Esatoglu Sinem Nihal, Ozdede Ayse, Ozguler Yesim, Tascilar Koray, Yazici Hasan
Division of Rheumatology, Department of Medicine, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey.
Department of Internal Medicine 3, Friedrich-Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Trials. 2025 Jan 25;26(1):28. doi: 10.1186/s13063-025-08732-x.
It was our impression that safety outcome trials were getting more frequent, raising ethical issues mainly related to patient autonomy. We and others had also proposed this autonomy would be best served if wording of the informed consents would be in the public domain.
Initially two observers and an arbiter tabulated the main aims of randomized controlled trials (RCTs) published in 1990-1991 vs. 2019-2020 as efficacy, safety, or undecided in four mainline medical journals, from the websites. A pragmatic design as well as other salient features was also tabulated. After noting too many trials were categorized as undecided, two additional independent observers and the arbiter did a reassessment.
In our reassessment of 889 RCTs, 309 in earlier and 580 in the later time period, 828 (93%) were categorized as efficacy and 47 (5%) as a safety trial. We were undecided in 14 (2%) trials. The proportion of safety outcome trials between the two time periods were similar [14/309 (5%) vs. 33/580 (6%)] while RCTs of any category conducted in the critical care settings notably increased in time [12/309 (4%) vs. 52/580 (9%) OR 2.4; 1.3-4.6]. Death was a primary outcome measure in 0/14 among the earlier and 16/33 (49%) among the later safety outcome trials. Stroke in 9 and myocardial infarction in 8 safety outcome trials were additional primary outcome measures in the same group. There were 2 pragmatic trials in the earlier and 93 in the later period.
Although we did not observe a differential increase among the safety outcome trials of all categories, those in critical care settings had significantly increased in time. So did the safety outcome trials with primary outcome measures like death, myocardial infarction, and stroke as well as randomized controlled trials with a pragmatic design. These raise the issue of autonomy related to how clearly the sought-after safety through designing empirical studies primarily to quantitate harm had been worded to the trial participants in plain language. We maintain this issue cannot be adequately addressed unless the informed consent forms, especially for safety outcome trials, are in the public domain.
我们的印象是，安全性结果试验越来越频繁，这引发了主要与患者自主权相关的伦理问题。我们和其他人还提出，如果知情同意书的措辞能公开，将最有利于维护这种自主权。
最初，两名观察员和一名仲裁员从网站上梳理了1990 - 1991年与2019 - 2020年在四种主流医学期刊上发表的随机对照试验（RCT）的主要目的，分为疗效、安全性或未明确，还梳理了实用设计以及其他显著特征。在注意到太多试验被归类为未明确后，另外两名独立观察员和仲裁员进行了重新评估。
在我们对889项RCT的重新评估中，早期有309项，后期有580项，其中828项（93%）被归类为疗效试验，47项（5%）为安全性试验。我们对14项（2%）试验未明确归类。两个时间段之间安全性结果试验的比例相似[14/309（5%）对33/580（6%）]，而在重症监护环境中进行的任何类别的RCT数量随时间显著增加[12/309（4%）对52/580（9%），比值比2.4；1.3 - 4.6]。在早期的14项安全性结果试验中，0项将死亡作为主要结局指标，而在后期的33项中，16项（49%）将死亡作为主要结局指标。在同一组安全性结果试验中，9项将中风和8项将心肌梗死作为额外的主要结局指标。早期有2项实用试验，后期有93项。
虽然我们没有观察到所有类别安全性结果试验的差异增加，但重症监护环境中的试验数量随时间显著增加。以死亡、心肌梗死和中风等为主要结局指标的安全性结果试验以及采用实用设计的随机对照试验也是如此。这就引发了自主权问题，即通过主要设计实证研究来量化伤害所追求的安全性，在向试验参与者表述时是否足够清晰易懂。我们坚持认为，除非知情同意书，尤其是安全性结果试验的知情同意书能公开，否则这个问题无法得到充分解决。
