Denise Napoli

Major Finding: Hepatitis C patients who discontinue ribavirin/pegylated interferon therapy before 12 weeks are significantly more likely to have cirrhosis (AOR, 1.42), diabetes (AOR, 1.25), or substance use disorder (AOR, 1.24), and less likely to take growth factor (AOR, 0.56), compared with patients who persist with therapy.

Data Source: A national sample of 11,019 veterans treated for genotype 1 hepatitis C virus infection within the VA health care system between 2002 and 2007.

Disclosures: The authors had no relevant financial disclosures. The study was supported by the Department of Veterans Affairs and the Northwest Hepatitis C Resource Center.

Having cirrhosis, diabetes, or substance use disorder increased the odds of treatment discontinuation in type 1 hepatitis C virus infection, but use of growth factor drugs correlated with treatment persistence, reported Dr. Lauren A. Beste and colleagues.

The investigators looked at 11,019 patients in the VA health care system with hepatitis C genotype 1 who received at least two prescriptions for pegylated interferon and ribavirin between Jan. 1, 2002, and Dec. 31, 2007.

Patients who completed at least 80% (38.4 weeks) of the standard 48-week treatment regimen were considered to have completed treatment; overall, 5,795 patients (52.6%) reached this goal (Clin. Gastroenterol. Hepatol. 2010 November [doi:10.1016/j.cgh.2010.07.012]).

Although “no indications currently exist for discontinuing treatment [before 12 weeks] due to lack of response,” a total of 1,184 patients (about 10% of the cohort) did just that, the authors said. Patients who stopped before 12 weeks were significantly more likely to have cirrhosis, compared with patients who persisted with therapy (adjusted odds ratio, 1.42), and also were more likely to have diabetes (AOR, 1.25) and pretreatment substance use disorder, or SUD (AOR, 1.24).

They were also half as likely to use growth factor as were those who continued therapy (AOR, 0.56; P less than .01). The growth factors included erythropoietin, darbepoetin, granulocyte colony-stimulating factor, and granulocyte macrophage colony-stimulating factor.

The authors also assessed patients who discontinued treatment between 12 and 24 weeks of therapy (including 317 patients with known early virologic response who discontinued despite their response). These patients were more likely to have pretreatment depression (AOR, 1.59), were slightly less likely to have other mental illnesses (AOR, 0.65), and – once again – were nearly half as likely to use growth factor as were patients who persisted with the therapy (AOR, 0.64).

Finally, the authors looked at patients who discontinued before 38.4 weeks. “No variables significantly predicted discontinuation in this time period in bivariate or multivariate analyses,” wrote Dr. Beste of the VA Puget Sound Healthcare System, Seattle, and her coauthors.

Regarding SUD as a predictor of discontinuation, the authors wrote that “patients with history of substance abuse may benefit from early support and intervention during treatment in order to continue antiviral therapy.”

Of the pretreatment depression that emerged as a predictor in the 12-24 week discontinuation group, they wrote, “Prior studies report that the depressive side effects of interferon peak by week 25, which may explain the observed association between depression and discontinuation midtreatment.”

Finally, Dr. Beste and colleagues commented on the use of growth factor, which correlated with reduced risk of discontinuation both before 12 weeks and from weeks 12 to 24. They speculated that growth factor use “leads to improvement in low blood counts, allowing providers to continue treatment when otherwise it would be stopped.”

Therefore, “appropriate use of growth factors should be prospectively evaluated as a modifiable means to prevent treatment discontinuation,” they said.

Major Finding: Hepatitis C patients who discontinue ribavirin/pegylated interferon therapy before 12 weeks are significantly more likely to have cirrhosis (AOR, 1.42), diabetes (AOR, 1.25), or substance use disorder (AOR, 1.24), and less likely to take growth factor (AOR, 0.56), compared with patients who persist with therapy.

Data Source: A national sample of 11,019 veterans treated for genotype 1 hepatitis C virus infection within the VA health care system between 2002 and 2007.

Disclosures: The authors had no relevant financial disclosures. The study was supported by the Department of Veterans Affairs and the Northwest Hepatitis C Resource Center.

Having cirrhosis, diabetes, or substance use disorder increased the odds of treatment discontinuation in type 1 hepatitis C virus infection, but use of growth factor drugs correlated with treatment persistence, reported Dr. Lauren A. Beste and colleagues.

The investigators looked at 11,019 patients in the VA health care system with hepatitis C genotype 1 who received at least two prescriptions for pegylated interferon and ribavirin between Jan. 1, 2002, and Dec. 31, 2007.

Patients who completed at least 80% (38.4 weeks) of the standard 48-week treatment regimen were considered to have completed treatment; overall, 5,795 patients (52.6%) reached this goal (Clin. Gastroenterol. Hepatol. 2010 November [doi:10.1016/j.cgh.2010.07.012]).

Although “no indications currently exist for discontinuing treatment [before 12 weeks] due to lack of response,” a total of 1,184 patients (about 10% of the cohort) did just that, the authors said. Patients who stopped before 12 weeks were significantly more likely to have cirrhosis, compared with patients who persisted with therapy (adjusted odds ratio, 1.42), and also were more likely to have diabetes (AOR, 1.25) and pretreatment substance use disorder, or SUD (AOR, 1.24).

They were also half as likely to use growth factor as were those who continued therapy (AOR, 0.56; P less than .01). The growth factors included erythropoietin, darbepoetin, granulocyte colony-stimulating factor, and granulocyte macrophage colony-stimulating factor.

The authors also assessed patients who discontinued treatment between 12 and 24 weeks of therapy (including 317 patients with known early virologic response who discontinued despite their response). These patients were more likely to have pretreatment depression (AOR, 1.59), were slightly less likely to have other mental illnesses (AOR, 0.65), and – once again – were nearly half as likely to use growth factor as were patients who persisted with the therapy (AOR, 0.64).

Finally, the authors looked at patients who discontinued before 38.4 weeks. “No variables significantly predicted discontinuation in this time period in bivariate or multivariate analyses,” wrote Dr. Beste of the VA Puget Sound Healthcare System, Seattle, and her coauthors.

Regarding SUD as a predictor of discontinuation, the authors wrote that “patients with history of substance abuse may benefit from early support and intervention during treatment in order to continue antiviral therapy.”

Of the pretreatment depression that emerged as a predictor in the 12-24 week discontinuation group, they wrote, “Prior studies report that the depressive side effects of interferon peak by week 25, which may explain the observed association between depression and discontinuation midtreatment.”

Finally, Dr. Beste and colleagues commented on the use of growth factor, which correlated with reduced risk of discontinuation both before 12 weeks and from weeks 12 to 24. They speculated that growth factor use “leads to improvement in low blood counts, allowing providers to continue treatment when otherwise it would be stopped.”

Therefore, “appropriate use of growth factors should be prospectively evaluated as a modifiable means to prevent treatment discontinuation,” they said.

Major Finding: Hepatitis C patients who discontinue ribavirin/pegylated interferon therapy before 12 weeks are significantly more likely to have cirrhosis (AOR, 1.42), diabetes (AOR, 1.25), or substance use disorder (AOR, 1.24), and less likely to take growth factor (AOR, 0.56), compared with patients who persist with therapy.

Data Source: A national sample of 11,019 veterans treated for genotype 1 hepatitis C virus infection within the VA health care system between 2002 and 2007.

Disclosures: The authors had no relevant financial disclosures. The study was supported by the Department of Veterans Affairs and the Northwest Hepatitis C Resource Center.

Having cirrhosis, diabetes, or substance use disorder increased the odds of treatment discontinuation in type 1 hepatitis C virus infection, but use of growth factor drugs correlated with treatment persistence, reported Dr. Lauren A. Beste and colleagues.

The investigators looked at 11,019 patients in the VA health care system with hepatitis C genotype 1 who received at least two prescriptions for pegylated interferon and ribavirin between Jan. 1, 2002, and Dec. 31, 2007.

Patients who completed at least 80% (38.4 weeks) of the standard 48-week treatment regimen were considered to have completed treatment; overall, 5,795 patients (52.6%) reached this goal (Clin. Gastroenterol. Hepatol. 2010 November [doi:10.1016/j.cgh.2010.07.012]).

Although “no indications currently exist for discontinuing treatment [before 12 weeks] due to lack of response,” a total of 1,184 patients (about 10% of the cohort) did just that, the authors said. Patients who stopped before 12 weeks were significantly more likely to have cirrhosis, compared with patients who persisted with therapy (adjusted odds ratio, 1.42), and also were more likely to have diabetes (AOR, 1.25) and pretreatment substance use disorder, or SUD (AOR, 1.24).

They were also half as likely to use growth factor as were those who continued therapy (AOR, 0.56; P less than .01). The growth factors included erythropoietin, darbepoetin, granulocyte colony-stimulating factor, and granulocyte macrophage colony-stimulating factor.

The authors also assessed patients who discontinued treatment between 12 and 24 weeks of therapy (including 317 patients with known early virologic response who discontinued despite their response). These patients were more likely to have pretreatment depression (AOR, 1.59), were slightly less likely to have other mental illnesses (AOR, 0.65), and – once again – were nearly half as likely to use growth factor as were patients who persisted with the therapy (AOR, 0.64).

Finally, the authors looked at patients who discontinued before 38.4 weeks. “No variables significantly predicted discontinuation in this time period in bivariate or multivariate analyses,” wrote Dr. Beste of the VA Puget Sound Healthcare System, Seattle, and her coauthors.

Regarding SUD as a predictor of discontinuation, the authors wrote that “patients with history of substance abuse may benefit from early support and intervention during treatment in order to continue antiviral therapy.”

Of the pretreatment depression that emerged as a predictor in the 12-24 week discontinuation group, they wrote, “Prior studies report that the depressive side effects of interferon peak by week 25, which may explain the observed association between depression and discontinuation midtreatment.”

Finally, Dr. Beste and colleagues commented on the use of growth factor, which correlated with reduced risk of discontinuation both before 12 weeks and from weeks 12 to 24. They speculated that growth factor use “leads to improvement in low blood counts, allowing providers to continue treatment when otherwise it would be stopped.”

Therefore, “appropriate use of growth factors should be prospectively evaluated as a modifiable means to prevent treatment discontinuation,” they said.

Major Finding: A new criteria set for rheumatoid arthritis identifies early disease based on a score of 6 or higher out of 10.

Data Source: An international committee of rheumatologists from both the European League Against Rheumatism and the American College of Rheumatology.

Disclosures: Several of the authors of the guidelines disclosed financial relationships with multiple drug makers.

The promised overhaul of treatment guidelines for rheumatoid arthritis has finally arrived, and with it, a “new paradigm” that focuses on early identification and treatment of the disabling disease.

The guidelines, which were developed by a joint committee from the American College of Rheumatology and the European League Against Rheumatism, are the latest update since the current guidelines were created in 1987.

Published jointly in the EULAR journal Annals of the Rheumatic Diseases (2010;69:1580-8) and the ACR's Arthritis & Rheumatism (2010;62:2569-81), the new guidelines were created in three phases over 2 years.

In the first phase, the goal was to “to identify the contributions of clinical and laboratory variables that in practice were the most predictive of the decision to initiate [disease-modifying antirheumatic drug] therapy in a population of patients with early undifferentiated synovitis,” wrote the authors, led by Dr. Daniel Aletaha of the Medical University of Vienna.

To do this, a working group from both societies looked at data from 3,115 patients, and correlated whether or not the patients were ultimately prescribed methotrexate to an “agreed-upon list of standardized clinical and laboratory variables collected at baseline.”

The odds of eventual methotrexate initiation were calculated for each variable. For example, swelling of the metacarpophalangeal joint had an odds ratio of 1.5, as did swelling of the proximal interphalangeal joint and the wrist. Tenderness of the hand (either the MCP, PIP, or wrist) was assigned an odds ratio of 2.0.

A moderate elevation of C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) was assigned an OR of 1.0; a high elevation of either assay carried an OR of 2.0.

Finally, moderate levels of either rheumatoid factor or anti–citrullinated protein antibodies had an OR of 2.0 for the eventual prescription of a DMARD; high levels had an OR of 4.0.

In phase II, an “expert panel” of 12 rheumatologists related the above clinical and laboratory factors to the “probability of developing 'persistent inflammatory and/or erosive arthritis that is currently considered to be RA.'”

The panel also looked at duration of symptoms (longer or shorter than 6 weeks) and the number and size of joints (large or small), in addition to the variables that were assessed in phase I. Using a computer program, the panel assigned each variable a point value of 1-100, with high scores indicating greater likelihood of RA.

Finally, phase III aimed to utilize the results of phases I and II “to develop a scoring system that would be applicable to newly presenting patients with undifferentiated inflammatory arthritis, to permit identification of those with a high probability of developing persistent and/or erosive RA.”

