A prospective cohort and extended comprehensive-cohort design provided insights about the generalizability of a pragmatic trial: the ProtecT prostate cancer trial

Jenny L. Donovan, Grace J. Young, Eleanor I. Walsh, Chris Metcalfe, J. Athene Lane, Richard M. Martin, Marta K. Tazewell, Michael Davis, Tim J. Peters, Emma L. Turner, Nicola Mills, Hanan Khazragui, Tarnjit K. Khera, David E. Neal, Freddie C. Hamdy, ProtecT Study Group, Prasad Bollina, James Catto, Andrew Doble, Alan Doherty & 13 others David Gillatt, Vincent Gnanapragasam, Peter Holding, Owen Hughes, Roger Kockelbergh, Howard Kynaston, Malcolm Mason, Jon Oxley, Alan Paul, Edgar Paez, Derek J. Rosario, Edward Rowe, John Staffurth

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objectives: Randomized controlled trials (RCTs) deliver robust internally valid evidence but generalizability is often neglected. Design features built into the Prostate testing for cancer and Treatment (ProtecT) RCT of treatments for localized prostate cancer (PCa) provided insights into its generalizability. Study Design and Setting: Population-based cluster randomization created a prospective study of prostate-specific antigen (PSA) testing and a comprehensive-cohort study including groups choosing treatment or excluded from the RCT, as well as those randomized. Baseline information assessed selection and response during RCT conduct. Results: The prospective study (82,430 PSA-tested men) represented healthy men likely to respond to a screening invitation. The extended comprehensive cohort comprised 1,643 randomized, 997 choosing treatment, and 557 excluded with advanced cancer/comorbidities. Men choosing treatment were very similar to randomized men except for having more professional/managerial occupations. Excluded men were similar to the randomized socio-demographically but different clinically, representing less healthy men with more advanced PCa. Conclusion: The design features of the ProtecT RCT provided data to assess the representativeness of the prospective cohort and generalizability of the findings of the RCT. Greater attention to collecting data at the design stage of pragmatic trials would better support later judgments by clinicians/policy-makers about the generalizability of RCT findings in clinical practice.

LanguageEnglish
Pages35-46
Number of pages12
JournalJournal of Clinical Epidemiology
Volume96
DOIs
Publication statusPublished - 1 Apr 2018
Externally publishedYes

Fingerprint

Pragmatic Clinical Trials
Prostatic Neoplasms
Randomized Controlled Trials
Prostate-Specific Antigen
Therapeutics
Prospective Studies
Random Allocation
Administrative Personnel
Occupations
Comorbidity
Cohort Studies

Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Clinical trial
  • Comprehensive cohort
  • External validity
  • Generalizability
  • Prostate cancer
  • Randomized

Cite this

Donovan, Jenny L. ; Young, Grace J. ; Walsh, Eleanor I. ; Metcalfe, Chris ; Lane, J. Athene ; Martin, Richard M. ; Tazewell, Marta K. ; Davis, Michael ; Peters, Tim J. ; Turner, Emma L. ; Mills, Nicola ; Khazragui, Hanan ; Khera, Tarnjit K. ; Neal, David E. ; Hamdy, Freddie C. ; ProtecT Study Group. / A prospective cohort and extended comprehensive-cohort design provided insights about the generalizability of a pragmatic trial : the ProtecT prostate cancer trial. In: Journal of Clinical Epidemiology. 2018 ; Vol. 96. pp. 35-46.
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title = "A prospective cohort and extended comprehensive-cohort design provided insights about the generalizability of a pragmatic trial: the ProtecT prostate cancer trial",
abstract = "Objectives: Randomized controlled trials (RCTs) deliver robust internally valid evidence but generalizability is often neglected. Design features built into the Prostate testing for cancer and Treatment (ProtecT) RCT of treatments for localized prostate cancer (PCa) provided insights into its generalizability. Study Design and Setting: Population-based cluster randomization created a prospective study of prostate-specific antigen (PSA) testing and a comprehensive-cohort study including groups choosing treatment or excluded from the RCT, as well as those randomized. Baseline information assessed selection and response during RCT conduct. Results: The prospective study (82,430 PSA-tested men) represented healthy men likely to respond to a screening invitation. The extended comprehensive cohort comprised 1,643 randomized, 997 choosing treatment, and 557 excluded with advanced cancer/comorbidities. Men choosing treatment were very similar to randomized men except for having more professional/managerial occupations. Excluded men were similar to the randomized socio-demographically but different clinically, representing less healthy men with more advanced PCa. Conclusion: The design features of the ProtecT RCT provided data to assess the representativeness of the prospective cohort and generalizability of the findings of the RCT. Greater attention to collecting data at the design stage of pragmatic trials would better support later judgments by clinicians/policy-makers about the generalizability of RCT findings in clinical practice.",
keywords = "Clinical trial, Comprehensive cohort, External validity, Generalizability, Prostate cancer, Randomized",
author = "Donovan, {Jenny L.} and Young, {Grace J.} and Walsh, {Eleanor I.} and Chris Metcalfe and Lane, {J. Athene} and Martin, {Richard M.} and Tazewell, {Marta K.} and Michael Davis and Peters, {Tim J.} and Turner, {Emma L.} and Nicola Mills and Hanan Khazragui and Khera, {Tarnjit K.} and Neal, {David E.} and Hamdy, {Freddie C.} and {ProtecT Study Group} and Prasad Bollina and James Catto and Andrew Doble and Alan Doherty and David Gillatt and Vincent Gnanapragasam and Peter Holding and Owen Hughes and Roger Kockelbergh and Howard Kynaston and Malcolm Mason and Jon Oxley and Alan Paul and Edgar Paez and Rosario, {Derek J.} and Edward Rowe and John Staffurth",
note = "Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",
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Donovan, JL, Young, GJ, Walsh, EI, Metcalfe, C, Lane, JA, Martin, RM, Tazewell, MK, Davis, M, Peters, TJ, Turner, EL, Mills, N, Khazragui, H, Khera, TK, Neal, DE, Hamdy, FC & ProtecT Study Group 2018, 'A prospective cohort and extended comprehensive-cohort design provided insights about the generalizability of a pragmatic trial: the ProtecT prostate cancer trial', Journal of Clinical Epidemiology, vol. 96, pp. 35-46. https://doi.org/10.1016/j.jclinepi.2017.12.019

