Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations

Lucy Webster, Derek Groskreutz, Anna Grinbergs-Saull, Rob Howard, John T. O'Brien, Gail Mountain, Sube Banerjee, Bob Woods, Robert Perneczky, Louise Lafortune, Charlotte Roberts, Jenny McCleery, James Pickett, Frances Bunn, David Challis, Georgina Charlesworth, Katie Featherstone, Chris Fox, Claire Goodman, Roy Jones & 19 others Sallie Lamb, Esme Moniz-Cook, Justine Schneider, Sasha Shepperd, Claire Surr, Jo Thompson-Coon, Clive Ballard, Carol Brayne, Orlaith Burke, Alistair Burns, Linda Clare, Peter Garrard, Patrick Kehoe, Peter Passmore, Clive Holmes, Ian Maidment, Fliss Murtagh, Louise Robinson, Gill Livingston

Research output: Contribution to journalReview article

Abstract

BACKGROUND: There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials.

OBJECTIVES: To agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI).

DATA SOURCES: We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches.

REVIEW METHODS: The project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes.

RESULTS: We included 149 papers from the 22,918 papers screened, referring to 125 individual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally.

LIMITATIONS: Most of the trials included participants with Alzheimer's disease, so recommendations may not apply to other types of dementia. We did not conduct economic analyses. The PPI consultation was limited to members of the Alzheimer's Society Research Network.

CONCLUSIONS: Cognitive outcomes and biological markers form the core outcome set for future disease modification trials, measured by the MMSE or ADAS-Cog, and structural MRI in a subset of participants.

FUTURE WORK: We envisage that the core set may be superseded in the future, particularly for other types of dementia. There is a need to develop an algorithm to compare scores on the MMSE and ADAS-Cog.

STUDY REGISTRATION: The project was registered with Core Outcome Measures in Effectiveness Trials [ www.comet-initiative.org/studies/details/819?result=true (accessed 7 April 2016)]. The systematic review protocol is registered as PROSPERO CRD42015027346.

FUNDING: The National Institute for Health Research Health Technology Assessment programme.

LanguageEnglish
Number of pages192
JournalHealth Technology Assessment
Volume21
Issue number26
DOIs
Publication statusPublished - 31 May 2017

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Dementia
Consensus
Referral and Consultation
Alzheimer Disease
Quality of Life
National Institutes of Health (U.S.)
Activities of Daily Living
Research
Cognition
Biomarkers
Magnetic Resonance Imaging
Biomedical Technology Assessment
Symptom Assessment
Health
Registries
Disease Progression
Nursing
Randomized Controlled Trials
Economics
Research Personnel

Bibliographical note

© Queen’s Printer and Controller of HMSO 2017. This work was produced by Webster et al. under the terms of a commissioning contract issued by the Secretary of State for Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

