FDA Seeks More Modern, Innovative Clinical Research Methods

Policy makers, sponsors and regulators are taking steps to promote alternative clinical study formats and methods that go beyond randomized clinical trials. The aim is to devise more efficient, less costly strategies for answering multiple questions about treatment effect and patient response, which is central to the shift to personalized medicine to treat rare diseases affecting more heterogeneous patient populations.

Modernizing FDA’s new drug regulatory program is a main goal for Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER), she said at the DIA/FDA annual Statistics Forum in Bethesda, MD. last month. This involves qualifying new biomarkers as “fit for purpose,” as directed by provisions in the 21st Century Cures legislation that FDA is beginning to implement. She described efforts to develop more sensitive measures of clinical outcomes, with performance standards for different diseases. And she aims to improve Patient Reported Outcomes (PROs) to better measure patient performance and opinions on how certain drugs may lessen the burden of treatment.

In the future, Woodcock looks to encourage platform trials with master protocols to evaluate disease outcomes and multiple treatments more efficiently. Such research programs may involve adaptive and pragmatic trials and studies of combination drugs, creating “huge statistical issues” that utilize Bayesian and other complex analytical methods. Those developing early master protocols will have “a rocky time,” Woodcock commented, adding that she hopes such approaches will be more broadly accepted over time.

Modern clinical trials also will incorporate more real world evidence (RWE) into research programs, an initiative also promoted by the “Cures” legislation. Challenges involve finding better ways to use health system data and methods for randomizing patients that remain in a health care system. RWE may be used initially more to support label changes and to validate new research study designs, than to support new drug approvals.

Ken Kaitin, director of the Tufts Center for the Study of Drug Development, agreed that the current clinical research approach needs to be transformed to deal with increasingly complex protocols involved in assessing rare diseases and specialty treatments targeted to certain patients, noted. Patients and payers are rejecting high-cost medicines, he noted at the Statistics Forum, and the vast majority of clinical trials fail to produce positive results.

Kaitin looks to overhaul the current biopharmaceutical R&D model by forming integrated partnerships that link sponsors, academia and disease foundations in establishing platforms that can accommodate multiple studies on a condition, such as diabetes, lupus or Alzheimer’s disease. While new drugs still will be costly to develop, approaches that leverage knowledge and resources from multiple sources can de-risk development and support access to new medicines.

Jill Wechsler is the Washington Correspondent for Applied Clinical Trials