Guidance

Regulatory research dementia workshop conclusions

Published 16 March 2015

On 10 November 2014 the UK government brought together 11 regulators from 10 authorities, leading clinical experts and a patient representative held talks in Geneva about dementia.

The meeting was chaired by Raj Long (Senior Regulatory Officer, Integrated Development, Global Health, Bill & Melinda Gates Foundation; Global Integrated Development Independent Expert; Regulatory Lead, World Dementia Council).

The meeting was the first time the regulators had met globally to discuss dementia. The meeting provided valuable insight into the need for a supportive regulatory approach to the development of new medicines in light of the high unmet medical need.

1. Problem statement

Scientists have made remarkable strides in understanding how Alzheimer’s disease and dementias affect the brain, since Alzheimer’s disease was first described in 1906. However, there remain important gaps in the understanding of dementias, hampering the discovery of effective treatments.

There is no regulatory solution for the scientific gaps in the understanding of the disease. Those gaps must be addressed by the scientific community in order for regulators to be able to contribute to strategies that can be used to bring innovative therapies to the market. All regulators present at the Geneva workshop agreed there is a need to work collaboratively to discuss and address the challenges facing dementia research and drug development.

Participants included:

• European Medicines Agency
• Italian Medicines Agency
• Danish Health and Medicines Authority
• Medicines and Healthcare products Regulatory Agency
• Medicines Evaluation Board
• Federal Institute for Drugs and Medical Devices
• Swissmedic
• US Food and Drug Administration
• Health Canada
• Pharmaceutical and Medicines Devices Agency, Japan

2. Six areas identified to work towards a solution and agreed way forward

1. Attrition analysis to examine the factors-features that triggered termination of development over the last 10 to 15 years. Regulatory experts, clinical experts and analysts will assemble and analyse a relevant sample of data and work with International Federation of Pharmaceutical Manufacturers & Associations to gain an industry perspective.

2. Clinical trial efficiency to improve the operational efficiency of clinical trials, particularly in later stages of development (after proof-of-concept), ie master protocols, basket trials; regulatory experts will draw together transferable insights from the changing conduct of oncology, rheumatology and antimicrobial resistance trials.

3. Modelling and extrapolation to incentivise the path forward, by developing extrapolation models that translate rare genetic forms of dementia and other psychiatric disorders to the wider population. Theoretical models and approaches taken from other psychiatric disorders will also be elaborated.

4. Composite end points to foster activities in the development of standardised and validated endpoint components for cognitive impairment, ADL/functioning, possibly lab values and imaging results at the early stages of Alzheimer’s disease (not mild to moderate or severe Alzheimer’s disease), which are reliable and sensitive to change.

5. Multilateral cooperation to build on existing international platforms and dialogue between regulatory agencies to foster opportunities for multilateral interactions in the specific situation of Alzheimer’s disease and promote global regulatory efficiency and consistency. This could, for example, include reducing unnecessary testing replication and methodology testing.

6. Benefit-risk balance to develop a concept paper considering how best to manage the likely high level of uncertainty at the time of regulatory submission. Due to high unmet medical need, expedited regulatory approval procedures will be considered.