Non-adjustment for Multiple Testing in Multi-arm Trials of Distinct Treatments: Rationale and Justification

Overview

Journal Clin Trials

Publisher Sage Publications

Date 2020 Jul 16

PMID 32666813

Citations 27

Authors

Richard A Parker

Christopher J Weir

Affiliations

Soon will be listed here.

Abstract

There is currently a lack of consensus and uncertainty about whether one should adjust for multiple testing in multi-arm trials of distinct treatments. A detailed rationale is presented to justify non-adjustment in this situation. We argue that non-adjustment should be the default starting position in simple multi-arm trials of distinct treatments.

Citing Articles

Limitation of site-stratified cox regression analysis in survival data: a cautionary tale of the PANAMO phase III randomized, controlled study in critically ill COVID-19 patients.

Sandrock C, Song P Trials. 2024; 25(1):822.

PMID: 39695734 PMC: 11654277. DOI: 10.1186/s13063-024-08679-5.

Conditional and Unconditional Social Transfers, Early-Life Nutrition, and Child Growth: A Randomized Clinical Trial.

Wallenborn J, Sonephet S, Sayasone S, Siengsounthone L, Kounnavong S, Fink G JAMA Pediatr. 2024; 179(2):129-136.

PMID: 39680397 PMC: 11791698. DOI: 10.1001/jamapediatrics.2024.5079.

Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension.

Sanusi A, Leach J, Boggess K, Dugoff L, Sibai B, Lawrence K Obstet Gynecol. 2024; 144(1):126-134.

PMID: 38949541 PMC: 11219006. DOI: 10.1097/AOG.0000000000005613.

Design of a dual randomized trial in a type 2 hybrid effectiveness-implementation study.

Stevens J, Mills S, Millett M, Millett T, Lin F, Leeman J Implement Sci. 2023; 18(1):64.

PMID: 37996884 PMC: 10666326. DOI: 10.1186/s13012-023-01317-9.

Predicting Fear Extinction in Posttraumatic Stress Disorder.

Lewis M, Webb C, Kuhn M, Akman E, Jobson S, Rosso I Brain Sci. 2023; 13(8).

PMID: 37626488 PMC: 10452660. DOI: 10.3390/brainsci13081131.

References

Wason J, Stecher L, Mander A . Correcting for multiple-testing in multi-arm trials: is it necessary and is it done?. Trials. 2014; 15:364. PMC: 4177585. DOI: 10.1186/1745-6215-15-364. View

Howard D, Brown J, Todd S, Gregory W . Recommendations on multiple testing adjustment in multi-arm trials with a shared control group. Stat Methods Med Res. 2016; 27(5):1513-1530. DOI: 10.1177/0962280216664759. View

Li G, Taljaard M, van den Heuvel E, Levine M, Cook D, Wells G . An introduction to multiplicity issues in clinical trials: the what, why, when and how. Int J Epidemiol. 2016; 46(2):746-755. DOI: 10.1093/ije/dyw320. View

Perneger T . What's wrong with Bonferroni adjustments. BMJ. 1998; 316(7139):1236-8. PMC: 1112991. DOI: 10.1136/bmj.316.7139.1236. View

Kelly P, Bell L, Amadi B, Bwakura-Dangarembizi M, VanBuskirk K, Chandwe K . TAME trial: a multi-arm phase II randomised trial of four novel interventions for malnutrition enteropathy in Zambia and Zimbabwe - a study protocol. BMJ Open. 2019; 9(11):e027548. PMC: 6887014. DOI: 10.1136/bmjopen-2018-027548. View

Freidlin B, Korn E, Gray R, Martin A . Multi-arm clinical trials of new agents: some design considerations. Clin Cancer Res. 2008; 14(14):4368-71. DOI: 10.1158/1078-0432.CCR-08-0325. View

Schulz K, Grimes D . Multiplicity in randomised trials I: endpoints and treatments. Lancet. 2005; 365(9470):1591-5. DOI: 10.1016/S0140-6736(05)66461-6. View

Jaki T, Parry A . Why are two mistakes not worse than one? A proposal for controlling the expected number of false claims. Pharm Stat. 2016; 15(4):362-7. PMC: 5021178. DOI: 10.1002/pst.1751. View

Chataway J, De Angelis F, Connick P, Parker R, Plantone D, Doshi A . Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART): a phase 2b, multiarm, double-blind, randomised placebo-controlled trial. Lancet Neurol. 2020; 19(3):214-225. PMC: 7029307. DOI: 10.1016/S1474-4422(19)30485-5. View

10.

Cristea I, Ioannidis J . P values in display items are ubiquitous and almost invariably significant: A survey of top science journals. PLoS One. 2018; 13(5):e0197440. PMC: 5953482. DOI: 10.1371/journal.pone.0197440. View

11.

Proschan M, Waclawiw M . Practical guidelines for multiplicity adjustment in clinical trials. Control Clin Trials. 2001; 21(6):527-39. DOI: 10.1016/s0197-2456(00)00106-9. View

12.

Ioannidis J . Why most published research findings are false. PLoS Med. 2005; 2(8):e124. PMC: 1182327. DOI: 10.1371/journal.pmed.0020124. View

13.

Stallard N, Todd S, Parashar D, Kimani P, Renfro L . On the need to adjust for multiplicity in confirmatory clinical trials with master protocols. Ann Oncol. 2019; 30(4):506-509. PMC: 6503623. DOI: 10.1093/annonc/mdz038. View

14.

Berger V . On the generation and ownership of alpha in medical studies. Control Clin Trials. 2004; 25(6):613-9. DOI: 10.1016/j.cct.2004.07.006. View

15.

Rothman K . No adjustments are needed for multiple comparisons. Epidemiology. 1990; 1(1):43-6. View

16.

Juszczak E, Altman D, Hopewell S, Schulz K . Reporting of Multi-Arm Parallel-Group Randomized Trials: Extension of the CONSORT 2010 Statement. JAMA. 2019; 321(16):1610-1620. DOI: 10.1001/jama.2019.3087. View

17.

Grieve A . How to test hypotheses if you must. Pharm Stat. 2015; 14(2):139-50. DOI: 10.1002/pst.1667. View