Guidance from key organisations on exploring, confirming and interpreting subgroup effects of medical treatments: a scoping review

Objectives With the increasing interest in personalised medicine, the use of subgroup analyses is likely to increase. Subgroup analyses are challenging and often misused, possibly leading to false interpretations of the effect. It remains unclear to what extent key organisations warn for such pitfal...

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Main Authors: Johannes B Reitsma, Maroeska M Rovers, Stan R W Wijn, Ly H Le, Michail Belias, Jeroen Hoogland, Joanna IntHout, Thomas Debray
Format: Article
Language:English
Published: BMJ Publishing Group 2019-08-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/9/8/e028751.full
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author Johannes B Reitsma
Maroeska M Rovers
Stan R W Wijn
Ly H Le
Michail Belias
Jeroen Hoogland
Joanna IntHout
Thomas Debray
author_facet Johannes B Reitsma
Maroeska M Rovers
Stan R W Wijn
Ly H Le
Michail Belias
Jeroen Hoogland
Joanna IntHout
Thomas Debray
author_sort Johannes B Reitsma
collection DOAJ
description Objectives With the increasing interest in personalised medicine, the use of subgroup analyses is likely to increase. Subgroup analyses are challenging and often misused, possibly leading to false interpretations of the effect. It remains unclear to what extent key organisations warn for such pitfalls and translate current methodological research to detect these effects into research guidelines. The aim of this scoping review is to determine and evaluate the current guidance used by organisations for exploring, confirming and interpreting subgroup effects.Design Scoping review.Eligibility criteria We identified four types of key stakeholder organisations: industry, health technology assessment organisations (HTA), academic/non-profit research organisations and regulatory bodies. After literature search and expert consultation, we identified international and national organisations of each type. For each organisation that was identified, we searched for official research guidance documents and contacted the organisation for additional guidance.Results Twenty-seven (45%) of the 60 organisations that we included had relevant research guidance documents. We observed large differences between organisation types: 18% (n=2) of the industry organisations, 64% (n=9) of the HTA organisations, 38% (n=8) of academic/non-profit research organisations and 57% (n=8) of regulatory bodies provided guidance documents. The majority of the documents (n=33, 63%) mentioned one or more challenges in subgroup analyses, such as false positive findings or ecological bias with variations across the organisation types. Statistical recommendations were less common (n=19, 37%) and often limited to a formal test of interaction.Conclusions Almost half of the organisations included in this scoping review provided guidance on subgroup effect research in their guidelines. However, there were large differences between organisations in the amount and level of detail of their guidance. Effort is required to translate and integrate research findings on subgroup analysis to practical guidelines for decision making and to reduce the differences between organisations and organisation types.
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spelling doaj-art-1447b7ee3f4342979dadfe76095d76bc2025-08-20T02:23:08ZengBMJ Publishing GroupBMJ Open2044-60552019-08-019810.1136/bmjopen-2018-028751Guidance from key organisations on exploring, confirming and interpreting subgroup effects of medical treatments: a scoping reviewJohannes B Reitsma0Maroeska M Rovers1Stan R W Wijn2Ly H Le3Michail Belias4Jeroen Hoogland5Joanna IntHout6Thomas Debray7Cochrane Netherlands, Julius Center for Health Sciences and Primary Care, Utrecht University, University Medical Center Utrecht, Utrecht, NetherlandsOperation Rooms, Health Evidence, Radboudumc, Nijmegen, The NetherlandsRadboud University Medical Center, Radboud Institute for Health Sciences, Department of Operating Rooms, Radboudumc, Nijmegen, The Netherlands2 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands3 Department for Health Evidence, Radboud Institute for Health Sciences, Radboudumc, Nijmegen, The NetherlandsJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsDepartment for Health Evidence, Radboudumc, Nijmegen, The Netherlandssenior statisticianObjectives With the increasing interest in personalised medicine, the use of subgroup analyses is likely to increase. Subgroup analyses are challenging and often misused, possibly leading to false interpretations of the effect. It remains unclear to what extent key organisations warn for such pitfalls and translate current methodological research to detect these effects into research guidelines. The aim of this scoping review is to determine and evaluate the current guidance used by organisations for exploring, confirming and interpreting subgroup effects.Design Scoping review.Eligibility criteria We identified four types of key stakeholder organisations: industry, health technology assessment organisations (HTA), academic/non-profit research organisations and regulatory bodies. After literature search and expert consultation, we identified international and national organisations of each type. For each organisation that was identified, we searched for official research guidance documents and contacted the organisation for additional guidance.Results Twenty-seven (45%) of the 60 organisations that we included had relevant research guidance documents. We observed large differences between organisation types: 18% (n=2) of the industry organisations, 64% (n=9) of the HTA organisations, 38% (n=8) of academic/non-profit research organisations and 57% (n=8) of regulatory bodies provided guidance documents. The majority of the documents (n=33, 63%) mentioned one or more challenges in subgroup analyses, such as false positive findings or ecological bias with variations across the organisation types. Statistical recommendations were less common (n=19, 37%) and often limited to a formal test of interaction.Conclusions Almost half of the organisations included in this scoping review provided guidance on subgroup effect research in their guidelines. However, there were large differences between organisations in the amount and level of detail of their guidance. Effort is required to translate and integrate research findings on subgroup analysis to practical guidelines for decision making and to reduce the differences between organisations and organisation types.https://bmjopen.bmj.com/content/9/8/e028751.full
spellingShingle Johannes B Reitsma
Maroeska M Rovers
Stan R W Wijn
Ly H Le
Michail Belias
Jeroen Hoogland
Joanna IntHout
Thomas Debray
Guidance from key organisations on exploring, confirming and interpreting subgroup effects of medical treatments: a scoping review
BMJ Open
title Guidance from key organisations on exploring, confirming and interpreting subgroup effects of medical treatments: a scoping review
title_full Guidance from key organisations on exploring, confirming and interpreting subgroup effects of medical treatments: a scoping review
title_fullStr Guidance from key organisations on exploring, confirming and interpreting subgroup effects of medical treatments: a scoping review
title_full_unstemmed Guidance from key organisations on exploring, confirming and interpreting subgroup effects of medical treatments: a scoping review
title_short Guidance from key organisations on exploring, confirming and interpreting subgroup effects of medical treatments: a scoping review
title_sort guidance from key organisations on exploring confirming and interpreting subgroup effects of medical treatments a scoping review
url https://bmjopen.bmj.com/content/9/8/e028751.full
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