Drug Safety

, Volume 28, Issue 1, pp 81–87 | Cite as

Effect of Information on Reported Adverse Events in a Placebo-Controlled Trial

  • Michael Ossege
  • Thomas Sycha
  • Martin Aigner
  • Leopold Schmetterer
  • Hans-Georg Eichler
  • Markus Müller
  • Franz König
  • Peter Bauer
Original Research Article

Abstract

Objective: Although placebo controls are a standard measure in clinical trials the mechanisms underlying placebo effects are still not fully understood. We hypothesised that information about the likelihood of receiving placebo might influence the perception of adverse effects in volunteers participating in a clinical trial.

Methods: Healthy subjects received either nifedipine 20mg or placebo in an adaptive two-stage crossover study. Sixty subjects were randomised to a group given either correct (50% chance) or misleading (100% chance) information about the likelihood of receiving the active drug. A sum of the severity scores from visual analogue scales over all individual adverse effects was defined as the primary endpoint.

Results: The analysis revealed no difference in the primary endpoint between the two groups. This lack of difference may in part be attributable to a conditioning effect as on the first study day higher symptom scores were reported by the participants than on the second study day. Furthermore, the day effect seemed to arise mainly when the first day treatment was the placebo. For the placebo the day effect was clearly significant (p = 0.012), with higher scores on the first day. A further explorative finding in patients given placebo was a tendency for higher scores in the group with the misleading information (p = 0.08). Nothing of that sort was found in the analysis for active treatment. The day effect collapsed and the factor information did not show any tendency of being a potential influence.

Conclusions: In the present study we did not find a statistically significant effect of misleading information on reported adverse events. The large treatment and day effects observed made it difficult to detect a potential small information effect. However, this study excluded a strong and relevant effect of information on the frequency and severity of reported adverse events.

Keywords

Placebo Nifedipine Interim Analysis Classical Conditioning Heat Sensation 

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

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Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Michael Ossege
    • 1
    • 2
  • Thomas Sycha
    • 3
  • Martin Aigner
    • 2
  • Leopold Schmetterer
    • 1
  • Hans-Georg Eichler
    • 1
  • Markus Müller
    • 1
  • Franz König
    • 4
  • Peter Bauer
    • 4
  1. 1.Department of Clinical PharmacologyMedical University of ViennaViennaAustria
  2. 2.Department of PsychiatryMedical University of Vienna, General Hospital ViennaViennaAustria
  3. 3.Department of NeurologyMedical University of ViennaViennaAustria
  4. 4.Department of Medical StatisticsMedical University of ViennaViennaAustria

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