Abstract
BackgroundResearchers have long posited that response-shift effects may obfuscate treatment effects. The present work investigated possible response-shift effects in a recent clinical trial testing a new treatment for Neuromyelitis Optica Spectrum Disorder (NMOSD). This pivotal trial provided impressive support for the drug Eculizumab in preventing relapse, but less strong or null results as the indicators became more subjective or evaluative. This pattern of results suggests that response-shift effects are present.MethodsThis secondary analysis utilized data from a randomized, double-blind trial evaluating the impact of Eculizumab in preventing relapses in 143 people with NMOSD. Treatment arm and then relapse status were hypothesized ‘catalysts’ of response shift in two series of analyses. We devised a “de-constructed” version of Oort structural-equation modeling using random-effects modeling for use in small samples. This method begins by testing an omnibus response-shift hypothesis and then, pending a positive result, implements a series of random-effects models to elucidate specific response-shift effects.ResultsIn the omnibus test, the ‘standard quality-of-life (QOL) model’ captured substantially less well the experience of placebo as compared to Eculizumab group. Recalibration and reconceptualization response-shift effects were detected. Detected relapse-related response shifts included recalibration, reprioritization, and reconceptualization.ConclusionsTrial patients experienced response shifts related to treatment- and relapse-related experiences. Published trial results likely under-estimated Eculizumab vs. Placebo differences due to recalibration and reconceptualization, and relapse effects due to recalibration, reprioritization, and reconceptualization. This novel random-effects- model application builds on response-shift theory and provides a small-sample method for better estimating treatment effects in clinical trials.
Highlights
Despite the advantages of rigorous clinical trial designs in providing unbiased estimates of treatment outcomes, these designs may lead to somewhat paradoxical findings
Two-thirds of the sample was on Eculizumab and one-third on placebo, and the sample evinced high levels of treatment adherence
The biggest decrements on the Social Functioning (SF)-36TM domain scores were in physical functioning and physical role performance
Summary
Despite the advantages of rigorous clinical trial designs in providing unbiased estimates of treatment outcomes, these designs may lead to somewhat paradoxical findings. The present work investigated possible response-shift effects in a recent clinical trial testing a new treatment for Neuromyelitis Optica Spectrum Disorder (NMOSD). This pivotal trial provided impressive support for the drug Eculizumab in preventing relapse, but less strong or null results as the indicators became more subjective or evaluative. Published trial results likely under-estimated Eculizumab vs Placebo differences due to recalibration and reconceptualization, and relapse effects due to recalibration, reprioritization, and reconceptualization This novel random-effects- model application builds on response-shift theory and provides a small-sample method for better estimating treatment effects in clinical trials
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