Progress to date is not sufficient
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Although women have been well represented recently in certain types of cardiovascular drug trials, they remain underrepresented in studies of heart failure, coronary artery disease, and acute coronary syndrome, a recent study authored by Food and Drug Administration researchers has revealed.

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Representation was favorable in trials of drugs treating hypertension, atrial fibrillation, and pulmonary arterial hypertension, authors of the study wrote in the Journal of the American College of Cardiology.

However, representation of women fell below an acceptable participation-to-prevalence ratio in those other trial types that were evaluated, according to researchers, including lead author Pamela E. Scott, PhD, of the FDA’s Office of Women’s Health.

“As we move into the era of precision medicine – that is, assessing the impact of a wide range of patient and disease characteristics on drug effects – it is imperative that clinical trial participants represent the full spectrum of patients for whom the drug will be prescribed,” Dr. Scott and her colleagues said in the report.

To quantify the participation of women in clinical trials, Dr. Scott and coinvestigators reviewed publicly available FDA reviews from 2005 to 2015 supporting the approval of 36 drugs.

They used a metric called the participation-to-prevalence ratio (PPR) to compare representation of women in a study relative to the representation of women in the disease population being studied. The range of PPR of 0.8-1.2 represented similar representation of women in the study and disease population.

Participation of women in drug trials varied widely – from a low of 22% to a high of 81% – with a mean of 46%, they found.

 

 


The PPR was within the desirable range for hypertension, at 0.9, and atrial fibrillation trials, at 0.8-1.1, while participation for pulmonary arterial hypertension trials was above the desirable range, at 1.4, according to the report.

However, a PPR of less than 0.8 was found for coronary artery disease trials, at 0.6; acute coronary syndrome/myocardial infarction trials, also at 0.6; and heart failure trials, at 0.5 to 0.6.

Few clinically meaningful gender differences were found in efficacy or safety, they added, noting that such differences were discussed in the prescribing information for four different drugs.

To ensure that representative patient populations are enrolled in drug trials, clinical researchers, patient advocacy groups, federal agencies, and the industry as a whole should work together, Dr. Scott and her colleagues said.

“These steps will move us closer toward the goal of providing the best information possible about the use of drugs for every patient,” they wrote.

Dr. Scott and coauthors reported that they had no relationships relevant to their study.

SOURCE: Scott PE et al. J Am Coll Cardiol. 2018 May 18;71:1960-9.

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Any optimism for results of this study by FDA authors are dampened significantly by the continued under-representation of women in heart failure and ischemic heart disease.

Even though progress has been made toward a higher participation of women in pivotal clinical trials, it still is not time to rest on our laurels.

One key contributor to the persistently low representation of women is the eligibility criteria of clinical trials. Those criteria often describe a male pattern of disease, particularly in drug trials for ischemic heart disease and heart failure.

As an example, heart failure trials have included eligibility criteria that consistently exclude women, such as a glomerular filtration rate less than 30 mL/min per 1.73 m2, and an ejection fraction of 40% or less.

The inclusion criteria in randomized, controlled trials impose homogeneous clinical characteristics for men and women and may be responsible for the lack of sex differences in efficacy outcomes.

Thus, the current analysis exposes not only successes but also failings of clinical trial design for FDA approval. We are still far from providing equitable cardiovascular health care for women.

Louise Pilote, MD, MPH, PhD, and Valeria Raparelli, MD, PhD, are both affiliated with McGill University Health Centre, Montreal. These comments are derived from their editorial in the Journal of the American College of Cardiology . Both reported that they had no relationships relevant to the contents of their editorial.

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Any optimism for results of this study by FDA authors are dampened significantly by the continued under-representation of women in heart failure and ischemic heart disease.

Even though progress has been made toward a higher participation of women in pivotal clinical trials, it still is not time to rest on our laurels.

One key contributor to the persistently low representation of women is the eligibility criteria of clinical trials. Those criteria often describe a male pattern of disease, particularly in drug trials for ischemic heart disease and heart failure.

As an example, heart failure trials have included eligibility criteria that consistently exclude women, such as a glomerular filtration rate less than 30 mL/min per 1.73 m2, and an ejection fraction of 40% or less.

The inclusion criteria in randomized, controlled trials impose homogeneous clinical characteristics for men and women and may be responsible for the lack of sex differences in efficacy outcomes.

Thus, the current analysis exposes not only successes but also failings of clinical trial design for FDA approval. We are still far from providing equitable cardiovascular health care for women.

Louise Pilote, MD, MPH, PhD, and Valeria Raparelli, MD, PhD, are both affiliated with McGill University Health Centre, Montreal. These comments are derived from their editorial in the Journal of the American College of Cardiology . Both reported that they had no relationships relevant to the contents of their editorial.

Body

 

Any optimism for results of this study by FDA authors are dampened significantly by the continued under-representation of women in heart failure and ischemic heart disease.

Even though progress has been made toward a higher participation of women in pivotal clinical trials, it still is not time to rest on our laurels.

One key contributor to the persistently low representation of women is the eligibility criteria of clinical trials. Those criteria often describe a male pattern of disease, particularly in drug trials for ischemic heart disease and heart failure.

As an example, heart failure trials have included eligibility criteria that consistently exclude women, such as a glomerular filtration rate less than 30 mL/min per 1.73 m2, and an ejection fraction of 40% or less.

The inclusion criteria in randomized, controlled trials impose homogeneous clinical characteristics for men and women and may be responsible for the lack of sex differences in efficacy outcomes.

Thus, the current analysis exposes not only successes but also failings of clinical trial design for FDA approval. We are still far from providing equitable cardiovascular health care for women.