This final scale assigns points in the following manner:

▸ One swollen “large joint” (defined as shoulders, elbows, hips, knees, and ankles) gets 0 points; involvement of 2-10 large joints gets 1 point.

▸ Involvement of 1-3 “small” joints (defined as metacarpophalangeal joints, proximal interphalangeal joints, second to fifth metatarsophalangeal joints, thumb interphalangeal joints, and wrists) gets 2 points, regardless of large-joint involvement; involvement of 4-10 small joints gets 3 points.

▸ Involvement of more than 10 joints, including at least one small joint, gets 5 points.

▸ Both a negative rheumatoid factor (RF) test and a negative anti–citrullinated protein antibody test (ACPA) gets 0 points, whereas having a “low-positive” RF or ACPA (defined as lower than three times the upper limit of normal) gets 2 points. A “high-positive” of either test gets 3 points.

▸ A normal CRP and normal ESR get 0 points, whereas at least one abnormal test gets 1 point.

▸ Symptom duration of fewer than 6 weeks gets 0 points; duration of 6 weeks or longer gets 1 point.

Scores of 6 or more out of 10 are classified as “definite RA.”

Commenting on the new criteria in an interview, Dr. Eric L. Matteson, who is a professor of medicine at the division of rheumatology at the Mayo Clinic in Rochester, Minn., and was not involved in the study, said, “A major useful feature is that the new guidelines do not require multiple joints to be inflamed before a diagnosis can be [made] of early inflammatory rheumatoid arthritis.”

Indeed, a patient may score 6 points without multiple joint inflammation, according to the new guidelines.

The authors also pointed out that symmetry is not a criterion for diagnosis, as it did not show significance in either phase of the new guidelines' development. Nevertheless, they wrote, “Inevitably,… the greater the number of involved joints the higher the likelihood of bilateral involvement.”

When Dr. Matteson was asked what was missing from the new guidelines, he pointed to a lack of awareness of extra-articular components of RA, which also can occur early in the course of the disease.

“When they do [occur], they can be very useful in identifying the disease, and they are important markers and predictors of disease severity and need for therapy,” he said.

The guidelines also lack biomarkers for treatment response, he added.

Several of the guideline authors disclosed financial and other relationships with multiple pharmaceutical companies; Dr. Matteson stated that he had no financial disclosures relative to his comments.

Major Finding: A new criteria set for rheumatoid arthritis identifies early disease based on a score of 6 or higher out of 10.

Data Source: An international committee of rheumatologists from both the European League Against Rheumatism and the American College of Rheumatology.

Disclosures: Several of the authors of the guidelines disclosed financial relationships with multiple drug makers.

The promised overhaul of treatment guidelines for rheumatoid arthritis has finally arrived, and with it, a “new paradigm” that focuses on early identification and treatment of the disabling disease.

The guidelines, which were developed by a joint committee from the American College of Rheumatology and the European League Against Rheumatism, are the latest update since the current guidelines were created in 1987.

Published jointly in the EULAR journal Annals of the Rheumatic Diseases (2010;69:1580-8) and the ACR's Arthritis & Rheumatism (2010;62:2569-81), the new guidelines were created in three phases over 2 years.

In the first phase, the goal was to “to identify the contributions of clinical and laboratory variables that in practice were the most predictive of the decision to initiate [disease-modifying antirheumatic drug] therapy in a population of patients with early undifferentiated synovitis,” wrote the authors, led by Dr. Daniel Aletaha of the Medical University of Vienna.

To do this, a working group from both societies looked at data from 3,115 patients, and correlated whether or not the patients were ultimately prescribed methotrexate to an “agreed-upon list of standardized clinical and laboratory variables collected at baseline.”

The odds of eventual methotrexate initiation were calculated for each variable. For example, swelling of the metacarpophalangeal joint had an odds ratio of 1.5, as did swelling of the proximal interphalangeal joint and the wrist. Tenderness of the hand (either the MCP, PIP, or wrist) was assigned an odds ratio of 2.0.

A moderate elevation of C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) was assigned an OR of 1.0; a high elevation of either assay carried an OR of 2.0.

Finally, moderate levels of either rheumatoid factor or anti–citrullinated protein antibodies had an OR of 2.0 for the eventual prescription of a DMARD; high levels had an OR of 4.0.

In phase II, an “expert panel” of 12 rheumatologists related the above clinical and laboratory factors to the “probability of developing 'persistent inflammatory and/or erosive arthritis that is currently considered to be RA.'”

The panel also looked at duration of symptoms (longer or shorter than 6 weeks) and the number and size of joints (large or small), in addition to the variables that were assessed in phase I. Using a computer program, the panel assigned each variable a point value of 1-100, with high scores indicating greater likelihood of RA.

Finally, phase III aimed to utilize the results of phases I and II “to develop a scoring system that would be applicable to newly presenting patients with undifferentiated inflammatory arthritis, to permit identification of those with a high probability of developing persistent and/or erosive RA.”

This final scale assigns points in the following manner:

▸ One swollen “large joint” (defined as shoulders, elbows, hips, knees, and ankles) gets 0 points; involvement of 2-10 large joints gets 1 point.

▸ Involvement of 1-3 “small” joints (defined as metacarpophalangeal joints, proximal interphalangeal joints, second to fifth metatarsophalangeal joints, thumb interphalangeal joints, and wrists) gets 2 points, regardless of large-joint involvement; involvement of 4-10 small joints gets 3 points.

▸ Involvement of more than 10 joints, including at least one small joint, gets 5 points.

▸ Both a negative rheumatoid factor (RF) test and a negative anti–citrullinated protein antibody test (ACPA) gets 0 points, whereas having a “low-positive” RF or ACPA (defined as lower than three times the upper limit of normal) gets 2 points. A “high-positive” of either test gets 3 points.

▸ A normal CRP and normal ESR get 0 points, whereas at least one abnormal test gets 1 point.

▸ Symptom duration of fewer than 6 weeks gets 0 points; duration of 6 weeks or longer gets 1 point.

Scores of 6 or more out of 10 are classified as “definite RA.”

Commenting on the new criteria in an interview, Dr. Eric L. Matteson, who is a professor of medicine at the division of rheumatology at the Mayo Clinic in Rochester, Minn., and was not involved in the study, said, “A major useful feature is that the new guidelines do not require multiple joints to be inflamed before a diagnosis can be [made] of early inflammatory rheumatoid arthritis.”

Indeed, a patient may score 6 points without multiple joint inflammation, according to the new guidelines.

The authors also pointed out that symmetry is not a criterion for diagnosis, as it did not show significance in either phase of the new guidelines' development. Nevertheless, they wrote, “Inevitably,… the greater the number of involved joints the higher the likelihood of bilateral involvement.”

When Dr. Matteson was asked what was missing from the new guidelines, he pointed to a lack of awareness of extra-articular components of RA, which also can occur early in the course of the disease.

“When they do [occur], they can be very useful in identifying the disease, and they are important markers and predictors of disease severity and need for therapy,” he said.

The guidelines also lack biomarkers for treatment response, he added.

Several of the guideline authors disclosed financial and other relationships with multiple pharmaceutical companies; Dr. Matteson stated that he had no financial disclosures relative to his comments.

Major Finding: A new criteria set for rheumatoid arthritis identifies early disease based on a score of 6 or higher out of 10.

Data Source: An international committee of rheumatologists from both the European League Against Rheumatism and the American College of Rheumatology.

Disclosures: Several of the authors of the guidelines disclosed financial relationships with multiple drug makers.

The promised overhaul of treatment guidelines for rheumatoid arthritis has finally arrived, and with it, a “new paradigm” that focuses on early identification and treatment of the disabling disease.

The guidelines, which were developed by a joint committee from the American College of Rheumatology and the European League Against Rheumatism, are the latest update since the current guidelines were created in 1987.

Published jointly in the EULAR journal Annals of the Rheumatic Diseases (2010;69:1580-8) and the ACR's Arthritis & Rheumatism (2010;62:2569-81), the new guidelines were created in three phases over 2 years.

In the first phase, the goal was to “to identify the contributions of clinical and laboratory variables that in practice were the most predictive of the decision to initiate [disease-modifying antirheumatic drug] therapy in a population of patients with early undifferentiated synovitis,” wrote the authors, led by Dr. Daniel Aletaha of the Medical University of Vienna.

To do this, a working group from both societies looked at data from 3,115 patients, and correlated whether or not the patients were ultimately prescribed methotrexate to an “agreed-upon list of standardized clinical and laboratory variables collected at baseline.”

The odds of eventual methotrexate initiation were calculated for each variable. For example, swelling of the metacarpophalangeal joint had an odds ratio of 1.5, as did swelling of the proximal interphalangeal joint and the wrist. Tenderness of the hand (either the MCP, PIP, or wrist) was assigned an odds ratio of 2.0.

A moderate elevation of C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) was assigned an OR of 1.0; a high elevation of either assay carried an OR of 2.0.

Finally, moderate levels of either rheumatoid factor or anti–citrullinated protein antibodies had an OR of 2.0 for the eventual prescription of a DMARD; high levels had an OR of 4.0.

In phase II, an “expert panel” of 12 rheumatologists related the above clinical and laboratory factors to the “probability of developing 'persistent inflammatory and/or erosive arthritis that is currently considered to be RA.'”

The panel also looked at duration of symptoms (longer or shorter than 6 weeks) and the number and size of joints (large or small), in addition to the variables that were assessed in phase I. Using a computer program, the panel assigned each variable a point value of 1-100, with high scores indicating greater likelihood of RA.

Finally, phase III aimed to utilize the results of phases I and II “to develop a scoring system that would be applicable to newly presenting patients with undifferentiated inflammatory arthritis, to permit identification of those with a high probability of developing persistent and/or erosive RA.”

This final scale assigns points in the following manner:

▸ One swollen “large joint” (defined as shoulders, elbows, hips, knees, and ankles) gets 0 points; involvement of 2-10 large joints gets 1 point.

▸ Involvement of 1-3 “small” joints (defined as metacarpophalangeal joints, proximal interphalangeal joints, second to fifth metatarsophalangeal joints, thumb interphalangeal joints, and wrists) gets 2 points, regardless of large-joint involvement; involvement of 4-10 small joints gets 3 points.

▸ Involvement of more than 10 joints, including at least one small joint, gets 5 points.

▸ Both a negative rheumatoid factor (RF) test and a negative anti–citrullinated protein antibody test (ACPA) gets 0 points, whereas having a “low-positive” RF or ACPA (defined as lower than three times the upper limit of normal) gets 2 points. A “high-positive” of either test gets 3 points.

▸ A normal CRP and normal ESR get 0 points, whereas at least one abnormal test gets 1 point.

▸ Symptom duration of fewer than 6 weeks gets 0 points; duration of 6 weeks or longer gets 1 point.

Scores of 6 or more out of 10 are classified as “definite RA.”

Commenting on the new criteria in an interview, Dr. Eric L. Matteson, who is a professor of medicine at the division of rheumatology at the Mayo Clinic in Rochester, Minn., and was not involved in the study, said, “A major useful feature is that the new guidelines do not require multiple joints to be inflamed before a diagnosis can be [made] of early inflammatory rheumatoid arthritis.”

Indeed, a patient may score 6 points without multiple joint inflammation, according to the new guidelines.

The authors also pointed out that symmetry is not a criterion for diagnosis, as it did not show significance in either phase of the new guidelines' development. Nevertheless, they wrote, “Inevitably,… the greater the number of involved joints the higher the likelihood of bilateral involvement.”

When Dr. Matteson was asked what was missing from the new guidelines, he pointed to a lack of awareness of extra-articular components of RA, which also can occur early in the course of the disease.

“When they do [occur], they can be very useful in identifying the disease, and they are important markers and predictors of disease severity and need for therapy,” he said.

The guidelines also lack biomarkers for treatment response, he added.

Several of the guideline authors disclosed financial and other relationships with multiple pharmaceutical companies; Dr. Matteson stated that he had no financial disclosures relative to his comments.

A combination of two oral drugs for reducing viral load in hepatitis C patients had good safety and tolerability in a small, phase I study.

The finding, published online Oct. 15 in the Lancet, points the way toward an alternative to the current standard of care – subcutaneous pegylated interferon-alfa plus oral ribavirin – which has limited tolerability and efficacy.

The novel therapies that were tested in this study are RG7128, a nucleoside polymerase inhibitor, and danoprevir, a protease inhibitor, wrote Dr. Edward J. Gane of Auckland (New Zealand) Clinical Studies Ltd., an early-phase clinical pharmacology unit, and his colleagues.

Both compounds have potent in vitro and in vivo activity against HCV, and at the time of this study, each was in phase I development, wrote the authors. Both agents are made by Roche, which funded the study and employed several of the researchers.

The study, known as INFORM-1 (Interferon-Free Regimen for the Management of HCV) was a randomized, double-blind, placebo-controlled, dose-escalation trial. Eligible patients were aged 18-65 years and had been chronically infected with HCV genotype 1, with a minimum HCV RNA of 105 IU/mL.

