowledged that questions can sometimes become outdated in a relatively short time, particularly for those taking the 10-year exam. But feedback from physicians helps committees analyze the relevancy of questions and how intensely an area should be tested. Committee members will even throw out questions if the literature changes significantly.
An Unnecessary Exercise
As criticism has mounted over the MOC, physicians have questioned whether recertification is necessary.
According to a survey of 1700 members of the American Society of Clinical Oncology (ASCO), most (64%) backed initial ABIM certification, but three quarters said the recertification process did not benefit their knowledge of clinical practice. More than 80% reported that Continuing Medical Education (CME) credits should suffice for ongoing learning, without having to be supplemented by the MOC exam. ASCO is considering alternative pathways to the current process based on their member feedback and plans to release a proposal to members in the first half of 2024.
Meanwhile, some cardiologists have called the MOC process “an onerous and unnecessary addition to continuing medical education requirements they already must meet at the state and hospital levels.”
The ABIM responded in part in a recent JAMA Viewpoint written by several members of the ABIM board of directors. They said board-certified physicians save the health system about $5 billion annually, compared with those who are not.
“Patients who are cared for by physicians who demonstrate more medical knowledge through certification and MOC have a better prognosis for a host of important outcomes including lower mortality from cardiovascular disease, fewer emergency department visits, and fewer unplanned hospitalizations,” the group wrote.
Certification provides a significant benefit, according to Dr. Ali. Some of his patients do ask about his credentials. He said he also finds keeping up with the latest information essential. Ongoing learning shows patients he is committed to providing the best care, he said. “It benefits me, and I’ve benefited my patients. When they come in with questions, I can speak knowledgeably,” he said.
Maintaining board certification is also not unique to internal medicine physicians or subspecialists. Other physician specialties mandate more frequent exams, include both oral and written portions, or administer exams totally online. The American Academy of Family Physicians (AAFP) has a longitudinal option, similar to the LKA, as an alternative to their 1-day exam.
Margo Savoy, MD, MPH, senior vice president of education, inclusiveness, and physician well-being at AAFP, said physicians should make the best choice for them.
“The AAFP welcomes the opportunity for family physicians to have options for how to demonstrate their competence and strongly encourages a balanced approach that avoids undue administrative burdens and fosters a culture of physician well-being and high-quality care,” Dr. Savoy said.
The ABIM has also been criticized for the fee structure for MOC, which some physicians consider excessive: $220 per year for the first certification and $120 for each additional certification. Physicians choosing to take the 10-year exam are charged an additional $700 testing center fee. Those charges do not include the cost of attending CME-related activities. One analysis estimated the cost of maintaining certification could reach into the tens of thousands of dollars, primarily from the time physicians must spend preparing for the long-form exam.
Dr. Chen pushed back on the contention that the ABIM is making a huge profit off of the 10-year exam. She called MOC fees reasonable when amortized over a 10-year cycle and noted the costs for longitudinal assessment are included in those charges.
Meanwhile, she encouraged physicians who were on the fence about maintaining board certification at all to consider both the benefit to their practice and to their patients, especially since the LKA has already demonstrated such popularity.
“There’s nothing like continuous learning to keep you humble,” Dr. Chen said. “You just don’t know everything.”
A version of this article appeared on Medscape.com.
, and what he hopes will prove less stressful approach to maintaining his credentials: The Longitudinal Knowledge Assessment (LKA).
Dr. Ali, assistant professor at the Icahn School of Medicine at Mount Sinai in New York City, is far from alone. Since the American Board of Internal Medicine (ABIM) launched the new method in 2022, approximately 80% of internists have chosen the LKA to maintain their board certification over the 10-year Maintenance of Certification (MOC) exam coupled with continuing education requirements.
“You have to keep learning. I think the LKA is good in that regard, as long as the questions are relevantly updated,” said Dr. Ali, who was first board-certified in 2018 and obtained his geriatrics certification in 2020.
Many other internists contend the MOC is too time-consuming and expensive and have taken action.
Some specialists, including a group of oncologists, argue the exam contains too much information that has become irrelevant to clinical practice. Members of the American College of Cardiology have even left ABIM over the certification process, as this news organization previously reported. After receiving criticism, the ABIM introduced longitudinal assessment as a less onerous means to maintain certification — although the group denies it succumbed to negative feedback.
One and Done, or More Flexibility?
Both the traditional 10-year exam and the LKA have their advantages and disadvantages, according to Helen Chen, MD, the chair of the Geriatric Medicine Board Exam–Writing Committee at ABIM.
The LKA is arguably easier to access and available for most internal medicine disciplines. It requires no preparation for studying, and internists can complete exam questions on their phone, computer, or tablet.
Participants receive 30 questions per quarter for 5 years. Feedback is immediate and includes links to references for further learning. Once the process is completed and a physician meets the performance standard, the next 5-year cycle begins.
Still, some physicians still prefer the traditional 10-year, long-form exam. Studying for the test can be intense and take months. Physicians also must travel to an exam center on a designated date. However, once the test is over, the certification test does not roll around for another decade.
“It’s really about choice. Some doctors want to sit down and do it all at once and get it over with; others prefer to do a few questions at a time and never feel rushed,” said Dr. Chen, who is triple-boarded in geriatrics, internal medicine, and hospice and palliative medicine.
In 2022, Dr. Chen opted to begin the LKA cycle; a cross-country move and new job would not have allowed her enough time to prepare for the long-form exam, she said.
The new exam challenged her knowledge in smaller bites, provided immediate feedback, and allowed her to satisfy her curiosity through additional reading, she said, even if some questions were not relevant to her clinical practice.
The LKA is not yet as specialized, and ABIM is working to refine questions to be more relevant for some subspecialties.
Questions for both the LKA and long-form exam are developed from physician input, according to Dr. Chen. They are regularly assessed for relevance, accuracy, and changes to practice guidelines.
She acknowledged that questions can sometimes become outdated in a relatively short time, particularly for those taking the 10-year exam. But feedback from physicians helps committees analyze the relevancy of questions and how intensely an area should be tested. Committee members will even throw out questions if the literature changes significantly.
An Unnecessary Exercise
As criticism has mounted over the MOC, physicians have questioned whether recertification is necessary.
According to a survey of 1700 members of the American Society of Clinical Oncology (ASCO), most (64%) backed initial ABIM certification, but three quarters said the recertification process did not benefit their knowledge of clinical practice. More than 80% reported that Continuing Medical Education (CME) credits should suffice for ongoing learning, without having to be supplemented by the MOC exam. ASCO is considering alternative pathways to the current process based on their member feedback and plans to release a proposal to members in the first half of 2024.
Meanwhile, some cardiologists have called the MOC process “an onerous and unnecessary addition to continuing medical education requirements they already must meet at the state and hospital levels.”
The ABIM responded in part in a recent JAMA Viewpoint written by several members of the ABIM board of directors. They said board-certified physicians save the health system about $5 billion annually, compared with those who are not.
“Patients who are cared for by physicians who demonstrate more medical knowledge through certification and MOC have a better prognosis for a host of important outcomes including lower mortality from cardiovascular disease, fewer emergency department visits, and fewer unplanned hospitalizations,” the group wrote.
Certification provides a significant benefit, according to Dr. Ali. Some of his patients do ask about his credentials. He said he also finds keeping up with the latest information essential. Ongoing learning shows patients he is committed to providing the best care, he said. “It benefits me, and I’ve benefited my patients. When they come in with questions, I can speak knowledgeably,” he said.
Maintaining board certification is also not unique to internal medicine physicians or subspecialists. Other physician specialties mandate more frequent exams, include both oral and written portions, or administer exams totally online. The American Academy of Family Physicians (AAFP) has a longitudinal option, similar to the LKA, as an alternative to their 1-day exam.
Margo Savoy, MD, MPH, senior vice president of education, inclusiveness, and physician well-being at AAFP, said physicians should make the best choice for them.
“The AAFP welcomes the opportunity for family physicians to have options for how to demonstrate their competence and strongly encourages a balanced approach that avoids undue administrative burdens and fosters a culture of physician well-being and high-quality care,” Dr. Savoy said.
The ABIM has also been criticized for the fee structure for MOC, which some physicians consider excessive: $220 per year for the first certification and $120 for each additional certification. Physicians choosing to take the 10-year exam are charged an additional $700 testing center fee. Those charges do not include the cost of attending CME-related activities. One analysis estimated the cost of maintaining certification could reach into the tens of thousands of dollars, primarily from the time physicians must spend preparing for the long-form exam.
Dr. Chen pushed back on the contention that the ABIM is making a huge profit off of the 10-year exam. She called MOC fees reasonable when amortized over a 10-year cycle and noted the costs for longitudinal assessment are included in those charges.
Meanwhile, she encouraged physicians who were on the fence about maintaining board certification at all to consider both the benefit to their practice and to their patients, especially since the LKA has already demonstrated such popularity.
“There’s nothing like continuous learning to keep you humble,” Dr. Chen said. “You just don’t know everything.”
A version of this article appeared on Medscape.com.
Poor Quality of Cancer Content on Social Media
This transcript has been edited for clarity.
I’m delighted to talk about a very interesting topic in this commentary. This is an area that we generally don’t discuss, but it’s one that’s obviously very topical, which includes the question of social media.
The paper I’m referring to is entitled, “More Than a Song and Dance”: Exploration of Patient Perspectives and Educational Quality of Gynecologic Cancer Content on TikTok. The paper was published in Gynecologic Oncology in 2023.
They had a total of 466.7 million views. They looked at 430 of the 500 top posts that were eligible, looked at 11 central themes, did an objective analysis of educational content based on published strategy for looking at this.
What they found, unfortunately but not surprisingly, overall was that the educational quality and reliability were quite poor. They also noticed considerable differences in disparities based on racial background and really emphasized in their analysis not only how common it is for individuals to look at this content on TikTok but also concerns about what it is that the public, patients, and their families are actually seeing.
