The Shape of Current Thought on Real-World Evidence and Its Use in HEOR and Healthcare Decisions
Rob Abbott, Chief Executive Officer, ISPOR
One of the most consequential developments in the recent history of health economics and outcomes research (HEOR) is the onset—and rapid acceleration—of real-world evidence (RWE) as a key element of value assessment. RWE bridges the gap between randomized clinical trials (RCTs) and everyday clinical practice. This has important implications for HEOR and healthcare decisions because RWE can provide insights into how medical interventions perform across diverse populations. This, in turn, can guide pricing, regulatory choices, and value-based care strategies. With this in mind, I’m proud to support this issue of Value and Outcomes Spotlight (VOS), which focuses squarely on the shape of current thought (and practice) in RWE. Has the hype been met by actual performance, and if not, where do we go from here?
From its origins in the late 1990s and early 2000s when studies using administrative claims and registry data first appeared, RWE has gathered considerable support. The reasons are many, but perhaps the most significant is the ability to compare (narrow) clinical trial data with actual patient outcomes across a diverse demographic range for a variety of clinical settings. This real-world context goes a long way toward proving the economic worth and comparative effectiveness of drugs and devices to health systems and payers. As a result, agencies such as the US Food and Drug Administration (FDA) use RWE to support label expansions and to monitor postmarket safety, and payers now use real-world data to determine drug reimbursement, pricing models, and formulary placement.
So far, so good. But is RWE mature enough to be—and be seen as—a central input in healthcare decisions? As the papers gathered here make clear, RWE can be a complementary input for healthcare decisions such as postmarket safety monitoring, labeling expansions, and health technology assessments (HTA), but it still faces methodological hurdles that prevent it from fully replacing RCTs as the gold standard.
These hurdles are threefold:
- Observational data often lack randomization, leaving analyses vulnerable to unmeasured patient confounders and missing information.
- Disparate electronic health records and claims data lack universal standardization and uniform quality control.
- Global regulatory and HTA expectations differ among nations, which can create regulatory uncertainty for cross-border submissions.
Against the backdrop I’ve described, it’s useful to consider the current state of alignment among regulators, payers, and HTA bodies in adopting RWE. This is a question that is of particular interest to ISPOR. I would suggest that these agents show growing support for RWE, but operational and methodological fragmentation persists. While regulators like the FDA focus on safety and efficacy for market authorization, HTA bodies and payers require local comparative effectiveness and cost-value data, leading to differing evidentiary thresholds. Put another way, regulators primarily review products for binary approval, whereas HTA bodies and payers evaluate relative value, pricing, and local population generalizability. At the same time, payers and HTA bodies often demand higher standards for causal inference and comparative effectiveness than what may satisfy regulatory safety needs. Finally, global or multicountry RWE data that is acceptable to a central regulator often faces strict local scrutiny or rejection by national or regional payers requiring context-specific data.
HEOR provides the scientific methods, data validation, and analytical frameworks needed to transform raw real-world evidence into trusted, bias-free insights for decision makers.
Our field of HEOR has played—and continues to play—a pivotal role in enhancing the credibility of RWE. We provide the scientific methods, data validation, and analytical frameworks needed to transform raw RWE into trusted, bias-free insights for decision makers. This is something that ISPOR has taken on in a very meaningful way, most recently by spearheading the Real-World Evidence Transparency Initiative alongside the International Society for Pharmacoepidemiology (ISPE) and the Duke-Margolis Center for Health Policy. This effort established ISPOR guidance and a free public protocol registry to prespecify observational study methods, which regulatory bodies like the FDA and the Centers for Medicaid and Medicare Services (CMS) now widely reference for assurances of credibility. Other important actions that bolster understanding, awareness, and use of RWE include our joint task forces with ISPE (and others) to issue methodological and procedural standards for RWE and our recommendations to improve study replicability, hypothesis evaluation, and appropriate data hierarchies for healthcare coverage decisions.
These developments, and those described in this issue of VOS, suggest that RWE should be seen as being in a transitional space. It is undeniably shaping health policy frameworks and managed entry agreements, yet HTA bodies and payers still consider it complementary to RCTs rather than a standalone replacement. This isn’t necessarily a bad thing; it could simply reflect the evolutionary arc of most new ideas and the need to address the pain points that inevitably arise as the “new thing” competes with the incumbent.
Moving forward, ISPOR will continue advancing into the RWE frontier and addressing the methodological concerns and infrastructure deficits that thwart wider adoption. I want payers, for example, to see that we are addressing vulnerabilities to bias, unstandardized endpoints, and confounding variables in observational data. Equally, I want to use the resources of ISPOR, particularly our global network of regional chapters, to help address the lack of internal frameworks, standardized data provenance guidelines, and analytical expertise needed at a local level across the world to appraise observational designs.
Moving RWE from novel concept to a central pillar of healthcare decision making is a journey, and we should celebrate the success and progress that has been achieved over the past 2 decades while acknowledging what is needed to move from validating or contextualizing trial outcomes to justifying an initial formulary listing in its own right. I want VOS readers to know I am committed to leading ISPOR’s RWE work toward this future state.
