The CHRU Community Advisory Board

Q&A

Clinical trials & scientific research

The Clinical HIV Research Unit

The Clinical HIV Research Unit (CHRU) is a division of the Wits Health Consortium, which is part of the Faculty of Health Sciences at the University of Witwatersrand (Wits) and affiliated to the Department of Internal Medicine at Wits. It was founded in 2001 and has run multi-disciplinary clinical trials and research to prevent, treat and manage HIV/Aids, TB and associated diseases. Its mission is to deliver excellence and quality in clinical research. CHRU is recognised internationally as one of South Africa’s leading research sites.

CHRU has long-standing collaborations with the National Health Laboratory Services (NHLS), its Department of Molecular Medicine and Haematology, and the National Institute of Communicable Diseases (NICD).

CHRU research sites are situated at:

  • The Helen Joseph Hospital, Westdene, Johannesburg, Gauteng
  • The Sizwe Tropical Disease Hospital, Sandringham, Johannesburg, Gauteng
  • The King DinuZulu Hospital, Sydenham, Durban, KwaZulu-Natal and
  • The Empilweni TB Hospital, Port Elizabeth, Eastern Cape.

What is a clinical trial?

Clinical trials test new methods of diagnosing, treating or preventing health conditions. The goal of a clinical trial is to determine whether a medical or behavioural intervention is both safe and effective. A clinical trial involves research using volunteers and its purposes is to add to medical knowledge.

In a clinical trial, participants receive specific interventions according to the research plan or protocol created by the study sponsor. A variety of interventions are evaluated through clinical trials, including:
• medications,
• medication combinations,
• new uses for existing medications,
• vaccines,
• medical devices and
behavioural changes, like diet.
Clinical trials may compare a new medical approach to either a standard one that is already available and in use, to a placebo that contains no active ingredients, or to no intervention at all. Some clinical trials compare interventions, that are already available, against each other to see which is best.

When a new product or approach is being studied, it is not usually known whether it will be helpful, harmful, or no different than available alternatives.

The investigators first study the product or approach in the lab and in animal trials to determine safety and whether the approach is effective. Once certain standards of safety are met in these early stages, they move onto different phases of the trial where they start testing the product or approach in people. They first assess the safety of the intervention by observing and measuring the responses of the participants.

In later phases, they look at the effectiveness of the intervention by measuring it against certain outcomes. For example, investigators may give a drug or treatment to participants who have high blood pressure to see whether their blood pressure decreases.

Remember that no treatment is completely safe for everyone, but a clinical trial helps make sure that the treatment is safe and effective for most people. Without clinical trials we would have no medications or agents to fight illness or to prevent illness.

Where are clinical trials held and who runs them?

Clinical trials can take place in many locations, including hospitals, universities, doctors’ offices, and community clinics. The location depends on who is conducting the trial and what is being tested.

Usually, trials are run at clinical research sites. Clinical studies can be sponsored, or funded, by pharmaceutical companies, academic medical centres, universities, voluntary groups, government agencies and a variety of other organisations.

Every clinical trial is led by a principal investigator, often a medical doctor. Clinical trials also have a research team that may include doctors, nurses, social workers, and other health care professionals.

Who benefits from clinical trials?

Everyone benefits from clinical trials. New medications and developments in the medical and health fields could not be found if it were not for clinical trials. Any medication that we take today, including something as basic as Panado, has come from clinical trials, and even science about lifestyle choices has been investigated using clinical trials.

Who participates in clinical trials?

Clinical trials have standards outlining who can participate. These standards are called eligibility criteria and are listed in the trial protocol. Some clinical trials seek participants who have the illnesses or conditions that will be studied, while some are looking for healthy participants, and others are limited to a set group of people who are asked by researchers to enrol.

The factors that allow someone to participate in a clinical trial are called inclusion criteria, and the factors that prevent someone from participating are called exclusion criteria. They are based on characteristics such as age, gender, the type and stage of a disease, previous treatment history, and other medical conditions.

How long do they take?

The length of a clinical trial varies, depending on what is being studied. Participants are told how long the study will last before they enrol.

Do people that take part in clinical trials get paid?

This depends on the trial and the risks involved. However, in most instances participants will be reimbursed for any costs required to participate. They often also receive free high-quality medical care for the duration of the trial.

How do we know clinical trials are safe for people that participate in them?

No treatment, even ‘natural’ treatments, are guaranteed to be completely safe for everyone even after clinical trials have been performed. The medications we take every day all have side effects and risks.

A clinical trial is designed to make sure that the benefits of the treatment, vaccine or drug outweigh the possible risks for most people.

In the early phases of the trial (phases 0, 1 and 2) the focus is predominantly on the correct dose and the safety of the drug or treatment. From phase 3 onwards, common side effects are established, and the main question is then about how effective the treatment or drug is. Safety monitoring continues, even after registration of the new medication.

In South Africa, the following regulatory bodies must approve the clinical research before any trial can commence:
• Research ethics committee – This committee is independent of the study sponsor and the clinical investigators. These committees are usually affiliated with a university scientist e.g. specialist, and also someone from the community e.g. pastors, lawyers and traditional healers.
• South African Health Products Regulatory Authority (SAHPRA) – This is an entity of the National Department of Health created to ensure that health and well-being is prioritised. SAHPRA is tasked with regulating (all health products. This includes clinical trials, complementary medicines and medical devices.