This, of course, specifically relates to gynecologic cancers, but almost certainly relates to other cancers as well. Clearly, this is a topic that needs to be discussed widely. It’s very complex and very controversial, but when you think about the information that might be provided to our patients and their families going to social media, it’s important that we understand what they’re seeing, what they’re hearing, what they’re viewing, and the impact this might have on their care and outcomes.
I encourage you to read this very interesting paper if you have an interest in this topic. Again, it was recently published in Gynecologic Oncology. I thank you for your attention.
Dr. Markman is professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California; president of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline and AstraZeneca.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I’m delighted to talk about a very interesting topic in this commentary. This is an area that we generally don’t discuss, but it’s one that’s obviously very topical, which includes the question of social media.
The paper I’m referring to is entitled, “More Than a Song and Dance”: Exploration of Patient Perspectives and Educational Quality of Gynecologic Cancer Content on TikTok. The paper was published in Gynecologic Oncology in 2023.
They had a total of 466.7 million views. They looked at 430 of the 500 top posts that were eligible, looked at 11 central themes, did an objective analysis of educational content based on published strategy for looking at this.
What they found, unfortunately but not surprisingly, overall was that the educational quality and reliability were quite poor. They also noticed considerable differences in disparities based on racial background and really emphasized in their analysis not only how common it is for individuals to look at this content on TikTok but also concerns about what it is that the public, patients, and their families are actually seeing.
This, of course, specifically relates to gynecologic cancers, but almost certainly relates to other cancers as well. Clearly, this is a topic that needs to be discussed widely. It’s very complex and very controversial, but when you think about the information that might be provided to our patients and their families going to social media, it’s important that we understand what they’re seeing, what they’re hearing, what they’re viewing, and the impact this might have on their care and outcomes.
I encourage you to read this very interesting paper if you have an interest in this topic. Again, it was recently published in Gynecologic Oncology. I thank you for your attention.
Dr. Markman is professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California; president of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline and AstraZeneca.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I’m delighted to talk about a very interesting topic in this commentary. This is an area that we generally don’t discuss, but it’s one that’s obviously very topical, which includes the question of social media.
The paper I’m referring to is entitled, “More Than a Song and Dance”: Exploration of Patient Perspectives and Educational Quality of Gynecologic Cancer Content on TikTok. The paper was published in Gynecologic Oncology in 2023.
They had a total of 466.7 million views. They looked at 430 of the 500 top posts that were eligible, looked at 11 central themes, did an objective analysis of educational content based on published strategy for looking at this.
What they found, unfortunately but not surprisingly, overall was that the educational quality and reliability were quite poor. They also noticed considerable differences in disparities based on racial background and really emphasized in their analysis not only how common it is for individuals to look at this content on TikTok but also concerns about what it is that the public, patients, and their families are actually seeing.
This, of course, specifically relates to gynecologic cancers, but almost certainly relates to other cancers as well. Clearly, this is a topic that needs to be discussed widely. It’s very complex and very controversial, but when you think about the information that might be provided to our patients and their families going to social media, it’s important that we understand what they’re seeing, what they’re hearing, what they’re viewing, and the impact this might have on their care and outcomes.
I encourage you to read this very interesting paper if you have an interest in this topic. Again, it was recently published in Gynecologic Oncology. I thank you for your attention.
Dr. Markman is professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California; president of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline and AstraZeneca.
A version of this article appeared on Medscape.com.
Communicating Bad News to Patients
Communicating bad news to patients is one of the most stressful and challenging clinical tasks for any physician, regardless of his or her specialty. This task is more frequent for physicians caring for oncology patients and can also affect the physician’s emotional state.
The manner in which bad news is communicated plays a significant role in the psychological burden on the patient, and various communication techniques and guidelines have been developed to enable physicians to perform this difficult task effectively.
Revealing bad news in person whenever possible, to address the emotional responses of patients or relatives, is part of the prevailing expert recommendations. However, it has been acknowledged that in certain situations, communicating bad news over the phone is more feasible.
Since the beginning of the COVID-19 pandemic, the disclosure of bad news over the phone has become a necessary substitute for in-person visits and an integral part of clinical practice worldwide. It remains to be clarified what the real psychological impact on patients and their closest relatives is when delivering bad news over the phone compared with delivering it in person.
Right and Wrong Ways
The most popular guideline for communicating bad news is SPIKES, a six-phase protocol with a special application for cancer patients. It is used in various countries (eg, the United States, France, and Germany) as a guide for this sensitive practice and for training in communication skills in this context. The SPIKES acronym refers to the following six recommended steps for delivering bad news:
- Setting: Set up the conversation.
- Perception: Assess the patient’s perception.
- Invitation: Ask the patient what he or she would like to know.
- Knowledge: Provide the patient with knowledge and information, breaking it down into small parts.
- Emotions: Acknowledge and empathetically address the patient’s emotions.
- Strategy and Summary: Summarize and define a medical action plan.
The lesson from SPIKES is that when a person experiences strong emotions, it is difficult to continue discussing anything, and they will struggle to hear anything. Allowing for silence is fundamental. In addition, empathy allows the patient to express his or her feelings and concerns, as well as provide support. The aim is not to argue but to allow the expression of emotions without criticism. However, these recommendations are primarily based on expert opinion and less on empirical evidence, due to the difficulty of studies in assessing patient outcomes in various phases of these protocols.
A recent study analyzed the differences in psychological distress between patients who received bad news over the phone vs those who received it in person. The study was a systematic review and meta-analysis.
The investigators examined 5944 studies, including 11 qualitative analysis studies, nine meta-analyses, and four randomized controlled trials.
In a set of studies ranging from moderate to good quality, no difference in psychological distress was found when bad news was disclosed over the phone compared with in person, regarding anxiety, depression, and posttraumatic stress disorder.
There was no average difference in patient satisfaction levels when bad news was delivered over the phone compared with in person. The risk for dissatisfaction was similar between groups.
Clinical Practice Guidelines
The demand for telemedicine, including the disclosure of bad news, is growing despite the limited knowledge of potential adverse effects. The results of existing studies suggest that the mode of disclosure may play a secondary role, and the manner in which bad news is communicated may be more important.
Therefore, it is paramount to prepare patients or their families for the possibility of receiving bad news well in advance and, during the conversation, to ensure first and foremost that they are in an appropriate environment. The structure and content of the conversation may be relevant, and adhering to dedicated communication strategies can be a wise choice for the physician and the interlocutor.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Communicating bad news to patients is one of the most stressful and challenging clinical tasks for any physician, regardless of his or her specialty. This task is more frequent for physicians caring for oncology patients and can also affect the physician’s emotional state.
The manner in which bad news is communicated plays a significant role in the psychological burden on the patient, and various communication techniques and guidelines have been developed to enable physicians to perform this difficult task effectively.
Revealing bad news in person whenever possible, to address the emotional responses of patients or relatives, is part of the prevailing expert recommendations. However, it has been acknowledged that in certain situations, communicating bad news over the phone is more feasible.
Since the beginning of the COVID-19 pandemic, the disclosure of bad news over the phone has become a necessary substitute for in-person visits and an integral part of clinical practice worldwide. It remains to be clarified what the real psychological impact on patients and their closest relatives is when delivering bad news over the phone compared with delivering it in person.
Right and Wrong Ways
The most popular guideline for communicating bad news is SPIKES, a six-phase protocol with a special application for cancer patients. It is used in various countries (eg, the United States, France, and Germany) as a guide for this sensitive practice and for training in communication skills in this context. The SPIKES acronym refers to the following six recommended steps for delivering bad news:
- Setting: Set up the conversation.
- Perception: Assess the patient’s perception.
- Invitation: Ask the patient what he or she would like to know.
- Knowledge: Provide the patient with knowledge and information, breaking it down into small parts.
- Emotions: Acknowledge and empathetically address the patient’s emotions.
- Strategy and Summary: Summarize and define a medical action plan.
The lesson from SPIKES is that when a person experiences strong emotions, it is difficult to continue discussing anything, and they will struggle to hear anything. Allowing for silence is fundamental. In addition, empathy allows the patient to express his or her feelings and concerns, as well as provide support. The aim is not to argue but to allow the expression of emotions without criticism. However, these recommendations are primarily based on expert opinion and less on empirical evidence, due to the difficulty of studies in assessing patient outcomes in various phases of these protocols.
A recent study analyzed the differences in psychological distress between patients who received bad news over the phone vs those who received it in person. The study was a systematic review and meta-analysis.
The investigators examined 5944 studies, including 11 qualitative analysis studies, nine meta-analyses, and four randomized controlled trials.
In a set of studies ranging from moderate to good quality, no difference in psychological distress was found when bad news was disclosed over the phone compared with in person, regarding anxiety, depression, and posttraumatic stress disorder.
There was no average difference in patient satisfaction levels when bad news was delivered over the phone compared with in person. The risk for dissatisfaction was similar between groups.
Clinical Practice Guidelines
The demand for telemedicine, including the disclosure of bad news, is growing despite the limited knowledge of potential adverse effects. The results of existing studies suggest that the mode of disclosure may play a secondary role, and the manner in which bad news is communicated may be more important.
Therefore, it is paramount to prepare patients or their families for the possibility of receiving bad news well in advance and, during the conversation, to ensure first and foremost that they are in an appropriate environment. The structure and content of the conversation may be relevant, and adhering to dedicated communication strategies can be a wise choice for the physician and the interlocutor.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Communicating bad news to patients is one of the most stressful and challenging clinical tasks for any physician, regardless of his or her specialty. This task is more frequent for physicians caring for oncology patients and can also affect the physician’s emotional state.
The manner in which bad news is communicated plays a significant role in the psychological burden on the patient, and various communication techniques and guidelines have been developed to enable physicians to perform this difficult task effectively.
