Department of Epidemiology, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Pharmacoepidemiol Drug Saf. 2022 Mar;31(3):261-269. doi: 10.1002/pds.5407. Epub 2022 Jan 27.
Confounding by indication poses a significant threat to the validity of nonexperimental studies assessing effectiveness and safety of medical interventions. While no different from other forms of confounding in theory, confounding by indication often requires specific methods to address the bias it creates in addition to common epidemiological adjustment or restriction methods. Clinical indication influencing treatment prescription is patient-specific and complex, making it challenging to measure within nonexperimental research. Restriction of the study population to patients with the indication for treatment would effectively mitigate confounding by indication and bring about comparability between exposure and comparator populations with respect to probability of the exposure. Active comparators are often an effective practical solution to restrict the study population in this manner when indication cannot be measured accurately. This article discusses various forms of confounding by indication, the utility of active comparators for nonexperimental studies of treatment effects, and the active comparator, new user (ACNU) study design to implicitly condition on indication. Considerations for selecting active comparators and conducting an ACNU study design are discussed to enable increased adoption of these methods, improve quality of nonexperimental studies, and ultimately strengthen our evidence base for intended and unintended treatment effects in relevant target populations.
意向性混杂对评估医疗干预措施的有效性和安全性的非实验性研究的有效性构成了重大威胁。虽然从理论上讲与其他形式的混杂没有区别，但意向性混杂通常需要特定的方法来解决它在除了常见的流行病学调整或限制方法之外所产生的偏差。影响治疗处方的临床指征是特定于患者的且复杂的，这使得在非实验性研究中难以测量。将研究人群限制为具有治疗指征的患者将有效地减轻意向性混杂，并使暴露组和对照组人群在暴露的可能性方面具有可比性。当无法准确测量指征时，主动对照剂通常是一种有效的实用方法，可以通过这种方式限制研究人群。本文讨论了各种形式的意向性混杂，以及主动对照剂在治疗效果的非实验性研究中的效用，以及主动对照剂、新使用者（ACNU）研究设计，以隐含地对指征进行条件处理。讨论了选择主动对照剂和进行 ACNU 研究设计的注意事项，以促进这些方法的更多采用，提高非实验性研究的质量，并最终加强我们在相关目标人群中对预期和非预期治疗效果的证据基础。
