From Novelty to Necessity: Real-World Evidence Is Redefining Healthcare Decisions

Zeba M. Khan, RPh, PhD, Editor-in-Chief, Value & Outcomes Spotlight

Real-world evidence (RWE) has earned a permanent seat at the healthcare decision-making table. What remains unsettled is how much authority comes with it.

A clear example (as highlighted in our feature article) comes from the regulatory approvals of Kymriah, a chimeric antigen receptor (CAR) T cell therapy cleared on the strength of single-arm trials with short follow-up. Rather than delay approval by years waiting for more mature data, Italy and Spain built patient registries after launch and used the resulting real-world findings to negotiate timed-payment and risk-sharing agreements with the manufacturer. It’s a clear example of RWE filling a gap that trials structurally cannot close. The question now is whether that kind of impact is becoming routine or remains the exception that proves how far the field still must go.

Regulators are aligning faster than payers are adapting. In December 2025, the US Food and Drug Administration (FDA) finalized guidance clarifying how real-world data can support medical device decisions, lowering some of the identifiability barriers that had discouraged sponsors from using large postmarket registries. In March 2026, FDA went further by adopting ICH M14, a set of principles for noninterventional studies developed jointly with the European Medicines Agency and Japan’s Pharmaceuticals and Medical Devices Agency; the initiative represented the first real harmonization of RWE methodology across major regulators. The European Union’s own HTA Regulation is scaling in parallel, with more than a dozen Joint Clinical Assessments underway in 2026, although researchers note that methodological guidance on how RWE should be used within those assessments is still underdeveloped.

Regulators are writing the rules of the game; payers are still hiring the referees. Providers sit in between, generating much of the electronic health record and claims data everyone else depends on, yet rarely consulted on what would make those data more usable downstream.

Payers are the laggards in this picture. A recent survey by the Academy of Managed Care Pharmacy (AMCP) Research Institute in the United States found that only about 18% of health plans and pharmacy benefit managers currently use RWE in formulary and coverage decisions, even though roughly 80% say they want to. The barrier isn’t appetite; it’s that most payer organizations lack the internal expertise to interpret and apply RWE with confidence.

Regulators are writing the rules of the game; payers are still hiring the referees. Providers sit in between, generating much of the electronic health record and claims data everyone else depends on, yet rarely consulted on what would make those data more usable downstream. It’s a missed opportunity, since data captured with reimbursement questions in mind from the outset tend to need far less cleanup later.

This is where HEOR can play a vital role, and the field is increasingly organizing around that need. ISPOR, the Duke-Margolis Institute for Health Policy, the International Society for Pharmacoepidemiology, and the National Pharmaceutical Council jointly run a Real-World Evidence Transparency Initiative that has produced a Harmonized Protocol Template to Enhance Reproducibility (HARPER) for hypothesis-testing studies and a public registry where researchers can preregister study designs before results are known—directly addressing the credibility problem that comes from studies designed after the fact to fit a preferred conclusion. AMCP has identified this type of standardization as an important way to address the barrier payers have described.

HEOR’s value, in other words, isn’t just running the analysis; it’s also building the shared infrastructure of trust—preregistration, harmonized reporting, transparent handling of confounding and missing data—that allows a payer or HTA reviewer who wasn’t in the room to still believe the results.

So, is RWE actually moving reimbursement and policy, or is it still supplementary? Both, depending on where you stand in the system.

HEOR’s value, in other words, isn’t just running the analysis; it’s also building the shared infrastructure of trust.

For high-cost, single-arm–approved therapies like cell and gene treatments, RWE has become close to indispensable, generating the postlaunch evidence that risk-sharing and outcomes-based contracts now depend on. For routine formulary and coverage decisions, the AMCP numbers are hard to argue around: at 18% actual use against 80% interest, RWE remains aspirational for most payers, not operational. What is changing is the direction of travel. Payers are signaling that the evidence bar is rising, that retrospective analyses without real-world relevance are losing influence, and that they specifically want RWE to underwrite utilization management criteria and outcomes-based contracts rather than sit alongside them as color commentary.

For health economists, regulators, payers, and providers, the honest read is that RWE has graduated from novelty to necessity for the hardest cases and remains a work in progress everywhere else. The path forward runs through the standards work already underway—harmonized regulatory principles, preregistered study designs, and payer-facing education—rather than through any single breakthrough dataset or method. RWE’s potential is no longer in question. Its consistency and transparency are.

As always, I welcome input from our readers. Please feel free to email me at zeba.m.khan@hotmail.com.

Zeba M. Khan, RPh, PhD
Editor-in-Chief, Value & Outcomes Spotlight