Discussion
To our knowledge, this is the first comprehensive analysis of PEP changes among phase 3 trials in clinical oncology that used 3 methods of detecting PEP changes. We found not only a high rate of PEP changes in clinical trials after trial initiation but also considerable variability in reporting of PEP changes across available methods. There was substantial underreporting of PEP changes within published articles, and only one-third of RCTs provided protocols. Furthermore, when assessing the association of PEP changes with trial masking, our data showed that more PEP changes occurred in trials that were listed as open label, whereas trials with no PEP change had similar numbers of trials that were listed as open label vs not open label. While ClinicalTrials.gov does not provide information regarding the masking of the sponsoring institution, the higher frequency of PEP changes in open-label trials suggests a need for greater transparency in reporting PEP changes.Prior studies assessing rates of PEP change among multiple trials have reported variable rates of PEP discrepancies.There are multiple reasons for changes in PEPs. Masked review of data may reveal a high rate of discontinuation of therapy or slow accrual, which makes it difficult to properly assess the impact of a specific intervention. Prior to unmasking, results of a similar trial may also suggest that a different PEP may be more optimal in assessing the outcome of treatment.These results highlight the need for increased transparency in reporting changes within trial protocols and within the article.