Response-shift effects in neuromyelitis optica spectrum disorder: a secondary analysis of clinical trial data
- PDF / 1,006,462 Bytes
- 16 Pages / 595.276 x 790.866 pts Page_size
- 110 Downloads / 248 Views
Response‑shift effects in neuromyelitis optica spectrum disorder: a secondary analysis of clinical trial data Carolyn E. Schwartz1,2 · Roland B. Stark1 · Brian D. Stucky1 Accepted: 11 November 2020 © The Author(s) 2020
Abstract Background Researchers 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. Methods This 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. Results In 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. Conclusions Trial 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. Keywords Neuromyelitis optica spectrum disorder · Definitive neuromyelitis optica · Neurologic · Response shift · Clinical trial · Patient-reported outcome · Clinician-assessed outcome Abbreviations MCS Norm-based mental component score of the SF-36™ NMOSD Neuromyelitis optica spectrum disorder OSIS Opticospinal impairment score
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11136-020-02707-y) contains supplementary material, which is available to authorized users. * Carolyn E. Schwartz [email protected] 1
DeltaQuest Foundation, Inc, 31 Mitchell Road, Concord, MA 01742, USA
Departments of Medicine and Orthopaedic Surgery, Tufts University Medical School, Boston, MA, USA
2
PCS Norm-based physical component score of the SF-36™ PRO Patient-reported outcome SF-36v2™ Shor
Data Loading...
