Design and analysis of a clinical trial using previous trials as historical control.
Bayesian
Historical controls
amyotrophic lateral sclerosis
clinical trials
phase II
Journal
Clinical trials (London, England)
ISSN: 1740-7753
Titre abrégé: Clin Trials
Pays: England
ID NLM: 101197451
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
pubmed:
2
7
2019
medline:
1
9
2020
entrez:
2
7
2019
Statut:
ppublish
Résumé
For single arm trials, a treatment is evaluated by comparing an outcome estimate to historically reported outcome estimates. Such a We fit a Bayesian hierarchical model, providing a sample from the posterior predictive distribution of the outcome estimand of a new trial, which, along with the standard error of the estimate, can be used to calculate the probability that the estimate exceeds a threshold. We then calculate criteria for statistical significance as a function of the standard error of the new trial and calculate sample size as a function of difference to be detected. We apply these methods to clinical trials for amyotrophic lateral sclerosis using data from the placebo groups of 16 trials. We find that when attempting to detect the small to moderate effect sizes usually assumed in amyotrophic lateral sclerosis clinical trials, historically controlled trials would require a greater total number of patients than concurrently controlled trials, and only when an effect size is extraordinarily large is a historically controlled trial a reasonable alternative. We also show that utilizing patient level data for the prognostic covariates can reduce the sample size required for a historically controlled trial. This article quantifies when historically controlled trials would not provide any sample size advantage, despite dispensing with a control group.
Sections du résumé
BACKGROUND/AIMS
For single arm trials, a treatment is evaluated by comparing an outcome estimate to historically reported outcome estimates. Such a
METHODS
We fit a Bayesian hierarchical model, providing a sample from the posterior predictive distribution of the outcome estimand of a new trial, which, along with the standard error of the estimate, can be used to calculate the probability that the estimate exceeds a threshold. We then calculate criteria for statistical significance as a function of the standard error of the new trial and calculate sample size as a function of difference to be detected. We apply these methods to clinical trials for amyotrophic lateral sclerosis using data from the placebo groups of 16 trials.
RESULTS
We find that when attempting to detect the small to moderate effect sizes usually assumed in amyotrophic lateral sclerosis clinical trials, historically controlled trials would require a greater total number of patients than concurrently controlled trials, and only when an effect size is extraordinarily large is a historically controlled trial a reasonable alternative. We also show that utilizing patient level data for the prognostic covariates can reduce the sample size required for a historically controlled trial.
CONCLUSION
This article quantifies when historically controlled trials would not provide any sample size advantage, despite dispensing with a control group.
Identifiants
pubmed: 31256630
doi: 10.1177/1740774519858914
pmc: PMC7008967
mid: NIHMS1530836
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
531-538Subventions
Organisme : NINDS NIH HHS
ID : K23 NS083715
Pays : United States
Références
Amyotroph Lateral Scler. 2009 Oct-Dec;10(5-6):324-31
pubmed: 19922119
Nat Biotechnol. 2015 Jan;33(1):51-7
pubmed: 25362243
BMJ. 2007 Feb 17;334(7589):349-51
pubmed: 17303884
Neurology. 2011 Oct 11;77(15):1432-7
pubmed: 21956723
Stat Med. 1984 Oct-Dec;3(4):315-24
pubmed: 6528131
BMJ. 2010 Mar 19;340:c1066
pubmed: 20304934
Biometrics. 2011 Sep;67(3):1047-56
pubmed: 21361892
Ann Neurol. 2006 Jul;60(1):22-31
pubmed: 16802291
Biometrics. 1997 Sep;53(3):937-47
pubmed: 9290224
Amyotroph Lateral Scler. 2008;9(1):16-23
pubmed: 18273715
N Engl J Med. 1974 Jan 24;290(4):198-203
pubmed: 4587632
Stat Med. 1990 Mar;9(3):215-28
pubmed: 2188324
J Chronic Dis. 1976 Mar;29(3):175-88
pubmed: 770493
N Engl J Med. 1990 Nov 8;323(19):1343-8
pubmed: 2215622
Amyotroph Lateral Scler Frontotemporal Degener. 2014 Dec;15(7-8):610-7
pubmed: 25286015
Neurology. 2014 Nov 4;83(19):1719-25
pubmed: 25298304
Amyotroph Lateral Scler Frontotemporal Degener. 2018 May;19(3-4):250-258
pubmed: 29191052
Biometrics. 1975 Jun;31(2):511-29
pubmed: 1100134
Stat Med. 2017 Mar 15;36(6):899-916
pubmed: 27925274
N Engl J Med. 1972 Jul 13;287(2):75-8
pubmed: 4555591
Biometrics. 1982 Dec;38(4):963-74
pubmed: 7168798