Real-World Evidence Use in Payer-Facing Drug Promotional Materials

Drug coverage choices present a paradox around real-world evidence: payers claim to desire it, yet almost none integrate it routinely into their determinations. A 2025 AMCP standards study quantified that gap. Survey respondents overwhelmingly expressed a desire to use RWE when making coverage choices, yet few applied it consistently, a pattern that persisted among those who explicitly affirmed its worth. Willingness poses no barrier. The real obstacles involve availability and expertise: decision-makers frequently lacked awareness of existing RWE for specific drugs, needed to contact manufacturers directly to obtain it, and possessed considerably less experience appraising observational research compared with randomized controlled trials.

In 2025, researchers writing in the International Journal of Technology Assessment, Health Care identified the main barrier as methodological credibility concerns and no common rules for RWE collection, analysis, and reporting, not weak payer demand. Randomized trials are still the standard payers fall back on trusting, so real-world evidence comes in as supplementary material that must prove it belongs next to that baseline. Three built-in pressures make that evidentiary hurdle hard to clear. Payers often decide on coverage only once seven to eleven post-approval years have passed, when sponsors are unlikely to run more trials. Payers actually cover patients who are more elderly and ill than standard study participants, the same people clinical trials exclude. Before now, payers lacked any evaluation framework designed around their own requirements. None of those three issues will fix themselves. Any drugmaker pursuing formulary success must now close that longstanding, well-documented divide.

IRA price negotiations and the demand for comparative RWE

By passing the Inflation Reduction Act, lawmakers transformed that gap from an overlooked opportunity into genuine financial exposure. Since comparative real-world evidence directly shapes how Medicare negotiates drug prices, manufacturers without solid RWE backing shoulder that risk. The 2022 IRA empowered CMS to negotiate directly with manufacturers on prices for Part B and Part D drugs, mandating that the agency weigh a therapy's clinical performance against comparable treatments when establishing the maximum fair price. The agency plans to examine published studies and real-world data during those talks to identify comparable therapies and determine a drug's place within the wider treatment landscape.

In the Journal of Comparative Effectiveness Research, a scoping review examined CMS's initial negotiation list, concluding that their comparative RWE base was lopsided: only a few products generated most of the comparative-study record, whereas many others offered little such evidence in Medicare populations. CMS and manufacturers should build strong head-to-head RWE for Medicare patients well ahead of negotiation, instead of racing to pull it together at the last minute, because the warning applies prospectively. When manufacturers wait until negotiation is imminent, the 2023 review's evidence gap shows the cost of mistaking that deadline for a research timetable.

The regulatory framework that now governs what manufacturers can share

Since 2023, the rules on what a manufacturer can legally say to a payer have shifted substantially, and any company still counting on the FDA to look the other way is misjudging both its latitude and its risk. The FDA's real-world evidence guidance still serves as the foundational document, released to fulfill 21st Century Cures Act requirements. It demands openness, sound data handling, protocols posted publicly, FDA access to the raw data, and early talks with the agency.

Where communications aimed at payers are concerned, the recent shift with greater consequence is FDA's draft guidance titled "Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities, Questions and Answers," which the Federal Register carried on June 3, 2026. It folds in statutory changes adopted via the PIE Act (Pre-Approval Information Exchange), which appears at Section 3630 within the 2023 Consolidated Appropriations Act. In King & Spalding's reading, the draft guidance's pivotal move is that the FD&C Act, at section 502(gg), now supplies a statutory safe harbor covering communications about products still under investigation and uses not yet approved, turning what had rested on FDA's forbearance into a standard written into law. That difference matters to firms mapping payer engagement before approval: the rules on what may be said are codified rather than read off agency conduct, and anyone crossing them faces a settled legal benchmark instead of a mutable policy preference.

FDA's January 7, 2025 directive concerning scientific details about unapproved applications, designed for health care providers instead of payers, runs parallel to, rather than at the heart of, this narrative. That guidance established its own tightly bounded safe harbors while overlapping with stepped-up FDA scrutiny from late 2025 into 2026, evidence that regulators are closely monitoring the boundary between permissible information sharing and improper marketing in all regulated channels. A third, distinct event underscores the overall trend: December 2025 brought revised FDA guidance easing a major hurdle for medical device RWE submissions, since patient-level information that can be traced back to individuals is no longer universally required, with the agency hinting that pharmaceuticals and biologic products could eventually receive identical treatment. As a whole, these three shifts point to a landscape giving manufacturers greater latitude to present real-world evidence to payers sooner in a product's lifecycle than three years prior, alongside clearer, more codified penalties for overstepping legal limits.

Regulatory clearance versus payer persuasion

Satisfying FDA's evidentiary threshold for RWE still does not mean a payer will be convinced by that same evidence. Payers use their own criteria, mostly not written down until recently, and existing rulemaking and methods advice was not made to answer them. Most RWE publications have emphasized strong study planning and execution, or proper presentation of results for journals, while overlooking the payer-specific issues that drive access, placement, and payment decisions. Even a study that satisfies journal-level methods review may leave a payer unmoved, since payers are less accustomed to assessing observational evidence alongside trial evidence, and no consensus defines which endpoints should guide its use in coverage. The gap is partly about literacy and partly about framing, and those are separate problems that need separate fixes.

