Introduction to Clinical Trials

What are clinical trials?

A clinical trial is a type of research study that involves human volunteers or participants. Clinical trials are designed to answer critical questions regarding the safety and efficacy of a specific intervention in order to determine whether it will be better, worse, or no different than current interventions at diagnosing, preventing, or treating a particular population or disease. The goal is to understand what intervention works best, taking into consideration factors such as age, sex, racial & ethnic background, stage and type of disease.

These interventions can include drugs, natural health products, lifestyle modifications (i.e., diet, exercise), rehabilitative practices, diagnostic or surgical procedures. Clinical trials can test novel interventions that have never been tested before or, repurposed interventions that have previously been tested in other health conditions. Often the intervention being tested is compared to the current standard of practice, to placebo or sham interventions that do not include the therapeutic ingredient or technique, or to no intervention.

What are the different phases of clinical trials? 

Pre-clinical research phase

A research question regarding a possible intervention for MS is often initially tested in a laboratory setting. This testing is done using cells and animal models of MS. One such model is called experimental autoimmune encephalomyelitis (EAE) in laboratory rodents. EAE animal models can replicate key features of MS in humans, including inflammation and demyelination, relapsing-remitting cycles, and chronic disability progression. Studies at this pre-clinical research phase allow for a preliminary evaluation of possible benefits as well as some indication of the safety and risks associated with the intervention. If the intervention is promising, it may then move further into clinical trials.

Clinical trial phase

Clinical trials consist of four phases (Table 1). Each phase of a clinical trial varies based on the purpose and size of the group that is receiving the intervention. In general, early clinical trials focus on establishing the appropriate dose that is safe, tolerated in the body, and produces a positive response. Later clinical trial phases generally test the established dose in larger groups of people to determine if significantly more people will benefit from the intervention and to identify any adverse side effects. Extension trials assess the long-term safety and efficacy of an intervention and include people from earlier clinical trials who sign on to continue the intervention.

Each clinical trial is different depending on factors such as the type of intervention, who the intervention is intended for, what the intervention is trying to achieve, and how the intervention’s success is measured. The information gathered in each phase is used to build knowledge about the intervention and support the subsequent phases of the research process. A clinical trial only progresses to the next phase when positive results are received from the previous phase.

What are the steps to 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 and type, number of participants to recruit, frequency of visits or MRI scans, data to be gathered, and specific step by step procedures for each phase of the study to ensure that all participants undergo the same protocol.
• Developing one or more “Informed Consent” documents. The informed consent process involves providing participants with the relevant information on the study, to help them understand the information, answer any questions they may have, and give them time to make an informed decision on their participation in the clinical trial. The participant is then required to sign the informed consent document indicating that they understand what is entailed and agree to being involved in the study.
• Applying for approval to begin the study from a Research Ethics Board (Canada) or an Institutional Review Board (U.S.), 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 or additional MRI scans, meaning additional clinic visits.
• Gathering and evaluating the cumulative data from all participants.
• Communicating and publishing results.

Participating in clinical trials and other MS-related research studies 

Who can participate?

Clinical trials have specific eligibility criteria outlining those who can participate in the study. Inclusion criteria outline factors that qualify a participant for a study, while exclusion criteria outline factors that disqualify a participant for a study. These eligibility criteria are based on participant characteristics including, age, sex, type/stage/duration of disease, treatment or medication history, and additional comorbidities.

People who are interested in participating in a clinical trial are encouraged to speak with their healthcare team to determine if they are eligible for a study and to ensure that participation will not hinder their current treatment and care.

Participation in a clinical trial is not complete without informed consent. An informed consent form detailing all relevant information about the clinical trial is provided to participants, with ample time to read and ask questions in order to make an informed decision. Upon agreement, the participant signs the form, but can still withdraw their consent at any point during the clinical trial.

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.

Questions to ask before participating in a clinical trial

• What intervention is being studied? What is currently known or unknown about the intervention?
• What are possible benefits and risks associated with the intervention (short-term, long-term)?
• How will the study be controlled?
• What measurements/assessments will be involved in the study?
• How frequently will I have to visit the study site and for how long?
• What data will be collected and how will it be shared?
• What costs will be covered/reimbursed?

For additional resources about participating in a clinical trial, visit the Clinical Trials Ontario page – here.

How to determine if a clinical trial is credible?

Whether or not a study can be considered credible and scientifically sound depends on many factors, including the following:

• Type of study being conducted
• Expertise and qualifications of the researchers (i.e., affiliation with an academic or clinical institution)
• Revision and approval by a regulator agency (i.e., Health Canada, FDA), a research ethics board (REB), and/or the affiliated institution where the study is taking place (i.e., university, clinic, hospital)
• Methods of data collection and analysis
• Rigour and quality of the external independent review of the results

Where to find more information on currently recruiting clinical trials and MS-related research? 

• Health Canada Clinical Trial Search – a search tool to assist Canadians in finding specific information on a clinical trial related to their medical condition.
• ClinicalTrials.gov – a public database by the U.S. National Library of Medicine of clinical trials from around the world.
• Clinical Trials Ontario Search Tool – a search tool to assist Canadians in finding clinical trials across Canada (not only Ontario) that are relevant to their medical condition.
• Clinical Trials Quebec – a bilingual, free, and user-friendly search tool to assist patients and caregivers residing in Quebec in their search for clinical trials.
• The MS Society of Canada’s Research Portal – a platform to promote research studies and clinical trials open to Canadian participants. Researchers may apply to have their research study posted on the Research Portal to assist with study recruitment. Once an application is approved by their institutional research and ethics board, the study may be shared on this site. The Research Portal does not post studies or trials from pharmaceutical or biotechnology companies, marketing research firms, or other for-profit enterprises.

Understanding clinical research terms

What is an open label versus a blinded study?

In an open-label study (usually phase I), both the researchers and participants know of the intervention the participant is receiving (i.e., experimental drug or placebo). In a blinded study (usually phase II-III), either the participants do not know (single-blinded) or both the participants and researchers do not know (double-blinded) the intervention the participant is taking, until the clinical trial is over.

What is randomization?

Randomization is the arbitrary assignment of participants to different intervention groups of the study to avoid potential bias in the results. This usually occurs in phase II-III clinical trials, when two or more interventions are being compared (for example, a new intervention versus a current intervention approved for MS). 

What is a control or control group?

A control is the standard against which experimental interventions are evaluated. In Phase II and III clinical trials, one group of participants will be given an experimental intervention, while the control group is given either a standard intervention for the health condition or a placebo/sham. A control is essential to compare the effect of the new intervention against a standard.

What is a placebo?

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

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.

What is a 'sham' procedure?

A sham procedure is analogous to a placebo drug. A trial participant may receive a 'sham' or 'fake' surgery, injection, or other procedure that removes the therapeutic step of the procedure being evaluated, as part of the control group.