Clinical drug testing/trials

Several consortia, primarily driven by pharmaceutical industry members and encouraged by health authorities, have been formed to evaluate and qualify safety biomarkers for use in early clinical drug development trials. In the remainder of this manuscript, we will focus on the safety biomarker qualification efforts of the Critical Path Institute s (C-Path) Predictive Safety Testing Consortium (PSTC), as well as the PSTC collaborations with the Foundation for the National Institutes of Health s Biomarkers Consortium s (FNIH BC) Kidney Safety Project (KSP) and the Innovative Medicines Initiative s (IMI) Safer and Faster Evidence-based Translation Consortium (SAFE-T). Both of these collaborations are driven by the common goal of modernizing safety science through the qualification of clinical safety biomarkers for use in drug development. 

After completing preclinical testing, a company files an Investigational New Drug (IND) application with the regulators (the FDA in the U.S.), so that clinical studies in man can begin. The IND shows results of all experiments to this point, a detailed proposal for the clinical study, the expected mode of action for the drug, and any side effects observed. All clinical trials will also be reviewed and approved by the Institutional Review Board (IRB) at the clinic where the trials will be run. 

With an approved IND, the drug company can place me in humans at lower doses, mainly to observe any overt symptoms of toxicity and to evaluate my PK characteristics, and the study may use 10 to 20 healthy subjects. These data are then resubmitted to FDA (Phase 1). After my Phase I is completed, drug testing begins for my clinical efficacy, with trials at different doses and given to different populations under strict supervision. A successful study may require a few thousand patients and the involvement of several study centers across the country (or perhaps across the world) to collect extensive data. It is not unusual to have 100,000 patients take me before the data are submitted to the FDA for drug approval — the so-called marketing approval. 

Clinical trials, also known as clinical studies, test potential treatments in human volunteers to see whether they should be approved for wider use in the general population. A treatment could be a drug, medical device, or biologic, such as a vaccine, blood product, or gene therapy. Potential treatments, however, must be studied in laboratory animals first to determine potential toxicity before they can be tried in people. Treatments having acceptable safety profiles and showing the most promise are then moved into clinical trials. 

It s important to test medical products in the people they are meant to help. In the past, most new drug testing had been done on white men. Groups such as women, blacks, and Hispanics often were not adequately represented. It s important to test medical products in a wide variety of people because drugs can work differently in people of various ages, races, ethnicity, and gender. The FDA seeks to ensure that people from many different groups are included in clinical trials. 

The blinding of clinical drug products for double-blind trials involves two steps making the test drug and the comparator drug as similar as possible... 

The pre-clinical drug development process has as its end product a drug candidate that is suitable for testing in human clinical trials. To achieve this, the candidate must pass pre-clinical toxicology testing, have its adsorption, distribution, metabolism and excretion understood in suitable animal models, and have good scientific evidence that it will provide medicinally beneficial effects. The latter normally requires showing efficacy in animal models of the disease. The early phase discovery process has usually... 

Clinical safety studies are conducted in human volunteers to determine the safety of chemicals, drugs, formulations, devices, or other products, which may come in contact with the human body. Clinical safety testing should always be conducted prior to efficacy investigations in order to determine the benefit/risk ratio of efficacy trials. When designing a study, benefits and risks shall be balanced and shown to be in a favorable ratio (The Belmont Report). The rights, safety and well-being of the trial subjects are the most important considerations. (ICH Guidelines 2.3). 

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