Clinical Trials Essentials

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?

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

Additional Independent Reviews and measures

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

Good Clinical Practices protect patients.

The regulations

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.

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. 

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.