Patients with cirrhosis, other hepatic or renal failure, and comorbid HIV were not included in this study – a potential limitation, the authors wrote (Lancet 2010 Oct. 14 [doi:10.1016/S0140-6736(10)61384-0]).

In all, 88 patients from six centers in New Zealand and Australia were randomized into seven groups, to receive either placebo or various doses of the novel treatment. Most were white (90%), male (80%), and infected with genotype 1a (79%). The mean age was roughly 47 years.

Overall, 73 patients were ultimately given at least one dose of the assigned treatment, and 14 received placebo.

The investigators found that among patients who received the highest doses of treatment (1,000 mg RG7128 twice daily plus 900 mg of danoprevir twice daily), “five of eight treatment-naive patients and two of eight [previous] null responders [to standard HCV therapy] had HCV RNA concentrations below the limit of detection (less than 15 IU/mL),” according to the authors.

Additionally, “seven of eight treatment-naive patients and four of eight null responders had HCV RNA concentrations below the limit of quantification (43 IU/mL).”

The median reduction in HCV RNA concentrations among the treatment-naive patients was 5.1 log10 IU/mL, and among the previous null responders it was 4.9 log10 IU/mL. In comparison, the mean baseline log10 plasma HCV RNA concentration was 6.4 IU/mL.

The treatment group who received the lowest dose (500 mg RG7128 twice daily, plus 100 mg danoprevir every 8 hours) also saw a median reduction in viral load of 3.7 log10 IU/mL. Of the eight patients in this low-dose cohort, one patient achieved viral levels below the level of detection at 14 days.

“No evidence of treatment-emergent resistance to either compound was identified during the study, and 72 of 73 patients in the treatment groups had a continuous decline in viral load, which was maintained throughout dosing,” wrote the investigators.

The authors noted that they did not find many serious adverse events during treatment. There was one case of severe back pain, and one instance of severe influenzalike illness. However, many patients experienced headache, lethargy, rash, gastrointestinal disorder, and nausea.

At 14 days – the study’s completion – patients continued therapy by switching to standard of care treatment with pegylated interferon alfa-2a and ribavirin.

“The INFORM-1 study provides proof of concept for an oral approach to the treatment of HCV, in which a combination of direct-acting antiviral drugs is safely coadministered without pegylated interferon,” wrote the investigators.

The study treatment “marks a major shift in the future management of HCV infection and the biggest development in treatment of the disease” for the past 2 decades, they added.

The study was funded by Roche, which developed RG7128 and recently bought the worldwide development and commercialization rights to danoprevir from InterMune Inc. Several investigators, including Dr. Gane, have received grants, travel fees, advisory board fees, and other support from Roche and other drug makers; several are employees of Roche or InterMune and have stock options in Roche.

A combination of two oral drugs for reducing viral load in hepatitis C patients had good safety and tolerability in a small, phase I study.

The finding, published online Oct. 15 in the Lancet, points the way toward an alternative to the current standard of care – subcutaneous pegylated interferon-alfa plus oral ribavirin – which has limited tolerability and efficacy.

The novel therapies that were tested in this study are RG7128, a nucleoside polymerase inhibitor, and danoprevir, a protease inhibitor, wrote Dr. Edward J. Gane of Auckland (New Zealand) Clinical Studies Ltd., an early-phase clinical pharmacology unit, and his colleagues.

Both compounds have potent in vitro and in vivo activity against HCV, and at the time of this study, each was in phase I development, wrote the authors. Both agents are made by Roche, which funded the study and employed several of the researchers.

The study, known as INFORM-1 (Interferon-Free Regimen for the Management of HCV) was a randomized, double-blind, placebo-controlled, dose-escalation trial. Eligible patients were aged 18-65 years and had been chronically infected with HCV genotype 1, with a minimum HCV RNA of 105 IU/mL.

Patients with cirrhosis, other hepatic or renal failure, and comorbid HIV were not included in this study – a potential limitation, the authors wrote (Lancet 2010 Oct. 14 [doi:10.1016/S0140-6736(10)61384-0]).

In all, 88 patients from six centers in New Zealand and Australia were randomized into seven groups, to receive either placebo or various doses of the novel treatment. Most were white (90%), male (80%), and infected with genotype 1a (79%). The mean age was roughly 47 years.

Overall, 73 patients were ultimately given at least one dose of the assigned treatment, and 14 received placebo.

The investigators found that among patients who received the highest doses of treatment (1,000 mg RG7128 twice daily plus 900 mg of danoprevir twice daily), “five of eight treatment-naive patients and two of eight [previous] null responders [to standard HCV therapy] had HCV RNA concentrations below the limit of detection (less than 15 IU/mL),” according to the authors.

Additionally, “seven of eight treatment-naive patients and four of eight null responders had HCV RNA concentrations below the limit of quantification (43 IU/mL).”

The median reduction in HCV RNA concentrations among the treatment-naive patients was 5.1 log10 IU/mL, and among the previous null responders it was 4.9 log10 IU/mL. In comparison, the mean baseline log10 plasma HCV RNA concentration was 6.4 IU/mL.

The treatment group who received the lowest dose (500 mg RG7128 twice daily, plus 100 mg danoprevir every 8 hours) also saw a median reduction in viral load of 3.7 log10 IU/mL. Of the eight patients in this low-dose cohort, one patient achieved viral levels below the level of detection at 14 days.

“No evidence of treatment-emergent resistance to either compound was identified during the study, and 72 of 73 patients in the treatment groups had a continuous decline in viral load, which was maintained throughout dosing,” wrote the investigators.

The authors noted that they did not find many serious adverse events during treatment. There was one case of severe back pain, and one instance of severe influenzalike illness. However, many patients experienced headache, lethargy, rash, gastrointestinal disorder, and nausea.

At 14 days – the study’s completion – patients continued therapy by switching to standard of care treatment with pegylated interferon alfa-2a and ribavirin.

“The INFORM-1 study provides proof of concept for an oral approach to the treatment of HCV, in which a combination of direct-acting antiviral drugs is safely coadministered without pegylated interferon,” wrote the investigators.

The study treatment “marks a major shift in the future management of HCV infection and the biggest development in treatment of the disease” for the past 2 decades, they added.

The study was funded by Roche, which developed RG7128 and recently bought the worldwide development and commercialization rights to danoprevir from InterMune Inc. Several investigators, including Dr. Gane, have received grants, travel fees, advisory board fees, and other support from Roche and other drug makers; several are employees of Roche or InterMune and have stock options in Roche.

A combination of two oral drugs for reducing viral load in hepatitis C patients had good safety and tolerability in a small, phase I study.

The finding, published online Oct. 15 in the Lancet, points the way toward an alternative to the current standard of care – subcutaneous pegylated interferon-alfa plus oral ribavirin – which has limited tolerability and efficacy.

The novel therapies that were tested in this study are RG7128, a nucleoside polymerase inhibitor, and danoprevir, a protease inhibitor, wrote Dr. Edward J. Gane of Auckland (New Zealand) Clinical Studies Ltd., an early-phase clinical pharmacology unit, and his colleagues.

Both compounds have potent in vitro and in vivo activity against HCV, and at the time of this study, each was in phase I development, wrote the authors. Both agents are made by Roche, which funded the study and employed several of the researchers.

The study, known as INFORM-1 (Interferon-Free Regimen for the Management of HCV) was a randomized, double-blind, placebo-controlled, dose-escalation trial. Eligible patients were aged 18-65 years and had been chronically infected with HCV genotype 1, with a minimum HCV RNA of 105 IU/mL.

Patients with cirrhosis, other hepatic or renal failure, and comorbid HIV were not included in this study – a potential limitation, the authors wrote (Lancet 2010 Oct. 14 [doi:10.1016/S0140-6736(10)61384-0]).

In all, 88 patients from six centers in New Zealand and Australia were randomized into seven groups, to receive either placebo or various doses of the novel treatment. Most were white (90%), male (80%), and infected with genotype 1a (79%). The mean age was roughly 47 years.

Overall, 73 patients were ultimately given at least one dose of the assigned treatment, and 14 received placebo.

The investigators found that among patients who received the highest doses of treatment (1,000 mg RG7128 twice daily plus 900 mg of danoprevir twice daily), “five of eight treatment-naive patients and two of eight [previous] null responders [to standard HCV therapy] had HCV RNA concentrations below the limit of detection (less than 15 IU/mL),” according to the authors.

Additionally, “seven of eight treatment-naive patients and four of eight null responders had HCV RNA concentrations below the limit of quantification (43 IU/mL).”

The median reduction in HCV RNA concentrations among the treatment-naive patients was 5.1 log10 IU/mL, and among the previous null responders it was 4.9 log10 IU/mL. In comparison, the mean baseline log10 plasma HCV RNA concentration was 6.4 IU/mL.

The treatment group who received the lowest dose (500 mg RG7128 twice daily, plus 100 mg danoprevir every 8 hours) also saw a median reduction in viral load of 3.7 log10 IU/mL. Of the eight patients in this low-dose cohort, one patient achieved viral levels below the level of detection at 14 days.

“No evidence of treatment-emergent resistance to either compound was identified during the study, and 72 of 73 patients in the treatment groups had a continuous decline in viral load, which was maintained throughout dosing,” wrote the investigators.

The authors noted that they did not find many serious adverse events during treatment. There was one case of severe back pain, and one instance of severe influenzalike illness. However, many patients experienced headache, lethargy, rash, gastrointestinal disorder, and nausea.

At 14 days – the study’s completion – patients continued therapy by switching to standard of care treatment with pegylated interferon alfa-2a and ribavirin.

“The INFORM-1 study provides proof of concept for an oral approach to the treatment of HCV, in which a combination of direct-acting antiviral drugs is safely coadministered without pegylated interferon,” wrote the investigators.

The study treatment “marks a major shift in the future management of HCV infection and the biggest development in treatment of the disease” for the past 2 decades, they added.

The study was funded by Roche, which developed RG7128 and recently bought the worldwide development and commercialization rights to danoprevir from InterMune Inc. Several investigators, including Dr. Gane, have received grants, travel fees, advisory board fees, and other support from Roche and other drug makers; several are employees of Roche or InterMune and have stock options in Roche.

A combination of two oral drugs for reducing viral load in hepatitis C patients had good safety and tolerability in a small, phase I study.

The finding, published online Oct. 15 in the Lancet, points the way toward an alternative to the current standard of care – subcutaneous pegylated interferon-alfa plus oral ribavirin – which has limited tolerability and efficacy.

The novel therapies that were tested in this study are RG7128, a nucleoside polymerase inhibitor, and danoprevir, a protease inhibitor, wrote Dr. Edward J. Gane of Auckland (New Zealand) Clinical Studies Ltd., an early-phase clinical pharmacology unit, and his colleagues.

Both compounds have potent in vitro and in vivo activity against HCV, and at the time of this study, each was in phase I development, wrote the authors. Both agents are made by Roche, which funded the study and employed several of the researchers.

The study, known as INFORM-1 (Interferon-Free Regimen for the Management of HCV) was a randomized, double-blind, placebo-controlled, dose-escalation trial. Eligible patients were aged 18-65 years and had been chronically infected with HCV genotype 1, with a minimum HCV RNA of 105 IU/mL.

Patients with cirrhosis, other hepatic or renal failure, and comorbid HIV were not included in this study – a potential limitation, the authors wrote (Lancet 2010 Oct. 14 [doi:10.1016/S0140-6736(10)61384-0]).

In all, 88 patients from six centers in New Zealand and Australia were randomized into seven groups, to receive either placebo or various doses of the novel treatment. Most were white (90%), male (80%), and infected with genotype 1a (79%). The mean age was roughly 47 years.

Overall, 73 patients were ultimately given at least one dose of the assigned treatment, and 14 received placebo.

The investigators found that among patients who received the highest doses of treatment (1,000 mg RG7128 twice daily plus 900 mg of danoprevir twice daily), “five of eight treatment-naive patients and two of eight [previous] null responders [to standard HCV therapy] had HCV RNA concentrations below the limit of detection (less than 15 IU/mL),” according to the authors.

Additionally, “seven of eight treatment-naive patients and four of eight null responders had HCV RNA concentrations below the limit of quantification (43 IU/mL).”

The median reduction in HCV RNA concentrations among the treatment-naive patients was 5.1 log10 IU/mL, and among the previous null responders it was 4.9 log10 IU/mL. In comparison, the mean baseline log10 plasma HCV RNA concentration was 6.4 IU/mL.

The treatment group who received the lowest dose (500 mg RG7128 twice daily, plus 100 mg danoprevir every 8 hours) also saw a median reduction in viral load of 3.7 log10 IU/mL. Of the eight patients in this low-dose cohort, one patient achieved viral levels below the level of detection at 14 days.