Revealing bad news in person whenever possible, to address the emotional responses of patients or relatives, is part of the prevailing expert recommendations. However, it has been acknowledged that in certain situations, communicating bad news over the phone is more feasible.
Since the beginning of the COVID-19 pandemic, the disclosure of bad news over the phone has become a necessary substitute for in-person visits and an integral part of clinical practice worldwide. It remains to be clarified what the real psychological impact on patients and their closest relatives is when delivering bad news over the phone compared with delivering it in person.
Right and Wrong Ways
The most popular guideline for communicating bad news is SPIKES, a six-phase protocol with a special application for cancer patients. It is used in various countries (eg, the United States, France, and Germany) as a guide for this sensitive practice and for training in communication skills in this context. The SPIKES acronym refers to the following six recommended steps for delivering bad news:
- Setting: Set up the conversation.
- Perception: Assess the patient’s perception.
- Invitation: Ask the patient what he or she would like to know.
- Knowledge: Provide the patient with knowledge and information, breaking it down into small parts.
- Emotions: Acknowledge and empathetically address the patient’s emotions.
- Strategy and Summary: Summarize and define a medical action plan.
The lesson from SPIKES is that when a person experiences strong emotions, it is difficult to continue discussing anything, and they will struggle to hear anything. Allowing for silence is fundamental. In addition, empathy allows the patient to express his or her feelings and concerns, as well as provide support. The aim is not to argue but to allow the expression of emotions without criticism. However, these recommendations are primarily based on expert opinion and less on empirical evidence, due to the difficulty of studies in assessing patient outcomes in various phases of these protocols.
A recent study analyzed the differences in psychological distress between patients who received bad news over the phone vs those who received it in person. The study was a systematic review and meta-analysis.
The investigators examined 5944 studies, including 11 qualitative analysis studies, nine meta-analyses, and four randomized controlled trials.
In a set of studies ranging from moderate to good quality, no difference in psychological distress was found when bad news was disclosed over the phone compared with in person, regarding anxiety, depression, and posttraumatic stress disorder.
There was no average difference in patient satisfaction levels when bad news was delivered over the phone compared with in person. The risk for dissatisfaction was similar between groups.
Clinical Practice Guidelines
The demand for telemedicine, including the disclosure of bad news, is growing despite the limited knowledge of potential adverse effects. The results of existing studies suggest that the mode of disclosure may play a secondary role, and the manner in which bad news is communicated may be more important.
Therefore, it is paramount to prepare patients or their families for the possibility of receiving bad news well in advance and, during the conversation, to ensure first and foremost that they are in an appropriate environment. The structure and content of the conversation may be relevant, and adhering to dedicated communication strategies can be a wise choice for the physician and the interlocutor.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Democratic Lawmakers Press Pfizer on Chemotherapy Drug Shortages
In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.
A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”
What is the basis for concern?
All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.
What has the government done in response to the recent shortages?
The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.
What can the lawmakers expect to achieve with their letter?
By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”
Why did the committee target Pfizer specifically?
Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”
The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.
What is being demanded of Pfizer?
Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.
In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.
A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”
What is the basis for concern?
All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.
What has the government done in response to the recent shortages?
The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.
What can the lawmakers expect to achieve with their letter?
By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”
Why did the committee target Pfizer specifically?
Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”
The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.
What is being demanded of Pfizer?
Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.
In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.
A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”
What is the basis for concern?
All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.
What has the government done in response to the recent shortages?
The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.
What can the lawmakers expect to achieve with their letter?
By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”
Why did the committee target Pfizer specifically?
Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”
The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.
What is being demanded of Pfizer?
Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.
Is Mammography Ready for AI? Opinions Mixed on Usage, Cost Methods
Screening mammograms miss close to one in eight breast cancers. But early research suggests artificial intelligence (AI) could close this detection gap and markedly improve early diagnosis of the disease. Still, questions remain regarding how to best incorporate AI into screenings and whether it’s too soon to deploy the technology.
Already, some radiology clinics are offering AI analysis of mammograms through an add-on cost method.
Mammography patients who visit RadNet facilities, for example, have the option of an additional AI screening of their images. RadNet, the largest national owner and operator of fixed-site diagnostic imaging centers in the United States with more than 370 locations, first launched its AI program in the Northeast. The company has now rolled out its product across all regions in the country.
Because the AI is not reimbursed by insurers, patients must pay a $40 out-of-pocket fee if they want the AI analysis.
“RadNet practices have identified more than 400 women whose cancer was found earlier than it would have been had the AI not been present,” said Greg Sorensen MD, chief science officer for RadNet.
How RadNet’s AI Program Works
Patients coming to RadNet facilities for screening mammography undergo 3D high-resolution mammography that includes the use of 70-micron resolution detector technology, said Dr. Sorensen. The mammogram is reviewed by a qualified radiologist with assistance from two Food and Drug Administration–cleared AI programs, Saige-Q and Saige-Density. The radiologist then makes an interpretation.
Saige-Q is an AI tool that helps identify more suspicious mammograms by providing a quick signal to radiologists if the AI considers a given mammogram to be in a suspicious category, according to Dr. Sorensen. Saige-Density provides a density rating for each mammogram using one of the four standard categories:
- A. Almost entirely fatty
- B. Scattered areas of fibroglandular density
- C. Heterogeneously dense
- D. Extremely dense
Starting in September 2024, the FDA will require all mammogram reports to indicate density.
For patients who choose the $40 add-on service, called Enhanced Breast Cancer Detection, two other FDA-registered AI programs are also applied: Saige-Dx and Saige-Assure. These AI programs go a step further by placing marks on areas within the images that they find suspicious. Mammograms flagged as “high-suspicion” by the AI are then reviewed by a second human radiologist. The first and second radiologists confer to agree on a final diagnosis, Dr. Sorensen explained.
“Our research shows that approximately 20% more cancers are found when the safeguard review process is in place,” Dr. Sorensen said. “We also have seen [30%] decreases in recall rates” — the percentage of screening cases in which further tests are recommended by the radiologist.
Bethesda radiologist Janet Storella, MD, has used the AI program for about 3 years and said the technology has improved her screening performance.
The AI is linked to her practice’s imaging software, and radiologists have the option of turning the AI on at any time during their reading of screening mammograms, Dr. Storella explained. Some radiologists review the mammogram first and then initiate the AI, while others like Dr. Storella turn it on at the start, she said. Once initiated, the AI draws bounding boxes — or outlines — around areas that it deems suspicious.
The AI helps focus Dr. Storella’s attention on suspicious areas and grades the level of suspicion into one of four categories: high, intermediate, low, and minimal, she said.
“I find it especially useful in patients who have dense breast tissue,” said Dr. Storella, medical director of women’s imaging at Community Radiology Associates, a RadNet practice. “In these situations, the tissue on the mammogram is a field of white, and cancers are also white, so you’re looking for that little white golf ball on a sea of snow. The AI really helps hone that down to specific areas.”
About 35% of RadNet’s screening mammography patients have enrolled in the Enhanced Breast Cancer Detection program, according to RadNet data. In a recent study of nine general radiologists and nine breast imaging specialists, all radiologists improved their interpretation performance of DBT screening mammograms when reading with RadNet’s AI versus without it. (An average AUC [area under the receiver operating characteristic curve] of 0.93 versus 0.87, demonstrating a difference in AUC of 0.06 (95% CI, 0.04-0.08; P < .001)
Is Mammography Ready for AI?
RadNet is among a growing number of commercial companies offering AI solutions for mammography. MammoScreen and Hologic, for example, are two other companies that provide AI programs to assist radiologists in reading screening mammograms.
“We are at the start of the AI integration into breast imaging at this point,” said Laura Heacock, MD, a breast imaging radiologist and associate professor of radiology at NYU Langone Health. “There are multiple commercial AI models now available to radiologists to use in their practice [ and] there will likely be more. We’re in the transition stage where people are still deciding: Which is the best model to go with? How do I put it in my system? How do I ensure it works they way it was intended? Every practice and medical system will have a different answer to that question.”
At NYU Langone Health, researchers have been developing and studying optimal AI models for breast imaging for several years, Dr. Heacock said. Researchers thus far, have developed AI models for 2D digital mammography, 3D mammograms, breast ultrasound, and breast MRI. Similar to commercial AI systems, the AI is embedded into the picture archiving and communication (PACS) system used by radiologists to review images. Radiologists press a button to launch the AI, which draws a box around suspicious areas of the image and scores the suspicion.
“I take a look of where it is on the mammogram and decide whether that fits my level of suspicion,” Dr. Heacock said. The AI may not understand things about the mammogram like we do. For example, surgical scars look very suspicious to an AI model. But if I’m looking at a mammogram where [the patient] has had a stable scar that hasn’t changed in 10 years, I’m not concerned that the AI found it suspicious. My clinical judgment is the ultimate decider. This is just an additional piece of information that’s helpful to me.”
Research by New York University (NYU) has shown that when used by an expert radiologist the AI models have improved breast cancer detection in all four modalities, she said.
However, the AI has not yet launched at NYU Langone. More research is needed before deploying the technology, according to Dr. Heacock.
“At NYU, we are still testing the benefits to patients,” she said. “We know it improves cancer detection, but we want to make sure there are no drawbacks. We are still exploring the best ways to put it into effect at our institution.”
Dr. Heacock pointed to recent studies on AI in screening mammography that show promise.
An analysis of more than 80,000 women, for example, published in The Lancet Oncology in August, found that AI-supported screen reading led to a similar cancer detection rate as compared with a two-person reader system. This screening resulted in 244 screen-detected cancers, 861 recalls, and a total of 46,345 screen readings, according to the study. Standard screening resulted in 203 screen-detected cancers, 817 recalls, and a total of 83,231 screen readings.
