In part 4 of our series, we examined the systems-level work of navigating cell and gene therapy (CGT) reimbursement: easing the burden on authorized treatment centers (ATCs), addressing durability skepticism, and reconciling one-time therapies with infrastructure built for chronic medicines. A common thread was the need for evidence to sustain payer confidence well beyond approval. Here we turn to the broader evidence agenda and why it is foundational to commercial success.

Many manufacturers still treat evidence generation as a regulatory exercise that ends at approval. For CGTs, that mindset is a liability. Approval is just the beginning, and companies that recognize this early are far better positioned to defend pricing, expand access, and grow stakeholder confidence over time.

Building the Evidence Package That Payers Actually Need

Pivotal trial data alone rarely supports a robust CGT value story. Trials are typically small, single-arm, and limited in follow-up duration. They show efficacy in a controlled setting but leave open the questions payers and providers care most about:

  • How does the therapy perform in real-world populations?
  • How long does the benefit last?
  • What’s the true treatment burden across the full patient journey?
  • How does the therapy compare economically to the alternatives?

Answering them requires a deliberate evidence strategy that begins well before launch:

  • Demonstrating unmet need (natural history or burden-of-illness studies)
  • Characterizing treatment burden for patients and the system
  • Collecting long-term safety data
  • Consistently accumulating evidence on durability of response

Each feeds payer dossiers, health technology assessment (HTA) submissions, and the narrative justifying a one-time, high-cost intervention. These needs also differ by geography: US payers reward real-world durability and budget impact. Ex-US, a formal HTA gate demands relative effectiveness versus the local standard of care, further sharpened since January 2025 by the EU’s Joint Clinical Assessment, which requires a single dossier to answer “compared to what?” across many member states at once. A single-arm trial built only for the FDA can therefore clear US payers yet stall in Europe, so comparator and endpoint strategy should be designed for both worlds before the pivotal trial locks.

Cost-effectiveness and budget-impact models are critical. They must be ready at launch and refined as real-world data accumulate since models built on assumptions alone lose credibility fast. Manufacturers that update and share them signal a confidence and transparency that can shift access conversations.

Value-Based Contracts: Sensible in Theory, Complicated in Practice

As we noted previously, value-based contracts (VBCs) are an increasingly common topic in CGT access discussions, for understandable reasons. Tying payment to demonstrated outcomes helps payers manage the financial uncertainty of one-time, high-cost therapies, and lets manufacturers put visible confidence behind durability.

On paper they are sensible; in practice the failure points are concrete. The outcome data that triggers payment lives in the EHR and clinical registries, not in any one system, so no one with a financial stake controls the number that settles the contract. While patient tokenization is meant to connect disparate healthcare datasets, it is still early and has yet to ease payer concerns. Attribution breaks the moment a patient changes plans, which is common over the multi-year windows these contracts require. Add in endpoints that are often hard to define and measure, and difficult to align upon, and most VBCs don’t stand a chance before the first patient is dosed.

The implication is straightforward: build the data-collection partnerships early. Companies that wait until coverage talks are underway find the operational lift too great for the timeframes payers demand. Those that did the groundwork in advance, i.e., mapping outcome definitions, securing data sources, and pre-aligning with delivery networks, can treat VBCs as a genuine option rather than an aspiration.

Beyond VBCs: Warranties and Pay-as-You-Go

Two adjacent tools remain under-utilized: warranties and pay-as-you-go installments. Both let value accrue over time against a one-time therapy, but through opposite mechanics. Installments defer the cash, and when tied to outcomes, finance can’t book full value at dosing, which can be a manufacturer-side friction. Warranties let the manufacturer collect up front and reserve for contingent payouts. They can also receive more favorable government price-reporting treatment than outcomes-based rebates. The harder constraint for both sits on the payer side: member turnover shifts the value off the payer who paid, and Medicaid generally can’t commit to multi-year payment absent an outcomes link.

Registries and RWE Partnerships as Strategic Infrastructure

Long-term follow-up registries and real-world evidence (RWE) partnerships are often foundational to commercialization strategy, not just supporting infrastructure. Registries such as CIBMTR (Center for International Blood and Marrow Transplant Research) have proven their value in CAR-T, supplying long-term outcomes data payers, providers, and regulators use to judge real-world performance.

The right approach usually blends three mechanisms: leverage existing registries, co-develop disease-specific ones where none exist, and build proprietary RWE that captures what neither provides. Each serves a different need. Registries supply credible, broadly accepted long-term safety and effectiveness data, while RWE programs enable flexible, hypothesis-driven work supporting label expansion, comparative-effectiveness claims, or sharper patient identification.

This is why data capture must be treated as shared infrastructure built once, not a fresh ask bolted onto every program. Each new registry or RWE request is incremental data-entry work for ATCs and community sites that are already stretched, and overburdened sites return thinner, slower, less reliable data. This leaves manufacturers who ignore site capacity with exactly the poor data quality they cannot afford. The structural problems compound it: full datasets are rarely digitized end-to-end, and what exists tends to sit in silos, inside a single manufacturer or within a registry like CIBMTR, constraining availability and access. Pharma-held RWE can also carry a credibility discount, since payers and HTA bodies weight evidence from the party that profits from it less heavily, which is a strong argument for routing key data through an independent third party.

Beyond access negotiations, this evidence builds confidence on the front line: a physician weighing referral with thin follow-up data, and the patient and caregivers facing the same choice, are far more comfortable when outcomes are collected systematically and shared.

The Bottom Line

For CGTs, evidence generation is an ongoing strategic commitment underpinning pricing, payer dossiers, value-based contracting, and stakeholder trust across the lifecycle. Manufacturers that invest early in follow-up infrastructure, RWE partnerships, and refined economic modeling are the ones whose value story holds up as the market matures. Those that treat it as a post-approval afterthought end up in defensive postures they could have avoided.

Next in the series: Success Factor 6 – Elevated Patient Experience and Engagement.