“No evidence of treatment-emergent resistance to either compound was identified during the study, and 72 of 73 patients in the treatment groups had a continuous decline in viral load, which was maintained throughout dosing,” wrote the investigators.

The authors noted that they did not find many serious adverse events during treatment. There was one case of severe back pain, and one instance of severe influenzalike illness. However, many patients experienced headache, lethargy, rash, gastrointestinal disorder, and nausea.

At 14 days – the study’s completion – patients continued therapy by switching to standard of care treatment with pegylated interferon alfa-2a and ribavirin.

“The INFORM-1 study provides proof of concept for an oral approach to the treatment of HCV, in which a combination of direct-acting antiviral drugs is safely coadministered without pegylated interferon,” wrote the investigators.

The study treatment “marks a major shift in the future management of HCV infection and the biggest development in treatment of the disease” for the past 2 decades, they added.

The study was funded by Roche, which developed RG7128 and recently bought the worldwide development and commercialization rights to danoprevir from InterMune Inc. Several investigators, including Dr. Gane, have received grants, travel fees, advisory board fees, and other support from Roche and other drug makers; several are employees of Roche or InterMune and have stock options in Roche.

A combination of two oral drugs for reducing viral load in hepatitis C patients had good safety and tolerability in a small, phase I study.

The finding, published online Oct. 15 in the Lancet, points the way toward an alternative to the current standard of care – subcutaneous pegylated interferon-alfa plus oral ribavirin – which has limited tolerability and efficacy.

The novel therapies that were tested in this study are RG7128, a nucleoside polymerase inhibitor, and danoprevir, a protease inhibitor, wrote Dr. Edward J. Gane of Auckland (New Zealand) Clinical Studies Ltd., an early-phase clinical pharmacology unit, and his colleagues.

Both compounds have potent in vitro and in vivo activity against HCV, and at the time of this study, each was in phase I development, wrote the authors. Both agents are made by Roche, which funded the study and employed several of the researchers.

The study, known as INFORM-1 (Interferon-Free Regimen for the Management of HCV) was a randomized, double-blind, placebo-controlled, dose-escalation trial. Eligible patients were aged 18-65 years and had been chronically infected with HCV genotype 1, with a minimum HCV RNA of 105 IU/mL.

Patients with cirrhosis, other hepatic or renal failure, and comorbid HIV were not included in this study – a potential limitation, the authors wrote (Lancet 2010 Oct. 14 [doi:10.1016/S0140-6736(10)61384-0]).

In all, 88 patients from six centers in New Zealand and Australia were randomized into seven groups, to receive either placebo or various doses of the novel treatment. Most were white (90%), male (80%), and infected with genotype 1a (79%). The mean age was roughly 47 years.

Overall, 73 patients were ultimately given at least one dose of the assigned treatment, and 14 received placebo.

The investigators found that among patients who received the highest doses of treatment (1,000 mg RG7128 twice daily plus 900 mg of danoprevir twice daily), “five of eight treatment-naive patients and two of eight [previous] null responders [to standard HCV therapy] had HCV RNA concentrations below the limit of detection (less than 15 IU/mL),” according to the authors.

Additionally, “seven of eight treatment-naive patients and four of eight null responders had HCV RNA concentrations below the limit of quantification (43 IU/mL).”

The median reduction in HCV RNA concentrations among the treatment-naive patients was 5.1 log10 IU/mL, and among the previous null responders it was 4.9 log10 IU/mL. In comparison, the mean baseline log10 plasma HCV RNA concentration was 6.4 IU/mL.

The treatment group who received the lowest dose (500 mg RG7128 twice daily, plus 100 mg danoprevir every 8 hours) also saw a median reduction in viral load of 3.7 log10 IU/mL. Of the eight patients in this low-dose cohort, one patient achieved viral levels below the level of detection at 14 days.

“No evidence of treatment-emergent resistance to either compound was identified during the study, and 72 of 73 patients in the treatment groups had a continuous decline in viral load, which was maintained throughout dosing,” wrote the investigators.

The authors noted that they did not find many serious adverse events during treatment. There was one case of severe back pain, and one instance of severe influenzalike illness. However, many patients experienced headache, lethargy, rash, gastrointestinal disorder, and nausea.

At 14 days – the study’s completion – patients continued therapy by switching to standard of care treatment with pegylated interferon alfa-2a and ribavirin.

“The INFORM-1 study provides proof of concept for an oral approach to the treatment of HCV, in which a combination of direct-acting antiviral drugs is safely coadministered without pegylated interferon,” wrote the investigators.

The study treatment “marks a major shift in the future management of HCV infection and the biggest development in treatment of the disease” for the past 2 decades, they added.

The study was funded by Roche, which developed RG7128 and recently bought the worldwide development and commercialization rights to danoprevir from InterMune Inc. Several investigators, including Dr. Gane, have received grants, travel fees, advisory board fees, and other support from Roche and other drug makers; several are employees of Roche or InterMune and have stock options in Roche.

A combination of two oral drugs for reducing viral load in hepatitis C patients had good safety and tolerability in a small, phase I study.

The finding, published online Oct. 15 in the Lancet, points the way toward an alternative to the current standard of care – subcutaneous pegylated interferon-alfa plus oral ribavirin – which has limited tolerability and efficacy.

The novel therapies that were tested in this study are RG7128, a nucleoside polymerase inhibitor, and danoprevir, a protease inhibitor, wrote Dr. Edward J. Gane of Auckland (New Zealand) Clinical Studies Ltd., an early-phase clinical pharmacology unit, and his colleagues.

Both compounds have potent in vitro and in vivo activity against HCV, and at the time of this study, each was in phase I development, wrote the authors. Both agents are made by Roche, which funded the study and employed several of the researchers.

The study, known as INFORM-1 (Interferon-Free Regimen for the Management of HCV) was a randomized, double-blind, placebo-controlled, dose-escalation trial. Eligible patients were aged 18-65 years and had been chronically infected with HCV genotype 1, with a minimum HCV RNA of 105 IU/mL.

Patients with cirrhosis, other hepatic or renal failure, and comorbid HIV were not included in this study – a potential limitation, the authors wrote (Lancet 2010 Oct. 14 [doi:10.1016/S0140-6736(10)61384-0]).

In all, 88 patients from six centers in New Zealand and Australia were randomized into seven groups, to receive either placebo or various doses of the novel treatment. Most were white (90%), male (80%), and infected with genotype 1a (79%). The mean age was roughly 47 years.

Overall, 73 patients were ultimately given at least one dose of the assigned treatment, and 14 received placebo.

The investigators found that among patients who received the highest doses of treatment (1,000 mg RG7128 twice daily plus 900 mg of danoprevir twice daily), “five of eight treatment-naive patients and two of eight [previous] null responders [to standard HCV therapy] had HCV RNA concentrations below the limit of detection (less than 15 IU/mL),” according to the authors.

Additionally, “seven of eight treatment-naive patients and four of eight null responders had HCV RNA concentrations below the limit of quantification (43 IU/mL).”

The median reduction in HCV RNA concentrations among the treatment-naive patients was 5.1 log10 IU/mL, and among the previous null responders it was 4.9 log10 IU/mL. In comparison, the mean baseline log10 plasma HCV RNA concentration was 6.4 IU/mL.

The treatment group who received the lowest dose (500 mg RG7128 twice daily, plus 100 mg danoprevir every 8 hours) also saw a median reduction in viral load of 3.7 log10 IU/mL. Of the eight patients in this low-dose cohort, one patient achieved viral levels below the level of detection at 14 days.

“No evidence of treatment-emergent resistance to either compound was identified during the study, and 72 of 73 patients in the treatment groups had a continuous decline in viral load, which was maintained throughout dosing,” wrote the investigators.

The authors noted that they did not find many serious adverse events during treatment. There was one case of severe back pain, and one instance of severe influenzalike illness. However, many patients experienced headache, lethargy, rash, gastrointestinal disorder, and nausea.

At 14 days – the study’s completion – patients continued therapy by switching to standard of care treatment with pegylated interferon alfa-2a and ribavirin.

“The INFORM-1 study provides proof of concept for an oral approach to the treatment of HCV, in which a combination of direct-acting antiviral drugs is safely coadministered without pegylated interferon,” wrote the investigators.

The study treatment “marks a major shift in the future management of HCV infection and the biggest development in treatment of the disease” for the past 2 decades, they added.

The study was funded by Roche, which developed RG7128 and recently bought the worldwide development and commercialization rights to danoprevir from InterMune Inc. Several investigators, including Dr. Gane, have received grants, travel fees, advisory board fees, and other support from Roche and other drug makers; several are employees of Roche or InterMune and have stock options in Roche.

Nearly one-quarter of high school students reported binge drinking in 2009, as did more than 25% of adults aged 18-34 years.

These findings, published online Oct. 5 in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report, are essentially unchanged from similar surveys conducted in 1993, wrote the authors, and indicate a need for community-specific, evidence-based interventions (MMWR 2010;59:1-6).

© godfer/Fotolia.com

“Although most binge drinkers are not alcohol dependent or alcoholics, they often engage in this high-risk behavior without realizing the health and social problems of their drinking. States and communities need to consider further strategies to create an environment that discourages binge drinking,” said Dr. Robert Brewer in a written statement also released Oct. 5. Dr. Brewer is the alcohol program leader at CDC and one of the authors of the report.

The CDC analyzed data from two sources. The first was the 2009 Behavioral Risk Factor Surveillance System, conducted among adults aged 18 years and older on both landline and cellular telephones. The second was the 2009 National Youth Risk Behavior Survey, filled out anonymously by students while in school.

The adult survey defined binge drinking as the consumption of four or more alcoholic drinks per occasion for women and five or more drinks per occasion for men during the preceding 30 days. Among the students, binge drinking was five or more drinks within “a couple of hours” in the preceding 30 days.

Among the landline respondents, the overall prevalence of binge drinking among adults in 2009 was 15.2% (compared to 14.2% in 1993), with more men reporting binge drinking than women (20.7% versus 10.0%, respectively). Among respondents aged 18-24, prevalence was 25.6%; among those aged 25-34, it fell slightly to 22.5%, and continued to decline with age.

Among the cellular respondents, the prevalence of binge drinking was slightly higher: 20.6% overall, with 26.5% for men and 14.5% for women. Among the 18- to 24-year age group, 35.4% reported binge drinking. As with the landline respondents, decline in prevalence continued with increase in age to 30.8% among 25- to 34-year-olds, and a further steady decline afterwards.

The survey also noted a higher prevalence of binge drinking among specific populations, including not only males and younger adults but also whites (at 16.0% among landline respondents, compared to 13.4% among Hispanics and 10.0% among blacks) and people with higher household incomes (above $75,000, the prevalence was 32.8%, compared to 16.3% for households with incomes between $50,000 and $75,000).

College graduates also reported binge drinking more frequently than did high school graduates with no college, as well as respondents with no high school diploma (34.7%, 28.2%, 10.5%, respectively).

Differences among the various population groups “might reflect differences in state and local laws that affect the price, availability, and marketing of alcoholic beverages,” postulated the authors.

High school students also reported frequent binge drinking, with 24.2% owning up to the practice in the last 30 days, including 25.0% of boys and 23.4% of girls.

Stratified further by grade, the prevalence among 9th graders was 15.3%, compared to 33.5% among 12th graders.

Overall alcohol use among high school students, including any drinking, not just bingeing, was 41.8%.

The researchers did cite several limitations, including the fact that data were self-reported and therefore likely underreported. Additionally, they stated that landline surveys may be less useful than cellular surveys, especially in ascertaining the drinking status of younger adults, since “an increasing proportion of youths and young adults aged 18-34 years use cellular telephones exclusively.”

Moreover, the response rate for both telephone surveys was low: 52.9% among landlines (comprising 412,005 respondents) and 37.6% for cell phone users (15,578 respondents).

Disclosures: There were no disclosures reported with this study.

Nearly one-quarter of high school students reported binge drinking in 2009, as did more than 25% of adults aged 18-34 years.

These findings, published online Oct. 5 in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report, are essentially unchanged from similar surveys conducted in 1993, wrote the authors, and indicate a need for community-specific, evidence-based interventions (MMWR 2010;59:1-6).

© godfer/Fotolia.com

“Although most binge drinkers are not alcohol dependent or alcoholics, they often engage in this high-risk behavior without realizing the health and social problems of their drinking. States and communities need to consider further strategies to create an environment that discourages binge drinking,” said Dr. Robert Brewer in a written statement also released Oct. 5. Dr. Brewer is the alcohol program leader at CDC and one of the authors of the report.

The CDC analyzed data from two sources. The first was the 2009 Behavioral Risk Factor Surveillance System, conducted among adults aged 18 years and older on both landline and cellular telephones. The second was the 2009 National Youth Risk Behavior Survey, filled out anonymously by students while in school.

The adult survey defined binge drinking as the consumption of four or more alcoholic drinks per occasion for women and five or more drinks per occasion for men during the preceding 30 days. Among the students, binge drinking was five or more drinks within “a couple of hours” in the preceding 30 days.

