Working Group Chair: Holly Posner, MD

In depth use of traditional and modern psychometric analyses (including Rasch analysis and various types of item-response theory) are becoming more common and can usher in a new era of robust clinical trial assessment and enhanced quality of decision-making.  All interested parties, including drug developers, regulatory authorities, key stakeholders, and academicians (clinicians, neuropsychologists, and psychometricians) need a common platform to evaluate and vet these methodologies side-by-side so that they may develop a common language and understanding for efficient and appropriate decision-making in drug development.  This dinner session will discuss these methods, the challenges for moving them forward into AD clinical trials, and will produce draft of recommendations for the next phase of research to accomplish this goal.

Chairs: A Mahableshwarkar, MD; S Romano, MD; R Keefe, PhD; J Rasmussen, MD; S Comfort, MD, B Lavenstein, MD

A large number of clinical trials in children have been conducted since the introduction of pediatric exclusivity. There have been, though, relatively few new treatments for this important patient segment. Using epilepsy and depression as models, the joint session of the ISCTM-ASENT will evaluate challenges, pitfalls and opportunities in the development of new therapies. Specific issues related to both drug and device development will be discussed by experts, and global regulatory perspectives shared . The larger group will then break into the following four working groups: 1) Specific challenges, PK/PD, potential for longer term effects 2) Animal models for diseases, drugs and devices 3) Pediatric outcomes and scales 4) IRB and ethics. Each working group will identify specific challenges and develop preliminary plans to address these, which will then be presented to the larger audience. The session will conclude with a discussion of these proposed solutions and recommendations on implementation. 

Chairs:  Richard Keefe PhD,  Andrew C. Leon PhD

As our field moves toward an increasingly personalized approach to medical treatment, biomarkers (including genomic, proteomic, imaging, etc.) become increasingly important for informing clinicians about the relative value of CNS products. In addition, biomarkers can serve to help screen for new therapeutic agents, identify susceptible populations, provide endpoints for trials and, potentially, predict efficacy, safety and outcomes of clinical trials.  This increasing interest raises challenges for many different stakeholders regarding the structure and elements of clinical trials that are needed to establish scientific data around biomarkers. This session will bring clinicians, designers of clinical trials, regulators, statisticians and payers together to more clearly identify issues relative to the use of biomarkers to meet these needs.  It will include formal presentations from experts, and will provide examples of  how  biomarkers   have   been   used in the Alzheimer’s  field  as an exemplar of hurdles to this work and how they might be  addressed.  In  the  afternoon, session will focus on statistical methods for defining clinically meaninful effect, followed by a panel discussion on implementation.

Chairs: Amir Kalali MD, Jill Rasmussen MD

Despite the emergence of new classes of antidepressants, the management of depression continues to be challenging with remission rates remaining around 33%. 

A number of studies have used new strategies in partial and non-responders, as well as treatment resistant patients.  This session will review and critically appraise the lessons learned from these studies.  Questions will be posed about the current concepts of early onset of response, partial response and treatment resistance and whether these should be refined.  Similarities and differences in regulatory thinking about clinical trial methodology and potential labelling will be explored and the potential relevance of these methodologies to inform other therapeutic areas will be discussed.

Chairs: Reuven Ferziger MD,  Larry Ereshefsky PharmD, BCPP, Ron Manderscheid, PhD

Drug development activities typically support relatively short-term clinical trials, often focused on improvement or resolution of more acute symptomatology.  Few clinical trials are designed to measure longer term outcomes associated with maintenance of improvement, earlier intervention or modification of disease progression.  However, for certain CNS conditions, such as schizophrenia or Alzheimer’s disease, the most effective therapies may need to be initiated early in the course of disease or even prior to symptomatic onset.  The evaluation of such long term interventions will present challenges to a research and pharmaceutical culture constrained by shorter term operating budgets and influenced by 5 year NIH grants, 4 year elected officials and myopic shareholder expectations.  The 2012 ISCTM Policy Forum will address the scientific and policy challenges of evaluating new treatments for CNS conditions that require intervention much earlier in the course of disease than most current therapies.

Working Group Chair: Charles Bowden, MD

Group will review recent publications on mitochondrial systems in CNS disorders, then address systematically by disease area potential mitochondria associated biological systems that could be targeted for development of new therapies.  This second focus, which links to specific ISCTM goals, will also include currently available drugs with actions in mitochondria.

Working Group Chair: Virginia Haynes, PhD

The adaptive design working group will share progress on ongoing simulation work for a Phase II trial for a mock compound in schizophrenia. The group will also discuss potential new projects related to the use of adaptive designs in CNS trials.