Approval is not access: five questions payers will ask

Your pivotal trial delivers. The regulator approves the medicine. The company celebrates. And rightly so. This is a huge achievement and several years, if not decades, in the making.

Then a payer asks a different question.

Why should we fund this treatment instead of what we already provide?

Regulatory approval and reimbursement are different decisions. The regulator assesses whether the benefits of a medicine outweigh its risks. Payers need to decide whether it improves on current care, whether the benefit justifies the cost and whether the health system can afford to provide it.[1-4]

Here, payer means the organisation that decides whether a health system or insurance plan will fund a treatment. In England, the payer is the NHS, with NICE assessing whether many new medicines should be recommended for NHS use. Other countries use different combinations of HTA bodies, public commissioners, formulary committees and price negotiation bodies. The exact process differs. The underlying questions recur.

The difference can begin with trial design. In an analysis of 31 parallel regulatory and HTA advice procedures, full agreement was lowest for the comparator, at 44%.[5]

Comparator choice matters. But it is only one sign of a wider problem. A development programme built for approval can leave unanswered questions about patient benefit, the treatment pathway, value for money and affordability.

We have written before that regulators, HTA bodies, payers and clinicians ask different questions. Here are the five payer questions that clinical development and medical affairs teams cannot afford to leave until launch.

Approval can still end without routine reimbursement

Aducanumab received accelerated approval from the US Food and Drug Administration based on its effect on amyloid plaque. In 2022, the Centers for Medicare & Medicaid Services limited Medicare coverage to people enrolled in qualifying randomised trials while clinical benefit remained uncertain.[6]

Sipuleucel-T received marketing authorisation for metastatic prostate cancer and improved overall survival compared with placebo. NICE did not recommend it for use in the NHS because its cost effectiveness was substantially above the range normally considered acceptable.[7]

Zynteglo received European marketing authorisation for transfusion-dependent beta-thalassaemia in 2019. Bluebird withdrew it from Germany in 2021 after reimbursement negotiations did not produce a price that the company considered to reflect its value.[8,9]

These were different routes from approval to restricted or absent routine access. Uncertain patient benefit. Poor cost effectiveness. A failed price negotiation.

Together, these are three examples of many that show why approval is not access.

1. Have you compared it with what patients actually receive?

A regulator may accept a placebo-controlled trial. A payer usually needs to understand what changes when the new treatment replaces care that is already being funded.

That makes the relevant comparator the treatment patients currently receive in the proposed reimbursed population. It may differ between countries, between lines of therapy and between patient subgroups.[2-4]

The pivotal trial may answer this directly. If it does not, a robust indirect treatment comparison or external control may sometimes bridge the gap. The important point is not that every programme needs another head-to-head trial. It is that the payer’s comparison must be anticipated while the evidence can still be shaped.

We cover the available methods in our field guide to indirect treatment comparisons and our insight on external control arms.

For this insight, the lesson is simpler. Approval shows that a treatment works well enough to be marketed. It does not necessarily show that it works better than what the payer already buys.

2. Does it improve outcomes that matter to patients?

Payers want to know whether patients feel better, function better or live longer.[10]

In oncology, overall survival may be critical. In other settings, the most important benefit may be fewer symptoms, better physical function, improved quality of life, fewer serious events or less burdensome treatment.

The question is not simply whether an endpoint changed. It is whether the change matters in patients’ everyday lives.

This is where a surrogate can become a problem. A surrogate is an earlier biological or clinical measure used to predict a later patient benefit. Tumour response, progression-free survival, amyloid plaque and a laboratory measurement may all be valuable. But they are not automatically evidence that patients live longer or live better.[1,10]

Aducanumab is a clear example. Reduction in amyloid plaque supported accelerated regulatory approval. CMS still wanted evidence that treatment improved health outcomes before permitting broader Medicare coverage.[6]

NHS England’s specialised commissioning process includes a patient impact assessment alongside the clinical evidence. Its decision process considers measurable benefit to the relevant patients, not simply a positive result on a trial endpoint.[2,11]

That evidence might come from survival, symptoms, physical function, health related quality of life, adherence, adverse effects or time to resume usual activities. Which outcomes matter will depend on the condition, treatment and decision.

