Department of Bioethics, Clinical Center, National Institutes of Health, Bethesda, Maryland.
Biostatistics and Clinical Epidemiology Service, Clinical Center, National Institutes of Health, Bethesda, Maryland.
JAMA Netw Open. 2018 Dec 7;1(8):e186149. doi: 10.1001/jamanetworkopen.2018.6149.
Pragmatic clinical trials that seek informed consent after randomization (ie, postrandomization consent) are increasingly used, but debate on ethics persists because control arm patients are not specifically informed about the trials and randomization occurs before consent for the trials. The public's attitude toward postrandomization consent trials is unknown, but the way the trials are described could bias people's views.
To assess the attitudes of the US general public toward postrandomization informed consent for pragmatic trials and to measure potential framing and other factors associated with those attitudes.
DESIGN, SETTING, AND PARTICIPANTS: An online, 2 × 2 experimental survey (fielded between February 23 and April 3, 2018) portraying 4 scenarios of postrandomization informed consent (with prior broad consent for medical record use) was conducted. These scenarios included traditional randomized clinical trial language framing vs alternative framing in a high-stakes trial (ie, survival in leukemia) or low-stakes trial (ie, blood glucose level in diabetes). A total of 3793 individuals invited to participate were part of an existing panel representative of the US general public (GfK KnowledgePanel).
The proportion of participants who would recommend that an ethics review board approve a postrandomization consent pragmatic trial.
A total of 2042 of 3739 invitees (54.6%) responded; after exclusion of 38 incomplete surveys, 2004 participants were included in the analysis. Of these, 997 (49.8%) were women, 1440 (71.9%) were white non-Hispanic, 199 (9.9%) were black non-Hispanic, and 233 (11.6%) were Hispanic. Mean (SD) age was 47.5 (17.4) years. Across scenarios, weighted data showed that 75.4% of the participants would recommend approval of the postrandomization consent pragmatic trial, 20.4% would probably not recommend approval, and 4.2% would definitely not recommend approval. Approval was not sensitive to framing language (traditional vs new framing in high-stakes scenario, 74.3% vs 76.8%, P = .40; in low-stakes scenario, 77.7% vs 72.9%, P = .10) or to the stakes (low vs high stakes in traditional framing, 77.7% vs 74.3%, P = .25; in new framing, 72.9% vs 76.8%, P = .18). Better understanding of the postrandomization consent design was associated with higher rate of approval (78.1% vs 65.0%, P = .002 for high-stakes scenario; 77.2% vs 64.9%, P = .004 for low-stakes scenario), especially among those with less education. However, opinions about personal involvement in the control arm were more cautious (range depending on scenario, 45.6%-59.7%) and sensitive to stakes but not to framing.
The public's generally high rate of approval of the ethics of postrandomization informed consent for pragmatic trial designs does not appear to be affected by whether postrandomization consent design is framed using traditional randomized clinical trial terminology, regardless of the stakes of the trial. Promoting better understanding of the design may increase its acceptance by the public.
越来越多的实用临床试验在随机化后寻求知情同意（即随机后同意），但关于伦理的争论仍在继续，因为对照臂患者未被告知试验的具体情况，并且在同意参加试验之前就已经进行了随机化。公众对随机后同意试验的态度尚不清楚，但试验的描述方式可能会影响人们的看法。
评估美国公众对实用试验随机后知情同意的态度，并测量与这些态度相关的潜在框架和其他因素。
设计、设置和参与者：2018 年 2 月 23 日至 4 月 3 日期间进行了一项在线、2×2 实验性调查（描绘了 4 种随机后知情同意情景），这些情景包括传统的随机临床试验语言框架与高风险试验（即白血病患者的生存）或低风险试验（即糖尿病患者的血糖水平）中的替代框架。共有 3793 名受邀参与的个体是代表美国普通公众的现有小组（GfK KnowledgePanel）的一部分。
赞成伦理审查委员会批准随机后同意实用试验的参与者比例。
共有 3739 名受邀者中的 2042 名（54.6%）做出了回应；排除 38 份不完整的调查后，共有 2004 名参与者被纳入分析。其中，997 名（49.8%）为女性，1440 名（71.9%）为白人非西班牙裔，199 名（9.9%）为黑人非西班牙裔，233 名（11.6%）为西班牙裔。参与者的平均年龄（标准差）为 47.5（17.4）岁。在所有情景中，加权数据显示，75.4%的参与者会赞成批准随机后同意的实用试验，20.4%的参与者可能不会赞成，4.2%的参与者肯定不会赞成。批准与否不受框架语言（高风险情景中的传统框架与新框架，74.3%与 76.8%，P=0.40；低风险情景，77.7%与 72.9%，P=0.10）或风险程度（传统框架的低风险与高风险，77.7%与 74.3%，P=0.25；新框架，72.9%与 76.8%，P=0.18）的影响。对随机后同意设计的更好理解与更高的批准率相关（高风险情景为 78.1%与 65.0%，P=0.002；低风险情景为 77.2%与 64.9%，P=0.004），尤其是在受教育程度较低的人群中。然而，关于在对照组中个人参与的看法更加谨慎（根据情景的不同，范围在 45.6%-59.7%），并且对风险程度敏感，但不受框架的影响。
公众对实用试验随机后知情同意的伦理普遍高度认可，这似乎不受试验风险程度的影响，也不受试验随机后同意设计是否采用传统的随机临床试验术语框架的影响。提高对设计的理解可能会增加公众的接受度。
