A guide to what RWE is, when to plan it, and what payers need from it.
Using Real-World Evidence to Earn and Keep Access
A guide to what RWE is, when to plan it, and what payers need from it
Real-world evidence shows how a disease and its treatments behave in routine care, outside the controlled conditions of a clinical trial.
Trials show whether a therapy works. Payers and HTA bodies also want to know who the patients in their population are, how the disease is managed today, and what the therapy will deliver and cost in practice. RWE helps answer those questions. Its value depends as much on when it is planned as on how well it is done.
RWE planning belongs in clinical development, not after approval.
Landscape RWE describes the disease and can start before launch. Product RWE describes the therapy and starts after.
Plan evidence backward from the access decisions it needs to inform.
Payers judge RWE on relevance to their population, fitness of the data, sound methods, and clearly stated limitations.
Health and care data collected outside a clinical trial: electronic health records, medical claims, disease registries, and patient-generated data from digital devices.
The clinical evidence produced by analyzing real-world data to answer a specific question.
The same dataset can produce very different evidence depending on the question, the study design, and the methods.
Randomized controlled trials remain the gold standard for showing that a therapy is safe and effective. RWE complements them. It does not usually replace them.
Trial populations often don't look like a payer's members. Payers want to know how a therapy performs, and what it costs, in the patients they actually cover.
RWE is not one activity. The most useful planning distinction is between evidence about the disease and evidence about the therapy. They need different data, study designs, and timelines.
Phase 2 through launch preparation
From first commercial sale onward
Describe the disease, the care pathway, and the patients the therapy will reach
Measure how the therapy performs in routine practice
What is the real-world burden? Who is diagnosed and treated, and who is not? Where does care fall short?
Who is using it? How long do patients stay on it? How does it compare with current care?
Endpoint choices, positioning, HTA preparation, early payer conversations
Formulary reviews, HTA updates, contracting, label expansion
Product RWE can't be generated before launch. The infrastructure for it can: data partnerships, registry design, and outcome definitions. Teams that build it early can start measuring on day one.
The AMCP RWE standards describe four stages where RWE can inform US payer decisions. Each lines up with a version of the AMCP dossier.
Epidemiology and natural history, treatment patterns, outcomes under current care, total cost of care
External control arms, indirect comparisons, compassionate-use outcomes, economic models
Real-world safety and effectiveness, adherence and persistence, long-term extension studies
Evidence from off-label use, external comparators, subgroup analyses
RWE establishes the baseline: the burden of disease, who the patients are, and where current care falls short. Every later value claim is measured against it.
RWE keeps the case current. It supports formulary and HTA reviews, contracting, and label expansion into populations the pivotal trials did not cover well.
Companies that define the disease baseline with their own evidence shape the comparison. Those that don't leave it to older literature or to competitors.
Coverage decisions tend to come down to five questions. Trials mainly answer the third. RWE contributes to all five.
Epidemiology and burden of illness in the payer's covered population, not the trial's
Treatment patterns, outcomes, and adherence under existing therapies
Real-world effectiveness, including patients the trials underrepresented
Real utilization, resource use, discontinuation, and total cost of care
Real-world inputs that reduce uncertainty in economic models
In an AMCP survey of 36 US payers, 80% were interested in using RWE, but only 18% used it regularly. The largest barrier was limited experience interpreting it. Payers valued comparative real-world safety and effectiveness most.
Source: Lockhart CM et al. AMCP real-world evidence standards. J Manag Care Spec Pharm. 2025;31(12):1230-1236.
Reviewers now have clear standards for RWE. A weak submission can hurt credibility more than no submission at all.
The data source, population, outcomes, and follow-up match the decision the evidence is meant to inform.
The protocol and analysis plan are finalized before anyone looks at the results.
The study names likely sources of bias, such as sicker patients getting the newer drug, and designs around them.
Methods, data sources, definitions, and limitations are fully documented.
The evidence reaches the decision-maker while the review is underway, not after.
AMCP's RWE standards include 29 payer criteria in six categories: study questions, data source, outcomes, analytics, results, and limitations. Manufacturers can use the checklist as a cover sheet when sharing studies with payers.
Rigorous evidence that arrives after a formulary vote has little access value.
Most RWE programs are planned forward from when a study can start. Backward planning starts from the access decisions that matter, such as HTA submissions, formulary reviews, and contract renewals, and works back to the latest date each study can begin.
Identify the access decision and when it happens.
Define the evidence the decision-maker will need.
Work out the last date the study can start and still be ready.
This exercise usually shows the window is earlier than teams expect, especially for studies that need data partnerships, registries, or long follow-up.
HEOR, market access, medical, and commercial teams should work from one plan. Each study should link to a named decision and a named audience, with one owner accountable for the whole.
A review of FDA supplemental approvals from January 2022 to May 2024 found that 55 of 218 label expansions (25.2%) included or likely included RWE.
EHR and claims data helped support FDA approval for men with HR-positive, HER2-negative advanced breast cancer, a population too small for a practical randomized trial.
An established RWE program also helps when something unexpected happens, such as a suspected class-wide safety issue. Companies with data already flowing can respond with evidence quickly. Companies without it have little to offer while restrictions are considered.
In each case, the evidence was useful because the infrastructure existed before anyone asked for it.
Sources: Cohen J, Felix A. Clin Pharmacol Ther. 2024. FDA Approval Summary: Palbociclib for Male Patients with Metastatic Breast Cancer. Clin Cancer Res. 2020;26(6):1208.
Usually not. RWE most often complements trials by answering questions they can't. The main exception is external control arms in rare disease and oncology, where randomization isn't feasible. Their credibility depends on whether the external patients are truly comparable to the treated ones.
Think of RWE as filling the gaps a trial leaves, not as a
shortcut around it.
Landscape RWE: disease burden, epidemiology, treatment patterns, care gaps, and patient experience. It uses existing data and doesn't depend on approval. You can also build what product RWE will need: data partnerships, registries, and outcome definitions.
Pre-launch RWE often gets the least investment and provides
the foundation for everything after.
Increasingly, but not yet routinely. Most payers see value in it, and few use it regularly, largely because they lack standards for judging it. The AMCP RWE standards were created to close that gap. Evidence designed and reported to those standards is easier for payers to assess and use.
Make your evidence easy to evaluate, and it is more likely to be used.
RWE works best as a shared plan rather than one function's project. HEOR, market access, medical affairs, and commercial teams should all contribute. One person should be accountable for keeping the portfolio coherent, so studies don't duplicate or contradict each other.
Evidence that is individually sound and collectively misaligned is a common and costly failure.
At Alkemi, we help biotechnology and pharmaceutical companies build RWE programs that inform real access decisions. We map evidence needs back from HTA, formulary, and contracting milestones, design studies that meet payer and HTA standards, and set up the infrastructure before it is needed.
If you're in Phase 2 or planning Phase 3 and want to know what RWE you should be generating now, let's talk.
