What are clinical trials?

After extensive testing in the laboratory, all new chemicals and devices that are intended for therapeutic use must undergo a process during which their therapeutic efficacy in humans is evaluated. Before any new product can begin such studies, documentation of existing information on the product and an application for performing clinical trials must be made. In Canada it is the Health Protection Branch (HPB) of Health Canada that provides authorization and monitors each step and result of the studies. If the clinical trials are successful, and show the new product to be safe and effective, HPB gives permission for the new product to be marketed.

Before a clinical trial can take place locally, the study design is evaluated by the Research Review Committee of the Atlantic Health Sciences Corporation. This Committee reviews up to 10 studies each month, and looks at both the ethics and science of the trial. This includes reviewing the scientific validity of the research, the reasons for undertaking the study, the competence of the investigators, the availability of any necessary resources, the quality of the information given to patients (informed consent), and the anticipated values and publication of the research.

All drugs and devices cause adverse, or unwanted, effects, so clinical trials study the benefit they provide in relation to the adverse effects they cause. In other words, their risk to benefit ratio is tested. This process commonly uses randomized, controlled trials' where equivalent groups of patients are randomly allotted to receive either the new drug or device, or to receive placebo (inactive substance) or current therapy. clinical trials are typically divided into 4 phases' that progressively provide more information.

Phase I Trials.
These establish the basic clinical pharmacology (drug biochemistry or pharmacokinetics) of the drug and biological effects of the drug or device. From 10 to 100 healthy volunteers may be required, and the study provides the first information on the safety, tolerance, and efficacy of the new product.

Phase II Trials.
Here the main focus is on using patients with the disease it is intended the product will treat. From 100 to 500 patients with the target disease will receive the product, and more details on the pharmacology (pharmacokinetics) will be found. Of most importance is evaluating the clinical effects on the target disease - how effective is the drug or device as a therapeutic agent (pharmacodynamics), and what dose of the drug is needed?

Phase III Trials.
During this phase the randomized, controlled clinical trial is typically used, involving perhaps from 500 to 3,000 patients in structured and systemized monitoring studies. These assess the efficacy and safety of the drug on a large scale at defined doses, and allow comparison with any other existing drug or treatment. Also during these studies, the potential toxicity of the drug or treatment is determined during the period of observation (usually weeks to months.) In this way safer and more effective drugs can be selected. After successful completion of these studies, the HPB would permit marketing of the new drug or product for a specific indication' or disease.

Phase IV Trials.
These are often termed post-marketing surveillance' trials. With the approved drug or device now being used in the general population, its performance in real life' situations can be evaluated. For example, the drug will be used in patients with additional diseases, and in patients who do not comply with the correct dosing. Post-marketing surveillance of a new drug or device can involve 10,000 patients worldwide. Phase IV Trials provide the most effective means of identifying and quantifying potential but rare toxic effects of new drugs, including the recognition of low frequency adverse events.

It is through the collective efforts of Pharmaceutical companies, Government regulatory agencies such as HPB, local research facilities such as the Atlantic Health Sciences Corporation, and dedicated health care professionals who implement the studies that the process of new drug or device development takes place. From discovery of a new drug, through laboratory studies and clinical trials, to routine use by medical professionals, the entire process can take 10 or more years, and cost several million dollars.