Current Statistical Challenges in Oncology Clinical Trials in the Era of Targeted Therapy

Abstract

The mapping of the human genome has led to rapid advances in our understanding of diseases at the molecular level. This new knowledge is shifting the drug development paradigm in cancer trials. For example, traditional Phase 1 to 3 trials of dose finding, evaluating activity, and confirming efficacy are becoming less common with all the three objectives accomplished within one protocol. Molecular marker-based clinical trials are also on the rise in place of the traditional disease-based clinical trials. In addition, patients receiving control treatment are routinely switched to the experimental treatment after disease progression, complicating the final comparison of survival rates between treatment groups. In this article, we describe these and other challenges in the regulatory review of cancer therapies as a result of this paradigm shift and also describe some innovative ideas that have the potential to improve evaluation of new agents to treat cancer in clinical trials.

Key Words:

• Expansion cohorts
• Master protocols
• Non-proportional hazards
• Treatment switch-over

Additional information

Notes on contributors

Rajeshwari Sridhara

Rajeshwari Sridhara (E-mail: [email protected]), Kun He (E-mail: [email protected]), Lei Nie (E-mail: [email protected]), Yuan-Li Shen (E-mail: [email protected]), Shenghui Tang (E-mail: [email protected]), Food and Drug Administration CDER/OTS/OB, 10903 New Hampshire Ave., WO21, Rm 3512, Silver Spring, MD 20993.

Kun He

Rajeshwari Sridhara (E-mail: [email protected]), Kun He (E-mail: [email protected]), Lei Nie (E-mail: [email protected]), Yuan-Li Shen (E-mail: [email protected]), Shenghui Tang (E-mail: [email protected]), Food and Drug Administration CDER/OTS/OB, 10903 New Hampshire Ave., WO21, Rm 3512, Silver Spring, MD 20993.

Lei Nie

Rajeshwari Sridhara (E-mail: [email protected]), Kun He (E-mail: [email protected]), Lei Nie (E-mail: [email protected]), Yuan-Li Shen (E-mail: [email protected]), Shenghui Tang (E-mail: [email protected]), Food and Drug Administration CDER/OTS/OB, 10903 New Hampshire Ave., WO21, Rm 3512, Silver Spring, MD 20993.

Yuan-Li Shen

Rajeshwari Sridhara (E-mail: [email protected]), Kun He (E-mail: [email protected]), Lei Nie (E-mail: [email protected]), Yuan-Li Shen (E-mail: [email protected]), Shenghui Tang (E-mail: [email protected]), Food and Drug Administration CDER/OTS/OB, 10903 New Hampshire Ave., WO21, Rm 3512, Silver Spring, MD 20993.

Shenghui Tang

Rajeshwari Sridhara (E-mail: [email protected]), Kun He (E-mail: [email protected]), Lei Nie (E-mail: [email protected]), Yuan-Li Shen (E-mail: [email protected]), Shenghui Tang (E-mail: [email protected]), Food and Drug Administration CDER/OTS/OB, 10903 New Hampshire Ave., WO21, Rm 3512, Silver Spring, MD 20993.