Human subjects, clinical trials

As mentioned earlier, biotextile retrieval studies can be carried out in animals (preclinical trials) as well as in human subjects (clinical trials). Retrieval studies using animal models are usually planned studies where the device to be tested is implanted in the animal for a fixed duration after which it is harvested and studied for the desired characteristics. 

The commencement of human pharmacology clinical trials (T ilH trials) can lead to a range of emotions for clinical researchers. It is a time of excitement (and quite possibly relief) that the drug has reached this milestone and a time of anticipation and hopeful expectation. Additionally, and possibly more so, it is a time of trepidation and anxiousness. As noted in Section 4.5, no animal model is a perfect predictor of the precise effects of the drug in humans, and there is the ever present possibility that serious safety issues may arise. On relatively rare occasions, life-threatening, drug-induced conditions have occurred in subjects in human pharmacology clinical trials. 

To generate sufficient data so as to convince the regulators that it safe and worthwhile to proceed to clinical trials with human subjects. 

The overall objective of clinical trials is to establish a drug therapy that is safe and effective in humans, to the extent that the risk-benefit relationship is acceptable. The ICH process has developed an internationally accepted definition of a clinical trial as Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of one or more investigational medicinal product(s), and/or to identify any adverse reactions to one or more investigational medicinal product(s) and/or to study absorption, distribution, metabolism and excretion of one or more investigational medicinal product(s) with the object of ascertaining its (their) safety and/or efficacy. ... 

Clinical trials must be conducted in accordance with the principles of Good Clinical Practice (GCP). GCP is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects. Its purpose is twofold ... 

Clinical trials shall be conducted in accordance with the Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects... 

Name and description of the investigational product(s). A summary of findings from non-clinical sfudies and from clinioal trials that is relevant to the trial. Summary of the known and potential risks and benefits, if any, to human subjects. Description of and justification for the route of administration, dosage, dosage regimen, and treatment period(s). A statement that the trial will be conducted in compliance with the protocol, GCP and the applicable regulatory requirement(s). Description of the population to be studied. References to literature and data that are relevant to the trial, and that provide background for the trial... 

Attempts to improve the bioavailability of the organotin(IV) cations by the formation of water-soluble complexes or by their inclusion into )S-cyclodex-trin have also been reported. In spite of their widespread activity, these antitumor organotin(IV) complexes have not yet been subjected to extensive clinical trials in humans. 

The first lead compounds for non-nucleoside reverse transcriptase (RT) inhibitors (NNRTl) were discovered about 15 years ago (Pauwels et al. 1990 Merluzzi et al. 1990 Goldman et al. 1991 De Clercq 1993 Riibsamen-Waigmann et al. 1997). Since then they have become an important ingredient of the dmg combination schemes that are currently used in the treatment of human immunodeficiency virus type 1 (HlV-1) infections. Starting from the HEPT and TIBO derivatives, numerous classes of compounds have been described as NNRTIs. Four compounds (nevirapine, delavirdine, efavirenz and etravirine) have so far been approved for clinical use and several others are the subject of clinical trials (Balzarini 2004 Stellbrink 2007). 

For any intervention intended to impact favorably upon human health, it is important to evaluate its safety and efficacy in order to demonstrate that it does not cause harm and it does provide the expected benefit. The gold standard method for evaluating any intervention, whether it be a botanical product, dietary supplement, drug, medical device or medical procedure, is the randomized, clinical trial (RCT). A clinical trial is a type of experiment conducted in human subjects where the effects of at least two interventions are compared. Often, the clinical trial takes the form of an active treatment compared to an inactive control or placebo. 

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