Novel method to select meaningful outcomes for evaluation in clinical trials

Charlie McLeod; Richard Norman; Jamie Wood; Siobhain Mulrennan; Sue Morey; André Schultz; Mitch Messer; Kate Spaapen; Matthew Stoneham; Yue Wu; Alan Smyth; Christopher Blyth; Steve Webb; Steven Mascaro; Owen Woodberry; Tom Snelling

doi:10.1136/bmjresp-2021-000877

Novel method to select meaningful outcomes for evaluation in clinical trials

Charlie McLeod, Richard Norman, Jamie Wood, Siobhain Mulrennan, Sue Morey, André Schultz, Mitch Messer, Kate Spaapen, Matthew Stoneham, Yue Wu, Alan Smyth, Christopher Blyth, Steve Webb, Steven Mascaro, Owen Woodberry, Tom Snelling

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

4 Citations (Scopus)

33 Downloads (Pure)

Abstract

Background: A standardised framework for selecting outcomes for evaluation in trials has been proposed by the Core Outcome Measures in Effectiveness Trials working group. However, this method does not specify how to ensure that the outcomes that are selected are causally related to the disease and the health intervention being studied. Causal network diagrams may help researchers identify outcomes that are both clinically meaningful and likely to be causally dependent on the intervention, and endpoints that are, in turn, causally dependent on those outcomes. We aimed to (1) develop a generalisable method for selecting outcomes and endpoints in trials and (2) apply this method to select outcomes for evaluation in a trial investigating treatment strategies for pulmonary exacerbations of cystic fibrosis (CF).

Methods: We conducted a series of online surveys and workshops among people affected by CF. We used a modified Delphi approach to develop a consensus list of important outcomes. A workshop involving domain experts elicited how these outcomes were causally related to the underlying pathophysiological processes. Meaningful outcomes were prioritised based on the extent to which each outcome captured separate rather than common aspects of the underlying pathophysiological process.

Results: The 10 prioritised outcomes were: breathing difficulty/pain, sputum production/clearance, fatigue, appetite, pain (not related to breathing), motivation/demoralisation, fevers/night sweats, treatment burden, inability to meet personal goals and avoidance of gastrointestinal symptoms.

Conclusions: This proposed method for selecting meaningful outcomes for evaluation in clinical trials may improve the value of research as a basis for clinical decisions.

Original language	English
Article number	e000877
Number of pages	21
Journal	BMJ Open Respiratory Research
Volume	8
Issue number	1
DOIs	https://doi.org/10.1136/bmjresp-2021-000877
Publication status	Published - 07 Oct 2021
Externally published	Yes

Bibliographical note

Funding Information:
Funding This work was supported by a Perth Children’s Hospital New Investigator grant (9757). CM is supported by an NHMRC post-graduate scholarship (GNT1150996), and top-up grants from the Wesfarmers Centre (top-up grant) and the Perth Children’s Hospital Foundation (9722). TS is supported by a Career Development Fellowship from the National Health and Medical Research Council (GNT1111657). CB is also supported by the National Health and Medical Research Council (1111596/1173163).

Publisher Copyright:
©

Keywords

cystic fibrosis
paediatric lung disaese
rare lung diseases
respiratory infection

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine

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10.1136/bmjresp-2021-000877Licence: CC BY-NC

Novel method to select meaningful outcomes for evaluation in clinical trials
Copyright 2021 the authors. This is an open access Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction for non-commercial purposes, provided the author and source are cited.
Final published version, 2.75 MBLicence: CC BY-NC

Cite this

McLeod, C., Norman, R., Wood, J., Mulrennan, S., Morey, S., Schultz, A., Messer, M., Spaapen, K., Stoneham, M., Wu, Y., Smyth, A., Blyth, C., Webb, S., Mascaro, S., Woodberry, O., & Snelling, T. (2021). Novel method to select meaningful outcomes for evaluation in clinical trials. BMJ Open Respiratory Research, 8(1), Article e000877. https://doi.org/10.1136/bmjresp-2021-000877

