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Evolving HTA frameworks to accelerate innovation

Evolving HTA frameworks to accelerate innovation

Iterative evidence generation and demonstrating value over time could help unlock delays in getting cures out, saving more lives, says Janssen’s Clare Hague

Innovation in the cancer treatment space offers great promise, but even when approved by the European Medicines Agency (EMA) and other national regulatory bodies, patients can still face protracted delays in accessing new treatments. 

Uncertainties in the evidence base for pioneering therapies can lead to delays from health technology assessment (HTA) agencies and payers in securing reimbursement. 

To accelerate progress here, HTA frameworks must evolve, says Clare Hague, Therapy Area Market Access Lead, Hematology at Janssen EMEA, speaking ahead of the upcoming eyeforpharma Barcelona 2020 conference.

“We need to look beyond overall survival (OS) when assessing the efficacy of innovative cancer medicines,” says Hague. “This is because the demonstration of a survival benefit may not be feasible or practical in situations where we see step-changes in the clinical benefit of our medicines and patients are living for a very long time. This is especially the case when the aim of treatment is moving towards disease modification, interception and, in earlier stage disease, the promise of cure or long-term durable remission. 

“Collectively, we must consider alternative endpoints and shift the focus away from static decision-making on the basis of data observed at a single point in time, towards iterative decision-making based on evolving information and knowledge over time.” 

“To achieve this, trusted partnerships between all stakeholders need to be formed to harness an ongoing dialogue around the capture of real-time outcomes to enable speedy patient access at value-based prices that reward innovation”.

More than overall survival data

Overall survival evidence has historically been a critical measure in assessing cancer treatments, but is often no longer the best method of evaluation; in part due to the increased efficacy of those treatments. The “one size fits all” value assessment framework should adapt and identify outcomes that are measurable, robust, predictive and clinically relevant to the tumor type and stage of disease.

“Ten or 15 years ago, cancer medicines would give patients three to four additional months of survival, but we’re now getting to the stage in multiple myeloma and CLL where we're extending survival by many years,” says Hague. “There needs to be flexibility in the system that recognises that life-extending treatment cannot be evaluated using overall survival, if you're waiting 10 years for that data to become available.”

This requires HTA agencies to accept and adopt alternative measures such as intermediate or surrogate endpoints, says Hague, supported by more diverse data sources – real-world evidence (RWE) in HTA appraisals, for example, to support single arm trials.  

“Not all diseases and cancers are the same and they shouldn't be evaluated in the same way,” she says. “Identifying relevant, validated markers of longterm outcome, together with patient relevant data, should form the basis for decision-making when OS data are not available".

While regulators such as the EMA are increasingly taking surrogate endpoints into consideration when granting approvals – such as exploring minimal residual disease, MRD negativity, as a surrogate endpoint in multiple myeloma – HTA agencies remain slower in recognising how to use such endpoints.  

“There is a bit of a disconnect between acceptance by the regulators of what they will use for approval of medicines, versus the evidence the HTA agencies and payers will accept for reimbursement,” says Hague. “We need the two to come closer together, at an earlier stage of development, to agree on what data is acceptable and for what purpose.”

Ongoing dialogues about value over time

Concerns from HTA agencies and payers focus on uncertainty around evidence generation and budget impact, says Hague. A shift from static decision-making to ongoing assessments of evidence could both alleviate HTA agency concerns around these uncertainties and speed the delivery of pioneering treatments to patients. 

Evidence generation for innovation should be an iterative process, says Hague, citing the example of CAR-T therapies coming to market with quite limited data on overall survival. “Rather than delay or restrict the decision to reimburse, let's explore solutions like managed entry agreements, which mean we can go back and demonstrate value and re-negotiate prices with payers as more and more data becomes available. Prices could go up as well as down, which is the nature of true risk-sharing.

“Do you wait until you have certainty of “proof”, which means denying patients access and saying, ‘come back in four or five years when there’s more information’, or do you make a decision that you revisit over time? It's more of an ongoing dialogue about value over time, rather than being forced to make a decision at a single point in time when there's uncertainty.”

Building trusted partnerships

When it comes to budget impact, Hague says there is a “fear of spiralling costs and how payers will cope with an increase in drug spend”, despite the fact that drug spend constitutes only a small proportion of overall health spend. 

Solutions being explored at Janssen include a more holistic determination of value (to incorporate a broader societal perspective, including cost savings from social services and impact on carers), and an increasing emphasis on novel payment mechanisms. Staged payment models can spread costs over time and link payments to patient outcomes, and new RWE methodologies could be used to bolster data from single arm clinical trials. 

One such methodology is the firm’s HONEUR (Haematology Outcomes Network in Europe) network, which links real-world federated data from hospitals across Europe through a secure, collaborative platform ( Other established registries such as the EBMT (European Society for Blood and Bone Marrow Transplantation) Registry also offer the potential to capture robust data on CAR-T therapies in the commercial (post-launch) setting and could be used to track outcomes data over time (

“For treatment like CAR-T therapy, where we have a single administration with one up-front cost, and where the treatment is likely to offer a very long-lasting improvement to health, we're keen to explore flexible innovative payment models. These might include outcomes-based or financial-based agreements, or a combination of both, to address some of the budget impact concerns from payers,” says Hague. “It’s critical to overcome some of the challenges associated with one-off treatment costs, and to improve access to patients, through the co-creation of solutions that address payers' concerns.”

More collaborative approaches will ensure success, says Hague, who stresses the importance of trusted partnerships between manufacturers, HTA agencies, payers and patient advocacy groups to agree solutions in a timely way. 

“Every problem has a solution, but we need to work in partnership,” she says. “18 months before marketing authorisation, we’re trying to find the best solution together so that patients can access the treatment at the appropriate time, rather than waiting until the drug has been approved and there’s a lot of pressure on payers to make decisions”. 

This article originally appeared on Reuters Events on March 14 2020.