2. Post-Authorisation Efficacy Studies (PAES)

1. Scope of Post-Authorisation Efficacy Studies (PAES)

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‘The aim is to enable regulators to request such studies when there are important questions about the efficacy of the medicine that can only be answered once the product is in general use, or when questions arise in the post-authorisation period.’ Dr Stella Blackburn, EMA, 2011 

PAES are imposed in accordance with the Commission Delegated Regulation (EU) No 357/2014 [1] . They mean an efficacy study which is requested by a Competent Authority based on at least one of the situations set out in this regulation.

The results from a PAES are considered important for complementing available efficacy data and must be submitted because they may have the potential to impact on the benefit-risk balance  of the medicinal product or product information. PAES should [2] not lead to the premature granting of marketing authorisations - they cannot be used to compromise the initial level of evidence that is required to grant a marketing authorisation.

A PAES conducted post-authorisation can be imposed either:

• At the time of granting the marketing authorisation:
• when concerns relating to some aspects of the efficacy are identified and can be resolved only after the medicine has been marketed.

• After granting the marketing authorisation:
  • when the understanding of the disease or the clinical methodology or the use of the medicinal product under real-life conditions indicate that previous efficacy evaluations might have to be revised significantly.
  
  

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  [1] COMMISSION DELEGATED REGULATION (EU) No 357/2014
  https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=OJ:JOL_2014_107_R_0001&from=EN

  [2] Legal requirements are identifiable by the modal verb “shall”. Recommendations that are not legal requirements are provided using the modal verb “should”.

  
  

2. Initiation of a PAES

A PAES may be required to be carried out by the holder of a marketing authorisation by:

• The national competent authorities (NCAs)
• The European Medicines Agency (EMA)
• The European Commission (EC)

A PAES shall only be required if one or more of the following cases arise:

1. An initial efficacy assessment based on surrogate endpoints which requires verification.
2. In case of medicinal products that are used in combination with other medicinal products, the need for further efficacy data to clarify uncertainties.
3. Uncertainties with respect to the efficacy of a medicinal product in certain sub-populations that could not be resolved prior to marketing authorisation.
4. The potential lack of efficacy in the long term that raises concerns with respect to the maintenance of a positive benefit-risk balance of the medicinal product.
5. Benefits of a medicinal product demonstrated in clinical trials are significantly affected by the use of the medicinal product under real-life conditions or, as for example in the case of vaccines, protective efficacy studies have not been feasible.
6. A change in the understanding of the standard of care for a disease or the pharmacology of a medicinal product that requires additional evidence on its efficacy.
7. New concrete and objective scientific factors that may constitute a basis for finding that previous efficacy evaluations might have to be revised significantly.

Irrespective of the above points it is also possible to impose the conduct of PAESs in the specific situations of a MA granted:

• conditionally
• in exceptional circumstances
• to an advanced therapy medicinal product
• the pediatric use of a medicinal product
• a referral procedure initiated.

To note: Health Technology Assessment results cannot trigger a PAES.