The Great Debate: What is Enough ... Women in Clinical Trials? May 16, 2018

Speech | In Person

• Speech by: Scott Gottlieb, M.D.

Remarks by Scott Gottlieb, M.D.
Commissioner of Food and Drugs
The Great Debate: What is Enough ... Women in Clinical Trials?
White Oak, MD

(Remarks as prepared for delivery)

Good afternoon. I’m delighted to join with you today to commemorate National Women’s Health Week, and to participate in this discussion on two critical issues.

First, on the importance of making sure women are appropriately represented in clinical trials. And second, that more research is focused on the development of innovations aimed at improving the lives of women; and addressing the medical conditions that can disproportionately affect their lives.

I want to start by recognizing Marsha Henderson, the Director of FDA’s Office of Women’s Health. She and her office have done extraordinary work to organize today’s event, and to advance the public health goals that we’re going to be addressing here today.

We recognize that there are meaningful differences between men and women when it comes to disease, and the role that sex plays in the onset of illness and the maintenance of health.

This wasn’t always the case. And years of neglect of these issues, and at times ignorance of them, have left us with disparities when it comes to the delivery of healthcare.

This is reflected in many places across our system.

One is the way that we enroll clinical trials. And make sure women are represented in appropriate numbers in studies.

Another is the manner in which we focus our efforts to develop new medical innovations, and how much of our emphasis is focused on diseases that affect women disproportionately. Or on medical conditions that are experienced only by women.

Sometimes the steps we take to address one of these challenges will impact the other. Investments in clinical trial capacity for screening and enrolling women can help make sure women are appropriately represented in clinical trials. These same capacities can also make it more efficient to develop new treatments for conditions that are unique to women.

Sometimes we need to address these two challenges separately, where the obstacles to each goal are unique.

I want to address both of these issues in turn.

Our Office of Women’s Health helps fund important regulatory research on this topic. Since its creation, it has provided more than $40 million for 371 projects to inform the FDA’s work about issues specific to women’s health and sex differences.

This scientific work is diverse. Some involves identifying and monitoring the progress of crosscutting and multidisciplinary women’s health initiatives, including efforts to develop policies that will help bring more women into clinical trials.

Take cardiovascular disease, which has surpassed breast cancer as the leading cause of death for women.

The Office of Women’s Health has been working across several FDA Centers to support a number of studies in this area, on topics ranging from sex differences in cardiac interventions to the cardiotoxicity of breast cancer drugs.

One of the earliest funded projects by FDA examined the connection between certain drugs and Torsade de Pointes – a rare but dangerous heart arrhythmia that can lead to sudden death, which women are more likely to have than men.

FDA has been leading an effort to evaluate better ways to screen drugs for their potential to cause this arrhythmia.

We understand the importance of collecting sufficient data to determine whether women might respond differently to a drug, device, or biologic than men. Or experience more risks.

That’s why FDA has guidance with specific recommendations for drug and device sponsors to include both sexes in clinical trials. It’s why our regulations require the presentation and inclusion of analyses of demographic data in marketing applications. And it’s why we’ve implemented guidelines on the completion of gender analysis.

Since 1998, the FDA has required reporting of clinical trial data for drug approvals by gender, race and ethnicity, and age.

We require this analysis to be done for all new drug applications. When clinically meaningful differences between men and women are seen, these are considered as a part of how we balance risk and benefit and how we label medicines.

The FDA annually reviews the extent to which women are enrolled in clinical trials supporting new molecular entity submissions. This analysis is led by our Office of Women’s Health. In 2015, 52 percent of the clinical trial participants were women in late phase clinical trials, up from 39 percent in 2000.

The launch of the Drug Trials Snapshots has also provided consumers with important, up-to-date information about who has participated in clinical trials, how the study was designed, the results of the efficacy and safety studies, and the differences in side effects and in benefits among sex, race and age groups.

This information is reported for every new drug application or therapeutic biologic application that FDA approves.

Since the site was launched, it has received more than 500,000 page visits. Of course, in order to have such data to produce, women need to participate in clinical trials. We’re working on new steps, and new policy measures, to encourage such participation.

Today’s discussion is part of that effort. These are just some of the ways that we’re taking steps to make sure women are appropriately included and represented in research trials.

One of the studies you’ll hear about today is the FDA-led Decadal Review. It’s the type of work we need more of.

