Real-world evidence can change the course of regulatory decisions. In February 2023, the U.S. Food and Drug Administration (FDA) approved Skyclarys (omaveloxolone) for the treatment of the rare neurological condition Friedreich’s ataxia (FA) on the basis of both clinical trial data and matched analyses with real-world patients in a natural history study. While ultimately accepted, regulators did critique the sponsor’s lack of prespecified analysis plan for their real-world analyses, highlighting increased demand for proactive and transparent RWE strategy. This critique is well in line with ISPE/ISPOR initiative to integrate open science practices into routine workflows for pharmacoepidemiologists—an initiative that was front and center in several informative ISPE sessions including Building Transparency and Reproducibility into the Practice of Pharmacoepidemiology and Outcomes Research. These sessions were great reminders that transparency should extend through the lifecycle of RWE fro

GLP-1 receptor agonists have become blockbuster drugs for weight loss, diabetes, cardiovascular risk reduction, kidney health, and just recently, metabolic dysfunction-associated steatohepatitis (MASH) . Randomized controlled trials (RCTs) launched these therapies, but leave gaps in our understanding about how they work in the real-world—and who they work for. Together with Humbi.ai, we analyzed claims data to describe characteristics, treatment patterns and outcomes among Medicare FFS beneficiaries who started using GLP-1s. This population is more representative of US seniors than typical trial populations, and specifically includes more rural seniors—who are generally underrepresented in RCTs but face higher cardiometabolic risk. We found semaglutide use surged over time, becoming the most prescribed GLP-1 RA in 2021, with primary care providers doing most of the prescribing. This data provides real-world benchmarks for myocardial infarction and overall survival in a Medicare populat

RWE Use in Prograf’s Successful Indication Expansion: Making the Case for Fit-for-Purpose Data and Data Transparency Astellas faced a high-stakes question: how do you structure a successful application for indication expansion when patients are already relying on your drug off-label? Their answer—fit-for-purpose real-world paired with data transparency to facilitate FDA replication of analyses. When Astellas aimed to expand the use of Prograf (tacrolimus) to prevent rejection in lung transplant patients, they faced a significant hurdle: conducting a randomized controlled trial wasn’t feasible or ethical. There was no approved immunosuppressive agent to prevent rejection in lung transplant patients, but Prograf was already approved for liver, kidney, and heart recipients—and was already the off-label standard of care for lung. So, the team turned to real-world evidence, drawing on a rich, fit-for-purpose data source—the Scientific Registry for Transplant Recipients (SRTR)—which comprehe

How Early and Ongoing Engagement Boosted Vijoice’s FDA Journey: A Case Study in Building Regulatory Confidence in RWE Facing the challenge of demonstrating treatment benefits for the ultra-rare and complex disease PIK3CA-related overgrowth spectrum (PROS), Novartis took an innovative approach with the evidence generation for Vijoice (alpelisib). With few patients worldwide and no approved therapies, clinical trials weren’t feasible—so they designed a retrospective, single-arm study using real-world data from patients in a Compassionate Use Program across multiple countries. From the start, Novartis engaged openly with the FDA, discussing whether this novel approach could support approval and aligning on study design, endpoints, and analysis plans. They focused on objective measures like tumor reduction assessed through independent radiology review to minimize investigator bias, while adhering to strict data management and regulatory standards. By submitting patient-level and standardiz

Drugs are developed to treat diseases in individual patients—but real-world use often depends more on systems than symptoms. For example, Medicaid Part D does not cover Wegovy® for weight loss, but started covering it to reduce cardiovascular risk in March of 2024. Together with Humbi.ai, we presented our initial results of an in-depth analysis of characteristics, treatment patterns and outcomes among Medicare FFS beneficiaries who used Wegovy® following this policy shift. These early adopters were typically older adults with existing cardiovascular risks, but were less likely than users of other GLP-1s to have diabetes. Over 95% continued this medication without switching during the study period, suggesting higher continuation rates than have been observed in studies of real-world semaglutide use for obesity. When prescribing becomes more (or less) accessible, it doesn’t just affect cost but also who gets treated and for what indications. RWE is needed to understand how the real-worl

There is plenty of high-level guidance on real-world evidence (RWE) use in regulatory submissions, but sponsors are often left wondering how to put those recommendations into practice. What does it take to transform complex real-world data (RWD) into regulatory-ready RWE? What can be done to help regulators trust your evidence—and approve your submission? We developed a clear step-by-step framework for the preparation of RWD for regulatory submission based on an in-depth review and synthesis of current FDA guidance and regulator feedback to real-world submissions containing RWE. Key steps include: Want to learn more about preparing RWD for regulatory review? Connect with our team to explore how to apply our framework to your next submission, or explore our other RWE services.