Clinical trials explained

Because we have largest HIV burden in the world, coupled with a very high TB burden, a number of new medicines, devices and vaccines are being trialled in South Africa. And there will be more to come in the next few years. What are clinical trials and what does it mean for someone to be part of one?

WHAT IS A CLINICAL TRIAL?

A clinical trial is a scientific experiment to understand the risks of a therapy, drug or medical device and whether it will work or not. Clinical trials are conducted on new treatments, but also to look at how existing medical interventions can be used to treat different illnesses or types of patients.

Clinical trials can be conducted using healthy volunteers or people who are sick, depending on the type of product and its stage of development.

WHY ARE THEY IMPORTANT?

Clinical trials look at new ways to prevent, find or treat disease. Without them, we would not now have effective antiretrovirals to treat HIV, vaccines for COVID-19 or antibiotics to cure tuberculosis, for example.

All medicines or treatment have both potential effects and side-effects or risks (even herbal remedies). To prevent people from getting more sick from medicines that are meant to help them and also to stop companies from selling medicines to people that don’t work, clinical trials are vital. They test objectively whether a medicine or device is safe to use and whether it works.

Medicines must undergo a series of clinical trials to be approved by the South African Health Products Regulatory Authority (SAHPRA) (formerly the South African Medicine Control Council) for treatment of a specific sickness. Medicines that have not been approved cannot be sold by a pharmacist, given by a nurse or prescribed by a doctor.

WHAT TYPES OF CLINICAL TRIALS ARE THERE?

• A single arm prospective study means everyone enrolled in the trial will be treated the same way.
• Randomised controlled trials (RCT) compare a group given the therapy (treatment group) with a similar group of people who are not given the therapy (called the ‘placebo’ group – placebo means a fake treatment). The results for both groups are then compared to see if one group does better than the other.
• A blind trial is a randomized controlled trial where the treatment and placebo groups don’t know whether they are given the therapy or not. This is to see if patients only improve a little because they believe they are being treated – a phenomenon known as the placebo effect.
• A double-blind trial is when the treatment and placebo groups AND the doctors or nurses who give out the trial medicine don’t know which patients are getting the treatment or the placebo. This is to make sure there is no unconscious bias on the part of clinicians when they are conducting the trial or reporting trial results.

The double-blind randomized controlled trial is the gold standard in clinical trials because it is seen as the most scientific and objective way to determine safety and efficacy.

WHAT ARE TRIAL PHASES?

New treatments usually undergo three phases of clinical trial before they are sent to the SAHPRA for approval and another phase of testing after they are approved.

• Phase I involves a small number of participants and tests the medicine for safety in the general population.
• Phase II tests for safety in the intended patient group and also tests to find out if the drug has some effect.
• Phase III tries to show scientifically, with a valid sample size (enough people to make the findings mean something), that the drug works. This is the information that the MCC uses before it is approved and labelled.
• Phase IV trials track the safety, effects and best use of a drug after it has been approved and made available to the public.

WHAT ARE ETHICAL GUIDELINES?

Clinical trials are experiments on humans so scientists have to be extra careful when they design them to ensure the safety and human dignity of the people participating. Ethical guidelines aim to protect participants and to preserve the integrity of the experiments. They were created after a number of very damaging and unethical experiments conducted on people during World War II and just afterwards.

Trials usually go before an ethics review panel before they are started. Seven main principles guide ethical research:

• Social and clinical value – the trial is testing something important for humankind
• Scientific validity – the results from the trial will be valid
• Fair subject selection – the people participating in the trial have been selected fairly
• Favourable risk-benefit ratio – the potential risks to the participant are not greater than the potential benefits
• Independent review – the trial design has been reviewed by an independent panel
• Informed consent – people who participate in the trial know what they are signing up for and have agreed to it
• Respect for potential and enrolled subjects – the trial design respects the privacy and dignity of both the people signed up for the trial and those that choose not to take part.

SHOULD I TAKE PART IN A CLINICAL TRIAL?

Being part of a clinical trial will give you access to new treatments before they are widely available and can help many other people by contributing to medical knowledge. Sometimes people are paid to be part of a trial to cover their expenses (although this practice is controversial as scientists worry that people will take part in trials without fully understanding the risks).

Ultimately, it is up to you whether you take part or not. Just make sure that you are fully aware of both the potential benefits and the potential risks (and inconvenience) to you of the trial.

Some questions to consider before you sign up:

• What is the reason for the trial?
• What type of trial is it and which phase is it in?
• What kinds of tests and treatments are involved?
• Has the trial been reviewed by an ethics panel?
• Will there be any compensation for trial participants?
• What type of long-term follow-up care is there?
• If I am part of the placebo group and the medicine is found to be very effective, will I have access to the treatment as soon as possible?
• Will the results of the trial be shared with me?

WHAT IS ‘EMERGENCY USE’ APPROVAL?

In an emergency, like a pandemic, it may not be possible to have all the information that SAHPRA would usually need before approving a treatment. In this case, SAHPRA can approve the use of a treatment for a certain time and based on special conditions that must be met at a later stage. SAHPRA will only give emergency use approval if they are confident that the treatment is safe and effective, but the information is not yet enough to meet all the requirements for full registration.

Find more information at the SAHPRA website

* This article was first published in 2017 and updated on 2 September 2021.