Select Co-primary functional endpoints for trials of drugs to enhance cognition in schizophrenia
The goal of Work Stream # 1 is to develop and to validate a single instrument or alternate instruments that can be used to monitor the ability of patients with schizophrenia to function in work, education, and social activities. This instrument or instruments would be used as a co-primary measure (along with change scores on a battery of neuropsychological tests as the MATRICS Consensus Cognitive Battery) for international trials of pharmacological agents for improving cognition in schizophrenia. The method for selection and validation will involve a consensus-building process that includes broad representation from the pharmacological industry, academia, government (including NIMH and FDA) and consumers.
The goal of this phase will be to reach consensus on the criteria for selecting instruments; to collect information regarding available instruments; to prioritize end user requirements; and to select members for a RAND panel.
- Convene a Selection Criteria Workgroup (SCWG) to generate initial selection criteria and end user requirements.
- Convene a meeting where a diverse group of individuals from industry, academia, government, and consumers will review the field and reach consensus on the final selection criteria.
- Convene meetings of the Scientific Board -- through conference calls and a live meeting -- to monitor the work stream processes and select members of the RAND Panel.
The goal of this phase will be to evaluate nominated instruments based on the consensus selection criteria and to present this information to a RAND Panel. The Panel will prioritize the instruments.
- UCLA staff will collect data on nominated instruments. Available data will be organized in Tables to permit Rand Panel to evaluate each test according to Selection Criteria.
- Prior to a live meeting, RAND Panel members will receive the organized information on nominated instruments. The Panel members will prioritize instruments based on consensus selection criteria. At the live meeting, differences in ratings will be discussed and consensus will be reached on rankings.
The goal of this phase will be to design Validation studies 1 and 2. This will include the selection of sites and the design of study instruments. Validation Study 1 will be a cross sectional study to evaluate the relationships of proposed items to neurocognition and real world functioning. Validation Study 2 will use a briefer version derived from the first study to evaluate the psychometric properties of the items. This second study will include evaluations of items at two time points.
- Validation study WG (VSWG) will generate draft of validation study designs, solicit academic/industry/regulatory expert input on design issues.
- The SB and the VSWG will select sites and develop implementation plans.
During this phase the two validation studies will be completed and the data will be analyzed.
- Validation Study 1 will be a cross sectional study where 100 patients with schizophrenia at 3-5 sites receive candidate instruments as well as measures of functional outcome and the MCCB. Using the consensus selection criteria, the VSWG will use the findings to narrow the measures for Validation Study 2. This will be considered the short list of measures.
- Validation Study 2 will evaluate the short list in 100 patients with schizophrenia on two occasions approximately one month apart. This will permit an assessment of test-retest reliability and other psychometric characteristics.
- The VSWG will supervise the data analysis of this study and propose a final instrument or instruments to the SB for discussion and approval.
The focus of Phase 5 will be to inform the field of the findings from the validation studies and address issues of instrument dissemination including publication and translation.
- The results of the validation study and the selection of the final instrument will be disseminated at a 1.5 day public meeting organized by the initiative.
- The VSWG will work with a non-profit such as Matrics Assessment, Inc to print, translate, and publicize the availability of the instrument.