Keywords

  • Meta-Analysis

Cite this

Webster, Lucy ; Groskreutz, Derek ; Grinbergs-Saull, Anna ; Howard, Rob ; O'Brien, John T. ; Mountain, Gail ; Banerjee, Sube ; Woods, Bob ; Perneczky, Robert ; Lafortune, Louise ; Roberts, Charlotte ; McCleery, Jenny ; Pickett, James ; Bunn, Frances ; Challis, David ; Charlesworth, Georgina ; Featherstone, Katie ; Fox, Chris ; Goodman, Claire ; Jones, Roy ; Lamb, Sallie ; Moniz-Cook, Esme ; Schneider, Justine ; Shepperd, Sasha ; Surr, Claire ; Thompson-Coon, Jo ; Ballard, Clive ; Brayne, Carol ; Burke, Orlaith ; Burns, Alistair ; Clare, Linda ; Garrard, Peter ; Kehoe, Patrick ; Passmore, Peter ; Holmes, Clive ; Maidment, Ian ; Murtagh, Fliss ; Robinson, Louise ; Livingston, Gill. / Development of a core outcome set for disease modification trials in mild to moderate dementia : a systematic review, patient and public consultation and consensus recommendations. In: Health Technology Assessment. 2017 ; Vol. 21, No. 26.
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abstract = "BACKGROUND: There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials.OBJECTIVES: To agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI).DATA SOURCES: We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches.REVIEW METHODS: The project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes.RESULTS: We included 149 papers from the 22,918 papers screened, referring to 125 individual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally.LIMITATIONS: Most of the trials included participants with Alzheimer's disease, so recommendations may not apply to other types of dementia. We did not conduct economic analyses. The PPI consultation was limited to members of the Alzheimer's Society Research Network.CONCLUSIONS: Cognitive outcomes and biological markers form the core outcome set for future disease modification trials, measured by the MMSE or ADAS-Cog, and structural MRI in a subset of participants.FUTURE WORK: We envisage that the core set may be superseded in the future, particularly for other types of dementia. There is a need to develop an algorithm to compare scores on the MMSE and ADAS-Cog.STUDY REGISTRATION: The project was registered with Core Outcome Measures in Effectiveness Trials [ www.comet-initiative.org/studies/details/819?result=true (accessed 7 April 2016)]. The systematic review protocol is registered as PROSPERO CRD42015027346.FUNDING: The National Institute for Health Research Health Technology Assessment programme.",
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note = "{\circledC} Queen’s Printer and Controller of HMSO 2017. This work was produced by Webster et al. under the terms of a commissioning contract issued by the Secretary of State for Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.",
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Webster, L, Groskreutz, D, Grinbergs-Saull, A, Howard, R, O'Brien, JT, Mountain, G, Banerjee, S, Woods, B, Perneczky, R, Lafortune, L, Roberts, C, McCleery, J, Pickett, J, Bunn, F, Challis, D, Charlesworth, G, Featherstone, K, Fox, C, Goodman, C, Jones, R, Lamb, S, Moniz-Cook, E, Schneider, J, Shepperd, S, Surr, C, Thompson-Coon, J, Ballard, C, Brayne, C, Burke, O, Burns, A, Clare, L, Garrard, P, Kehoe, P, Passmore, P, Holmes, C, Maidment, I, Murtagh, F, Robinson, L & Livingston, G 2017, 'Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations' Health Technology Assessment, vol. 21, no. 26. https://doi.org/10.3310/hta21260

Development of a core outcome set for disease modification trials in mild to moderate dementia : a systematic review, patient and public consultation and consensus recommendations. / Webster, Lucy; Groskreutz, Derek; Grinbergs-Saull, Anna; Howard, Rob; O'Brien, John T.; Mountain, Gail; Banerjee, Sube; Woods, Bob; Perneczky, Robert; Lafortune, Louise; Roberts, Charlotte; McCleery, Jenny; Pickett, James; Bunn, Frances; Challis, David; Charlesworth, Georgina; Featherstone, Katie; Fox, Chris; Goodman, Claire; Jones, Roy; Lamb, Sallie; Moniz-Cook, Esme; Schneider, Justine; Shepperd, Sasha; Surr, Claire; Thompson-Coon, Jo; Ballard, Clive; Brayne, Carol; Burke, Orlaith; Burns, Alistair; Clare, Linda; Garrard, Peter; Kehoe, Patrick; Passmore, Peter; Holmes, Clive; Maidment, Ian; Murtagh, Fliss; Robinson, Louise; Livingston, Gill.

In: Health Technology Assessment, Vol. 21, No. 26, 31.05.2017.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Development of a core outcome set for disease modification trials in mild to moderate dementia

T2 - Health Technology Assessment

AU - Webster, Lucy

AU - Groskreutz, Derek

AU - Grinbergs-Saull, Anna

AU - Howard, Rob

AU - O'Brien, John T.