A prospective cohort and extended comprehensive-cohort design provided insights about the generalizability of a pragmatic trial : the ProtecT prostate cancer trial. / Donovan, Jenny L.; Young, Grace J.; Walsh, Eleanor I.; Metcalfe, Chris; Lane, J. Athene; Martin, Richard M.; Tazewell, Marta K.; Davis, Michael; Peters, Tim J.; Turner, Emma L.; Mills, Nicola; Khazragui, Hanan; Khera, Tarnjit K.; Neal, David E.; Hamdy, Freddie C.; ProtecT Study Group.

In: Journal of Clinical Epidemiology, Vol. 96, 01.04.2018, p. 35-46.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - A prospective cohort and extended comprehensive-cohort design provided insights about the generalizability of a pragmatic trial

T2 - Journal of Clinical Epidemiology

AU - Donovan, Jenny L.

AU - Young, Grace J.

AU - Walsh, Eleanor I.

AU - Metcalfe, Chris

AU - Lane, J. Athene

AU - Martin, Richard M.

AU - Tazewell, Marta K.

AU - Davis, Michael

AU - Peters, Tim J.

AU - Turner, Emma L.

AU - Mills, Nicola

AU - Khazragui, Hanan

AU - Khera, Tarnjit K.

AU - Neal, David E.

AU - Hamdy, Freddie C.

AU - ProtecT Study Group

AU - Bollina, Prasad

AU - Catto, James

AU - Doble, Andrew

AU - Doherty, Alan

AU - Gillatt, David

AU - Gnanapragasam, Vincent

AU - Holding, Peter

AU - Hughes, Owen

AU - Kockelbergh, Roger

AU - Kynaston, Howard

AU - Mason, Malcolm

AU - Oxley, Jon

AU - Paul, Alan

AU - Paez, Edgar

AU - Rosario, Derek J.

AU - Rowe, Edward

AU - Staffurth, John

N1 - Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Objectives: Randomized controlled trials (RCTs) deliver robust internally valid evidence but generalizability is often neglected. Design features built into the Prostate testing for cancer and Treatment (ProtecT) RCT of treatments for localized prostate cancer (PCa) provided insights into its generalizability. Study Design and Setting: Population-based cluster randomization created a prospective study of prostate-specific antigen (PSA) testing and a comprehensive-cohort study including groups choosing treatment or excluded from the RCT, as well as those randomized. Baseline information assessed selection and response during RCT conduct. Results: The prospective study (82,430 PSA-tested men) represented healthy men likely to respond to a screening invitation. The extended comprehensive cohort comprised 1,643 randomized, 997 choosing treatment, and 557 excluded with advanced cancer/comorbidities. Men choosing treatment were very similar to randomized men except for having more professional/managerial occupations. Excluded men were similar to the randomized socio-demographically but different clinically, representing less healthy men with more advanced PCa. Conclusion: The design features of the ProtecT RCT provided data to assess the representativeness of the prospective cohort and generalizability of the findings of the RCT. Greater attention to collecting data at the design stage of pragmatic trials would better support later judgments by clinicians/policy-makers about the generalizability of RCT findings in clinical practice.

AB - Objectives: Randomized controlled trials (RCTs) deliver robust internally valid evidence but generalizability is often neglected. Design features built into the Prostate testing for cancer and Treatment (ProtecT) RCT of treatments for localized prostate cancer (PCa) provided insights into its generalizability. Study Design and Setting: Population-based cluster randomization created a prospective study of prostate-specific antigen (PSA) testing and a comprehensive-cohort study including groups choosing treatment or excluded from the RCT, as well as those randomized. Baseline information assessed selection and response during RCT conduct. Results: The prospective study (82,430 PSA-tested men) represented healthy men likely to respond to a screening invitation. The extended comprehensive cohort comprised 1,643 randomized, 997 choosing treatment, and 557 excluded with advanced cancer/comorbidities. Men choosing treatment were very similar to randomized men except for having more professional/managerial occupations. Excluded men were similar to the randomized socio-demographically but different clinically, representing less healthy men with more advanced PCa. Conclusion: The design features of the ProtecT RCT provided data to assess the representativeness of the prospective cohort and generalizability of the findings of the RCT. Greater attention to collecting data at the design stage of pragmatic trials would better support later judgments by clinicians/policy-makers about the generalizability of RCT findings in clinical practice.

KW - Clinical trial

KW - Comprehensive cohort

KW - External validity

KW - Generalizability

KW - Prostate cancer

KW - Randomized

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