Your Guide to Clinical Trials

Researchers begin with a question or questions that need answers. In MS, they may want to know:  

• Whether a new medicine reduces relapses or slows progression better than a placebo or another already approved medicine and 

• Whether the new treatment is safe in terms of its side effects and risks  

Before a new medicine is tested in clinical trials involving people, pre-clinical research is done in the laboratory and with laboratory animals. These studies provide information about how effective the medication is in treating an animal model of MS (EAE) and what side effects it causes in animals.   

Once the pre-clinical research has been reviewed and approved by the FDA, clinical trials in people determine the correct dose of the medicine, the benefits of the medicine in a specific population, and the safety of the medicine. Clinical trials are done in phases and the results from each phase are reviewed by the FDA before the next phase can begin.  

A university or community review board, known as the Institutional Review Board (IRB) must grant approval for the trial to be conducted at each trial location. The IRB’s responsibility is to review the clinical trial medicine and trial procedures to ensure the safety of every participant. IRBs are made up of healthcare professionals, other local professionals, people with the condition, and others in the community.  

In clinical trials of new medicines, an agency such as the National Institutes of Health (NIH) may fund (sponsor) the trial, but typically a pharmaceutical company sponsors large clinical trials.  

Pre-clinical research may be done by university researchers and may be funded by various agencies such as the National MS Society or the NIH. Each agency funds diverse types of research. Pharmaceutical company researchers may also conduct pre-clinical research. Pre-clinical research and the phases of clinical trials can take many years and the cost is very high. It may cost 1-2 billion dollars to conduct all the research needed to establish the benefit and safety of a single drug. 

• Phase 1 trials include 20-100 healthy volunteers, or people with the disease or condition, who are given the new medicine to determine the optimal dose and identify any safety issues. These trials generally last several months. 

• Phase 2 trials include up to several hundred participants and last from several months to 1-2 years. Researchers are looking at side effects and benefit. In MS, MRI findings are important measures of benefit. Many of these trials are conducted at multiple locations 

• Phase 3 trials are much larger, with three hundred to several thousand participants. These trials evaluate safety and side effects as well as efficacy or benefit. More than one phase 3 trial is often needed to establish benefits and safety. Trials are conducted at many locations around the world. Results from Phase 3 trials determine whether the trial sponsor applies to the FDA for review and approval. 

• Phase 4 clinical trials, which are done after the medicine receives FDA approval, collect longer-term data and answer questions about the medicine that were not answered in the clinical trial. 

Before any clinical trial procedures are initiated, your consent, or agreement to participate in the trial must be obtained. This is the informed consent process. 

During informed consent, an investigator or staff person on the research team will review the consent form with you to be sure that you have a clear understanding of the medicine or device under study and all procedures involved: 

• Schedule of in-person and/or virtual visits  

• Tests you will undergo such as MRIs or blood samples 

• Information about how the medication is administered (by mouth, injection, infusion) and any known side effects 

• Information about whom to call if you have any concerns 

• Reassurance that you can withdraw from the trial at any time, without impact on your care 

Before any clinical trial activities take place, you will be asked to sign the form – but only if you are clear on all responsibilities and procedures, have had all your questions answered, and have decided that you wish to participate. Your signature does not make the consent form a legally binding document; it only verifies that you understand what you have signed. 

Your willingness to volunteer is a very important first step but does not guarantee that you will be able to participate. 

Researchers develop criteria for clinical trial participation. These are known as “inclusion” and “exclusion” criteria.  

Inclusion criteria are the specific characteristics required to be included in the trial. In MS, these criteria usually include a confirmed diagnosis of MS, a type of MS (relapsing or progressive), years with MS, MRI findings, level of disability or relapse history, as well as sex and age within a defined range. 

Exclusion criteria are characteristics that are not allowed in the clinical trial. These might include the presence of other illnesses or other medications, people out of the age range, people with too little or too much disability, or the inability to understand the trial procedures and responsibilities. 

These criteria are essential to ensure that the participants are sufficiently alike to determine whether the medication works in that particular group. In the case of MS, a trial of a medicine for relapsing forms of MS would not include people with progressive MS since the medication could perform differently in those individuals and make the results difficult to interpret.  

So, do not be discouraged if you do not meet the criteria for a particular trial. In all likelihood,  you will meet the criteria for another trial.  

As trial volunteers meet criteria and are entered into a clinical trial, they are assigned an identifying number. and are randomized, by computer, to be in the group that receives the new medication or the group that receives the placebo or active comparator.  

Randomization is necessary to ensure that group selection is without bias – which means that the treatment and control groups are equivalent and unlikely to respond differently to the intervention.  

Most clinical trials are “double-blind,” meaning that at no time during the trial do the study participants or the clinical research staff know who is receiving the new medication and who is receiving the placebo or comparator drug. This “blinding” of all study participants is also essential for ensuring the absence of bias in the trial results.  

Clinical trials follow a specific study plan, called a protocol, which is developed by the researcher or manufacturer and approved by the IRB. Clinical trials are conducted over a specified period, such as weeks, months, or years.  

During the clinical trial:  

• Volunteers are asked to take the clinical trial medication at specific times and will be asked to come to the clinical trial site or participate in virtual visits at specified dates and times.  

• During the visits, volunteers are asked: how they are feeling, if they are taking the study medication as directed, if there are any new MS symptoms or any other medical issues that have occurred since the previous visit.  

• Several tests may be done such as a neurological exam, MRI, blood tests, or vision and walking tests. Participants may be asked to complete questionnaires about symptoms.

Sometimes, after everyone has completed the study, the sponsor may invite everyone to participate in an “open – label extension.” This means everyone who participated – treatment and control group participants – is given the new medication. Clinical trial visits and tests may continue for several more months or even years. In this extension, more can be learned about benefits, side effects and any risks. 

It is especially important that clinical trial include participants that are representative of the people who have the disease or condition. So, if the population includes different races and ethnicities, ideally, people from these groups should be represented in the clinical trial population. Historically, however, this has not been the case in many clinical trials. 

There are many reasons for the lack of diversity in clinical trials, including limited healthcare access, lack of information, transportation issues, child care, family and job responsibilities.  

Another reason is lack of trust that the research process is safe, transparent, and fair. In the 20th century, there were several instances where people of color were unknowing participants in clinical trials. There was no informed consent and no oversight to ensure that people were fully informed and treated fairly and safely. They were not made aware of the risks involved or given any opportunity to stop their participation. Deaths occurred due to these unsafe practices. These instances were tragic and should never have been allowed to occur.  

Today, many safety procedures and guardrails are in place so that participants are informed volunteers with responsibilities, but also with rights. 

Clinical trial participation is a personal decision. If you are interested or just have questions about clinical trials, please discuss them with your MS doctor, nurse practitioner or physician assistant. Additional information can be found at  

https://www.clinicaltrials.gov 

https://www.fda.gov