Clinical Research in South Africa

A large, vibrant country located at the southern most tip of Africa, South Africa is as diverse in it’s population and culture as in it’s varied geographic landscapes of the sea, game reserves, semi desert and first world cities. It is there where one can find one of the most exciting and challenging environments within which to conduct clinical research. Classed as an emerging market, South Africa is typically competing with India, Eastern Europe, China and South America for opportunities to participate in international clinical trials, as part of the trend to shift the mix of recruitment into clinical trials globally.

South Africa has a population of approximately 45 million with diverse population groups. The significant differences between social classes and living conditions exposes the population to disease entities both typically inherent in an economically challenged environment such as infectious diseases, malaria, TB, AIDS, as well as diseases which more conventionally affluent social classes exhibit such as diabetes, cardiovascular, hypertension and obesity.

The South African medical environment operates in both the public and private sectors. The public sector is typically affiliated to academic and university institutions, with a provincial affiliation in terms of legislation and regulation. Although, as is the trend globally, the public sector is stretched in terms of resource, both professional and financial, typically medical care is classed as of a high quality, and in many specialities, comparable to that of first world institutions. Clinical research in South Africa is not new, with internationally recognised research being conducted as early as in the 1950s in the area of tuberculosis. Now with over twenty years in the formal, ICH-GCP-regulated clinical research arena, South Africa has hundreds of highly skilled and experienced investigators in varied therapeutic areas.

South African clinical research personnel are typically highly qualified, well educated, and have had the opportunity to participate in high standards of training in the field. Many senior clinical research professionals have had the opportunity to run global studies out of South Africa. Others have made a meaningful scientific contribution to studies by being engaged right from protocol conception and design through to execution.

Sponsor and in-house audits are frequently conducted, with positive feedback, reinforcing the fact that clinical research is conducted to a high standard, in accordance with ICH / GCP and the EMEA guidelines. FDA audits have also been conducted in South Africa, with no significant deficiencies documented.

Pharmaceutical companies and other sponsors interested in conducting clinical research in South Africa will find conflict between the need to conduct clinical trials for disease entities of high prevalence and economic significance to South, and indeed, Southern Africa such as malaria, TB and AIDS, or the need to participate in clinical trials from the perspective of contributing to the advancement of medical science globally, and bringing in much needed foreign revenue streams.

There is a strong correlation between the requirement and desire to participate in global clinical research, while maintaining the capacity building demands of a developing country. The dichotomy between social classes can positively translate into the country embracing and benefiting from clinical trials. A large segment of the patient population has minimal or inadequate basic health care in terms of access to adequate treatment. Clinical trials ensure that many members of the patient population are afforded the opportunity to be exposed to adequate treatment management, and consequently compliance and eagerness to participate is extremely high. The capacity building mandate is not only extended to patient selection, however. A regulatory requirement, supported by the ethical authorities, encourage under utilised or naïve investigators to participate in clinical trials. This trend is supported by the clinical research professional body at large. As the regulatory authority approves all site personnel selected for inclusion in a study, it requires that no investigator may be a Principal Investigator without having had the opportunity to hold the role of a co-investigator at least twice. Thus, this ensures that all participating investigators have had adequate experience and training prior to running a clinical site.

As would be expected, many patient populations that are targeted for inclusion into clinical trials can be classed as vulnerable. This offers additional challenges in terms of conducting clinical trials within South Africa, particularly surrounding informed consent development and execution. Researchers investigating the possibility of utilising South Africa for the purposes of conducting clinical trials should liaise with local research professionals to better understand the political, social and economic milieu. Considerations in this regard include that the clinical research must be relevant to those who suffer from the disease (Department of Health 1999), the study design should be appropriate to local settings and the standard of care on a par with that of developed countries. Should the research not be conducted in the country of origin, this should be justified in the initial applications to the regulatory authority. The research itself should not be exploitative, and there should be some form of provision for post trial access, should this be appropriate.

Clinical trials in South Africa typically cost 25% - 50% less than in Europe and USA due to the favourable exchange rate. Shorter recruitment times also contribute to significant reduction in overall costs. Patients are eager to participate in clinical trials, as, for many patients, they are afforded the opportunity to have much needed medical attention, which they may otherwise not have had. South Africa has the opportunity to include more “treatment naïve” patients into clinical trials, which lends itself to a more robust design concept. South Africa being located in the southern hemisphere also holds an advantage, in that seasonal studies can be placed in the country, where it would not be appropriate in the Northern Hemisphere.

