This section has been inserted from the Health Canada Website:

http://www.hc-sc.gc.ca/english/media/releases/2001/2001_69ebk1.htm

What is a clinical trial?

When a drug manufacturer applies to have a new drug approved for sale in Canada, they are expected to show scientific evidence of the drug's safety, efficacy and quality in humans. While the effects of a new drug on people can be measured in other ways such as astute observation or anecdotal evidence a clinical trial is the best scientific approach to provide clear and reliable data. Specifically, a clinical trial is used to determine whether a drug is safe and effective, what dosages are most effective, and what side effects a drug may cause in people.

In a controlled clinical trial, comparable groups of people receive different forms of treatments. One group may receive the drug being tested, while another group may receive a treatment already known to be effective, or a placebo (an inactive substance that looks like the drug being tested). Once the trial is complete, the outcomes of the separate groups are compared and analysed to determine the effect of the drug.

Who regulates clinical trials? Who runs them?

Clinical trials in Canada are most often cooperative projects undertaken by many players including the drug industry, research granting councils, medical community, ethics community and the federal government. When a sponsor generally a pharmaceutical company wants to conduct a clinical trial in Canada, they must apply to Health Canada. In their application, they submit a "protocol" that outlines the objectives, methods and rules by which they will function during the trial. They must also justify that a clinical trial is worth whatever potential risks the drug might have and that the patients will not be exposed to undue risk. Health Canada reviews the application to make sure all the necessary components have been included in the trial and that the scientific methods are sound. The application is also reviewed by an independent research ethics board, for example a hospital review board, who examine the protocols.

Once approved, experienced clinical investigators within the medical community initiate the clinical study under the supervision of the ethics review board, and with the funding of the sponsor. Within the process of clinical trials, Health Canada regulates the science by ensuring that the clinical trial is designed properly, while the sponsor, investigators and research ethics boards oversee the operation of the clinical trials, ensuring that all protocols are being followed. It is the researcher's responsibility to maintain the protocols and gather the data.

Are drugs tested before they get to the clinical trial stage?

Before a new drug gets to the clinical trial stage, it has to be tested in the laboratory, to analyse the drug's makeup, and study its effects on laboratory animals. Only if the results of these initial studies demonstrate potential benefits and show no serious safety concerns, will a clinical trial be considered.

What exactly is a protocol?

Every clinical trial must begin with a set of protocols. Protocols are sets of procedures that ensure the research objectives can be accomplished and make it possible for others to replicate the study. Although a set of protocols will be designed specifically for a drug, there are standard practices in each trial.

Are there different types of clinical trials?

Clinical trials are normally done in four phases, each successive phase involving a larger number of people. Phase I studies, often referred to as "first in humans studies", are primarily concerned with assessing the drug's safety. Testing is usually done in a small number of healthy volunteers, who are usually paid for participating in the study. Phase I trials may be conducted in patients when administration of the drug to healthy volunteers is not ethical. Once a drug has been shown to be safe, it is then tested for efficacy in a Phase II study. These Phase II trials involve several hundred patients who are usually separated into two groups, that are randomized to be as similar as possible in age, gender distribution and medical history. One group of patients then receives the experimental drug, while a second "control" group receives standard treatment or a placebo. Often these studies are "blinded", so that the patient does not know which treatment he or she is receiving. "Double blinded" studies mean that neither the patient, nor the researchers know who is getting the treatment. This ensures that the data collected will not be affected by the bias of a patient or researcher.

Once the safety and efficacy of a particular drug has been shown, it is then tested on a much larger scale (several hundred to several thousand patients) in a Phase III study, to give researchers a more thorough understanding of the drug's efficacy, benefits, and the range of possible negative reactions. Most Phase III studies are randomized and blinded, lasting several years. After successfully completing Phase III testing, the drug is ready to be reviewed for approval.

Phase IV trials are performed after the drug is on the market. These trials relate to the approved indication for the drug and are important for optimizing the drug's use.

How are patients protected during clinical trials?

The interests and rights of patients and other clinical trial participants are protected in a variety of ways and by various players in the clinical trial process. Ethical standards require that participants in a clinical trial be fully informed of the potential risks and benefits associated with the drug, as well as the availability of alternative treatments. This process, known as informed consent, ensures that the participants are aware of their rights, as well as their responsibilities within the study. In order for the trial to be reliable, participants are expected to strictly follow the rules of the study, however, no one is penalized for declining to participate or withdrawing from the study.

Every institution that conducts medical research has a Research Ethics Board, made up of scientists, doctors and members of the public, who will make sure that the rights and interests of the participants are protected.

What happens to the results of clinical trials after they are finished?

Once a clinical trial is completed, the research results are analysed and often subjected to "peer review." Peer review ensures that research is evaluated by experts in a particular field before being published and accepted by the scientific community as valid research. Results from clinical trials are also used to support an application by a pharmaceutical manufacturer for market approval.