RWE, Gene Therapy, IRA Evidence Challenges

MarcusWelcome to Access Brief, the daily AI podcast on HEOR, HTA, and market access. I'm Marcus, with Sara. Today: real-world evidence in HTA submissions, gene therapy cost-effectiveness challenges, and the IRA's impact on evidence generation. Let's get into it.

MarcusStarting with real-world evidence in HTA submissions post-JCA rollout. HTA bodies are increasingly accepting RWE for decision-making, especially for products with limited clinical trial data. The JCA framework explicitly allows for RWE integration in joint clinical assessments. Sara, this seems like a structural shift toward pragmatic evidence.

SaraStructural shift? I see it as a reactive concession. HTA bodies are overwhelmed with novel therapies and lack robust RWE governance frameworks. Accepting RWE often happens when trial data is insufficient, not by preference. The variability in RWE acceptance across jurisdictions creates evidence strategy fragmentation. We're trading methodological rigor for expediency.

MarcusThat's unduly pessimistic. RWE fills critical evidence gaps, particularly for rare diseases or real-world effectiveness. HTA bodies are developing structured RWE guidelines—this isn't fragmentation but evolution.

SaraEvolution with risk. Without standardized RWE validation, we're introducing heterogeneity that undermines cross-jurisdictional value demonstrations. The burden of proof remains on manufacturers to justify RWE quality, not HTA bodies to accept it. That's a commercial framing masquerading as progress.

MarcusShifting to gene therapy cost-effectiveness challenges. These therapies face inherent value hurdles due to high upfront costs and uncertain long-term outcomes. HTA bodies are adapting with flexible thresholds, but the evidence generation timeline often misaligns with clinical development. Sara, isn't this a fundamental market access tension?

SaraAbsolutely. The tension isn't just cost—it's about defining value beyond clinical endpoints. HTA bodies demand long-term RWE to justify pricing, but developers can't generate it pre-approval. We're forcing evidence generation into post-launch phases where commercial viability is already at risk. The system penalizes innovation by demanding perfect foresight.

MarcusPost-launch RWE is inevitable for gene therapies. The alternative is denying patient access to transformative treatments. HTA bodies are increasingly accepting surrogate endpoints with confirmatory RWE plans—this balances innovation with accountability.

SaraAcceptance isn't the issue; it's the timeline. By the time RWE confirms value, market exclusivity erodes. The system requires manufacturers to bear both development and evidence-generation costs simultaneously. That's not balance—it's a structural disadvantage for novel therapies.

MarcusThird, the IRA's impact on HEOR evidence generation. The IRA mandates real-world data collection for drugs entering Medicare negotiation. This shifts HEOR focus toward post-launch evidence generation. Sara, is this creating new evidence priorities?

SaraIt's creating a bifurcated evidence strategy. Companies now prioritize RWE for US negotiations while maintaining separate HTA dossiers for Europe. The IRA forces evidence generation for pricing, not necessarily for patient value. We're optimizing for negotiation leverage, not clinical utility.

MarcusThat's a narrow view. The IRA accelerates real-world evidence generation that benefits global HTA submissions. Post-launch RWE from the US can inform international value assessments—this is efficiency, not fragmentation.

SaraEfficiency only if the RWE is jurisdictionally transferable. US-specific data may not reflect European healthcare systems or patient populations. We're generating evidence for one market while assuming applicability elsewhere. That's a commercial assumption, not evidence-based strategy.

MarcusFourth, HTA methodologies for digital health technologies. HTA bodies are developing frameworks for digital therapeutics and AI-driven interventions, but methodologies lag behind innovation. Sara, what's the core challenge here?

SaraThe core challenge is defining endpoints. Digital health interventions often measure process outcomes (e.g., engagement metrics) rather than clinical outcomes. HTA bodies struggle to translate these into meaningful value metrics. We're forcing square pegs into round holes—applying traditional HTA to novel data types.

MarcusProcess metrics are valid proxies for clinical impact when properly validated. HTA bodies are establishing novel endpoints for digital health—this is methodological adaptation, not failure.

SaraAdaptation without standardization. Until HTA bodies agree on core outcome sets, digital health submissions will face inconsistent assessments. The burden falls on manufacturers to justify each endpoint individually, creating regulatory uncertainty.

MarcusFinally, patient-reported outcomes in value assessments. PROs are increasingly central to HTA submissions, capturing patient experience beyond clinical metrics. Sara, are we over-indexing on subjective data?

SaraOver-indexing? PROs are essential for holistic value assessment. Ignoring patient experience is methodologically negligent. HTA bodies are incorporating PROs more systematically—this reflects a shift toward patient-centered value.

MarcusSystematic incorporation doesn't resolve validity issues. PROs are susceptible to response bias and lack standardization across diseases. HTA bodies need stronger PRO validation frameworks, not just inclusion.

SaraValidation is the manufacturer's responsibility. HTA bodies are rightly demanding PRO data that reflects real-world patient experience. This isn't over-indexing—it's correcting historical neglect of patient perspectives in value assessments.

MarcusSara, we've covered RWE, gene therapy, IRA impacts, digital health, and PROs. Critical tensions across the board.

SaraTensions that define our field. Evidence demands are evolving faster than methodologies—forcing strategic tradeoffs we can't ignore.

MarcusBack tomorrow on Access Brief. Show notes at outcomes-analytica.no.