The process of Health Technology Assessment (HTA) is central to determine the fair, systematic, robust and unbiased evaluation of health technologies both on the medical, social, economic and ethical point of view. The process aims to provide patients’ access to innovative medicinal and medtech products while ensuring the best value for healthcare systems.
The European Commission adopted the draft text of the new HTA regulation on 31 January 2018. The text is expected to be examined and finally approved by the Parliament and Council of Europe by 2019, to then enter into force after three years in Member states. A further transition period of three years is planned from this date.

Four areas of cooperation

The proposal considers four possible different scenarios for cooperation in HTA, starting from the joint clinical assessments to be run on the most innovative health technologies. Joint scientific consultations will be the preferential tool for developers to seek advice from HTA authorities. These will be also involved in the identification of emerging health technologies, and might continue as well voluntary cooperation in other areas. Individual EU countries will continue to be responsible for assessing non-clinical (e.g. economic, social, ethical) aspects of health technology, and making decisions on pricing and reimbursement.
The proposal of the new regulation focuses its attention on the clinical part of the assessment, as it represents the common base shared at the global level for the evidence to be provided to competent authorities to reach regulatory approval (in the case of medicines as well as medical devices or diagnostics). The Coordination Group will be the central point for the coordination of all efforts under the provision of the new regulation.

Overcome the current duplication of efforts

The final outcome of the proposed regulation directly impacting on the pharmaceutical and medtech industries is an improvement of business predictability and a long-term sustainability of HTA cooperation with Member states, thanks to the convergence in HTA tools, procedures and methodologies, the reduction of duplicate efforts for HTA bodies and industry and the use of joint outputs.
Many initiatives to support HTA have been launched since the 1980s; the main actions at the European level are currently undertaken by EUnetHTA (the European network for Health Technology Assessment). The third action launched by the network for years 2017-2020 focuses on developing common assessment methodologies, piloting and producing joint clinical assessments and full HTA reports, and on developing and maintaining common ICT tools. But the efficacy of this project is undermined by the voluntary participation of different countries, leaving behind a still fragmented scenario, which is now addressed by the proposal of the new regulation.
Among issues to be solved in order to harmonise the modalities for HTA in the European Union are the differences in data and evidence requested by the different national authorities in charge of the procedure, which also use different methodologies to run the assessment. According to the Commission, this leads to an impeded and distorted market access, lack of business predictability, higher costs and negative effects on innovation. The already available tool of joint clinical assessments is still not widely used and adds a further level of duplication. Furthermore, according to the proposal, funding of HTA projects occurs on the short term, mining the long-term stability of the process.

Four scenarios for the impact assessment

Together with the proposal of the new regulation, the Commission also published the report of the Impact assessment run to estimate outcomes that might be expected under four different scenarios, starting from the baseline option 1 (no joint actions after 2020) to project-based cooperation on HTA activities (option 2), permanent cooperation on common tools, procedures and early dialogues (option 3) or, finally, permanent cooperation on common tools, procedures, early dialogues and joint clinical assessments (option 4).

Option 4 has been the preferred one, with integration of some elements of option 2 and some adjustments regarding transitional arrangements for Member states and progressive implementation of the product scope for joint clinical assessments. This approach has been considered to provide the best combination of effectiveness and efficiency in reaching the policy objectives, while respecting the principles of subsidiarity and proportionality, and it forms the base for the proposal of the new regulation.
The European Commission also launched between October 2016 and January 2017 an online public consultation on the initiative, those results are also summarised in the impact assessment report and were taken in due consideration during the development of the legislative proposal.

The comments from the Parliament’s subcommittees

In April 2018 the Committee on Industry, Research and Energy of the European Parliament published its draft comments of the proposal, highlighting the fact that “a reinforced cooperation would boost the efficiency and cost-effectiveness of industries and manufacturers involved in the healthcare sector and thus their competitiveness on a global scale”.
The Rapporteur Lieve Wierinck underlined the lack of a clear definition of the methodologies within the proposal, something to be better developed in the future. Top level scientific evidence should be used for the joint HTAs, is the suggestion; the Committee also approved the role of the Coordination Group and the use of mandatory uptake of joint clinical assessments and asked for a more structured involvement of patient organisations, industry and other stakeholders. A negative opinion has been issued on the possibility to include also medical device in the scope of the regulation, recommending their exclusion from the final version as national HTA bodies already have other useful tools to evaluate them.

