AB1614 THE INCREASE IN SAFETY OUTCOME TRIALS AND THE ISSUE OF INFORMED CONSENT

Abstract

BackgroundThe randomized controlled trial (RCT) remains a most important research as well as a tool for drug licensing. Informed consent also remains an integral component of this tool. The exact wording of this consent is not in the public domain and we had previously raised that concern and had pointed out it should [1, 2]. As we previously indicated such transparency was important from the point of an organized skepticism an essential element of scientific inquiry [3]. Moreover, we had also indicated that this transparency was even more important in safety outcome trials (SOT)s. We have the impression that such SOTs are becoming more frequent especially with the increasing popularity of pragmatic trials [4] where the safety outcome measures are not infrequently as severe as death.ObjectivesTo tabulate the frequency of RCTs with the primary outcome measure of safety in mainline general medicine journals at two time points, thirty years apart.MethodsRCTs published in 1990-1991 vs 2019-2020 in NEJM, JAMA, LANCET and BMJ were searched by 2 independent reviewers (AO and SNE). Phase 1-2 RCTs, post-hoc analyses of RCTs and RCTs reporting long term follow-up data were excluded. RCTs with an undisputable primary endpoint of efficacy were defined as an ‘A trial’. Those trials with declared or obvious primary endpoints of ‘safety’, ‘efficacy and safety’ or simply as ‘efficacy’ in which we unanimously considered the presence of serious harm to the patients in the control arms were defined as a ‘B trial’. Finally, the trials that we could not unanimously decide whether designate A or B, were designated as C. Discrepancies were resolved after discussion with the senior author (HY) and if, even then, there was no consensus the trial remained as a C. We then compared the frequencies of the types of RCTs which were published in 1990-1991 vs 2019-2020. Other salient features, like the type and the practice setting, of these patients were also tabulated.ResultsThere were 309 RCTs published in 1990-1991 and 600 RCTs published in 2019-2020. Nineteen RCTs on COVID-19 infection were excluded for fair comparisons. As seen in the Table 1 there was a significant increase in the number SOTs in the later years. Moreover, the number of intensive care unit (ICU) trials, a setting in which obtaining informed consents can often be problematic, significantly increased.ConclusionRecently, there is a significant increase in the number of SOTs. Moreover, they are more frequently conducted in the ICUs. We strongly re-emphasize that the informed consents of all RCTs, particularly, those related to SOTs should be public. We strongly consider that such action is necessary a. to continue receiving our patients’ vital consent to enable us to continue conducting RCTs and b. for justly addressing the organized skepticism of our peers.