Department of Health and Human Services
National Institutes of Health
National Institutes of Mental Health

FDA-NIMH-MATRICS Workshop on Clinical Trial Designs for Neurocognitive Drugs for Schizophrenia

Neuroscience Center, Conference Room C
6001 Executive Boulevard, Rockville, Maryland 20852

April 23, 2004

DRAFT AGENDA

Friday, April 23rd
Time Topic Presenter
8:00 am–8:15* am Welcome/Update on MATRICS Process and NIMH Goals for Workshop Ellen Stover, Ph.D. & Wayne Fenton, M.D.
8:15 am–8:30 am FDA Goals for Workshop Tom Laughren, M.D.
8:30 am–8:35 am Overview and Consensus Process Robert Buchanan, M.D. - Meeting Chairman
Inclusion Criteria
8:35 am–8:50 am

Topic: The Pattern of Cognitive Impairments in Patients with Schizophrenia

 Keith Nuechterlein, Ph.D.
 

Question to be Addressed by Presenter:

1. Among the major psychotic disorders, what is the evidence that that schizophrenia and related disorders (i.e, Schizoaffective disorder, Schizophreniform disorder) are characterized by a unique pattern of cognitive impairments?
8:50 am–9:05 am

Topic: The Relationship of Neuropsychological Measures to Symptoms: Design Approaches to Isolate Specific Domains for Investigation.

 Robert Buchanan, M.D.
 

Questions to be Addressed by Presenter:

2. What is the optimal phase of illness for patient inclusion?
3. What design approaches should be used to isolate change in neurocognitive domains from change in other symptom domains?

  1. In studies with adjunctive agents
  2. In studies with broad spectrum agents
9:05 am–9:35 am

Topics: Relevent Differences in the Pharmacological Profiles of Antipsychotic Agents;
The Effect of Commonly Used Concomitant Medications on Cognition;
How to Control for Potential Pharmacokinetic Interactions

 Donald Goff, M.D.
 

Question to be Addressed by Presenter:

4. In studies with adjunctive agents:

  1. Should patients be allowed to be treated with any antipsychotic, i.e., conventional and second generation antipsychotics; only second generation antipsychotics; or only a single second generation antipsychotic?
  2. Should patients be allowed to be treated only with one antipsychotic or can they receive more than one?
  3. Should patients be allowed to be treated with commonly used concomitant medications (i.e., antidepressants, antianxiety agents, mood stabilizers)?
5. In studies with broad spectrum agents:
  1. Should patients be allowed to be treated with an antipsychotic?
  2. Should patients be allowed to be treated with commonly used concomitant medications (i.e., antidepressants, anti-anxiety agents, mood stabilizers)?
9:35 am -9:50 am Topic: Severity of Cognitive Impairment
 Richard Keefe, Ph.D.
 

Question to be Addressed by Presenter:

6. In order to detect a therapeutic effect, should a minimal level of cognitive impairment be specified in the inclusion criteria?
7. In order to detect a therapeutic effect, should a maximum level of cognitive impairment be specified?
8. If patients are screened for inclusion based upon their level of cognitive impairment, how should screening assessments be conducted?

9:55 am–10:45 am Discussion of Inclusion Criteria Study Design Questions
10:45 am–11:00 am Break
Outcome Measures
11:00 am–11:10 am Introduction to Session: Symptom, Function, and Safety Measures

 Robert Buchanan, M.D.
11:10 am–11:30 noon Topics: Update on the Matrics Consensus Cognitive Battery and Assessment of the Necessity and Feasibility of Co-primary Outcome Measures Michael Green, Ph.D.
 

Question to be Addressed by Presenter:

9. Should a co-primary outcome measure be required in addition to cognitive
performance?

If so, what are the ideal characteristics of a co-primary outcome measure?

10. What is the best approach to assess the validity of proxy measures of functional outcome and interview-based measures of cognition?
11:35 am–12:15 pm Discussion of Outcome Measure Study Design Questions
12:15 pm–1:00 pm Lunch Break
Other Design and Statistical Issues
1:00 pm–1:05 pm Introduction to Session Robert Buchanan, M.D.
1:05 pm–1:35 pm Topic: Issues in Design and Statistical Analysis of Studies with Adjunctive Agents and Broad Spectrum Agents Andrew Leon, Ph.D.
 

Question to be Addressed by Presenter:

11. What are the different statistical approaches for:

  1. A single global measure; and
  2. Individual cognitive domain measures
12. How many testing occasions should be included?
13. In light of the expected heterogeneity of severity and response within and across different cognitive domains, what statistical approaches should be used to detect a therapeutic effect?
14. What statistical approach should be used to control for potentially concurrent changes in other symptom domains for:
  1. Adjunctive agents; and
  2. Broad spectrum agents?
15. What is an appropriate duration for a clinical trial of an agent targeting cognition in schizophrenia?
1:40 pm–2:30 pm Discussion of Other Design Issues and Statistical Study Design Questions
2:30 pm–2:45 pm Break
Labeling Issues
2:45 pm–2:50 pm Introduction to Session Robert Buchanan, M.D.
2:50 pm–3:20 pm Topic: FDA's Perspective on Labeling Issues for Adjunctive Agents and Broad Spectrum Agents, Including the Problem of Pseudospecificity Thomas Laughren, M.D.
3:20 pm–4:20 pm Discussion Of Labeling Issues For Adjunctive and Broad Spectrum Agents
4:20 pm–4:30 pm Wrap-up

*All Times are tentative
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Revised: Tuesday, 13-Apr-2004 13:45:09 PDT