Evaluation of functionally meaningful measures for clinical trials of cognition enhancement in schizophrenia

Michael F. Green, Nina R. Schooler, Robert S. Kern, Fred J. Frese, Wendy Granberry, Philip D Harvey, Craig N. Karson, Nancy Peters, Michelle Stewart, Larry J. Seidman, John Sonnenberg, William S. Stone, David Walling, Ellen Stover, Stephen R. Marder

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Objective: Because reduction of psychotic symptoms in schizophrenia does not result in adequate community functioning, efforts have shifted to other areas, such as cognitive impairment. The U.S. Food and Drug Administration requires that drugs for cognition enhancement in schizophrenia show improvement on two distinct outcome measures in clinical trials: an accepted cognitive performance battery and a functionally meaningful coprimary measure. The authors examined the reliability, validity, and practicality of functionally meaningful measures. Method: In this four-site validation study, schizophrenia patients were assessed at baseline (N=166) and 4 weeks later (N=144) on performance-based (Independent Living Scales, Test of Adaptive Behavior in Schizophrenia [TABS], and UCSD Performance-based Skills Assessment [UPSA]) and interview-based (Cognitive Assessment Interview and Clinical Global Impression Scale for Cognition) candidate coprimary measures. In addition, cognitive performance, community functioning, and clinical symptoms were assessed. Both full and short forms of the performancebased measures were evaluated. Results: All measures were well tolerated by patients, had adequate test-retest reliability, and showed good utility as a repeated measure. Measures differed in their correlation with cognitive performance, with performance-based measures having stronger correlations than interview-based measures. None of the measures had notable floor or ceiling effects or missing data. Conclusions: Among the full-form measures, the UPSA was judged to have the strongest overall properties. Among the short forms, the TABS and UPSA appeared to have the strongest features. Use of the short forms saves time, but at the cost of lower test-retest reliability and weaker correlations with cognitive performance.

Original languageEnglish
Pages (from-to)400-407
Number of pages8
JournalAmerican Journal of Psychiatry
Volume168
Issue number4
DOIs
StatePublished - Apr 1 2011
Externally publishedYes

Fingerprint

Cognition
Schizophrenia
Clinical Trials
Reproducibility of Results
Psychological Adaptation
Interviews
Independent Living
Validation Studies
United States Food and Drug Administration
Outcome Assessment (Health Care)
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Evaluation of functionally meaningful measures for clinical trials of cognition enhancement in schizophrenia. / Green, Michael F.; Schooler, Nina R.; Kern, Robert S.; Frese, Fred J.; Granberry, Wendy; Harvey, Philip D; Karson, Craig N.; Peters, Nancy; Stewart, Michelle; Seidman, Larry J.; Sonnenberg, John; Stone, William S.; Walling, David; Stover, Ellen; Marder, Stephen R.

In: American Journal of Psychiatry, Vol. 168, No. 4, 01.04.2011, p. 400-407.

Research output: Contribution to journalArticle

Green, MF, Schooler, NR, Kern, RS, Frese, FJ, Granberry, W, Harvey, PD, Karson, CN, Peters, N, Stewart, M, Seidman, LJ, Sonnenberg, J, Stone, WS, Walling, D, Stover, E & Marder, SR 2011, 'Evaluation of functionally meaningful measures for clinical trials of cognition enhancement in schizophrenia', American Journal of Psychiatry, vol. 168, no. 4, pp. 400-407. https://doi.org/10.1176/appi.ajp.2010.10030414
Green, Michael F. ; Schooler, Nina R. ; Kern, Robert S. ; Frese, Fred J. ; Granberry, Wendy ; Harvey, Philip D ; Karson, Craig N. ; Peters, Nancy ; Stewart, Michelle ; Seidman, Larry J. ; Sonnenberg, John ; Stone, William S. ; Walling, David ; Stover, Ellen ; Marder, Stephen R. / Evaluation of functionally meaningful measures for clinical trials of cognition enhancement in schizophrenia. In: American Journal of Psychiatry. 2011 ; Vol. 168, No. 4. pp. 400-407.
@article{607895c81f674259a1f5351776e8f132,
title = "Evaluation of functionally meaningful measures for clinical trials of cognition enhancement in schizophrenia",
abstract = "Objective: Because reduction of psychotic symptoms in schizophrenia does not result in adequate community functioning, efforts have shifted to other areas, such as cognitive impairment. The U.S. Food and Drug Administration requires that drugs for cognition enhancement in schizophrenia show improvement on two distinct outcome measures in clinical trials: an accepted cognitive performance battery and a functionally meaningful coprimary measure. The authors examined the reliability, validity, and practicality of functionally meaningful measures. Method: In this four-site validation study, schizophrenia patients were assessed at baseline (N=166) and 4 weeks later (N=144) on performance-based (Independent Living Scales, Test of Adaptive Behavior in Schizophrenia [TABS], and UCSD Performance-based Skills Assessment [UPSA]) and interview-based (Cognitive Assessment Interview and Clinical Global Impression Scale for Cognition) candidate coprimary measures. In addition, cognitive performance, community functioning, and clinical symptoms were assessed. Both full and short forms of the performancebased measures were evaluated. Results: All measures were well tolerated by patients, had adequate test-retest reliability, and showed good utility as a repeated measure. Measures differed in their correlation with cognitive performance, with performance-based measures having stronger correlations than interview-based measures. None of the measures had notable floor or ceiling effects or missing data. Conclusions: Among the full-form measures, the UPSA was judged to have the strongest overall properties. Among the short forms, the TABS and UPSA appeared to have the strongest features. Use of the short forms saves time, but at the cost of lower test-retest reliability and weaker correlations with cognitive performance.",
author = "Green, {Michael F.} and Schooler, {Nina R.} and Kern, {Robert S.} and Frese, {Fred J.} and Wendy Granberry and Harvey, {Philip D} and Karson, {Craig N.} and Nancy Peters and Michelle Stewart and Seidman, {Larry J.} and John Sonnenberg and Stone, {William S.} and David Walling and Ellen Stover and Marder, {Stephen R.}",
year = "2011",
month = "4",
day = "1",
doi = "10.1176/appi.ajp.2010.10030414",
language = "English",
volume = "168",
pages = "400--407",
journal = "American Journal of Psychiatry",
issn = "0002-953X",
publisher = "American Psychiatric Association",
number = "4",

