In-depth: SA’s remarkable TB clinical trial capacity
Several of the world’s most important tuberculosis (TB) clinical trials of the last two decades were done in part or entirely in South Africa. These include several trials that helped establish the safety and efficacy of the medicines the World Health Organization (WHO) now recommends for the treatment of drug-resistant forms of TB.
It also includes several trials of experimental TB vaccines, one of which was a landmark phase 2 trial of the M72 vaccine – it seems likely the phase 3 trial of the vaccine will also include study sites in South Africa.
According to Global Data (a research and consulting company), of 1 925 clinical trials started and completed in Sub-Saharan Africa from 2012 to 2023 (not just TB trials), 930 were conducted in South Africa. Roughly half of the clinical trials in the region related to infectious diseases. Africa as a whole had just over 5 000 clinical trials in the period, 2.2% of the global tally. With more than 2 900 clinical trials, Egypt accounted for almost 6 out of every 10 clinical trials conducted on the continent.
One reason why so much TB and HIV research can be done in South Africa is quite simply that we have large epidemics of both diseases here. Around 13% of South Africa’s population are living with HIV and the country is on both the WHO’s lists of 30 high TB burden and 30 high DR-TB burden countries. The WHO estimates that around 280 000 people in South Africa fell ill with TB in 2022 and 54 000 died of the disease.
Yet, while some TB clinical trials are conducted in other countries with large TB epidemics, South Africa seems to be something of an outlier in terms of just how many TB clinical trials are conducted here. There are thus clearly other factors involved.
The research environment
Dr Angelique Luabeya, Chief Research Officer at the South African Tuberculosis Vaccine Initiative (SATVI), says the country’s capacity to run successful clinical trials is derived from a combination of factors like infrastructure, skilled human resources, funding, regulatory and ethical oversight, community engagement, and sustained political and organisational commitment.
Similar factors are pointed out by Dr Francesca Conradie, an infectious diseases researcher in the School of Clinical Medicine at Wits. She says South Africa has a high burden of TB disease, an excellent laboratory service and a robust regulatory environment.
“We can make the diagnosis of TB and trials can be run to the highest standards. Our TB program is excellent and engaged in the research agenda,” Conradie says.
Conradie led the landmark NiX trial that up-ended traditional notions of TB treatment by showing that tough to treat forms of TB could successfully be treated with just three drugs taken for just six months – previously four or more drugs were used for 18 to 24 months, and cure rates were much lower.
In South Africa clinical trials are regulated by the South African Health Products Regulatory Authority (SAHPRA). TB clinical trials in the country are typically funded by entities such as the United States National Institutes of Health, the European and Developing Countries Clinical Trials Partnership, the Bill and Melinda Gates Foundation, and in some limited cases by the South African government through the South African Medical Research Council or the Department of Science and Innovation (This Treatment Action Group report shows who funds TB research around the world).
Dr Limakatso Lebina, Clinical Trials Unit Lead at the African Health Research Institute (AHRI), stresses that South African researchers have extensive experience conducting clinical trials and says that in her view there are adequate regulations and sufficient infrastructure in place in the country.
“As part of the global research world,” Lebina says, “people conduct research across many countries and include diverse groups of populations to gather adequate evidence to change guidelines.”
Her last point hints at an important benefit of conducting TB trials in South Africa – it helps us understand how well experimental TB treatments work in our population. For example, given South Africa’s very high rates of HIV/TB coinfection, it is important for us that new TB treatments are tested in people with such coinfection rather than just in people who have TB, but who are not living with HIV.
Laboratories, roads and electricity are all part of the infrastructure needed to make it all come together, as are so-called clinical trial units. As Lebina explains it, clinical trial units are research sites specifically designed to evaluate new medicinal products, diagnostic tools, surgical procedures, vaccines, nutritional measures, and psychological interventions. She says these units design, conduct and analyse studies ranging from phase one (that evaluate safety and pharmacodynamics in humans) to phase four (that continue to monitor side effects after treatment has been approved).
Lebina says setting up a clinical trial unit requires specialised infrastructure and skilled personnel depending on the disease focus and the type of studies that are planned. On the one hand she says there are several similarities between such units and a normal healthcare facility, “such as equipment to conduct medical examinations and management of medical emergencies and a pharmacy”, but on the other, these units also require “specialist equipment such as freezers for storage of vaccines, easy access to laboratory for immediate processing of specimens and regular calibration of equipment.”