The answer is not to measure everything. As we argued in Beyond endpoints, every outcome should have a clear route into the decision.

3. Where does it fit, and what must change to deliver it?

A medicine does not enter an empty health system. It enters an existing pathway.

The payer therefore needs to understand what happens before, during and after treatment. Who identifies eligible patients? Is a new diagnostic test required? Who prescribes and administers the treatment? Where does monitoring happen? What happens after response, progression or an adverse event?

The proposed pathway should be compared with the current one. That reveals what the treatment replaces, what it adds and which costs or services move elsewhere.[3,4]

Some changes are easy to overlook during clinical development:

A new diagnostic or biomarker test.
Additional imaging or laboratory monitoring.
Infusion capacity or an inpatient stay.
Specialist centres, equipment or storage.
Training for clinicians, pharmacists or nurses.
Travel and time costs for patients and carers.
Changes to later treatments or supportive care.

These are not operational details to resolve after reimbursement. They affect the treatment’s costs, uptake, feasibility and equality of access.

An effective medicine that cannot be delivered to the eligible population is not a complete payer proposition.

4. Does it provide value for money?

Clinical benefit and value are related. They are not the same.

Cost effectiveness asks what additional health the treatment provides and what the health system must give up to obtain it. The analysis brings together comparative outcomes, quality of life, treatment costs, other healthcare use and the duration of benefit.[2-4]

The assumptions matter. How long does the treatment effect last? What happens after the trial ends? Which treatment is displaced? Are later costs avoided or simply delayed? How uncertain are the survival and quality of life estimates?

Sipuleucel-T shows why survival evidence alone is not enough. Trials supported an overall survival benefit compared with placebo. In the Evidence Review Group’s preferred analysis, its incremental cost effectiveness was £108,585 per quality adjusted life year compared with best supportive care in the licensed population. NICE concluded that it was well above the range normally considered cost effective and did not recommend the treatment.[7]

The payer was not asking whether sipuleucel-T had a biological effect. It was asking whether its additional benefit justified its additional cost compared with the available alternatives.

5. How many patients need it, and can the system afford it?

A treatment can be cost effective and still be difficult to afford.

Budget impact asks what will happen to spending when the treatment is used in practice. It begins with the number of patients, but prevalence alone is not enough.[12]

The payer needs to know:

How many patients meet the proposed reimbursement criteria?
Is there an existing group who may become eligible immediately?
How quickly will clinicians adopt the treatment?
How long will patients remain on it?
Which treatments and services will it replace?
What will administration, monitoring and adverse events cost?
Will savings arise elsewhere in the pathway, and when?

These inputs should describe the payer’s population and health system. A global prevalence estimate, list price and optimistic market share assumption will not do that.

NHS England models the financial effect of moving from the current pathway to the proposed pathway over five years. Its analysis includes total budget impact, net cost per treated patient and uncertainty in the assumptions.[11]

Zynteglo shows the commercial consequence when value and price cannot be reconciled. The medicine received European approval, but Bluebird withdrew it from Germany after reimbursement negotiations failed to produce an acceptable price.[8,9]

The clinical evidence had reached the regulator. The commercial proposition had not reached agreement with the payer.

Health inequalities run through all five questions

Health inequality is not an optional paragraph at the back of the dossier.

The trial population may not represent the people who will be eligible in practice. Outcomes may differ across relevant groups. A diagnostic requirement, specialist centre or complex administration schedule may make access harder for some patients. The proposed pathway may reduce an existing inequality or make it worse.[2-4]

Ask who can reach the treatment, not only who meets its clinical criteria.

This can also change the budget and implementation assumptions. If equitable access requires additional centres, transport support, workforce or diagnostic capacity, those requirements belong in the plan.

Five questions do not mean five new studies

The answer is not to add a separate study for every payer concern.

It is to define the decisions early and work backwards to the minimum evidence needed. One well-designed trial may provide comparative outcomes, quality of life and resource use. One registry may estimate eligible patients, uptake, longer-term outcomes and treatment duration. One systematic review may support the comparator landscape, an indirect comparison and the economic model.

