Comprehensive review of statistical methods for analysing patient-reported outcomes (PROs) used as primary outcomes in randomised controlled trials (RCTs) published by the UK’s Health Technology Assessment (HTA) journal (1997–2020)

Objectives: To identify how frequently patient-reported outcomes (PROs) are used as primary and/or secondary outcomes in randomised controlled trials (RCTs) and to summarise what statistical methods are used for the analysis of PROs.

Design: Comprehensive review.

Setting: RCTs funded and published by the United Kingdom’s (UK) National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme.

Data sources and eligibility: HTA reports of RCTs published between January 1997 and December 2020 were reviewed.

Data extraction: Information relating to PRO use and analysis methods was extracted.

Primary and secondary outcome measures: The frequency of using PROs as primary and/or secondary outcomes; statistical methods that were used for the analysis of PROs as primary outcomes.

Results: In this review, 37.6% (114/303) of trials used PROs as primary outcomes, and 82.8% (251/303) of trials used PROs as secondary outcomes from 303 NIHR HTA reports of RCTs. In the 114 RCTs where the PRO was the primary outcome, the most used PRO was the Short-Form 36 (8/114); the most popular methods for multivariable analysis were linear mixed model (45/114), linear regression (29/114) and analysis of covariance (13/114); logistic regression was applied for binary and ordinal outcomes in 14/114 trials; and the repeated measures analysis was used in 39/114 trials.

Conclusion: The majority of trials used PROs as primary and/or secondary outcomes. Conventional methods such as linear regression are widely used, despite the potential violation of their assumptions. In recent years, there is an increasing trend of using complex models (eg, with mixed effects). Statistical methods developed to address these violations when analysing PROs, such as beta-binomial regression, are not routinely used in practice. Future research will focus on evaluating available statistical methods for the analysis of PROs.