Deep Dive Into Clinical Trials

• The opportunity to play an active role in your own health care
• Access to an expert team that can give you a deeper understanding of your condition
• Access to new research, medications or treatments
• Additional care/tests specific to the trial
• The knowledge that you’re helping others

Any medical treatment carries potential risk, and clinical trials are no exception. Trial patients should be mindful of the chance of harm occurring, or the degree of harm.

Examples of risks:

• Possible side effects from the medication, from minor and unpleasant to serious complications requiring medical attention
• Finding the trial more demanding and time-consuming than regular care
• Being required to alter or abstain from the treatment you were receiving prior to the trial
• Discomfort associated with additional medical tests and procedures

The benefits and risks vary from one trial to another. Ask the trial’s staff which of the benefits and risks above may apply to the trial you‘re considering.

Are patients paid to participate?

Patients are not paid for participation in phase II, III and IV clinical trials. Only healthy volunteers participating in phase I (first testing) trials are sometimes paid.

Will I have to pay for anything?

The test drug or treatment in a clinical trial is free of charge. Costs you might need to consider are for travel (to and from the research site), childcare, lost income (if any) due to time away from work, etc. A clinical research coordinator can help you determine your costs over the full trial period and whether any are reimbursed.

Trials often require frequent checkups and regular collection of data, which could involve tests or procedures you wouldn’t normally have. You’ll also be more closely monitored than usual, by a trial doctor specialized in the subject being studied. That means expert care. This applies to information, too: research team members are there to answer any questions you have at any stage of the trial.

Great care is taken with medications in clinical trials, but some patients do experience side effects. The first trial phases are conducted in part because all the drug’s effects aren’t yet known — the research is to identify the drug’s possible risks as well as its benefits. When previous studies have shown a drug’s potential adverse effects, this is always shared with participants before the trial.

The trial team is qualified and equipped to care for you in all scenarios, so if you do experience an adverse reaction, whether it is a known side effect or a new one, you must notify the research team right away for your own safety. If you are not at the research site, you contact the emergency contact person indicated on your consent form.

Emergency contact

Your consent form has the name and number of the person you can call right away if you think you are having a serious side effect or complication.

A member of the research team

If there is no immediate threat to your health but you have other concerns, speak to the trial investigator, clinical research coordinator or any team member. Responsible for your peace of mind, they must keep patients informed and address any of their concerns.

Note: If you do think there is a threat to your health, you should go to the Emergency at your nearest hospital.

Ethics Committee representative

Remember, the Ethics Committee (EC) — an independent body not affiliated with the study — is in charge of overseeing the trial in which you are participating. Contact the EC representative if you:

• Have questions about your role and rights as a participant
• Have concerns, complaints about the research
• Wish to provide input about the research trial

As a volunteer, you can withdraw at any time for any reason. Researchers will definitely use the data collected from your participation up to that point.

However, it’s crucial that you report any side effects or downturn in your condition to the team before you leave the study. They can document your information, which might be very significant to the trial data. More importantly, they are there to help you get better, whether or not the deterioration in your health is caused by the study treatment, so you will continue to get appropriate care even after you withdraw.

Yes, absolutely. The patients’ safety is built into the trial rules, so respect them. Keep lines of communication open. And follow these straightforward steps:

• Make sure your regular health care provider(s) and trial doctors crosscheck the care you are receiving in and outside the trial
• Closely follow instructions about the trial drug dosage, and other medications you can or cannot take
• Keep accurate notes about how you’re feeling. If you feel side effects, report them immediately
• Mistakes do happen. If you realize you missed a dose or did something not in keeping with the instructions, just write down what happened and tell the team right away

By signing the consent form, you acknowledge in writing that you fully understand the trial process, the benefits and the risks before enrolling in the trial, and that you understand you will be continually informed throughout the trial process. This is for your own protection as well as that of the trial’s organizers.

This document is first reviewed by the Ethics Committee to ensure it accurately reflects the trial protocol. All potential trial participants receive the consent form, which details the purpose of the study, what procedures will be performed, potential risks and benefits, responsibilities, alternative treatments, cost of participation, and compensation, if applicable. It also explains:

• How your privacy will be protected
• How the collected data will be kept confidential and non-identifiable
• Who your contacts are should you have any questions or issues at any time

Yes. As a volunteer, you can leave a trial at any time, even if you’ve signed. But the researchers will need to know the details as to why, because what is affecting you might have an impact on what is happening to other patients in the trial.

