Evaluating the usefulness of randomized clinical trials in prostate cancer screening: A systematic review

Background: Prostate Cancer screening plays a crucial role in identifying the second leading cause of cancerrelated deaths worldwide, with more than 1.2 million cases reported in 2018 alone. Effective screening methods aim to achieve early detection and prompt management, while limiting overdiagnosis and treatment. Randomized controlled trials serve as the gold standard for evaluating screening methods and form the foundation for developing screening guidelines. However, there is concern in the research community about accumulating waste in clinical literature as some of these studies lack critical elements necessary for reproducibility and validity. This study aims to evaluate both the usefulness and transparency of randomized controlled trials on prostate cancer screening, utilizing a previously published 13-item usefulness criteria developed by van ’t Hooft et al. The goal is to ultimately evaluate the overall utility of the trials.

Methods: This systematic review analyzes the 13 criteria in 147 RCTs on prostate cancer screening identified through PubMed and Embase published between 1994 and 2024. Articles were screened in a double blind, masked fashion by two examiners, with discrepancies resolved by a third examiner. The usefulness criteria that were assessed were scored on a point system, with 0-2 points available for each item leading to a total possible score of 26. Statistical analysis included descriptive statistics on the number and proportion of criteria met, along with linear regression plots comparing the sum of the satisfied usefulness criteria over time with the sum of transparency criteria met over time.

Results: Ninety-five percent of studies scored within the lower two thirds of the total 26-point scale, with a mean score of 10.3. Criteria such as problem-base (n=144, 98%) scored highly in terms of satisfaction while key areas like patient-centeredness (n = 68, 46.3%) and information gain (n=103.0 70.1%) were largely absent in most of the studies. Regarding the transparency criteria, there was generally low satisfaction, as indicated in absence of preregistration (n=111.0, 75.5%), and publicly published protocols (n=130, 88.4%). However, overtime there is an upward trend in satisfaction of both usefulness and transparency (r = 0.21, p = 0.010) criteria with a greater positive correlation between the sum of transparency criteria overtime.

Discussion: Although there are areas within these clinical trials that satisfy the usefulness criteria, significant gaps remain, contributing to literature that lacks reproducibility, generalizability or validity. Existing transparency guidelines may explain the observed upward trend of satisfaction over time. However, it has become clear that incorporating the usefulness criteria is essential to further improve the effectiveness of clinical trials and reduce waste. The application of the usefulness criteria has shown its ability to identify areas of weakness and potentially aid in the development of future guidelines during the planning phase of clinical trials.

Conclusion: This study emphasizes the importance of incorporating standardized usefulness assessment tools, like the one studied, to optimize resources in clinical trial development and information reporting, ultimately improving the effectiveness of screening for life-threatening cancers.

Level of Evidence: Level II