EU regulators are preparing a new guideline to assist companies in the development of treatments for Autism Spectrum Disorder (ASD), a collective term referring to the wide range of disorders that make up autism, saying that companies could stand to benefit from a clear framework by which they could bring new treatments to market.
Autism encompasses a number of classifications beyond "classic" autism, including Asperger's disorder, Rett's disorder, Childhood Disintegrative Disorder, and Pervasive Developmental Disorder. These conditions vary wildly in their severity and particular impairments, which range from relatively minor impairments (Asperger's) to the most severe ("classic" autism).
Collectively, the disorders affect approximately 1% of the population, though this number has risen in recent years along with a greater and more nuanced understanding of ASD.
Regulators Ask How to Move Treatments Forward
The problem from a regulatory perspective, however, is determining how to test pharmacological or biological treatments that might benefit patients.
The European Medicines Agency (EMA) notes that researchers presently lack any validated or reliable biomarkers, the likes of which are often used to show evidence of efficacy in clinical trials. Without such biomarkers, it is therefore difficult for both companies and regulators to effectively assess both patients and treatments, both of which are necessary for final approval of a product.
"Although various therapies and interventions are available, few are supported by scientific studies," EMA explained in a concept paper on the topic. "Pharmacotherapies approved to date for the management of autism have been non-specific for the condition (e.g. atypical antipsychotics for control of behavioural disturbance)."
While new treatments are being developed, the companies in charge of development are largely doing it in an area uncharted by regulatory officials-something EMA says it now wants to change.
Guidance is Needed
"Guidance is needed especially with regard to diagnostic criteria, definition of target treatment populations, efficacy criteria, specific age-category problems (childhood versus adulthood), and the need for comparative studies," EMA wrote.
In addition, because autism is a life-long condition, EMA said it's particularly interested in making sure that any treatments are studies in patients of all age groups and over a sufficient time frame to show if a product is safe for long-term use.
EMA goes on to explain in the concept paper that any guideline on the safety and efficacy of ASD treatments would need to address numerous clinical trials considerations, including how patients are identified and selected for a trial, which subgroups of ASD a patient belongs to, whether patients would be allowed to concomitantly take any medications during the trial, if any exclusion criteria exist for a trial, the age cohorts for patients, and whether results might be able to be extrapolated to other disorders on the ASD spectrum.
Trial Design Considerations
In addition, EMA wants the guideline to focus heavily on the design of the clinical trial, including the use or choice of comparator products, standards of care, strategies for dose-finding in early-stage trials, the choice of endpoints (including whether to use validated symptom rating scales), the assessment of long-term safety data, and the extrapolation of data to non-EU patients (such as those in the US).
EMA noted that it hopes to have such a guideline published in 2014, with a six-month comment period open to allow for public comment.
The current concept paper is open for comment until 4 July 2013, after which time those comments will be incorporated into the development of the guideline.