Optimizing the design of invasive placebo interventions in randomized controlled trials

S. Cousins; N. S. Blencowe; C. Tsang; K. Chalmers; A. Mardanpour; A. J. Carr; M. K. Campbell; J. A. Cook; D. J. Beard; J. M. Blazeby

doi:10.1002/bjs.11509

Optimizing the design of invasive placebo interventions in randomized controlled trials

S. Cousins^* (Corresponding Author), N. S. Blencowe, C. Tsang, K. Chalmers, A. Mardanpour, A. J. Carr, M. K. Campbell, J. A. Cook, D. J. Beard, J. M. Blazeby

^*Corresponding author for this work

School of Medicine, Medical Sciences & Nutrition

Medical Research Council ConDuCT-II Hub for Trials Methodology Research, Bristol Centre for Surgical Research, Population Health Sciences, Bristol Medical School.
University Hospitals Bristol NHS Foundation Trust
Royal College of Surgeons (England) Surgical Interventional Trials Unit, University of Oxford
University of Oxford
National Institute for Health Research (NIHR) Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and University of Bristol
Medical Research Council ConDuCT-II Hub for Trials Methodology Research, Bristol Centre for Surgical Research, Population Health Sciences, Bristol Medical School

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

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Abstract

BACKGROUND: Placebo-controlled trials play an important role in the evaluation of healthcare interventions. However, they can be challenging to design and deliver for invasive interventions, including surgery. In-depth understanding of the component parts of the treatment intervention is needed to ascertain what should, and should not, be delivered as part of the placebo. Assessment of risk to patients and strategies to ensure that the placebo effectively mimics the treatment are also required. To date, no guidance exists for the design of invasive placebo interventions. This study aimed to develop a framework to optimize the design and delivery of invasive placebo interventions in RCTs.

METHODS: A preliminary framework was developed using published literature to: expand the scope of an existing typology, which facilitates the deconstruction of invasive interventions; and identify placebo optimization strategies. The framework was refined after consultation with key stakeholders in surgical trials, consensus methodology and medical ethics.

RESULTS: The resulting DITTO framework consists of five stages: deconstruct treatment intervention into constituent components and co-interventions; identify critical surgical element(s); take out the critical element(s); think risk, feasibility and role of placebo in the trial when considering remaining components; and optimize placebo to ensure effective blinding of patients and trial personnel.

CONCLUSION: DITTO considers invasive placebo composition systematically, accounting for risk, feasibility and placebo optimization. Use of the framework can support the design of high-quality RCTs, which are needed to underpin delivery of healthcare interventions.

Original language	English
Pages (from-to)	1114-1122
Number of pages	9
Journal	British Journal of Surgery
Volume	107
Issue number	9
Early online date	18 Mar 2020
DOIs	https://doi.org/10.1002/bjs.11509
Publication status	Published - 1 Aug 2020

Bibliographical note

The authors thank A. Skilton for preparing Fig. 1. This study was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol National Health Service (NHS) Foundation Trust and the University of Bristol, MRC ConDuCT‐II (Collaboration and innovation for Difficult and Complex randomised controlled Trials In Invasive procedures) Hub for Trials Methodology Research (MR/K025643/1) (http://www.bristol.ac.uk/population‐health‐sciences/centres/conduct2), a NIHR senior investigator award (NF‐SI‐0514‐10114) and the Bristol Royal College of Surgeons Trials Centre. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The funders played no role in any aspect of the study design, analysis or publication decisions.

Keywords

GASTROESOPHAGEAL-REFLUX DISEASE
SHAM SURGERY
VERTEBROPLASTY
VOLUME

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Cite this

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title = "Optimizing the design of invasive placebo interventions in randomized controlled trials",

