How many times in our lives have we tried something that worked in theory; that “looked good on paper,” but did not work out in practice? In healthcare, differences between what succeeds at a research site and what happens at a clinic can be frustrating, disappointing, or even tragic. The carefully controlled circumstances of a randomized clinical trial can provide key insights into new treatments, but sometimes that isolated environment may not anticipate what occurs in the messy, largely uncontrolled context of healthcare in the real world. A type of study called the pragmatic clinical trial offers a means to close potential gaps between a research study and clinical practice. Pragmatic clinical trial design employs aspects of a clinical trial in a hospital or other treatment setting. It applies some of the rigor of a randomized clinical trial to the diverse, information-filled environment of a clinic or hospital. Pragmatic clinical trial designs have produced important insights just in the past year, such as expanding our understanding of pain management and delivery room practices.
Research in the Real World
Typically, a pragmatic trial protocol has two medical interventions to compare; it assigns the interventions randomly as treatments within a patient population and tracks the results (the randomization may happen within one institution or across multiple institutions). Researchers can compare effects of the two interventions over time, for a comprehensive look at how well the interventions perform. In the pain management study mentioned above, clinics prescribed either opioid or non-opioid painkillers after surgery. Over time, after tracking 240 people, the study results suggested that opioids did no better than non-opioids in managing pain. This result, which may be possible only with a pragmatic protocol design, has clear implications for clinicians.
This Time Is the Right Time
The pragmatic clinical trial concept has been around for decades, but a number of developments suggest this is a key moment to consider such a study design. For one, the regulatory environment is supportive. The 21st Century Cures Act called on regulatory agencies and researchers to expand the use of innovative trial designs, to use real-world evidence to guide approvals, and to utilize large data sets to improve health care. Insurance companies, pharmaceutical companies, and healthcare providers all face pressure to reduce costs, improve effectiveness, and prove that their solutions work. A well-designed pragmatic clinical trial can check all of those boxes.
What Is the IRB’s Role?
An innovative trial design demands innovative and flexible analyses. That means any reviewing committee should understand the implications of a protocol that may not fit traditional or typical structures. Our reviews of pragmatic trial protocols have raised some key, recurring questions about human subjects protections within these innovative designs:
- Where is the research happening, and what capabilities are needed there?
- How will the planned randomization affect the healthcare of patients?
- With large sets of medical information in play, how will confidentiality and privacy concerns be addressed?
- How much research experience or training is necessary (and practical) for clinicians in these studies?
- How can a pragmatic clinical trial operate within a clinical setting and adequately protect vulnerable populations?
- How can a pragmatic clinical trial ensure informed consent, provide subjects the opportunity to refuse to participate, and ensure the research results accurately reflect effects in the patient population?
If you would like to learn more about pragmatic clinical trials, how they compare to other study designs, or what regulatory and human subject protection issues they raise, be sure to sign up for this upcoming Quorum webinar, Elevating Research Impact: Pragmatic Clinical Trials and the IRB. IRB/REB Chair Dr. Stephen Rosenfeld and Executive Vice President and General Counsel Mitchell Parrish will share critical information about designing and conducting pragmatic clinical trials.