This is the logic of an integrated evidence plan. Start with the questions that regulators, payers, HTA bodies and clinicians will ask. Identify the gaps that could change their decisions. Then design the smallest set of evidence activities that can close them.

At Evidax, we bring the internal evidence and published landscape together, map each gap to a decision-maker and build a practical plan to close the gaps that matter.

Approval is a milestone. Access needs its own evidence.

Take home

Regulatory approval and reimbursement are different decisions.
Compare the treatment with what eligible patients currently receive.
Measure whether patients feel better, function better or live longer. Do not assume a surrogate answers that question.
Show where the treatment fits and what the health system must change to deliver it.
Demonstrate value for money and budget impact separately.
Estimate eligible patients, uptake, treatment duration and resource use for the payer’s setting.
Consider health inequalities across the whole evidence package.
Build the minimum payer evidence into development before the questions arrive.

Find your evidence gaps with our free survey

References

Bognar K, Romley JA, Bae JP, et al. The role of imperfect surrogate endpoint information in drug approval and reimbursement decisions. Journal of Health Economics. 2017;51:1-12. https://doi.org/10.1016/j.jhealeco.2016.12.001
NHS England. Specialised commissioning service development policy. Published 18 May 2026. https://www.england.nhs.uk/long-read/nhs-england-specialised-commissioning-service-development-policy/
Academy of Managed Care Pharmacy. AMCP Format for Formulary Submissions 5.0. Journal of Managed Care & Specialty Pharmacy. 2024;30(4-b Suppl):1-64. https://doi.org/10.18553/jmcp.2024.30.4-b.s1
Australian Government Department of Health. Guidelines for preparing a submission to the Pharmaceutical Benefits Advisory Committee. Version 5.0. September 2016. https://pbac.pbs.gov.au/content/information/files/pbac-guidelines-version-5.pdf
Tafuri G, Pagnini M, Moseley J, et al. How aligned are the perspectives of EU regulators and HTA bodies? A comparative analysis of regulatory-HTA parallel scientific advice. British Journal of Clinical Pharmacology. 2016;82(4):965-973. https://doi.org/10.1111/bcp.13023
Centers for Medicare & Medicaid Services. CMS finalizes Medicare coverage policy for monoclonal antibodies directed against amyloid for the treatment of Alzheimer’s disease. 7 April 2022. https://www.cms.gov/newsroom/press-releases/cms-finalizes-medicare-coverage-policy-monoclonal-antibodies-directed-against-amyloid-treatment
Simpson EL, Davis S, Thokala P, et al. Sipuleucel-T for the treatment of metastatic hormone-relapsed prostate cancer: a NICE single technology appraisal; an Evidence Review Group perspective. PharmacoEconomics. 2015;33(11):1187-1194. https://doi.org/10.1007/s40273-015-0296-5
European Medicines Agency. Zynteglo: EPAR. https://www.ema.europa.eu/en/medicines/human/EPAR/zynteglo
bluebird bio. bluebird bio Reports First Quarter Financial Results and Highlights Operational Progress. 5 May 2021. https://www.businesswire.com/news/home/20210505006054/en/bluebird-bio-Reports-First-Quarter-Financial-Results-and-Highlights-Operational-Progress
Toumi M, Jarosławski S, Sawada T, Kornfeld Å. The use of surrogate and patient-relevant endpoints in outcomes-based market access agreements: current debate. Applied Health Economics and Health Policy. 2017;15(1):5-11. https://doi.org/10.1007/s40258-016-0274-x
NHS England. Methods: national clinical policies. Published 18 May 2026. https://www.england.nhs.uk/long-read/methods-national-clinical-policies/
Sullivan SD, Mauskopf JA, Augustovski F, et al. Budget impact analysis: principles of good practice. Report of the ISPOR 2012 Budget Impact Analysis Good Practice II Task Force. Value in Health. 2014;17(1):5-14. https://doi.org/10.1016/j.jval.2013.08.2291