EMA drafts scientific guidance on post-authorisation efficacy studies
The advice focuses on methodological considerations and the potential role of particular study designs
The European Medicines Agency (EMA) has released scientific guidance for marketing-authorisation holders and national regulators staging post-authorisation efficacy studies.
The advice focuses on methodological considerations and the potential role of particular study designs. These studies can either be staged voluntarily by pharmaceutical companies or under order by a regulator, investigating 'well-reasoned scientific uncertainties on aspects of the evidence of benefits that should be, or can only be, addressed post-authorisation', said the guidance.
It added that it should be ethical and feasible to design studies with a suitable methodology to give reliable and interpretable answers, giving information on a medicine’s usage and labelling. 'Agreement should be sought as early as possible between the regulator and sponsor on the appropriateness of a study design to achieve this,' it said.
The choice of study design should be based on the scientific uncertainty being addressed, enabling it to be completed within a reasonable timeframe. Pre-authorisation clinical trial methods should also be used, including placebos and controls with an established medicinal product of proven therapeutic value. For instance, data can be collected from a focused study and previously collected data from electronic patient healthcare records.
The guidance outlines when pharmaceutical companies should use explanatory clinical trials, pragmatic trials, observational studies, studies with concurrent controls and studies with historical comparison data. For instance, non-randomised observational studies may be considered for investigating benefits where randomisation is unethical or unfeasible; outcomes are infrequent or far in the future; the generalisability of randomised trials is limited; outcomes are highly predictable; or effect sizes are very large.
The guidance also advises on specific scientific situations such as exploring uncertainties within patient sub-groups; benefits from end-points; treatment over time; co-treatment with other products; and real life use. It added that a post-authorisation study may be needed looking at vaccines where protective efficacy studies have not been feasible or could further determine the impact of microbial epidemiology and immunity.