The most challenging element of conducting clinical trials within South Africa, would be the regulatory environment. The Regulatory Authority, the Medicines Control Council (MCC) propagates itself as not only a scientific body, but also an ethical and political body as well. Thus, the application process of a clinical trial needs to address all three requirements to the satisfaction of the MCC. The MCC also requires that clinical trials be conducted according to SA GCP. However, these requirements certainly do not preclude ICH-GCP and are non-conflicting. The process is relatively laborious, with an interim evaluator review prior to a final council meeting to afford a final approval. The current difficulty is the volume of clinical trials being submitted for clinical review, whereby occasional submissions are referred to an additional meeting, which lends itself to a delay commonly of a few weeks. The MCC acknowledges the current resource predicament, and is actively working with task and working groups to shorten the approval time and schedule more submission dates.

However, due to the large availability of patients, and skilled site and clinical research professionals, despite these delays, more often than not the study milestones for recruitment and study end are met and sometimes exceeded.

80 to 100 new applications are submitted to the Medicines Control Council on average each cycle. The South African Department of Health mandates that all clinical trials be registered on the National Clinical Trials Register of ongoing studies. Currently, 400 trials are logged on the register, and in excess of 700 new applications were submitted during the 2007 calendar year.

As one would expect, the South African medical fraternity, government and regulatory agency are also focused and render priority to research being conducted in areas of concern to the local population. These overwhelmingly would be TB and AIDS, with malaria to a lesser extent. HIV / AIDS remains a significant health concern to South Africa, and the region in general. The disease contains to increase rapidly in the country and WHOStat 2007 indicates the incidence of HIV and TB in South Africa is 16% and 5% respectively. The research environment within South Africa is significantly focused on HIV research, whether it be vaccine or other. The HIV infected population has a seroprevalence rate of 10%, and is the largest HAART patient base in the world. This lends itself to ethical issues, with again this type of patient population being classed as vulnerable. South Africa has guidelines within which to conduct HIV research including, but not limited to the following: Declaration of Helsinki, SA GCP, SA National Department of Health guidelines on ethical conduct of vaccine trials and UNAIDS guidelines for HIV preventative vaccine research. These guidelines focus on elements such as the limited ability of the individual to provide informed consent, understanding of their care and treatment within their cultural framework and experience as well as the limited availability of health care and treatment options.

The past few years have emerged with South Africa becoming a base for clinical research to be conducted into Africa. Collaborations with organizations such as UN AIDS, WHO, Gates Foundation, NIH, and many other NGO and NPO organizations have resulted in CRO’s, and other organizations based in South Africa to conduct research in other countries in Africa. These include, but are not limited to, Burkina Faso, Ghana, Kenya, Malawi, Botswana, Mozambique, Rwanda, Tanzania, Mali, Uganda and Zambia. Most commonly, TB and malaria vaccine studies are conducted. Investigators located in these countries are desperate for clinical trials to be placed at their centres. The investigators understand the huge need to have not only access to very limited treatment, but the opportunity to upgrade their facilities through grant funding from the clinical trials. These investigators are commonly very well versed in ICH / GCP principles and research is conducted in an ethical and scientific manner.

South Africa is not just content to wait for international initiatives for clinical research, but are locally actively instituting research programs to address their immediate and most concerning health needs. One such example is the Thibela Study, being conducted under the auspices of AURUM Health, in collaboration with John Hopkins University, amongst others. This is a preventative program based on the premise that providing TB prevention treatment to entire communities will ultimately reduce the incidence of the disease. 68 000 miners will be enrolled into this study. This program has now been internationally recognised at the Good Clinical Practice Journal, held in London, 2007. The organisation received the award in the category: Most Innovative Patient Recruitment Strategy as well as runner up in the category of Clinical Research Programme which Best Promoted Access to Medicine.

Currently, less than 1% of global trials are placed in South Africa. The current capacity of the country in terms of experienced researchers and professionals is poised to conduct far more research than is currently being allocated. CROs, biotech companies and pharmaceutical companies looking for alternative, cost effective locations which produce recruitment at a rapid rate, would do well to consider South Africa for their future clinical development programs.