Setting the bar in phase II trials: The use of historical data for determining "go/no go" decision for definitive phase III testing Journal Article


Authors: Vickers, A. J.; Ballen, V.; Scher, H. I.
Article Title: Setting the bar in phase II trials: The use of historical data for determining "go/no go" decision for definitive phase III testing
Abstract: Purpose: Phase II trials aim to determine whether a cancer treatment is sufficiently promising to justify phase III study. Whether an agent is declared promising in a phase II trial depends on prespecified "null" and "alternative" rates of an outcome of interest such as tumor response. In some cases, the null must be determined with reference to historical data. We sought to determine the proportion of phase II trials that require historical data to establish the null and to determine how these historical estimates were derived. Experimental Design: We conducted a systematic review of phase II trials published in the Journal of Clinical Oncology or Cancer in the 3 years to June 2005. Data were extracted following a prespecified protocol. Results: We retrieved 251 papers, of which 117 were found to be ineligible; 70 of 134 included trials (52%) were defined as requiring historical data for design. Nearly half (32, 46%) of these papers did not cite the source of the historical data used, and just 9 (13%) clearly gave a single historical estimate as the rationale for the null. Trials that failed to cite prior data appropriately were significantly more likely to declare an agent to be active (82% versus 33%; P = 0.005). No study incorporated statistical methods to account for either sampling error or possible differences in case mix between the phase II sample and the historical cohort. Conclusions: Many phase II trials require historical data to determine null response rates. Simple guidelines may improve design and reporting of such trials. © 2007 American Association for Cancer Research.
Keywords: cancer chemotherapy; treatment outcome; treatment response; disease-free survival; clinical trial; antineoplastic agents; research design; antineoplastic agent; neoplasms; medical decision making; cancer research; randomized controlled trials; systematic review; clinical research; medical oncology; clinical trials, phase ii; clinical trials, phase iii
Journal Title: Clinical Cancer Research
Volume: 13
Issue: 3
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2007-02-01
Start Page: 972
End Page: 976
Language: English
DOI: 10.1158/1078-0432.ccr-06-0909
PUBMED: 17277252
PROVIDER: scopus
PMCID: PMC2529160
DOI/URL:
Notes: --- - "Cited By (since 1996): 20" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus"
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MSK Authors
  1. Andrew J Vickers
    556 Vickers
  2. Howard Scher
    816 Scher
  3. Venus Jennifer Ballen
    1 Ballen