While some progress has been made in terms of scientific development in Neuroscience and Neuropsychiatry indications, the pace of translation into more effective treatments remains elusive.
At the recent Cytel seminar co-hosted with Pfizer, Abdul J. Sankoh of Sage Therapeutics presented on some of the challenges in these therapeutic areas and discusses strategies moving forward. He bases his presentation on his broad industry experience.
What’s the situation?
The figures make for sobering reading- 99% of Alzheimer’s drug trials in past decade have failed and the likelihood of approval in neuroscience indications is only around 8.4 %, with neuropsychiatry standing at 6.2%. Only oncology fares worse with a likelihood of approval of only 5.1%.
The high failure rate, says Sankoh, can be attributed to a series of intrinsic and extrinsic factors. Intrinsic factors center around uncertainties of disease etiology. For example, in schizophrenia there is lack of clarity and agreement over the impact of socio-economic versus genetic factors.
The extrinsic factors include poorly understood endpoints, inefficient trial execution and patient recruitment issues, including a prevalence of professional and recreational patients in some settings.
It is sometimes the case that to compensate for poorly understood characteristics larger trials may be conducted leading to wide inter subject and inter site variability.
In the video presentation, Sakoh walks through the issues, and focuses on the example of a Phase 3 schizophrenia study which was derailed by trial design and execution issues. Factors in play included randomization of placebo responders, and protocol amendments which relaxed the original, and well placed exclusion criteria.
He goes on to discuss the opportunities of innovative trial design strategies in the neuroscience area, including use of population enriched design to detect and reduce high placebo responders, as well as mitigate the participation of professional and recreational subjects in trials.
To watch the video click below.
To download Sankoh's slides click the button below.
Sequential Parallel Comparison Designs[SPCD]. SPCDs are two-stage designs meant for therapeutic areas known to have high levels of placebo response. The second stage of an SPCD trial offers the chance to compare efficacy only amongst placebo non-responders. To read the blog, click the link below.