A recently published manuscript in the Journal Schizophrenia Research by Dr. Luca Pani and Dr. Richard Keefe of VeraSci provides an overview of the regulatory and policy issues related to the treatment of CNS disorders, with a focus on attenuated psychosis syndrome (APS) and schizophrenia. Schizophrenia has undergone a reconceptualization as a psychotic spectrum disorder, rather than a progressive or continuum disorder such as Alzheimer’s Disease or Parkinson’s Disease that follow a pattern of increasing severity over time. The current diagnostic and statistical manual (DSM-5) classification of schizophrenia as a spectrum disorder has been accepted as a welcome change from DSM-IV because it reflects the genetic and neurobiological relationship between schizophrenia, schizoaffective disorder, and schizotypal personality disorder. This conceptualization also considers the clinical manifestations of being at risk for psychosis, referred to as the attenuated psychosis syndrome, or APS.
The increased focus on the prodromal stages of schizophrenia is placing increased pressure on the regulatory system. APS represents one of the earliest manifestations of the psychosis spectrum, and regulators are now realizing the importance of therapies that target these initial stages. The subsequent interest in biomarkers for the identification of patients with prodromal CNS disease is essential; however, it can be challenging due to the various molecular and environmental complexities involved. To guide treatment, regulators would prefer biomarkers linked to a drug mechanism of action and disease neurobiology to allow a disease-modifying claim within the product label. In addition, the European Medicines Agency has recently highlighted a need for the co-development of biomarkers alongside corresponding assays that can be successfully transitioned into clinical practice.
There are no approved medications for APS, and there is no established regulatory standard for the conduct of clinical trials in this area. Research into the accurate and sensitive inclusion of individuals within clinical trials, and the conduct of such trials within the global regulatory environment, requires further consideration. Moving forward, translational science should be applied to regulatory concepts and measures, and it is essential that regulatory guidelines are followed for the certification of such measures. Finally, digital technologies that enable active measurement of key endpoints in both clinical trials and real-world settings will shortly be available, paving the way for a new era in patient identification and monitoring.
Read the full Schizophrenia Research: Cognition article, Approaches to attenuated psychosis syndrome treatments: A perspective on the regulatory issues, here.