Institute for History, Ethics and Philosophy of Medicine, Hannover Medical School, Hannover, Germany.
Forschungszentrum Jülich, Jülich, Germany.
Clin Trials. 2021 Feb;18(1):71-80. doi: 10.1177/1740774520971770. Epub 2020 Nov 24.
Informed consent documents for clinical studies should disclose all reasonably foreseeable risks and benefits. Little guidance exists on how to navigate the complexities of risk-benefit communication, especially in early clinical research. Practice-oriented development of such guidance should be informed by evidence on what and how details of risks and benefits are currently communicated.
We surveyed the responsible parties of phase I/II trials registered in ClinicalTrials.gov that started 2007 or later and completed between 2012 and 2016 to sample informed consent documents from a broad spectrum of early phase clinical trials. Based on an assessment matrix, we qualitatively and quantitatively assessed the informed consent documents for details of risk-benefit communication.
The risk-benefit communication in the 172 informed consent documents differed substantially in several regards. The outcome, extent, and likelihood of health risks, for example, were described in 83%, 32%, and 63% of the informed consent documents. Only 45% of informed consent documents specified the outcome of mentioned health benefits, and the extent and likelihood of health benefits were never specified. From those informed consent documents reporting risk likelihoods, only 57% added frequency numbers to words such as "common" or "rare," and even in these cases, we found strong variations for presented frequency ranges. Substantial heterogeneity also exists for how informed consent documents communicate other risk and benefit types and related safeguards.
Our study points to several shortcomings and heterogeneities in how informed consent documents communicate risks and benefits to potential research participants. Health risks, for example, should be specified with frequency numbers, and health benefits should be specified at least by mentioning their outcomes. Further demand for research and policy development is needed to harmonize risk-benefit communication and to clarify ways to specify the likelihood of health benefits.
临床研究的知情同意文件应披露所有可合理预见的风险和获益。在早期临床研究中，如何应对风险获益沟通的复杂性，几乎没有相关指导。这种指导的实践发展应该基于目前关于风险和获益的细节如何以及以何种方式进行沟通的证据。
我们调查了 2007 年或之后开始、2012 年至 2016 年期间完成的在 ClinicalTrials.gov 注册的 I/II 期试验的责任方，从广泛的早期临床试验中抽取知情同意文件样本。基于评估矩阵，我们对知情同意文件进行了定性和定量评估，以了解风险获益沟通的详细信息。
172 份知情同意文件中的风险获益沟通在几个方面存在显著差异。例如，研究结果、健康风险的程度和可能性在 83%、32%和 63%的知情同意文件中有所描述。只有 45%的知情同意文件明确了所提到的健康获益的结果，而健康获益的程度和可能性从未被明确说明。在那些报告风险可能性的知情同意文件中，只有 57%的文件在“常见”或“罕见”等词语后添加了频率数字，即使在这些情况下，我们也发现呈现的频率范围存在很大差异。知情同意文件传达其他风险和获益类型以及相关保障措施的方式也存在很大的异质性。
我们的研究表明，知情同意文件在向潜在研究参与者传达风险和获益方面存在一些不足和异质性。例如，健康风险应该用频率数字来具体说明，健康获益至少应该通过提及其结果来具体说明。需要进一步进行研究和政策制定，以协调风险获益沟通，并明确说明健康获益可能性的方法。
