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. 2019 Jul;106(1):103-115.
doi: 10.1002/cpt.1480. Epub 2019 Jun 12.

A Structured Preapproval and Postapproval Comparative Study Design Framework to Generate Valid and Transparent Real-World Evidence for Regulatory Decisions

Nicolle M Gatto  1   2   3 , Robert F Reynolds  1   2 , Ulka B Campbell  1   3
Affiliations

A Structured Preapproval and Postapproval Comparative Study Design Framework to Generate Valid and Transparent Real-World Evidence for Regulatory Decisions

Nicolle M Gatto et al. Clin Pharmacol Ther. 2019 Jul.

Abstract

Real-world evidence provides important information about the effects of medicines in routine clinical practice. To engender trust that evidence generated for regulatory purposes is sufficiently valid, transparency in the reasoning that underlies study design decisions is critical. Building on existing guidance and frameworks, we developed the Structured Preapproval and Postapproval Comparative study design framework to generate valid and transparent real-world Evidence (SPACE) as a process for identifying design elements and minimal criteria for feasibility and validity concerns, and for documenting decisions. Starting with an articulated research question, we identify key components of the randomized controlled trial needed to maximize validity, and pragmatic choices are considered when required. A causal diagram is used to justify the variables identified for confounding control, and key decisions, assumptions, and evidence are captured in a structured way. In this way, SPACE may improve dialogue and build trust among healthcare providers, patients, regulators, and researchers.

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Conflict of interest statement

N.M.G., R.F.R, and U.B.C. are full‐time employees and stock/shareholders of Pfizer.

Figures

Figure 1
Figure 1
Step 1: Articulate research question and operationalize design elements. RCT, randomized controlled trial
Figure 2
Figure 2
Step 2a: Draw causal diagram.
Figure 3
Figure 3
Step 2b: Describe and conceptualize potential confounder capture.
Figure 4
Figure 4
Step 3: Specify requirements to validly capture design elements.
Figure 5
Figure 5
Step 4: Answer questions in flowchart.
Figure 6
Figure 6
Structured Preapproval and Postapproval Comparative study design framework to generate valid and transparent real‐world Evidence (SPACE) flowchart.
See this image and copyright information in PMC

References

    1. Dreyer, N.A. Advancing a framework for regulatory use of real‐world evidence: when real is reliable. Ther. Innov. Regul. Sci. 52, 362–368 (2018). - PMC - PubMed
    1. US Food and Drug Administration (FDA) . Framework for FDA's Real‐World Evidence Program. 1−37 <https://www.fda.gov/downloads/ScienceResearch/SpecialTopics/RealWorldEvi...> (2018). Accessed April 15, 2019
    1. European Medicines Agency . Adaptive Pathways Workshop: Report on a Meeting with STAKEHOLDERS at EMA on 8 December 2016 (European Medicines Agency, London, England, 2017).
    1. Franklin, J.M. , Glynn, R.J. , Martin, D. & Schneeweiss, S. Evaluating the use of nonrandomized real‐world data analyses for regulatory decision making. Clin. Pharmacol. Ther. 105, 2019 (2019). - PubMed
    1. Berger, M.L. et al Good practices for real‐world data studies of treatment and/or comparative effectiveness: recommendations from the joint ISPOR‐ISPE Special Task Force on real‐world evidence in health care decision making. Pharmacoepidemiol. Drug Saf. 26, 1033–1039 (2017). - PMC - PubMed

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