Clinical Trials Essentials

The Basics

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Patients at Heart means just that — we respect and care about the people who participate in clinical trials. We’ve made it our mission to help you understand the essentials — this section will tell you about the types of trials, who initiates, regulates and runs them, patients’ rights and protections, and what to expect if you or a loved one participates in a trial.

A clinical trial is defined as a study that observes or treats patients in order to develop or discover new treatments or medications. Virtually all medical advances are thanks to the dedicated volunteers who participate in clinical trials — without them, the medical community couldn’t go on to help thousands — even millions of patients.

These carefully planned-out research studies allow scientists to answer questions like: “Does drug A work better than drug B?” or “Do patients recover faster if they get this new drug before or after cardiac surgery?” Scientists can accurately evaluate medications by studying the effects on healthy people and those with the condition the drug is designed to target.

Have the drugs been tested before the clinical trial?

Every new drug goes through rigorous preclinical lab testing on cells and animals. If and when — and only then — the drug shows potential as effective does it proceed to human clinical trials.

What guides researchers during a clinical trial?

Each different trial follows a strict research plan — a protocol — established by researchers before the trial begins. This is the trial’s blueprint, describing in detail:

  • The background, i.e., what we know about the disease and the study drug so far
  • The rationale, i.e. why we need to conduct this particular study and the question(s) we want to answer
  • The objective(s), i.e. how we’ll know the drug works, and which measures we will use
  • The study design and methods, i.e., what scientific rules the researchers will follow to test their hypotheses
  • The overall organization of the trial, i.e., how often patients will be seen and the study team’s various tasks

Why is a clinical trial so structured?

Above all, this kind of discipline assures the safety of the participants through close contact and monitoring. It also ensures that results are accurate, well-documented, reliable and can be trusted. 

We do clinical research to improve — or save — lives. Every advance in medical knowledge gets us closer to better, more effective treatments and relief for people suffering with a medical condition. In fact, science is all about constantly questioning, and clinical trials are where so many of the answers are found.

Researchers want to see how well a drug works and how it can be used safely, and learn how to prevent, screen for, diagnose and treat health issues.

What researchers might be asking:

  • How can we diagnose this condition better, and identify its risk factors?
  • Is this new drug safe?
  • Which one of these existing drugs works better?
  • Is this existing drug more effective taken orally or by injection?
  • How can we safely use this medication in a different population (e.g. children)?
  • How can we prevent the development or recurrence of this condition?

The group that initiates a clinical trial is called a sponsor.  This can be a company; a university or health care institution; a private or public group; even an individual.

The doctor who carries out the research itself and interacts with the patients is called the investigator or principal investigator. These highly qualified physicians typically have their own patients outside the trial setting. Doctors who dedicate their careers exclusively to clinical trials have the same medical training and qualifications.

All trial doctors complete additional training on conducting clinical trials and research, and the particular understanding and attention paid to trial patients. 

Rest assured: who can conduct a clinical trial, and under what conditions, is highly regulated by governments.

International: Good Clinical Practices
National: Health Canada

Additional Independent Reviews and measures

Before and during a trial: Ethics Committee
Individual Patient Protection: Informed Consent

This ensures that trials are as safe as possible, ethical, and least likely to cause harm of affect a patient's well-being.

Good Clinical Practices protect patients.

The regulations applied in different countries are usually quite similar, as they are based on international standards called “Good Clinical Practices” and developed by the International Conference on Harmonisation (ICH).

Health Canada protects patients.

In Canada, clinical trials are regulated by Health Canada. Similarly, they are regulated by the Food and Drug Administration (FDA) in the United States and the European Medicines Agency in the European Union.

As the government agency responsible for national public health in Canada, Health Canada has a duty to make sure sponsors protect their participants’ safety. It oversees and regulates phases I through III of all clinical trials conducted in Canada. 

Ethics Committees protect patients.

An Ethics Committee (EC) is sometimes also called an Independant Ethics Committee (IEC), an Institutional Review Board (IRB), an Ethical Review Board (ERB) or a Research Ethics Board (REB).

Each trial regulated by Health Canada must also be reviewed, approved, and monitored by an Ethics Committee (EC).

Made up of physicians, researchers and community members, an EC makes sure that research risks are minimized and reasonable in relation to the potential benefits. Before a clinical trial can begin in Canada, its principal investigator must present a detailed request to the EC assigned to review the trial. ECs initially approve clinical trials and periodically review them while they are ongoing in order to safeguard the participants’ rights.

Find out more.

Informed Consent protects patients.

Anyone who decides to take part in a clinical trial must give their consent before the trial begins. This ensures that patients fully understand the trial specifics and objectives, and are kept informed as the trial progresses.

Informed Consent is very important both for the patients and the researchers. Every participant should know all the details, and how Informed Consent protects the clinical trial patient.

Find out more

Each clinical trial’s specific guidelines — its protocol — dictates how the trial is to be run including who may and may not participate.

