CLINICAL TRIALS of medications…phases…the pros and cons…the rights of “subjects”…are trials necessary?

Clinical trials make up a large proportion of all clinical research performed at the CHUM. Although clinical trials are conducted on different types of therapeutic and diagnostic procedures, most of them are aimed at developing new medications.

Basic research always precedes clinical research in the development process of a new medication. Thousands of molecules are chemically tested to identify those that contain therapeutic properties most likely to be useful. Some of these molecules are therefore selected and go on to the pre-clinical phase, meaning that their toxicity is tested on laboratory animals. If a molecule appears to be promising for human application, it must then be tested in clinical research where its effectiveness and toxicity will be verified.

A clinical study is in fact a series of procedures that have been specifically elaborated to study a particular aspect of a medication’s effect on a population of well-defined patients. Clinical studies follow a strict methodology. Several trials must be carried out in a pre-established order before governmental control agencies can accept a molecule as a medication for humans.

Every clinical study is part of one of four successive phases. The first three must be performed before a product can be commercialized.


Phases

Phase I: Kinetics (evolution in the organism over time), toxicity and human tolerance to the product are tested in this phase.  A very small number of healthy subjects (between 20 and 80), or patients for whom all other treatments have been ineffective are placed under constant medical observation.

Phase II: The objective here is to evaluate the therapeutic action and toxicity of different doses of the product on a small number of people (usually a few hundred). The minimal dosage needed to obtain a therapeutic effect as well as the maximal non-toxic dosage for humans are determined.

Phase III: Experimentation on the therapeutic activity of a given product is extended to a larger number of subjects (often hundreds or even thousands) to compare it to standard treatment, if one exists, or to a placebo if there is no reference therapy.   Government agencies such as Health Canada’s Therapeutic Products Directorate and the U.S. Food and Drug Administration that are in charge of approving medications then analyze the results obtained during these first phases and authorize or refuse the product’s commercialization and establish guidelines regulating its use.  Laws also govern the process itself.

Phase IV: Companies manufacturing the product are obligated to perform “post-commercialization” studies once the product is on the market.  The medication’s secondary effects can therefore be observed on a larger population and in normal-use situations. 


The Pros and Cons

People choose to be “subjects“ in a clinical trial for different reasons.  For some, it is a way to contribute to the advancement of science.  For others, it is chance to obtain a product they would not normally have access to.  Some people appreciate the close medical attention they receive during the project.   Others see it as a way to receive free investigative procedures and medications.  Participation in a clinical study must always be voluntary.   Some subjects may receive compensation for certain expenses, but none should ever receive payment as an incentive.

The main disadvantage to participating in a clinical trial is the risk of taking a product of which all the beneficial effects and secondary effects are not yet known. Participants also run the risk of receiving an inactive product (a placebo) and may therefore have to undergo frequent evaluations.  That said, there are no particular pre-requisites.  It is usually a doctor who will suggest participation in a clinical trial. To do so, the doctor or one of his or her colleagues coordinating the clinical study must be a researcher, and the study must pertain to the pathology for which the person is being treated.


The Rights of ¨Subjects¨

When a doctor thinks that a patient is eligible to participate in a clinical study, he or she must:
• explain the objectives and expected benefits to the patient;
• explain the treatment that is to be administered as well as any possible secondary effects;
• explain the monitoring examinations that will be conducted.

Written consent must be obtained.  Once the clinical trial has been explained, the patient must be given a sufficient amount of time to decide whether or not he/she wishes to participate. Refusal to enrol in a clinical trial must not jeopardize the doctor-patient relationship, or the quality of the treatment that is to follow.  Even after accepting to participate in a clinical trial and having given written consent, the patient can reverse his or her decision at any time without fear of repercussions on the quality of future medical care.


Are Trials Necessary?

Clinical trials not only allow us to study new medications, they also give us a better understanding of a disease’s characteristics and help us to determine which types of patients will benefit most from these medications. In short, they are essential to getting approval for all new molecules: no trials, no new medications.  In conclusion, these trials open up the way to questioning how things are done and help to establish practices that are based on fact (factual medicine).