A summary of the FDA-NIMH-MATRICS workshop on clinical trial design for neurocognitive drugs for schizophrenia.
OBJECTIVE
On April 23, 2004, a joint meeting of the FDA, NIMH, MATRICS investigators, and experts from academia and the pharmaceutical industry was convened to develop guidelines for the design of clinical trials of cognitive-enhancing drugs for neurocognitive impairments in patients with schizophrenia.


METHODS
Experts were asked to address specific questions relating to clinical trial design of adjunctive/co-treatment and broad spectrum agents. At the workshop, experts reviewed relevant evidence before offering the discussion panel proposed guidelines for a given subset of questions. The discussion panel, which consisted of presenters and representatives from FDA, NIMH, academia, and industry, deliberated to reach consensus on suggested guidelines. When evidence was insufficient, suggested guidelines represent the opinion of a cross-section of the presenters and discussion panel.


RESULTS
Guidelines were developed for inclusion criteria, the use of co-primary outcome measures, and statistical approaches for study design. Consensus was achieved regarding diagnostic and concomitant medication inclusion criteria and on the use of cognitive screening measures. A key guideline was to limit the trial to patients in the residual phase of their illness, who have a predefined level of positive, negative, and affective symptoms. The most difficult issues were the feasibility of including a co-primary measure of functional improvement and the choice of comparator agent for a trial of a broad spectrum agent (with antipsychotic and cognitive-enhancing effects).


CONCLUSIONS
The suggested guidelines represent reasonable starting points for trial design of cognitive-enhancing drugs, with the understanding that new data, subsequent findings, or other methodological considerations may lead to future modifications.
Buchanan
Robert W
RW
Maryland Psychiatric Research Center, P.O. Box 21247, Baltimore, MD 21228, USA. RWBuchanan@mprc.umaryland.edu
Davis
Miriam
M
Goff
Donald
D
Green
Michael F
MF
Keefe
Richard S E
RS
Leon
Andrew C
AC
Nuechterlein
Keith H
KH
Laughren
Thomas
T
Levin
Robert
R
Stover
Ellen
E
Fenton
Wayne
W
Marder
Steve R
SR
D014150:Antipsychotic Agents; D010054:Brief Psychiatric Rating Scale; D002986:Clinical Trials as Topic / Q000592:standards*; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy*; D003131:Combined Modality Therapy; D017408:Guidelines as Topic; D006293:Health Promotion; D006801:Humans; D008605:Mental Health Services / Q000592:standards; D009315:National Institute of Mental Health (U.S.); D019338:Polypharmacy; D011613:Psychotherapy; D012559:Schizophrenia / Q000150:complications* / Q000175:diagnosis / Q000628:therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
D014150:Antipsychotic Agents