A scoping review of statistical methods in studies of biomarker-related treatment heterogeneity for breast cancer.
Biomarker
Breast cancer
Interaction
Predictive
Review
Statistical methods
Treatment heterogeneity
Journal
BMC medical research methodology
ISSN: 1471-2288
Titre abrégé: BMC Med Res Methodol
Pays: England
ID NLM: 100968545
Informations de publication
Date de publication:
29 06 2023
29 06 2023
Historique:
received:
08
11
2022
accepted:
19
06
2023
medline:
3
7
2023
pubmed:
30
6
2023
entrez:
29
6
2023
Statut:
epublish
Résumé
Many scientific papers are published each year and substantial resources are spent to develop biomarker-based tests for precision oncology. However, only a handful of tests is currently used in daily clinical practice, since development is challenging. In this situation, the application of adequate statistical methods is essential, but little is known about the scope of methods used. A PubMed search identified clinical studies among women with breast cancer comparing at least two different treatment groups, one of which chemotherapy or endocrine treatment, by levels of at least one biomarker. Studies presenting original data published in 2019 in one of 15 selected journals were eligible for this review. Clinical and statistical characteristics were extracted by three reviewers and a selection of characteristics for each study was reported. Of 164 studies identified by the query, 31 were eligible. Over 70 different biomarkers were evaluated. Twenty-two studies (71%) evaluated multiplicative interaction between treatment and biomarker. Twenty-eight studies (90%) evaluated either the treatment effect in biomarker subgroups or the biomarker effect in treatment subgroups. Eight studies (26%) reported results for one predictive biomarker analysis, while the majority performed multiple evaluations, either for several biomarkers, outcomes and/or subpopulations. Twenty-one studies (68%) claimed to have found significant differences in treatment effects by biomarker level. Fourteen studies (45%) mentioned that the study was not designed to evaluate treatment effect heterogeneity. Most studies evaluated treatment heterogeneity via separate analyses of biomarker-specific treatment effects and/or multiplicative interaction analysis. There is a need for the application of more efficient statistical methods to evaluate treatment heterogeneity in clinical studies.
Sections du résumé
BACKGROUND
Many scientific papers are published each year and substantial resources are spent to develop biomarker-based tests for precision oncology. However, only a handful of tests is currently used in daily clinical practice, since development is challenging. In this situation, the application of adequate statistical methods is essential, but little is known about the scope of methods used.
METHODS
A PubMed search identified clinical studies among women with breast cancer comparing at least two different treatment groups, one of which chemotherapy or endocrine treatment, by levels of at least one biomarker. Studies presenting original data published in 2019 in one of 15 selected journals were eligible for this review. Clinical and statistical characteristics were extracted by three reviewers and a selection of characteristics for each study was reported.
RESULTS
Of 164 studies identified by the query, 31 were eligible. Over 70 different biomarkers were evaluated. Twenty-two studies (71%) evaluated multiplicative interaction between treatment and biomarker. Twenty-eight studies (90%) evaluated either the treatment effect in biomarker subgroups or the biomarker effect in treatment subgroups. Eight studies (26%) reported results for one predictive biomarker analysis, while the majority performed multiple evaluations, either for several biomarkers, outcomes and/or subpopulations. Twenty-one studies (68%) claimed to have found significant differences in treatment effects by biomarker level. Fourteen studies (45%) mentioned that the study was not designed to evaluate treatment effect heterogeneity.
CONCLUSIONS
Most studies evaluated treatment heterogeneity via separate analyses of biomarker-specific treatment effects and/or multiplicative interaction analysis. There is a need for the application of more efficient statistical methods to evaluate treatment heterogeneity in clinical studies.