The AI system also reduced the screen-reading workload for radiologists by 44%, the study found.
Meanwhile, a September 2023 study, published in The Lancet Digital Health, found that replacing one radiologist with AI resulted in more cancer detection without a large increase in false-positive cases. The AI led to a 4% higher, noninferior cancer detection rate, compared with radiologist double reading, the study found.
Dr. Heacock emphasized that both studies were conducted in Europe where the standard is for two radiologists to evaluate mammograms.
“That makes the results exciting, but not directly applicable to US practice just yet,” she said.
What Do the Experts Recommend?
Stamatia V. Destounis, MD, FACR, chair of the American College of Radiology (ACR) Breast Imaging Commission, said the college welcomes ongoing research into the efficacy of AI technologies and that AI may prove to be beneficial as an improved workflow tool.
The ACR has not released any guidance about the use of AI for radiologists and have no recommendation about best practices, Dr. Destounis said.
“The decisions regarding which technologies that various health systems and radiology sites choose to use are made by those facilities,” she said.
Dr. Destounis said more research is needed to demonstrate whether or not AI technologies help radiologists produce better results in identifying disease, injury, and illnesses among the general population or in specific groups — whether based on age, physical characteristics, race, ethnicity or risk status for breast cancer.
“Also, a way to measure each AI product is needed so that we can be certain they are relatively equivalent in their efficacy and accuracy — initially and over a prolonged period of time,” she said.
No consensus or concrete recommendation exists about the use of AI in mammography screening, adds Peter P. Yu, MD, FACP, FASCO, physician-in-chief at the Hartford HealthCare Cancer Institute and a member of the newly-created American Society of Clinical Oncology AI task force.
One of the many discussions concerning AI is to what degree patients should be aware that AI is being used in their healthcare and whether they should be required to give consent to its use, Dr. Yu said.
If AI is used to assist radiologists with mammographic interpretation, radiologists should discuss with patients how it’s being used and explain the ultimate reading is in the hands of their physician radiologist, he said.
“In the unlikely situation where there wasn’t a human in the loop and AI was in effect making a medical decision, the patient needs to be aware,” he said. “I’m not aware that any such situation exists today. AI is more likely to be subtly embedded in the software that operates technology, much like it is embedded in manufacturing and transportation.”
Who Will Pay for AI?
When it comes to payment, Dr. Yu said shifting the cost of AI to patients creates serious risk.
“It has enormous potential to increase health inequities,” he said. “If we believe health care is a fundamental human right, AI should inure to the benefit of all, not just those who can afford it. Healthcare should not be a luxury item; if it works, it works for all.”
In general, the issue of payment for AI is still pretty “thorny,” Dr. Heacock noted. Currently, there’s no way for physicians to request direct reimbursement for AI reads of mammograms.
While Dr. Heacock says she is sympathetic to the companies that spend significant time and effort on their AI technology, she doesn’t think charging patients is the right solution.
“We know that many women already have difficulty in paying for mammography-related services and this is just one more charge to confuse them or that they can’t pay,” she said.
Dr. Sorensen expects that, similar to 3D mammography, payers will eventually cover RadNet’s AI technology and that patients will no longer need to pay out of pocket. One Blue Cross carrier will start covering the AI in April 2024, he said.
Screening mammograms miss close to one in eight breast cancers. But early research suggests artificial intelligence (AI) could close this detection gap and markedly improve early diagnosis of the disease. Still, questions remain regarding how to best incorporate AI into screenings and whether it’s too soon to deploy the technology.
Already, some radiology clinics are offering AI analysis of mammograms through an add-on cost method.
Mammography patients who visit RadNet facilities, for example, have the option of an additional AI screening of their images. RadNet, the largest national owner and operator of fixed-site diagnostic imaging centers in the United States with more than 370 locations, first launched its AI program in the Northeast. The company has now rolled out its product across all regions in the country.
Because the AI is not reimbursed by insurers, patients must pay a $40 out-of-pocket fee if they want the AI analysis.
“RadNet practices have identified more than 400 women whose cancer was found earlier than it would have been had the AI not been present,” said Greg Sorensen MD, chief science officer for RadNet.
How RadNet’s AI Program Works
Patients coming to RadNet facilities for screening mammography undergo 3D high-resolution mammography that includes the use of 70-micron resolution detector technology, said Dr. Sorensen. The mammogram is reviewed by a qualified radiologist with assistance from two Food and Drug Administration–cleared AI programs, Saige-Q and Saige-Density. The radiologist then makes an interpretation.
Saige-Q is an AI tool that helps identify more suspicious mammograms by providing a quick signal to radiologists if the AI considers a given mammogram to be in a suspicious category, according to Dr. Sorensen. Saige-Density provides a density rating for each mammogram using one of the four standard categories:
- A. Almost entirely fatty
- B. Scattered areas of fibroglandular density
- C. Heterogeneously dense
- D. Extremely dense
Starting in September 2024, the FDA will require all mammogram reports to indicate density.
For patients who choose the $40 add-on service, called Enhanced Breast Cancer Detection, two other FDA-registered AI programs are also applied: Saige-Dx and Saige-Assure. These AI programs go a step further by placing marks on areas within the images that they find suspicious. Mammograms flagged as “high-suspicion” by the AI are then reviewed by a second human radiologist. The first and second radiologists confer to agree on a final diagnosis, Dr. Sorensen explained.
“Our research shows that approximately 20% more cancers are found when the safeguard review process is in place,” Dr. Sorensen said. “We also have seen [30%] decreases in recall rates” — the percentage of screening cases in which further tests are recommended by the radiologist.
Bethesda radiologist Janet Storella, MD, has used the AI program for about 3 years and said the technology has improved her screening performance.
The AI is linked to her practice’s imaging software, and radiologists have the option of turning the AI on at any time during their reading of screening mammograms, Dr. Storella explained. Some radiologists review the mammogram first and then initiate the AI, while others like Dr. Storella turn it on at the start, she said. Once initiated, the AI draws bounding boxes — or outlines — around areas that it deems suspicious.
The AI helps focus Dr. Storella’s attention on suspicious areas and grades the level of suspicion into one of four categories: high, intermediate, low, and minimal, she said.
“I find it especially useful in patients who have dense breast tissue,” said Dr. Storella, medical director of women’s imaging at Community Radiology Associates, a RadNet practice. “In these situations, the tissue on the mammogram is a field of white, and cancers are also white, so you’re looking for that little white golf ball on a sea of snow. The AI really helps hone that down to specific areas.”
About 35% of RadNet’s screening mammography patients have enrolled in the Enhanced Breast Cancer Detection program, according to RadNet data. In a recent study of nine general radiologists and nine breast imaging specialists, all radiologists improved their interpretation performance of DBT screening mammograms when reading with RadNet’s AI versus without it. (An average AUC [area under the receiver operating characteristic curve] of 0.93 versus 0.87, demonstrating a difference in AUC of 0.06 (95% CI, 0.04-0.08; P < .001)
Is Mammography Ready for AI?
RadNet is among a growing number of commercial companies offering AI solutions for mammography. MammoScreen and Hologic, for example, are two other companies that provide AI programs to assist radiologists in reading screening mammograms.
“We are at the start of the AI integration into breast imaging at this point,” said Laura Heacock, MD, a breast imaging radiologist and associate professor of radiology at NYU Langone Health. “There are multiple commercial AI models now available to radiologists to use in their practice [ and] there will likely be more. We’re in the transition stage where people are still deciding: Which is the best model to go with? How do I put it in my system? How do I ensure it works they way it was intended? Every practice and medical system will have a different answer to that question.”
At NYU Langone Health, researchers have been developing and studying optimal AI models for breast imaging for several years, Dr. Heacock said. Researchers thus far, have developed AI models for 2D digital mammography, 3D mammograms, breast ultrasound, and breast MRI. Similar to commercial AI systems, the AI is embedded into the picture archiving and communication (PACS) system used by radiologists to review images. Radiologists press a button to launch the AI, which draws a box around suspicious areas of the image and scores the suspicion.
“I take a look of where it is on the mammogram and decide whether that fits my level of suspicion,” Dr. Heacock said. The AI may not understand things about the mammogram like we do. For example, surgical scars look very suspicious to an AI model. But if I’m looking at a mammogram where [the patient] has had a stable scar that hasn’t changed in 10 years, I’m not concerned that the AI found it suspicious. My clinical judgment is the ultimate decider. This is just an additional piece of information that’s helpful to me.”
Research by New York University (NYU) has shown that when used by an expert radiologist the AI models have improved breast cancer detection in all four modalities, she said.
However, the AI has not yet launched at NYU Langone. More research is needed before deploying the technology, according to Dr. Heacock.
“At NYU, we are still testing the benefits to patients,” she said. “We know it improves cancer detection, but we want to make sure there are no drawbacks. We are still exploring the best ways to put it into effect at our institution.”
Dr. Heacock pointed to recent studies on AI in screening mammography that show promise.
An analysis of more than 80,000 women, for example, published in The Lancet Oncology in August, found that AI-supported screen reading led to a similar cancer detection rate as compared with a two-person reader system. This screening resulted in 244 screen-detected cancers, 861 recalls, and a total of 46,345 screen readings, according to the study. Standard screening resulted in 203 screen-detected cancers, 817 recalls, and a total of 83,231 screen readings.
The AI system also reduced the screen-reading workload for radiologists by 44%, the study found.
Meanwhile, a September 2023 study, published in The Lancet Digital Health, found that replacing one radiologist with AI resulted in more cancer detection without a large increase in false-positive cases. The AI led to a 4% higher, noninferior cancer detection rate, compared with radiologist double reading, the study found.
Dr. Heacock emphasized that both studies were conducted in Europe where the standard is for two radiologists to evaluate mammograms.
“That makes the results exciting, but not directly applicable to US practice just yet,” she said.
