Statement of Laurén Doamekpor on the Importance of Including Women, Minorities, and the Elderly in Studies of the Safety and Effectiveness of New Drugs and Devices (FDASIA Section 907 Hearing)

April 1st, 2014

My name is Laurén Doamekpor, a senior fellow speaking on behalf of the National Research Center for Women & Families and our Cancer Prevention and Treatment Fund. Thank you for the chance to speak today.

Our research center evaluates data and provides objective health information to patients, providers and policy makers. We strongly support the inclusion of women, racial and ethnic minorities, and the elderly in clinical trials for drugs and devices.

The Section 907 report reveals that there is more work to be done to achieve greater diversity in clinical trials.  We believe that the key question today should be: what can the FDA do to ensure:

  1. greater diversity in clinical trials submitted to FDA,
  2. subgroup analyses submitted to the FDA
  3. Information from subgroup analyses are used as a basis of approval and labeling decisions, and made widely available in a user-friendly format to providers, patients, and other stakeholders.

The responsibility of collecting sufficiently representative demographic subgroup data sits solely on the shoulders of device and drug companies. The companies know how to persuade – they do it everyday in commercials.  Similarly, if they identify persuasive incentives for patients to participate in studies, and minimize disincentives, patients will participate and be available for follow-up.

The FDA’s crucial role is to hold companies accountable. The FDA guidance regarding diversity and subgroup analyses is regularly ignored by companies, and unfortunately the FDA then approves their drugs and devices anyway.  If the FDA’s actions clearly showed that sponsor applications will be rejected — or perhaps approved for White men under 60 only — if companies do not include the relevant demographic data and conduct the necessary subgroup analyses – we are confident that companies will find a way to comply.

To successfully persuade companies to conduct subgroup analyses for the major subpopulations that will use their products, the FDA must consistently demonstrate that they believe those data are essential for proving safety and efficacy.

This is essential because research tells us that naturally occurring genetic variations may influence the way certain drugs are metabolized and work in women compared to men, older patients compared to younger, and certain racial and ethnic groups. Currently, the main challenges in conducting subgroup analyses is that the sample sizes are too small, and get miniscule when age and race and sex are all considered.  We understand that not every ethnic group or age group can be separately analyzed. However, we disagree with the assumption that it is not feasible to power studies to detect subgroup differences. It can be done, and should be done for major subgroups. If the FDA required this practice and held companies accountable, companies will find a way to achieve this.

Our Center participates in many FDA Advisory Committee meetings, and rarely is the lack of diversity in clinical trial data mentioned for more than one second by anyone other than us.  When the FDA’s clinical summaries provided to Advisory Committee members and the public, do not criticize the lack of diversity or lack of subgroup analyses, the FDA sends the message that safety and efficacy for all subgroups are not important.

In the last week, for example, we spoke at one FDA Advisory Committee meetings for a drug for heart failure and 2 for drugs forMRSA. Heart failure is the #1 killer of men and women of all races in the U.S. and MRSA disproportionately harms minority patients.  However, African American patients comprised less than 5% of the cardiac drug trial and less than 6% for one of the MRSA drugs.  NONE of the companies did subgroup analyses for all the primary and secondary endpoints. The lack of data was similar for Hispanic patients.

And, although many of these drugs are used primarily on elderly patients, few patients over 65 were included.  For one of the MRSA drugs, only one analysis of efficacy for patients over 65 was conducted and it clearly showed that the new drug was less effective than the comparison drug.  But, the FDA didn’t even mention that in their summary and the Advisory Committee recommended approval of the drug for all adults over 18 anyway.

On the rare occasion when our concerns about diversity inspires Advisory Committee members to speak up, the result is usually a recommendation to achieve better diversity in the post-market study.  Unfortunately, companies rarely do better in post-market studies, because the incentives to please FDA weaken greatly once their drug or device has already been approved for the general population.

In addition to showing companies that they must achieve diversity and conduct subgroup analyses, there is another action that the FDA should take.  FDA should gather information comparing recruitment and retention strategies from companies that are achieving greater and lesser diversity in their trials to determine which strategies are successful, and share that information with companies that need to improve.

Ultimately, patients and providers need to know whether subgroup data were collected, what the findings are, and how scientifically solid those results are. This information is essential for providers and patients to make well-informed medical decisions. The FDA should require that subgroup data be provided on labels and promotional efforts, using wording that is easy to understand by patients and providers.

Again, thank you for the opportunity to speak at this meeting. We hope that you will incorporate our comments and recommendations into the Action Plan.