Clinical trials safety studies

In recent years in some developed countries, the requisite of presenting economic evaluation (that is, pharmacoeconomic) studies of new dmgs has been introduced alongside the existing one of clinical trials. These studies have to provide proof of their efficiency (or cost-effectiveness) as a condition for the public financing of the new product. These studies improve information and market transparency and may help to make competition keener, but like the earlier requirements regarding effectiveness and safety, they constitute an additional cost factor and as such raise further barriers to entry. 

Nonclinical Studies In vitro (laboratory) or in vivo (animal) pharmacology, toxicology and pharmacokinetic studies that support the testing of a product in humans. Usually at least two species are evaluated prior to Phase I clinical trials. Nonclinical studies continue throughout all phases of research to evaluate long-term safety issues. 

O Sullivan MJ, Boyer PJ, Scott GB, Parks PW, Weller S, Blum R, Balsley J, Bryson YJ. The pharmacokinetics and safety of zidovudine in the third trimester of pregnancy for women infected with human immunodeficiency virus and their infants Phase I Acquired Immunodeficiency Syndrome Clinical Trial Group Study (protocol 082) Zidovudine Collaborative Working Group. Am J Obstet Gynecol 1993 168 1510-6. 

Insull W Jr, Isaacsohn J, Kwiterovich P, Ra P, Brazg R, Dujovne C, Shan M, Shugrue-Crowley E, Ripa S, Tota R. Efficacy and safety of cerivastatin 0.8 mg in patients with hypercholesterolaemia the pivotal placebo-controUed clinical trial. Cerivastatin Study Group. J Int Med Res 2000 28(2) 47-68. 

With the support that has been provided since its creation, NCCAM has invested in a broad array of scientific research projects that span the spectrum from basic research, such as interactions between botanical products and conventional drags, to the conduct of clinical trials to study the safety and efficacy of CAM modalities. The NCCAM portfolio also includes support for research training and education grants. In addition, the Center disseminates information through the NCCAM Clearinghouse (info nccam.nih.gov) and the NCCAM website (http //www.nccam.nih.gov). 

Clinical trials (intervention studies) research that involves the administration of a test regimen to evaluate its safety and efficacy... 

Clinical trials are studies to evaluate the effectiveness, pharmacokinetics, and safety of medications or medical devices by monitoring their effects on large groups of people. Clinical research trials may be conducted by government health agencies, researchers affiliated with a hospital or university, independent researchers, or private industry. The use of an approved medicinal product in nonapproved conditions (different administration route, dose, clinical indications, etc.) requires also a new clinical trial. 

Safety-oriented clinical trial A study that usually involves vital sign measures (e.g., heart rate, blood pressure, respiration rate), clinical laboratory tests (e.g., blood chemistries, urinalysis, ECG), and adverse reaction tests (both mental and physical performance capacities) to evaluate the risk of an intervention. 

Clinical trials are carried out on a defined human population to assess the safety and the efficacy of a new TE product compared to a current standard treatment. A clinical trial design must define the main criteria type of study (including duration and randomization of volunteers in assigning them either the treatment or the control), patient population, exclusion and inclusion of a volunteer in the clinical trial, safety, and efficacy end points. Clinical trials are typically divided into four phases ... 

A meta-analysis of 11 randomised clinical trials also studied the efficacy and safety of roflumilast versus placebo. This meta-analysis included a total population of 9675 patients, with the study duration ranging from 12 to 52 weeks [9qM] meta-analysis did not find any effect of roflumilast on mortality. However, there were more withdrawals due to adverse effects in roflumilast arm (RR = 1.62,95% Cl = 1.44,1.82). Marginally more patients experienced an adverse effect compared to control (RR = 1.08,95% Cl = 1.02,1.14). 

Dooley KE, Park JG, Swindells S, AUen R, Haas DW, Cramer Y, et al. Safety, tolerabiEty, and pharmacokinetic interactions of the antituberculous agent TMC207 (bedaquiEne) with efavirenz in healthy volunteers AIDS Clinical Trials Group Study A5267. J Acquir Immtme Defic Syndr 2012 59(5) 455-62. 

The preclinical trials are performed in in vitro and animal studies to assess the biological activity of the new compound. In phase 1 of the clinical trials the safety of a new drug is examined and the dosage is determined by administering the compound to about 20 to 100 healthy volunteers. The focus in phase II is directed onto the issues of safety, evaluation of efficacy, and investigation of side effects in 100 to 300 patient volimteers. More than 1000 patient volunteers are treated with the new drug in phase 111 to prove its efficacy and safety over long-term use. 

All preparations of enzymes intended for parenteral use are tested for safety in lower animals under the conditions anticipated in clinical trials ie, their use must be nonpyrogenic in the USP rabbit assay (255), and must be sterile. Such toxicologic studies are usually a prerequisite for approval by the FDA for the sale of such pharmaceuticals. 

Vertex also put in clinical trial VX-765, another caspase-1 -specific, YVAD-derived peptidomimetic that is in vitro slightly more potent then pralnacasan (IC50 0.8 nM). Evaluation of VX-765 in a mouse model of oxazolone-induced dermatitis showed a dose-dependent (10-100 mg/kg) inhibition of ear inflammation. Consequently, VX-765 was enrolled in a 4-week phase Ila safety and pharmacokinetic study for psoriasis. However, Vertex has not communicated any results yet. 

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. ... 

Please describe planned study population. Choice of participants should be appropriate for the indication proposed. Subjects should not have enrolled in a clinical trial during the preceding 12 weeks. Please describe how special populations such as women of childbearing age, children and the elderly will be handled in this study. Please comment on the special need for close monitoring due to safety considerations. 

Clinical trials must be conducted to establish safety in each target animal species which, in the majority of cases, will include food-producing species. Although the same types of animal may be involved in both pre-clinical and clinical trials, dear distinctions can be drawn between each type of study. Pre-clinical studies are only conducted in animals that are kept for the purposes of laboratory research, and that are usually maintained in a very controlled environment. Clinical trials, on the other hand, are conducted in animals that are representative of the normal conditions (field conditions) and purposes for which they are maintained. 

The first study to demonstrate the activity of enfuvirtide in HIV-infected patients (Kilby et al. 1998) showed that patients receiving the maximum 100 mg intravenous dose had maximum median declines in HIV-1 RNA of -1.96 logjo copies/mL through 14 days. Several additional studies (Kilby et al. 2002 Lalezari et al. 2003a, b) further demonstrated the safety and efficacy of enfuvirtide and led to the selection of twice-daily subcutaneous injections of a 90 mg nominal dose for testing in the TORO (T-20 vs. optimized regimen only) pivotal clinical trials. 

Dunn B, Davis LA, Todd JW, Chalela JA, Warach S, NINDS/NIH, Bethesda, MD for the ROSIE Investigators. Reperfusion of Stroke Safety Study Imaging Evaluation (ROSIE). Ongoing Clinical Trials Session, 29th International Stroke Conference 2004. 

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