Can FDA and Industry Give Patients and Providers the Evidence They Need to Make Informed Decisions?

| 03 March 2014 |  By 

The US Food and Drug Administration (FDA) soon plans to hold a hearing on the extent to which historically under-represented subgroups of patients are included in clinical trials, and whether their lack of inclusion may have implications for the efficacy and safety of products given to those patients.


When the Food and Drug Administration Safety and Innovation Act (FDASIA) was signed into law in 2012, among its many provisions was Section 907. The section required FDA to publish a report "addressing the extent to which clinical trial participation and the inclusion of safety and effectiveness data by demographic subgroups-including sex, age, race and ethnicity-is included in product applications submitted to FDA."

The thinking of regulators and legislators was that if a trial does not adequately represent patients who will ultimately use a medical product, that product may be more or less effective or safe in some of those populations.

For example, if a statin drug would be used equally by both men and women, a clinical trial that included mostly men might hide some adverse events experienced exclusively by women.

Similarly, if a trial does not break out patient data by subgroup, it might not discover that a drug is less effective in patients of a particular race. Some ethnic subgroups, such as Asians, respond differently (i.e. more strongly) to certain types of drugs like lithium, antidepressants and antipsychotics. Patients of Chinese or African ethnicities, meanwhile, are more sensitive to beta-blockers and other heart rate and blood pressure medications.

Sex-, age- and genetic-based variations can be difficult to detect, particularly in smaller trials, resulting in a product that may be found by regulators to have a positive benefit-risk assessment, but in reality has unique risks that some patients must take into account.

Section 907 Report

FDA's Section 907 report was released for public review in August 2013. In it, regulators said that these variations and their underlying causes are being increasingly understood and focused on during the product development process, particularly as industry begins to focus more on the concept of "personalized medicine"-the notion that each treatment can be narrowly tailored to a person's genetic profile.

But while absolutely personalized medicine remains a far-off dream, FDA notes that "it remains important that clinical trials include diverse populations, whenever possible and appropriate."

In general, most companies were found to submit data indicating differences (if any) in sex and age, but factors of ethnicity and race were less frequently taken into account.

Regulators also found that "the extent to which demographic subset data were analyzed varied across medical product types," with devices falling far short of their drug and biological counterparts, which are required to collect much of the data by law.

Regulators also cautioned about the usefulness of certain data they received. While some companies did submit data on age or sex differences, the size of the trial can limit the power and usefulness of that data, especially when subgroups are underrepresented to begin with.

Public Discussion

Now regulators are set to discuss and obtain public feedback on the Section 907 report at an upcoming hearing, FDA announced in a 3 March 2014 Federal Register report.

"As is required by section 907 of FDASIA, in response to the findings in the report, FDA is developing an action plan to address improving the completeness and quality of analyses of data on demographic subgroups in labeling, the inclusion of such data in labeling, and improving the public availability of information on demographic subgroups to patients, health care providers, and researchers," FDA wrote.

To assist the development of that plan, FDA is asking for "input on the issues and challenges associated with the collection, analysis and availability of demographic subgroup data in applications for approval of FDA-regulated human medical products."

Nine questions have been released for public consideration:

A. Demographic Subgroup Representation in Clinical Trials

1. What approaches might be used to encourage enrollment of representative proportions of subgroup participants in clinical trials consistent with disease prevalence in the underlying population being studied?

2. What sources could be used to define disease prevalence among subgroups? Are there priority areas for study in terms of disease/condition, or in terms of demographic subgroup?

3. What are best practices and considerations for developing inclusion and exclusion criteria for clinical trials generally and for the early stages of research?

4. What approaches should FDA use to standardize the capture of race and ethnicity information, including for studies conducted outside the United States?

B. Analysis of Demographic Subgroup Data

1. What are the statistical challenges in analyzing clinical trial data to evaluate subgroup differences? 

2. Given that it is not feasible to power most studies to detect subpopulation differences, what approaches should be used to analyze subgroups to explore clinically relevant information?

3. How might additional clinically relevant information about subgroups be obtained in the postmarket setting?

C. Communication of Demographic Subgroup Information to the Public

1. What information regarding demographic subgroups is helpful to health care professionals to make informed decisions about the use of medical products? To consumers/patients? To researchers?

2. What is the best way for FDA to communicate and make accessible such information to health care professionals? To consumers/patients? To researchers?

The hearing will be held on 1 April 2013.


Federal Register Notice


© 2022 Regulatory Affairs Professionals Society.

Discover more of what matters to you

No taxonomy