Congress, FDA Look to Improve Clinical Trial Practices & Policies

The mounting outrage over exorbitant prices for new medicines increases the importance of reducing the cost of biomedical product development by modernizing the long and expensive clinical research process for documenting the safety and efficacy of experimental treatments. Members of Congress are urging the Food and Drug Administration (FDA) and National Institutes of Health (NIH) to do more in this area, while championing targeted research initiatives. Last year the legislators approved a measure authorizing NIH to establish a national pediatric research network. More recent legislation provides $13 million a year (up to $126 million over 10 years) to support an NIH pediatric research fund. A measure providing additional incentives for developing new antibiotics and antimicrobials has gained support and may move forward in coming months.

The House Energy & Commerce Committee’s “21st Century Cures” initiative has heard from FDA and NIH leaders and research experts on strategies for accelerating development and approval of new treatments, with a focus on streamlining FDA regulation and providing added incentives for developing important therapies. Patient advocates have pressed for broader use of the accelerated approval process and other programs to speed new therapies to market, considered key to maintaining US leadership in biomedical innovation. Oncologists recently urged more focus on innovative R&D for new cancer treatments, and more hearings and white papers are scheduled.

FDA has signaled strong support for initiatives to move important new drugs quickly through its regulatory process, as seen in its final guidance on “Expedited Programs for Serious Conditions” (published May 30, 2014). The revised advisory clarifies the process for sponsors to gain the breakthrough therapy designation, with clearer definition of “available therapy” and other key terms, and more information on use of biomarkers and a rolling review option. The guidance also clarifies the accelerated approval process by providing more information on “intermediate clinical endpoints” and requirements for postmarketing confirmatory trials.

Seeking research transformation

FDA also considers the Clinical Trials Transformation Initiative (CTTI) key to improving the clinical research process, as seen in its recent announcement of plans to continue funding the program with $7 million a year, and up to $37.5 million over five years. This project is managed by the Duke (University) Translational Medicine Institute and was launched in 2007 as a private-public partnership to identify practices that can improve the quality and efficiency of clinical research. Leading pharma and biotech companies support the program, as does FDA and other federal health agencies and a host of academic and research organizations. CTTI projects are examining strategies for using central IRBs, organizing large simple trials, engaging patient groups, monitoring trials, improving patient recruitment and retention, and conducting studies to assess antibacterials.

And FDA’s latest “wish-list” of research that could enhance regulatory science includes a number of projects for refining clinical trial designs, endpoints and analysis. The agency recently proposed to provide between $200,000 and $50 million, depending on Congressional funding, on contracts with industry, academia, and research entities. Possible research projects could evaluate new biomarkers and study endpoints; develop computer models for assessing drug targets and clinical trial models; improve the evaluation of generic drugs; and develop tools for assessing novel treatments, such as those involving cell therapy and antisense products. While FDA is likely to fund only a handful of the many topics in its May announcement, the list provides a good picture of those areas that agency leaders consider important for improving the evaluation and approval of new medical products.

Improving outcomes research

Effective design of randomized clinical trials to inform comparative effectiveness research (CER) is a key assignment for the Patient-Centered Outcomes Research Institute (PCORI), as seen in initiatives to improve methods for conducting such studies as part of its mission. PCORI recently established an advisory panel on clinical trials to update research standards in this area and to help the Institute review clinical trials in its research portfolio, particularly those designed to directly compare different treatments. The panel will work with PCORI’s Methodology Committee to examine cross-cutting research issues such as ensuring patient-centeredness, dealing with missing data, examining heterogeneity of treatment effects, and devising standards for data registries.

PCORI also is funding a National Patient-Centered Clinical Research Network to conduct clinical research and observational studies more efficiently. Initial network research topics include comparative effectiveness of anticoagulants for atrial fibrillation and optimal second-line treatment for glycemic control in type 2 diabetes. While network studies won’t support product registration with FDA, its activities should assist the commercial research process by exploring options for fitting clinical trials into healthcare operations and for using electronic health records to identify patients and report outcomes.