Synergy in Action

12th Annual Working Group Dinner Session Descriptions

Adaptive Design (Kando, Marcus)
The Adaptive Design Working Group (ADWG) will develop a plan for a series of webinars to be executed over the ensuing months. The group will discuss number of sessions, topics, possible presenters, timing and execution.

Addressing Methodological Challenges in International CNS Clinical Trials (Keefe, Kalali)
We will continue to work on the paper we are submitting on recommended processes for translating, culturally adapting, and implementing clinician reported outcomes (ClinROs) in international trials.  The workgroup time will be utilized to get input from the paper authors and to get feedback from working group participants.

Algorithms/Flags to Identify Clinical Inconsistency in the Use of Rating Scales in CNS RCTs (Rabinowitz, Schooler)
The working group will commence its work on developing consistency flags for the MADRS after having successfully completed a set of flags for the PANSS.  The group is seeking to include additional members with relevant MADRS experience.

Biomarkers in Schizophrenia (Potkin, Goff)
Group will receive update on manuscript and develop objectives for next phase of working group.

Behavioral and Psychiatric Symptoms and Dementia (Ereshefsky, Miller, Pani)
The Working Group at our second meeting at ISCTM Amsterdam had a robust discussion on next steps forward and on WG priorities.  There was substantive agreement (though not completely so) with the results of our survey findings (sent out to WG participants following our inaugural meeting in Washington DC in February 2015.)  These survey results and follow-on discussions form the basis for next steps to be considered at the February 2016 meeting.

Summary of key BPSD Working Group Survey Results:

  • We had 19 responses out of 37 survey recipients (51%).  The Working Group participants in Amsterdam supported the survey results to focus our efforts on Alzheimer’s disease and AD spectrum i.e., pre-clinical/MCI (18 top rank votes), rather than on all Dementia and Neurodegenerative disorders (2 top rank votes).
  • The top three neuropsychiatric symptoms or symptom clusters receiving the most support to focus our effort on were: Agitation/Aggression; Depression/Affective disturbances, Apathy/Amotivation/Anhedonia.
  • 90% of respondents agree with the following statement from the EMA workshop on BPSD:

In order to be considered as a stand-alone indication it is expected that the mechanism of action of the medicinal product would be relevant and specific for the treated neuropsychiatric symptoms. This requires reliable and valid measurement tools for the studied patient population in the specific stages of the disease…”

  • The highest endorsement for a specific element of the EMA Workshop Paper (November 2014) was: An indication “requires reliable and valid measurement tools for the studied patient population”.
  • In a question ranking potential priorities for the WG, both the greatest number in support (n=9) and strongly disagree (n=10) were associated with the statement: “Assess the current state of the BPSD drug development literature and review current study methodologies for BPSD indications in order to identify experimental medicine strategies and ‘fit for purpose’ designs suitable for a clinical development plan (IND-Phase I-III)”

Cognitive Assessment in CTs of AD and its Precursors (Posner, Harvey)
The next version of the Cognition in Alzheimer’s Disease working group will focus on a single highly important topic: 

Drawing from the insights from prior meetings and the previous two white papers produced by the working group, the February 2016 session will discuss and debate the merits and risks of various possible Alzheimer’s prevention trial designs.

There are several critical topics contained in this discussion, which include brief presentations and extensive discussion by the working group members.

These include:

  1. What is the treatment population and how would they be identified and selected?
  2. What are the key inclusion criteria?
  3. Is there a need or place for a longitudinal  low risk comparison group?
  4. What are the outcomes assessments?
  5. How long should the trial last?
  6. How often should the assessments performed?
  7. Is it possible to compare different drugs or even different doses of drugs in a study such as this.

These are complex questions and will require careful consideration.  By their very nature, prevention trials are high risk and uncertain in their formulations and this working group will start toward consensus on optimal research designs.    

Identifying and Analyzing Adverse Events Related to Abuse and Dependence Potential in CTs (Setnick, Sokolowska, Klein)
The purpose of this session is to discuss the varying lists of adverse event terms related to abuse and dependence that have been utilized across CNS clinical drug development programs, compare these to the recommendations in the FDA guidance and discuss which terms may be routinely examined.   Recommendations regarding abuse related adverse event collection and presentation will be reviewed with specific case examples discussed.  Additional data sources in clinical trials (e.g. drug accountability, withdrawal scales) that may be relevant to abuse and dependence potential will also be reviewed.