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The Phase III Trial in the Era of Targeted Therapy: Unraveling the "Go or No Go" Decision

Thomas G. Roberts, Jr, Thomas J. Lynch, Jr, Bruce A. Chabner

From the Division of Hematology/Oncology, Massachusetts General Hospital, Harvard Medical School, Boston; and the Program on the Pharmaceutical Industry, Massachusetts Institute of Technology, Cambridge, MA.

Address reprint requests to Thomas G. Roberts Jr, MD, Massachusetts General Hospital, Cox 640, 100 Blossom St, Boston, MA 02114; e-mail: troberts{at}partners.org.

Purpose: To review characteristics of contemporary phase III oncology trials and create an explicit framework to help clinical researchers prioritize novel therapies for phase III testing.

Methods: We searched the MEDLINE and EMBASE databases for all reviews of phase III trials; cataloged all phase III trials in two national clinical trial databases; and reviewed approval criteria of recently approved oncology drugs from public data provided by the US Food and Drug Administration. Industry data not available elsewhere in the medical literature were obtained from a sourcebook published by a large contract research organization.

Results: Phase III oncology trials are the most expensive and time-consuming aspect of the drug development process. The results of these trials continue to exert the greatest influence on the treatment decision of oncologists and remain pivotal to the granting of drug approval. Making optimal decisions about which agents to advance to phase III testing may decrease the overall cost of cancer drug development and limit the number of patients exposed to ineffective drugs. A conceptual decision model for prioritizing novel therapies for phase III testing is presented.

Conclusion: Cancer drug development has become more complex and expensive, whereas overall clinical progress remains slow. The transition from phase II to phase III requires a strategic decision that is based on new considerations. A greater investment in phase I and II drug trials may be required to provide the information necessary for phase III planning.

T.G.R. is supported in part by National Cancer Institute grant R25T CA 92203.

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