May 16, 2019: NIH Collaboratory Investigators Author Recommendations for Responding to Guideline or Policy Changes That Affect Ongoing Pragmatic Trials

A new perspective article by NIH Collaboratory investigators describes the unique, unexpected challenges researchers face when clinical practice guidelines and policies change during the conduct of a pragmatic clinical trial (PCT). The article was published online this week in Clinical Trials.

The NIH Collaboratory Demonstration Projects are PCTs that test interventions to address urgent public health problems. They involve hundreds to thousands of participants and generally include usual care as a control arm. During the course of these years-long trials, clinical practice guidelines and policies changed due to new evidence from observational studies, small trials, and shifting expert opinion. Such changes can have profound effects on usual care and, therefore, threaten the ability of the PCTs to address the questions they were designed to answer. Investigators must strike a balance between the primary ethical obligation to protect patients by adhering to new best-practice guidelines and policy and the secondary, yet crucial, obligation to develop high-quality evidence to improve care.

“PCTs are an important means of producing high-quality evidence needed to better inform clinical practice. However, when guidelines or reimbursement policies change during the conduct of a PCT, the ethical obligation to gather information to develop evidence-based practices may conflict with the primary ethical obligation to participants.” — Curtis et al, Clinical Trials, 2019

Based on their aggregate experience with the NIH Collaboratory, the authors provide broad recommendations and strategies for overcoming these challenges, including protecting the well-being of patients; involving stakeholders, health system leaders, and the entity charged with data and safety monitoring; and actively monitoring changes and site-level responses to them. If changes to the standard of care are merited, investigators should provide equal opportunity and support for the recommended changes. Finally, during the design phase, investigators should communicate with the entities charged with creating guidelines to see what is needed and to anticipate possible future changes.

“The ability to appropriately address the tension between modifications to clinical guidelines and the need to generate quality evidence to support those guidelines is a crucial consideration for the fulfilment of a learning health system.” — Curtis et al, Clinical Trials, 2019