Introduction to Clinical Trials

Approximately 2,000 MS-related research papers are published every year - that's about seven studies each day.

Often the results of one study seem to contradict another study. How do you make sense of these scientific findings? The following information is to help put the scientific findings you encounter in context.

Whether or not a study can be considered credible and scientifically sound depends on many factors, including the type of study conducted, the expertise of the researchers, the statistical analyses used and the rigour and quality of the external independent review of the results.

Basic research phase

Many hypotheses regarding possible treatments for MS begin in the lab. In these studies, the treatments are often assessed at a very basic level through the use of cells and cultures as well as an experimental, animal model of MS called experimental allergic encephalomyelitis (EAE) in laboratory rodents. These studies allow for a preliminary evaluation of the possible benefits of a treatment, as well as some idea of the safety and risks of that treatment. If the study is promising, it might move after further study into clinical trials.

Clinical trials

Clinical trials are research studies that involve testing or studying a treatment in people to see if it is safe and effective. Each phase of a clinical trial follows a protocol and has a specific goal. The information gathered in a trial is used to build knowledge about the new treatment and support the subsequent phases of the research process.

Steps for launching a clinical trial

Defining the study concept, securing financial resources to support the study, and seeking out new
collaborations with various experts who haven’t necessarily worked together before.
Developing a detailed protocol or blueprint of the study’s scope, type and number of participants to recruit, frequency of visits or scans, data to be gathered, and specific step by step procedures for each phase of the study to ensure that each participant undergoes the same protocol.
Developing one or more “Informed Consent” documents. These are explained to participants, and they are required to sign them indicating that they understand what is entailed and agree to being involved in the study.
Applying for approval to begin the study from an Institutional Review Board (U.S.) or Research Ethics Board (Canada), including approval of the Consent Form and other plans. This step is required by governments to ensure adherence to guidelines related to the protection of human subjects in research.
Establishing a monitory committee to provide oversight and feedback on any research or safety issues
encountered.
Recruiting and screening participants and obtaining their informed consent.
Conducting the study, including performing scanning, clinical evaluations and other data collection. Some protocols require repeated scans or additional scans, meaning additional clinic visits.
Gathering and evaluating the cumulative data from all participants.
Communicating and publishing results.

Clinical trial phases

	Purpose	Study Design	Participants
Phase I	To determine safety and tolerability of treatment.	Usually open-label (both the researchers and participants know what the participant is taking as a medication).	20-80
Phase II	To look more closely at safety and efficacy and how the treatment affects the body.	Usually includes control and non-control groups are often double-blind.	100-300
Phase III	Last step before treatment is submitted to Health Canada. Done to confirm treatment's efficacy, monitor side effects, and compare it commonly used treatments.	Can last up to five years or more and are randomized, double-blind and placebo-controlled trials.	1000-3000 (multi-centre)
Phase IV	Once Health Canada has approved treatment, this study is often done to identify further information about risks, benefits, side effects, and optimal use.		Several hundred- several thousand

What is a control or control group?

A control is the standard against which experimental treatments are evaluated. In Phase II and III clinical trials, one group of patients will be given an experimental treatment, while the control group is given either a standard treatment for the illness or a placebo. A control is part of the criteria of evidence-based medicine.

What is a placebo?

A placebo is an 'inert' pill, liquid, or powder with no active ingredients. In phase II and III trials, experimental treatments are compared with placebos to assess the experimental treatment's efficacy and safety.

What is a 'sham' procedure?

A sham procedure is a placebo form of a procedure. A trial participant may receive a 'sham' or 'fake' surgery, injection or other medical procedure, so that there is a control group.

What is the placebo effect?

The placebo effect is a scientifically recognized, measurable reality. There are measurable changes that occur in the brain when someone is given a placebo that they expect or hope will benefit them. The effect tends to be the greatest in symptoms with a subjective component, such as pain, but it can affect physical function too.