Phases Of Clinical Drug Development

The case described represents just one of many decisions that must be made before beginning clinical trials. Clinical drug trials are described as Phases I-V. The first trials in humans that test the drug for safety are considered Phase I. These studies usually employ normal volunteers, and may expose about 50 individuals to the drug. For known toxic compounds such as anticancer agents, only patients with the targeted illness would be used. The first studies to define efficacy are considered...

When Is an IND required

An IND is always required prior to initiation of a clinical study of an investiga-tional new drug in the United States. In addition, an IND is required before initiation of a clinical study of a drug approved for some uses, but to be studied clinically for a new indication or at unapproved doses or if the new clinical study is intended to support promotion of the product. The following examples may be helpful. A sponsor wants to initiate animal toxicology studies of an investigational new drug...

Surrogate Endpoints

Ideally, the primary efficacy endpoint(s) should be a direct measure of clinical benefit. Such endpoints are clinically meaningful, facilitate communication of observed benefits, and generally allow quantification of benefit that can be weighed against toxicity to assess net clinical value. However, direct measurement of clinical benefit may require large, lengthy trials or may otherwise be impractical or impossible to accomplish. Therefore, in many trials, efficacy of a therapy is measured...

Balancing Benefits and Risks

The norm that the balance of benefits and risks be favorable rests on the principles of beneficence and respect for persons. This norm is expressed in all codes of ethics and is a specific duty of IRBs. The federal regulations state that IRBs must determine that ''risks to subjects are reasonable in relation to anticipated benefits to the subjects and the importance of the knowledge to be gained'' (38). To balance the benefits and risks of a clinical trial, IRBs must consider the disease being...

Compliance with New Federal Regulations

To comply with the assurances filed with HHS and FDA, IRBs are required to adjust their policies and procedures to conform with newly promulgated federal guidelines and procedures. In order to do so, either the staff of IRBs or the office of legal counsel for the institution must be responsible for knowing when such guidelines or regulations are issued. The IRBs must then incorporate any such changes into their operations and advise investigators of the new requirements. An example of one...

Rocco L Brunelle

Eli Lilly and Company, Indianapolis, Indiana Michael G. Wilson Michael G. Wilson and Company, Inc., New Palestine, Indiana Symptoms, signs, and laboratory tests are the inputs to health decisions about prognosis, diagnosis, and treatment. The quality with which they are elicited and interpreted limits the quality of health decisions. Symptoms are God's reminders to visit your physician or modify your behavior. Symptoms are elicited from patients or their companions, and a skilled practitioner...

Example 1 Tracrium

Tracrium atracurium besylate , is a nondepolarizing neuromuscular blocking agent with an intermediate duration of action 45 min . 1. Severity of the disease. This compound was intended for use during surgery, and hence would be considered a clinically significant agent. 2. Availability of alternative therapy. No other agents of intermediate duration were available the commonly used neuromuscular blocking agents available for children at that time were either very short or very long in duration...

Pharmacokinetic and ADME Studies

As part of the drug discovery and development process, pharmacokinetic and ADME studies have become an integral step in the early evaluation of drug candidates. Absorption, half-life, and metabolism are being measured early in the development of a drug candidate in order to exclude those compounds that are poorly absorbed or rapidly metabolized or eliminated. Traditionally, most ADME studies have been carried out in vivo, usually in mice, rats, and dogs. However, increased knowledge of human...