During an October 2025 Harvard Medical School session, FDA, NICE, ICER, TLV, ZIN, PMDA, plus BfArM sent delegates to expressly discuss this inconsistency. Their conclusion was that each organization applies its own internal validity criteria to identical RWE submissions, meaning evidence tailored for one authority might be rejected by another entirely unrelated body. Certain drugmakers assume that securing publication in a refereed journal resolves questions about payer trustworthiness. While journal acceptance shows methodological transparency, broad scientific periodicals never evaluate if an investigation's architecture, reference arm, outcome measures, or cohort criteria actually match a given reimbursement body's needs. Satisfying regulators and convincing payers demand distinct things, so firms treating them as one will continue generating data that passes a single checkpoint yet fails the next.

What the AMCP RWE standards require from manufacturers

AMCP released its RWE standards during September 2025, providing that concrete answer. Drugmakers now hold a checklist crafted by payers, functioning as the benchmark for evaluating their submissions. IQVIA collaborated with the AMCP Research Institute to build these guidelines, gathering input from payers, drugmakers, and real-world evidence specialists via questionnaires, discussion sessions, plus a Partnership Forum hosted by AMCP.

The standards rest on two components. The first is a lifecycle framework that maps which types of RWE studies and which endpoints make sense at each stage of a product's life, from before approval through the years after launch, matching study design to the decision a payer is actually facing at that moment. The second is a 29-criteria checklist organized into six domains, built specifically for how payers assess real-world evidence rather than for general methodological review, and it extends past questions of rigor into whether a study's population resembles the payer's own membership, whether its findings generalize, and whether its results are actually interpretable for a coverage decision.

Its lifecycle element has strategic importance apart from how it is engineered. It encourages manufacturers to start building payer-relevant evidence before launch, an early orientation that aligns squarely with the new PIE Act statutory safe harbor for communications about investigational products. When a company designs its RWE effort with the 29 criteria in mind from the outset, before study planning begins, rather than reshaping completed work to match a checklist later, payers are more likely to view the evidence as trustworthy than to scrutinize it with doubt. The framework also tackles the main concern about industry-backed evidence: sponsors may shape RWE design in ways that favor positive findings, so the standards require open reporting and advance method commitments to limit that effect and make any remaining bias apparent to those reviewing the study.

The Eliquis evidence program as a model for meeting that standard

Eliquis's RWE program demonstrates the AMCP standard working in practice rather than being described on paper. Credibility with payers begins when the data inputs and outcomes reflect the same membership and decision setting the payer itself confronts. Bristol Myers Squibb and Pfizer designed apixaban's real-world evidence in nonvalvular atrial fibrillation around claims data whose enrollees skewed substantially older, sicker, and more comorbid than the trial cohort, a gap that resonated with payers underwriting the very same population. The bleeding analysis anchored on warfarin as comparator and on bleeding as endpoint, both picked because they resonated with formulary committees rather than merely with regulators, and that lens drove the coverage choices insurers and Medicare went on to make.

The payoff shows up in the IRA price-setting figures covered earlier. According to the scoping review, apixaban possessed an exceptionally robust body of head-to-head real-world evidence relative to other drugs in that initial IRA round, representing an outsized portion of every such study located and proving the long-term worth of its research strategy beyond market entry. That result was not luck when negotiation arrived. Years of deliberate research design drove that outcome, choosing reference treatments and clinical measures with payer needs in mind from day one, whereas the other negotiated drugs saw comparative RWE remain sparse since it was never planned, only tacked on later.

Where current manufacturer practice still falls short

Frameworks keep improving, yet the RWE programs most manufacturers run continue to stumble with payers for the same few foreseeable, correctable reasons: the population studied bears little resemblance to the people a payer covers, the design tilts in the sponsor's favor, and what gets communicated describes the findings rather than addressing the question a payer actually posed. Of the three, population mismatch happens most often. Research carried out among the commercially insured, or defined so loosely that no single payer recognizes its own members in it, leaves a Medicare payer's question unaddressed; per the scoping review, comparative RWE studies on the first IRA-negotiated drug cohort that drew on Medicare data amounted to just 32.4%. No matter how sound its design may be otherwise, research grounded in the wrong population responds to a question no one ever posed.

A second, related failure stems from comparator selection. A trial built around a placebo, or a rival the payer dropped from its formulary long ago, says nothing about the coverage decision that payer faces now, since the right benchmark is the set of therapies under active consideration today rather than those relevant when the study was first designed. A third failure stems from endpoint selection. Endpoints picked to please a journal, such as mortality and hospitalization, frequently miss the utilization and cost measures that drive a payer's formulary tier decisions, so a manufacturer focused solely on publication will keep generating evidence that wins over reviewers but fails to move payers. Eliquis succeeded because its program was designed around what payers needed to know from the outset. With the AMCP checklist's current standard and the legal flexibility provided by the recent draft guidance from 2026, manufacturers can now intentionally develop such programs instead of learning too late that their evidence fails to address the actual question.