Among the landline respondents, the overall prevalence of binge drinking among adults in 2009 was 15.2% (compared to 14.2% in 1993), with more men reporting binge drinking than women (20.7% versus 10.0%, respectively). Among respondents aged 18-24, prevalence was 25.6%; among those aged 25-34, it fell slightly to 22.5%, and continued to decline with age.

Among the cellular respondents, the prevalence of binge drinking was slightly higher: 20.6% overall, with 26.5% for men and 14.5% for women. Among the 18- to 24-year age group, 35.4% reported binge drinking. As with the landline respondents, decline in prevalence continued with increase in age to 30.8% among 25- to 34-year-olds, and a further steady decline afterwards.

The survey also noted a higher prevalence of binge drinking among specific populations, including not only males and younger adults but also whites (at 16.0% among landline respondents, compared to 13.4% among Hispanics and 10.0% among blacks) and people with higher household incomes (above $75,000, the prevalence was 32.8%, compared to 16.3% for households with incomes between $50,000 and $75,000).

College graduates also reported binge drinking more frequently than did high school graduates with no college, as well as respondents with no high school diploma (34.7%, 28.2%, 10.5%, respectively).

Differences among the various population groups “might reflect differences in state and local laws that affect the price, availability, and marketing of alcoholic beverages,” postulated the authors.

High school students also reported frequent binge drinking, with 24.2% owning up to the practice in the last 30 days, including 25.0% of boys and 23.4% of girls.

Stratified further by grade, the prevalence among 9th graders was 15.3%, compared to 33.5% among 12th graders.

Overall alcohol use among high school students, including any drinking, not just bingeing, was 41.8%.

The researchers did cite several limitations, including the fact that data were self-reported and therefore likely underreported. Additionally, they stated that landline surveys may be less useful than cellular surveys, especially in ascertaining the drinking status of younger adults, since “an increasing proportion of youths and young adults aged 18-34 years use cellular telephones exclusively.”

Moreover, the response rate for both telephone surveys was low: 52.9% among landlines (comprising 412,005 respondents) and 37.6% for cell phone users (15,578 respondents).

Disclosures: There were no disclosures reported with this study.

Nearly one-quarter of high school students reported binge drinking in 2009, as did more than 25% of adults aged 18-34 years.

These findings, published online Oct. 5 in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report, are essentially unchanged from similar surveys conducted in 1993, wrote the authors, and indicate a need for community-specific, evidence-based interventions (MMWR 2010;59:1-6).

© godfer/Fotolia.com

“Although most binge drinkers are not alcohol dependent or alcoholics, they often engage in this high-risk behavior without realizing the health and social problems of their drinking. States and communities need to consider further strategies to create an environment that discourages binge drinking,” said Dr. Robert Brewer in a written statement also released Oct. 5. Dr. Brewer is the alcohol program leader at CDC and one of the authors of the report.

The CDC analyzed data from two sources. The first was the 2009 Behavioral Risk Factor Surveillance System, conducted among adults aged 18 years and older on both landline and cellular telephones. The second was the 2009 National Youth Risk Behavior Survey, filled out anonymously by students while in school.

The adult survey defined binge drinking as the consumption of four or more alcoholic drinks per occasion for women and five or more drinks per occasion for men during the preceding 30 days. Among the students, binge drinking was five or more drinks within “a couple of hours” in the preceding 30 days.

Among the landline respondents, the overall prevalence of binge drinking among adults in 2009 was 15.2% (compared to 14.2% in 1993), with more men reporting binge drinking than women (20.7% versus 10.0%, respectively). Among respondents aged 18-24, prevalence was 25.6%; among those aged 25-34, it fell slightly to 22.5%, and continued to decline with age.

Among the cellular respondents, the prevalence of binge drinking was slightly higher: 20.6% overall, with 26.5% for men and 14.5% for women. Among the 18- to 24-year age group, 35.4% reported binge drinking. As with the landline respondents, decline in prevalence continued with increase in age to 30.8% among 25- to 34-year-olds, and a further steady decline afterwards.

The survey also noted a higher prevalence of binge drinking among specific populations, including not only males and younger adults but also whites (at 16.0% among landline respondents, compared to 13.4% among Hispanics and 10.0% among blacks) and people with higher household incomes (above $75,000, the prevalence was 32.8%, compared to 16.3% for households with incomes between $50,000 and $75,000).

College graduates also reported binge drinking more frequently than did high school graduates with no college, as well as respondents with no high school diploma (34.7%, 28.2%, 10.5%, respectively).

Differences among the various population groups “might reflect differences in state and local laws that affect the price, availability, and marketing of alcoholic beverages,” postulated the authors.

High school students also reported frequent binge drinking, with 24.2% owning up to the practice in the last 30 days, including 25.0% of boys and 23.4% of girls.

Stratified further by grade, the prevalence among 9th graders was 15.3%, compared to 33.5% among 12th graders.

Overall alcohol use among high school students, including any drinking, not just bingeing, was 41.8%.

The researchers did cite several limitations, including the fact that data were self-reported and therefore likely underreported. Additionally, they stated that landline surveys may be less useful than cellular surveys, especially in ascertaining the drinking status of younger adults, since “an increasing proportion of youths and young adults aged 18-34 years use cellular telephones exclusively.”

Moreover, the response rate for both telephone surveys was low: 52.9% among landlines (comprising 412,005 respondents) and 37.6% for cell phone users (15,578 respondents).

Disclosures: There were no disclosures reported with this study.

ACR Asks for Relief

The American College of Rheumatology said that “patient access to necessary care will be compromised” if parts of the 2011 Medicare Physician Fee Schedule are implemented as proposed. Specifically, the ACR asked for reversal of existing policies on consultation codes and the Physician Quality Reporting Initiative program. In a letter to the Centers for Medicare and Medicaid Services, ACR President Stanley Cohen said that the CMS's decision to eliminate reimbursable consultation codes has been “devastating” to rheumatologists. On PQRI, he said that physicians too often lose out on deserved quality payments when they inadvertently file incorrect reports, an event that also can publicly label them as poor-quality providers. “The ACR requests that CMS implement a program to instruct physicians on proper reporting,” Dr. Cohen wrote.

Study: Mistake Policies Needed

When several patients are affected by a medical mistake — even one that probably will harm none of them — the event ought to be disclosed to the public, said authors of a study funded by the Agency for Healthcare Research and Quality (N. Engl. J. Med. 2010;363:978-86). The authors said that “large-scale adverse events” from around the world have included everything from malfunctioning to poorly sterilized lab equipment. They advocated timely disclosure of such mistakes to government authorities, to potentially affected patients, and to the media. Health care facilities should follow up on possible physical and psychological effects of adverse events. In a statement, AHRQ Director Carolyn M. Clancy said, “It's clear that health care organizations face a dilemma regarding disclosure of large-scale adverse events — whether these events lead to patient harm or not.”

Stop-Smoking Coverage Expanded

Physicians will be reimbursed for counseling any Medicare patient about smoking cessation, not just those with tobacco-related illness, under new guidelines approved by the CMS. Previously, a patient needed to at least show signs of illness related to smoking before Medicare would pay. Now, any smoker covered by Medicare can have up to eight smoking cessation sessions per year from a physician or another Medicare-recognized health practitioner, CMS said. American Medical Association President Cecil Wilson applauded the coverage expansion. “More than 400,000 Americans die needlessly every year as a direct result of tobacco use,” Dr. Wilson said in a statement. “This expansion of coverage takes an important step toward helping Medicare patients lead healthier, tobacco-free lives.”

$14 Million for Minority Research

Economic stimulus funds totalling $14.2 million have been allocated to “patient-centered outcomes research” among racial and ethnic minorities with diseases including arthritis, the U.S. Department of Health and Human Services announced. The money is part of the $1.1 billion earmarked for outcomes research in the American Recovery and Reinvestment Act of 2009. “Patient-centered outcomes research must become a critical part of our strategy as a nation to understand and eliminate health disparities,” said John Ruffin, Ph.D., director of the National Institute on Minority Health and Health Disparities.

Worries About Pharma Influence

Almost 70% of Americans who take prescription drugs believe that drug makers have too much influence over doctors when it comes to those prescriptions, and 50% believe that doctors prescribe drugs even when a person's condition could be managed without medication. The data are the result of a Consumer Reports magazine poll. On the basis of the survey of more than 1,150 adults, the magazine asserted that 51% of Americans don't think their doctors consider patients' ability to pay for prescribed drugs, 47% think gifts from pharmaceutical companies influence doctors' drug choices, 41% think their doctors tend to prescribe newer and more expensive drugs, and 20% have asked for a drug they've seen advertised. In those cases, 59% of the respondents said their doctors prescribed what they requested.

Deals Keep Generics Off Market

Branded- and generic-drug manufacturers have made at least 21 deals so far this year that potentially delay the production of cheaper, generic versions of existing brand-name drugs, the Federal Trade Commission said. In three-quarters of the settlements reported to the FTC, the branded- and generic-drug makers came to terms without money changing hands. The agency, which is attempting to crack down on these “pay-for-delay” deals, told congressional lawmakers that generic- and branded-drug manufacturers inked 19 such deals in 2009, and 16 in 2008. The 2010 deals protect $9 billion in brand-name drug sales from generic competition, FTC Chairman Jon Leibowitz told a House subcommittee. The FTC estimated that “pay-for-delay” deals cost consumers $3.5 billion each year.

ACR Asks for Relief

The American College of Rheumatology said that “patient access to necessary care will be compromised” if parts of the 2011 Medicare Physician Fee Schedule are implemented as proposed. Specifically, the ACR asked for reversal of existing policies on consultation codes and the Physician Quality Reporting Initiative program. In a letter to the Centers for Medicare and Medicaid Services, ACR President Stanley Cohen said that the CMS's decision to eliminate reimbursable consultation codes has been “devastating” to rheumatologists. On PQRI, he said that physicians too often lose out on deserved quality payments when they inadvertently file incorrect reports, an event that also can publicly label them as poor-quality providers. “The ACR requests that CMS implement a program to instruct physicians on proper reporting,” Dr. Cohen wrote.

Study: Mistake Policies Needed

When several patients are affected by a medical mistake — even one that probably will harm none of them — the event ought to be disclosed to the public, said authors of a study funded by the Agency for Healthcare Research and Quality (N. Engl. J. Med. 2010;363:978-86). The authors said that “large-scale adverse events” from around the world have included everything from malfunctioning to poorly sterilized lab equipment. They advocated timely disclosure of such mistakes to government authorities, to potentially affected patients, and to the media. Health care facilities should follow up on possible physical and psychological effects of adverse events. In a statement, AHRQ Director Carolyn M. Clancy said, “It's clear that health care organizations face a dilemma regarding disclosure of large-scale adverse events — whether these events lead to patient harm or not.”

Stop-Smoking Coverage Expanded

Physicians will be reimbursed for counseling any Medicare patient about smoking cessation, not just those with tobacco-related illness, under new guidelines approved by the CMS. Previously, a patient needed to at least show signs of illness related to smoking before Medicare would pay. Now, any smoker covered by Medicare can have up to eight smoking cessation sessions per year from a physician or another Medicare-recognized health practitioner, CMS said. American Medical Association President Cecil Wilson applauded the coverage expansion. “More than 400,000 Americans die needlessly every year as a direct result of tobacco use,” Dr. Wilson said in a statement. “This expansion of coverage takes an important step toward helping Medicare patients lead healthier, tobacco-free lives.”

$14 Million for Minority Research

Economic stimulus funds totalling $14.2 million have been allocated to “patient-centered outcomes research” among racial and ethnic minorities with diseases including arthritis, the U.S. Department of Health and Human Services announced. The money is part of the $1.1 billion earmarked for outcomes research in the American Recovery and Reinvestment Act of 2009. “Patient-centered outcomes research must become a critical part of our strategy as a nation to understand and eliminate health disparities,” said John Ruffin, Ph.D., director of the National Institute on Minority Health and Health Disparities.

Worries About Pharma Influence

Almost 70% of Americans who take prescription drugs believe that drug makers have too much influence over doctors when it comes to those prescriptions, and 50% believe that doctors prescribe drugs even when a person's condition could be managed without medication. The data are the result of a Consumer Reports magazine poll. On the basis of the survey of more than 1,150 adults, the magazine asserted that 51% of Americans don't think their doctors consider patients' ability to pay for prescribed drugs, 47% think gifts from pharmaceutical companies influence doctors' drug choices, 41% think their doctors tend to prescribe newer and more expensive drugs, and 20% have asked for a drug they've seen advertised. In those cases, 59% of the respondents said their doctors prescribed what they requested.