What Do the Experts Recommend?
Stamatia V. Destounis, MD, FACR, chair of the American College of Radiology (ACR) Breast Imaging Commission, said the college welcomes ongoing research into the efficacy of AI technologies and that AI may prove to be beneficial as an improved workflow tool.
The ACR has not released any guidance about the use of AI for radiologists and have no recommendation about best practices, Dr. Destounis said.
“The decisions regarding which technologies that various health systems and radiology sites choose to use are made by those facilities,” she said.
Dr. Destounis said more research is needed to demonstrate whether or not AI technologies help radiologists produce better results in identifying disease, injury, and illnesses among the general population or in specific groups — whether based on age, physical characteristics, race, ethnicity or risk status for breast cancer.
“Also, a way to measure each AI product is needed so that we can be certain they are relatively equivalent in their efficacy and accuracy — initially and over a prolonged period of time,” she said.
No consensus or concrete recommendation exists about the use of AI in mammography screening, adds Peter P. Yu, MD, FACP, FASCO, physician-in-chief at the Hartford HealthCare Cancer Institute and a member of the newly-created American Society of Clinical Oncology AI task force.
One of the many discussions concerning AI is to what degree patients should be aware that AI is being used in their healthcare and whether they should be required to give consent to its use, Dr. Yu said.
If AI is used to assist radiologists with mammographic interpretation, radiologists should discuss with patients how it’s being used and explain the ultimate reading is in the hands of their physician radiologist, he said.
“In the unlikely situation where there wasn’t a human in the loop and AI was in effect making a medical decision, the patient needs to be aware,” he said. “I’m not aware that any such situation exists today. AI is more likely to be subtly embedded in the software that operates technology, much like it is embedded in manufacturing and transportation.”
Who Will Pay for AI?
When it comes to payment, Dr. Yu said shifting the cost of AI to patients creates serious risk.
“It has enormous potential to increase health inequities,” he said. “If we believe health care is a fundamental human right, AI should inure to the benefit of all, not just those who can afford it. Healthcare should not be a luxury item; if it works, it works for all.”
In general, the issue of payment for AI is still pretty “thorny,” Dr. Heacock noted. Currently, there’s no way for physicians to request direct reimbursement for AI reads of mammograms.
While Dr. Heacock says she is sympathetic to the companies that spend significant time and effort on their AI technology, she doesn’t think charging patients is the right solution.
“We know that many women already have difficulty in paying for mammography-related services and this is just one more charge to confuse them or that they can’t pay,” she said.
Dr. Sorensen expects that, similar to 3D mammography, payers will eventually cover RadNet’s AI technology and that patients will no longer need to pay out of pocket. One Blue Cross carrier will start covering the AI in April 2024, he said.
Screening mammograms miss close to one in eight breast cancers. But early research suggests artificial intelligence (AI) could close this detection gap and markedly improve early diagnosis of the disease. Still, questions remain regarding how to best incorporate AI into screenings and whether it’s too soon to deploy the technology.
Already, some radiology clinics are offering AI analysis of mammograms through an add-on cost method.
Mammography patients who visit RadNet facilities, for example, have the option of an additional AI screening of their images. RadNet, the largest national owner and operator of fixed-site diagnostic imaging centers in the United States with more than 370 locations, first launched its AI program in the Northeast. The company has now rolled out its product across all regions in the country.
Because the AI is not reimbursed by insurers, patients must pay a $40 out-of-pocket fee if they want the AI analysis.
“RadNet practices have identified more than 400 women whose cancer was found earlier than it would have been had the AI not been present,” said Greg Sorensen MD, chief science officer for RadNet.
How RadNet’s AI Program Works
Patients coming to RadNet facilities for screening mammography undergo 3D high-resolution mammography that includes the use of 70-micron resolution detector technology, said Dr. Sorensen. The mammogram is reviewed by a qualified radiologist with assistance from two Food and Drug Administration–cleared AI programs, Saige-Q and Saige-Density. The radiologist then makes an interpretation.
Saige-Q is an AI tool that helps identify more suspicious mammograms by providing a quick signal to radiologists if the AI considers a given mammogram to be in a suspicious category, according to Dr. Sorensen. Saige-Density provides a density rating for each mammogram using one of the four standard categories:
- A. Almost entirely fatty
- B. Scattered areas of fibroglandular density
- C. Heterogeneously dense
- D. Extremely dense
Starting in September 2024, the FDA will require all mammogram reports to indicate density.
For patients who choose the $40 add-on service, called Enhanced Breast Cancer Detection, two other FDA-registered AI programs are also applied: Saige-Dx and Saige-Assure. These AI programs go a step further by placing marks on areas within the images that they find suspicious. Mammograms flagged as “high-suspicion” by the AI are then reviewed by a second human radiologist. The first and second radiologists confer to agree on a final diagnosis, Dr. Sorensen explained.
“Our research shows that approximately 20% more cancers are found when the safeguard review process is in place,” Dr. Sorensen said. “We also have seen [30%] decreases in recall rates” — the percentage of screening cases in which further tests are recommended by the radiologist.
Bethesda radiologist Janet Storella, MD, has used the AI program for about 3 years and said the technology has improved her screening performance.
The AI is linked to her practice’s imaging software, and radiologists have the option of turning the AI on at any time during their reading of screening mammograms, Dr. Storella explained. Some radiologists review the mammogram first and then initiate the AI, while others like Dr. Storella turn it on at the start, she said. Once initiated, the AI draws bounding boxes — or outlines — around areas that it deems suspicious.
The AI helps focus Dr. Storella’s attention on suspicious areas and grades the level of suspicion into one of four categories: high, intermediate, low, and minimal, she said.
“I find it especially useful in patients who have dense breast tissue,” said Dr. Storella, medical director of women’s imaging at Community Radiology Associates, a RadNet practice. “In these situations, the tissue on the mammogram is a field of white, and cancers are also white, so you’re looking for that little white golf ball on a sea of snow. The AI really helps hone that down to specific areas.”
About 35% of RadNet’s screening mammography patients have enrolled in the Enhanced Breast Cancer Detection program, according to RadNet data. In a recent study of nine general radiologists and nine breast imaging specialists, all radiologists improved their interpretation performance of DBT screening mammograms when reading with RadNet’s AI versus without it. (An average AUC [area under the receiver operating characteristic curve] of 0.93 versus 0.87, demonstrating a difference in AUC of 0.06 (95% CI, 0.04-0.08; P < .001)
Is Mammography Ready for AI?
RadNet is among a growing number of commercial companies offering AI solutions for mammography. MammoScreen and Hologic, for example, are two other companies that provide AI programs to assist radiologists in reading screening mammograms.
“We are at the start of the AI integration into breast imaging at this point,” said Laura Heacock, MD, a breast imaging radiologist and associate professor of radiology at NYU Langone Health. “There are multiple commercial AI models now available to radiologists to use in their practice [ and] there will likely be more. We’re in the transition stage where people are still deciding: Which is the best model to go with? How do I put it in my system? How do I ensure it works they way it was intended? Every practice and medical system will have a different answer to that question.”
At NYU Langone Health, researchers have been developing and studying optimal AI models for breast imaging for several years, Dr. Heacock said. Researchers thus far, have developed AI models for 2D digital mammography, 3D mammograms, breast ultrasound, and breast MRI. Similar to commercial AI systems, the AI is embedded into the picture archiving and communication (PACS) system used by radiologists to review images. Radiologists press a button to launch the AI, which draws a box around suspicious areas of the image and scores the suspicion.
“I take a look of where it is on the mammogram and decide whether that fits my level of suspicion,” Dr. Heacock said. The AI may not understand things about the mammogram like we do. For example, surgical scars look very suspicious to an AI model. But if I’m looking at a mammogram where [the patient] has had a stable scar that hasn’t changed in 10 years, I’m not concerned that the AI found it suspicious. My clinical judgment is the ultimate decider. This is just an additional piece of information that’s helpful to me.”
Research by New York University (NYU) has shown that when used by an expert radiologist the AI models have improved breast cancer detection in all four modalities, she said.
However, the AI has not yet launched at NYU Langone. More research is needed before deploying the technology, according to Dr. Heacock.
“At NYU, we are still testing the benefits to patients,” she said. “We know it improves cancer detection, but we want to make sure there are no drawbacks. We are still exploring the best ways to put it into effect at our institution.”
Dr. Heacock pointed to recent studies on AI in screening mammography that show promise.
An analysis of more than 80,000 women, for example, published in The Lancet Oncology in August, found that AI-supported screen reading led to a similar cancer detection rate as compared with a two-person reader system. This screening resulted in 244 screen-detected cancers, 861 recalls, and a total of 46,345 screen readings, according to the study. Standard screening resulted in 203 screen-detected cancers, 817 recalls, and a total of 83,231 screen readings.
The AI system also reduced the screen-reading workload for radiologists by 44%, the study found.
Meanwhile, a September 2023 study, published in The Lancet Digital Health, found that replacing one radiologist with AI resulted in more cancer detection without a large increase in false-positive cases. The AI led to a 4% higher, noninferior cancer detection rate, compared with radiologist double reading, the study found.
Dr. Heacock emphasized that both studies were conducted in Europe where the standard is for two radiologists to evaluate mammograms.
“That makes the results exciting, but not directly applicable to US practice just yet,” she said.
What Do the Experts Recommend?
Stamatia V. Destounis, MD, FACR, chair of the American College of Radiology (ACR) Breast Imaging Commission, said the college welcomes ongoing research into the efficacy of AI technologies and that AI may prove to be beneficial as an improved workflow tool.
The ACR has not released any guidance about the use of AI for radiologists and have no recommendation about best practices, Dr. Destounis said.
“The decisions regarding which technologies that various health systems and radiology sites choose to use are made by those facilities,” she said.
