EMA releases new guidance on methods to be used in the design and conduct of post-authorisation efficacy studies

Cell-based, gene-based and tissue engineering products are Advanced Therapy Medicinal Products (ATMPs) as established by European Union (EU) Regulation 1394/2007/EC, and as such they are regulated as medicinal products.

With the aim to provide support for better use of medicines, including ATMPs, the European Medicines Agency (EMA) has published a new draft scientific guideline for post-authorisation efficacy studies (PAES), which describes how these should be designed in case additional evidence of efficacy is required following marketing authorisation (MA) of medicinal products.

PAES have to be generated within the authorised indication to support regulatory decision making in the European Union (EU) if, post standard MA, a well-reasoned scientific uncertainty arises, the resolution of which is linked to a better understanding of both therapeutic efficacy and benefit–risk balance. The situations where a PAES can be required by medicines regulatory authorities in the EU were specified by the European Commission in April 2014. Prior to that date, regulators could request these types of studies in certain cases such as in the context of non-standard MAs (including conditional MAs and MAs under exceptional circumstances), paediatric use or referral procedures.

The knowledge generated by PAES is intended to provide complementary information about the benefits of the product that were assessed during its MA process. As such, it can be originated voluntarily by companies or imposed by regulators. In the latter case, PAES can be required at MA recommendation when there are questions about the efficacy of the medicine that can only be answered once the medicine has been marketed, or even after a MA has been granted if new data indicate that the benefits of the medicine should be further explored.

Overall, these studies are conducted to collect evidence data on the benefit aspects of a medicine which can be observed only once the product is marketed. For instance, a well-reasoned scientific uncertainty can emerge from the use of the medicinal product in certain patient target sub-populations, when clinical outcomes were measurable only until MA but endpoints in the long-term have never been characterised, or for treatment on an intermittent, repeated or continuous basis, as well as with concurrent treatment with other medicinal products. In addition, it can also arise from real life usage, e.g. when it emerges that the product usage impacts on the behaviour of the recipients and on its therapeutic benefit.

It is established that PAES studies must be conducted according to ethical standards, be feasible, and provide reliable and interpretable results which ultimately translate into better use of the tested medicinal products in clinical practice. As such, methodologies to be followed include randomised clinical trials, observational studies, data collection and safety aspects.

The draft scientific guideline applies to imposed and voluntary PAES. It has been developed in collaboration with the EU Member States and other interested parties and is released for a three-month public consultation.

EMA invites comments on the scientific guideline until 31 January 2016. They should be sent to paesconsultation@ema.europa.eu using the form provided on the EMA website.

Author: Giulia Detela

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