AU - Mountain, Gail

AU - Banerjee, Sube

AU - Woods, Bob

AU - Perneczky, Robert

AU - Lafortune, Louise

AU - Roberts, Charlotte

AU - McCleery, Jenny

AU - Pickett, James

AU - Bunn, Frances

AU - Challis, David

AU - Charlesworth, Georgina

AU - Featherstone, Katie

AU - Fox, Chris

AU - Goodman, Claire

AU - Jones, Roy

AU - Lamb, Sallie

AU - Moniz-Cook, Esme

AU - Schneider, Justine

AU - Shepperd, Sasha

AU - Surr, Claire

AU - Thompson-Coon, Jo

AU - Ballard, Clive

AU - Brayne, Carol

AU - Burke, Orlaith

AU - Burns, Alistair

AU - Clare, Linda

AU - Garrard, Peter

AU - Kehoe, Patrick

AU - Passmore, Peter

AU - Holmes, Clive

AU - Maidment, Ian

AU - Murtagh, Fliss

AU - Robinson, Louise

AU - Livingston, Gill

N1 - © Queen’s Printer and Controller of HMSO 2017. This work was produced by Webster et al. under the terms of a commissioning contract issued by the Secretary of State for Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

PY - 2017/5/31

Y1 - 2017/5/31

N2 - BACKGROUND: There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials.OBJECTIVES: To agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI).DATA SOURCES: We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches.REVIEW METHODS: The project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes.RESULTS: We included 149 papers from the 22,918 papers screened, referring to 125 individual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally.LIMITATIONS: Most of the trials included participants with Alzheimer's disease, so recommendations may not apply to other types of dementia. We did not conduct economic analyses. The PPI consultation was limited to members of the Alzheimer's Society Research Network.CONCLUSIONS: Cognitive outcomes and biological markers form the core outcome set for future disease modification trials, measured by the MMSE or ADAS-Cog, and structural MRI in a subset of participants.FUTURE WORK: We envisage that the core set may be superseded in the future, particularly for other types of dementia. There is a need to develop an algorithm to compare scores on the MMSE and ADAS-Cog.STUDY REGISTRATION: The project was registered with Core Outcome Measures in Effectiveness Trials [ www.comet-initiative.org/studies/details/819?result=true (accessed 7 April 2016)]. The systematic review protocol is registered as PROSPERO CRD42015027346.FUNDING: The National Institute for Health Research Health Technology Assessment programme.

AB - BACKGROUND: There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials.OBJECTIVES: To agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI).DATA SOURCES: We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches.REVIEW METHODS: The project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes.RESULTS: We included 149 papers from the 22,918 papers screened, referring to 125 individual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally.LIMITATIONS: Most of the trials included participants with Alzheimer's disease, so recommendations may not apply to other types of dementia. We did not conduct economic analyses. The PPI consultation was limited to members of the Alzheimer's Society Research Network.CONCLUSIONS: Cognitive outcomes and biological markers form the core outcome set for future disease modification trials, measured by the MMSE or ADAS-Cog, and structural MRI in a subset of participants.FUTURE WORK: We envisage that the core set may be superseded in the future, particularly for other types of dementia. There is a need to develop an algorithm to compare scores on the MMSE and ADAS-Cog.STUDY REGISTRATION: The project was registered with Core Outcome Measures in Effectiveness Trials [ www.comet-initiative.org/studies/details/819?result=true (accessed 7 April 2016)]. The systematic review protocol is registered as PROSPERO CRD42015027346.FUNDING: The National Institute for Health Research Health Technology Assessment programme.

KW - Meta-Analysis

UR - https://www.journalslibrary.nihr.ac.uk/hta/hta21260#/abstract

UR - http://www.scopus.com/inward/record.url?scp=85021259340&partnerID=8YFLogxK

U2 - 10.3310/hta21260

DO - 10.3310/hta21260

M3 - Review article

VL - 21

JO - Health Technology Assessment

JF - Health Technology Assessment

SN - 1366-5278

IS - 26

ER -