Dr. Destounis said more research is needed to demonstrate whether or not AI technologies help radiologists produce better results in identifying disease, injury, and illnesses among the general population or in specific groups — whether based on age, physical characteristics, race, ethnicity or risk status for breast cancer.
“Also, a way to measure each AI product is needed so that we can be certain they are relatively equivalent in their efficacy and accuracy — initially and over a prolonged period of time,” she said.
No consensus or concrete recommendation exists about the use of AI in mammography screening, adds Peter P. Yu, MD, FACP, FASCO, physician-in-chief at the Hartford HealthCare Cancer Institute and a member of the newly-created American Society of Clinical Oncology AI task force.
One of the many discussions concerning AI is to what degree patients should be aware that AI is being used in their healthcare and whether they should be required to give consent to its use, Dr. Yu said.
If AI is used to assist radiologists with mammographic interpretation, radiologists should discuss with patients how it’s being used and explain the ultimate reading is in the hands of their physician radiologist, he said.
“In the unlikely situation where there wasn’t a human in the loop and AI was in effect making a medical decision, the patient needs to be aware,” he said. “I’m not aware that any such situation exists today. AI is more likely to be subtly embedded in the software that operates technology, much like it is embedded in manufacturing and transportation.”
Who Will Pay for AI?
When it comes to payment, Dr. Yu said shifting the cost of AI to patients creates serious risk.
“It has enormous potential to increase health inequities,” he said. “If we believe health care is a fundamental human right, AI should inure to the benefit of all, not just those who can afford it. Healthcare should not be a luxury item; if it works, it works for all.”
In general, the issue of payment for AI is still pretty “thorny,” Dr. Heacock noted. Currently, there’s no way for physicians to request direct reimbursement for AI reads of mammograms.
While Dr. Heacock says she is sympathetic to the companies that spend significant time and effort on their AI technology, she doesn’t think charging patients is the right solution.
“We know that many women already have difficulty in paying for mammography-related services and this is just one more charge to confuse them or that they can’t pay,” she said.
Dr. Sorensen expects that, similar to 3D mammography, payers will eventually cover RadNet’s AI technology and that patients will no longer need to pay out of pocket. One Blue Cross carrier will start covering the AI in April 2024, he said.
How to Navigate Challenging Patient Encounters in Dermatology Residency
Dermatologists in training are exposed to many different clinical scenarios—from the quick 15-minute encounter to diagnose a case of atopic dermatitis to hours of digging through a medical record to identify a culprit medication in a hospitalized patient with a life-threatening cutaneous drug reaction. Amidst the day-to-day clinical work that we do, there inevitably are interactions we have with patients that are less than ideal. These challenging encounters—whether they be subtle microaggressions that unfortunately enter the workplace or blatant quarrels between providers and patients that leave both parties dissatisfied—are notable contributors to physician stress levels and can lead to burnout.1,2 However, there are positive lessons to be learned from these challenging patient encounters if we manage to withstand them. When we start to understand the factors contributing to difficult clinical encounters, we can begin to develop and apply effective communication tools to productively navigate these experiences.
Defining the Difficult Patient
In 2017, the Global Burden of Disease study revealed that skin disease is the fourth leading cause of nonfatal disease burden worldwide.3 Based on this statistic, it is easy to see how some patients may experience frustration associated with their condition and subsequently displace their discontent on the physician. In one study, nearly 1 of every 6 (16.7%) outpatient encounters was considered difficult by physicians.4 Family medicine physicians defined the difficult patient as one who is violent, demanding, aggressive, and rude.5 Others in primary care specialties have considered difficult patients to have characteristics that include mental health problems, more than 5 somatic symptoms, and abrasive personalities.4,6
Situational and Physician-Centered Factors in Difficult Patient Encounters
In our medical system, the narrative often is focused on the patient, for better or worse—the patient was difficult, thereby making the encounter difficult. However, it is important to remember that difficult encounters can be attributed to several different factors, including those related to the physician, the clinical situation, or both. For example, dermatology residents juggle their clinical duties; academic work including studying, teaching, and/or research; and systemic and personal pressures at all times, whether they are cognizant of it or not. For better or worse, by virtue of being human, residents bring these factors with them to each clinical encounter. The delicate balance of these components can have a considerable impact on our delivery of good health care. This is particularly relevant in dermatology, where residents are subject to limited time during visits, work culture among clinic staff that is out of our control, and prominent complex social issues (for those of us practicing in medically underserved areas). Poor communication skills, underlying bias toward specific health conditions, limited knowledge as a trainee, and our own personal stressors also may play large roles in perceiving a clinical encounter as difficult during dermatology residency.7
Strategies to Mitigate Difficult Encounters
As a resident, if you make a statement that sparks a negative response from the patient, acknowledge their negative emotion, try to offer help, or rephrase the original statement to quickly dispel the tension. Validating a patient’s emotions and helping them embrace uncertainty can go a long way in the therapeutic relationship, especially in dermatology where so many of our diseases are chronic and without a definite cure.8 Additionally, it is important to apply strategies to redirect and de-escalate the situation during emotionally charged conversations, such as active listening, validating and empathizing with emotions, exploring alternative solutions, and providing closure to the conversation. Consensus recommendations for managing challenging encounters established by the American Academy of Family Physicians in 2013 include setting boundaries or modifying schedules, as needed, to handle difficult encounters; employing empathetic listening skills and a nonjudgmental attitude to facilitate trust and adherence to treatment; and assessing for underlying psychological illnesses with referral for appropriate diagnosis and treatment. Finally, the CALMER method—catalyst for change, alter thoughts to change feelings, listen and then make a diagnosis, make an agreement, education and follow-up, reach out and discuss feelings—is another approach that may be useful.7 In dermatology, this approach may not only dissipate unwanted tension but also make progress toward a therapeutic relationship. We cannot control the patient’s behavior in a visit, but we need to keep in mind that we are in control of our own reactions to said behavior.9 After first acknowledging this, we can then guide patients to take steps toward overcoming the issue. Within the time restrictions of a dermatology clinic visit, residents may use this approach to quickly feel more in control of a distressing situation and remain calm to better care for the patient.
Final Thoughts
Difficult patient encounters are impossible to avoid in any field of medicine, and dermatology is no exception. It will only benefit residents to recognize the multiple factors impacting a challenging encounter now and learn or enhance conflict resolution and communication skills to navigate these dissatisfying and uncomfortable situations, as they are inevitable in our careers.
- Bodner S. Stress management in the difficult patient encounter. Dent Clin North Am. 2008;52:579-603, ix-xx. doi:10.1016/j.cden.2008.02.012
- West CP, Dyrbye LN, Shanafelt TD. Physician burnout: contributors, consequences and solutions. J Intern Med. 2018;283:516-529. doi:10.1111/joim.12752
- Seth D, Cheldize K, Brown D, et al. Global burden of skin disease: inequities and innovations. Curr Dermatol Rep. 2017;6:204-210. doi:10.1007/s13671-017-0192-7
- An PGRabatin JSManwell LB, et al. Burden of difficult encounters in primary care: data from the minimizing error, maximizing outcomes study. Arch Intern Med. 2009;169:410-414. doi:10.1001/archinternmed.2008.549
- Steinmetz D, Tabenkin H. The ‘difficult patient’ as perceived by family physicians. Fam Pract. 2001;18:495-500. doi:10.1093/fampra/18.5.495
- Breuner CC, Moreno MA. Approaches to the difficult patient/parent encounter. Pediatrics. 2011;127:163-169. doi:10.1542/peds.2010-0072
- Cannarella Lorenzetti R, Jacques CH, Donovan C, et al. Managing difficult encounters: understanding physician, patient, and situational factors. Am Fam Physician. 2013;87:419-425.
- Bailey J, Martin SA, Bangs A. Managing difficult patient encounters. Am Fam Physician. 2023;108:494-500.
- Pomm HA, Shahady E, Pomm RM. The CALMER approach: teaching learners six steps to serenity when dealing with difficult patients. Fam Med. 2004;36:467-469.
Dermatologists in training are exposed to many different clinical scenarios—from the quick 15-minute encounter to diagnose a case of atopic dermatitis to hours of digging through a medical record to identify a culprit medication in a hospitalized patient with a life-threatening cutaneous drug reaction. Amidst the day-to-day clinical work that we do, there inevitably are interactions we have with patients that are less than ideal. These challenging encounters—whether they be subtle microaggressions that unfortunately enter the workplace or blatant quarrels between providers and patients that leave both parties dissatisfied—are notable contributors to physician stress levels and can lead to burnout.1,2 However, there are positive lessons to be learned from these challenging patient encounters if we manage to withstand them. When we start to understand the factors contributing to difficult clinical encounters, we can begin to develop and apply effective communication tools to productively navigate these experiences.
