About Clinical Trials

Before getting involved in a clinical research trial, it’s important to understand exactly what you are signing up for. Many clinical trials are placebo-controlled, randomized and double blind. What does this mean for you and your child?

Placebo-controlled

A placebo is a fake, harmless version of a drug that looks like and is taken exactly like the actual drug. Volunteers are assigned to either the experimental group that gets the intervention or the control group that receives the inactive substance. Why is this necessary? Often, a patient will perform better if they think they are receiving a treatment that can help them. This way, there is no psychological advantage for the patients receiving the experimental product over and above the patients who are not getting it.

Randomized

Patients in a clinical trial are placed into separate groups at random. This means that patients are not categorized by any specific characterizations when put into the different groups in a trial.

Double Blind

A single-blind clinical trial would mean that the patients/caregivers do not know which group they have been placed in for the trial. In the double-blind clinical trial, both the patient/caregivers and the researchers at the trial site do not know who is in which group. Usually, third-party study coordinators are the only ones who know which group each patient is in. These people typically do not have anything to do with taking measurements or tracking progress. This is done to prevent researchers from being biased in recording the progress they see in patients if they are expecting to see a change because they know who is receiving the experimental drug.

If the researchers knew who was getting the actual treatment or who was getting more of the treatment, they might expect certain patients to do better than others. This could affect how they record data or how much they encourage patients during testing. This could result in incorrect data being collected, making it seem like treatment was beneficial when it was not.

Designing a trial this way allows for a more accurate evaluation of the experimental treatment. By using a placebo, the results are free from favouritism (unbiased), and there can be an accurate comparison between the drug and the current standard of care. It is the best way to determine to which degree a treatment is helpful.

Choosing to participate in a clinical trial is often a difficult decision. While there are many potential benefits, there are also many potential risks. As a result, the decision shouldn’t be taken lightly. It’s important you understand the potential risks and requirements before agreeing to participate in a trial. Be it time away from work, driving long distances or dietary restrictions, there are a number of demands placed on patient families during clinical trials. The more fully aware you are of these commitments, the better able you will be to make the best-possible decision for your child and family.

Benefits

If a trial is successful, patients will be able to receive the newest treatment for their condition as soon as possible. In a disease, like Duchenne, with few interventions currently available, this is an especially powerful motivator. Participants in the clinical trial will often have access to the treatment much sooner than anyone else.

In addition to having access to the treatment during the trial, patients will usually also have access in the period between when the clinical trial ends and when the treatment is approved by governmental regulatory bodies. This means, if a clinical trial is successful, patients will have access to the new treatment long before they are even available. Participating in a clinical trial can also be very rewarding because you are able to contribute to your disease community by helping cultivate important knowledge about new treatments, the natural history of the disease or new procedures. Even if a trial is not successful, the information gathered will be used to improve future trials and scientific approaches.

Participating at a trial site other than your home site will also give you access to other medical teams and doctors for second opinions about how your condition is progressing. It also usually means that your condition is being monitored more closely. You may even have access to testing that you would not be able to access in your home clinic such as MRI.

Risks

Participating in clinical trials always involves potential risks. There is a risk the therapy or treatment might not work. Additionally, although your safety is the top priority, there may be unexpected serious or life-threatening complications from participating in experimental treatments. Your clinical trial team should discuss any possible risks or side effects that could occur and will be monitoring each patient very closely. It is very important to listen to all directions and instructions you receive from the team. If you are worried or have any concerns about this, discuss them with the clinical trial team before you sign the consent form.

Participating in a clinical trial may require more time and attention than standard treatments would. For example, you may need to visit study sites, more blood tests, more procedures, hospital stays or complex dosage schedules. Clinical trials require a large time commitment and require a lot of travel, depending on how far you live from the study site. You may need to take time off school, work and away from your family to complete the study visit appointments.

You may be participating in a placebo-controlled trial. This means you may not be given the study drug but a fake, harmless version of the drug. The study team will explain this to you, and you will know if there is a chance you might be given a placebo before you agree to sign your consent to participate. However, you will not know if you are taking the placebo drug while participating in the study. It is important you understand this as it may impact your decision to participate.

