When the Food and Drug Administration Safety and Innovation Act (FDASIA) was signed into law in 2012, among its many provisions was one not noticed by many: Section 907. The section requires FDA, within one year of the law's passage, 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."
Now the report required under Section 907 has been published by FDA, leaving FDA asking for public input as it prepares to develop a corresponding action plan intended to make policy changes.
The report's existence is owed to a long-standing problem, one that has its roots in ethics: How do you ensure that products are safe for an entire population of likely patients, and not just the majority of them?
For example, if a clinical trial sponsor needed 1,000 participants for a trial on an investigational cancer therapy intended to treat breast cancer, it might focus its recruiting efforts on women, resulting in a trial that is heavily (or perhaps entirely) skewed toward the female gender. But that raises a question: While the therapy might be shown to be effective in women, would it be just as effective in men, who can also (albeit rarely) develop breast cancer?
This problem becomes increasingly subtle when factors of age, race and ethnicity come into play. Some ethnic subgroups, such as Asians, respond differently (i.e. strongly) to certain types of drugs like lithium, antidepressants and antipsychotics. Patients of Chinese or African ethnicities, however, are more sensitive to beta-blockers and other heart rate and blood pressure medications.
These 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 have unique risks that some patients must take into account.
The good news, according to FDA's report, is 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."
FDA explains in its report that it took a sample of 72 applications approved during 2011 for new molecular entities, original biologics and Class III medical devices (presumably without predicates), and analyzed them to determine the current state of the industry.
What it found was generally encouraging, though not universally so. For example, industry is already required to submit demographic data and demographic analyses on trial participants when submitting data to the agency. Further, regulatory review staff takes this data into account as part of the overall review process.
However, the extent of the demographic analysis was limited, FDA found. For example, factors of sex and age were regularly taken into account, while ethnicity and race were less commonly analyzed, particularly in device applications, where such factors admittedly play less of a role.
FDA added an additional caveat: Just because the data was submitted for analysis doesn't mean it was necessarily useful. Factors like small clinical trials, for example, could limit the power of any analysis. "In many cases, [non-white] racial subgroups were underrepresented [in trials]," FDA noted.
And this lack of actionable data had an effect on FDA's ability to communicate potentially relevant information to the public. FDA said it often utilizes an approach that favors communicating to specific subgroups after an initial approval announcement is published, either communicating through product labeling, posted clinical reviews, consumer updates, label changes or other mechanisms.
The report is now slated to be turned over to Congress, but not before the public has a chance to weigh in. FDA announced on 20 August 2013 that it would be establishing a docket in the Federal Register to allow for the submission of comments to FDA, which would then be used to help FDA develop an "action plan" based on the report.
Federal Register notice
Section 907 Report: Collection, Analysis, and Availability of Demographic Subgroup Data for FDA-Approved Medical Products (August 2013)