Deals Keep Generics Off Market

Branded- and generic-drug manufacturers have made at least 21 deals so far this year that potentially delay the production of cheaper, generic versions of existing brand-name drugs, the Federal Trade Commission said. In three-quarters of the settlements reported to the FTC, the branded- and generic-drug makers came to terms without money changing hands. The agency, which is attempting to crack down on these “pay-for-delay” deals, told congressional lawmakers that generic- and branded-drug manufacturers inked 19 such deals in 2009, and 16 in 2008. The 2010 deals protect $9 billion in brand-name drug sales from generic competition, FTC Chairman Jon Leibowitz told a House subcommittee. The FTC estimated that “pay-for-delay” deals cost consumers $3.5 billion each year.

ACR Asks for Relief

The American College of Rheumatology said that “patient access to necessary care will be compromised” if parts of the 2011 Medicare Physician Fee Schedule are implemented as proposed. Specifically, the ACR asked for reversal of existing policies on consultation codes and the Physician Quality Reporting Initiative program. In a letter to the Centers for Medicare and Medicaid Services, ACR President Stanley Cohen said that the CMS's decision to eliminate reimbursable consultation codes has been “devastating” to rheumatologists. On PQRI, he said that physicians too often lose out on deserved quality payments when they inadvertently file incorrect reports, an event that also can publicly label them as poor-quality providers. “The ACR requests that CMS implement a program to instruct physicians on proper reporting,” Dr. Cohen wrote.

Study: Mistake Policies Needed

When several patients are affected by a medical mistake — even one that probably will harm none of them — the event ought to be disclosed to the public, said authors of a study funded by the Agency for Healthcare Research and Quality (N. Engl. J. Med. 2010;363:978-86). The authors said that “large-scale adverse events” from around the world have included everything from malfunctioning to poorly sterilized lab equipment. They advocated timely disclosure of such mistakes to government authorities, to potentially affected patients, and to the media. Health care facilities should follow up on possible physical and psychological effects of adverse events. In a statement, AHRQ Director Carolyn M. Clancy said, “It's clear that health care organizations face a dilemma regarding disclosure of large-scale adverse events — whether these events lead to patient harm or not.”

Stop-Smoking Coverage Expanded

Physicians will be reimbursed for counseling any Medicare patient about smoking cessation, not just those with tobacco-related illness, under new guidelines approved by the CMS. Previously, a patient needed to at least show signs of illness related to smoking before Medicare would pay. Now, any smoker covered by Medicare can have up to eight smoking cessation sessions per year from a physician or another Medicare-recognized health practitioner, CMS said. American Medical Association President Cecil Wilson applauded the coverage expansion. “More than 400,000 Americans die needlessly every year as a direct result of tobacco use,” Dr. Wilson said in a statement. “This expansion of coverage takes an important step toward helping Medicare patients lead healthier, tobacco-free lives.”

$14 Million for Minority Research

Economic stimulus funds totalling $14.2 million have been allocated to “patient-centered outcomes research” among racial and ethnic minorities with diseases including arthritis, the U.S. Department of Health and Human Services announced. The money is part of the $1.1 billion earmarked for outcomes research in the American Recovery and Reinvestment Act of 2009. “Patient-centered outcomes research must become a critical part of our strategy as a nation to understand and eliminate health disparities,” said John Ruffin, Ph.D., director of the National Institute on Minority Health and Health Disparities.

Worries About Pharma Influence

Almost 70% of Americans who take prescription drugs believe that drug makers have too much influence over doctors when it comes to those prescriptions, and 50% believe that doctors prescribe drugs even when a person's condition could be managed without medication. The data are the result of a Consumer Reports magazine poll. On the basis of the survey of more than 1,150 adults, the magazine asserted that 51% of Americans don't think their doctors consider patients' ability to pay for prescribed drugs, 47% think gifts from pharmaceutical companies influence doctors' drug choices, 41% think their doctors tend to prescribe newer and more expensive drugs, and 20% have asked for a drug they've seen advertised. In those cases, 59% of the respondents said their doctors prescribed what they requested.

Deals Keep Generics Off Market

Branded- and generic-drug manufacturers have made at least 21 deals so far this year that potentially delay the production of cheaper, generic versions of existing brand-name drugs, the Federal Trade Commission said. In three-quarters of the settlements reported to the FTC, the branded- and generic-drug makers came to terms without money changing hands. The agency, which is attempting to crack down on these “pay-for-delay” deals, told congressional lawmakers that generic- and branded-drug manufacturers inked 19 such deals in 2009, and 16 in 2008. The 2010 deals protect $9 billion in brand-name drug sales from generic competition, FTC Chairman Jon Leibowitz told a House subcommittee. The FTC estimated that “pay-for-delay” deals cost consumers $3.5 billion each year.

Investigational new drugs, including biologic drugs, will face new safety reporting requirements designed to increase timeliness as well as decrease unnecessary reporting of events not likely to be causal.

The changes bring the Food and Drug Administration's reporting policies in line with international agencies, including the World Health Organization (WHO).

The changes focus on the reporting of adverse events clearly linked to the drug that occur during animal or human testing of the agent.

Adherence to the former rule often resulted in reporting of events not likely to be associated with the drug, slowing recognition of truly causal effects, according to the draft guidance.

Under the new rule, applicants may submit only “suspected adverse reactions,” defined as events for which there is “evidence to suggest a causal relationship between the drug and the adverse event,” according to a FDA draft guidance for investigators.

Other reportable findings include data concerning bioequivalence of generic biologic drugs, compared with their name-brand counterparts — for example, differing rates of absorption into the bloodstream.

To see the full text of the final rule, visit http://tinyurl.com/36fld9u

Investigational new drugs, including biologic drugs, will face new safety reporting requirements designed to increase timeliness as well as decrease unnecessary reporting of events not likely to be causal.

The changes bring the Food and Drug Administration's reporting policies in line with international agencies, including the World Health Organization (WHO).

The changes focus on the reporting of adverse events clearly linked to the drug that occur during animal or human testing of the agent.

Adherence to the former rule often resulted in reporting of events not likely to be associated with the drug, slowing recognition of truly causal effects, according to the draft guidance.

Under the new rule, applicants may submit only “suspected adverse reactions,” defined as events for which there is “evidence to suggest a causal relationship between the drug and the adverse event,” according to a FDA draft guidance for investigators.

Other reportable findings include data concerning bioequivalence of generic biologic drugs, compared with their name-brand counterparts — for example, differing rates of absorption into the bloodstream.

To see the full text of the final rule, visit http://tinyurl.com/36fld9u

Investigational new drugs, including biologic drugs, will face new safety reporting requirements designed to increase timeliness as well as decrease unnecessary reporting of events not likely to be causal.

The changes bring the Food and Drug Administration's reporting policies in line with international agencies, including the World Health Organization (WHO).

The changes focus on the reporting of adverse events clearly linked to the drug that occur during animal or human testing of the agent.

Adherence to the former rule often resulted in reporting of events not likely to be associated with the drug, slowing recognition of truly causal effects, according to the draft guidance.

Under the new rule, applicants may submit only “suspected adverse reactions,” defined as events for which there is “evidence to suggest a causal relationship between the drug and the adverse event,” according to a FDA draft guidance for investigators.

Other reportable findings include data concerning bioequivalence of generic biologic drugs, compared with their name-brand counterparts — for example, differing rates of absorption into the bloodstream.

To see the full text of the final rule, visit http://tinyurl.com/36fld9u

The promised overhaul of treatment guidelines for rheumatoid arthritis has finally arrived, and with it, a “new paradigm” that focuses on early identification and treatment of the disabling disease.

The guidelines, which were developed by a joint committee from the American College of Rheumatology and the European League Against Rheumatism, are the latest update since the current guidelines were created in 1987.

Published jointly in the EULAR journal Annals of the Rheumatic Diseases (2010;69:1580-8) and the ACR's Arthritis & Rheumatism (2010;62:2569-81), the new guidelines were created in three phases over 2 years.

In the first phase, the goal was to “to identify the contributions of clinical and laboratory variables that in practice were the most predictive of the decision to initiate [disease-modifying antirheumatic drug] therapy in … patients with early undifferentiated synovitis,” wrote the authors, led by Dr. Daniel Aletaha of the Medical University of Vienna.

To do this, a working group from both societies looked at data from 3,115 patients and correlated whether or not the patients were ultimately prescribed methotrexate to an “agreed-upon list of standardized clinical and laboratory variables collected at baseline.”

The odds of eventual methotrexate initiation were calculated for each variable. For example, swelling of the metacarpophalangeal joint had an odds ratio of 1.5, as did swelling of the proximal interphalangeal joint and the wrist. Tenderness of the hand (either the MCP, PIP, or wrist) was assigned an odds ratio of 2.0.

Moderate elevation of C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) was assigned an OR of 1.0; high elevation of either assay got an OR of 2.0.

In phase II, a panel of 12 rheumatologists related the above clinical and laboratory factors to the “probability of developing 'persistent inflammatory and/or erosive arthritis that is currently considered to be RA.'”

Finally, phase III aimed to utilize the results of phases I and II “to develop a scoring system that would be applicable to newly presenting patients with undifferentiated inflammatory arthritis, to permit identification of those with a high probability of developing persistent and/or erosive RA.”

This final scale assigns points in the following manner:

▸ One swollen “large joint” (defined as shoulders, elbows, hips, knees, and ankles) gets 0 points; involvement of 2-10 large joints gets 1 point.

▸ Involvement of 1-3 “small” joints (defined as metacarpophalangeal joints, proximal interphalangeal joints, second to fifth metatarsophalangeal joints, thumb interphalangeal joints, and wrists) gets 2 points, regardless of large-joint involvement; involvement of 4-10 small joints gets 3 points.

▸ Involvement of more than 10 joints, including at least 1 small joint, gets 5 points.

▸ Both a negative rheumatoid factor (RF) test and a negative anti—citrullinated protein antibody (ACPA) testgets 0 points, whereas having a “low-positive” RF or ACPA (defined as lower than three times the upper limit of normal) gets 2 points. A “high-positive” of either test gets 3 points.

▸ A normal CRP and normal ESR get 0 points, whereas at least one abnormal test gets 1 point.

▸ Symptom duration of fewer than 6 weeks gets 0 points; duration of 6 weeks or longer gets 1 point.

Scores of 6 or more out of 10 are classified as “definite RA.”

Commenting on the new criteria in an interview, Dr. Eric L. Matteson, who is with the Mayo Clinic in Rochester, Minn., and was not involved with the new guidelines, said, “A major useful feature is that the new guidelines do not require multiple joints to be inflamed before a diagnosis can be [made] of early inflammatory rheumatoid arthritis.”

Indeed, a patient may score 6 points without multiple joint inflammation, according to the new guidelines.

When asked what was missing from the new guidelines, he pointed to a lack of awareness of extra-articular components of RA, which also can occur early in the course of the disease.

Disclosures: Several of the guideline authors disclosed financial and other relationships with multiple pharmaceutical companies; Dr. Matteson stated that he had no financial disclosures relative to his comments.

The promised overhaul of treatment guidelines for rheumatoid arthritis has finally arrived, and with it, a “new paradigm” that focuses on early identification and treatment of the disabling disease.

The guidelines, which were developed by a joint committee from the American College of Rheumatology and the European League Against Rheumatism, are the latest update since the current guidelines were created in 1987.

Published jointly in the EULAR journal Annals of the Rheumatic Diseases (2010;69:1580-8) and the ACR's Arthritis & Rheumatism (2010;62:2569-81), the new guidelines were created in three phases over 2 years.

In the first phase, the goal was to “to identify the contributions of clinical and laboratory variables that in practice were the most predictive of the decision to initiate [disease-modifying antirheumatic drug] therapy in … patients with early undifferentiated synovitis,” wrote the authors, led by Dr. Daniel Aletaha of the Medical University of Vienna.

To do this, a working group from both societies looked at data from 3,115 patients and correlated whether or not the patients were ultimately prescribed methotrexate to an “agreed-upon list of standardized clinical and laboratory variables collected at baseline.”

The odds of eventual methotrexate initiation were calculated for each variable. For example, swelling of the metacarpophalangeal joint had an odds ratio of 1.5, as did swelling of the proximal interphalangeal joint and the wrist. Tenderness of the hand (either the MCP, PIP, or wrist) was assigned an odds ratio of 2.0.

Moderate elevation of C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) was assigned an OR of 1.0; high elevation of either assay got an OR of 2.0.

In phase II, a panel of 12 rheumatologists related the above clinical and laboratory factors to the “probability of developing 'persistent inflammatory and/or erosive arthritis that is currently considered to be RA.'”

Finally, phase III aimed to utilize the results of phases I and II “to develop a scoring system that would be applicable to newly presenting patients with undifferentiated inflammatory arthritis, to permit identification of those with a high probability of developing persistent and/or erosive RA.”

This final scale assigns points in the following manner:

▸ One swollen “large joint” (defined as shoulders, elbows, hips, knees, and ankles) gets 0 points; involvement of 2-10 large joints gets 1 point.