It depends on the type of research, and often on the patients’ safety. For example, a cardiac drug may affect someone with diabetes differently, so people with diabetes are excluded. Sometimes the trial requires patients with a specific condition, or a particular stage of a disease. Sometimes healthy volunteers are needed.

The reasons that allow you to volunteer for a trial are called “inclusion criteria” and the reasons that disallow it are called “exclusion criteria”.

Find out whether participating in a clinical trial is right for you. 

Clinical Lingo

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Trials use various methods depending on the research objectives. Here we explain essentially how each one works, along with the vocabulary used for each method. The three key terms a patient is likely to hear during a clinical trial are: randomized, blinded, and placebo-controlled.

The aim of a randomized trial is to divide patients into comparable groups — called "arms". For example, by randomly assigning patients, each group can have:

  • People of similar age
  • A similar distribution of men and women
  • The same average disease severity

In randomized trials, the investigator also determines at random which treatment each patient receives — drug 1 or drug 2. At this stage, it isn't know which drug works better, even if, for example, drug 2 is the "newest".

In a blinded trial, patients don’t know which medication they are receiving. This lets researchers compare the effects in the most impartial way possible.

Placebo-controlled trials compare results by giving the study drug to one group, and a placebo (also called a sugar pill) to another group.

Find out more.

Government review agencies require that randomized, blinded and placebo-controlled trials are done before a medication can be considered for marketing approval. This is to ensure drug effectiveness and impartial trial results.  

Find out more about Good Clinical Practices

The Research Phases

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Any new drug or pharmaceutical product has to go through three mandatory phases of clinical research, to validate the drug’s safety and effectiveness before it can be approved for general use. All medications in Canada have completed these phases — and when a medication for one condition is being considered to treat another condition, it must also undergo new testing phases.

All phases are strictly monitored by several regulatory levels. The whole process can often take years, and completely relies on collaboration with patients and the trial site staff.

 

Target Patient Population

Average Number of Patients

Phase I

Healthy patients

20 to 80 participants

Phase II

First evaluation in patients with the target disease

100 to 300 participants

Phase III

Patients with the target disease

300 to 3,000 participants

Health Canada approval for use in the general population

Phase IV

Patients with the target disease

Variable – large numbers

Once the preclinical studies have shown that a drug may work and appears safe, it is tested on a very small group of healthy volunteers. There can be exceptions in phase I trials if they involve oncology or rare diseases where patients are very sick with no other alternatives.

Researchers’ key questions:

  • How does the drug affect humans?
  • What’s the safest dose?
  • What is the best way to take it (e.g. by injection, pill, etc.)?
  • What are the drug’s pharmacokinetics?:
    • How is it absorbed?
    • How is it distributed in the body, e.g., does a pill reach all organs or stay in the stomach? (Important if we want to treat a liver disease and the drug doesn’t get to the liver in good concentrations.)
    • How is it transformed by the body and eliminated?

At the end of phase I, if the drug appears safe in healthy people, it proceeds to phase II, where the drug is tested on a small number of people with the targeted disease. 

This will be the first time the drug is tested on patients with the disease targeted in the study. Researchers are looking for the efficacy and safety of the drug over a relatively short period of time, with 100 to 300 patients tested, often in randomized, blinded, or placebo-controlled trials.

Researchers’ key questions:

  • How effective is the drug on the targeted disease? 
  • What’s its safety profile?
  • What dosage is the most effective with the fewest side effects?

Once phase II has tested efficacy, safety and optimal dosage with positive results, the drug can move on to phase III testing on more patients for a longer period.

The trial is now expanded to include many more patients with the targeted disease, tested over a longer period of time. This phase involves 300 to 3,000 patients, with tests designed to challenge the drug’s longer-term effects. There is usually more than one phase III trial, since the drug is also compared to current medications or a placebo, in randomized, blinded or placebo-controlled trials.

Researchers’ key questions:

  • How safe and effective is the drug over a longer term?
  • How does this drug compare to current medications for the same condition?
  • How does this drug compare to a placebo?

After phase III is completed successfully, the drug can be submitted for Health Canada approval and eventual use by the general population. Once approved, the new medication can then be marketed. 

Also called Post-Marketing trials, phase IV collects results after the medication has been introduced into the general population. This data complements all the results from the previous trial phases.

Sometimes, regulatory agencies like Health Canada approve a medication for marketing only if the effects of the medication are further monitored in phase IV trials, in slightly different patient groups than in phase III, or for a longer period of time. Most often, these are observational studies that collect data from “real life” patients taking the medication as prescribed by their doctors.

Researchers’ key questions:

  • What are the new medication’s long-term conditions for optimal use, efficacy and safety?
  • How does the new medication compare with others already on the market?
  • How does the medication affect the patients’ quality of life?

Bringing a drug through all phases of research usually takes years, and isn’t even possible without the collaboration of patients, doctors and study site staff. Every medication available to Canadians has followed this long, rigorous path, closely monitored throughout by numerous levels of regulation.