This study analyzed clinical trial safety and efficacy by sex across 34 drugs and five cardiovascular disease indications from 2005 to 2015. This important research, published last week in the Journal of the American College of Cardiology, also performed an exploratory analysis of the inclusion and exclusion criteria for five of the trials. The aim was to assess whether these criteria influenced the enrollments of participants.

The study found minimal gender differences in drug efficacy and safety profiles. It also found that women were well represented in trials of drugs for hypertension and atrial fibrillation, and overrepresented for pulmonary arterial hypertension (PAH). At the same time, based on disease prevalence, women were underrepresented in trials studying therapies for heart failure, coronary artery disease (CAD) and acute coronary syndrome (ACS).

In short, we still have more work to do.

These findings support the need for the FDA to issue a call to action to clinical investigators. In this case, the bottom line was that more work is needed to identify factors leading to under-participation of women in cardiovascular clinical trials in certain areas, notably heart failure, coronary artery disease, and acute coronary syndrome. More specifically, we need to identify and correct the factors that lead to the screening of fewer women.

Advanced age at disease onset may contribute to under-enrollment of women. And so prevalence-adjusted representation of women in cardiovascular clinical trials across relevant age categories is also an area for future inquiry.

To advance all of our shared goals, the FDA and its Office of Women’s Health are leading a number of other initiatives. The overarching aim is to encourage the inclusion of more women in clinical trials. Among the steps we’re taking are our Diverse Women in Clinical Trials Initiative, which involves a consumer awareness campaign, as well as resources and workshops for health professionals and researchers. We’re also organizing training webinars with national organizations on recruitment and retention of women in clinical trials – nationally and globally; and we’re funding and conducting research initiatives that facilitate the FDA’s regulatory decision making to advance the understanding of sex differences.

We’re also disseminating free FDA health educational materials through outreach activities and collaborative partnerships.

These are just some of the steps we’re taking to make sure women are appropriately represented in clinical trials.

At the same time, we’re also taking new steps to make sure that the process for developing treatments targeting conditions that are unique to women is efficient and up-to-date. We don’t want regulatory uncertainty, or the lack of regulatory capacity in these areas, to be a barrier to innovation and investment.

One of the impediments to drug development for conditions affecting younger women is a concern about exposing new and expectant moms to drugs, for fear of the unknown risk on a developing child, or on a new mother who is breast feeding.

This is, by no means, the only reason drug developers sometimes shun investing in the development of medical products that target conditions that are more prevalent in women. But it’s one of the often-cited reasons. Especially when it comes to conditions that affect younger women. Yet we know a lot of diseases are far more prevalent in younger women. This includes a number of autoimmune conditions.

So we’ve taken steps to address these uncertainties. For example, the FDA has invested in predictive modeling to try to anticipate how pregnant women might respond to a drug without exposing a woman to the drug during a clinical trial.

Through the Medication Exposure in Pregnancy Risk Evaluation Program -- which is a multi-site research collaboration between FDA, academia and health insurers – the FDA is doing research to learn more about medication effects. We’re doing this by linking healthcare records for moms and babies.

Under this effort, we’ve pursued a number of important projects. This includes a key, ongoing study of sulfonamide use during pregnancy and the risk of congenital anomalies.

Under this program, we’re also currently conducting a three-year study to evaluate a potential association between neural tube defects and maternal exposure to prescription opioids.

And we’re also taking new steps to facilitate the development of safe, effective medical devices that address conditions unique to women. As part of our new Device Safety Action Plan, the FDA will establish a registry network focused on health technologies to provide more data in clinical areas unique to women, such as uterine fibroids and pelvic floor disorders.

To inform better clinical trial design and make the process for the development of medical devices for women more efficient, the FDA is developing ways to capture real world evidence of device performance by building the Women’s Health Technologies Strategically Coordinated Registry Network.

To improve this data collection and analysis, common data elements for sex and gender are being developed for incorporation in some prominent medical device registries.

Today’s discussion is an important effort for dedicating our attention to all of these critical issues.  I know that the FDA and the Office of Women’s Health will remain dedicated to addressing these challenges.  They are critically important to the FDA, and as the father of three young girls, they are critically important to me personally. We appreciate you’re joining us today. And we look forward to your engagement.

Thank you.