OptumInsight, Life Sciences, New York, NY 10026, USA.
Value Health. 2012 Mar-Apr;15(2):217-30. doi: 10.1016/j.jval.2011.12.010.
In both the United States and Europe there has been an increased interest in using comparative effectiveness research of interventions to inform health policy decisions. Prospective observational studies will undoubtedly be conducted with increased frequency to assess the comparative effectiveness of different treatments, including as a tool for "coverage with evidence development," "risk-sharing contracting," or key element in a "learning health-care system." The principle alternatives for comparative effectiveness research include retrospective observational studies, prospective observational studies, randomized clinical trials, and naturalistic ("pragmatic") randomized clinical trials.
This report details the recommendations of a Good Research Practice Task Force on Prospective Observational Studies for comparative effectiveness research. Key issues discussed include how to decide when to do a prospective observational study in light of its advantages and disadvantages with respect to alternatives, and the report summarizes the challenges and approaches to the appropriate design, analysis, and execution of prospective observational studies to make them most valuable and relevant to health-care decision makers.
The task force emphasizes the need for precision and clarity in specifying the key policy questions to be addressed and that studies should be designed with a goal of drawing causal inferences whenever possible. If a study is being performed to support a policy decision, then it should be designed as hypothesis testing-this requires drafting a protocol as if subjects were to be randomized and that investigators clearly state the purpose or main hypotheses, define the treatment groups and outcomes, identify all measured and unmeasured confounders, and specify the primary analyses and required sample size. Separate from analytic and statistical approaches, study design choices may strengthen the ability to address potential biases and confounding in prospective observational studies. The use of inception cohorts, new user designs, multiple comparator groups, matching designs, and assessment of outcomes thought not to be impacted by the therapies being compared are several strategies that should be given strong consideration recognizing that there may be feasibility constraints. The reasoning behind all study design and analytic choices should be transparent and explained in study protocol. Execution of prospective observational studies is as important as their design and analysis in ensuring that results are valuable and relevant, especially capturing the target population of interest, having reasonably complete and nondifferential follow-up. Similar to the concept of the importance of declaring a prespecified hypothesis, we believe that the credibility of many prospective observational studies would be enhanced by their registration on appropriate publicly accessible sites (e.g., clinicaltrials.gov and encepp.eu) in advance of their execution.
在美国和欧洲，人们越来越关注利用干预措施的有效性比较研究来为卫生政策决策提供信息。为了评估不同治疗方法的相对有效性，无疑将越来越频繁地进行前瞻性观察性研究，包括将其作为“证据开发覆盖范围”、“风险分担合同”或“学习型医疗保健系统”的关键要素的工具。有效性比较研究的主要替代方案包括回顾性观察性研究、前瞻性观察性研究、随机临床试验和自然主义（“务实”）随机临床试验。
本报告详细介绍了一项关于前瞻性观察性研究的良好研究实践工作组的建议，该研究旨在比较有效性。讨论的关键问题包括，鉴于替代方案的优缺点，何时决定进行前瞻性观察性研究，以及总结了适当设计、分析和执行前瞻性观察性研究以使其对医疗保健决策者最有价值和相关的挑战和方法。
工作组强调需要精确和明确地说明要解决的关键政策问题，并且研究应尽可能以得出因果推论为目标进行设计。如果进行研究是为了支持政策决策，那么它应该作为假设检验来设计-这需要起草一份方案，就好像受试者将被随机分组一样，并且研究人员应明确说明目的或主要假设，定义治疗组和结果，确定所有测量和未测量的混杂因素，并指定主要分析和所需的样本量。除了分析和统计方法外，研究设计选择可以增强解决前瞻性观察性研究中潜在偏倚和混杂的能力。使用起始队列、新用户设计、多个比较组、匹配设计以及评估被认为不受正在比较的治疗方法影响的结果是几种策略，应给予强烈考虑，同时认识到可能存在可行性限制。所有研究设计和分析选择的理由都应该透明，并在研究方案中解释。前瞻性观察性研究的执行与设计和分析同样重要，以确保结果具有价值和相关性，特别是要捕捉到感兴趣的目标人群，并且要有合理完整和非差异性的随访。与预先声明预设假设的重要性概念类似，我们认为，许多前瞻性观察性研究的可信度将通过在执行之前在适当的公共可访问网站（例如 clinicaltrials.gov 和 encepp.eu）上进行注册而得到提高。
