Methods Reference Guide for Effectiveness and Comparative Effectiveness Reviews Assessing Harms When Comparing Medical Interventions

Comparative Effectiveness Reviews are systematic reviews of existing research on the effectiveness, comparative effectiveness, and harms of different health care interventions. They provide syntheses of relevant evidence to inform real-world health care decisions for patients, providers, and policymakers. Strong methodologic approaches to systematic review improve the transparency, consistency, and scientific rigor of these reports. Through a collaborative effort of the Effective Health Care (EHC) Program, the Agency for Healthcare Research and Quality (AHRQ), the EHC Program Scientific Resource Center, and the AHRQ Evidence-based Practice Centers have developed a Methods Guide for Comparative Effectiveness Reviews. This Guide presents issues key to the development of Comparative Effectiveness Reviews and describes recommended approaches for addressing difficult, frequently encountered methodological issues. The Methods Guide for Comparative Effectiveness Reviews is a living document, and will be updated as further empiric evidence develops and our understanding of better methods improves. Comments and suggestions on the Methods Guide for Comparative Effectiveness Reviews and the Effective Health Care Program can be made at www.effectivehealthcare.ahrq.gov. The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ, the Assess all important harms, whenever possible. Use multiple sources of information, including clinical experts and stakeholders, to identify important harms. Use consistent and precise terminology when reporting data on harms, and avoid terms implying causality unless causality is reasonably certain. Gather evidence on harms from a broad range of sources, including observational studies, particularly when clinical trials are lacking; when generalizability is uncertain; or when investigating rare, long-term, or unexpected harms. Do not assume studies adequately assess harms because methods used to assess and report benefits are appropriate; rather, evaluate how well studies identify and analyze harms. Be cautious about drawing conclusions on harms when events are rare and estimates of risk are imprecise. Include placebo-controlled trials, particularly for assessing uncommon or rare harms, but be cautious about relying on indirect comparisons to judge comparative risks, and evaluate whether studies being considered for indirect comparisons meet assumptions for consistency of treatment effects. Avoid inappropriate combining of data on harms, and thoroughly investigate inconsistent results. Introduction Comparative Effectiveness Reviews (CERs) are systematic reviews that evaluate evidence on alternative interventions in order to help clinicians, policymakers, and patients make informed treatment choices. 1 To generate balanced results and conclusions, it is important for CERs to …