What is a clinical trial?

Clinical trials are carefully designed experiments that allow scientists to test their research questions with people. There are many different kinds of research questions, and have evolved over time. In HIV, the early clinical trials tested new drugs for treatment of the disease and associated opportunistic infections. More recently, researchers have been testing potential vaccines, microbicides and New Prevention Technologies, which could prevent infection or limit its effect. The goal is to determine if the treatment being tested is safe, how well it works, and if it should be approved for use in the general population.

New prevention technologies are also known as biomedical interventions. This refers to a group of HIV prevention tools that employ medical interventions to reduce the risk of HIV infection. This category of HIV prevention includes male circumcision, microbicides, PEP, PrEP, preventive and therapeutic vaccines, and treatment as prevention.

How does a trial work?

A clinical trial is just one stage in the process of developing a new treatment. The entire process includes several steps: identifying a possible treatment; testing it on animals; getting approval for a clinical trial; running the trial; analyzing the results; applying for a license; and getting approval to use the treatment in the general population. This process can take many years. Even when a treatment is put on the market, researchers may want to continue to investigate new ways of using it to reduce the frequency of dosage, to reduce side effects or to test it in new ways to administer the treatment.

Pre-clinical Testing: in vitro and animal studies

When a new treatment is developed, it must first be carefully tested before it can be given to people. These pre-clinical tests include in vitro studies and animal studies.

In vitro studies are laboratory experiments that examine how a new treatment works on animal or human cells in test tubes. For example, the new treatment may be mixed with some healthy human cells and some HIV-infected cells to see if it will kill infected cells without damaging healthy ones. In vitro studies are repeated many times to ensure the results are repeatable and dependable and not just due to chance. If in vitro studies show promise, researchers then proceed to the next stage: animal studies.

Animal studies test new treatments on living animals. Toxicity studies are designed to determine if a treatment harms the body’s organs. Some drugs can cause illnesses or reactions that don’t show up unless the drugs are used for a long time. Other medications may be fine for the people taking them, but may cause problems such as birth defects in future generations. Animals that reproduce quickly and have short life spans, such as mice and rats, are used to study both these problems. Other animals, such as monkeys, are used in certain studies because they are more like people and can have similar diseases. Testing new drugs or vaccines on these animals gives scientists a better idea of how they may affect people.

Clinical Trials: testing new treatments on people

If pre-clinical studies indicate that a treatment is useful and safe in animals, the treatment developer (pharmaceutical company, biotech company, university, etc.) asks Health Canada for permission to test it in people. To get approval for a clinical trial, a company must submit all the documentation and data from pre-clinical studies, including data that demonstrates the treatment is safe enough to be tested in people. The company must also provide a detailed written plan or protocol for the trial. A protocol is a researcher’s description of why and how a study will be conducted.

Testing in people is done in four phases of trials:

Testing in people is done in four phases of trials:

Phase I: Researchers give the treatment to a small number of people (with or without HIV) to see what dose is safe, starting with single administration. Different participants receive different doses to determine which dose is safest. Phase I trials are riskier than later phases, because typically little is known of the treatment’s effects on humans. These trials are short, usually no more than two or three months, and generally involve 20 to 80 participants.

Phase II: Researchers give the treatment to a larger number of participants (several hundred) over a longer period of time to determine the most effective dose, to see if it is working and to learn whether it has any medium-term side effects. These trials normally span a few months to a year.

Phase III: Researchers give the treatment to a much larger group of people over several months or years to determine whether the treatment remains effective or has any side effects that only show up after a longer period of time. Researchers also compare new treatments with treatments that are already in use. If a treatment is successful at this point, it may be approved for general use.

Phase IV: Researchers often continue to study a treatment after it has been approved in what are called “post-marketing” trials. They watch for any side effects or problems that may show up only after several years of use, or test the treatment in different prevention and/or treatment strategies.

Today, many clinical trials combine phases. For example, Phase I/II trials might study a treatment dose and how it works, while Phase II/III trials might study both how the treatment works and how effective it is at the same time.

Approval of a new treatment

New treatments are continually re-assessed for their effectiveness and for the benefits and risks observed at each stage of the clinical trial process. A trial can only proceed to the next phase of testing with approval from Health Canada. Once a treatment has been tested successfully in the first three phases of clinical trials, the manufacturer can apply to Health Canada for formal approval to market or sell the treatment.

Federal government approval of a treatment doesn’t necessarily mean that a particular treatment is effective or safe for all people at all times. It only means that the treatment has proven useful in enough people to be worth trying in a larger population and that, in most cases, its known side effects do not outweigh its benefits.

What do HIV trials test?

Most treatments that are tested fall into the following categories:

  • Drugs that fight the HIV virus, called antiretrovirals (ARVs).
  • Treatments that prevent or treat side effects of antiretrovirals (e.g., high blood fat levels).
  • Treatments for co-infections such as hepatitis B or C, or HPV (human papilloma virus).
  • Treatments that reinforce the immune system, known as immunostimulators or immunomodulators.
  • Vaccines that could prevent, limit the effects of, or cure HIV infection (preventative or therapeutic vaccines).
  • Gene therapies.
  • Microbicides (products that, when applied topically, are able to prevent the sexual transmission of HIV and other sexually transmitted diseases).
  • Pre-exposure prophylaxis (ARVs that, when taken daily by HIV- individuals, prevent the acquisition of HIV).

About Clinical Trials

Participating in a Clinical Trial

Once You’re Enrolled

Other Things to Consider

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