Clinical Trials:  What the patient participant needs to know

As patients we are never far from science in its various forms. We look for best-evidence treatment information, collaborate on basic research projects and many of us, altruistically – and with hope, participate as subjects in clinical trials. It's natural then that we should pay close attention to the recent nightmarish scenario created in London, UK, by the Phase I clinical trial for TGN1412, a type of monoclonal antibody developed as a potential treatment for some autoimmune diseases – including RA. Eight healthy young men were enrolled in the trial, two received a placebo and all six that received the test medication suffered catastrophic adverse reactions. An excellent editorial by Michael Goodyear, Dalhousie University, in the March 25, British Medical Journal raises many valid concerns. Click here to access the article. Be sure to scroll to the bottom of the subsequent page to see the article.

The following basic information on clinical trials (CTs) may help you to better understand some of the many issues under discussion.

New drug interventions undergo four phases of clinical trials. The first time a new medication is tried in humans is in a Phase I trial, which examines acute, dose-related drug toxicities. These CTs are usually conducted on a small number of healthy young subjects, but sometimes they may involve patients in studies with interventions that are known to be toxic. (TGN1412 was undergoing Phase I trials.) Phase II clinical trials examine the short-term drug toxicities of new drugs, and to a lesser extent examine how well the drug works on patients. These trials are usually conducted on a small number of carefully selected patients with specific diseases. Phase III clinical trials are what we usually think of when we hear the term 'clinical trials'. These trials are typically conducted as multi-centre trials with a large number of participants, and are designed to determine how well a new drug treats a disease, and to a lesser extent, looks at short term toxicities of the drug. Most of us who have participated in a clinical trial have participated in a Phase III CT. Phase IV trials are also known as post-marketing surveillance studies and are used – when they are conducted – to determine the long-term efficacy and toxicity of already marketed drugs.

All CTs conducted in Canada must be authorized by Health Canada, and must be approved by a Research Ethics Board (REB). Bio-medical REBs have at least five members, two of whom should have a broad expertise in the methods or area of research to be undertaken, one knowledgeable in ethics, one knowledgeable in the relevant law, and one member from the community who has no affiliation with the research institution. It must always be remembered – no matter what the circumstance – that the research subject bears the risks of research.

What should we do as patients who at some time may volunteer to be clinical trial subjects? We are asked to give our informed consent to joining a clinical trial. We should read the information on the consent form and ask questions until we understand it. We should know the name and contact information of the researcher conducting the trial, the pharmaceutical company sponsoring the trial, which REB approved it and how to contact it, if necessary. We should know what phase trial is being conducted, why the trial is being conducted, potential risks and benefits, what happens if we should have an adverse reaction, and what happens if the trial medication produces no apparent results. We should know if we are required to stop taking current medication, and whether we risk not receiving timely treatment by participating. We should also know whether this CT has been fully registered, and how research results – whether negative or positive – will be disseminated to the public. And will we, as a trial participant, receive this information? We should ask if the information about the trial and information gained from the tests to which we submitted during our participation will become part of our medical records. There are times when we may not want this to occur, and this should always be our decision. Also, we should ask how our medical information will be handled, who will see it, and if our identity will be stripped from it. And finally, we need to ask whether there will be any secondary use of our information or tissues such as blood samples taken during the trial. And we must understand that even if we have joined a clinical trial, we can withdraw from it at any time without penalty.

The distinctly Canadian, Tri-Council Policy Statement: Ethical conduct for research involving humans, (TCPS) is used by researchers and institutions that receive funding from the Canadian Institute of Health Research (CIHR). Section 7 provides ethical guidance on conducting clinical trials; Section two provides information on REBs. http://www.pre.ethics.gc.ca/english/index.cfm This site also offers an excellent ethics self-tutorial that will take about three hours to complete, but that can be taken in bits and pieces as you have the time. It's fun to do, and an eye opener! Make sure you log on, and when you finish remember to print out the certificate. The Ottawa Statement on Trial Registration provides information about clinical trial registries and the issues involved. http://ottawagroup.ohri.ca/ Clinical trials are for us and about us. The more we know, the better.