Prospective Registration of Trials: Where we are, why, and how we could get better

Objectives: Transparent trial conduct requires prospective registration of a randomized controlled trial before the enrolment of the first participant. Registration aims to minimize potential biases through unjustified or hidden modification of trial design. We aimed to (1) estimate the proportion of randomized controlled trials that are prospectively registered and determine the time trends and the factors associated with prospective registration; (2) evaluate the reasons for non-adherence with prospective registration and explore potential mechanisms to enhance adherence with prospective registration. We studied trials published in rheumatology as a case study. Design and setting: We searched for reports of trials in rheumatology published between January 2009 and December 2022 using MEDLINE-PubMed. We retrieved trial registration numbers using metadata and reviewed full texts. We conducted a multivariable logistic regression to identify factors associated with prospective trial registration. We sent an online survey to authors of trials that were not prospectively registered. We inquired about possible reasons for non-adherence with prospective registration and asked about potential solutions. Results: We identified 1093 primary reports of randomized controlled trials; 453 (41.4%) were not prospectively registered. Of these, 130 (11.9%) were not registered, and 323 (29.5%) were retrospectively registered. Prospective registration increased over time at a rate of 3% per year (p<0.001), with only 13.3% (2/15) trials prospectively registered in 2009 to 73.2% (112/153) trials in 2022. Even among journals publicly supporting ICMJE recommendation, 16% of the trials published in 2022 were not prospectively registered. In the multivariable model, prospective registration was associated with a larger sample size, recruitment conducted across countries, and publication in a journal with a higher impact factor. Trial evaluating non pharmaceutical intervention, especially education, delivery of health care or wellness, had a lower rate of prospective registration. Investigators reported lack of knowledge, or organizational problems as the main reasons for retrospective registration. Authors also suggested linking ethical approval to trial registration as the best option to ensure prospective registration. Conclusions: Despite significant improvement, adherence to prospective registration remains unsatisfactory in rheumatology. Different strategies targeting journal editors, healthcare professionals, and researchers may improve trial registration.