Cargando…
A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results
Randomized controlled trials (RCTs) are conducted under idealized and rigorously controlled conditions that may compromise their external validity. A literature review was conducted of published English language articles that reported the findings of studies assessing external validity by a comparis...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632358/ https://www.ncbi.nlm.nih.gov/pubmed/26530985 http://dx.doi.org/10.1186/s13063-015-1023-4 |
_version_ | 1782399011900096512 |
---|---|
author | Kennedy-Martin, Tessa Curtis, Sarah Faries, Douglas Robinson, Susan Johnston, Joseph |
author_facet | Kennedy-Martin, Tessa Curtis, Sarah Faries, Douglas Robinson, Susan Johnston, Joseph |
author_sort | Kennedy-Martin, Tessa |
collection | PubMed |
description | Randomized controlled trials (RCTs) are conducted under idealized and rigorously controlled conditions that may compromise their external validity. A literature review was conducted of published English language articles that reported the findings of studies assessing external validity by a comparison of the patient sample included in RCTs reporting on pharmaceutical interventions with patients from everyday clinical practice. The review focused on publications in the fields of cardiology, mental health, and oncology. A range of databases were interrogated (MEDLINE; EMBASE; Science Citation Index; Cochrane Methodology Register). Double-abstract review and data extraction were performed as per protocol specifications. Out of 5,456 de-duplicated abstracts, 52 studies met the inclusion criteria (cardiology, n = 20; mental health, n = 17; oncology, n = 15). Studies either performed an analysis of the baseline characteristics (demographic, socioeconomic, and clinical parameters) of RCT-enrolled patients compared with a real-world population, or assessed the proportion of real-world patients who would have been eligible for RCT inclusion following the application of RCT inclusion/exclusion criteria. Many of the included studies concluded that RCT samples are highly selected and have a lower risk profile than real-world populations, with the frequent exclusion of elderly patients and patients with co-morbidities. Calculation of ineligibility rates in individual studies showed that a high proportion of the general disease population was often excluded from trials. The majority of studies (n = 37 [71.2 %]) explicitly concluded that RCT samples were not broadly representative of real-world patients and that this may limit the external validity of the RCT. Authors made a number of recommendations to improve external validity. Findings from this review indicate that there is a need to improve the external validity of RCTs such that physicians treating patients in real-world settings have the appropriate evidence on which to base their clinical decisions. This goal could be achieved by trial design modification to include a more representative patient sample and by supplementing RCT evidence with data generated from observational studies. In general, a thoughtful approach to clinical evidence generation is required in which the trade-offs between internal and external validity are considered in a holistic and balanced manner. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-015-1023-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4632358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46323582015-11-05 A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results Kennedy-Martin, Tessa Curtis, Sarah Faries, Douglas Robinson, Susan Johnston, Joseph Trials Review Randomized controlled trials (RCTs) are conducted under idealized and rigorously controlled conditions that may compromise their external validity. A literature review was conducted of published English language articles that reported the findings of studies assessing external validity by a comparison of the patient sample included in RCTs reporting on pharmaceutical interventions with patients from everyday clinical practice. The review focused on publications in the fields of cardiology, mental health, and oncology. A range of databases were interrogated (MEDLINE; EMBASE; Science Citation Index; Cochrane Methodology Register). Double-abstract review and data extraction were performed as per protocol specifications. Out of 5,456 de-duplicated abstracts, 52 studies met the inclusion criteria (cardiology, n = 20; mental health, n = 17; oncology, n = 15). Studies either performed an analysis of the baseline characteristics (demographic, socioeconomic, and clinical parameters) of RCT-enrolled patients compared with a real-world population, or assessed the proportion of real-world patients who would have been eligible for RCT inclusion following the application of RCT inclusion/exclusion criteria. Many of the included studies concluded that RCT samples are highly selected and have a lower risk profile than real-world populations, with the frequent exclusion of elderly patients and patients with co-morbidities. Calculation of ineligibility rates in individual studies showed that a high proportion of the general disease population was often excluded from trials. The majority of studies (n = 37 [71.2 %]) explicitly concluded that RCT samples were not broadly representative of real-world patients and that this may limit the external validity of the RCT. Authors made a number of recommendations to improve external validity. Findings from this review indicate that there is a need to improve the external validity of RCTs such that physicians treating patients in real-world settings have the appropriate evidence on which to base their clinical decisions. This goal could be achieved by trial design modification to include a more representative patient sample and by supplementing RCT evidence with data generated from observational studies. In general, a thoughtful approach to clinical evidence generation is required in which the trade-offs between internal and external validity are considered in a holistic and balanced manner. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-015-1023-4) contains supplementary material, which is available to authorized users. BioMed Central 2015-11-03 /pmc/articles/PMC4632358/ /pubmed/26530985 http://dx.doi.org/10.1186/s13063-015-1023-4 Text en © Kennedy-Martin et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Review Kennedy-Martin, Tessa Curtis, Sarah Faries, Douglas Robinson, Susan Johnston, Joseph A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results |
title | A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results |
title_full | A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results |
title_fullStr | A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results |
title_full_unstemmed | A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results |
title_short | A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results |
title_sort | literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632358/ https://www.ncbi.nlm.nih.gov/pubmed/26530985 http://dx.doi.org/10.1186/s13063-015-1023-4 |
work_keys_str_mv | AT kennedymartintessa aliteraturereviewontherepresentativenessofrandomizedcontrolledtrialsamplesandimplicationsfortheexternalvalidityoftrialresults AT curtissarah aliteraturereviewontherepresentativenessofrandomizedcontrolledtrialsamplesandimplicationsfortheexternalvalidityoftrialresults AT fariesdouglas aliteraturereviewontherepresentativenessofrandomizedcontrolledtrialsamplesandimplicationsfortheexternalvalidityoftrialresults AT robinsonsusan aliteraturereviewontherepresentativenessofrandomizedcontrolledtrialsamplesandimplicationsfortheexternalvalidityoftrialresults AT johnstonjoseph aliteraturereviewontherepresentativenessofrandomizedcontrolledtrialsamplesandimplicationsfortheexternalvalidityoftrialresults AT kennedymartintessa literaturereviewontherepresentativenessofrandomizedcontrolledtrialsamplesandimplicationsfortheexternalvalidityoftrialresults AT curtissarah literaturereviewontherepresentativenessofrandomizedcontrolledtrialsamplesandimplicationsfortheexternalvalidityoftrialresults AT fariesdouglas literaturereviewontherepresentativenessofrandomizedcontrolledtrialsamplesandimplicationsfortheexternalvalidityoftrialresults AT robinsonsusan literaturereviewontherepresentativenessofrandomizedcontrolledtrialsamplesandimplicationsfortheexternalvalidityoftrialresults AT johnstonjoseph literaturereviewontherepresentativenessofrandomizedcontrolledtrialsamplesandimplicationsfortheexternalvalidityoftrialresults |