EMA Issues Draft Guidance on Post-Authorization Efficacy Studies

Regulatory News

The European Medicines Agency (EMA) today issued draft scientific guidance intended to help sponsors design post-authorization efficacy studies (PAES).

The guidance, which comes a year after a new regulation, known as the Commission Delegated Regulation (EU) No 357/2014, established circumstances in which EU regulators could require PAES for all medicines. In the past, PAES were typically only required for medicines approved conditionally or under exceptional circumstances.

In addition to its scientific guidance, EMA also released a new questions and answers guideline intended to answer regulatory and procedural questions related to PAES.

Post-Authorization Efficacy Studies

PAES are sometimes required to determine aspects of a medicine's benefits "that can only be or need to be explored" after a product is approved. The studies can help clarify a products benefits in clinical practice or in other real-world scenarios that would be difficult or unnecessary to demonstrate in clinical testing.

However, the Commission cautions that these studies "should not be used as a justification for the premature granting of a marketing authorization."

Under Commission Delegated Regulation (EU) No 357/2014, national regulatory authorities, EMA or the EC can require PAES:

1. "where concerns relating to some aspects of efficacy of the medicinal product are identified and can be resolved only after the medicinal product has been marketed;
2. where the understanding of the disease, 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."

EMA says it expects these studies will "translate into better labelling and better use of medicines by patients and prescribers in clinical practice."

EMA Guidance

EMA says in the draft guidance, Scientific guidance on post-authorisation efficacy studies, can be applied to both imposed and voluntary PAES.

The agency says sponsors should select a study methodology "based on the scientific uncertainty to be addressed," and should be "feasible, ethically acceptable and of a design known to return reliable and interpretable results."

The guidance goes into additional detail on the specific circumstances in which a PAES may be imposed, including when there are uncertainties related to specific patient sub-populations, surrogate endpoints used to support marketing authorization or changes in scientific knowledge that "bring into question the criteria used to establish the efficacy of a medicinal product."

While PAES studies can be randomized or non-randomized, EMA says "studies involving randomization may be … preferred," but acknowledges that in some situations non-randomized studies may be appropriate, "where measures are included to minimize limitations/biases."

The agency says non-randomized observational studies should be conducted only when "randomization is unethical or unfeasible, outcomes are infrequent or are far in the future, the generalisability of randomized trials is limited, outcomes are highly predictable, or effect sizes are very large."

EMA

Scientific guidance on post-authorisation efficacy studies

Post-Authorisation Efficacy Studies: Questions and Answers