Into the future: a single EU body assessing relative effectiveness of medicines?
This article was originally published in SRA
A fully centralized European health technology assessment is probably not a possibility as member states individually are responsible for decisions on access to medicines via their respective national health systems. But what about a central EU expert body responsible for producing a single relative effectiveness assessment that national committees could use in their own HTA and pricing/reimbursement discussions and decisions?
That's one of a number of scenarios put forward in a new report commissioned by the European Parliament's environment and public health committee (ENVI) on the feasibility of a harmonized EU approach to assessing the added therapeutic value (ATV) of new medicines1.
The report acknowledges that while there are differences in how ATV is defined and assessed across EU member states, "the underlying principles are not fundamentally incompatible and share the same goals and concepts". It says agreeing on a shared definition of ATV is a "desirable and logical next step", and that "a shared definition and methodology to determine ATV would facilitate communication between all stakeholders, allow member states to build on each other’s expertise and make joint assessments easier".
"Moreover, the existence of a shared methodology would reduce the administrative burden for pharmaceutical manufacturers, who would need to invest fewer resources in tailoring their dossiers to each member state where they wish to apply for reimbursement. A shared definition would also clarify the expected benefits of new medicinal products, incentivising the production of innovative medicines and hopefully reducing the burden of unmet medical need."
Most EU member states carry out some form of relative effectiveness assessments (REAs) on newly authorized drugs or indications, as well as cost-effectiveness evaluations, against existing therapies or standard of care, usually as part of broader health technology assessments (HTAs), which take account of other factors such as economic, social and ethical considerations.
However, because the countries often use different methodologies, outcomes and comparators, efforts are sometimes duplicated and different conclusions reached.
Moves are under way to increase collaboration and information sharing by way of various EU initiatives, such as the "Joint Actions" run by the HTA network EUnetHTA and the parallel regulatory/HTA assessment pilot being explored by the European Medicines Agency and HTA bodies.
Joint assessments, which have already been conducted through EUnetHTA Joint Actions 1 and 2, have the added benefit of concentrating expertise that is not usually found within a single national agency and, once there is an agreement on their methodology, saving time, the report says.
The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) recently noted that while economic evaluations that inform reimbursement decisions cannot be standardized across Europe, it is possible in principle to standardize the means for determining relative clinical effectiveness and for countries to at least agree on common terminology and methodologies2. The report from the European Parliament draws a similar conclusion.
Single EU REA body
But the report goes further, raising the possibility of a single European joint committee of experts that would carry out REAs on products nearing marketing authorization before they are submitted to national reimbursement authorities.
This new body would replace the current parallel assessments by national authorities of similar clinical evidence. It would consist of a team of multidisciplinary experts nominated by each member state depending on their particular expertise. Working procedures would be "inspired by best practices from selected member states and by those from regulatory assessment committees such as the [EMA's] CHMP."
"Such an assessment committee could build on the exchange of expertise and good practices which currently take place in the European Joint Action," the report says. It would not infringe on national responsibilities for reimbursement decisions, as each member state would be free to use or not use the joint assessment report.
In order to comply with the requirements of the EU price transparency directive in terms of pricing and reimbursement decision timelines, the joint report would be made available near the time of marketing authorization.
The committee would be limited to carrying out relative efficacy assessments and would not itself have any involvement in pricing and reimbursement matters. ATV should be evaluated by a team of experts in areas like technology assessment, clinical pharmacology, clinical practice, observational research and biostatistics, and these experts should work independently from the bodies that are in charge of pricing and reimbursement, the report says.
It does not give any likely timescale for setting up such a body, or suggest where it might be based.
Industry reaction
Whether pharmaceutical companies would welcome the creation of a single REA body is another matter. The European industry federation EFPIA said it recognized that payers had to rely on sound evidence on the value of medicines, and that assessments of relative efficacy conducted jointly by member states at European level might improve the clinical appropriateness and scientific rigor of the process.
The federation suggested that having a science-based agency such as the EMA co-ordinate European REA could overcome the delays created by widely differing country interpretations of the same clinical data.
But EFPIA seems to prefer collaboration and co-ordination rather than centralization, saying it wants to work with other stakeholders to jointly develop mechanisms, methodologies and processes to support scientific assessments that meet the needs of the member states and patients, and are well aligned with innovation. "EFPIA and its member companies support the creation of a strong scientific evidence base to support the assessment of the clinical value of innovative medicines," said the federation's director general, Richard Bergström.