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abstract = "Background: A standardised framework for selecting outcomes for evaluation in trials has been proposed by the Core Outcome Measures in Effectiveness Trials working group. However, this method does not specify how to ensure that the outcomes that are selected are causally related to the disease and the health intervention being studied. Causal network diagrams may help researchers identify outcomes that are both clinically meaningful and likely to be causally dependent on the intervention, and endpoints that are, in turn, causally dependent on those outcomes. We aimed to (1) develop a generalisable method for selecting outcomes and endpoints in trials and (2) apply this method to select outcomes for evaluation in a trial investigating treatment strategies for pulmonary exacerbations of cystic fibrosis (CF). Methods: We conducted a series of online surveys and workshops among people affected by CF. We used a modified Delphi approach to develop a consensus list of important outcomes. A workshop involving domain experts elicited how these outcomes were causally related to the underlying pathophysiological processes. Meaningful outcomes were prioritised based on the extent to which each outcome captured separate rather than common aspects of the underlying pathophysiological process. Results: The 10 prioritised outcomes were: breathing difficulty/pain, sputum production/clearance, fatigue, appetite, pain (not related to breathing), motivation/demoralisation, fevers/night sweats, treatment burden, inability to meet personal goals and avoidance of gastrointestinal symptoms. Conclusions: This proposed method for selecting meaningful outcomes for evaluation in clinical trials may improve the value of research as a basis for clinical decisions.",

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AU - Norman, Richard

AU - Wood, Jamie

AU - Mulrennan, Siobhain

AU - Morey, Sue

AU - Schultz, André

AU - Messer, Mitch

AU - Spaapen, Kate

AU - Stoneham, Matthew

AU - Wu, Yue

AU - Smyth, Alan

AU - Blyth, Christopher

AU - Webb, Steve

AU - Mascaro, Steven

AU - Woodberry, Owen

AU - Snelling, Tom

N1 - Funding Information: Funding This work was supported by a Perth Children’s Hospital New Investigator grant (9757). CM is supported by an NHMRC post-graduate scholarship (GNT1150996), and top-up grants from the Wesfarmers Centre (top-up grant) and the Perth Children’s Hospital Foundation (9722). TS is supported by a Career Development Fellowship from the National Health and Medical Research Council (GNT1111657). CB is also supported by the National Health and Medical Research Council (1111596/1173163). Publisher Copyright: ©

PY - 2021/10/7

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N2 - Background: A standardised framework for selecting outcomes for evaluation in trials has been proposed by the Core Outcome Measures in Effectiveness Trials working group. However, this method does not specify how to ensure that the outcomes that are selected are causally related to the disease and the health intervention being studied. Causal network diagrams may help researchers identify outcomes that are both clinically meaningful and likely to be causally dependent on the intervention, and endpoints that are, in turn, causally dependent on those outcomes. We aimed to (1) develop a generalisable method for selecting outcomes and endpoints in trials and (2) apply this method to select outcomes for evaluation in a trial investigating treatment strategies for pulmonary exacerbations of cystic fibrosis (CF). Methods: We conducted a series of online surveys and workshops among people affected by CF. We used a modified Delphi approach to develop a consensus list of important outcomes. A workshop involving domain experts elicited how these outcomes were causally related to the underlying pathophysiological processes. Meaningful outcomes were prioritised based on the extent to which each outcome captured separate rather than common aspects of the underlying pathophysiological process. Results: The 10 prioritised outcomes were: breathing difficulty/pain, sputum production/clearance, fatigue, appetite, pain (not related to breathing), motivation/demoralisation, fevers/night sweats, treatment burden, inability to meet personal goals and avoidance of gastrointestinal symptoms. Conclusions: This proposed method for selecting meaningful outcomes for evaluation in clinical trials may improve the value of research as a basis for clinical decisions.

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KW - cystic fibrosis

KW - paediatric lung disaese

KW - rare lung diseases

KW - respiratory infection

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JO - BMJ Open Respiratory Research

JF - BMJ Open Respiratory Research

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M1 - e000877

ER -

Novel method to select meaningful outcomes for evaluation in clinical trials

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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