Clinical innovation has never moved faster. Tools like single-arm designs, novel surrogates, and adaptive trials promise efficiency and flexibility, yet for payers they create uncertainty. Contextual, real-world decision-making means payers must determine not only if a treatment provides benefit, but also how confidently that benefit can be measured, compared, and therefore priced.
Turning innovation into access, now more than ever, depends on aligning regulatory and payer evidence needs from the outset. These five design decisions can distinguish trials that only prove efficacy from those that can also deliver value and support access ambitions.
1. Choose your comparator wisely
Comparator choice remains one of the most decisive and most debated factors in HTA. A trial can be methodologically sound yet miss payer expectations when its comparator no longer aligns with current clinical practice. Given long trial timelines, sponsors must anticipate standard of care drift and evolving treatment sequences that can quickly erode relevance. Early scientific advice and cross-stakeholder input can help ensure payer expectations are met, especially given the high degree of heterogeneity observed across regions. In rapidly evolving therapeutic areas, adaptive or multi-arm designs may help maintain comparator relevance as standards of care change. However, payer confidence depends on clear clinical rationale and transparent statistical and sensitivity analyses. Ultimately, getting comparator alignment right protects both methodological integrity and price potential, ensuring added benefit is judged against the standard that truly matters to payers.
2. Capture payer-acceptable endpoint hierarchy
Endpoints drive the value narrative but not all endpoints “count” for HTA. While regulators assess efficacy and safety, payers look for evidence of demonstrable patient benefit translating to longer survival, improved function, quality of life, or reduced care burden. Endpoints that stop short of this, such as unvalidated surrogates, introduce uncertainty that can lower added-benefit ratings and slow reimbursement decisions (see our article Surrogates Under Scrutiny). Sponsors should validate surrogate–outcome links early, documenting clinical and statistical correlations and drawing on precedents accepted by HTA bodies. Endpoints must also connect directly to economic modelling, enabling credible QALY estimation and price justification. Alignment across stakeholders on what constitutes meaningful benefit, including patients and clinicians, ensures evidence resonates with HTA expectations. Exploratory or secondary endpoints add context but rarely drive value, as such anchoring studies around established payer-relevant, patient-centred outcomes remains essential to support robust value-based pricing decisions
3. Design for duration and manage cross-over effectively
Timing and treatment switching can make or break HTA credibility. Data maturity and whether key outcomes are fully observed at assessment directly affects payer confidence. Trials with immature overall survival in oncology, or short follow-up in chronic conditions can risk conditional reimbursement or conservative pricing decisions. Sponsors can consider event-triggered analyses and plan adequate follow-up to ensure evidence maturity and credibility at the time of HTA review. Similarly, crossover and treatment switching, while often ethically necessary, can distort comparative effectiveness. HTA bodies expect clear, pre-specified handling plans. Transparent sensitivity analyses, including the impact on cost-effectiveness, can also help to preserve trust. Early dialogue with HTA bodies allows sponsors to confirm that timing, switching rules, and adjustment methods meet payer expectations and support credible, evidence-based conclusions.
4. Account for your reimbursement population
Getting the study population right is critical for both regulatory clarity and payer relevance. Overly narrow inclusion criteria or trial cohorts that diverge from everyday treatment settings can limit generalisability and restrict reimbursement scope. Early alignment with regulators and HTA bodies on target population, disease severity, and treatment history or concomitant therapy assumptions helps ensure evidence remains translatable and payer-relevant. While defining the overall study population is essential, credible subgroup analyses can further strengthen value, but only if prospectively defined, biologically or clinically justified, and adequately powered. Post-hoc findings rarely influence added-benefit ratings or price negotiations. Designing trials with clear estimands, stratification, and pre-specified subgroup hypotheses allows sponsors to show that the treatment works, but also for whom it delivers the greatest value.
5. Plan your total evidence package
Even the best-designed trial will not answer every question payers will ask. Increasingly, payer-ready development means thinking beyond the pivotal study and integrating supplementary evidence to bridge the inevitable gaps in comparators, maturity, or generalisability. Sponsors should identify early which uncertainties will remain at submission and design a lifecycle evidence plan to address them. Real-world evidence can contextualise outcomes, validate external controls, or confirm benefit in broader populations. Post-launch registries and observational extensions can capture long-term survival, quality of life, or resource-use data to feed reassessments. Transparent modelling of uncertainty in cost-effectiveness and value frameworks supports credibility even where data are incomplete. Ultimately, payer confidence comes not from eliminating uncertainty, but from demonstrating foresight, showing how evidence will evolve to confirm value over time. Building that package from day one ensures the evidence tells a complete and credible access story.
Designing payer-ready trials isn’t about perfection, but anticipation, it’s about shaping evidence to meet payer requirements before they become obstacles. Each design decision determines how convincingly a treatment’s value can be demonstrated in real-world reimbursement settings. Success depends on planning for payer needs as deliberately as for regulatory ones. Sponsors that embed payer thinking early will accelerate access and also protect long-term value. In today’s environment, it’s not enough to prove a medicine works, you must show it delivers benefit in a real-world context.
Designing studies, planning for HTA, or needing support with mitigation mid-process? Remap partners with companies to provide evidence generation and HTA strategy expertise. Get in touch with us.