Pitfalls in the Drug Approval Process: Dose-Effect,Experimental Design,and Risk-Benefit Issues

Delays in the approval of new drugs are often due to the failure of pharmaceutical sponsors to address particular scientific issues necessary to the preparation of adequate labeling. This may result in the issuance of extensive deficiency letters which prolong review of applications by The Food and Drug Administration (FDA) and hence, drug development. The purpose of this paper is to outline the most common problems or pitfalls in drug development which often contribute to these delays. Some of the more common pitfalls are: (a) failure to adequately characterize dose-effect relationships; (b) designing experiments which do not address proposed indications and/or developing clinical plans which become overextended; and (c) failure to adequately address risk-benefit issues. It is concluded that attention be payed to these variables early on in drug development. A formalized developmental plan which incorporates dose-response studies, specifics of the experimental designs of pivotal studies and a risk-benefit analysis for the product being developed is a useful tool in anticipating potential pitfalls in the development process.