EMA "road map" calls for more collaborative approach to drug regulation

The European Medicines Agency (EMA) has outlined a vision of the future EU regulatory environment where regulators and industry start working together earlier on in the drug development process to improve the chances of approval, and information on discontinued drugs is shared with the scientific community to help avoid repetition of studies and reduce the drug development attrition rate.

In this scenario, "staggered" or accelerated approval systems will be used to speed up the availability of certain products for limited initial populations or for neglected diseases, and patient safety will be increased through more efficient post-authorisation monitoring of the benefits and risks of drugs in the real-life setting.

The EMA will work more closely with health technology assessment bodies to ensure they do not diverge too much in their respective assessments, and will be recognised as a "leading authority" in the evaluation and supervision of medicines.

These are among the objectives and aspirations outlined in the agency's draft "Road Map to 2015", which was put out for a three-month consultation on January 26th – a date that also marks the 15th anniversary of the agency's creation in 1995.

Like the 2010 version before it, the new road map assesses achievements so far and looks at what needs to be done over the coming years to ensure the regulatory system is up to speed and that the agency continues to fulfil its public health role.

The 2010 document focused on the need to ensure high-quality assessment of new drug applications, allow rapid access to safe and effective medicines, improve safety monitoring and information for patients and healthcare professionals, and strengthen the EMA's role as a public health-oriented, science-driven and transparent agency working in a network with the other EU regulatory bodies.

The new road map takes these and other priorities forward, with a particular focus on improving pre- and post-authorisation benefit-risk assessment and safety monitoring, reducing the failure rate for new drugs, and boosting the approval of medicines for neglected diseases and specific populations. Many of these topics were raised by EMA executive director Thomas Lönngren at the EMA/TOPRA meeting last December (scripnews.com, December 4th, 2009).

All these issues, says the agency, will need to be addressed within the context of increasing globalisation, advances in medicine, science and technology, and an increasingly risk-averse and information-hungry public – not to mention developments such as the European Commission's review of legislation on pharmacovigilance, counterfeiting and medical devices.

priority areas

The EMA breaks down its objectives for the next five years into three priority areas: addressing public health needs, improving access to medicines, and optimising the safe use of medicines.

1) Addressing public health needs

Ways are needed to stimulate the development of drugs for unmet medical needs and neglected diseases (including rare diseases and the need for novel antibiotics), says the agency. It makes a number of suggestions, including an accelerated assessment scheme for medicines for unmet needs and giving the agency more of a role in advising the EU institutions on gaps in drug development (including those for use in developing countries).

More generally, it says the EU regulatory system will need to be adapted to take account of new and significant challenges on the horizon, notably nanotechnologies, synthetic biology, and regenerative and personalised medicine. The agency already has some experience in the personalised medicine field: some centrally authorised drugs have pharmacogenomics indications.

To meet these challenges, the agency proposes to use existing specialist expertise to look at how the regulatory framework can adapted to these new technologies, alongside existing initiatives such as the biomarker qualification procedure and the agency's provision of support to the Innovative Medicines Initiative.

2) Improving access to medicines

In the area of access to medicines, the EMA's priorities include tackling the high attrition rate in the drug development process, strengthening benefit-risk assessments and improving the consistency of new product review outcomes.

It says that attrition (a major target of the IMI initiative) could be addressed by improving the scientific advice process and ensuring that companies adhere to the advice it gives them. "Feedback has indicated that both the suboptimal management of the medicine development process by sponsors as well as new requirements for medicine development have been identified as important contributing factors[to the attrition rate]", the agency comments.

It will also be important to ensure that the regulatory authorities get involved with companies' early-phase development plans so that they can gain more timely knowledge of the data, which in turn will facilitate the scientific review process. The agency suggests expanding the scientific advice concept to provide "continuous scientific support" during the development process, and appointing rapporteurs for each approval dossier at an earlier stage.

Steps should be taken to make information on drugs that have fallen by the wayside available to the scientific community, the EMA suggests, noting that even a failed development process can generate useful data that is normally lost either because it is considered proprietary information or the regulators do not have access to it.

