Journal Article

The analysis and reporting of multiple outcomes in mental health trials: a methodological systematic review

Carter, Ben, Stringer, Dominic, Payne, Mollie, Emsley, Richard

2024

Overview

Background The choice of a single primary outcome in randomised trials can be difficult, especially in mental health where interventions may be complex and target several outcomes simultaneously. We carried out a systematic review to assess the quality of the analysis and reporting of multiple outcomes in mental health RCTs, comparing approaches with current CONSORT and other regulatory guidance. Methods The review included all late-stage mental health trials published between 1st January 2019 to 31st December 2020 in 9 leading medical and mental health journals. Pilot and feasibility trials, non-randomised trials, and early phase trials were excluded. The total number of primary, secondary and other outcomes was recorded, as was any strategy used to incorporate multiple primary outcomes in the primary analysis. Results There were 147 included mental health trials. Most trials (101/147) followed CONSORT guidance by specifying a single primary outcome with other outcomes defined as secondary and analysed in separate statistical analyses, although a minority (10/147) did not specify any outcomes as primary. Where multiple primary outcomes were specified (33/147), most (26/33) did not correct for multiplicity, contradicting regulatory guidance. The median number of clinical outcomes reported across studies was 8 (IQR 5–11 ). Conclusions Most trials are correctly following CONSORT guidance. However, there was little consideration given to multiplicity or correlation between outcomes even where multiple primary outcomes were stated. Trials should correct for multiplicity when multiple primary outcomes are specified or describe some other strategy to address the multiplicity. Overall, very few mental health trials are taking advantage of multiple outcome strategies in the primary analysis, especially more complex strategies such as multivariate modelling. More work is required to show these exist, aid interpretation, increase efficiency and are easily implemented. Registration Our systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 11th January 2023 (CRD42023382274).

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Child & adolescent psychiatry / Clinical outcomes / Clinical trials / Cognitive ability / Complex interventions / CONSORT / Electronic data processing / Evidence / Health Sciences / Humans / Hypothesis testing / Intervention / Medicine / Medicine & Public Health / Mental disorders / Mental Disorders - therapy / Mental health / Mental Health - statistics & numerical data / Methods / Multiplicity / Outcome Assessment, Health Care - methods / Outcome Assessment, Health Care - standards / Outcome Assessment, Health Care - statistics & numerical data / Outcomes / Psychiatric research / Randomized Controlled Trials as Topic - methods / Randomized Controlled Trials as Topic - standards / Randomized Controlled Trials as Topic - statistics & numerical data / Research Design - standards / Statistical Theory and Methods / Statistics for Life Sciences / Systematic review / Theory of Medicine/Bioethics / Treatment Outcome