}

TY - JOUR

T1 - Evaluation of functionally meaningful measures for clinical trials of cognition enhancement in schizophrenia

AU - Green, Michael F.

AU - Schooler, Nina R.

AU - Kern, Robert S.

AU - Frese, Fred J.

AU - Granberry, Wendy

AU - Harvey, Philip D

AU - Karson, Craig N.

AU - Peters, Nancy

AU - Stewart, Michelle

AU - Seidman, Larry J.

AU - Sonnenberg, John

AU - Stone, William S.

AU - Walling, David

AU - Stover, Ellen

AU - Marder, Stephen R.

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Objective: Because reduction of psychotic symptoms in schizophrenia does not result in adequate community functioning, efforts have shifted to other areas, such as cognitive impairment. The U.S. Food and Drug Administration requires that drugs for cognition enhancement in schizophrenia show improvement on two distinct outcome measures in clinical trials: an accepted cognitive performance battery and a functionally meaningful coprimary measure. The authors examined the reliability, validity, and practicality of functionally meaningful measures. Method: In this four-site validation study, schizophrenia patients were assessed at baseline (N=166) and 4 weeks later (N=144) on performance-based (Independent Living Scales, Test of Adaptive Behavior in Schizophrenia [TABS], and UCSD Performance-based Skills Assessment [UPSA]) and interview-based (Cognitive Assessment Interview and Clinical Global Impression Scale for Cognition) candidate coprimary measures. In addition, cognitive performance, community functioning, and clinical symptoms were assessed. Both full and short forms of the performancebased measures were evaluated. Results: All measures were well tolerated by patients, had adequate test-retest reliability, and showed good utility as a repeated measure. Measures differed in their correlation with cognitive performance, with performance-based measures having stronger correlations than interview-based measures. None of the measures had notable floor or ceiling effects or missing data. Conclusions: Among the full-form measures, the UPSA was judged to have the strongest overall properties. Among the short forms, the TABS and UPSA appeared to have the strongest features. Use of the short forms saves time, but at the cost of lower test-retest reliability and weaker correlations with cognitive performance.

AB - Objective: Because reduction of psychotic symptoms in schizophrenia does not result in adequate community functioning, efforts have shifted to other areas, such as cognitive impairment. The U.S. Food and Drug Administration requires that drugs for cognition enhancement in schizophrenia show improvement on two distinct outcome measures in clinical trials: an accepted cognitive performance battery and a functionally meaningful coprimary measure. The authors examined the reliability, validity, and practicality of functionally meaningful measures. Method: In this four-site validation study, schizophrenia patients were assessed at baseline (N=166) and 4 weeks later (N=144) on performance-based (Independent Living Scales, Test of Adaptive Behavior in Schizophrenia [TABS], and UCSD Performance-based Skills Assessment [UPSA]) and interview-based (Cognitive Assessment Interview and Clinical Global Impression Scale for Cognition) candidate coprimary measures. In addition, cognitive performance, community functioning, and clinical symptoms were assessed. Both full and short forms of the performancebased measures were evaluated. Results: All measures were well tolerated by patients, had adequate test-retest reliability, and showed good utility as a repeated measure. Measures differed in their correlation with cognitive performance, with performance-based measures having stronger correlations than interview-based measures. None of the measures had notable floor or ceiling effects or missing data. Conclusions: Among the full-form measures, the UPSA was judged to have the strongest overall properties. Among the short forms, the TABS and UPSA appeared to have the strongest features. Use of the short forms saves time, but at the cost of lower test-retest reliability and weaker correlations with cognitive performance.

UR - http://www.scopus.com/inward/record.url?scp=79955137651&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955137651&partnerID=8YFLogxK

U2 - 10.1176/appi.ajp.2010.10030414

DO - 10.1176/appi.ajp.2010.10030414

M3 - Article

C2 - 21285142

AN - SCOPUS:79955137651

VL - 168

SP - 400

EP - 407

JO - American Journal of Psychiatry

JF - American Journal of Psychiatry

SN - 0002-953X

IS - 4

ER -