No one should enrol in a trial until all the information is clear, nor should anyone sign a consent form until they understand everything contained in it. The researcher’s job is to make sure you make an informed decision. You can take the time you need with a researcher, and/or take the form home to look it over with family and friends. Alternatively, you can bring someone with you when you meet with the research staff.

What is a placebo?

A placebo is a treatment that contains no active medicinal ingredients. It will look and/or taste the same as the medication being studied, contain the same non-medicinal ingredients, and be in the same form (e.g. pill, injection, etc.). For instance, a placebo can be a “sugar pill”, or an injection of saline solution if the treatment is given by injection.

When is a placebo used or not used?

A placebo is often used in clinical trials to test how well a new drug works. If effective, the drug should produce better results than the placebo.

Comparing a new drug with a placebo can be the fastest and most reliable way to demonstrate the new drug’s therapeutic effectiveness. However, assigning a patient to a placebo group can pose an ethical problem if it violates their right to receive the best available treatment. Placebos are never used if a patient would be put at risk by not having effective therapy — particularly in the case of serious illnesses, where most studies compare new drugs with an approved medication.

What is “the placebo effect”?

This is when a patient’s symptoms improve after receiving a placebo. It seems to be due to the patient’s strong belief or expectation that the treatment will work, along with the doctor’s conviction that the treatment will work.

This is perfectly normal and does not mean that the patient’s symptoms are not real. Scientists think the brain may produce substances that make the patient feel better and reduce their symptoms.

Will I know if placebos are going to be used in a trial?

Yes. You will be informed before participating in the clinical trial that you will either receive the medication being studied or a placebo, at random. It is unethical to not divulge this information.

What is an active-controlled trial?

Active-controlled trials compare a new drug to one that is already available — or compare approved medications to each other. There have been more of these recently than placebo-controlled studies, because researchers can see how well a new drug works compared to a current standard-of-care medication. They are also always used when it would be unsafe or unethical to use a placebo on certain patients.

Is it better to be in the group getting the study drug?

Not necessarily. Until the clinical trial is completed and the trial findings are known, it isn’t possible to know which of the two treatments is better. Regardless of the trial group you are in, the process ensures that you receive the same excellent medical care.

What is randomization in trials?

In many trials, a patient is assigned to a specific study group. Randomization is a process by which two different treatments or more are assigned by chance rather than by choice. This is done to avoid any bias while assigning patients to one group or another.

Why is randomization used?

It is very important to properly randomize patients between treatment groups that are being compared: randomization ensures that any differences in results are due to the different treatments each group received and not other factors that make them dissimilar.

What is blinding?

Blinding — or masking — is the process by which one or more parties involved with the trial do not know which patients have been assigned to which treatments. Types of blinding are explained below: single-blind, double-blind, triple-blind and no blinding (called open-label).

Why is blinding used?

The purpose of blinding is to prevent biases: if researchers knew which patient was getting the study treatment and which was getting the placebo, they might be tempted to give the (presumably helpful) study drug to a patient who could more easily benefit from it. A researcher might also give extra care to only the patients taking placebos to compensate for their ineffectiveness.

Not knowing which participants are receiving the active treatment allows the trial doctor and research staff to objectively observe patients during the study. Regardless of which treatment the patients get, however, the level of medical attention and care they receive is the same.

Similarly, a patient who does not know which treatment they are receiving cannot form an opinion about it that could unfairly influence the trial results.

What types of blinding can be used in trials?

Single-blind: The researchers are aware of the treatment they are administrating but patients don’t know which treatment they are receiving.

Double-blind: Two of the parties involved with the trial do not know which patients have been assigned to which treatments. Typically, this includes the researchers and the patients.

Triple-blind: Three of the parties involved do not know which patients have been assigned to which treatments. This often includes the researchers conducting the study, the patients, and the researchers analyzing the results collected.

Open-label: A trial in which blinding is not used. All parties involved know which patients have been assigned to which treatments.