Louise Pilote, MD, MPH, PhD, and Valeria Raparelli, MD, PhD, are both affiliated with McGill University Health Centre, Montreal. These comments are derived from their editorial in the Journal of the American College of Cardiology . Both reported that they had no relationships relevant to the contents of their editorial.

Title
Progress to date is not sufficient
Progress to date is not sufficient

 

Although women have been well represented recently in certain types of cardiovascular drug trials, they remain underrepresented in studies of heart failure, coronary artery disease, and acute coronary syndrome, a recent study authored by Food and Drug Administration researchers has revealed.

Tashatuvango/Thinkstock
Representation was favorable in trials of drugs treating hypertension, atrial fibrillation, and pulmonary arterial hypertension, authors of the study wrote in the Journal of the American College of Cardiology.

However, representation of women fell below an acceptable participation-to-prevalence ratio in those other trial types that were evaluated, according to researchers, including lead author Pamela E. Scott, PhD, of the FDA’s Office of Women’s Health.

“As we move into the era of precision medicine – that is, assessing the impact of a wide range of patient and disease characteristics on drug effects – it is imperative that clinical trial participants represent the full spectrum of patients for whom the drug will be prescribed,” Dr. Scott and her colleagues said in the report.

To quantify the participation of women in clinical trials, Dr. Scott and coinvestigators reviewed publicly available FDA reviews from 2005 to 2015 supporting the approval of 36 drugs.

They used a metric called the participation-to-prevalence ratio (PPR) to compare representation of women in a study relative to the representation of women in the disease population being studied. The range of PPR of 0.8-1.2 represented similar representation of women in the study and disease population.

Participation of women in drug trials varied widely – from a low of 22% to a high of 81% – with a mean of 46%, they found.

 

 


The PPR was within the desirable range for hypertension, at 0.9, and atrial fibrillation trials, at 0.8-1.1, while participation for pulmonary arterial hypertension trials was above the desirable range, at 1.4, according to the report.

However, a PPR of less than 0.8 was found for coronary artery disease trials, at 0.6; acute coronary syndrome/myocardial infarction trials, also at 0.6; and heart failure trials, at 0.5 to 0.6.

Few clinically meaningful gender differences were found in efficacy or safety, they added, noting that such differences were discussed in the prescribing information for four different drugs.

To ensure that representative patient populations are enrolled in drug trials, clinical researchers, patient advocacy groups, federal agencies, and the industry as a whole should work together, Dr. Scott and her colleagues said.

“These steps will move us closer toward the goal of providing the best information possible about the use of drugs for every patient,” they wrote.

Dr. Scott and coauthors reported that they had no relationships relevant to their study.

SOURCE: Scott PE et al. J Am Coll Cardiol. 2018 May 18;71:1960-9.

 

Although women have been well represented recently in certain types of cardiovascular drug trials, they remain underrepresented in studies of heart failure, coronary artery disease, and acute coronary syndrome, a recent study authored by Food and Drug Administration researchers has revealed.

Tashatuvango/Thinkstock
Representation was favorable in trials of drugs treating hypertension, atrial fibrillation, and pulmonary arterial hypertension, authors of the study wrote in the Journal of the American College of Cardiology.

However, representation of women fell below an acceptable participation-to-prevalence ratio in those other trial types that were evaluated, according to researchers, including lead author Pamela E. Scott, PhD, of the FDA’s Office of Women’s Health.

“As we move into the era of precision medicine – that is, assessing the impact of a wide range of patient and disease characteristics on drug effects – it is imperative that clinical trial participants represent the full spectrum of patients for whom the drug will be prescribed,” Dr. Scott and her colleagues said in the report.

To quantify the participation of women in clinical trials, Dr. Scott and coinvestigators reviewed publicly available FDA reviews from 2005 to 2015 supporting the approval of 36 drugs.

They used a metric called the participation-to-prevalence ratio (PPR) to compare representation of women in a study relative to the representation of women in the disease population being studied. The range of PPR of 0.8-1.2 represented similar representation of women in the study and disease population.

Participation of women in drug trials varied widely – from a low of 22% to a high of 81% – with a mean of 46%, they found.

 

 


The PPR was within the desirable range for hypertension, at 0.9, and atrial fibrillation trials, at 0.8-1.1, while participation for pulmonary arterial hypertension trials was above the desirable range, at 1.4, according to the report.

However, a PPR of less than 0.8 was found for coronary artery disease trials, at 0.6; acute coronary syndrome/myocardial infarction trials, also at 0.6; and heart failure trials, at 0.5 to 0.6.

Few clinically meaningful gender differences were found in efficacy or safety, they added, noting that such differences were discussed in the prescribing information for four different drugs.

To ensure that representative patient populations are enrolled in drug trials, clinical researchers, patient advocacy groups, federal agencies, and the industry as a whole should work together, Dr. Scott and her colleagues said.

“These steps will move us closer toward the goal of providing the best information possible about the use of drugs for every patient,” they wrote.

Dr. Scott and coauthors reported that they had no relationships relevant to their study.

SOURCE: Scott PE et al. J Am Coll Cardiol. 2018 May 18;71:1960-9.

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FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

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Key clinical point: Although women are well represented in clinical trials for hypertension, atrial fibrillation, and pulmonary arterial hypertension, they are not well represented in other trial types.

Major finding: The participation-to-prevalence ratio fell below 0.8 (that is, the bottom end of the range reflecting a similar representation of women) for coronary artery disease, acute coronary syndrome, and heart failure.

Study details: An assessment of publicly available FDA data from 2005 to 2015 on enrollment of women in clinical trials representing 36 drug approvals.

Disclosures: Authors reported that they had no relationships relevant to their report.

Source: Scott PE et al. J Am Coll Cardiol. 2018 May 18;71:1960-9.

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