This kind of data can help to avoid repetitive and redundant studies in humans or animals, as well as the use of inappropriate parameters, it observes. "The agency is of the view that it would seem appropriate to explore what incentives could be offered to make this otherwise lost information available to the scientific community."

benefit-risk assessments

A good benefit-risk assessment is vital to ensuring new drugs are made available as early as possible without undue risks to patients. The EMA says it will continue to improve this assessment by introducing more quantitative elements into the methodology and taking account of "patients' values" and the availability of other therapies for the disease in question.

It will also press on with efforts to increase the transparency of its benefit-risk assessments, including a justification for any decisions taken. This, it says, is particularly important if its views are not in line with those of other (non-EU) regulatory authorities. (It does not mention this, but divergences of opinion are often seen between the EMA and its US counterpart, the FDA.)

The benefit-risk assessment should be improved by more continuous dialogue during the assessment of an approval application, the use of more statistical expertise, and involving patients' views more closely, according to the EMA.

In some cases, early availability could be achieved through a "staggered approval" system, where the drug is initially approved for a better defined or more restricted population, and then broadened to a wider population when more "real-life" data are available.

Not content with that, the agency proposes broadening the concept of the risk management plan (RMS), which is now a core requirement for most new drugs. It says that while RMSs have been "a real step forward", the concept now needs to be expanded to include information on benefits too, so that the benefit-risk assessment can more easily be continued throughout the product's life cycle. "Therefore, the current risk management plan for medicines for human use should be converted into a benefit-risk management plan," it declares.

health technology assessments

Another aspect to be considered when discussing access to medicines is the health technology assessment (HTA). Following on from a recommendation by the Pharmaceutical Forum in 2008, the agency has been looking at how it should become more involved in providing data for HTA bodies.

It says that the drug licensing process and the relative effectiveness/cost-benefit process are two separate things, and should remain so. However, because they can differ in terms of clinical endpoints, efficacy versus effectiveness, relative efficacy versus placebo, etc, regulators and HTA bodies often take very different approaches to the same product, the EMA observes.

To help address this problem, it has been suggested that the European Public Assessment Report (EPAR) – the summary of the outcome of the new drug evaluation– should be improved to make the data more useful to HTA bodies. The EMA says that it will look at how this can be done, "while continuing to ensure that cost-benefit assessment remains distinct and separate to the licensing process".

One way would be to give more information on the scientific evaluation as summarised in the EPAR, including the rationale for the decision or opinion, and putting more emphasis on the quantitative aspects of the evaluation, the agency says. It also plans to work with HTA bodies early on in the development process "to avoid as much as possible the appearance of two different medicine development programmes".

3) Optimising the safe use of medicines

Drug safety is never far from the public eye, and it is no doubt partly with what it calls the "increasingly risk-averse" public in mind that the EMA has come up with a number of measures to help ensure patient safety. One of these is to obtain more information on the "real-life" use of medicines, perhaps by including post-authorisation drug development in the scientific advice process.

More post-authorisation data on the benefits and risks of new drugs will come from the growing use of conditional marketing authorisations (where the manufacturer agrees to provide more information after approval) and the introduction of new biomarkers, the agency says. "This should ultimately lead to an integrated assessment of benefits and risks under real life conditions."

leading the way

The EMA is also making a bid to be recognised as "a leading authority in the field of evaluation and supervision of medicinal products". It says: "Irrespective of the currently ongoing political debate on the best way forward for providing information on medicines to patients, the agency should strive to become the authoritative source of information for all medicines evaluated by it."

Over the coming years, it wants to analyse the impact of regulatory decisions on public health, and has already begun outcomes research to this end. Activities will include studies on how medicines are actually being used as compared with their intended use, the effectiveness of risk-minimisation measures, and how far the current regulatory model is contributing to better therapy outcomes.

As part of the public consultation process on the road map, the EMA plans to hold a number of workshops and face-to-face discussions this year. Regular updates on progress will be provided before the final document is adopted by the agency's management board, probably in December.