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Superiority and Non-inferiority Phase III Oncology Trials

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Methods and Biostatistics in Oncology

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Abstract

Phase III trials occupy the top hierarchical position in clinical research, because they are the ideal scenario for comparing two or more competing therapies. Most phase III trials in oncology aim to demonstrate the superiority of a new treatment in comparison with control, but so-called non-inferiority phase III trials assess whether a more convenient, less toxic, or more affordable intervention is at least as efficacious as an existing standard of care. Ideally, the control arm in phase III trials should be the best available standard of care at the time of trial design and conduct. Determining the sample size is of special importance in phase III trials, given their attempt to allow for sound statistical conclusions upon their completion. A simple mnemonic (the ABCDE of sample-size calculation; alpha, or the type-I error; beta, or the type-II error; control, or the expected result in the control arm; dropout, or the expected rate of loss to follow-up or loss of data; experimental, or the desired result in the experimental arm, using the same parameter type as for C) is offered to facilitate interaction between clinical trialists and statisticians. Blocked randomization, stratification, minimization, blinding, and analyses based on the intent-to-treat principle are additional safeguards for reaching unbiased conclusions from phase III trials, whereas non-inferiority and factorial trials present some additional features that warrant special attention in their design and interpretation.

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Authors and Affiliations

  1. Dendrix Research, São Paulo, SP, Brazil

    Everardo D. Saad M.D.

  2. IDDI, Louvain-la-Neuve, Belgium

    Everardo D. Saad M.D.

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  1. Everardo D. Saad M.D.
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Correspondence to Everardo D. Saad M.D. .

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Editors and Affiliations

  1. Hospital do Câncer de Barretos, Barretos, São Paulo, Brazil

    Raphael. L.C Araújo

  2. AC Camargo Cancer Center, Dir - Brazil Gastrointestinal Tumor Grup, São Paulo, São Paulo, Brazil

    Rachel P. Riechelmann

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Saad, E.D. (2018). Superiority and Non-inferiority Phase III Oncology Trials. In: Araújo, R., Riechelmann, R. (eds) Methods and Biostatistics in Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-71324-3_12

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  • DOI: https://doi.org/10.1007/978-3-319-71324-3_12

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