▸ Involvement of 1-3 “small” joints (defined as metacarpophalangeal joints, proximal interphalangeal joints, second to fifth metatarsophalangeal joints, thumb interphalangeal joints, and wrists) gets 2 points, regardless of large-joint involvement; involvement of 4-10 small joints gets 3 points.

▸ Involvement of more than 10 joints, including at least 1 small joint, gets 5 points.

▸ Both a negative rheumatoid factor (RF) test and a negative anti—citrullinated protein antibody (ACPA) testgets 0 points, whereas having a “low-positive” RF or ACPA (defined as lower than three times the upper limit of normal) gets 2 points. A “high-positive” of either test gets 3 points.

▸ A normal CRP and normal ESR get 0 points, whereas at least one abnormal test gets 1 point.

▸ Symptom duration of fewer than 6 weeks gets 0 points; duration of 6 weeks or longer gets 1 point.

Scores of 6 or more out of 10 are classified as “definite RA.”

Commenting on the new criteria in an interview, Dr. Eric L. Matteson, who is with the Mayo Clinic in Rochester, Minn., and was not involved with the new guidelines, said, “A major useful feature is that the new guidelines do not require multiple joints to be inflamed before a diagnosis can be [made] of early inflammatory rheumatoid arthritis.”

Indeed, a patient may score 6 points without multiple joint inflammation, according to the new guidelines.

When asked what was missing from the new guidelines, he pointed to a lack of awareness of extra-articular components of RA, which also can occur early in the course of the disease.

Disclosures: Several of the guideline authors disclosed financial and other relationships with multiple pharmaceutical companies; Dr. Matteson stated that he had no financial disclosures relative to his comments.

The promised overhaul of treatment guidelines for rheumatoid arthritis has finally arrived, and with it, a “new paradigm” that focuses on early identification and treatment of the disabling disease.

The guidelines, which were developed by a joint committee from the American College of Rheumatology and the European League Against Rheumatism, are the latest update since the current guidelines were created in 1987.

Published jointly in the EULAR journal Annals of the Rheumatic Diseases (2010;69:1580-8) and the ACR's Arthritis & Rheumatism (2010;62:2569-81), the new guidelines were created in three phases over 2 years.

In the first phase, the goal was to “to identify the contributions of clinical and laboratory variables that in practice were the most predictive of the decision to initiate [disease-modifying antirheumatic drug] therapy in … patients with early undifferentiated synovitis,” wrote the authors, led by Dr. Daniel Aletaha of the Medical University of Vienna.

To do this, a working group from both societies looked at data from 3,115 patients and correlated whether or not the patients were ultimately prescribed methotrexate to an “agreed-upon list of standardized clinical and laboratory variables collected at baseline.”

The odds of eventual methotrexate initiation were calculated for each variable. For example, swelling of the metacarpophalangeal joint had an odds ratio of 1.5, as did swelling of the proximal interphalangeal joint and the wrist. Tenderness of the hand (either the MCP, PIP, or wrist) was assigned an odds ratio of 2.0.

Moderate elevation of C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) was assigned an OR of 1.0; high elevation of either assay got an OR of 2.0.

In phase II, a panel of 12 rheumatologists related the above clinical and laboratory factors to the “probability of developing 'persistent inflammatory and/or erosive arthritis that is currently considered to be RA.'”

Finally, phase III aimed to utilize the results of phases I and II “to develop a scoring system that would be applicable to newly presenting patients with undifferentiated inflammatory arthritis, to permit identification of those with a high probability of developing persistent and/or erosive RA.”

This final scale assigns points in the following manner:

▸ One swollen “large joint” (defined as shoulders, elbows, hips, knees, and ankles) gets 0 points; involvement of 2-10 large joints gets 1 point.

▸ Involvement of 1-3 “small” joints (defined as metacarpophalangeal joints, proximal interphalangeal joints, second to fifth metatarsophalangeal joints, thumb interphalangeal joints, and wrists) gets 2 points, regardless of large-joint involvement; involvement of 4-10 small joints gets 3 points.

▸ Involvement of more than 10 joints, including at least 1 small joint, gets 5 points.

▸ Both a negative rheumatoid factor (RF) test and a negative anti—citrullinated protein antibody (ACPA) testgets 0 points, whereas having a “low-positive” RF or ACPA (defined as lower than three times the upper limit of normal) gets 2 points. A “high-positive” of either test gets 3 points.

▸ A normal CRP and normal ESR get 0 points, whereas at least one abnormal test gets 1 point.

▸ Symptom duration of fewer than 6 weeks gets 0 points; duration of 6 weeks or longer gets 1 point.

Scores of 6 or more out of 10 are classified as “definite RA.”

Commenting on the new criteria in an interview, Dr. Eric L. Matteson, who is with the Mayo Clinic in Rochester, Minn., and was not involved with the new guidelines, said, “A major useful feature is that the new guidelines do not require multiple joints to be inflamed before a diagnosis can be [made] of early inflammatory rheumatoid arthritis.”

Indeed, a patient may score 6 points without multiple joint inflammation, according to the new guidelines.

When asked what was missing from the new guidelines, he pointed to a lack of awareness of extra-articular components of RA, which also can occur early in the course of the disease.

Disclosures: Several of the guideline authors disclosed financial and other relationships with multiple pharmaceutical companies; Dr. Matteson stated that he had no financial disclosures relative to his comments.

Major Finding: The proton pump inhibitor rabeprazole significantly reduced laryngopharyngeal reflux symptoms on the nine-item reflux symptom index at week 6 and week 12 of treatment, compared with placebo.

Data Source: A study appearing in the September issue of the journal Clinical Gastroenterology and Hepatology.

Disclosures: The authors disclosed that the study was partially sponsored by the developer of rabeprazole, Esai Co. Ltd. They added that the researchers had no personal conflicts of interest.

The proton pump inhibitor rabeprazole had a small but significant effect in reducing laryngopharyngeal reflux symptoms after 12 weeks of treatment, Dr. Paul K.Y. Lam and his colleagues reported in an article appearing in September.

The results are in contrast to those of previous, smaller studies that did not find PPIs to be of benefit in laryngopharyngeal reflux (LPR), wrote the authors.

This study also was one of the first to use both the nine-item Reflux Symptom Index questionnaire (J. Voice 2002;16:274–7) and the Reflux Finding Score to measure both laryngopharyngeal reflux (LPR) symptoms and physical findings.

According to Dr. Lam, of the department of surgery at the University of Hong Kong, the researchers looked at patients referred to the Voice & Laryngeal Pathology Laboratory at his institution between November 2004 and June 2007. To be included in the prospective, double-blind, placebo-controlled, randomized study, patients needed to have either hoarseness, globus (a feeling of a lump in the throat), persistent throat discomfort, or frequent throat clearing for at least 1 month in the preceding year, as well as videostroboscopic evidence of LPR with a corresponding “reflux finding score” above 7.

The reflux finding score, or RFS, is “an 8-item clinical severity scale based on findings during fiberoptic laryngoscopy” that ranges from 0, indicating no abnormal findings, to 26 (Laryngoscope 2001;111:1313–7).

Participants also had to have a negative history for any upper respiratory tract infection or allergic laryngitis in the 4 weeks prior to evaluation, and could not be younger than age 18 years, have any other laryngeal pathology, or have a history of gastroesophageal x-ray or surgery.

Patients who had been taking an acid suppressive drug any time during the month prior to enrollment were also excluded.

A total of 82 patients were randomized and completed the study at 6, 12, and 18 weeks follow-up. Overall, 42 patients took rabeprazole 20 mg twice daily for 12 weeks, 30 minutes prior to lunch and dinner (mean age, 46 years; 15 males), while the remaining 40 subjects were given placebo (mean age, 47 years; 8 males).

All patients also were taught to abstain from caffeine, alcohol, smoking, spicy food, and other potential triggers of reflux. They were advised to avoid eating less than 3 hours before bedtime and to drink plenty of water.

“The rabeprazole group had a significantly reduced total RSI score at week 6 (−3.03 plus or minus 1.05, P = .003) and at week 12 (−3.73 plus or minus 1.18, P = .002) compared to the placebo group,” wrote the authors (Clin. Gastroenterol. Hepatol. 2010;8:770–6).

However, the improvement on the RSI did not persist at week 18, which was 6 weeks after the conclusion of the PPI regimen (−1.48 plus or minus 1.26, P = .124).

In contrast, when looking at physical improvement as measured on the RFS, the investigators found no significant difference between groups at weeks 6, 12, or 18, with significance set at the 0.01 level.

Rather, both groups showed improvement, possibly due to the effects of education regarding abstinence from smoking, alcohol, and caffeine, although “this did not translate into significant improvement in RSI in the placebo patient group,” according to the authors.

Indeed, within the rabeprazole group, Dr. Lam did find improvement from baseline at both week 12 (−2.21 plus or minus 0.64. P = .002) and week 18 (−3.21 plus or minus 0.57, P = .0001), especially relating to laryngeal and vocal cord edema.

Dr. Lam and his colleagues conceded that “despite the improvement in both RSI and RFS in the rabeprazole group at week 12, the actual change was not much (only 2.81 and 2.21, respectively).”

Furthermore, the total average scores for both the RSI and the RFS were still high even after a period of 12 weeks of therapy with rabeprazole, “with RSI score well above 10 and RFS more than 7,” which was positive for a laryngopharyngeal reflux condition.

Major Finding: The proton pump inhibitor rabeprazole significantly reduced laryngopharyngeal reflux symptoms on the nine-item reflux symptom index at week 6 and week 12 of treatment, compared with placebo.

Data Source: A study appearing in the September issue of the journal Clinical Gastroenterology and Hepatology.

Disclosures: The authors disclosed that the study was partially sponsored by the developer of rabeprazole, Esai Co. Ltd. They added that the researchers had no personal conflicts of interest.

The proton pump inhibitor rabeprazole had a small but significant effect in reducing laryngopharyngeal reflux symptoms after 12 weeks of treatment, Dr. Paul K.Y. Lam and his colleagues reported in an article appearing in September.

The results are in contrast to those of previous, smaller studies that did not find PPIs to be of benefit in laryngopharyngeal reflux (LPR), wrote the authors.

This study also was one of the first to use both the nine-item Reflux Symptom Index questionnaire (J. Voice 2002;16:274–7) and the Reflux Finding Score to measure both laryngopharyngeal reflux (LPR) symptoms and physical findings.

According to Dr. Lam, of the department of surgery at the University of Hong Kong, the researchers looked at patients referred to the Voice & Laryngeal Pathology Laboratory at his institution between November 2004 and June 2007. To be included in the prospective, double-blind, placebo-controlled, randomized study, patients needed to have either hoarseness, globus (a feeling of a lump in the throat), persistent throat discomfort, or frequent throat clearing for at least 1 month in the preceding year, as well as videostroboscopic evidence of LPR with a corresponding “reflux finding score” above 7.

The reflux finding score, or RFS, is “an 8-item clinical severity scale based on findings during fiberoptic laryngoscopy” that ranges from 0, indicating no abnormal findings, to 26 (Laryngoscope 2001;111:1313–7).

Participants also had to have a negative history for any upper respiratory tract infection or allergic laryngitis in the 4 weeks prior to evaluation, and could not be younger than age 18 years, have any other laryngeal pathology, or have a history of gastroesophageal x-ray or surgery.

Patients who had been taking an acid suppressive drug any time during the month prior to enrollment were also excluded.

A total of 82 patients were randomized and completed the study at 6, 12, and 18 weeks follow-up. Overall, 42 patients took rabeprazole 20 mg twice daily for 12 weeks, 30 minutes prior to lunch and dinner (mean age, 46 years; 15 males), while the remaining 40 subjects were given placebo (mean age, 47 years; 8 males).

All patients also were taught to abstain from caffeine, alcohol, smoking, spicy food, and other potential triggers of reflux. They were advised to avoid eating less than 3 hours before bedtime and to drink plenty of water.

“The rabeprazole group had a significantly reduced total RSI score at week 6 (−3.03 plus or minus 1.05, P = .003) and at week 12 (−3.73 plus or minus 1.18, P = .002) compared to the placebo group,” wrote the authors (Clin. Gastroenterol. Hepatol. 2010;8:770–6).

However, the improvement on the RSI did not persist at week 18, which was 6 weeks after the conclusion of the PPI regimen (−1.48 plus or minus 1.26, P = .124).

In contrast, when looking at physical improvement as measured on the RFS, the investigators found no significant difference between groups at weeks 6, 12, or 18, with significance set at the 0.01 level.

Rather, both groups showed improvement, possibly due to the effects of education regarding abstinence from smoking, alcohol, and caffeine, although “this did not translate into significant improvement in RSI in the placebo patient group,” according to the authors.

Indeed, within the rabeprazole group, Dr. Lam did find improvement from baseline at both week 12 (−2.21 plus or minus 0.64. P = .002) and week 18 (−3.21 plus or minus 0.57, P = .0001), especially relating to laryngeal and vocal cord edema.

