There’s a lot of buzz in the world of research and in the media about clinical trials. Indeed, just a few weeks ago there was a great deal of excitement surrounding our announcement of the MESCAMS trial investigating the safety and efficacy of mesenchymal stem cell therapy in people living with MS. Yet for all the attention they receive, clinical trials are quite often a misunderstood topic. Since clinical trials represent the final link between the laboratory discovery of a therapy, and having that therapy be made readily available to the public, it’s important to clear up any confusion about the subject and ensure the process is transparent and understandable.
In this week’s Research Decoder, I’ll be debunking some of the most common misconceptions about clinical trials. There are already many fantastic resources available online explaining what clinical trials are, why they’re important, and what some of the jargon means (not least of all our very own Introduction to Clinical Trials), so I won’t be retreading charted territory. Instead, I’ll focus on three statements I hear regularly from people who ask me about the ins and outs of clinical trials.
Myth: Clinical trials are used to test risky, completely unproven treatments.
While every clinical trial carries some element of risk, all therapies that reach the clinical trial stage have undergone a long process of rigorous preclinical testing. Preclinical testing is performed in the laboratory using cells, tissue samples and animal models to help researchers determine the mechanisms underlying how a potential treatment works, whether the treatment is effective in modifying a certain disease condition, and whether there are intolerable side effects.
Once the potential treatment passes the preclinical testing stage, which can usually take many years, it can then go on to clinical trials. At this stage, evaluation of the treatment moves through several phases to help researchers answer specific questions about the treatment. These questions can cover a range of topics, such as how safe is the treatment and what are its side-effects, what is the best dose to use, and how effective is it compared to either a placebo or other commonly-used treatment. Each phase acts as a checkpoint, wherein the proposal to conduct the clinical trial must be reviewed, approved, and monitored by an institutional Ethics Review Board (REB). The job of the REB, which is composed of physicians, researchers, and community members, is to ensure that there is sufficient scientific evidence to justify studying the treatment, that the risks of the study are minimized, and that the informed consent document equips participants with the necessary knowledge to make an informed decision.
Myth: Once I sign up for a clinical trial, I’m stuck until the trial ends.
In order to participate in a study, every participant must be provided with detailed information about the risks and potential benefits of the clinical study and sign an informed consent document. The purpose of the informed consent process is to protect participants and ensure that they are armed with all of the information that they need to make such an important personal decision.
Signing the informed consent document, however, does not lock the participant into a contract, and the participant may withdraw from the study at any time and for any reason, even before it is completed. Reasons for withdrawal may include side-effects, inconvenience, or a change in personal circumstances. Sometimes, a participant may choose to withdraw from the interventional portion of the study (i.e. receiving the treatment) but will agree to continue to provide follow-up information (e.g. assessment interviews, imaging scans, blood tests, etc.). In order to ensure that withdrawal from the study is done in as safe a manner as possible, the investigator will attempt to conduct a follow-up safety assessment to determine, for example, that a drug is tapered rather than being discontinued “cold turkey”. In the end, participating in a clinical trial is a completely voluntary process from start to finish.
Myth: When enrolling in a clinical trial, I always have a 50% chance of getting a sugar pill or sham treatment.
“Sugar pills” – capsules containing no active ingredients – and sham treatments are collectively referred to as placebos, and in a blinded study are meant to control for other factors that may influence a disease and to prevent bias when evaluating the effects of the treatment. Placebos, however, are rarely used in a trial when a standard treatment is already available, and many studies will compare the safety and efficacy of a new therapy to the treatment that is already used in the clinical care of a particular condition (i.e. the first-line treatment), ensuring that the risk to each participant is minimized.
For example, the CARE-MS I clinical trial, the results of which were published in 2012, compared the safety and efficacy of Lemtrada™ (alemtuzumab) with the first-line drug interferon beta 1a, rather than a placebo, to determine the more effective therapy for people with active relapsing-remitting MS.
In the case of a cross-over study, all participants receive both the placebo and the intervention; the only difference is the order in which the treatments are administered. MESCAMS is an example of such a study: half the participants receive the stem cell therapy at the beginning of the trial and the other half receive placebo. At the midpoint of the trial, the groups switch to receive the opposite intervention.
In some cases, however, there are no effective existing treatments for a condition and so the “best-case scenario” is to conduct a placebo-controlled trial. For example, there are no proven effective therapies available for modifying disease progression in either primary- or secondary-progressive MS. For that reason, clinical trials evaluating a potential new treatment of progressive MS tend to compare the treatment to placebo.
Let me know your thoughts on clinical trials by leaving a comment below!
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