Does different information disclosure on placebo control affect blinding and trial outcomes? A case study of participant information leaflets of randomized placebo-controlled trials of acupuncture

Abstract

Background: While full disclosure of information on placebo control in participant information leaflets (PILs) in a clinical trial is ethically required during informed consent, there have been concerning voices such complete disclosures may increase unnecessary nocebo responses, breach double-blind designs, and/or affect direction of trial outcomes. Taking an example of acupuncture studies, we aimed to examine what participants are told about placebo controls in randomized, placebo-controlled trials, and how it may affect blinding and trial outcomes.

Methods: Authors of published randomized, placebo-controlled trials of acupuncture were identified from PubMed search and invited to provide PILs for their trials. The collected PILs were subjected to content analysis and categorized based on degree of information disclosure on placebo. Blinding index (BI) as a chance-corrected measurement of blinding was calculated and its association with different information disclosure was examined. The impact of different information disclosure from PILs on primary outcomes was estimated using a random effects model.

Results: In 65 collected PILs, approximately 57% of trials fully informed the participants of placebo control, i.e. full disclosure, while the rest gave deceitful or no information on placebo, i.e. no disclosure. Placebo groups in the studies with no disclosure tended to make more opposite guesses on the type of received intervention than those with disclosure, which may reflect wishful thinking (BI -0.21 vs. -0.16; p = 0.38). In outcome analysis, studies with no disclosure significantly favored acupuncture than those with full disclosure (standardized mean difference - 0.43 vs. -0.12; p = 0.03), probably due to enhanced expectations.

Conclusions: How participants are told about placebos can be another potential factor that may influence participant blinding and study outcomes by possibly modulating patient expectation. As we have few empirical findings on this issue, future studies are needed to determine whether the present findings are relevant to other medical disciplines and at the same time a routine practice of fully disclosing placebo information in PILs calls for reevaluation.

Keywords: Blinding; Information disclosure; Informed consent; Outcome; Participant information leaflet; Placebo; Randomized controlled trial.

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Kyung Hee University Ethics Committee (KHSIRB-13-052 (EA)).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

Flow diagram for selection of studies. aAmong included studies, only those providing extractable data for calculating blinding index were included here. bStudies that clearly indicated and reported specific data of primary outcome were eligible for meta-analysis. RCT, randomized controlled trial

Fig. 2

BI values by PIL categories. a BI values of real acupuncture group from FD category; b BI values of real acupuncture group from DD/MI category; c BI values of placebo acupuncture group from FD category; d BI values of placebo acupuncture group from DD/MI category. Negative values indicate opposite guessing of allocated arm, 0 refers to random guessing, and positive values indicate correct guessing of allocated arm (e.g. guessed real acupuncture when assigned to real acupuncture). This study defined BI value between − 0.2 and 0.2, presented in the shaded area in each graph, as random guess [10]. BI, blinding index; DD, deceptive disclosure of placebo acupuncture; FD, full disclosure of placebo acupuncture; MI, missing information on placebo acupuncture; PIL, participant information leaflet

Fig. 3

Clinical outcomes by PIL categories. Anonymized studies are from (a) FD category, and (b) DD category, respectively. A test for subgroup differences indicates that studies from DD category report greater effects of real acupuncture compared to those from FD category. CI, confidence intervals; DD, deceptive disclosure of placebo acupuncture; FD, full disclosure of placebo acupuncture; PIL, participant information leaflet; SE, standard error; Std., standardized