Dr. Lam and his colleagues conceded that “despite the improvement in both RSI and RFS in the rabeprazole group at week 12, the actual change was not much (only 2.81 and 2.21, respectively).”

Furthermore, the total average scores for both the RSI and the RFS were still high even after a period of 12 weeks of therapy with rabeprazole, “with RSI score well above 10 and RFS more than 7,” which was positive for a laryngopharyngeal reflux condition.

Major Finding: The proton pump inhibitor rabeprazole significantly reduced laryngopharyngeal reflux symptoms on the nine-item reflux symptom index at week 6 and week 12 of treatment, compared with placebo.

Data Source: A study appearing in the September issue of the journal Clinical Gastroenterology and Hepatology.

Disclosures: The authors disclosed that the study was partially sponsored by the developer of rabeprazole, Esai Co. Ltd. They added that the researchers had no personal conflicts of interest.

The proton pump inhibitor rabeprazole had a small but significant effect in reducing laryngopharyngeal reflux symptoms after 12 weeks of treatment, Dr. Paul K.Y. Lam and his colleagues reported in an article appearing in September.

The results are in contrast to those of previous, smaller studies that did not find PPIs to be of benefit in laryngopharyngeal reflux (LPR), wrote the authors.

This study also was one of the first to use both the nine-item Reflux Symptom Index questionnaire (J. Voice 2002;16:274–7) and the Reflux Finding Score to measure both laryngopharyngeal reflux (LPR) symptoms and physical findings.

According to Dr. Lam, of the department of surgery at the University of Hong Kong, the researchers looked at patients referred to the Voice & Laryngeal Pathology Laboratory at his institution between November 2004 and June 2007. To be included in the prospective, double-blind, placebo-controlled, randomized study, patients needed to have either hoarseness, globus (a feeling of a lump in the throat), persistent throat discomfort, or frequent throat clearing for at least 1 month in the preceding year, as well as videostroboscopic evidence of LPR with a corresponding “reflux finding score” above 7.

The reflux finding score, or RFS, is “an 8-item clinical severity scale based on findings during fiberoptic laryngoscopy” that ranges from 0, indicating no abnormal findings, to 26 (Laryngoscope 2001;111:1313–7).

Participants also had to have a negative history for any upper respiratory tract infection or allergic laryngitis in the 4 weeks prior to evaluation, and could not be younger than age 18 years, have any other laryngeal pathology, or have a history of gastroesophageal x-ray or surgery.

Patients who had been taking an acid suppressive drug any time during the month prior to enrollment were also excluded.

A total of 82 patients were randomized and completed the study at 6, 12, and 18 weeks follow-up. Overall, 42 patients took rabeprazole 20 mg twice daily for 12 weeks, 30 minutes prior to lunch and dinner (mean age, 46 years; 15 males), while the remaining 40 subjects were given placebo (mean age, 47 years; 8 males).

All patients also were taught to abstain from caffeine, alcohol, smoking, spicy food, and other potential triggers of reflux. They were advised to avoid eating less than 3 hours before bedtime and to drink plenty of water.

“The rabeprazole group had a significantly reduced total RSI score at week 6 (−3.03 plus or minus 1.05, P = .003) and at week 12 (−3.73 plus or minus 1.18, P = .002) compared to the placebo group,” wrote the authors (Clin. Gastroenterol. Hepatol. 2010;8:770–6).

However, the improvement on the RSI did not persist at week 18, which was 6 weeks after the conclusion of the PPI regimen (−1.48 plus or minus 1.26, P = .124).

In contrast, when looking at physical improvement as measured on the RFS, the investigators found no significant difference between groups at weeks 6, 12, or 18, with significance set at the 0.01 level.

Rather, both groups showed improvement, possibly due to the effects of education regarding abstinence from smoking, alcohol, and caffeine, although “this did not translate into significant improvement in RSI in the placebo patient group,” according to the authors.

Indeed, within the rabeprazole group, Dr. Lam did find improvement from baseline at both week 12 (−2.21 plus or minus 0.64. P = .002) and week 18 (−3.21 plus or minus 0.57, P = .0001), especially relating to laryngeal and vocal cord edema.

Dr. Lam and his colleagues conceded that “despite the improvement in both RSI and RFS in the rabeprazole group at week 12, the actual change was not much (only 2.81 and 2.21, respectively).”

Furthermore, the total average scores for both the RSI and the RFS were still high even after a period of 12 weeks of therapy with rabeprazole, “with RSI score well above 10 and RFS more than 7,” which was positive for a laryngopharyngeal reflux condition.

Investigational new drugs, including biologic drugs, will face new safety reporting requirements designed to increase timeliness as well as decrease unnecessary reporting of events not likely to be causal.

The changes bring the Food and Drug Administration’s reporting policies in line with international agencies, including the World Health Organization, in an effort to “help ensure harmonized reporting of globally conducted clinical trials.”

The requirements are the result of a final rule issued by the FDA and published in the Federal Register on Sept. 29.

The rule represents the culmination of work on a proposed rule, issued in 2003, and will go into effect 180 days from its publication, according to Karen Riley, an FDA spokeswoman.

Investigational new drug (IND) applications are submitted to the FDA prior to the onset of clinical trials. IND must be filed for any approval request, regardless of whether it is an application for a wholly novel compound or an application for a new indication of existing drugs, according to the agency.

Safety reports on these INDs must be submitted to the FDA and assessed by institutional review boards before clinical trials can begin.

Under the former rule, “sponsors investigating a drug ... were required to notify FDA and all participating investigators, in a written IND safety report, of any adverse experience associated with the use of the drug that was both serious and unexpected, and any finding from tests in laboratory animals that suggested a significant risk for human subjects.”

This requirement often resulted in reporting of events not likely to be associated with the drug, bogging down the agency and leading to slower recognition of truly causal effects, according to the draft guidance.

According to the new rule, rather than submitting details about all adverse events, applicants may submit only “suspected adverse reactions,” defined as events for which there is “evidence to suggest a causal relationship between the drug and the adverse event,” according to a FDA draft guidance for investigators.

For example, any “single occurrence of an event that is uncommon and known to be strongly associated with drug exposure (e.g., angioedema, hepatic injury, Stevens-Johnson syndrome)” would meet this definition, as well as “one or more occurrences of an event that is not commonly associated with drug exposure, but is otherwise uncommon in the population exposed to the drug (e.g., tendon rupture),” according to the guidance.

Other reportable findings include data concerning bioequivalence of generic biologic drugs, compared with their name-brand counterparts – for example, differing rates of absorption into the bloodstream.

Another change concerns timeliness of reporting. The new rules clarify that “expedited” reporting must occur within 15 days of the drug sponsor determining that given data meet the qualifications for reporting.

“For a serious and unexpected suspected adverse reaction from a clinical trial, this would be the day the sponsor receives information from the clinical investigator,” states the rule.

Moreover, it clarifies that “If any information necessary to evaluate and report the suspected adverse reaction is missing or unknown, the sponsor should actively seek such information.”

In a press release, Dr. Rachel E. Behrman, the associate director for medical policy at the FDA’s Center for Drug Evaluation and Research (CDER), said, “This final rule will expedite FDA’s review of critical safety information and help the agency monitor the safety of investigational drugs and biologics.”

“These changes will better protect people who are enrolled in clinical trials.”

Investigational new drugs, including biologic drugs, will face new safety reporting requirements designed to increase timeliness as well as decrease unnecessary reporting of events not likely to be causal.

The changes bring the Food and Drug Administration’s reporting policies in line with international agencies, including the World Health Organization, in an effort to “help ensure harmonized reporting of globally conducted clinical trials.”

The requirements are the result of a final rule issued by the FDA and published in the Federal Register on Sept. 29.

The rule represents the culmination of work on a proposed rule, issued in 2003, and will go into effect 180 days from its publication, according to Karen Riley, an FDA spokeswoman.

Investigational new drug (IND) applications are submitted to the FDA prior to the onset of clinical trials. IND must be filed for any approval request, regardless of whether it is an application for a wholly novel compound or an application for a new indication of existing drugs, according to the agency.

Safety reports on these INDs must be submitted to the FDA and assessed by institutional review boards before clinical trials can begin.

Under the former rule, “sponsors investigating a drug ... were required to notify FDA and all participating investigators, in a written IND safety report, of any adverse experience associated with the use of the drug that was both serious and unexpected, and any finding from tests in laboratory animals that suggested a significant risk for human subjects.”

This requirement often resulted in reporting of events not likely to be associated with the drug, bogging down the agency and leading to slower recognition of truly causal effects, according to the draft guidance.

According to the new rule, rather than submitting details about all adverse events, applicants may submit only “suspected adverse reactions,” defined as events for which there is “evidence to suggest a causal relationship between the drug and the adverse event,” according to a FDA draft guidance for investigators.

For example, any “single occurrence of an event that is uncommon and known to be strongly associated with drug exposure (e.g., angioedema, hepatic injury, Stevens-Johnson syndrome)” would meet this definition, as well as “one or more occurrences of an event that is not commonly associated with drug exposure, but is otherwise uncommon in the population exposed to the drug (e.g., tendon rupture),” according to the guidance.

Other reportable findings include data concerning bioequivalence of generic biologic drugs, compared with their name-brand counterparts – for example, differing rates of absorption into the bloodstream.

Another change concerns timeliness of reporting. The new rules clarify that “expedited” reporting must occur within 15 days of the drug sponsor determining that given data meet the qualifications for reporting.

“For a serious and unexpected suspected adverse reaction from a clinical trial, this would be the day the sponsor receives information from the clinical investigator,” states the rule.

Moreover, it clarifies that “If any information necessary to evaluate and report the suspected adverse reaction is missing or unknown, the sponsor should actively seek such information.”

In a press release, Dr. Rachel E. Behrman, the associate director for medical policy at the FDA’s Center for Drug Evaluation and Research (CDER), said, “This final rule will expedite FDA’s review of critical safety information and help the agency monitor the safety of investigational drugs and biologics.”

“These changes will better protect people who are enrolled in clinical trials.”

Investigational new drugs, including biologic drugs, will face new safety reporting requirements designed to increase timeliness as well as decrease unnecessary reporting of events not likely to be causal.

The changes bring the Food and Drug Administration’s reporting policies in line with international agencies, including the World Health Organization, in an effort to “help ensure harmonized reporting of globally conducted clinical trials.”

The requirements are the result of a final rule issued by the FDA and published in the Federal Register on Sept. 29.

The rule represents the culmination of work on a proposed rule, issued in 2003, and will go into effect 180 days from its publication, according to Karen Riley, an FDA spokeswoman.

Investigational new drug (IND) applications are submitted to the FDA prior to the onset of clinical trials. IND must be filed for any approval request, regardless of whether it is an application for a wholly novel compound or an application for a new indication of existing drugs, according to the agency.

Safety reports on these INDs must be submitted to the FDA and assessed by institutional review boards before clinical trials can begin.

Under the former rule, “sponsors investigating a drug ... were required to notify FDA and all participating investigators, in a written IND safety report, of any adverse experience associated with the use of the drug that was both serious and unexpected, and any finding from tests in laboratory animals that suggested a significant risk for human subjects.”

This requirement often resulted in reporting of events not likely to be associated with the drug, bogging down the agency and leading to slower recognition of truly causal effects, according to the draft guidance.

According to the new rule, rather than submitting details about all adverse events, applicants may submit only “suspected adverse reactions,” defined as events for which there is “evidence to suggest a causal relationship between the drug and the adverse event,” according to a FDA draft guidance for investigators.

For example, any “single occurrence of an event that is uncommon and known to be strongly associated with drug exposure (e.g., angioedema, hepatic injury, Stevens-Johnson syndrome)” would meet this definition, as well as “one or more occurrences of an event that is not commonly associated with drug exposure, but is otherwise uncommon in the population exposed to the drug (e.g., tendon rupture),” according to the guidance.

Other reportable findings include data concerning bioequivalence of generic biologic drugs, compared with their name-brand counterparts – for example, differing rates of absorption into the bloodstream.

Another change concerns timeliness of reporting. The new rules clarify that “expedited” reporting must occur within 15 days of the drug sponsor determining that given data meet the qualifications for reporting.

“For a serious and unexpected suspected adverse reaction from a clinical trial, this would be the day the sponsor receives information from the clinical investigator,” states the rule.

Moreover, it clarifies that “If any information necessary to evaluate and report the suspected adverse reaction is missing or unknown, the sponsor should actively seek such information.”

In a press release, Dr. Rachel E. Behrman, the associate director for medical policy at the FDA’s Center for Drug Evaluation and Research (CDER), said, “This final rule will expedite FDA’s review of critical safety information and help the agency monitor the safety of investigational drugs and biologics.”

“These changes will better protect people who are enrolled in clinical trials.”