Multi-Dimensional Capture of Patient-Relevant Endpoints in Regulatory Trials and Health Technology Assessments in Oncology Two Years After Introduction of the German Amnog Health Care Reform

Abstract

A575Objectives: There is a growing interest from health technology assessment agencies in determining the clinical outcomes assessments and endpoint strategies that can establish treatment benefits. We describe a systematic literature review of endpoints and outcomes used in schizophrenia trials to determine treatment benefit. MethOds: The therapies selected in the search strategy included pharmacological interventions, cognitive-behavioural therapies, family intervention, and music therapy. These were chosen to reflect the range of interventions in current use, and to allow comparison between outcomes reported for different therapies. The search terms were designed to include all outcomes for each therapy area, and were used to search four electronic databases for published English language studies. Randomised controlled trials (RCTs) were retrieved if they included patients with schizophrenia treated with the chosen therapies, and clinical outcomes from a predefined list (e.g. symptom improvement, functionality, quality of life, remission rates, response rates, and recovery). Results: Of 2,221 RCTs identified, 271 progressed to data extraction; 225 assessed pharmacological interventions and 46 nonpharmacological interventions. Approximately 76 outcomes were measured across the trials. The most common scale used in pharmacological trials was the Positive and Negative Syndrome Scale (PANSS) total score (76.9%), and the PANSS positive subscale in non-pharmacological trials (50%). However, even within the common outcomes, the specified level of reduction to define a relevant response varied; among trials reporting PANSS total, five different levels of reduction were defined (≥ 20%, ≥ 25%, ≥ 30%, ≥ 40%, ≥ 50%). Common outcomes were also measured differently in terms of improvement from baseline and proportion achieving response/ remission, with little consensus on clinical meaningfulness. cOnclusiOns: The RCTs included in this review reported a broad range of outcomes, making comparison of different therapies a complex task. The disparity in outcomes between pharmacological and non-pharmacological outcomes scales highlights the challenges in designing trials to demonstrate clinical benefit.