Reporting of justifications for withholding established effective interventions in randomised placebo-controlled trials: a systematic review.
5 affiliations
- 1University of Birmingham, Dubai, United Arab Emirates. [email protected].
- 2University of Birmingham, Birmingham, UK.
- 3Methodological and Implementation Research Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
- 4School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.
- 5University of Birmingham, Birmingham, UK. [email protected].
Abstract
Background
Randomised-controlled-trials (RCTs) are crucial for assessing the efficacy of new treatments. Some RCTs are placebo-controlled, which is uncontroversial when there is no established effective intervention or when a placebo is added to one. However, withholding an established effective intervention from participants requires justification.Aim and objectives
This systematic review aims to examine reporting practices around withholding established effective interventions from participants in placebo-controlled RCTs. Our objectives are (i) to determine the frequency with which established effective interventions are withheld in placebo-controlled RCTs without reported justification; (ii) to ascertain whether these relate to control arms only or both; (iii) to ascertain whether research participants are communicated this information; and (iv) explore factors associated with this practice.Methods
Protocols of placebo-controlled RCTs, published in the journal Trials in 2022, were identified. Full-text of included protocols and available materials were accessed to estimate the proportion that withheld established effective interventions without reported justification. The withholding of effective interventions was categorised as either withholding a known effective intervention from the placebo arm or withholding a known effective concomitant treatment from both arms. We explored associations with: study conduct region, industry sponsorship, therapeutic area and complementary medicine.Results
A total of 134 protocols met the inclusion criteria. Only a minority (27, 20%) provided participant-facing material. Of these 134 protocols, (14, 10%) were identified as withholding effective interventions without reported justification. The majority (12, 86%) involved withholding concomitant medications in both arms, whilst (2,14%) withheld effective interventions from only the placebo arm; none reported justification in the participant-facing materials (although in only one was this material available). Most (9, 64%) of the protocols that withheld effective interventions, without reported justification, were conducted in Asia; most were testing complementary medicines (10, 71%); only (3, 21%) were industry-sponsored.Conclusion
In this sample of protocols published in Trials in 2022, 10% withheld an established effective intervention without a reported justification, and this mostly related to withholding effective concomitant medications from both study arms. The majority of studies do not make their participant facing material available and so it cannot be determined what information is provided to study participants.
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BibTeX
@article{abdallah2026reporting,
title = {{Reporting of justifications for withholding established effective interventions in randomised placebo-controlled trials: a systematic review.}},
author = {Hadeer Ghareeb Abdallah and Karla Hemming and Cory E Goldstein and Alexander Gough},
journal = {Trials},
year = {2026},
month = aug,
doi = {10.1186/s13063-026-09897-9},
url = {https://europepmc.org/article/MED/42972473},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Reporting of justifications for withholding established effective interventions in randomised placebo-controlled trials: a systematic review.
AU - Hadeer Ghareeb Abdallah
AU - Karla Hemming
AU - Cory E Goldstein
AU - Alexander Gough
PY - 2026
DA - 2026/08/01
JO - Trials
DO - 10.1186/s13063-026-09897-9
UR - https://europepmc.org/article/MED/42972473
AB - Background Randomised-controlled-trials (RCTs) are crucial for assessing the efficacy of new treatments. Some RCTs are placebo-controlled, which is uncontroversial when there is no established effective intervention or when a placebo is added to one. However, withholding an established effective intervention from participants requires justification.Aim and objectives This systematic review aims to examine reporting practices around withholding established effective interventions from participants in placebo-controlled RCTs. Our objectives are (i) to determine the frequency with which established effective interventions are withheld in placebo-controlled RCTs without reported justification; (ii) to ascertain whether these relate to control arms only or both; (iii) to ascertain whether research participants are communicated this information; and (iv) explore factors associated with this practice.Methods Protocols of placebo-controlled RCTs, published in the journal Trials in 2022, were identified. Full-text of included protocols and available materials were accessed to estimate the proportion that withheld established effective interventions without reported justification. The withholding of effective interventions was categorised as either withholding a known effective intervention from the placebo arm or withholding a known effective concomitant treatment from both arms. We explored associations with: study conduct region, industry sponsorship, therapeutic area and complementary medicine.Results A total of 134 protocols met the inclusion criteria. Only a minority (27, 20%) provided participant-facing material. Of these 134 protocols, (14, 10%) were identified as withholding effective interventions without reported justification. The majority (12, 86%) involved withholding concomitant medications in both arms, whilst (2,14%) withheld effective interventions from only the placebo arm; none reported justification in the participant-facing materials (although in only one was this material available). Most (9, 64%) of the protocols that withheld effective interventions, without reported justification, were conducted in Asia; most were testing complementary medicines (10, 71%); only (3, 21%) were industry-sponsored.Conclusion In this sample of protocols published in Trials in 2022, 10% withheld an established effective intervention without a reported justification, and this mostly related to withholding effective concomitant medications from both study arms. The majority of studies do not make their participant facing material available and so it cannot be determined what information is provided to study participants.
SN - 1745-6215
ER -