The brain decade in debate: II. Panic or anxiety? From animal models to a neurobiological basis

This article is a transcription of an electronic symposium sponsored by the Brazilian Society of Neuroscience and Behavior (SBNeC). Invited researchers from the European Union, North America and Brazil discussed two issues on anxiety, namely whether panic is a very intense anxiety or something else, and what aspects of clinical anxiety are reproduced by animal models. Concerning the first issue, most participants agreed that generalized anxiety and panic disorder are different on the basis of clinical manifestations, drug response and animal models. Also, underlying brain structures, neurotransmitter modulation and hormonal changes seem to involve important differences. It is also common knowledge that existing animal models generate different types of fear/anxiety. A challenge for future research is to establish a good correlation between animal models and nosological classification.Universidade Federal do Paraná Departamento de Farmacologia Laboratório de Fisiologia e Farmacologia do Sistema Nervoso CentralUniversity of Hawaii Department of NeurobiologyUniversity of Hawaii Department of PsychologyUniversidade de São Paulo Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Departamento de PsicobiologiaUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de FisiologiaUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de NeuropsiquiatriaUniversidade Federal de Santa Catarina Departamento de FarmacologiaCentral Nervous System Research Department Sanofi SynthelaboAston University Institute of Pharmaceutical SciencesHoffmann-La Roche Ltd.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PsicologiaUniversity of Leeds Department of Psychology Ethopharmacology LaboratoryUniversidade Federal do Espírito Santo Centro de Biomedicina Departamento de Ciências FisiológicasUNIFESP, EPM, Depto. de PsicologiaSciEL

Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson’s disease

An increase in the efficiency of clinical trial conduct has been successfully demonstrated in the oncology field, by the use of multi-arm, multi-stage trials allowing the evaluation of multiple therapeutic candidates simultaneously, and seamless recruitment to phase 3 for those candidates passing an interim signal of efficacy. Replicating this complex innovative trial design in diseases such as Parkinson’s disease is appealing, but in addition to the challenges associated with any trial assessing a single potentially disease modifying intervention in Parkinson’s disease, a multi-arm platform trial must also specifically consider the heterogeneous nature of the disease, alongside the desire to potentially test multiple treatments with different mechanisms of action. In a multi-arm trial, there is a need to appropriately stratify treatment arms to ensure each are comparable with a shared placebo/standard of care arm; however, in Parkinson’s disease there may be a preference to enrich an arm with a subgroup of patients that may be most likely to respond to a specific treatment approach. The solution to this conundrum lies in having clearly defined criteria for inclusion in each treatment arm as well as an analysis plan that takes account of predefined subgroups of interest, alongside evaluating the impact of each treatment on the broader population of Parkinson’s disease patients. Beyond this, there must be robust processes of treatment selection, and consensus derived measures to confirm target engagement and interim assessments of efficacy, as well as consideration of the infrastructure needed to support recruitment, and the long-term funding and sustainability of the platform. This has to incorporate the diverse priorities of clinicians, triallists, regulatory authorities and above all the views of people with Parkinson’s disease