Abstract
During clinical development of new medicinal products, phase II is one of the most important stages. The first phase II trial is typically a Proof of Concept (PoC) study with limited sample size. To reduce the bias, one needs to discount the phase II estimate of the treatment effect. Under some mild conditions, the estimated assurances are increasing functions of the per group number of patients and the scaled observed treatment effect of the phase II trial for the three cases (no, additive, and multiplicative bias adjustment); and for multiplicative bias adjustment, the estimated assurance is an increasing function of the retention factor. The theoretical assurances are increasing functions of the per group number of patients of the phase II trial and the scaled true treatment effect of the phase III trial. The numerical simulations illustrate the above theoretical results. After obtaining the results of the phase II trial, it is still difficult for the project team (and the company) to make the Go/No Go decision. Finally, in addition to the investment and the statistical points of view, the Go/No Go decision is also affected by many other factors.
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References
Chuang-Stein C, Kirby S, French J, Kowalski K, Marshall S, Smith MK, Bycott P, Beltangady M (2011) A quantitative approach for making go/no go decisions in drug development. Drug Inf J 45:187–202
Emerson JD, Tritchler D (1987) The three-decision problem in medical decision making. Stat Med 6:101–112
Fleming TR (1982) One-sample multiple testing procedures for phase II clinical trials. Biometrics 38:143–151
Hong S, Wang Y (2007) A three-outcome design for randomized comparative phase II clinical trials. Stat Med 26:3525–3534
Kirby S, Burke J, Chuang-Stein C, Sin C (2012) Discounting phase 2 results when planning phase 3 clinical trials. Pharm Stat 11:373–385
O’Hagan A, Stevens JW, Campbell MJ (2005) Assurance in clinical trial design. Pharm Stat 4:187–201
Sargent DJ, Chan V, Goldberg RM (2001) A three-outcome design for phase II clinical trials. Control Clin Trials 22:117–125
Shuster J (2002) Optimal two-stage designs for single arm phase II cancer trials. J Biopharm Stat 12:39–51
Storer BE (1992) A class of phase II designs with three possible outcomes. Biometrics 48:55–60
Thall PF, Simon RM, Estey EH (1995) Bayesian sequential monitoring designs for single-arm clinical trials with multiple outcomes. Stat Med 14:357–379
Ting N (2011) Phase 2 clinical development in treating chronic diseases. Drug Inf J 45:431–442
Ting N, Chen D, Ho S, Cappelleri J (2017) Phase II clinical development of new drugs. Springer, New York
Wang SJ, Hung HMJ, O’Neill RT (2006) Adapting the sample size planning of a phase III trial based on phase II data. Pharm Stat 5:85–97
Zhang YY, Rong TZ, Li MM (2020) The estimated and theoretical assurances and the probabilities of launching a phase III trial. Chin J Appl Probab Stat (under review)
Acknowledgements
The authors would like to thank the Editor and the reviewers for their constructive comments, which have led a substantial improvement of the paper.
Funding
The research was supported by the Fundamental Research Funds for the Central Universities (2019CDXYST0016, 2018CDXYST0024), China Scholarship Council (201606055028), National Natural Science Foundation of China (11671060), MOE Project of Humanities and Social Sciences on the West and the Border Area (20XJC910001, 14XJC910001), and Chongqing Key Laboratory of Analytic Mathematics and Applications.
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Zhang, YY., Ting, N. Can the Concept Be Proven?. Stat Biosci 13, 160–177 (2021). https://doi.org/10.1007/s12561-020-09290-3
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DOI: https://doi.org/10.1007/s12561-020-09290-3