Prospective Observational Studies to Assess Comparative Effectiveness: The ISPOR Good Research Practices Task Force Report

Abstract

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.

Randomized controlled trials and neurosurgery: the ideal fit or should alternative methodologies be considered?

“…11 Furthermore, criteria for the design and evaluation of prospective observational studies have also been established. 4 Registries that are amenable to multicenter studies are particularly helpful.…”

“…These and other considerations have been comprehensively outlined in the 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR) position statement. 4 The ISPOR group further suggests that a detailed and accurate protocol be established and registered upfront to increase the validity of the study and its findings. A commitment to publishing the results, regardless of whether a positive or negative outcome was attained, is also essential.…”

Generating and evaluating evidence of the clinical utility of molecular diagnostic tests in oncology

“…Factors influencing the decision include the state of clinical equipoise for the MDx test of interest and whether the proposed study design and analysis plan will sufficiently address potential problems with time-varying and time-invariant confounding and bias. 27 A prospective observational study should adopt best practices to minimize threats to validity. A full protocol with corresponding hypotheses and specified intervention groups, definitions of outcome measures as well as subgroups, power calculations, and an analysis plan that describes how to handle potential confounding, missing data, loss to follow-up, and heterogeneity of treatment effects is essential.…”

“…28 Various user guides on best practices for designing observational studies have been prepared by the Agency for Healthcare Research and Quality and other expert task forces, and researchers are encouraged to consult these guides before planning an observational study. 27,[29][30][31] Recommendation 10. Use formal decision-analytic modeling techniques to elucidate the relationship between test results, corresponding clinical pathways, and downstream patient outcomes in cases where an MDx test has established evidence of CV and plausible evidence of CU based on modeling of the initial scenario (a simplified approach for outcomes: base case, best case, worst case).…”

Modern needs in health technology assessment: a study of comparative effectiveness

“…[1]. Данный подход приме-няют в большинстве развитых стран мира, и он имеет существенное значение при принятии решений о целе-сообразности внедрения той или иной технологии, при-меняемой в медицине [1][2][3]. Целью проведения ОМТ является помощь в разработке безопасной, эффектив-ной политики здравоохранения, которая ориентируется на нужды больных и стремится достичь наилучшего вло-жения финансовых средств [1].…”