July 15, 2016: FDA and Pragmatic Clinical Trials of Marketed Medical Products

July 15, 2016: FDA and Pragmatic Clinical Trials of Marketed Medical Products


Monique Anderson, MD, MHS, Assistant Professor of Medicine, Division of Cardiology, Duke University School of Medicine, Duke Clinical Research Institute


FDA and Pragmatic Clinical Trials of Marketed Medical Products


FDA regulations; Pragmatic clinical trials; Informed consent; Regulatory oversight; Institutional review boards; Human subjects protection; Investigational new drug (IND); Investigational device exemption (IDE); PCORI; PCORnet

Key Points

  • Pragmatic clinical trials (PCTs) are designed to evaluate the comparative effectiveness of interventions within routine clinical settings. PCTs are expected to be a major vehicle for evaluating the comparative effectiveness of healthcare strategies that involve FDA-regulated products.
  • PCTs involving FDA-approved treatments that are considered to be standard of care present different and often smaller risks to human subjects. For example, the ADAPTABLE aspirin study is a PCT comparing the effectiveness of two doses of aspirin for the secondary prevention of cardiovascular disease in 20,000 patients. In this case, the risks and benefits of aspirin are well known, and a patient could be prescribed either dose within the course of clinical practice.
  • It’s important to clarify the FDA’s jurisdiction and oversight of PCTs involving FDA-regulated medical products so as to enable the conduct of pragmatic trials that are essential to achieving national priorities.
  • To facilitate broader use of PCTs involving FDA-regulated medical products, the writing group recommends that the FDA adopt a risk-based approach to its jurisdiction for IND- and IDE-exempt trials. In the future, FDA should develop a regulatory scheme that provides explicit authority to consider alteration or waiver of informed consent for low-risk PCTs when deemed appropriate.

Discussion Themes

PCTs conducted within healthcare systems are meant to address gaps in our knowledge of the relative safety and effectiveness of standard medical products. How can we facilitate the conduct of low-risk PCTs that could address those gaps?

Should a risk-based classification be based on regulatory approval or on patterns of practice?

We need to better understand the utility of the existing “short form” informed consent process, which still may have limitations or be impracticable for cluster-randomized pragmatic trials.

For More Information

Read more about FDA-regulated products and PCTs in Anderson et al., Clinical Trials (2015) http://www.ncbi.nlm.nih.gov/pubmed/26374684

To read about ongoing PCTs supported by the NIH Health Care Systems Research Collaboratory, go to the Demonstration Projects website.

#TheAspirinStudy, #ADAPTABLE, #pctGR
@ADAPTABLEstudy, @PCTGrandRounds, @Collaboratory1, @PCORnetwork