All European patients should have fast, equal and comprehensive access to medicines across all 28 member states, Mr Bergström told Scrip Regulatory Affairs. "EFPIA believes that European REA holds potential benefits in addressing barriers that are unique to the European HTA context. However, this approach – by definition – cannot be applied outside Europe," he added.
Mapping exercise
Much of the data in the report, which was produced by the parliament's economic and scientific policy department, is based on a mapping exercise conducted in all EU member states, which revealed that 26 of the 28 carried out some form of ATV assessment. Countries used different ways to measure added value, such as a classification that rates the ATV level (France, Germany, Spain, Italy and Austria), a "categorical" classification where the drug either has an ATV or it has not (the Netherlands, Belgium, the Czech Republic, Hungary), or the quality-adjusted life year (QALY) system preferred by the UK, Croatia and Sweden.
Once it is assessed, ATV can be used as an explicit or implicit criterion for price regulation or negotiation, or it can be used to inform other decisions, the report notes. "In Germany, for example, medicines with ATV are not clustered in reference price groups and are given a price premium over comparators." Similar implicit or explicit rules are applied in most member states (Belgium, Denmark, Estonia, Ireland, Spain, France, Italy, Latvia, Luxembourg, Hungary, Malta, the Netherlands, Austria, Poland, Slovakia, Finland and Sweden).
"In the Czech Republic," it continues, "medicines with a high ATV are exempt from having to prove their cost effectiveness. In the UK, where the pricing of medicines is only indirectly regulated through the Pharmaceutical Price Regulation Scheme (PPRS), ATV has no impact on prices."
The report's authors conducted in-depth studies in six countries (Austria, France, Italy, Poland, Slovakia and Sweden), looking at how ATV is assessed and the role it plays in pricing and reimbursement decisions. These six were chosen to ensure a balance in geographical coverage and country size, as well as a mix of member states with longstanding experience using HTA or REA and those that that are relatively new to these types of assessment. Also, the final decision-makers differ in these countries (eg, reimbursement agencies in Austria and Sweden, sections of bodies under the direction of the health ministry in France, Poland, Slovakia and Italy).
"France is an interesting case because it recently introduced the analysis of cost effectiveness", the report says. "Austria was selected because it provides an example of a drug reimbursement decision-making process which leads to different outcomes when compared to other countries. Sweden was included as it has a long history of using REA in reimbursement decision-making. In addition, it applies a regional implementation, while other countries implement at national level. Italy is an interesting example of a country assessing purely technological innovations. Poland and Slovakia have a relatively short experience in assessing ATV, but have developed interesting and innovative solutions."
This sub-survey found among other things that there was relatively little difference in the choice of comparator among the six countries, with most using "best standard care" as the main comparator, although some used additional comparisons with the "best possible care" or the "cheapest alternative". Moreover, REAs were conducted in a relatively similar way, using comparable data sources and preferring clinical endpoints to surrogate endpoints and direct rather than indirect comparisons.
Recommendations for action
While its key long-term suggestion is a central REA body, the report puts forward a number of other proposals for action in the meantime:
- Further strengthening co-operation among the competent authorities, EUnetHTA and other stakeholders and identifying current similarities and differences in areas like the acceptability of surrogate endpoints, clinical relevance of statistically significant differences, the importance of patient input, and the applicability of indirect treatment comparisons.
- Agreeing a common set of criteria for assessing ATV, starting with the five that many member states already have in common: efficacy, safety, effectiveness, applicability and ease of use.
- Having multidisciplinary expert panels produce REAs at national level, instead of panels of stakeholders, with expertise in medicine, clinical R&D, clinical pharmacology, biostatistics, epidemiology, and specialised medical topics (eg autoimmune diseases, oncology), rare diseases and advanced therapies.
- Developing good practice in the field of REA, with formal endorsement of REA standards by the authorities and applicants, and publication of REA methods and assessment reports.
References
- Towards a harmonised EU Assessment of the Added Therapeutic Value of Medicines, June 2015, http://www.europarl.europa.eu/RegData/etudes/STUD/2015/542219/IPOL_STU(2015)542219_EN.pdf
- ISPOR, The increasing need to harmonize evidence demands of regulators, payers and health technology assessment bodies in Europe, http://www.ispor.org/news/articles/july-aug2011/harmonize-evidence-demands-of-regulators-payers-and-health-technology-assessment-bodies-in-europe.asp