American Society of Clinical Oncology policy statement update: the critical role of phase I trials in cancer research and treatment.

Abstract

The American Society of Clinical Oncology (ASCO) represents more than 35,000 oncologists and other health care professionals who care for people with cancer and conduct research to improve cancer treatment. ASCO approved a policy statement on the importance of phase I trials in cancer treatment in 1996 and published it in 1997.1 ASCO and its member clinicians have repeatedly used this statement as evidence that phase I trials have therapeutic intent (ie, potential to provide patients with clinical benefit) and to argue for insurance coverage of routine patient costs in these trials. Since the 1997 statement was published, there have been significant developments in cancer care and research. The Patient Protection and Affordable Care Act (ACA) of 20102 has led to enormous changes in the health care delivery system by increasing the number of individuals with health insurance and improving patients' access to many high-quality and preventive care services. The number of people diagnosed with cancer3 and surviving cancer4 is also rapidly increasing. Thus, there is an increase in the number of patients in need of cancer care, and these patients are more likely than in the past to have health insurance that covers the cost of their treatment. The ACA requires payers to cover routine patient costs in phase I to IV trials. Simultaneously, the biopharmaceutical industry has been investing in molecularly targeted agents and immunotherapies for cancer, leading to an increase in the number of promising new agents that need testing in phase I trials.5 Researchers are also exploring innovative trial designs, which may decrease patient risk, expose fewer patients to less-than-optimal drug doses, increase patients' potential for clinical benefit from trial participation, better identify subpopulations of patients likely to benefit from an agent, and reduce the chance of ineffective agents continuing through the development process.6–14 The result is that phase I trials in cancer have greater potential as a treatment option for many patients with cancer than they did in 1997. To address this changing landscape in cancer, ASCO convened a working group of the Cancer Research Committee to review and update the ASCO policy statement on phase I trials. This update reaffirms the critical importance of phase I trials in cancer research and treatment and emphasizes their therapeutic intent. The first section of the statement defines phase I trials in cancer and underscores the importance of trial design in the drug development process. Subsequent sections review the evidence that phase I trials provide patients with clinical benefit and make a series of recommendations on how to increase participation in these trials. The statement concludes with a section on special issues in pediatric phase I trials.