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, 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, 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, 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

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.

Trial registration: ClinicalTrials.gov NCT02044172.

Keywords: Clinical trial; Comprehensive cohort; External validity; Generalizability; Prostate cancer; Randomized.

Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Fig. 1
Fig. 1
CAP trial framework and comparison points in the ProtecT prospective study of PSA testing and diagnosis. PSA, prostate-specific antigen; CAP, Cluster randomized trial of PSA testing for prostate cancer.
Fig. 2
Fig. 2
ProtecT RCT extended comprehensive-cohort study and comparison points. ProtecT, prostate testing for cancer and treatment; RCT, randomized controlled trial.

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Source: PubMed

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