While you may not get access to the drug at the beginning of the trial, you will usually get access to it later in the clinical trial. Or, if the trial is successful, you will often be able to have access to it once the trial is completed and before it is approved for widespread use. A placebo-controlled study is a requirement of drug regulatory authorities and, unfortunately, remains unavoidable. We understand how frustrating it may be to realize your child has been designated to the placebo group, but their participation is still a key part of the study.

When determining if a clinical trial is right for you, researchers in charge of the clinical trial are there to answer your questions about the risk and benefits of participating before you agree to the trial. Do not be too shy to ask all your questions. There is no such thing as a silly or wrong question when making such an important decision.  

Sign a Consent Form

Before being part of a clinical trial, there are several things we recommend you consider to ensure you are as prepared and informed as possible:

• Make sure you read and understand all the documentation provided to you
• Make a list of any questions you may have
• Use your opportunity to meet with the investigator or a clinical trial coordinator to discuss what will be required and answer your questions
• Once you fully understand what the trial is about and what will be required of you, you will be asked to sign an informed consent form before starting the study. Ensure you are completely clear on what the form outlines.
• By signing the form, you are indicating you understand what is involved, all your questions have been addressed and that you acknowledge the risks of being part of an experimental clinical trial
• Take your time to understand and read this form before signing.
• If your son is seven years or older, he may be asked to sign an assent form. This is similar to a consent form but with more straightforward language to help your son understand the purpose of the study and what will be asked of him.

Complete a Screening Visit

Before starting a clinical trial, the doctor running the trial (who may not be your doctor) or the study staff will have to ensure that you are eligible to join the clinical trial. They will ask you many questions and may ask you to provide recent medical reports such as your last lung or heart function tests. In some cases, they may have to perform these tests and additional tests to decide if you meet the inclusion and exclusion criteria. This is called the screening process.

Complete a Baseline Visit

If you are accepted into the trial, your first visit will be what is called a “baseline” visit. Usually, researchers will use a series of tests throughout the clinical trial to track everyone’s progress throughout. Data must be collected over time to show whether there is improvement in patients who are given the experimental treatment. For a drug to be approved for use, there must be evidence that there is a benefit to patients who are on the treatment. The first visit is important because the researchers can gather data on how you do on these tests before you are given the treatment or placebo.

First Study Visit

Once you have signed the consent form, completed the screening visit and baseline visit, the study will start. You will be required to attend all the trial site visits as per the schedule the clinical team provides you. If you are going to a trial site far away, this may require a lot of time away from home. Depending on the trial, it could be a great deal of commitment for both the patient and their family. Usually, studies require you to receive the investigational treatment and undergo a series of tests before and/or after receiving the treatment. If at any point you decide you no longer want to participate in the trial, you will need to discuss this with your trial team and follow their instructions on how to leave the study.

Different clinical trials will involve different types of interventions. Some investigational drugs will be given orally and usually include taking the medication once a day or more. Others may be administered when you go for a trial site visit and may be given as an injection or through an IV (intravenous injection given through a small tube directly into the vein). The types of testing you will have to undergo also vary from trial to trial. Some examples of tests typically done in clinical trials for Duchenne muscular dystrophy include drawing blood, measuring cardiac and respiratory function, along with additional functional tests, such as the 6-minute walk test, 100-meter run, time to rise or the four-stair climb.

The study team will let you know when the trial has ended. Depending on the results, you may be able to stay on an extension trial and continue taking the drug. If the study has finished and there is no extension trial, the study sponsor may be willing to continue providing the medication after the study has been completed while you wait for the drug to be approved in Canada. If the drug is not found to be effective or it is found to be unsafe, the trial will end, and there will not be further access to the drug.

For many clinical trials, the sponsor may offer reimbursement for costs such as gas, airfare or hotels. In the event that travel and other expenses are not paid for, the family or individual may have to take on some of these costs.

