Clinical evaluation, drugs phase

The clinical evaluation of a new drug is divided into three phases. The first phase of human testing considers what chemical actions a drug has, how it is... 

PVC s alone with Class IC drugs was not sufficient to reduce mortality in the specific post-infarction population chosen for the CAST study. The failure of Class IC agents in the CAST study and their low efficacy in preventing induction of SVT during electrophysiological testing has increased the interest in alternative approaches to antiarrhythmic therapy, particularly towards Class III agents, a number of which are in Phase II clinical evaluation. 

Most physicians in the pharmaceutical industry work in one of three main areas, which correspond to the well-defined phases through which a drug passes in its clinical evaluation, namely ... 

The clinical development of new drugs usually takes place in steps or phases conventionally described as clinical pharmacology phase I), clinical investigation (phase II), clinical trials (phase III), and postmarketing studies (phase IV). Table 1.1 summarizes the four phases of clinical evaluation. 

The NME can now be administered to humans. The first step in clinical evaluation is one or more phase I studies designed to assess the drug s safety and pharmacokinetic profile. Phase I studies usually involve a small number of healthy volunteers who are closely monitored after receiving escalating doses of the drug candidate. Phase I studies of drugs for cancer or HIV infection must be carried out in patients, not in healthy subjects. Ordinarily, until more information is available, the minimum dose to induce side effects is stipulated as the upper dose limit for subsequent administration to human subjects. 

Clinical phase II trials are conducted to evaluate the effectiveness of a drug for a particular indication or indications in patients with the targeted disease. These studies also help to determine the common short-term side effects and risks associated with the drug. Phase II studies are typically well controlled, closely monitored, and conducted in a relatively small number of patients, usually no more than several hundred. 

Phase III. Clinical evaluation is expanded to include more patients (several hundred to several thousand) as well as more evaluators. Additional information is obtained regarding the drug s safety and effectiveness in a large patient population. 

A potential new drug candidate faces a well-defined clinical and product development process that has been refined over several decades. The development phase of a new dmg product usually consists of two main activities clinical evaluation (safety and efficacy), and product development (dmg substance and dosage form). As shown in Table 1.1, the process can last as long as 7-9.5 years and the cost can be approximately 50% of the entire expense for development of a new medicine.8 At this stage, some programs would be terminated for various reasons, such as lack of clinical efficacy, clinical toxicity, or dmg developability. 

If a sponsor has conducted phase 1 trials outside of the United States and believes that there are adequate human safety studies already available, it may not be necessary to conduct any phase 1 trials in the United States. In such a case, the sponsor would prepare an IND and include in the initial IND submission a clinical protocol for phase 2 or 3. This IND, because it will involve exposure of more patients to the drug for the purposes of safety testing as well as efficacy evaluations, will require a greater level and depth of manufacturing and nonclinical data. The next section will describe the requirements for such an advanced-stage IND. 

Figure 13-15. A simplified/generic representation of clinical trials involving Phases I (safety and tolerability in healthy participants and/or patients), II (to evalnate effectiveness of the drug in patients), and III (to perform expanded controlled and uncontrolled trials and gather benefit-risk data). About 70-90% of drugs entering Phase III studies successfully complete this phase of evaluation. For more details see the glossary at www.clinicaltrials.gov.

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