Guidelines and evaluation of new anti-infective drugs for treatment of urinary tract infections

Abstract

Government regulatory agencies have the responsibility to protect the public by certifying new drugs as safe and effective. In the United States, the Food and Drug Administration (FDA) is solely responsible for setting these standards. It has the option to request assistance from consultants and advisory committees, but the ultimate decision belongs with the agency. To comply with the law, maintain the public trust and avoid conflict of interest, the FDA needs to base its decisions on the best available evidence. It must be sensitive to the medical needs of the public and carefully assess the claims made by industry. The FDA has jealously guarded its prerogatives, as it should. A revolutionary concept was proposed about 10 years ago by the Antimicrobial Agents Committee of the Infectious Disease Society of America (IDSA) [1]. The major concern was that for many bacterial infections there were no standard accepted definitions of the disease process or of criteria by which to appraise treatment or outcome. After long and sometimes difficult negotiations, a contract was awarded to the IDSA from the FDA to devise standards for evaluation of new anti-infective drug products. This culminated in the development of the IDSA guidelines [2]. The information was shared with colleagues in Europe and resulted in the publication of the ESCMID guidelines. The strengths of the guidelines include careful attention to legal requirements and precedent set by the FDA, the experience of the members of the advisory committees in conducting clinical trials and the inclusion of experts from the pharmaceutical industry. In the spirit of cooperation, publication of the final report was subsidized by the Pharmaceutical Manufacturers Association. Development of the IDSA guidelines was a major step in providing a rational basis for evaluation of anti-infective drugs. The infectious diseases community benefits by resolving many difficult diagnostic issues, the industry benefits by being able to construct sound protocols for clinical trials and the FDA benefits by being better able to serve the public interest. It is important to note that the FDA reserves the right to accept or reject any part of the guidelines. It is inappropriate for investigators or industry to use IDSA guidelines to design clinical trials without FDA approval. In the special case of urinary tract infection, the committee recommendations for quantitative counts to designate significant bacteriuria [3] remain controversial [4] and FDA criteria are the only ones acceptable for the purpose of clinical trials. The infectious diseases community must convince the FDA and other government agencies that newly proposed guidelines are rational, practical, and meet the current state of the art. Dr Naber and his colleagues have made a thoughtful contribution to this endeavor. My comments on several of these issues are as follows. * Present address: Room M110 Starling Loving Hall, 320 West 10th Avenue, Columbus, OH 43210, USA. Tel: +1-614-293-8975; fax: +1-614-293-5627.