Safety in Canada

In Canada, sponsors, such as pharmaceutical companies, must get approval from institutional ethics committees for their clinical trials. For example, if you were involved in a clinical trial at The Hospital for Sick Children, that trial would have to be approved by an ethics committee at SickKids. These institutional ethics committees follow an ethics policy that was developed by three federal agencies:

• The Canadian Institutes of Health Research (CIHR)
• The Natural Sciences and Engineering Research Council of Canada (NSERC)
• The Social Sciences and Humanities Research Council (SSHRC).

These ethics councils are usually made up of several individuals with a variety of backgrounds, including members of the public, members who are knowledgeable on the topic of ethics and members who understand Canadian biomedical research laws.

The role of an ethics board is to review proposed research trials to ensure they are designed to be as safe as possible. For example, they review and approve the safeguards in place to ensure the well-being of the patients in the trial is being monitored over the duration of the trial. They also ensure that the trial procedures meet the requirements for reporting unexpected adverse or serious adverse events or medical complications during clinical trials in Canada.

In the event that your or your child experience an adverse event while participating in a study, regardless of how mild and whether or not you feel it’s related to the study drug, you must report it to the study team as soon as possible. If a serious or life-threatening event occurs, which is thought to be related to the study drug, all patients in the study must be informed to ensure their ongoing informed consent. This information also must be made publicly available. If, at any time, a patient does not feel comfortable participating in the trial, they can talk to their clinical trial team about being removed from the study.

If you are interested in participating in a clinical trial in another country, their processes and requirements might be slightly different. While most countries have similar laws and guidelines designed to ensure that patient safety is a priority, it’s essential you are clear on any distinctions that may affect you.

Ethics reviews and approvals can sometimes take a long time, this can often delay start dates to clinical trials.

Privacy in Canada

The Canadian government has very specific guidelines about how the sponsors should go about protecting patient information and privacy. Sponsors must have a reliable system for ensuring that data is protected and that the trial results are reliable and not tampered with. Any electronic data processing systems must be validated to ensure they are accurate, reliable and that patient data is secure. All patients in a study are given a study number so their recorded results and information cannot be linked back to them. 

While the trial is ongoing, your results will not be shared with you, as this might compromise the outcome of the study. For example, it may reveal if you were in the treatment or placebo group. Once the study is complete, the results are locked, and you will not be able to access your results. However, sponsors will share the general study results in a publication that you will be able to access. Your personal information will not be made available to you unless under exceptional circumstances. Currently, patient advocacy groups, like ours, are working on trying to change this, so patients can gain access to their results. At the same time, it must be done in a way that does not compromise the results of the study and affect the drug’s approval by our regulatory agencies.

As the parent of a child potentially joining a clinical trial, you will have to give your consent or permission for your child to participate in a clinical trial. This part of the process is called “informed consent.” Informed consent means you should be fully informed about what will be involved in the clinical trial and have all your questions answered before agreeing to participate.

It is important your child understands and is part of the decision-making process. It’s also essential they are willing to participate. Some days will be tough for your child and their buy-in will help them – and you – stay focused on why your family chose to get involved.

Assent is the word used when a child agrees to participate in the study. Just like you, they should understand what will happen in a clinical trial before either of you give your consent. Your child should also have a clear understanding of what they are agreeing to and feel comfortable asking questions. The clinical trial coordinator should explain everything in ways that are appropriate to your child’s age before asking for their assent.

Assent is “affirmative agreement to participate in research,” which means the child should clearly communicate they agree to participate. If a child does not object but still does not clearly agree to participate, this is NOT considered assent. As a parent, you want to do whatever is best for your child. Most likely, you will do a lot of research and ask many questions before you agree to enter your child in a clinical trial. While you are doing your best to protect your child, remember that part of this involves communicating with your child about the trial and not making any assumptions or decisions on their behalf.

To ensure your child has the opportunity to participate in informed assent, you may want to ask questions such as:

• Do you understand what the doctors are telling you?
• Do you feel like you can talk to your doctor about things that worry you?
• Do you know why your doctor wants you to take this medicine/this test?

If the answer to any of these questions is “no,” consider working with a Child Life Specialist and/or ask the doctors to clarify things and reiterate them to your child in ways you are both comfortable and confident they understand. It is important to know that some researchers will have more of a commitment to ensuring children are engaged in the assent process. If you do not feel like your child is being involved enough in this process, you should advocate for them. Your child deserves to be and feel respected and heard.

