It’s an increasing challenge for the pharmaceutical industry. In today’s diverse global healthcare systems, how do you develop robust but flexible reimbursement and evidence generation strategies that support funding and reimbursement, and thus patient access, to life-changing therapies?
Is it possible to design a clinical trial and evidence generation programme that meets the needs of all stakeholders? Is a one size fits all approach fit for purpose?
Increasingly the answer to these questions is no. There are now such differences in assessment requirements between some countries that to develop an all-encompassing trial programme for all markets at launch would be impractical and not cost effective.
But that doesn’t mean that comprehensive market access evidence generation strategies should be abandoned. Quite the opposite. And having a clear understanding of the evidence requirements for individual markets and healthcare systems is now crucial for optimising patient access to new therapies.
Divergence in health technology assessment across key markets
Take the UK and Germany as examples. These countries have health technology assessment (HTA) processes that challenge pharmaceutical companies to prove the additional clinical benefit or added value of new therapeutic interventions. But they take very different approaches to conducting assessments, and in what they consider represents value.
In Germany, the Institute for Quality and Efficiency in Healthcare (IQWiG) and the Federal Joint Committee Gemeinsamer Bundesausschuss (G-BA) assess the additional clinical benefit of new therapies compared with an active comparator of their choice, typically standard of care. Applications for reimbursement must be based on active-controlled randomised controlled clinical trial data, and be submitted for the full marketing authorisation for a product. While, at the present time, Germany does not formally assess the economic value of new therapies at a national level, the level of additional clinical benefit gained influences the price that a new therapy can achieve relative to competitors.
By contrast, the National Institute for Health and Care Excellence (NICE) in the UK has a more flexible approach to acceptance of clinical trial data, allowing placebo-controlled clinical trial data and indirect treatment comparisons as well as non-randomised trial data. However, cost–effectiveness, or more correctly cost–utility, analysis plays a much greater role in the assessment process in the UK and all drugs assessed by NICE need to provide a supporting economic model that demonstrates the cost of achieving quality of life year (QALY) gains over a comparator.
In both cases, however, pharmaceutical companies likely need to approach reimbursement assessments in these markets with data based on the same clinical trial programme, albeit supplemented with key local data developed specifically for individual submissions.
So how is it possible to square the circle?
HTA challenges in practice
In many cases, it’s not. Evidence that is acceptable to NICE is excluded by IQWiG and the G-BA, with consequences for patient access to new therapies.
Take multiple sclerosis (MS) as an example. We recently conducted an analysis of parallel HTA assessments for MS therapies from 2011 (after pharmaceutical market reorganisation in Germany –i.e. post AMNOG) to 2015. Three disease-modifying therapies (DMTs) were assessed by both NICE and IQWiG during this period: fingolimod, dimethyl fumarate and teriflunomide.
All three manufacturers faced challenges from NICE and IQWiG around patient populations (specifically utilisation of patient subgroups), choice of comparator (particularly the lack of available of trial data vs. an active comparator) and, for NICE, technical economic modelling challenges. Only by understanding the specific requirements for NICE and IQWiG were the manufacturers able to adapt their submissions to make best use of the evidence available.
Patient impact of health technology assessment?
These aspects of HTA have a direct impact on the ability of patients to get appropriate treatment for their condition. Reimbursement and access is a binary decision for an individual patient. They either receive the therapy, or they don’t.
In case of the MS therapies above, fingolimod was reimbursed in Germany across its full marketing authorisation, despite only achieving “minor/marginal” additional benefit in one of the patient subgroups assessed by IQWiG (incidentally highlighting the importance in Germany of achieving at least minor additional clinical benefit in at least a small subgroup of patients). For the other two DMTs, patients were able to access the therapies across their full marketing authorizations, despite IQWiG finding “no additional benefit”. This was only achieved at a cost to the manufacturers, however, who needed to offer acquisition cost discounts of around 20–45% (based on the German launch price).
By contrast, all three therapies were approved by NICE in more restricted populations than in Germany, limiting the patient populations with access to these therapies. Approval was contingent in all cases on manufacturers offering the therapies within a Patient Access Scheme, an unspecified and confidential list price discount.
Optimising evidence generation and strategy for reimbursement
So what does this mean for companies bringing new therapies to market? In lieu of a long list of components of a robust market access strategy, we’ve included a few key thoughts below:
- A well-designed clinical trial programme is crucial for optimising access. Are the right comparators included? Do you know what endpoints payers want to see? Are you collecting sufficient quality of life data? Have you pre-specified your subgroup analyses?
- It’s important to recognise that a one size fits all approach to generating evidence for is no longer appropriate. Flexible strategies, supported by robust local data, are important for developing compelling value arguments. Often now it is the supplemental, non-RCT data generated both before and after launch that provides compelling differentiation vs. competitors.
- Focus on communication with both external stakeholders, and with internal colleagues. Market access and R&D teams should be engaging early during the clinical development process so that the trial design team understand the challenges of reimbursement, and the outcomes that payers will want to see from trials. Developing an external stakeholder engagement plan to feed into reimbursement strategy is also important to gain insights into price, unmet need, comparators and evidence requirements.
While developing an optimal reimbursement strategy is challenging, understanding key evidence requirements for stakeholders in individual markets and talking to those stakeholders early and often, will give those key decision makers the information they need to support patient access to life-changing therapies.
For more information on OPEN Access Consulting's HTA strategy and dossier development support, and internal communications programmes, please do contact us at email@example.com