Response-adaptive treatment randomization for multiple comparisons of treatments with recurrent event responses

Abstract

Recurrent event responses are frequently encountered during clinical trials of treatments for certain diseases, such as asthma. The recurrence rates of different treatments are often compared by applying the negative binomial model. In addition, a balanced treatment-allocation procedure that assigns the same number of patients to each treatment is often applied. Recently, a response-adaptive treatment-allocation procedure has been developed for trials with recurrent event data, and has been shown to be superior to balanced treatment allocation. However, this response-adaptive treatment allocation procedure is only applicable for the comparison of two treatments. In this paper, we derive response-adaptive treatment-allocation procedures for trials which comprise several treatments. As pairwise comparisons and multiple comparisons with a control are two common multiple-testing scenarios in trials with more than two treatments, corresponding treatment-allocation procedures for these scenarios are also investigated. The redesign of two clinical studies illustrates the clinical benefits that would be obtained from our proposed response-adaptive treatment-allocation procedures.

Keywords

Response-adaptive design allocation rule recurrent events negative binomial model test power

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References

Hanania

Noonan

Corren

, et al. Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies. Thorax 2015; 70: 748–756.

Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon-beta-1a in MS (SPECTRIMS) Study Group. Randomized controlled trial of interferon-beta-1a in secondary progressive MS. Neurology 2001; 56: 1496–1504.

Rogers

Pocock

McMurray

JJV

, et al. Analysing recurrent hospitalizations in heart failure: a review of statistical methodology, with application to CHARM-preserved. Eur J Heart Failure 2014; 16: 33–40.

Cook

Lawless

. The statistical analysis of recurrent events. Springer: New York, 2007.

Chandereng

Wei

Chappell

. Imbalanced randomization in clinical trials. Stat Med 2020; 39: 2185–2196.

United States Food and Drug Administration. Adaptive designs for clinical trials of drugs and biologics: guidance for industry. Silver Spring, MD, USA. 2019. https://www.fda.gov/media/78495/download.

Flournoy

Rosenberger

(eds). Adaptive Designs. Bethesda, MD: Institute of Mathematical Statistics, 1995.

Gao

et al. Adaptive treatment allocation for comparative clinical studies with recurrent events data. Biometrics 2020; 76: 183–196.

Zhang

. Asymptotic properties of doubly adaptive biased coin designs for multitreatment clinical trials. Ann Stat 2004; 32: 268–301.

10.

Rosenberger

. The theory of response-adaptive randomization in clinical trials. New Jersey: Wiley, 2006.

11.

Corren

Parnes

Wang

et al. Tezepelumab in adults with uncontrolled asthma. New Engl J Med 2017; 377: 936–946.

12.

Weitz

Lensing

AWA

Prins

et al. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. New Engl J Med 2017; 376: 1211–1222.

13.

Lawless

. Negative binomial and mixed poisson regression. Can J Stat 1987; 15: 209–225.

14.

Dunnett

. Algorithm AS251: Multivariate normal probability integrals with product correlation structure. Appl Statist 1989; 38: 564–579.

15.

Lin

Cheung

Poon

, et al. Pairwise comparisons with ordered categorical data. Stat Med 2013; 32: 3192–3205.

16.

Thompson

. On the likelihood that one unknown probability exceeds another in view of the evidence of two samples. Biometrika 1933; 25: 285–294.

17.

Rosenberger

. Optimality, variability, power. J Amer Statist Assoc 2003; 98: 671–678.

18.

Tymofyeyev

Rosenberger

. Implementing optimal allocation in sequential binary response experiments. J Amer Statist Assoc 2007; 102: 224–234.

19.

Abraham

Stevenson

Bourge

, et al., CHAMPION Trial Study Group. Sustained efficacy of pulmonary artery pressure to guide adjustment of chronic heart failure therapy: complete follow-up results from the CHAMPION randomised trial. Lancet 2016; 387: 453–461.

20.

Horn

Dunnett

. Power and sample size comparisons of stepwise FWE and FDR controlling test procedures in the normal many-one case. In Benjamini Y, Bretz F and Sarkar S(eds) Lecture Notes - Monograph Series, 47, Institute of Mathematical Statistics, 2004, 48–64.

21.

Gao

, et al. Response-adaptive treatment allocation for non-inferiority trials with heterogeneous variances. Computat Stat Data Analys 2018; 124: 168–179.

22.

Cheung

. Adaptive designs for non-inferiority trials with multiple experimental treatments. Stat Methods Med Res 2018; 27: 3255–3270.

23.

Dunnett

. A multiple comparison procedure for comparing several treatments with a control. J Amer Statist Assoc 1955; 50: 1096–1121.

24.

Zhang

Rosenberger

. Response-adaptive randomization for clinical trials with continuous outcomes. Biometrics 2006; 62: 562–569.

25.

Rosenberger

Zhang

L-X

. Asymptotically best response-adaptive randomization procedures. J Stat Plan Inference 2006; 136: 1911–1922.

26.

Rondeau

Commenges

Joly

. Maximum penalized likelihood estimation in a gamma-frailty model. Lifetime Data Anal 2003; 9: 139–153.

27.

Jennison

Turnbull

. Group sequential methods with applications to clinical trials. Boca Raton: Chapman and Hall., 2000.

28.

Zhu

. Sequential monitoring of response-adaptive randomized clinical trials. Ann Stat 2010; 38: 2218–2241.

29.

Magirr

Jaki

Whitehead

. A generalized Dunnett test for multi-arm multi-stage clinical studies with treatment selection. Biometrika 2012; 99: 494–501.