Limitations
Our analysis has several limitations. The results are based on only publicly available data; therefore, detectable changes relied on consistent and available reporting with each method. It is also not possible to know whether unintentional errors occurred during the initial reporting of PEPs on ClinicalTrials.gov that led to the discrepancies in PEPs observed in the study. Similar errors in reporting primary completion dates and changes on ClinicalTrials.gov may have led to our observation of PEP changes following the primary completion date. Studies have reported discrepancies in clinical trial registries related to listing of the principal investigatorsIn addition, there could be multiple confounding variables related to the association between PEP change and trial positivity. Trials that justifiably change PEPs prior to unmasking and analysis because of internal or external factors may be more likely to have positive outcomes. Furthermore, trial positivity may be associated with variables not tested in the multivariable analysis, including statistical power or patient accrual. Although we could not fully elaborate on or determine the validity of PEP changes and its causal relationship to trial positivity, our study found a high rate of PEP changes that were not properly highlighted or justified.