The Committee on the Internal Market and Consumer Protection published its draft opinion on May 2018 (Cristian-Silviu Buşoi as Rapporteur). Proposed amendments include the possibility for certain Member States to start clinical assessmentseven before the marketing authorisation has been granted by the Commission”. To avoid delays compared to the status quo, the process should be completed in any case by the time of the publication of the Commission decision granting MA. The Committee also proposed to take into account the methodological guidelines and evidence submission template developed by EUnetHTA and asked for a periodical revision of the methodological framework used for assessment in order to adapt it to scientific advances. Special features characterising certain technology (e.g. AMTPs) might also require a more specific clinical study design, which is already often accepted for the purposes of regulatory assessments. The methodology should thus be sufficiently flexible to include the acceptance of the best available scientific evidence at the time of the submission. The Committee also proposed that each Member state shall appoint to the Coordination Group at least one authority or body with expertise in medicinal products, one with expertise in medical devices and one for in vitro diagnostics. At the end of the transitional period, the identification of emerging health technologies in the field of medicinal products shall reflect EMA pre-notification prior to MA applications; the Coordination Group shall thus initiate joint clinical assessments according to this. A procedure is also suggested to allow developers to object in writing to the results of the approved joint clinical assessment report and summary report.

The Committee on the Environment, Public Health and Food Safety published in May 2018 its draft comments (Soledad Cabezón Ruiz as Rapporteur). Among main requests, the Committee underlines that a high percentage of marketing authorisations for medicinal products are not accompanied by a comparative effectiveness study and the fact “the high price of medicines, in many cases without these being of added therapeutic value, and the lack of new treatments for certain diseases” are among the main barriers to access.
The comments also contains the proposal to move towards a centralised authorisation system for medical devices based on safety, efficacy and quality. The transparency of the procedure should be guaranteed by the public availability of all data used for the HTA, including clinical data, studies, the methodology and the clinical results. “The highest possible level of public openness in scientific data and assessments will allow progress to be made in biomedical research and ensure the highest possible level of confidence in the system”, wrote the Committee, while the Commission’s proposal indicated the way of wide consultations with the interested parties. From this point of view, the Committee also asks that all “stakeholders involved (ndr. in HTA) are neither profit-making entities nor funded by technology developers”.
The Committee also suggests that the cooperation in the field of HTA may also cover areas such as complementary diagnosis, surgical procedures, prevention and health promotion programmes, information and communications technology (ICT) tools and integrated care processes. According its comments, the approval of the assessment should not be based on a simple majority (as proposed by the Commission), but instead on the consensus or, where not possible, by a two-thirds majority of Member states present. The conclusions of the joint clinical assessment report, asks the Committee, shall “include” (and not “be limited to”) the requirements indicated by the regulation and be based on the best” available “clinical” evidence. The conclusions and all documentation supporting HTA shall be made public available on the common IT platform for HTA to be created at the European level. This also applies to any decision to withdrawn the application or to stop the assessment made by EMA. The Summary report of all assessed technologies should be included at the end of the procedure in a positive or negative list. These lists shall represent the reference for Member states to not duplicate efforts at the local level. The joint assessment should be reviewed at least every five years to update it to new evidence.

Questions to the European Parliament

Some written questions to the European Parliament on the draft proposal have been also presented.
Deputy Alfred Sant (S&D) asked information about how the Commission run the calculations in order to estimate the total costs involved in undertaking an HTA for a new medicine across EU Member States and the potential cost savings from a unified approach to HTA as recommended in its proposal. Mr Sant was also interested in better knowing the estimated extent to which delays in assessing a medicine or technology can be reduced through the introduction of a joint HTA assessment.
Deputy Roberto Metsola (PPE) asked if the Commission’s proposal will focus on the issue of having multiple national assessments for the same products that sometimes produce different results for patients and industry.

