What are the problems with CNS research?
Great difficulties are encountered in clinical trials for the development of new central nervous system (CNS) – related psychiatric drugs. While drugs intended for CNS pathologies constitute 21 percent of the pharmaceutical market, only 8 percent of them get past their clinical trials.
CNS clinical studies often fail, because they try to produce too many results for too many issues, making the effort more difficult for participants, more expensive and slower. That issue was addressed by an official from Takeda Pharmaceuticals USA, a subsidiary of the largest Japanese drug company, Takeda, which markets metabolic and cardiovascular, respiratory and immunology, central nervous system, oncology and general medicine products.
In an interview in Applied Clinical Trials, Dr. Atul Mahableshwarkar, senior medical director for Takeda Pharmaceuticals USA, said, “We do not know the pathophysiology of psychiatric illnesses, and so a single diagnosis could be made up of a number of different conditions. There is a lack of complete knowledge of the brain and brain illnesses, and this leads to challenges of designing and running trials. There is also the problem of methodology. Since we do not have clearly defined assessments, we need to rely on asking patients questions or receiving patient-reported outcomes. This results in great data variability and difficulty in translating the data.”
One answer could be the use of computer-generated methods for investigating CNS issues. This might involve ranking the severity of symptoms on a fixed scale.
Data would then be more uniform. The eventual hope is for the appearance of Device Reported Outcomes (DROs), so that clinical trial subjects would not be directly asked any questions. Instead, overt acts performed by the subjects would be recorded by portable sensors and would serve as objective expressions of their psychiatric state.
“We may be able to, for instance, identify, different subsets of populations in a disorder such as Major Depression Disorder,” Dr. Mahableshwarkar continued. “Or, conversely, we may be able to identify the source of a certain symptom, let’s say attention, hypomania, cyclothymia or major depression. As our understanding of CNS biomarkers advances, we may be able to identify appropriate sub-populations to develop more effective targeted therapies.”
CNS has not had a breakthrough product in several years, especially in the area of psychiatric illnesses. Dr. Mahableshwarkar does not expect to see one in the near future.
“We are still a few years away from such a breakthrough. Once we are able to better sort and understand the source of symptoms, we may be able to identify what may not work in a broad population but may work for a particular sub-population and get better treatment for patients. With such approaches, not only may we be able to develop new and effective treatments, but we may also be able to go back and look at drugs that have failed in the past, but could get new efficient data for regulatory standards,” he concluded.