HTA Methodology Shifts & FDA Accelerated Approvals

MarcusWelcome to the Access Brief — your daily briefing on what's moving in HEOR, HTA, and market access. I'm Marcus, health economist, and it's great to have you with us today.

SaraAnd I'm Sara, market access strategy. Always good to be here — and I'll say, I've had today's topics circled since this morning.

MarcusSame here. We're looking at HTA methodological shifts in Asia-Pacific — which are reshaping how value is assessed across diverse health systems. Then Canadian pricing policy developments — with significant implications for global benchmarking. And RWE integration challenges in Latin America — where data gaps are complicating access decisions.

SaraThat second one is particularly interesting to me — the budget impact question there is one the field hasn't fully worked out yet, especially with cross-jurisdictional reference pricing.

MarcusExactly. Let's get into it.

MarcusStarting with Asia-Pacific HTA shifts. We're seeing more countries adopting hybrid value frameworks beyond pure cost-per-QALY models. Singapore's Health Sciences Authority just piloted a multi-criteria decision analysis tool incorporating equity weighting for rare diseases. This isn't just incremental; it's a structural shift toward contextualizing value within regional health priorities.

SaraWhat strikes me about that is how it mirrors European JCA principles but with local adaptation. The equity weighting component is new though — I wonder if that's the full picture though? We've seen similar frameworks in Thailand struggle to operationalize equity without clear thresholds.

MarcusFair point. Singapore's pilot includes explicit equity thresholds tied to orphan status, which Thailand's lacked. But the bigger implication is how this affects global submissions. Companies now need jurisdiction-specific value dossiers for Asia-Pacific, not just Western repackaging.

SaraThat connects to something I keep coming back to — the opportunity cost implications. If Singapore prioritizes equity, does that mean less budget space for other innovations? The trade-offs aren't transparent yet.

MarcusExactly. And it's not just Singapore. Malaysia's new HTA framework now includes technology appraisals for digital therapeutics, which they previously excluded. This is one of those stories where regional fragmentation is creating both challenges and opportunities for evidence generation.

SaraI'd push back slightly on that — Malaysia's inclusion of digital health isn't new; it's formalizing existing pilot programs. The real challenge is harmonization. How do you compare a Malaysian digital health appraisal to a Japanese one when their endpoints differ fundamentally?

MarcusThat's where the RWE piece comes in. Japan's PMDA is now accepting RWE for real-world effectiveness in their HTA submissions, specifically for drugs with limited trial data in Asian populations. This could be a bridge for cross-jurisdictional evidence.

SaraRight, and from the payer side, the question is whether that RWE meets evidentiary standards. We've seen cases where RWE was accepted but then downweighted in final decisions due to methodological concerns. The credibility gap remains.

MarcusWhich brings us to the next topic — Canada's pricing reforms. Their new Canadian Drug Agency has just published guidance on value-based pricing models, moving beyond the outdated Patented Medicine Prices Review Board caps. They're now considering cost-effectiveness thresholds that vary by disease severity.

SaraThe part that gives me pause is the disease severity adjustment. How do you operationalize that without creating perverse incentives? We saw similar approaches in Australia that led to higher prices for oncology but squeezed other budgets. The budget impact question there is one the field hasn't fully worked out yet.

MarcusThat's one read — I'd frame it slightly differently. Canada's approach explicitly links severity to willingness-to-pay thresholds, which could be more transparent than their previous system. But the implementation details are still vague. What strikes me here is how this affects US-Canada reference pricing dynamics.

SaraAbsolutely. If Canada adopts higher thresholds for severe diseases, US payers might point to that as precedent for higher domestic prices. The cross-border spillover effects are significant, especially with IRA negotiations looming.

MarcusAnd it's not just thresholds. Canada's new guidance also requires companies to submit RWE for post-marketing surveillance, which wasn't previously mandated. This could create a more robust evidence base over time.

SaraThough I suspect payers will question the quality of that RWE. We've seen cases where companies cherry-picked real-world data to support higher prices. The governance around that RWE collection will be critical.

MarcusWhich leads us to Latin America's RWE challenges. Brazil's CONITEC recently published a position statement on RWE use in HTA, but their health technology assessment agencies remain skeptical. The main barrier isn't methodology — it's data infrastructure. Most countries lack centralized electronic health records.

SaraThat's fair, though I think payers would see it differently. The bigger issue is how to validate RWE in fragmented health systems. In Mexico, for example, public and private data are siloed, making longitudinal studies nearly impossible. The methodological gaps are real.

MarcusExactly. And it's not just about data availability. Colombia's INVIMA now requires RWE submissions for orphan drugs, but they don't have guidelines on how to assess it. This creates uncertainty for sponsors and inconsistent decisions across countries.

SaraThe unpredictability is problematic. Companies can't standardize their evidence strategies when each country has different expectations. This is one of those stories where regional fragmentation is actually hindering innovation access.

MarcusRight. And it connects to our final topic — gene therapy HEOR in Asia. Japan's PMDA has just approved a new gene therapy for spinal muscular atrophy using a novel endpoint: motor function preservation rather than traditional survival metrics. This is a significant methodological shift.

SaraWhat strikes me about that is how it challenges conventional HTA frameworks. If you're measuring preservation rather than improvement, how do you calculate cost-effectiveness? The denominator becomes harder to define. I wonder if that's the full picture though? We've seen similar endpoints in Europe that struggled with interpretation.

MarcusFair point. Japan's approach includes a hybrid model combining the new endpoint with quality-of-life measures. But the bigger implication is how this affects global evidence packages. Companies now need to justify why their endpoints are superior to traditional ones, which requires strong HEOR storytelling.

SaraAnd that storytelling has to account for payer skepticism. In South Korea, the HIRA recently rejected a gene therapy submission because the evidence didn't sufficiently demonstrate superiority over existing treatments. The burden of proof remains high.

MarcusWhich is why we're seeing more companies investing in local HEOR capacity in Asia. Novartis just established a regional HEOR hub in Singapore specifically for gene therapy evidence generation. This isn't just about compliance; it's about building credibility.

SaraI'd push back slightly on that — it's more about risk mitigation than credibility. Companies are trying to avoid HTA rejections by preemptively addressing local evidence gaps. The operational challenges are immense, especially with gene therapies' long follow-up requirements.

MarcusThat's one read — I'd frame it slightly differently. These hubs represent a strategic shift toward localized evidence generation, which could ultimately benefit patients by ensuring therapies are assessed in relevant populations. But the cost is significant, especially for smaller biotechs.

SaraThe budget impact question there is one the field hasn't fully worked out yet. If only large players can afford localized evidence, we risk entrenching inequities in access. That's a tension worth sitting with.

SaraA lot to think about today. I'll be watching how Canada's disease severity thresholds evolve and whether they create a new global benchmark for value assessment.

MarcusSame — and for me the thread running through today is how regional fragmentation is driving both innovation in evidence generation and significant operational hurdles. The localization paradox is real.

SaraThanks so much for listening — really glad you're here with us.

MarcusWe'll be back tomorrow. Show notes and transcripts at outcomes-analytica.no. See you then.

SaraThanks for listening — see you tomorrow.

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