Wednesday, 18 May 2016

Phase 0 of Clinical Trials

Excerpted from: Mahan, V.L. (2014) Clinical Trial Phases. International Journal of Clinical Medicine, 5, 1374-1383. Available from: Link

Phase 0 Clinical Trials:

The concern was stagnation and declining innovation with a widening gap between knowledge and clinical use. A drug entering Phase I trials in 2000 was not more likely to come to market than one entering Phase I trials in 1985 [23]. Improvement in prediction of failure during early clinical trials saves in development costs and time to market [24]. The concept of exploratory investigation new drug (IND) studies was a result of this FDA analysis and can help with determining whether a defined mechanism of action can also be observed in humans, provide information on pharmacokinetics, select promising products from a group of candidates, and evaluate biodistribution. The purpose of these studies is to help in the go versus no-go decision making process of a drug’s fate early in the development process using human models rather than relying on animal data.

Exploratory IND studies (also known as Phase 0 studies) are conducted early in clinical phase studies and involve limited human exposure and have no therapeutic or diagnostic intent. Doses are subtherapeutic and patients are monitored by the clinical researcher and involve about 10 study patients. Duration of a patient’s participation is usually less than 1 week. Phamacodynamics and pharmacokinetics are studied. These trials are before the traditional dose escalation, safety, and tolerance studies, do not replace the Phase I clinical trials and do not indicate whether a therapy has a positive impact on the targeted pathology. These studies help in eliminating candidate therapies before they reach Phase I studies [25]-[27]. These trials were developed to shorten the critical path for drug development, to explore pharmacokinetic and pharmacodynamic profiles of IND’s in humans, to help in accelerating identification of promising drugs, and to reduce development time and costs. Limitations of these trials include lack of therapeutic intent, motivation of patients to participate, may delay or exclude patients from other clinical trials that may have therapeutic intent, microdosing pharmacokinetics and relationship to therapeutic dose, and availability of sensitive analytical methods [28]. Attrition rates are high and only about 8% come to market.


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