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Placebo Response and Practice Effects in Schizophrenia Cognition Trials.

Publication ,  Journal Article
Keefe, RSE; Davis, VG; Harvey, PD; Atkins, AS; Haig, GM; Hagino, O; Marder, S; Hilt, DC; Umbricht, D
Published in: JAMA Psychiatry
August 1, 2017

IMPORTANCE: Patients' previous experience with performance-based cognitive tests in clinical trials for cognitive impairment associated with schizophrenia can create practice-related improvements. Placebo-controlled trials for cognitive impairment associated with schizophrenia are at risk for these practice effects, which can be difficult to distinguish from placebo effects. OBJECTIVES: To conduct a systematic evaluation of the magnitude of practice effects on the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) in cognitive impairment associated with schizophrenia and to examine which demographic, clinical, and cognitive characteristics were associated with improvement in placebo conditions. DESIGN, SETTING, AND PARTICIPANTS: A blinded review was conducted of data from 813 patients with schizophrenia who were treated with placebo in 12 randomized placebo-controlled clinical trials conducted mostly in outpatient clinics in North America, Europe, Asia, and Latin America from February 22, 2007, to March 1, 2014. A total of 779 patients provided data for the primary outcome measure at baseline and at least 1 follow-up. Seven trials had prebaseline assessments wherein the patients knew that they were not receiving treatment, allowing a comparison of practice and placebo effects in the same patients. INTERVENTIONS: Placebo compared with various experimental drug treatments. MAIN OUTCOMES AND MEASURES: Composite score on the MCCB. RESULTS: Of the 813 patients in the study (260 women and 553 men; mean [SD] age, 41.2 [11.5] years), the mean MCCB composite score at baseline was 22.8 points below the normative mean, and the mean (SEM) total change in the MCCB during receipt of placebo was 1.8 (0.2) T-score points (95% CI, 1.40-2.18), equivalent to a change of 0.18 SD. Practice effects in the 7 studies in which there was a prebaseline assessment were essentially identical to the postbaseline placebo changes. Baseline factors associated with greater improvements in the MCCB during receipt of placebo included more depression/anxiety (F1,438 = 5.41; P = .02), more motivation (F1,272 = 4.63; P = .03), and less improvement from screening to baseline (F1,421 = 59.32; P < .001). CONCLUSIONS AND RELEVANCE: Placebo effects were minimal and associated with the number of postbaseline assessments and several patient characteristics. Given that the patients performed 2.28 SDs below normative standards on average at baseline, a mean placebo-associated improvement of less than 0.2 SD provides evidence that ceiling effects do not occur in these trials. These minimal changes in the MCCB could not be responsible for effective active treatments failing to separate from placebo.

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Published In

JAMA Psychiatry

DOI

EISSN

2168-6238

Publication Date

August 1, 2017

Volume

74

Issue

8

Start / End Page

807 / 814

Location

United States

Related Subject Headings

  • Young Adult
  • Schizophrenic Psychology
  • Schizophrenia
  • Practice, Psychological
  • Placebo Effect
  • Neuropsychological Tests
  • Male
  • Humans
  • Female
  • Controlled Clinical Trials as Topic
 

Citation

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Keefe, R. S. E., Davis, V. G., Harvey, P. D., Atkins, A. S., Haig, G. M., Hagino, O., … Umbricht, D. (2017). Placebo Response and Practice Effects in Schizophrenia Cognition Trials. JAMA Psychiatry, 74(8), 807–814. https://doi.org/10.1001/jamapsychiatry.2017.1574
Keefe, Richard S. E., Vicki G. Davis, Philip D. Harvey, Alexandra S. Atkins, George M. Haig, Owen Hagino, Stephen Marder, Dana C. Hilt, and Daniel Umbricht. “Placebo Response and Practice Effects in Schizophrenia Cognition Trials.JAMA Psychiatry 74, no. 8 (August 1, 2017): 807–14. https://doi.org/10.1001/jamapsychiatry.2017.1574.
Keefe RSE, Davis VG, Harvey PD, Atkins AS, Haig GM, Hagino O, et al. Placebo Response and Practice Effects in Schizophrenia Cognition Trials. JAMA Psychiatry. 2017 Aug 1;74(8):807–14.
Keefe, Richard S. E., et al. “Placebo Response and Practice Effects in Schizophrenia Cognition Trials.JAMA Psychiatry, vol. 74, no. 8, Aug. 2017, pp. 807–14. Pubmed, doi:10.1001/jamapsychiatry.2017.1574.
Keefe RSE, Davis VG, Harvey PD, Atkins AS, Haig GM, Hagino O, Marder S, Hilt DC, Umbricht D. Placebo Response and Practice Effects in Schizophrenia Cognition Trials. JAMA Psychiatry. 2017 Aug 1;74(8):807–814.

Published In

JAMA Psychiatry

DOI

EISSN

2168-6238

Publication Date

August 1, 2017

Volume

74

Issue

8

Start / End Page

807 / 814

Location

United States

Related Subject Headings

  • Young Adult
  • Schizophrenic Psychology
  • Schizophrenia
  • Practice, Psychological
  • Placebo Effect
  • Neuropsychological Tests
  • Male
  • Humans
  • Female
  • Controlled Clinical Trials as Topic