Reporting to Improve Reproducibility and Facilitate Validity Assessment for Healthcare Database Studies V1.0

The US Sentinel System and the Canadian Network for Observational Drug Effect Studies (CNODES) are two medical product safety surveillance networks. Using Sentinel's preprogrammed, parameterizable analytic tools, we reproduced two protocol‐based studies conducted by CNODES to assess the risks of acute pancreatitis and heart failure (HF) associated with the use of incretin‐based drugs, compared with use of ≥ 2 oral hypoglycemic agents. Results from the replication new‐user cohort analyses aligned with those from the CNODES nested case‐control studies. The adjusted hazard ratios were 0.95 (0.81–1.12; vs. 1.03 (0.87–1.22) in CNODES) for acute pancreatitis and 0.91 (0.84–1.00; vs. 0.82 (0.67–1.00) in CNODES) for HF among patients without HF history. The CNODES's common protocol approach allows studies tailored to specific safety questions, whereas the Sentinel's common data model plus pretested program approach enables more rapid analysis. Despite these differences, it is possible to obtain comparable results using both approaches.

Section: Discussionsupporting

confidence: 62%

Reproducing Protocol‐Based Studies Using Parameterizable Tools—Comparison of Analytic Approaches Used by Two Medical Product Surveillance Networks

Huang

Welch

Shinde

et al. 2019

“…In addition, the use of an analytics platform that can be shared with the FDA allows for transparency in study implementation for reviewers at the FDA, but does not guarantee that the rationale for all study decisions is completely described. Other approaches for documenting RWE studies could promote understanding of study rationale …”

Section: Discussionmentioning

confidence: 99%

Nonrandomized Real‐World Evidence to Support Regulatory Decision Making: Process for a Randomized Trial Replication Project

Franklin

Pawar

Martín

et al. 2019

Self Cite

132

Recent legislation mandates that the US Food and Drug Administration issue guidance regarding when real‐world evidence (RWE) could be used to support regulatory decision making. Although RWE could come from randomized or nonrandomized designs, there are significant concerns about the validity of RWE assessing medication effectiveness based on nonrandomized designs. We propose an initiative using healthcare claims data to assess the ability of nonrandomized RWE to provide results that are comparable with those from randomized controlled trials (RCTs). We selected 40 RCTs, and we estimate that approximately 30 attempted replications will be completed after feasibility analyses. We designed an implementation process to ensure that each attempted replication is consistent, transparent, and reproducible. This initiative is the first to systematically evaluate the ability of nonrandomized RWE to replicate multiple RCTs using a structured process. Results from this study should provide insight on the strengths and limitations of using nonrandomized RWE from claims for regulatory decision making.

“…Second, the number of prescriptions and patients were estimated at any time in the lifecycle of the database until August 31, 2018, in order to reflect initial analyses performed to evaluate the feasibility of a study on specific products. We did not apply criteria for inclusion of the practice or study‐specific restrictions in terms of medical history, patient characteristics (e.g., age and sex) or exposure time windows . Applying such decisions would sharply decrease the number of patients eligible to enter the study population.…”

Section: Discussionmentioning

confidence: 99%

Ability of Primary Care Health Databases to Assess Medicinal Products Discussed by the European Union Pharmacovigilance Risk Assessment Committee

Flynn

Hedenmalm

Murray‐Thomas

et al. 2020

This study measured the exposure to different categories of medicinal products discussed by the European Union (EU) Pharmacovigilance Risk Assessment Committee from September to November 2018 in four electronic primary care health databases: IQVIA Medical Research Data‐UK, IQVIA Medical Research Data‐France, IQVIA Medical Research Data‐Germany, and Clinical Practice Research Datalink Aurum, in the entire lifespan of each database until August 31, 2018. The assessment of 83 centrally authorized products and 45 nationally authorized products showed that coverage was better for products marketed for longer duration and worse for orphan drugs. The ability to detect associations against hypothetical comparators was better for more common events and for larger effect sizes. Coverage of advanced therapies was worse for those typically administered in a specialized rather than primary care setting. This study shows that to enable better informed regulatory decisions there is a need to access complementary data sources, particularly capturing secondary care prescribing.