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Abstract

In phase II clinical trials on cancer, it is of great interest to establish the efficacy and safety of a new treatment simultaneously. Existing hypotheses may not achieve this goal effectively. We introduce two new sets of hypotheses that consider the association between the two factors, then construct the optimal two-stage designs for the hypotheses. The proposed designs strictly control the maximum type I error rate at the given nominal level $α$ , maintain the minimum power at least the given $1 - β$ , and have the smallest expected total sample size under the null hypothesis. Furthermore, an algorithm is provided to compute these designs. R-codes are given in the Supplemental Material.

Keywords

Dimensionality reduction exact test expected sample size multinomial distribution phase II clinical trial

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References

Simon

. Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989; 10: 1–10.

Banerjee

Tsiatis

. Adaptive two-stage designs in phase II clinical trials. Stat Med 2006; 25: 3382–3395.

Englert

Kieser

. Optimal adaptive two-stage designs for phase II cancer clinical trials. Biometrical J 2013; 55: 955–968.

Shan

Wilding

Hutson

, et al. Optimal adaptive two-stage designs for early phase II clinical trials. Stat Med 2016; 35: 1257–1266.

Yin

Wang

Zhang

. Exact tests using binary data in adaptive two or multi-stage designs. Stat Methods Med Res 2020; 29: 2269–2281.

Therasse

Arbuck

Eisenhauer

et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000; 92: 205–216.

Grayling

Dimairo

Mander

, et al. A review of perspectives on the use of randomization in phase II oncology trials. J Natl Cancer Inst 2019; 111: 1255–1262.

Jin

Lamborn

. A design of phase II cancer trials using total and complete response endpoints. Stat Med 2005; 24: 3155–3170.

Ivanova

Monaco

Stinchcombe

. Efficient designs for phase II oncology trials with ordinal outcome. Stat Interface 2012; 5: 463–469.

10.

Conaway

Petroni

. Bivariate sequential designs for phase II trials. Biometrics 1995; 51: 656–664.

11.

Conway

Petroni

. Designs for phase II trials allowing for a trade-off between response and toxicity. Biometrics 1996; 52: 1375–1386.

12.

Bryant

Day

. Incorporating toxicity considerations into the design of two-stage phase II clinical trials. Biometrics 1995; 51: 1372–1383.

13.

Jin

. Alternative designs of phase II trials considering response and toxicity. Contemp Clin Trials 2007; 28: 525–531.

14.

Tournoux

Rycke

Médioni

, et al. Methods of joint evaluation of efficacy and toxicity in phase II clinical trials. Contemp Clin Trials 2007; 28: 514–524.

15.

Chen

Chi

. Curtailed two-stage designs with two dependent binary endpoints. Pharm Stat 2012; 11: 57–62.

16.

Jin

Chen

. Two-stage phase II trials with early stopping for effectiveness and safety as well as ineffectiveness and harm. Comm Stat Theory Meth 2018; 47: 5626–5638.

17.

Wei

Esserman

Kane

, et al. Unified exact design with early stopping rules for single arm clinical trials with multiple endpoints. Stat Meth Med Res 2021; 30: 1575–1588.

18.

Yin

Wang

Zhang

. On construction of single-arm two-stage designs with consideration of both response and toxicity. Biometrical J 2019; 61: 1462–1476.

19.

Kepnerb

Bundy

. Exact power calculations for detecting hypotheses involving two correlated binary outcomes. Stat Probabil Lett 2007; 77: 288–294.

20.

Biswas

Hwang

. A new bivariate binomial distribution. Stat Probabil Lett 2002; 60: 231–240.

21.

Ray

Rai

. An evaluation of a simon 2-stage phase II clinical trial design incorporating toxicity monitoring. Contemp Clin Trials 2011; 32: 428–436.

22.

Sill

Rubinstein

Litwin

, et al. A method for utilizing co-primary efficacy outcome measures to screen regimens for activity in two-stage phase II clinical trials. Clin Trials 2012; 9: 385–395.

23.

Cohen

. A coefficient of agreement for nominal scales. Educ Psychol Meas 1960; 20: 37–46.

24.

Yin

Wang

Zhang

. Optimal two-stage designs with consideration of response and safety and their correlation. J Beijing Univ Technol 2019; 45: 1269–1276.

25.

Faes

Geys

Molenberghs

et al. A flexible method to measure synchrony in neuronal firing. J Am Stat Assoc 2008; 103: 149–161.

26.

Lui

. Exact confidence limits on some new measures of concordance and discordance in binary outcomes. Ther Innov Regul Sci 2020; 54: 437–443.

Supplementary Material

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Optimal single-arm two-stage designs with consideration of dependency on efficacy and safety

Abstract

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