European Medicines Agency: leave the UK but remain the same

Introduction

The current period of unprecedented financial crisis has raised growing doubts on the results so far achieved by the European Union, starting from economy and welfare, and pharmaceuticals are hardly an exception. The so-called ‘Brexit’ has formally raised the question of the European Medicines Agency moving from Great Britain to an EU Member State in the near future. After its inception in 2005, the European Medicines Agency – a big agency indeed, with a budget of €324.7 million and 890 employees in 2015 – has been mainly criticised as being too cosy with the pharmaceutical industry, which contributes around 70% of its budget, rather than patients’ interests. ¹ Here we discuss the European Medicines Agency's role so far in the different steps of the European drug regulatory procedure and envisage an alternative scenario for the future, with a general proposal for redesigning its scope before the presumed move.

EU regulatory procedure

The European Medicines Agency's role has been limited from its start to the evaluation of drug efficacy and safety for market approval, like the Food and Drug Administration in the USA, while pricing and reimbursement are managed on a country basis by the regulatory authorities of each EU State. ² After centralised drug registration for market approval by the European Medicines Agency, the regulatory procedure of an ethical drug proceeds at national level for pricing and reimbursement. The management of this process can vary a lot by country. It can involve a single agency, as in Italy (AIFA, Agenzia Italiana del Farmaco) or more than one, as in France and Germany. In general, decision-making is claimed to be based on clinical evidence for efficacy (overall, including effectiveness) and safety, and on economic evaluation for cost-effectiveness.

The most recent European Medicines Agency tendency is to fast-track drugs to marketing through what is known as ‘adaptive licensing’. ³ Once preliminary efficacy and safety have been assessed, the evaluation of comparative efficacy and cost-effectiveness is entirely devolved to national authorities. The underlying strategy is to make new drugs available as soon as possible to patients, empowering each EU nation to negotiate the best drug price and reimbursement conditions.

An alternative scenario

An alternative European pharmaceutical policy would be to strengthen the European Medicines Agency's role and expand its tasks. In contrast to the current trend, the European Medicines Agency could require a comparison of a new drug from the very beginning with the best treatments available and then assess, through ‘head-to-head’ clinical trials for market approval, their ‘added therapeutic value’ at European level. ¹ The evidence on comparative efficacy would enable the European Medicines Agency to classify the new drugs approved according to their innovation potential and group them in at least two categories: (1) drugs offering limited therapeutic gains and (2) innovative drugs addressing important ‘unmet needs’. The European Medicines Agency could cluster the drugs in the first group with those already marketed and therapeutically overlapping. Then national authorities could price the new drugs on the basis of the actual prices of their ‘competitors’ in domestic markets. The second group, presumably fairly small, could be subject to a value-based approach for pricing. ⁴ The European Medicines Agency could develop internal skills to consult national authorities and increase the credibility of the inevitable economic modelling necessary for assessing the cost-effectiveness of an innovative drug, at the same time deterring companies from submitting flawed economic evaluations. ⁵

In general, this ‘dual approach’ could support national authorities better in negotiating discounts, to make the budget impact of new drugs on public pharmaceutical expenditure more sustainable in relation to local income, epidemiology and prescription patterns. It should also eventually generate ‘economies of scale’ in the long run for the regulatory authorities of the EU Member States.

Policy implications

When the European Medicines Agency was established two decades ago, expectations were very high, like for any other EU agency. The centralised procedure would have gradually replaced mutual recognition among EU Member States ⁶ and – hopefully – would contribute to harmonisation of European pharmaceutical policy. In the last decade, however, the European Medicines Agency has increasingly restricted its decisional scope to preliminary efficacy and safety. This has led national authorities to strive to exploit their purchasing power in pricing and reimbursement negotiations at best, without being backed by robust clinical evidence, especially in the last few years of deep crisis and boom of sky-high priced bioagents. ⁷ This trend has made the ‘puzzle’ of pricing and reimbursement at national level even more fragmented ⁴ and has hardly reduced the overall administrative burden of national regulatory authorities. For instance, AIFA in Italy has increased its employees from 260 to 385 in the last five years.

The underlying strategy of constraining companies’ requirements for new drug approval mainly to less risky clinical trials (of superiority versus placebo and/or non-inferiority versus active comparators) ¹ and then postpone assessment of effectiveness and cost-effectiveness to real-world evidence after marketing seems to be long on promise and short on delivery. ⁸ The proposed benefits are unlikely to be seen in the short run for effectiveness and even in the longer run for costs.

To sum up, in the absence of a drastic change of strategy in the near future, the European Medicines Agency risks becoming mainly an ‘added cost’ for the European pharmaceutical regulation, with little (if any) ‘synergy’ for the Member States.

Comment

We question the present European strategy of limiting the European Medicines Agency's role to preliminary efficacy and safety for market approval and of passing down to the regulatory authorities of each Member State the assessment of comparative efficacy and cost-effectiveness for domestic pricing and reimbursement. We are firmly convinced that the European Medicines Agency would do better to press the pharmaceutical industry to show evidence of comparative efficacy for new drugs before market approval, thus contributing to setting domestic prices and lists according to their incremental efficacy when evident. We are offering this as a proposal open to debate.