Prostate cancer trial design is structured following the Prostate Cancer Clinical Trials Working Group (PCWG) guidelines which focus on harmonization of inclusion criteria and outcome data. The PCWG, however, does not provide clear outlines for reporting of safety data. In fact, there is a perceived lack of widely accepted guidelines for safety reporting.
A PubMed search of phase II and III clinical trials published until 2015 (included) was conducted using keywords “prostate cancer” and “docetaxel.” Docetaxel-naïve CRPC patients who received 75 mg/m2 docetaxel monotherapy every three weeks were included. To assess quality of toxicity reporting, the Consolidated Standards of Reporting Trials (CONSORT) harms checklist was adapted and each trial scored by two independent reviewers. CONSORT scores as well as PSA and radiological response rates over time were examined with Spearman correlation coefficients. Univariable and multivariable linear regression examined associations between scores and phase II versus III trials, publication year, midpoint of accrual, number of patients, sponsor type, journal impact factor, presence of supplementary data, and geographical region.
From 21 clinical trials including 5,460 patients in docetaxel monotherapy arms, the median CONSORT score was 15.3 (IQR 13.7–16.5) out of 22. Correlation coefficients were not significant for all comparisons of CONSORT scores and response rates versus years of accrual or year of publication. In univariable linear regression, phase III clinical trials were associated with a significantly higher CONSORT score (p = 0.01) as was a journal impact factor greater than 15 (p = 0.02). In exploratory analyses, none of the examined factors were significant in multivariable linear regression.
CONSORT scores and thus toxicity reporting quality in CRPC trials studying docetaxel show need for improvement and should be subject to further discussion. There has been no significant improvement in toxicity reporting quality over time. It remains to be studied if our findings also apply to other agents used for the treatment of CRPC. Legal entity responsible for the study: Sunnybrook Research Institute.
Clinical trial identification
Joseph and Silvana Melara Cancer Fund.
All authors have declared no conflicts of interest.