Clinical Trials Transformation Initiative, Duke University School of Medicine, Durham, North Carolina.
Department of Population Health Sciences, Duke University School of Medicine, Durham, North Carolina.
JAMA Netw Open. 2018 Dec 7;1(8):e185816. doi: 10.1001/jamanetworkopen.2018.5816.
Better treatment options are needed in life-threatening infections, including health care-associated pneumonia. Enrolling patients in antibacterial clinical trials before diagnosis may circumvent existing time-to-enrollment constraints. However, the acceptability of an early enrollment strategy using advance consent is unknown.
To assess the perceived acceptability of an early enrollment strategy for enrolling patients in an antibacterial clinical trial before a pneumonia diagnosis.
DESIGN, SETTING, AND PARTICIPANTS: This qualitative, descriptive study used semistructured telephone interviews. Framed within a planned noninferiority pneumonia antibiotic trial, an early enrollment strategy was described and perceptions were assessed. Using this strategy, patients give consent to enroll before developing pneumonia, to be monitored by study staff, and to be randomly assigned a study antibiotic if pneumonia develops. All interviews were audiorecorded, transcribed verbatim, and analyzed using applied thematic analysis. Fifty-two key stakeholders from across the United States, including 18 patients at risk of pneumonia, 12 caregivers, 10 representatives of institutional review boards, 7 investigators, and 5 study coordinators, were interviewed from June 20 to August 19, 2016.
Perceived acceptability of the early enrollment strategy.
Among the 52 stakeholders interviewed (ages 29-75 years; 14 women), patients and caregivers expressed no concerns about patients being approached about participation before developing pneumonia; however, some patients may experience anxiety on learning about their risk for pneumonia. No concerns with study staff accessing patients' medical records were expressed. The clarity of consent information was important for understanding the study rather than having the condition under investigation. Among patients, caregivers, and institutional review board representatives, preferences varied regarding opt-out and precedent autonomy procedures. Nearly all patients would be willing to join a trial using the early enrollment strategy and caregivers would be willing to provide proxy consent. Institutional review board representatives were supportive of the strategy and made recommendations for the study protocol, primarily around informed consent. Investigators and study coordinators believed the strategy would not be burdensome and offered suggestions to ensure its feasibility.
Results of the study suggest that the early enrollment strategy is acceptable. Future research should evaluate whether the strategy improves enrollment rates in registrational pneumonia trials and in trials of other acute infection syndromes with narrow enrollment windows and/or patients with transient decisional incapacity.
重要的是，在危及生命的感染中，包括与医疗保健相关的肺炎，需要更好的治疗选择。在诊断前让患者参与抗菌临床试验可能会规避现有的入组时间限制。然而，使用预先同意的早期入组策略的可接受性尚不清楚。
评估在肺炎诊断前使用预先同意对患者进行抗菌临床试验的早期入组策略的可接受性。
设计、设置和参与者：这项定性、描述性研究使用了半结构化电话访谈。在一项计划的非劣效性肺炎抗生素试验框架内，描述了早期入组策略，并评估了其看法。使用该策略，患者在发生肺炎前同意入组，由研究人员进行监测，如果发生肺炎，患者将被随机分配研究用抗生素。所有访谈均进行了录音、逐字转录，并使用应用主题分析进行了分析。2016 年 6 月 20 日至 8 月 19 日，来自美国各地的 52 名利益攸关方（包括 18 名有肺炎风险的患者、12 名护理人员、10 名机构审查委员会代表、7 名研究者和 5 名研究协调员）接受了采访。
对早期入组策略的可接受性的看法。
在接受采访的 52 名利益攸关方（年龄 29-75 岁；14 名女性）中，患者和护理人员对在发生肺炎之前接触患者参与研究没有任何顾虑；然而，一些患者在了解到自己患肺炎的风险时可能会感到焦虑。没有对研究人员查阅患者病历表示担忧。知情同意书的信息是否清晰对于理解研究很重要，而不是调查中的病情。在患者、护理人员和机构审查委员会代表中，关于选择退出和先例自主权程序的偏好存在差异。几乎所有患者都愿意参加使用早期入组策略的试验，护理人员愿意提供代理同意。机构审查委员会代表对该策略表示支持，并就研究方案提出了建议，主要是围绕知情同意书。研究者和研究协调员认为该策略不会带来负担，并提出了确保其可行性的建议。
研究结果表明，早期入组策略是可以接受的。未来的研究应该评估该策略是否能提高注册肺炎试验以及其他具有狭窄入组窗口和/或短暂决策能力丧失的急性感染综合征试验的入组率。