Before agreeing to allow your child to participate in a research trial, you may want to ask the research team questions such as:

• How will you explain the child’s illness and proposed treatment to them?
• How will you explain procedures to the child to help them understand what it will be like from their perspective (i.e. “medicine goes into your arm, a machine that takes pictures of your insides, etc.)?
• How will you explain how the medicine or procedure will affect their body and the impact it could have on their illness?
• How will you communicate that if they choose to, or their parents decide, they can end the treatment?

It is important to allow children to have a say in what happens to their bodies. Studies have shown that involving children at an appropriate decision-making level reduces anxiety and helps prevent their experience of medical trauma. Involving children in the decision-making process and answering their questions shows them respect, helps them feel safer and more committed to participating in the study.

As a parent, it is important to have realistic expectations for a clinical trial, both for your own well-being and the well-being of your child. Remember, clinical trials are experimental, and sometimes even very promising clinical trials do not have the outcomes we are looking for. Help your child have realistic expectations when you are talking about clinical trials by managing your language and the ways you discuss potential outcomes.

There are a variety of organizations and individuals that sponsor clinical trials. Usually, there is a pharmaceutical/biotech company that sponsors the clinical trial. Another major sponsor of clinical trials is often governmental health organizations. For example, trials in the United States usually are funded by federal agencies such as the National Institutes of Health (NIH).

Additionally, other groups like medical institutions, individual researchers, foundations and advocacy groups run their own studies or partner with pharmaceutical companies and government organizations to run studies. There are no financial costs to families who are chosen to participate in these trials, so they are accessible to anyone meeting the eligibility requirements.

Clinical trials vary in length, with some being as short as one day to others lasting years. Before beginning a clinical trial, be sure you understand the time commitment and what will be required of you. It’s always a good idea to make a list of questions before you speak to the clinical trial coordinator. 

Before a clinical trial begins, the researchers running the trial clearly define what are referred to as “Endpoints.” They are the measures determined for how the benefits and safety of the treatment will be measured. There can be primary and secondary endpoints. Primary endpoints are the most important measures that need to show benefit first. If these endpoints are successful, then the secondary endpoints can provide additional value and information about other ways the treatment is effective. An example of a primary endpoint in DMD would be that more dystrophin would be produced in the muscles, which would likely be found by comparing muscle biopsies from before and after treatment. Another example would be an improvement in walking speed. 

In order to be deemed effective, a trial must reach their endpoints. As a potential participant, understanding what the primary and secondary endpoints are can be useful because they tell you how researchers and regulatory agencies will determine if the treatment is effective or not. If primary endpoints are not successful, the trial is considered to be a failure. No other endpoints are considered and the drug is re-evaluated or discontinued. At the end of a trial, whether it is successful or not, the data from all the patients is collected and reported to the scientific community. However, as discussed above, you will not be told your individual results. 

When a clinical trial is completed, there will be a time period where researchers collect and analyze data. The final study results are either published or communicated to the participants and the scientific community through press releases or at scientific meetings. However, this information is usually presented as overall results from the trial. This means, there will be lots of information about how all participants performed in the trial on average, but you will not know how you performed in the clinical trial.

As an advocacy organization, Defeat Duchenne Canada supports FAIR (Findable, Accessible, Interpretable, Re-usable) data sharing. We believe that patients, and their healthcare providers should be able to have access to information that was gathered in clinical trials they participated in.

Refers to the investigational drug, therapy, procedure or action that is given/performed by the participant and is the focus of the clinical study. There are several kinds of trials with different purposes:

• Natural history studies provide valuable information about how a disease progresses. In this case, no treatment or intervention is given, but the information generated can be valuable for future treatment-oriented studies.
• Treatment trials test experimental drugs or new combinations of drugs.
• Trials that evaluate new procedures, tests, approaches to surgery or radiation therapy.
• Quality of Life trials (or Supportive Care trials) evaluate methods of improving the comfort and quality of life of patients with chronic illness.