More Streamlined Clinical Research Arises from Collaborative Effort

Leaders of the biomedical research community recently celebrated progress over the last decade in devising strategies to improve the quality and efficiency of clinical trials. The 10th anniversary of the Clinical Trials Transformative Initiative (CTTI) last week provided an opportunity for FDA officials to join with study sponsors and research experts to examine the policy achievements and plans for future efforts of this multi-faceted initiative.

The CTTI public-private partnership was established in 2008 by FDA and Duke University to collaborate on strategies for advancing the design and conduct of clinical research, which often faced criticism for being too slow and expensive to support efficient development of needed medicines. The group now has 80 member organizations from academia, government, industry, the patient community, and health care providers that have worked to develop and implement a broad range of proposals for streamlining clinical trial methods [see https://www.ctti-clinicaltrials.org/ for more information].

Former FDA commissioner Robert Califf, who was involved with CTTI as a leading clinician at Duke before coming to Washington, outlined the accomplishments of the initiative and its continuing challenges. CTTI was formed as a broad coalition of stakeholders to examine ways to modify the rules and practices that were making clinical trials increasingly expensive, complex, irrelevant, and unattractive to potential investigators. An important outcome has been to expand clinical trial registration and reporting on the ClinicalTrials.gov website. The partnership also has devised policies to advance the use of registries and central institutional review boards (IRBs), to simplify the informed consent process, and to clarify the use of study monitors and data monitoring committees.

Robert Temple, deputy director of the Center for Drug Evaluation and Research (CDER), described progress in promoting a “quality by design” (QbD) approach to devising and launching clinical studies. The CTTI QbD project encourages careful thinking about the purpose and requirements of the study protocol to focus on those research activities that are essential to the credibility of the study outcomes, explained Ann Meeker-O’Connell, head of bioresearch quality & compliance at Johnson & Johnson Consumer Health. Studies should collect only data needed to document valid endpoints and provide rationales for choice of study population, sample size, inclusion/exclusion criteria, data collected, procedures and assays and study endpoints. On-site monitoring should be limited to those sites with problems. QbD does not mean eliminating all errors, but taking actions to eliminate “errors that matter.”

Another CTTI initiative provides guidance for utilizing a “single IRB of record” for multi-center trials. This has involved defining the role and responsibilities of study sites, IRBs, research institutions, and sponsors in supporting and implementing this complex change in policy and practice for study oversight. The payoff is faster study launches and more efficient oversight of trials for research organizations participating in multi-site studies.

CTTI also has advanced efforts to improve investigator training, facilitate the use of registries in trial design and execution, implement pediatric studies for antibacterial drugs, and support more effective patient engagement in clinical trial design and implementation. A notable milestone is the recent use of FDA’s Sentinel Initiative data base to conduct a randomized controlled trial evaluating the benefits of increased use of anticoagulant medicines by patients with atrial fibrillation (IMPACT-AFib). This exercise sets the stage for tapping into health system records on millions of individuals to inform interventional studies.

These initiatives set the stage for dramatic change in the clinical trials enterprise over the next five to ten years, Califf predicted. He expects that greater use of “Big Data” and new quantitative methods arising from the digital revolution will create the long-sought “learning health care system” that will transform health care and biomedical innovation. More data sharing and transparency “is inevitable,” Califf observed, as patients and health care providers align to produce real world evidence able to guide medical product use and support innovative and high-quality trial designs.