Monday, December 3, 2018

Research Shorts: Surrogate endpoints using the example of hepatitis C virus

Contributed by Claudia Dobler, MD, PhD
2018 U.S. GRADE Workshop Scholarship Recipient

Surrogate endpoints (for example laboratory or imaging results) are commonly used in clinical trials, as they require less participants and can be done in a shorter period of time compared to trials that use clinically important outcome measures such as mortality. When evidence for an intervention is almost exclusively based on trials that used surrogate outcomes, it is challenging for decision makers to determine the appropriateness of the use and reimbursement of an intervention. The common tendency in evidence-based medicine is to view results based on surrogate endpoints as less certain than results based on long term, final patient-important outcomes. The authors of this paper use the contemporary and highly debated example of the surrogate endpoint ‘sustained viral response’ (i.e., viral eradication considered to represent successful treatment) in patients treated for chronic hepatitis C virus infection to demonstrate how the validity of a surrogate endpoint can be critically appraised to assess the trustworthiness of the evidence and the implications for decision-making. They outline how the GRADE system for determining the certainty in the evidence can be used in situations where decisions for clinical practice and health policy have to be based on evidence that mainly comes from trials with indirect outcome measures.

Beyond assessing the quality of the evidence, potential benefits and harms of the intervention need to be weighed against each other and factors such as patient values, impact on healthcare equity, acceptability by patients and feasibility of the intervention need to be considered. The authors conclude that considering all these factors, a conditional recommendation for direct acting antiviral agents to treat chronic hepatitis C virus infection may be appropriate.

Reference: Dobler CC, Morgan RL, Falck-Ytter Y, Montori VM, Murad MH. Assessing the validity of surrogate endpoints in the context of a controversy about the measurement of effectiveness of hepatitis C virus treatment. BMJ evidence-based medicine 2018: 23(2): 50-53