The majority of clinical development plans submitted for scientific advice to the European Medicines Agency (EMA) prior to a marketing authorization application were found not suitable for future benefit-risk assessment. Companies that changed their clinical development plans in accordance with the recommendation from EMA were more likely to be granted a marketing authorization.

These are the main findings of an analysis of marketing authorization application outcomes between 2008 and 2012, conducted by staff members of EMA and its Scientific Advice Working Party (SAWP) and published in Nature Reviews Drug Discovery.

EMA, through its SAWP, provides scientific advice to sponsors during development of their medicines to help them design trials that are scientifically sound and generate adequate data for the benefit-risk assessment by EMA’s Committee for Medicinal Products for Human Use (CHMP).

Scientific advice is the agency’s key instrument to support the development of high-quality, effective and safe medicines that meet the needs of patients. By providing scientific advice to medicine developers, EMA also protects patients from participating in clinical trials unlikely to lead to the approval of new medicines.

Detailed analysis of marketing authorization applications received by EMA that had an opinion between 2008 and 2012 and of the scientific advice provided to these applicants shows that:

• two out of three programs submitted for scientific advice had poor clinical trial designs inadequate to generate data for the assessment of the benefits and risks of the medicine;
• an acceptable trial design at the time of scientific advice, or a change of a deficient trial design to conform with scientific advice recommendations, equally increased the likelihood of a positive outcome with success rates of 84% and 86%, respectively, compared with only 41% when a deficient clinical trial design was not adapted according to recommendations;
• compliance with scientific advice on clinical trial design was associated with a reduction in major objections raised by CHMP during the assessment of the application, and a 61-day shorter assessment procedure on average, meaning these medicines may be available to patients earlier.

A number of medicines fail to obtain marketing authorization due to deficiencies in clinical trial design and the inability to demonstrate that the benefits of the medicine outweigh its risks. This not only deprives patients of new medicines but also means patients may participate in clinical trials not suitable for generating data for regulatory assessment.

Scientific advice offers an opportunity to initiate a scientific dialogue on all aspects of the development of a medicine including clinical trial design. Scientific advice should be sought sufficiently early in the development of a medicine to ensure appropriate changes can be implemented where necessary.

A request for scientific advice is voluntary and sponsors are not obliged to comply with it. Provision of scientific advice is not a guarantee sponsors will obtain marketing authorization. The assessment of the data generated through the development program is independent from scientific advice.

A positive recommendation on marketing authorization by EMA’s CHMP is based on an assessment concluding an overall positive benefit-risk balance.