Factors like closeness to laboratories and willingness of people in the area to participate in trials are considered when deciding on the location of clinical trial units. For this reason, these units tend to be situated in cities or large towns.
Lebina says AHRI is aiming to turn this around with a clinical trial unit launched last year in Somkhele in rural northern KwaZulu-Natal. She says the uniqueness of the unit “is that it is in a rural setting and gives access to participation in clinical trials to a population that is often neglected or overlooked and underrepresented in the conduct of clinical trials”.
“We believe inclusion of diverse groups of people in research is essential to develop safe and effective medications and to offer clinical trials as a treatment option for all patients in need, irrespective of where they live or their socio-economic status,” Lebina says.
The unit has a staff complement of 50 – comprised of medical doctors, nurses, pharmacists, clinical research assistants, data managers, laboratory personnel and administrative staff. Studies that are being conducted or planned at the unit include research on two new TB vaccines, HIV pre-exposure prophylaxis trials that combine innovative treatment delivery options, HIV treatment with newer regimens, and asthma treatment studies.
‘Problems with the system’
Professor Keertan Dheda, a pulmonologist and critical care specialist who heads up the Division of Pulmonology at Groote Schuur Hospital and the University of Cape Town, says although South Africa has done well with clinical trials, there are major challenges on the horizon and problems within the system.
Chief among these, according to Dheda, is how long it takes to obtain the various different and sequential approvals required for these studies. Beyond ethical and SAHPRA approval, he says there are often biosafety approvals, provincial level approvals, city-wide approvals to access healthcare facilities as well as export permits to ship samples. He says huge delays can happen when obtaining some of these approvals and thus a more streamlined process is required.
Dheda points out that high crime rates have also impacted research activities due to hijackings, research staff being robbed of reimbursement money for participants, and theft of computers from research staff. “This has escalated alarmingly in the last three years and is a major problem. This is especially true for trials involving TB and HIV because these often recruit participants in previously disadvantaged areas where crime is very high,” he says.
He says the ability to carry out high quality clinical studies is impacted by “the wider South Africa macrocosm” becoming unstable because of things like electricity interruptions, skills shortages, immigration, and concerns about corruption.
Lebina says that setting up clinical trials comes with several challenges including delays in regulatory and administrative approvals, having very few skilled personnel in the trials, and limited funding.
Prospects for young researchers
Luabeya says that South Africa offers ample opportunities for careers in the research fields. This is due to the country’s strong legacy in medical research, especially in areas like HIV, TB, and more recently, COVID-19. The country also has several renowned universities, research institutes, and organisations dedicated to health research.
However, she says that like many countries, South Africa does face challenges including funding constraints, administrative hurdles and the “brain drain” phenomenon where skilled professional seek opportunities abroad.
“South Africa trains young researchers and offers them career paths in clinical trials. While challenges exist, the country has a resilient and growing research ecosystem, and there’s a concerted effort to strengthen its capacity further,” Luabeya says.
According to Conradie, while the country is making progress in this area, there is still some way to go. “Being a clinical triallist is not yet seen as a career path. Most clinical triallist come from an academic background but it should be seen as a career path for GPs and even specialists,” she says.
Dheda says we are not training enough scientists and clinician scientists to undertake clinical trials and also highlights the lack of a fixed career path for academic scientists and clinicians.
“The MRC [Medical Research Council] must be credited for taking steps in the right direction by providing funding for postdoctoral training and for training of clinician scientists but a much more comprehensive and structured programme is required,” he says.
Dheda adds that South Africa needs information and solutions so that we can solve our own clinical problems including those relevant to TB and HIV.
“It is also important to support and drive a knowledge-based economy which is a major strategic objective of organisations such as the Department of Science and Technology and the SAMRC. For example, we are unsure about exactly how much TB costs the country, but it’s been estimated that it reduces our GDP by about 3%, not taking into account the chronic disease associated with TB and also not taking into account HIV. Put together (TB and HIV), this represents a huge negative impact on our GDP in the region of about 4 to 5% which is far more than our entire health spend,” he says. He adds that therefore it makes sense for us to invest in research infrastructure that will generate solutions for our country and for our people.
“We are simply not investing enough into an exercise that will be extremely cost-effective,” says Dheda.
Note: The Bill and Melinda Gates Foundation (BMGF) is mentioned in this article. Spotlight receives funding from the BMGF. Spotlight is editorially independent and a member of the South African Press Council.