NCDEU Poster Session 2012

Attitudes of Investigators and Site Staff Toward Placebo Response in International CNS Clinical Trials

David G. Daniel, MD; Antony Loebel, MD; Josephine Cucchiaro, PhD; and Jean Dries, RN, MSN
From Bracket (a division of United BioSource), McLean, Virginia (Dr Daniel), Sunovion Pharmaceuticals, Inc, Fort Lee, New Jersey (Drs Cucchiaro and Loebel), and Bracket Global, Wayne, Pennsylvania (Ms Dries).

This poster presentation was supported by Sunovion Pharmaceuticals, Inc, and Bracket (United BioSource).

Background: In CNS clinical trials there is increased concern with signal detection capability in part due to increased placebo response (1). We recently reported the attitudes of 63 US investigators and their staffs with respect to their ability to influence placebo response (2). In the current report we expanded this sample to include additional international trialists.

Methods: 165 site investigators and staff from the US, central Europe, India and Japan attending regional industry sponsored investigators’ meetings for a double blind, placebo controlled, bipolar depression clinical trial, answered questions administered by an audience response system addressing their ability to influence placebo response. Subsequently investigators and staff were trained in placebo response management using interactive slide presentations and case oriented discussion. The associations of responses to role in the study, the number of previous trainings aimed at reducing placebo response and the proportion of time spent in clinical activities or care unrelated to research were evaluated using the chi-square test statistic.

Results:


Question

Markedly

Moderately

Slightly

Not at All

“I can influence the magnitude of response in a clinical trial.”

34.4%
(n=52)

31.8%
(n=48)

17.2%
(n=26)

16.6%
(n=25)

“The behavior of site staff in a clinical trial can influence the magnitude of placebo response.”

43.4%
(n=66)

37.5%
(n=57)

15.1%
(n=23)

4.0%
(n=6)

Question

Disagree

Agree

“My role in a clinical trial includes ensuring that subjects improve clinically.”

75.5%
(n=117)

24.5%
(n=38)

“It is unethical to continue subjects in a clinical trial who are not improving”

62.9%
(n=95)

37.1%
(n=56)


69.3% (n=109) had previously received training to reduce placebo response. 48.9% (n=65) identified themselves as “Study Coordinators/Raters” and 51.1% (n=68) as “Investigators/Sub-Investigators”. Investigators/Sub-investigators were more likely than Study Coordinators/Raters to disagree that “My role in a clinical trial includes ensuring that subjects improve clinically.”(p<0.05). Increased exposure to placebo response training was associated with 1) increased confidence that the respondent’s individual behavior (p<0.01) or the site staff’s behavior (p<0.01) can influence the magnitude of placebo response in a clinical trial; 2) and disagreement with the notions that the respondent’s role in a clinical trial includes ensuring that patients improve clinically (p=0.001) or that it is unethical to continue subjects in a clinical trial who are not improving (p<0.05). Attitudes toward placebo response did not vary significantly with the proportion of time spent in clinical activities or care unrelated to research.

Conclusions: Investigators and site staff in this international cohort reported a high level of agreement on the importance of placebo response and their ability to influence it in clinical trials. Increased exposure to placebo response training was associated with increased confidence in the ability to modulate placebo response and diminished belief that patients should improve during clinical trial participation. Future presentations will address specific regional findings. Further research should investigate which approaches to placebo response minimization are most effective.

Learning Objectives:
Inform audience of attitudes of clinical trialists toward placebo response

Inform audience of association between exposure to placebo response training and attitudes toward placebo response

References
1. Yang H, Cusin C, Fava M. Is there a placebo problem in antidepressant trials? Curr Top Med Chem. 2005;5(11):1077–1086. PubMed

2. Daniel DG, Loebel A, Cuchiarro J, et al. Understanding of Influence on Placebo Response by Investigators and Site Staff in CNS Clinical Trials. Poster presented at: 51st NCDEU annual meeting: June 13–16, 2011; Boca Raton, Florida.

Back       Poster