This Article Full Text Full Text (PDF) All Versions of this Article: 1078-0432.CCR-06-0909v1 13/3/972    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vickers, A. J. Articles by Scher, H. I. Search for Related Content PubMed PubMed Citation Articles by Vickers, A. J. Articles by Scher, H. I. Related Collections Commentary

Setting the Bar in Phase II Trials: The Use of Historical Data for Determining "Go/No Go" Decision for Definitive Phase III Testing

Authors' Affiliations: Departments of ¹ Medicine and ² Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY

Requests for reprints: Andrew J. Vickers, Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY 10021. Phone: 212-639-4910; Fax: 212-639-4953; E-mail: vickersa{at}mskcc.org.

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.

Commentary

Testing the Wrong Hypothesis in Phase II Oncology Trials: There Is a Better Alternative

Mark J. Ratain and Theodore G. Karrison
Clin. Cancer Res. 2007 13: 781-782. [Full Text] [PDF]

This article has been cited by other articles:

				H. I. Scher, S. Halabi, I. Tannock, M. Morris, C. N. Sternberg, M. A. Carducci, M. A. Eisenberger, C. Higano, G. J. Bubley, R. Dreicer, et al. Design and End Points of Clinical Trials for Patients With Progressive Prostate Cancer and Castrate Levels of Testosterone: Recommendations of the Prostate Cancer Clinical Trials Working Group J. Clin. Oncol., March 1, 2008; 26(7): 1148 - 1159. [Abstract] [Full Text] [PDF]

				W. M. Stadler Tumor Burden Endpoints and Phase II Clinical Trial Design ASCO Educational Book, January 1, 2008; 2008(1): 89 - 93. [Abstract] [Full Text] [PDF]

				M. J. Ratain and T. G. Karrison Testing the Wrong Hypothesis in Phase II Oncology Trials: There Is a Better Alternative Clin. Cancer Res., February 1, 2007; 13(3): 781 - 782. [Full Text] [PDF]

				M. R. Tomblyn and J. D. Rizzo Are There Circumstances in Which Phase 2 Study Results Should Be Practice-Changing? Hematology, January 1, 2007; 2007(1): 489 - 492. [Abstract] [Full Text] [PDF]