Feys F, Bekkering T, Singh K, Devroey D. Do randomized clinical trials with inadequate blinding report enhanced placebo effects for intervention groups and nocebo effects for placebo groups? A protocol for a meta-epidemiological study of PDE-5 inhibitors. Syst Rev. 2012 Nov 14;1(1):54.
Eerste auteur: Feys F.
Jaar: 2012
Type: Publicatie
Abstract:
Background: Patients’ expectations of treatment effects may contribute to positive (placebo) and negative (nocebo) outcomes. The effect of patient expectations may be pronounced in subjectively assessed conditions, such as male erectile dysfunction. The aim of this project is to examine the magnitude of expectancy in trials of phosphodiesterase-5 inhibitors. We hypothesize that randomized controlled trials with inadequate blinding will report enhanced placebo effects for intervention groups and nocebo effects for placebo groups, compared with adequately blinded studies.
Methods: We will quantify the magnitude of expectancy by comparing the effect estimates of trials with inadequate and adequate blinding. Blinding will be assessed using four risk of bias domains from the Cochrane Risk of Bias tool: allocation concealment, blinding of patient, caregiver, and outcome assessor. Our secondary aim is to identify factors that can modify expectations, such as prior experience with the intervention and drug side-effects.
Search methods: We will perform an electronic search using a combination of controlled vocabulary and free text words in the following databases: MEDLINE, EMBASE, CENTRAL, and a clinical trials register.
Selection criteria: We will include randomized controlled trials, with either parallel or crossover design, that compare one phosphodiesterase-5 inhibitor with placebo. The study's primary aim should be to investigate the efficacy of phosphodiesterase-5 inhibitors for treating male erectile dysfunction.
Screening and Data Extraction: Screening will take place at two levels, first of abstracts/titles and followed by full text reports. Two reviewers will independently extract data on the primary outcome and assess risk of bias.
Data Analysis: We will meta-analyze treatment effects if appropriate to assess the magnitude of enhanced placebo effects and nocebo effects in intervention and placebo groups respectively. We will explore possible mediators of placebo and nocebo effects with subgroup and meta-regression analyses.
Discussion: Treatments may confer significant costs and risk of adverse effects; it is important, therefore, to determine if the effects of treatments are larger than expectancy alone. If treatment expectations can be used in a non-deceptive way to produce clinically advantageous outcomes, then it may be possible to incorporate such mechanisms into evidence-based health care decision-making.
Trefwoorden: placebo; nocebo; phosphodiesterase-5 inhibitor; randomized controlled trial; expectancy; blinding; bias