What if I figure out which group I’m in, even though I’m not supposed to know?

It’s unlikely that patients guess or figure out which treatment group they’re in, but even if you think you know which treatment you’re getting, it’s very important that you follow the assigned treatment plan for your group.

What if I don’t want to be in the group to which I’m assigned?

Occasionally patients change their minds about participating once they find out which trial group they’re assigned to (i.e. in an open-label trial). Don’t let anyone talk you into starting or continuing a trial if you don’t want to. It is your right as a trial patient to change your mind.

Your doctor may direct you to a trial you might be interested in and qualified to join. You may also have seen ads for trials in newspapers and on television, or heard them on the radio. Databases and Web sites are also good resources to see lists of clinical trials. Go to Browse Trials to look through some of the studies conducted by AbbVie.

You can also browse trials at other reputable sources, including Clinicaltrials.gov, a Web site developed by the National Institute of Health that provides current and unbiased information about clinical trials for a wide range of conditions.

Health Canada oversees the public information about a clinical trial, including advertising. The Ethics Committee also evaluates and approves ads as part of their review process.

Expect to find basic information in an ad for a clinical trial: the title and purpose of the study, main inclusion and exclusion criteria, the study site location(s), and how to contact the research site for more information.

Health Canada will not let any ad imply that an experimental treatment is safe or effective for the condition under investigation — nor can any ad promise or imply a certainty of cure or complete symptom relief.

It makes sense to discuss anything to do with your health with your doctor, including participation in a clinical trial. Doctors have their patients’ best interests at heart, and will let you know if there are any medical reasons you shouldn’t participate.

We encourage you to do your own research as well to find trials in your region dedicated to your condition. Ask family and close friends to help in your learning and decision-making process. When they are included early on, they will be in a better position to provide support if you decide to join a trial.

There can be significant differences among patients with the same disease — differences that require different treatments. And patients may have other health conditions that make their treatment more complex.

In a clinical trial, researchers need to be able to account for everything that might affect the study results. That’s why, even if you have the medical condition, it may not be enough to be eligible.

Criteria for patient inclusion and exclusion are detailed in the study protocol and are generally listed in trial databases and briefly in ads. These criteria are in place to safeguard patients and ensure that the researchers glean the information they need from the trial. The trial’s objectives will dictate the patients required: healthy, or with specific illnesses or conditions.

Other inclusion and exclusion criteria may include:

• Age
• Gender
• Stage or severity of a disease
• Previous treatments a patient did or did not take
• Medications a patient is currently taking
• Medical conditions other than the one being studied

In order to qualify for a clinical trial, you must satisfy both the inclusion and exclusion criteria. Once you’ve contacted the research team, they will go through the Informed Consent process with you. When you have signed your consent form, you may undergo an additional screening process as outlined in the specific trial protocol.

After a clinical trial is done, researchers carefully analyze all the data they collected. If findings are positive overall, or there is further analysis to do or more questions to answer, they may decide to move on to the next phase of testing. Or, they may decide to stop testing because the drug was not safe or effective enough.

When a phase III trial is completed, the researchers examine the data and decide if the study results warrant submission to government agencies for the medication’s marketing approval.

Most clinical trials run for the planned length of time. Sometimes, though, Health Canada, the Ethics Committee or the sponsor may end the trial early. The medication may be producing unexpected or more severe side effects — its harms outweighing its benefits. Another reason could be that not enough patients were recruited in the allotted time.

In some cases, a trial might be stopped because results are more positive than expected, i.e., if there is clear evidence early on that the new drug is effective, the trial may be halted so that the new treatment can be made widely available as soon as possible.

If your trial is stopped early for any reason, the research team notifies you immediately and advises you on the next steps. The trial doctors are still committed to providing you with ongoing care: with your consent, they will consult with your usual health care provider(s), fully inform them as to your health status, and transfer you back into their care.

Results from clinical trials are often published in peer-reviewed scientific or medical journals. This means that before trial results are approved for publication, the findings are evaluated and supported by peers, who are researchers and experts in the same field as the trial researchers. Peer review ensures that the analysis and conclusions of the trial are sound. If the results are significant, they may also be discussed at scientific meetings before they are published.

You can ask the research team if your trial’s results have been or will be published.