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.

International standards for the analysis of quality-of-life and patient-reported outcome endpoints in cancer randomised controlled trials: recommendations of the SISAQOL Consortium

“…Four key findings were highlighted: a lack of specific PRO hypotheses, use of various analysis methods, failure to address the clinical relevance of PRO findings, and ignoring missing data. These findings were also consistent with systematic reviews evaluating inclusion of PROs in protocols 10 , and reporting of PROs in publications [11][12][13][14][15] .…”

“…Research objectives working group. Systematic reviews consistently showed a lack of well-defined PRO research hypotheses in cancer RCTs 5,6,10,13,15 . A well-defined PRO hypothesis is needed to provide a clear understanding of what needs to be estimated from the PRO data, which can then inform appropriate analysis decisions.…”

Investigating the impact of open label design on patient‐reported outcome results in prostate cancer randomized controlled trials

“…Recent reviews pointed out that PRO reporting is far from the high-quality standards emphasized by regulatory stakeholders and panel expert recommendations. 16 Only 30% of the trials submitted by the sponsor to the FDA reported PRO compliance. 38 Furthermore, in our analysis, the quality of PRO reporting according to ISOQOL recommendations was globally equivalent between open-label and blinded RCTs.…”

“…However, the overall quality of the reports is far from what we would expect as highlighted in a recent review. 16 However, it is difficult to provide a definitive answer on the actual role of the open-label design on PROs in RCT settings. To further explore it, a case-control study or meta-analysis which includes RCTs evaluating the same treatment in open-label and blinded RCTs and using the same PRO questionnaires could provide additional insights.…”

“…12,13 However, several systematic reviews have highlighted that a high proportion of RCTs including PROs poorly report on these measurements, with missing information being very common. [14][15][16] Another important methodological issue with the reporting of PROs in RCTs is the open-label setting. 17,18 Hence, the FDA rarely considers open-label RCTs adequate for PRO based claims.…”