Answer to this last question was provided by Health Commissioner Andriukaitis, according to which the proposal is appropriate and proportionate to the problems identified in the impact assessment report, including duplication and divergent outcomes. The unique European framework proposed for joint clinical assessment of the most innovative health technologies should prevent duplications at the national level. “Harmonised rules will be developed on how clinical assessments are carried out. These rules are foreseen both for clinical assessments at Union level and for those assessments that have not been prioritised for assessment at Union-level and are therefore carried out at national level”, said Mr Andriukaitis. Member States shall also have the opportunity to cooperate, on a voluntary basis, on the non-clinical aspects of HTA.

Some examples at the national level

In France, taken as an example of country with well established procedures, policies for HTA and pricing and reimbursement of medicines are established by the Haute Autorité de Santé (HAS, see for example this presentation).
The benefit/risk evaluation that leads to MA is run by the Agence nationale de sécurité du médicament et des produits de santé (ANSM), or by EMA in the case of centralised procedures. After the opinion on HTA issued by the Transparency Committee of HAS, the final decisions on price, level of co-payment and inscription into lists are taken by the Ministry of Health.
All medicines have to be assessed by HAS on the base of medical evidence to be included in the positive list of reimbursed products, under a separate process with respect to price determination run by the Economic Committee for Health Products (CEPS). Assessment is renewed at least every five years for products listed as available in community pharmacies, or when new evidence is available.
Effectiveness, relative efficacy and healthcare need form the base to calculate price and reimbursement. Required data include results from randomised clinical trials or meta-analysis, tolerance data and pharmacovigilance. A discussion of comparators and therapeutic strategy is also requested. Reimbursement rates are linked to the effective benefit provided, ranging from important (65%) to moderate (30%) and mild (15%). Products showing an insufficient benefit are not included in the positive list. The assessment takes also into consideration how the new medicinal product can ameliorate the patient situation (on a five degrees’ scale) in comparison to already available therapeutics, in order to establish its relative value.

In Poland, the Agency for Health Technology Assessment (AHTAPol) is quite young, as it was established in 2005. It acts as an advisory body to support the Minister of Health in the decision-making process and is responsible for running HTAs, produce reports, and for the collection and dissemination of all information on the process, including methodologies to be used. AHTAPol structure has been developed under the Transition Facility 2005 Project financed by the EU Commission, that shall also contribute to future expansion of its capabilities and to training of its workforce.
The four main departments of AHTAPol (for a total of 40 permanent staff) are in charged respectively of HTA, international cooperation, economic analysis and monitoring costs of health services. Appraisal of HTA reports and issuing of the recommendations for the assessed technologies are under the responsibility of the Consultative Council, made of 8 members appointed for five years. AHTAPol Director presents the final recommendations to the Minister of Health. Assessment reports are published on the AHTAPol website, with abstracts available also in English.

Greece greatly suffered the effect of the 2015 economic crisis, resulting in the deterioration of its public healthcare system. Since then, the country is undergoing a profound programme of reforms with the aid of the European Union and other international institutions. Several actions are already in place also to strengthen the capacity of national competent authorities to perform HTA’s activities.
A WHO/Europe mission, for example (see here for more information), took place in Greece in 2017 under the Strengthening Capacity for Universal Coverage (SCUC2) initiative with the aim to assess previous actions, provide technical and legal support to the authorities on the proposed new legislative framework, and identify short- and medium-term objectives to create a suitable environment for HTA-based decision-making.
The SCUC initiative aims to support authorities in the move towards health universal coverage and the transformation of the Greece’s medicines reimbursement system. During the meeting the parties agreed on future steps in HTA policy implementation, related mainly to developing national capacities to run the assessment. The discussion saw the participation of Greece’s Ministry of Health, members of the HTA Working Group and its legal team, the director of the National Organisation for Medicines (EOF), members of the Negotiating Committee and the current Positive List Committee, and the director of the Institute of Pharmaceutical Research and Technology (IFET). Technical support and inputs to the discussions and development of the legal framework was provided by experts from Portugal’s HTA agency, INFARMED, being part of the WHO team.