Director of Ethics and Spiritual Care
Toronto Rehabilitation Institute
Marleen Van Laethem
Toronto Rehabilitation Institute
What is a major misunderstanding people have about clinical trials?
A clinical trial is a research study testing a new potential treatment. “Therapeutic misconception” is the name ethicists give to the misconception or confusion people have that what’s being offered is always therapeutic (or for their benefit). Let’s say, you have been newly-diagnosed and your healthcare provider says, “These are the current available treatments. They all have some potential problems or side-effects; however, we have a research study looking at something new.” The patient may think, these are all potential therapies for me, but if they look more closely at the details of the clinical trial, they may find that the study is going to compare a new treatment against placebo, which is essentially a non-treatment. It is important that people read the details of clinical trials very carefully.
Where does conflict of interest arise?
One form of conflict of interest is known as a tension of obligations. A physician-researcher wears two hats: As a physician, the primary obligation is to recommend the best treatment for the patient. But as a researcher, the primary obligation is to the integrity of the study, which could mean that half the patients will go on placebo as a control and the other half will get the active new substance. The patients on placebo may later wonder: Why did my doctor put me in that group? However, researchers typically don’t have control over that. Participants are assigned to groups through mass randomization to try to eliminate bias.
Conflict of interest may also relate to financial incentives. A researcher may have a patent on a new molecule or new device that is being tested. He/she may accept speaker’s fees, or act as an advisor to the company sponsoring the research. In cases like these, financial interests may influence judgement. An interest in making money shouldn’t take precedence over sound research principles or the obligation to care for patients, and most of the time the potential for conflict will be manageable with appropriate disclosure. However, financial interests should be described in the informed consent document because they may affect a participant’s desire to be involved in a trial.
What is the purpose of informed consent?
“Informed consent” means providing people with all the information they need to make a full decision concerning whether they want to be in a study. Many ethicists refer to it as “informed choice.” It has to be voluntary. You make a choice based on all the information that is relevant to you. The information should include the procedures you have to undergo, the time commitment, the known side-effects and any other potential harms. These may include physical harm, psychological harm and, in this computer age, informational harm. For example, if participation in a genetic study could have insurance or employment implications for the participant, that risk should be spelled out in the consent form, in plain language, so that people know there is a potential risk to their privacy.
Is the informed consent document a contract?
No. Contracts have binding qualities. They impose obligations. Informed consent documents are not binding at any stage. Participants must be able to withdraw from a trial without damaging the relationship with their clinical team and without offending the researchers or upsetting the hospital or organization sponsoring the research.
Can a trial participant withdraw at any time?
In principle, you can withdraw from a study at any time. However, if a study includes a surgical procedure, and the procedure has already taken place, the surgery cannot be undone. A person can say: “I don’t want to continue with this study. I don’t want you to continue collecting my data and I don’t want my data being used in your research analysis.”
Is the use of placebo ethical?
Many hold the view that when there is an established effective therapy for a condition it would be unethical to place some participants on a placebo. Ethically, it is easier to defend comparing an experimental drug against the current established effective therapy. If researchers believe that it is essential to compare the experimental drug against a placebo they must meet stringent conditions. (It may be argued, for example, that a sub-set of patients find current treatment intolerable or ineffective or there may be no other way to isolate the effects of the new drug.)
Another way that a placebo could be used is to add it onto existing treatment. If there is an established effective therapy and there are two arms in the trial: group A gets the established effective therapy plus placebo and group B gets the established effective therapy plus the experimental drug. In this scenario, the placebo arm is not placed at a disadvantage.
What happens if the trial reveals new side-effects?
Those running trials are obliged to share new information concerning side-effects which may affect research subjects’ desire to continue to participate.
Should participants have access to beneficial treatment after a trial ends?
People often enrol in trials hoping to get early access to experimental treatments. Treatments can be expensive but in clinical trials they are usually provided free of charge. If a research participant finds an experimental treatment to be beneficial, he/she may want to continue taking the treatment until it is Health Canada-approved and available on the market. Some may even argue that they are owed access because they have placed themselves at risk by participating in a trial. At minimum, the informed consent form should state clearly whether or not the person will have access to the treatment after the trial concludes. Researchers don’t want to make promises that they can’t keep. Also, there is no guarantee that the treatment will be found to be effective.
Can a trial participant sue?
If people have been negligent in the way they conducted the trial, or if the research ethics board has been negligent in reviewing the trial proposal, then trial participants can exercise any and all of their legal rights. You don’t waive your legal rights by agreeing to participate in a trial.
World Medical Association Declaration of Helsinki
(Ethical Principles for Medical Research Involving Human Subjects)