Other regulatory approvals are also required, for example from the Department of Health and the hospital or clinic involved in the trial.

Internationally, there are also research networks that provide oversight to trials taking place all over the world and all clinical trials are conducted in accordance with World Health Organisation regulations.

Additional safety factors for participants are that:
• Independent data safety monitoring boards monitor trial results and side-effects throughout the process and will pause or halt the trial if they have any concerns regarding the safety of participants.
• The clinicians who take part in and run the trial also put the interests of the participants first. They work independently and are not dictated to by the sponsors of the trial. As local doctors who are part of the local communities, they really do have the participant’s best interests as their primary focus.
• All trial participants complete an informed consent form, which details exactly what the trial involves and any potential risks. All participants will therefore have all the aspects of the trial explained to them, and have all their questions answered in advance. Informed consent is only valid if the person fully understands what is required, and has voluntarily confirmed their willingness to participate.
• All participants may withdraw from a trial at any time.

What are the phases of a clinical trial?

Clinical trials used in drug development are described by a phase once they are ready to test in people. These phases are pre-defined and provide structure to the process.

Phase 0 involves fewer than 15 participants.

Phase 1 normally has between 20 and 80 participants, who are all in good health. In this phase the dosing is tested, to establish the highest dose that can be tolerated.

In Phase 2 there are several hundreds of participants. In this phase, the safety of the medication or treatment continues to be evaluated, and commonly some people with underlying conditions are now involved, to again establish safety.

In Phase 3 there are commonly a few thousand participants. The aim of this phase is to evaluate the effectiveness of the medication or treatment being tested, with safety having been established in phases 0-2. Side effects are monitored. The medication or treatment will be tested in the healthy population, as well as in those with underlying conditions and comorbidities.

Phase 4 trials occur after the drugs have been approved for use by the public. These trials look at long term safety data.

Are people coerced or forced to participate in a clinical trial?

No one is ever forced or coerced to participate. It is voluntary. It is a decision every individual makes for him or herself. People that are considering participating will be provided with comprehensive information about the clinical trial. If they choose to participate in the trial, they will sign a voluntary informed consent form. Voluntary informed consent is the cornerstone of health research ethics.

What is voluntary informed consent?

Voluntary informed consent is a procedure through which a competent volunteer, after having received and understood all the research-related information, can voluntarily provide his or her willingness to participate in a clinical trial. He or she is provided with information about the trial, its aims, benefits, and potential risks. Only after signing a voluntary informed consent form can a participant take part in the trial.

The Clinical HIV Research Unit (CHRU) ensures that all the ethical and legal requirements for voluntary informed consent for clinical research participation are fulfilled. It also adheres to the South African guidelines for good practice in the conduct of clinical trials with human participants in South Africa.

If the study sponsor of a clinical trial just wants results, who looks out for the participants and protects their interests?

Research sites across the world have community advisory boards (CABs). A CAB is an independent body and acts as a watch dog to ensure that studies proceed properly and trial participants’ concerns are accommodated and their rights are protected. Members of a CAB reflect a diverse mix of experiences, profiles and skills, and have cultural insight into the communities participating in the clinical trials. They are volunteers who are trained on good clinical practice. They educate people about clinical trials and about studies taking place at the research site, and they advocate for participants, give feedback on cultural and religious sensitivities and raise community concerns.

The research team, made up of doctors, nurses, social workers and other healthcare professionals also put the interests of trial participants first. They work independently and are not dictated to by the sponsors of the trial. As local doctors who are part of the local communities, they really do have the participant’s best interests as their primary focus.

Does a participant know what risks s/he will face?

Clinical trials are designed to improve the science of medicine. They are not designed to put people at risk. Everything about a trial is made clear to a participant before they sign the voluntary informed consent form:
• What is required from them
• How long they will be involved in the study
• How often they need to go to the research site
• The tests and procedures involved in assessing their health and response to the study

What happens if someone wants to stop half way through the trial?

Participants can withdraw from a study at any time. The informed consent process includes counselling which makes it clear that someone can withdraw at any time. The only thing the participant must do is inform the principal investigator of the study that she or he is withdrawing. They do not need to provide a reason.

What happens if someone on a trial gets sick or has a reaction?

When a participant enrols for the trial, they are given a card with the names of their healthcare team at the research site, and their contact information. If a participant develops any symptoms or feels unwell in any way, they need to contact the healthcare providers immediately and discuss their symptoms. The healthcare provider may decide that they want to see the patient to assess them, in which case they will be assisted with transport, or, they may refer the patient to a healthcare facility.

Data safety monitoring boards monitor the safety of a clinical trial at regular intervals. Should there be a signal that there is an increase in side effects, they will halt the trial while they investigate the issues and start-up the trial once they are satisfied with all safety aspects.

When a participant alerts the study team to a symptom or side-effect and the scientists respond quickly, it shows that the safety protocols are working and that the safety measures are in place.

How do I get in touch with the Clinical HIV Research Unit?

Tel: +27 (11) 276 8800
E-mail: info@chru.co.za