About Phase 1 Clinical Trials and Why We Need a Public Clinical Trials Registry in Canada

We all depend on clinical drug trials to access new drugs and treatments for illnesses like cancer. The people who volunteer to participate in clinical trials are the unsung heroes of our medical system, often sacrificing their own well-being for the benefit of us all.

But is the safety of clinical trial volunteers and that of the public adequately protected by the current system of clinical trial regulation and oversight in Canada? Competing interests between consumer protection and big business may be putting us at risk.

Here we will show you how clinical trials in Canada are regulated and how a Canadian Clinical Trials Registry is important to your health and the development of effective new drugs in the future.

Clinical Trials Frequently Asked Questions

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What are clinical trials, and why are they important?

Clinical trials are medical experiments that use living people as test subjects, people who permit researchers to try investigational drugs or medical devices out on them to track how the new product affects the human body. The data collected from these experiments is used to obtain governmental approval for marketing new medical products to the general public.

What is the clinical trials process?

A clinical trial has actually three separate phases of research studies. In an investigational drug trial, the three stages are:

Phase 1: Often called a ”toxicity” trial, the phase to establish the drug’s toxic dose in humans. From that data, the “safe” dose can be determined.

Phase 2: The phase to determine if the “safe” dose is effective.
Phase 3: The phase to determine if that drug’s safe dose is any better than the medical products currently in use.

These stages are carried out on humans only after the concept and development stages for a new medical product has been completed. Before ever using human subjects, scientists perform extensive computer calculations and simulations, apply the new product to cell and tissue cultures and then test out the investigational product on laboratory animals.

The clinical trial process for a new cancer remedy can take 10-12 years to complete and can use thousands of human subjects who live here in Canada and in other parts of the world.

Less than 10% of drugs beginning the clinical trial process receive marketing approval; the others fail for various reasons – the drug doesn’t work, the side effects are horrendous, other already-approved drugs are more effective, the research company runs out of money, etc.

Without clinical trials, the development of new treatments for cancer and other illness would cease as there would be no way to test how safe or effective new drugs are in human beings.

Why do people volunteer to participate in clinical trials?

People who take part in clinical trials offer their bodies as test subjects to contribute to scientists’ knowledge about cancer or other illness and to help in the development of improved treatments. The reasons for making such a life-impacting contribution are as varied as the people.

Some people volunteer to receive access to tests or medical resources and in the hopes that this untried treatment might have a therapeutic benefit and halt or slow down the progress of their disease. However, in Phase 1 cancer trials, there is almost no chance that the treatment will have any positive personal benefit. As well, there is a high likelihood that the volunteer will suffer severe side effects as the main purpose of Phase 1 drug trials is to determine the toxicity level of the new drug.

Thus, volunteers are more likely to have altruistic motivations. Many people who volunteer for clinical trials express the wish to do something positive with their lives, to “make a difference” by contributing to science and helping to find new treatments for cancer and other life-threatening diseases.

How are clinical trials regulated?

Sponsors/funders intending to initiate a clinical trial in Canada apply to Health Canada, Therapeutic Products Division, and also to each Research Ethics Board (REB) of the institutions being contracted to conduct the clinical trial. An REB establishes the “plan of action” or protocol for the clinical trial which determines the contents of the Subject Information & Consent form. This form must be signed by the person recruited to act as a test subject in a clinical trial and by a representative of the institution contracted to conduct the clinical trial. The signed consent form signifies that informed consent has been obtained.

The qualifications for REB members are set by Health Canada but are minimal, relying on the integrity of the contracted institution.

Once the protocol is approved by the REB, the conduct of the trial and the protection of the clinical trial volunteers are left to the researchers hired by the sponsor of the trial.

Health Canada is ultimately responsible for governing clinical trials. However, less than 2% of clinical trials are inspected by Health Canada and then usually only if an official audit is ordered. Health Canada sets standards for conducting clinical trials but often in the form of guidelines rather than requirements.

As a federal government agency, Health Canada has no authority over medical staff conducting clinical trials as the governance of medical professionals is the jurisdiction of the provincial College of Physicians & Surgeons and the College of Nurses. Only Alberta and, recently, Newfoundland have set standards for physicians facilitating clinical trials.

If something untoward happens to a clinical trial volunteer, the contracted institution may convene a “morbidity and mortality committee” or Q & A panel. The clinical trial volunteer and their personal representatives are not invited to such a hearing – only the medical professionals involved have input. The resulting confidential report is held by the institution and, by provincial law, is not available to any other entity.

What are the ethical concerns about using human clinical trial volunteers?

Clinical trial volunteers in general, and Phase 1 volunteers in particular, are the unsung heroes of our medical research system.

Without their altruistic contribution to the advancement of scientific knowledge, we would not be able to develop new therapies for treating illness.

Conducting potentially life-threatening experiments on human beings for the benefit of others carries an ethical obligation to make sure that the research volunteers are never marginalized as a means to an end and that their safety and wellbeing is paramount in the research process and in the minds of the researchers. This involves designing research trials that minimize risks and maintaining the highest respect for the volunteers.

In particular, we must honour the self-sacrificing contributions of these volunteers by ensuring that the results of the clinical trials are put to the best possible use.

How are the results of clinical trials disclosed in Canada?

When drug companies seek approval for new drugs, they must file information with Health Canada on all trials that have been conducted on the drug, whether done in Canada or in other countries. In addition, all safety information must be submitted. Health Canada regards this information as proprietary and commercially confidential and does not release it without the permission of the drug company.

