An optimal two-stage phase II design utilizing complete and partial response information separately Journal Article


Authors: Panageas, K. S.; Smith, A.; Gonen, M.; Chapman, P. B.
Article Title: An optimal two-stage phase II design utilizing complete and partial response information separately
Abstract: Phase II clinical trials in oncology are performed to evaluate the therapeutic efficacy of a new treatment regimen. A common measure of efficacy for these trials is the proportion of patients who obtain a response measured by tumor shrinkage. It is standard practice to classify this response into the following categories: (1) complete response (CR); (2) partial response (PR); (3) stable disease; and (4) progression of disease. Tumor response is then treated as a binary variable whereby patients who achieve either a CR or a PR are considered responders and all others nonresponders. A two-stage design that allows for early termination of the trial if the treatment shows little efficacy such as Gehan or Simon gives equal weight to a CR and a PR. However, a CR, defined as complete disappearance of the tumor, is more likely than a PR to signal an important antitumor effect and result in a survival advantage. We argue that CRs and PRs should be considered separately, and hence we propose a two-stage design with a multilevel endpoint (i.e., CR, PR, and nonresponders). This design is an extension of Simon's optimal two-stage design and is based on a trinomial model. For most scenarios the proposed design results in an improvement in expected sample size compared to Simon's optimal design. Design optimization was performed by a direct search based on enumerating exact trinomial probabilities. Sample size tables are provided for parameter sets commonly used in the oncologic setting. Software is available by contacting the authors. © 2002 Elsevier Science Inc. All rights reserved.
Keywords: cancer survival; treatment outcome; research design; clinical practice; neoplasms; phase 2 clinical trial; classification; tumor volume; oncology; probability; models, statistical; parameter; computer program; phase ii; experimental design; sample size; clinical trials, phase ii; humans; article; optimal; trinomial
Journal Title: Controlled Clinical Trials
Volume: 23
Issue: 4
ISSN: 0197-2456
Publisher: Elsevier Science, Inc.  
Date Published: 2002-08-01
Start Page: 367
End Page: 379
Language: English
DOI: 10.1016/s0197-2456(02)00217-9
PUBMED: 12161080
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 14 November 2014 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Mithat Gonen
    716 Gonen
  2. Alexander D Smith
    28 Smith
  3. Paul Chapman
    252 Chapman
  4. Katherine S Panageas
    331 Panageas