Systematic Evaluation of Patient-Reported Outcome Protocol Content and Reporting in Cancer Trials

Abstract

Background: Patient-reported outcomes (PROs) are captured within cancer trials to help future patients and their clinicians make more informed treatment decisions. However, variability in standards of PRO trial design and reporting threaten the validity of these endpoints for application in clinical practice.

Methods: We systematically investigated a cohort of randomized controlled cancer trials that included a primary or secondary PRO. For each trial, an evaluation of protocol and reporting quality was undertaken using standard checklists. General patterns of reporting where also explored.

Results: Protocols (101 sourced, 44.3%) included a mean (SD) of 10 (4) of 33 (range = 2-19) PRO protocol checklist items. Recommended items frequently omitted included the rationale and objectives underpinning PRO collection and approaches to minimize/address missing PRO data. Of 160 trials with published results, 61 (38.1%, 95% confidence interval = 30.6% to 45.7%) failed to include their PRO findings in any publication (mean 6.43-year follow-up); these trials included 49 568 participants. Although two-thirds of included trials published PRO findings, reporting standards were often inadequate according to international guidelines (mean [SD] inclusion of 3 [3] of 14 [range = 0-11]) CONSORT PRO Extension checklist items). More than one-half of trials publishing PRO results in a secondary publication (12 of 22, 54.5%) took 4 or more years to do so following trial closure, with eight (36.4%) taking 5-8 years and one trial publishing after 14 years.

Conclusions: PRO protocol content is frequently inadequate, and nonreporting of PRO findings is widespread, meaning patient-important information may not be available to benefit patients, clinicians, and regulators. Even where PRO data are published, there is often considerable delay and reporting quality is suboptimal. This study presents key recommendations to enhance the likelihood of successful delivery of PROs in the future.

Figure 1.

Study flow diagram. CONSORT = Consolidated Standards of Reporting Trials; NIHR = National Institute for Health Research; PRO = patient-reported outcome; RCT = randomized controlled trial; SPIRIT = Standard Protocol Items: Recommendations for Interventional Trials.

Figure 2.

Percentage of protocols (n = 101) including each patient-reported outcome (PRO) protocol checklist item (adjusted for denominator variation). PROM = patient-reported outcome measure; CRF = case report form.

Figure 3.

Percentage of publications (n = 99) including each Consolidated Standards of Reporting Trials (CONSORT) patient-reported outcomes (PRO) Extension Checklist item (adjusted for denominator variation). *PRO elaboration to CONSORT checklist item 2a: “Scientific background and explanation of rationale.” ^†PRO elaboration to CONSORT checklist item 4a: “Eligibility criteria for participants.” ^‡PRO elaboration to CONSORT checklist item 7a: “How sample size was determined.” ^§PRO elaboration to CONSORT checklist item 13a: “For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analyzed for the primary outcome.” ^‖PRO elaboration to CONSORT checklist item 15: “A table showing baseline demographic and clinical characteristics for each group.” ^¶PRO elaboration to CONSORT checklist item 16: “For each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups.” ^#PRO elaboration to CONSORT checklist item 17a: “For each primary and secondary outcome, results for each group, the estimated effect size, and its precision (such as 95% confidence interval).” **PRO elaboration to CONSORT checklist item 18: “Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory.”

Figure 4.

Summary of key recommendations and resources. CONSORT = Consolidated Standards of Reporting Trials; CPROR = Centre for Patient-Reported Outcomes Research; FDA = Food & Drug Administration; EMA = European Medicines Agency; ISOQOL = International Society for Quality of Life Research; PPI = patient and public involvement; PRO = patient-reported outcome; SISAQOL = Setting International Standards in Analysing Patient-Reported Outcomes and Quality of Life Endpoints Data; SPIRIT = Standard Protocol Items: Recommendations for Interventional Trials.