abstract = "BACKGROUND: Placebo-controlled trials play an important role in the evaluation of healthcare interventions. However, they can be challenging to design and deliver for invasive interventions, including surgery. In-depth understanding of the component parts of the treatment intervention is needed to ascertain what should, and should not, be delivered as part of the placebo. Assessment of risk to patients and strategies to ensure that the placebo effectively mimics the treatment are also required. To date, no guidance exists for the design of invasive placebo interventions. This study aimed to develop a framework to optimize the design and delivery of invasive placebo interventions in RCTs.METHODS: A preliminary framework was developed using published literature to: expand the scope of an existing typology, which facilitates the deconstruction of invasive interventions; and identify placebo optimization strategies. The framework was refined after consultation with key stakeholders in surgical trials, consensus methodology and medical ethics.RESULTS: The resulting DITTO framework consists of five stages: deconstruct treatment intervention into constituent components and co-interventions; identify critical surgical element(s); take out the critical element(s); think risk, feasibility and role of placebo in the trial when considering remaining components; and optimize placebo to ensure effective blinding of patients and trial personnel.CONCLUSION: DITTO considers invasive placebo composition systematically, accounting for risk, feasibility and placebo optimization. Use of the framework can support the design of high-quality RCTs, which are needed to underpin delivery of healthcare interventions.",

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author = "S. Cousins and Blencowe, {N. S.} and C. Tsang and K. Chalmers and A. Mardanpour and Carr, {A. J.} and Campbell, {M. K.} and Cook, {J. A.} and Beard, {D. J.} and Blazeby, {J. M.}",

note = "The authors thank A. Skilton for preparing Fig. 1. This study was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol National Health Service (NHS) Foundation Trust and the University of Bristol, MRC ConDuCT‐II (Collaboration and innovation for Difficult and Complex randomised controlled Trials In Invasive procedures) Hub for Trials Methodology Research (MR/K025643/1) (http://www.bristol.ac.uk/population‐health‐sciences/centres/conduct2), a NIHR senior investigator award (NF‐SI‐0514‐10114) and the Bristol Royal College of Surgeons Trials Centre. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The funders played no role in any aspect of the study design, analysis or publication decisions. ",

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T1 - Optimizing the design of invasive placebo interventions in randomized controlled trials

AU - Cousins, S.

AU - Blencowe, N. S.

AU - Tsang, C.

AU - Chalmers, K.

AU - Mardanpour, A.

AU - Carr, A. J.

AU - Campbell, M. K.

AU - Cook, J. A.

AU - Beard, D. J.

AU - Blazeby, J. M.

N1 - The authors thank A. Skilton for preparing Fig. 1. This study was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol National Health Service (NHS) Foundation Trust and the University of Bristol, MRC ConDuCT‐II (Collaboration and innovation for Difficult and Complex randomised controlled Trials In Invasive procedures) Hub for Trials Methodology Research (MR/K025643/1) (http://www.bristol.ac.uk/population‐health‐sciences/centres/conduct2), a NIHR senior investigator award (NF‐SI‐0514‐10114) and the Bristol Royal College of Surgeons Trials Centre. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The funders played no role in any aspect of the study design, analysis or publication decisions.

PY - 2020/8/1

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N2 - BACKGROUND: Placebo-controlled trials play an important role in the evaluation of healthcare interventions. However, they can be challenging to design and deliver for invasive interventions, including surgery. In-depth understanding of the component parts of the treatment intervention is needed to ascertain what should, and should not, be delivered as part of the placebo. Assessment of risk to patients and strategies to ensure that the placebo effectively mimics the treatment are also required. To date, no guidance exists for the design of invasive placebo interventions. This study aimed to develop a framework to optimize the design and delivery of invasive placebo interventions in RCTs.METHODS: A preliminary framework was developed using published literature to: expand the scope of an existing typology, which facilitates the deconstruction of invasive interventions; and identify placebo optimization strategies. The framework was refined after consultation with key stakeholders in surgical trials, consensus methodology and medical ethics.RESULTS: The resulting DITTO framework consists of five stages: deconstruct treatment intervention into constituent components and co-interventions; identify critical surgical element(s); take out the critical element(s); think risk, feasibility and role of placebo in the trial when considering remaining components; and optimize placebo to ensure effective blinding of patients and trial personnel.CONCLUSION: DITTO considers invasive placebo composition systematically, accounting for risk, feasibility and placebo optimization. Use of the framework can support the design of high-quality RCTs, which are needed to underpin delivery of healthcare interventions.

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KW - VOLUME

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Optimizing the design of invasive placebo interventions in randomized controlled trials

Abstract

Bibliographical note

Keywords

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