Identifiants
pubmed: 37386356
doi: 10.1186/s12874-023-01982-w
pii: 10.1186/s12874-023-01982-w
pmc: PMC10308726
doi:
Substances chimiques
Biomarkers
0
Types de publication
Review
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
154Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
Références
Breast Cancer Res Treat. 2019 May;175(1):149-163
pubmed: 30680659
Health Technol Assess. 2001;5(33):1-56
pubmed: 11701102
Ann Oncol. 2019 Nov 1;30(11):1776-1783
pubmed: 31504126
BMC Med. 2012 May 29;10:51
pubmed: 22642691
J Natl Cancer Inst. 2019 Jan 1;111(1):86-94
pubmed: 29878225
Breast Cancer Res. 2019 Mar 11;21(1):39
pubmed: 30867034
J Clin Oncol. 2019 Apr 1;37(10):799-808
pubmed: 30785826
Clin Cancer Res. 2019 Jul 15;25(14):4422-4430
pubmed: 30808774
Ann Oncol. 2019 Jun 1;30(6):945-952
pubmed: 30860573
Breast Cancer Res. 2019 Feb 22;21(1):30
pubmed: 30795773
Sci Transl Med. 2013 Mar 27;5(178):178sr3
pubmed: 23536014
Gen Psychiatr. 2019 Aug 8;32(4):e100069
pubmed: 31552383
Int J Cancer. 2020 Jan 1;146(1):262-271
pubmed: 31162838
J Clin Oncol. 2019 Dec 10;37(35):3425-3435
pubmed: 31622131
Ann Oncol. 2019 Mar 1;30(3):418-423
pubmed: 30657852
Int J Cancer. 2019 May 15;144(10):2578-2586
pubmed: 30411790
Stat Med. 2022 Jul 20;41(16):3199-3210
pubmed: 35491401
NPJ Breast Cancer. 2021 Dec 1;7(1):150
pubmed: 34853355
PLoS Med. 2005 Aug;2(8):e124
pubmed: 16060722
Am J Epidemiol. 1990 Mar;131(3):552-66
pubmed: 2301364
Breast Cancer Res Treat. 2019 Feb;174(1):79-91
pubmed: 30470977
J Clin Oncol. 2019 Mar 10;37(8):624-635
pubmed: 30702971
Breast Cancer Res Treat. 2019 Dec;178(3):647-656
pubmed: 31451979
Breast Cancer Res Treat. 2019 Aug;176(3):569-577
pubmed: 31069590
J Clin Oncol. 2005 Mar 20;23(9):2020-7
pubmed: 15774793
Int J Cancer. 2019 Aug 1;145(3):857-868
pubmed: 30694523
J Clin Epidemiol. 2004 Mar;57(3):229-36
pubmed: 15066682
Am J Epidemiol. 1999 Apr 15;149(8):689-92
pubmed: 10206617
Breast Cancer Res Treat. 2019 Jan;173(1):93-102
pubmed: 30306428
Nat Rev Clin Oncol. 2011 Aug 23;8(10):587-96
pubmed: 21862978
J Natl Cancer Inst. 2013 Nov 20;105(22):1677-83
pubmed: 24136891
Ann Intern Med. 2020 Jan 7;172(1):W1-W25
pubmed: 31711094
J Natl Cancer Inst. 2009 Nov 4;101(21):1446-52
pubmed: 19815849
J Clin Oncol. 2019 May 10;37(14):1169-1178
pubmed: 30807234
Biometrics. 2007 Dec;63(4):1181-8
pubmed: 17489968
Int J Cancer. 2020 Apr 15;146(8):2348-2359
pubmed: 31490549
Int J Cancer. 2020 Apr 1;146(7):1917-1929
pubmed: 31330065
Breast Cancer Res Treat. 2019 Jul;176(2):377-386
pubmed: 31041683
Breast Cancer Res Treat. 2019 Apr;174(2):433-442
pubmed: 30536182
Ann Intern Med. 2018 Oct 2;169(7):467-473
pubmed: 30178033
Nature. 2013 Oct 17;502(7471):317-20
pubmed: 24132288
Clin Cancer Res. 2019 Jul 15;25(14):4351-4362
pubmed: 31036541
Ann Intern Med. 2020 Jan 7;172(1):35-45
pubmed: 31711134
Breast Cancer Res Treat. 2019 Nov;178(2):317-325
pubmed: 31432366
Breast Cancer Res Treat. 2019 May;175(1):129-139
pubmed: 30673970
J Clin Oncol. 2013 Sep 1;31(25):3158-61
pubmed: 23569306
Int J Biostat. 2014;10(1):99-121
pubmed: 24695044
N Engl J Med. 2017 Aug 10;377(6):523-533
pubmed: 28578601
Breast Cancer Res Treat. 2019 Feb;174(1):121-127
pubmed: 30478785
Ann Oncol. 2019 Aug 1;30(8):1279-1288
pubmed: 31095287
Breast Cancer Res Treat. 2019 Nov;178(2):389-399
pubmed: 31428908
Ann Oncol. 2019 Aug 1;30(8):1194-1220
pubmed: 31161190
Stat Med. 2000 Oct 15;19(19):2595-609
pubmed: 10986536
Breast Cancer Res. 2019 Sep 18;21(1):108
pubmed: 31533777
Lancet. 2011 Aug 27;378(9793):771-84
pubmed: 21802721
N Engl J Med. 2021 Jun 24;384(25):2394-2405
pubmed: 34081848
J Natl Cancer Inst. 2019 Jan 1;111(1):69-77
pubmed: 29788230
J Clin Oncol. 2020 Apr 1;38(10):1059-1069
pubmed: 32031889
J Thorac Oncol. 2021 Apr;16(4):537-545
pubmed: 33545385
Clin Cancer Res. 2019 Jul 1;25(13):3986-3995
pubmed: 30979740