Listening to the elephant in the room: response-shift effects in clinical trials research

Abstract

BackgroundWhile a substantial body of work postulates that adaptation (response-shift effects) may serve to hide intervention benefits, much of the research was conducted in observational studies, not randomized-controlled trials. This scoping review identified all clinical trials that addressed response shift phenomena, and characterized how response-shift effects impacted trial findings.MethodsA scoping review was done of the medical literature from 1968 to 2021 using as keywords “response shift” and “clinical trial.” Articles were included if they were a clinical trial that explicitly examined response-shift effects; and excluded if they were not a clinical trial, a full report, or if response shift was mentioned only in the discussion. Clinical-trials papers were then reviewed and retained in the scoping review if they focused on randomized participants, showed clear examples of response shift, and used reliable and valid response-shift detection methods. A synthesis of review results further characterized the articles’ design characteristics, samples, interventions, statistical power, and impact of response-shift adjustment on treatment effect.ResultsThe search yielded 2148 unique references, 25 of which were randomized-controlled clinical trials that addressed response-shift effects; 17 of which were retained after applying exclusion criteria; 10 of which were adequately powered; and 7 of which revealed clinically-important response-shift effects that made the intervention look significantly better.ConclusionsThese findings supported the presumption that response shift phenomena obfuscate treatment benefits, and revealed a greater intervention effect after integrating response-shift related changes. The formal consideration of response-shift effects in clinical trials research will thus not only improve estimation of treatment effects, but will also integrate the inherent healing process of treatments.Key pointsThis scoping review supported the presumption that response shift phenomena obfuscate treatment benefits and revealed a greater intervention effect after integrating response-shift related changes.The formal consideration of response-shift effects in clinical trials research will not only improve estimation of treatment effects but will also integrate the inherent healing process of treatments.