Defining the Difficult Patient
In 2017, the Global Burden of Disease study revealed that skin disease is the fourth leading cause of nonfatal disease burden worldwide.3 Based on this statistic, it is easy to see how some patients may experience frustration associated with their condition and subsequently displace their discontent on the physician. In one study, nearly 1 of every 6 (16.7%) outpatient encounters was considered difficult by physicians.4 Family medicine physicians defined the difficult patient as one who is violent, demanding, aggressive, and rude.5 Others in primary care specialties have considered difficult patients to have characteristics that include mental health problems, more than 5 somatic symptoms, and abrasive personalities.4,6
Situational and Physician-Centered Factors in Difficult Patient Encounters
In our medical system, the narrative often is focused on the patient, for better or worse—the patient was difficult, thereby making the encounter difficult. However, it is important to remember that difficult encounters can be attributed to several different factors, including those related to the physician, the clinical situation, or both. For example, dermatology residents juggle their clinical duties; academic work including studying, teaching, and/or research; and systemic and personal pressures at all times, whether they are cognizant of it or not. For better or worse, by virtue of being human, residents bring these factors with them to each clinical encounter. The delicate balance of these components can have a considerable impact on our delivery of good health care. This is particularly relevant in dermatology, where residents are subject to limited time during visits, work culture among clinic staff that is out of our control, and prominent complex social issues (for those of us practicing in medically underserved areas). Poor communication skills, underlying bias toward specific health conditions, limited knowledge as a trainee, and our own personal stressors also may play large roles in perceiving a clinical encounter as difficult during dermatology residency.7
Strategies to Mitigate Difficult Encounters
As a resident, if you make a statement that sparks a negative response from the patient, acknowledge their negative emotion, try to offer help, or rephrase the original statement to quickly dispel the tension. Validating a patient’s emotions and helping them embrace uncertainty can go a long way in the therapeutic relationship, especially in dermatology where so many of our diseases are chronic and without a definite cure.8 Additionally, it is important to apply strategies to redirect and de-escalate the situation during emotionally charged conversations, such as active listening, validating and empathizing with emotions, exploring alternative solutions, and providing closure to the conversation. Consensus recommendations for managing challenging encounters established by the American Academy of Family Physicians in 2013 include setting boundaries or modifying schedules, as needed, to handle difficult encounters; employing empathetic listening skills and a nonjudgmental attitude to facilitate trust and adherence to treatment; and assessing for underlying psychological illnesses with referral for appropriate diagnosis and treatment. Finally, the CALMER method—catalyst for change, alter thoughts to change feelings, listen and then make a diagnosis, make an agreement, education and follow-up, reach out and discuss feelings—is another approach that may be useful.7 In dermatology, this approach may not only dissipate unwanted tension but also make progress toward a therapeutic relationship. We cannot control the patient’s behavior in a visit, but we need to keep in mind that we are in control of our own reactions to said behavior.9 After first acknowledging this, we can then guide patients to take steps toward overcoming the issue. Within the time restrictions of a dermatology clinic visit, residents may use this approach to quickly feel more in control of a distressing situation and remain calm to better care for the patient.
Final Thoughts
Difficult patient encounters are impossible to avoid in any field of medicine, and dermatology is no exception. It will only benefit residents to recognize the multiple factors impacting a challenging encounter now and learn or enhance conflict resolution and communication skills to navigate these dissatisfying and uncomfortable situations, as they are inevitable in our careers.
Dermatologists in training are exposed to many different clinical scenarios—from the quick 15-minute encounter to diagnose a case of atopic dermatitis to hours of digging through a medical record to identify a culprit medication in a hospitalized patient with a life-threatening cutaneous drug reaction. Amidst the day-to-day clinical work that we do, there inevitably are interactions we have with patients that are less than ideal. These challenging encounters—whether they be subtle microaggressions that unfortunately enter the workplace or blatant quarrels between providers and patients that leave both parties dissatisfied—are notable contributors to physician stress levels and can lead to burnout.1,2 However, there are positive lessons to be learned from these challenging patient encounters if we manage to withstand them. When we start to understand the factors contributing to difficult clinical encounters, we can begin to develop and apply effective communication tools to productively navigate these experiences.
Defining the Difficult Patient
In 2017, the Global Burden of Disease study revealed that skin disease is the fourth leading cause of nonfatal disease burden worldwide.3 Based on this statistic, it is easy to see how some patients may experience frustration associated with their condition and subsequently displace their discontent on the physician. In one study, nearly 1 of every 6 (16.7%) outpatient encounters was considered difficult by physicians.4 Family medicine physicians defined the difficult patient as one who is violent, demanding, aggressive, and rude.5 Others in primary care specialties have considered difficult patients to have characteristics that include mental health problems, more than 5 somatic symptoms, and abrasive personalities.4,6
Situational and Physician-Centered Factors in Difficult Patient Encounters
In our medical system, the narrative often is focused on the patient, for better or worse—the patient was difficult, thereby making the encounter difficult. However, it is important to remember that difficult encounters can be attributed to several different factors, including those related to the physician, the clinical situation, or both. For example, dermatology residents juggle their clinical duties; academic work including studying, teaching, and/or research; and systemic and personal pressures at all times, whether they are cognizant of it or not. For better or worse, by virtue of being human, residents bring these factors with them to each clinical encounter. The delicate balance of these components can have a considerable impact on our delivery of good health care. This is particularly relevant in dermatology, where residents are subject to limited time during visits, work culture among clinic staff that is out of our control, and prominent complex social issues (for those of us practicing in medically underserved areas). Poor communication skills, underlying bias toward specific health conditions, limited knowledge as a trainee, and our own personal stressors also may play large roles in perceiving a clinical encounter as difficult during dermatology residency.7
Strategies to Mitigate Difficult Encounters
As a resident, if you make a statement that sparks a negative response from the patient, acknowledge their negative emotion, try to offer help, or rephrase the original statement to quickly dispel the tension. Validating a patient’s emotions and helping them embrace uncertainty can go a long way in the therapeutic relationship, especially in dermatology where so many of our diseases are chronic and without a definite cure.8 Additionally, it is important to apply strategies to redirect and de-escalate the situation during emotionally charged conversations, such as active listening, validating and empathizing with emotions, exploring alternative solutions, and providing closure to the conversation. Consensus recommendations for managing challenging encounters established by the American Academy of Family Physicians in 2013 include setting boundaries or modifying schedules, as needed, to handle difficult encounters; employing empathetic listening skills and a nonjudgmental attitude to facilitate trust and adherence to treatment; and assessing for underlying psychological illnesses with referral for appropriate diagnosis and treatment. Finally, the CALMER method—catalyst for change, alter thoughts to change feelings, listen and then make a diagnosis, make an agreement, education and follow-up, reach out and discuss feelings—is another approach that may be useful.7 In dermatology, this approach may not only dissipate unwanted tension but also make progress toward a therapeutic relationship. We cannot control the patient’s behavior in a visit, but we need to keep in mind that we are in control of our own reactions to said behavior.9 After first acknowledging this, we can then guide patients to take steps toward overcoming the issue. Within the time restrictions of a dermatology clinic visit, residents may use this approach to quickly feel more in control of a distressing situation and remain calm to better care for the patient.
Final Thoughts
Difficult patient encounters are impossible to avoid in any field of medicine, and dermatology is no exception. It will only benefit residents to recognize the multiple factors impacting a challenging encounter now and learn or enhance conflict resolution and communication skills to navigate these dissatisfying and uncomfortable situations, as they are inevitable in our careers.
- Bodner S. Stress management in the difficult patient encounter. Dent Clin North Am. 2008;52:579-603, ix-xx. doi:10.1016/j.cden.2008.02.012
- West CP, Dyrbye LN, Shanafelt TD. Physician burnout: contributors, consequences and solutions. J Intern Med. 2018;283:516-529. doi:10.1111/joim.12752
- Seth D, Cheldize K, Brown D, et al. Global burden of skin disease: inequities and innovations. Curr Dermatol Rep. 2017;6:204-210. doi:10.1007/s13671-017-0192-7
- An PGRabatin JSManwell LB, et al. Burden of difficult encounters in primary care: data from the minimizing error, maximizing outcomes study. Arch Intern Med. 2009;169:410-414. doi:10.1001/archinternmed.2008.549
- Steinmetz D, Tabenkin H. The ‘difficult patient’ as perceived by family physicians. Fam Pract. 2001;18:495-500. doi:10.1093/fampra/18.5.495
- Breuner CC, Moreno MA. Approaches to the difficult patient/parent encounter. Pediatrics. 2011;127:163-169. doi:10.1542/peds.2010-0072
- Cannarella Lorenzetti R, Jacques CH, Donovan C, et al. Managing difficult encounters: understanding physician, patient, and situational factors. Am Fam Physician. 2013;87:419-425.
- Bailey J, Martin SA, Bangs A. Managing difficult patient encounters. Am Fam Physician. 2023;108:494-500.
- Pomm HA, Shahady E, Pomm RM. The CALMER approach: teaching learners six steps to serenity when dealing with difficult patients. Fam Med. 2004;36:467-469.
- Bodner S. Stress management in the difficult patient encounter. Dent Clin North Am. 2008;52:579-603, ix-xx. doi:10.1016/j.cden.2008.02.012
- West CP, Dyrbye LN, Shanafelt TD. Physician burnout: contributors, consequences and solutions. J Intern Med. 2018;283:516-529. doi:10.1111/joim.12752
- Seth D, Cheldize K, Brown D, et al. Global burden of skin disease: inequities and innovations. Curr Dermatol Rep. 2017;6:204-210. doi:10.1007/s13671-017-0192-7
- An PGRabatin JSManwell LB, et al. Burden of difficult encounters in primary care: data from the minimizing error, maximizing outcomes study. Arch Intern Med. 2009;169:410-414. doi:10.1001/archinternmed.2008.549
- Steinmetz D, Tabenkin H. The ‘difficult patient’ as perceived by family physicians. Fam Pract. 2001;18:495-500. doi:10.1093/fampra/18.5.495
- Breuner CC, Moreno MA. Approaches to the difficult patient/parent encounter. Pediatrics. 2011;127:163-169. doi:10.1542/peds.2010-0072
- Cannarella Lorenzetti R, Jacques CH, Donovan C, et al. Managing difficult encounters: understanding physician, patient, and situational factors. Am Fam Physician. 2013;87:419-425.
- Bailey J, Martin SA, Bangs A. Managing difficult patient encounters. Am Fam Physician. 2023;108:494-500.
- Pomm HA, Shahady E, Pomm RM. The CALMER approach: teaching learners six steps to serenity when dealing with difficult patients. Fam Med. 2004;36:467-469.
RESIDENT PEARLS
- Challenging patient encounters are inevitable in our work as dermatology residents. Both physician- and patient-related factors can contribute.
- Setting boundaries, active listening, and addressing emotions during and after the visit can help to mitigate challenging encounters.