How big a business are clinical drug trials?

Clinical drug trials are a growing business in Canada with more than 80% of trials funded by the pharmaceutical industry. Canada has the 5th largest bio-medical research industry in the world. The government of Canada is marketing Canada as an “innovation partner” to international pharmaceutical companies. Their marketing brochure outlines the business advantages of conducting clinical trials in Canada, including:

  • An expedited ethics review process
  • A streamlined regulatory process
  • Access to a well-organized patient population
  • Strong collaborative networks between cancer research and treatment

From 2001-2006, the number of clinical trial applications in Canada more than doubled and spending increased from $425.7 million to $567.1 million dollars (CLINICAL TRIALS IN CANADA: WHOSE INTERESTS ARE PARAMOUNT? Joel Lexchin, International Journal of Health Services, Volume 38, Number 3, Pages 525–542, 2008).

What are the risks of nondisclosure of information in clinical trials?

Nondisclosure of the information in clinical trials has serious disadvantages for Health Canada, health professionals, and the Canadian public. Deprived of any independent access to information, health professionals and the public must accept Health Canada’s judgment about the safety and effectiveness of products
(Joel Lexchin, International Journal of Health Services, Volume 38, Number 3, Pages 525–542, 2008).

Nondisclosure calls into question the integrity of Health Canada, obstructs the research process by restricting the amount of information that is available for the peer review process, and prevents doctors and researchers from accessing full information on drugs.

As a result, healthcare decisions may be based on incomplete data and ultimately harm the patients and the public. In addition, trials may be duplicated, wasting precious research money and putting trial volunteers at unnecessary risk.

Clinical Trials Registry Frequently Asked Questions

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What is clinical trials registration?

Clinical trial registration is defined by the World Health Organization (WHO) as the publication of an internationally-agreed set of guidelines about the design, conduct and administration of clinical trials. The International Committee of Medical Journal Editors (ICMJE) defines a clinical trial registry as a comprehensive, publicly available database of clinical trials.

Why is a public clinical trials registry important?

A number of scandals that involve either drug companies suppressing negative information about particular drugs or about drug trial volunteers becoming seriously ill and even dying as a result of participating in clinical trials have led to a call worldwide for more transparency and accountability in publishing the results of clinical research.

In Canada, the information regarding clinical trials is particularly opaque, according to UBC Medical Ethics professor Dr. Michael McDonald.

In an effort to address the need for transparency and accessibility of information gained in clinical trials, many organizations are calling for compulsory clinical trial registration.

 

According to the International Committee of Medical Journal Editors (ICMJE), the compulsory registration of clinical trials on a public registry of clinical trials is a scientific, ethical and moral responsibility for the following reasons:

 

  • There is a need to ensure that those making pivotal decisions about health care are informed by all of the available evidence. It is difficult to make informed decisions if publication bias and selective reporting are present. The Declaration of Helsinki states that "Every clinical trial must be registered in a publicly accessible database before recruitment of the first subject."
  • Improving awareness of similar or identical trials will make it possible for researchers and funding agencies to avoid unnecessary duplication.
  • Describing clinical trials in progress can make it easier to identify gaps in clinical trials research.
  • Making researchers and potential participants aware of recruiting trials may facilitate recruitment.
  • Enabling researchers and health care practitioners to identify trials in which they may have an interest could result in more effective collaboration among researchers. The type of collaboration may include prospective meta-analysis.
  • Registries checking data as part of the registration process may lead to improvements in the quality of clinical trials by making it possible to identify potential problems (such as problematic randomization methods) early in the research process.
  • Public registries honour the promises made to the clinical trial volunteers. "When members of the public agree to participate in trials, it is on the understanding that they are contributing to the global body of health-related knowledge.  It is thus unethical to conduct human research without ensuring that valid descriptions of the study and its findings are publicly available" (The Ottawa Group).

What is Health Canada’s position on a Canadian clinical trials registry?

Health Canada has held many discussions about registering clinical trials conducted in Canada. However, after more than six years of fact finding, as yet Health Canada has made no commitment to a compulsory public clinical trials registry and no time line or process is given for making the final decision. Some experts feel that Health Canada’s policies “demonstrate a prioritization of industry’s needs over those of the public” (Joel Lexchin).

How does Canada compare to other countries?

Canada does not have a public registry of clinical trials and does not make it compulsory for the 80% of clinical trials conducted in Canada that are funded by pharmaceutical companies to register their trials. Instead, Health Canada “encourages” pharmaceutical companies to register on whichever registry they choose. For the 20% of trials that are instead funded by tax-payers, registration is mandatory but no single specific registry is specified; it can potentially be a registry from any country.   Countries who have established primary public clinical trial registries include:

  • Australia/New Zealand
  • Brazil
  • China
  • Korea
  • India
  • Cuba
  • EU
  • Germany
  • Iran
  • Netherlands
  • Japan
  • Pan Africa
  • Sri Lanka
  • UK
  • USA  

Many others countries are in the process of establishing trial registries, but Canada’s process is stalled.

CANADA NEEDS A CLINICAL TRIALS REGISTRY

A mandatory Canadian public clinical trial registry that ensures that results from all clinical trials are accessible to the public is necessary to protect the safety of Canadians and to honour the contributions of clinical trial volunteers. Research with Respect is calling for Canada to establish a Canadian registry and to require mandatory registration of all clinical trials conducted in Canada.