Real-world evidence (RWE), the understanding of treatment effectiveness in clinical practice generated from longitudinal patient-level data from the routine operation of the healthcare system, is ...thought to complement evidence on the efficacy of medications from randomized controlled trials (RCTs). RWE studies follow a structured approach. (1) A design layer decides on the study design, which is driven by the study question and refined by a medically informed target population, patient-informed outcomes, and biologically informed effect windows. Imagining the randomized trial we would ideally perform before designing an RWE study in its likeness reduces bias; the new-user active comparator cohort design has proven useful in many RWE studies of diabetes treatments. (2) A measurement layer transforms the longitudinal patient-level data stream into variables that identify the study population, the pre-exposure patient characteristics, the treatment, and the treatment-emergent outcomes. Working with secondary data increases the measurement complexity compared to primary data collection that we find in most RCTs. (3) An analysis layer focuses on the causal treatment effect estimation. Propensity score analyses have gained in popularity to minimize confounding in healthcare database analyses. Well-understood investigator errors, like immortal time bias, adjustment for causal intermediates, or reverse causation, should be avoided. To increase reproducibility of RWE findings, studies require full implementation transparency. This article integrates state-of-the-art knowledge on how to conduct and review RWE studies on diabetes treatments to maximize study validity and ultimately increased confidence in RWE-based decision making.
Decision makers in health care increasingly rely on nonrandomized database analyses to assess the effectiveness, safety, and value of medical products. Health care data scientists use data-adaptive ...approaches that automatically optimize confounding control to study causal treatment effects. This article summarizes relevant experiences and extensions.
The literature was reviewed on the uses of high-dimensional propensity score (HDPS) and related approaches for health care database analyses, including methodological articles on their performance and improvement. Articles were grouped into applications, comparative performance studies, and statistical simulation experiments.
The HDPS algorithm has been referenced frequently with a variety of clinical applications and data sources from around the world. The appeal of HDPS for database research rests in 1) its superior performance in situations of unobserved confounding through proxy adjustment, 2) its predictable efficiency in extracting confounding information from a given data source, 3) its ability to automate estimation of causal treatment effects to the extent achievable in a given data source, and 4) its independence of data source and coding system. Extensions of the HDPS approach have focused on improving variable selection when exposure is sparse, using free text information and time-varying confounding adjustment.
Semiautomated and optimized confounding adjustment in health care database analyses has proven successful across a wide range of settings. Machine-learning extensions further automate its use in estimating causal treatment effects across a range of data scenarios.
Frailty is a key determinant of health status and outcomes of health care interventions in older adults that is not readily measured in Medicare data. This study aimed to develop and validate a ...claims-based frailty index (CFI).
We used data from Medicare Current Beneficiary Survey 2006 (development sample: n = 5,593) and 2011 (validation sample: n = 4,424). A CFI was developed using the 2006 claims data to approximate a survey-based frailty index (SFI) calculated from the 2006 survey data as a reference standard. We compared CFI to combined comorbidity index (CCI) in the ability to predict death, disability, recurrent falls, and health care utilization in 2007. As validation, we calculated a CFI using the 2011 claims data to predict these outcomes in 2012.
The CFI was correlated with SFI (correlation coefficient: 0.60). In the development sample, CFI was similar to CCI in predicting mortality (C statistic: 0.77 vs. 0.78), but better than CCI for disability, mobility impairment, and recurrent falls (C statistic: 0.62-0.66 vs. 0.56-0.60). Although both indices similarly explained the variation in hospital days, CFI outperformed CCI in explaining the variation in skilled nursing facility days. Adding CFI to age, sex, and CCI improved prediction. In the validation sample, CFI and CCI performed similarly for mortality (C statistic: 0.71 vs. 0.72). Other results were comparable to those from the development sample.
A novel frailty index can measure the risk for adverse health outcomes that is not otherwise quantified using demographic characteristics and traditional comorbidity measures in Medicare data.
Large health care utilization databases are frequently used in variety of settings to study the use and outcomes of therapeutics. Their size allows the study of infrequent events, their ...representativeness of routine clinical care makes it possible to study real-world effectiveness and utilization patterns, and their availability at relatively low cost without long delays makes them accessible to many researchers. However, concerns about database studies include data validity, lack of detailed clinical information, and a limited ability to control confounding.
We consider the strengths, limitations, and appropriate applications of health care utilization databases in epidemiology and health services research, with particular reference to the study of medications.
Progress has been made on many methodologic issues related to the use of health care utilization databases in recent years, but important areas persist and merit scrutiny.
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