Patients Want the Facts Delivered in a Personal Story
Poor communication between physician and patient can cause a lot of harm, according to Joseph N. Cappella, PhD, Gerald R. Miller Professor Emeritus of Communication at the University of Pennsylvania in Philadelphia, and Richard N. Street Jr, PhD, professor of communication and media science at Texas A&M University in Houston, Texas. When a physician and patient talk past each other, it may impair the patient’s compliance with preventive measures, screening, and treatment; undermine the physician-patient relationship; exacerbate fears and concerns; and possibly lead patients to rely on misleading, incomplete, or simply incorrect information, turning away from evidence-based medicine.
Drs. Cappella and Street made these points in an essay recently published in JAMA. The essay marks the beginning of the JAMA series Communicating Medicine.
“Helping clinicians deliver accurate information more effectively can lead to better-informed patients,” wrote Anne R. Cappola, MD, professor of endocrinology, diabetes, and metabolism at the University of Pennsylvania, and Kirsten Bibbins-Domingo, MD, PhD, professor of medicine at the University of California, San Francisco, in an accompanying editorial. Drs. Cappola and Bibbins-Domingo also are editors of JAMA.
To establish a common understanding between physician and patient, Drs. Cappella and Street identified the following four responsibilities of the physician:
- Discover what the patient understands and why
- Provide accurate information in an understandable manner
- Promote the credibility of the information
- Verify whether the patient has understood.
“Research has shown that although medical facts need to be the basis for the clinician’s core message, those facts are more effectively communicated in a patient-clinician relationship characterized by trust and cooperation and when the information is presented in a manner that fosters patient understanding,” wrote Drs. Cappella and Street. This approach includes using interpreters for patients who do not fluently speak the physician’s language and supplementing explanations with simple written information, images, and videos.
Patients generally believe their physician’s information, and most patients view their physicians as a trustworthy source. Trust is based on the belief that the physician has the patient’s best interests at heart.
However, patients may be distrustful of their physician’s information if it contradicts their own belief system or personal experiences or because they inherently distrust the medical profession.
In addition, patients are less willing to accept explanations and recommendations if they feel misunderstood, judged, discriminated against, or rushed by the physician. The basis for effective communication is a relationship with patients that is built on trust and respect. Empirically supported strategies for expressing respect and building trust include the following:
- Affirming the patient’s values
- Anticipating and addressing false or misleading information
- Using simple, jargon-free language
- Embedding facts into a story, rather than presenting the scientific evidence dryly.
“Conveying factual material using these techniques makes facts more engaging and memorable,” wrote Drs. Cappella and Street. It is crucial to inquire about and consider the patient’s perspective, health beliefs, assumptions, concerns, needs, and stories in the conversation.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Poor communication between physician and patient can cause a lot of harm, according to Joseph N. Cappella, PhD, Gerald R. Miller Professor Emeritus of Communication at the University of Pennsylvania in Philadelphia, and Richard N. Street Jr, PhD, professor of communication and media science at Texas A&M University in Houston, Texas. When a physician and patient talk past each other, it may impair the patient’s compliance with preventive measures, screening, and treatment; undermine the physician-patient relationship; exacerbate fears and concerns; and possibly lead patients to rely on misleading, incomplete, or simply incorrect information, turning away from evidence-based medicine.
Drs. Cappella and Street made these points in an essay recently published in JAMA. The essay marks the beginning of the JAMA series Communicating Medicine.
“Helping clinicians deliver accurate information more effectively can lead to better-informed patients,” wrote Anne R. Cappola, MD, professor of endocrinology, diabetes, and metabolism at the University of Pennsylvania, and Kirsten Bibbins-Domingo, MD, PhD, professor of medicine at the University of California, San Francisco, in an accompanying editorial. Drs. Cappola and Bibbins-Domingo also are editors of JAMA.
To establish a common understanding between physician and patient, Drs. Cappella and Street identified the following four responsibilities of the physician:
- Discover what the patient understands and why
- Provide accurate information in an understandable manner
- Promote the credibility of the information
- Verify whether the patient has understood.
“Research has shown that although medical facts need to be the basis for the clinician’s core message, those facts are more effectively communicated in a patient-clinician relationship characterized by trust and cooperation and when the information is presented in a manner that fosters patient understanding,” wrote Drs. Cappella and Street. This approach includes using interpreters for patients who do not fluently speak the physician’s language and supplementing explanations with simple written information, images, and videos.
Patients generally believe their physician’s information, and most patients view their physicians as a trustworthy source. Trust is based on the belief that the physician has the patient’s best interests at heart.
However, patients may be distrustful of their physician’s information if it contradicts their own belief system or personal experiences or because they inherently distrust the medical profession.
In addition, patients are less willing to accept explanations and recommendations if they feel misunderstood, judged, discriminated against, or rushed by the physician. The basis for effective communication is a relationship with patients that is built on trust and respect. Empirically supported strategies for expressing respect and building trust include the following:
- Affirming the patient’s values
- Anticipating and addressing false or misleading information
- Using simple, jargon-free language
- Embedding facts into a story, rather than presenting the scientific evidence dryly.
“Conveying factual material using these techniques makes facts more engaging and memorable,” wrote Drs. Cappella and Street. It is crucial to inquire about and consider the patient’s perspective, health beliefs, assumptions, concerns, needs, and stories in the conversation.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Poor communication between physician and patient can cause a lot of harm, according to Joseph N. Cappella, PhD, Gerald R. Miller Professor Emeritus of Communication at the University of Pennsylvania in Philadelphia, and Richard N. Street Jr, PhD, professor of communication and media science at Texas A&M University in Houston, Texas. When a physician and patient talk past each other, it may impair the patient’s compliance with preventive measures, screening, and treatment; undermine the physician-patient relationship; exacerbate fears and concerns; and possibly lead patients to rely on misleading, incomplete, or simply incorrect information, turning away from evidence-based medicine.
Drs. Cappella and Street made these points in an essay recently published in JAMA. The essay marks the beginning of the JAMA series Communicating Medicine.
“Helping clinicians deliver accurate information more effectively can lead to better-informed patients,” wrote Anne R. Cappola, MD, professor of endocrinology, diabetes, and metabolism at the University of Pennsylvania, and Kirsten Bibbins-Domingo, MD, PhD, professor of medicine at the University of California, San Francisco, in an accompanying editorial. Drs. Cappola and Bibbins-Domingo also are editors of JAMA.
To establish a common understanding between physician and patient, Drs. Cappella and Street identified the following four responsibilities of the physician:
- Discover what the patient understands and why
- Provide accurate information in an understandable manner
- Promote the credibility of the information
- Verify whether the patient has understood.
“Research has shown that although medical facts need to be the basis for the clinician’s core message, those facts are more effectively communicated in a patient-clinician relationship characterized by trust and cooperation and when the information is presented in a manner that fosters patient understanding,” wrote Drs. Cappella and Street. This approach includes using interpreters for patients who do not fluently speak the physician’s language and supplementing explanations with simple written information, images, and videos.
Patients generally believe their physician’s information, and most patients view their physicians as a trustworthy source. Trust is based on the belief that the physician has the patient’s best interests at heart.
However, patients may be distrustful of their physician’s information if it contradicts their own belief system or personal experiences or because they inherently distrust the medical profession.
In addition, patients are less willing to accept explanations and recommendations if they feel misunderstood, judged, discriminated against, or rushed by the physician. The basis for effective communication is a relationship with patients that is built on trust and respect. Empirically supported strategies for expressing respect and building trust include the following:
- Affirming the patient’s values
- Anticipating and addressing false or misleading information
- Using simple, jargon-free language
- Embedding facts into a story, rather than presenting the scientific evidence dryly.
“Conveying factual material using these techniques makes facts more engaging and memorable,” wrote Drs. Cappella and Street. It is crucial to inquire about and consider the patient’s perspective, health beliefs, assumptions, concerns, needs, and stories in the conversation.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Unleashing Our Immune Response to Quash Cancer
This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”
It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.
Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.
Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.
And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.
As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.
Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.
An Ever-Expanding Armamentarium
Immune Checkpoint Inhibitors
The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.
But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.
Therapeutic Cancer Vaccines
There are many therapeutic cancer vaccines in the works, as reviewed in depth here.
Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.
An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.
Antibody-Drug Conjugates (ADC)
There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.
A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.
This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.
Oncolytic Viruses
Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.
After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.
Engineering T Cells (Chimeric Antigen Receptor [CAR-T])
As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.
As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.
Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.
Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.
Summary
Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.
Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.
Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.
Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.
Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.
A version of this article appeared on Medscape.com.
This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”
It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.
Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.
Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.
And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.
As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.
Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.
An Ever-Expanding Armamentarium
Immune Checkpoint Inhibitors
The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.
But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.
Therapeutic Cancer Vaccines
There are many therapeutic cancer vaccines in the works, as reviewed in depth here.
Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.
An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.
Antibody-Drug Conjugates (ADC)
There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.
A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.
This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.
Oncolytic Viruses
Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.
After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.
Engineering T Cells (Chimeric Antigen Receptor [CAR-T])
As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.
As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.
Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.
Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.
Summary
Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.
Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.
Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.
Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.
Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.
A version of this article appeared on Medscape.com.
This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”
It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.
Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.
Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.
And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.
As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.
Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.
An Ever-Expanding Armamentarium
Immune Checkpoint Inhibitors
The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.
But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.
Therapeutic Cancer Vaccines
There are many therapeutic cancer vaccines in the works, as reviewed in depth here.
Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.
An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.
Antibody-Drug Conjugates (ADC)
There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.
A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.
This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.
Oncolytic Viruses
Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.
After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.
Engineering T Cells (Chimeric Antigen Receptor [CAR-T])
As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.
As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.
Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.
Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.
Summary
Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.
Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.
Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.
Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.
Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.
A version of this article appeared on Medscape.com.