11 - Regulatory Considerations in Clinical Trials of Novel Anticancer Drugs

Abstract

This chapter discusses regulatory considerations in clinical trials of novel anticancer drugs. The responsibilities of the Food and Drug Administration (FDA) and of sponsors of New Drug Application (IND) are outlined in the Code of Federal Regulations (CFR) 21 part 312. The sponsor initiates and assumes responsibility for the clinical investigation. The sponsor is usually a pharmaceutical company, but individuals or academic institutions may also serve as sponsors. The IND process is initiated by submission of an IND application and continues throughout the period a drug is under investigation. A new agent will be reviewed by either the FDA's CDER or the Center for Biologics Evaluation and Research (CBER). The intensity of FDA involvement in the design and analysis of cancer clinical trials varies with the stage of drug development. The FDA frequently offers input to sponsors during planning of early trials and late trials. It is found that during pre-IND meetings, the FDA indicates the toxicology testing required to support initial clinical trials. The FDA does not usually require chronic animal studies prior to phase I clinical testing of cytotoxic drugs because these drugs are administered periodically. It is found that for accelerated approval, the FDA relies upon surrogate end points that are not completely validated, but are reasonably likely to predict clinical benefit.