OBJECTIVES: Placebo effects in clinical trials may occur for various reasons, including 1) the Hawthorne effect, where patients report better outcomes due to being observed; 2) regression to the mean, where patients get better over time; or 3) true placebo effect, which is the response to placebo if other non-specific effects are removed. Currently, the National Institute for Health and Care Excellence (NICE) has no methodological guidance on how to account for significant observed placebo effects within cost-effectiveness analyses, making it a blind spot in the development of economic models that are fit-for-purpose. This study aimed to identify which placebo effect adjustment methods have been used in previous NICE submissions to determine potential best practices.

METHODS: A targeted search of the NICE website was conducted using the terms: “placebo effect adjustment”, “Hawthorne effect”, and “true placebo”. The company method, NICE committee preferred method and Evidence Assessment Group (EAG) comments were subsequently collected to identify best practices.

RESULTS: Searches yielded a total of 31 unique results: 30 for “placebo effect adjustment”, two for “Hawthorne effect” (both also within the first search), and one for “true placebo”. Following screening, ten of the appraisals contained mentions of placebo effect adjustment in their cost-effectiveness analyses. True placebo effect adjustment and Hawthorne effect were considered in six and three final appraisals, respectively. One appraisal had no adjustment for placebo effect implemented in the model, this adjustment was instead applied to the clinical data.

CONCLUSIONS: A variety of placebo effect adjustment methods have been used in cost-effectiveness analyses within NICE submissions. There does not appear to be a preference by NICE for one method over another. Further work using data from other national health authorities is needed to determine if best practice can be established.