Abstract
BackgroundWhile 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.MethodsAuthors 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.ResultsIn 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.ConclusionsHow 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.
Highlights
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
One author generously provided two extra PILs on top of the requested documents and final 65 PILs from 15 different countries were collected for analysis (Fig. 1; Additional file 1: Appendix 1)
Findings of the current study show change of practice ever since, showing number of studies that accurately inform the use of placebo control, being more than a half: out of 70 placebo groups from 65 PILs, 40 were classified into Full disclosure (FD) category, and 12 of those 40 were from the older studies that were included in the previous review
Summary
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. In non-pharmacological trials, it has been challenging since detailed information on study hypothesis may compromise the success of blinding while ensuring participant’s autonomy is an essential ethical research conduct. Placebo-controlled trials of acupuncture have been in particular criticized for being stingy with placebo information disclosure to their participants [3, 4] Such practice, i.e. partial or no information on study hypothesis and methods to the study participants, is line with one of the strategies used in studies assessing non-pharmacological treatment to achieve successful blinding [2]
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