Natural history studies and clinical trial readiness for genetic developmental and epileptic encephalopathies

Title: Natural History Studies and Clinical Trial Readiness for Genetic Developmental and Epileptic Encephalopathies

Affiliation: University of New South Wales and University of Melbourne

Authors: Elizabeth Palmer, Katherine Howell and Ingrid Scheffer

Reference: Neurotherapeutics 2021;18:1432-1444

We thank Dr David Cunnington for providing us with a summary of this work.



What did they do? 
This article isn’t a research project. It is a summary of the role of Natural History Studies (NHS) to prepare for clinical trials and inform development of treatments for Developmental and Epileptic Encephalopathies. Dr Palmer and the other authors have broken down the role of NHS in a thoughtful and structured way, which helps to understand why NHS are so important. 
What were the main points? 
Some of the key points highlighted by the authors are: 
  • Assessing the effectiveness of new treatments requires a deep understanding of the interaction between gene changes and physical symptoms as well as how a condition evolves or changes over time. 
  • NHS provide this in a way that simpler registry studies do not, as the breadth of data collected prospectively over time gives valuable information that helps with: 
    • Design of clinical trials and selection of outcome measures that are important and relevant to patients and their families as well as reducing disability and mortality.  
    • Providing historical control data – ie what happens to people with a particular DEE without treatment – which is essential for drug registration and ultimately reimbursement. Without this data to demonstrate ‘bang for buck’ with these expensive treatments they may never be funded. 
    • Identifying sub-groups of patients within specific DEEs who may derive greater, or lesser, benefit from a particular treatment
What does this mean? 
This article highlights the critical nature of NHS in DEEs and other rare genetic disorders in providing a core data set to inform the development of treatments, clinical trials of their effectiveness and if shown to be effective, support their registration, reimbursement and ultimately use to help reduce the disability and mortality associated with DEEs