Applied Clinical Trials
Agency is asking sponsors to propose demonstration projects that test the use of electronic health records and standards-based technology solutions. Ensuring trials assess new drugs in diverse patient populations is also a priority focus for FDA.
A main goal for FDA leaders in the coming months is to refine clinical trial design and analysis so that studies can have smaller patient populations and achieve better outcomes. With clinical research expert Robert Califf slated to take the helm of the agency, initiatives to streamline trials will be a prime area of focus in facilitating biomedical discovery and bringing more new drugs to patients.
A December draft guidance, for example, lays out a process for sponsors to consult with agency staff during product development. Encouraging such communication aims to ensure that biopharma investigational plans and clinical trial designs produce adequate data to support product evaluation and approval, particularly for drugs developed under expedited programs (see here).
FDA also is soliciting comments from the research community on how new technologies and innovative methods can improve the investigational process. Topics include how study participants may use personal devices, such as smartphones and tablets, in “nontraditional settings” to collect data, and how such methods may alter informed consent procedures. Similarly, the Center for Drug Evaluation and Research (CDER) is asking sponsors and research organizations to propose demonstration projects that test the use of electronic health records and standards-based technology solutions to improve clinical trial data capture. These methods should limit errors, while reducing on-site data monitoring and other high-resource processes.
A main policy issue for FDA and sponsors is to ensure that clinical studies assess new medical products in a broad range of patient populations. Despite years of seeking diversity in clinical trials and adequate subgroup analysis in applications, FDA and other federal agencies continue to encounter studies with limited exposure to patients with differences in age, sex, race and ethnicity. A November report from the Government Accountability Office (GAO) found that research supported by the National Institute of Health (NIH) often fails to assess outcomes by gender to determine if men and women respond differently to a test therapy.
FDA will hold a public meeting at the end of February to hear from the research community on how well the agency is implementing its Action Plan to Enhance the Collection and Availability of Demographic Subgroup Data, which was issued in August 2014 as directed by the FDA Safety and Innovation Act (FDASIA) of 2012. The Plan contains 27 action items for improving subgroup participation and data transparency. FDA would like input from stakeholders on successful approaches for recruiting diverse clinical trial populations, limitations in meaningful data analysis of underrepresented groups, and how best to communicate with and present information on subgroup analysis (see here).
Some of the methodological and policy challenges in ensuring diversity in clinical trials were discussed by research experts at a workshop in December 2015 hosted by FDA and the Johns Hopkins Center for Excellence in Regulatory Science and Innovation (JH-CERSI). Participants examined ways to improve the completeness and quality of demographic subgroup data collection and analysis, and to assess whether clinical trial findings are generalizability when not derived from studies of diverse populations. Key topics included barriers to enrolling subgroups in clinical trials, strategies for encouraging greater participation, and ways to make demographic subgroup data more available and transparent (see here).
In a keynote address, Califf commented on a range of important clinical research issues. He noted the “inherent tension” between inclusive and targeted studies and the need for balance between clinical trials large enough to assess all relevant populations, and sufficiently small to provide deep data on each patient. He also observed that the challenges in conducting complex studies may be alleviated by greater use of electronic health records to obtain information on treatment impacts, and by tapping non-randomized epidemiological data to draw causal inferences about the presence or absence of a safety issue in a sub-population.
Social media also may be helpful in identifying meaningful outcomes for diverse populations. “It’s not just who we go out and include, but how we bring people from diverse neighborhoods into the design of the trials themselves” and how we identify what is important to them.
With more evidence coming from studies conducted outside the U.S., FDA needs to consider when to require data on U.S. populations and how to deal with differences related to geography, Califf observed. Most important, he commented, is to have well-designed clinical studies that can support the use of a product based on good evidence. Studies should be published in journals and posted on the ClinicalTrials.gov. website and then submitted to FDA for independent evaluation. FDA decisions are critical to whether a product gets to market-“and we very much want to stay as the gold standard for that.”