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Apr 07 2011

Clinical Trials in South Africa 101

Flag-map of South Africa.

Image via Wikipedia

South Africa has a mixture of both first and third world diseases and a large number of experienced research sites, making the country an excellent location for clinical trials in many indications. As we are a southern hemisphere country, recruitment for seasonal diseases can be maintained when the seasons change in the northern hemisphere.

Trials need to address the health needs of the country and placebo controlled trials in indications where there are already commercially available treatments are unlikely to be approved. Sponsors should intend to register their product in South Africa if the clinical development of the drug or device is successful.

According to research by the South African Medical Research Council, the leading causes of mortality and disability in South Africa include:

  • HIV/AIDS
  • Tuberculosis
  • Lower respiratory infection
  • Stroke
  • Low birth weight
  • Heart disease
  • Diabetes

and the top 5 cancers are:

  • Prostate
  • Breast
  • Lung
  • Oesophagus
  • Colorectal

However, these are by no means the only diseases of concern for the country. Recent trials conducted in South Africa by various companies include multiple sclerosis, Crohn’s disease, Parkinson’s disease, Alzheimer’s disease, degenerative disc disease and hyperlipidemia.

Public and Private Divide

Healthcare in South Africa can either be provided in the large, government funded public sector or the smaller private healthcare sector. Standards of care vary widely between the two sectors and many items readily available in the private sector may be difficult to access in the public sector. In instances where protocols are conducted in the public sector, protocol driven assessments such as more frequent CT scans and specified background therapies for oncology studies may need to be sourced in the private sector and funded by the sponsor. However the large volumes of patients and the quality research conducted in these public sector centers may justify the additional costs for many sponsors.

Regulatory process

All investigational drug protocols need to be reviewed and approved by two bodies, the regulatory authority and an ethics committee. These two applications can be done in parallel and each body is notified of the other’s approval once it has been received. Drug trials may not start until both approvals are in place.

Device trials and Phase IV drug trials, where the drug is used in a registered indication at the registered dose, are currently not reviewed by the regulatory authority, only the ethics committees. The regulatory authority is only notified that these trials are being conducted. Trials may begin once ethics approval has been received.

In some cases trials conducted in hospital settings or at a site based in a private hospital may additionally require review by the hospital’s internal review board. This review is usually very quick and is done after the other approvals are in place.

The regulatory authority is called the Medicines Control Council (MCC), meetings of the clinical trials committee are held on average every 2 months and the total time from application date to final approval is roughly 4 months but could be longer. In general there are 2 rounds of review, the first is purely administrative and occurs within 2 weeks of submission, the second is both ethical and scientific and all queries are provided to the applicant once the clinical trials committee has met. Timelines for responding to these queries are short and once reviewed, the approval of the trial has to be ratified at the next MCC meeting.

There are a number of ethics committees in South Africa. Those overseeing high-risk research, which includes drug and device trials, need to have a Level 2 accreditation from the National Health Research Ethics Council (NHREC). Public sector sites are generally associated with a university and all research proposals are reviewed by the university’s ethics committee. The meeting dates and timelines from application to approval are variable, but most committees meet monthly except during examination periods and holidays. Approval timelines are, in most cases, shorter than those of the MCC.

There are 2 ethics committees overseeing research conducted in private institutions. Both have regular meetings (monthly or more often) and approval timelines are predictable and take approximately 2 months from application.

Contract Negotiations and Costs

Whilst the regulatory process in South Africa may seem lengthy, the good news is that in most instances contract negotiations are relatively simple. Doctors in private institutions are self-employed and negotiate the contracts themselves, the largest amount of haggling occurs over the budget.  Public sector sites may require additional documentation but even these negotiations can be finalized before MCC approval is received. This means that once the MCC approval is in place, sites can usually be initiated shortly thereafter.

As the South African Rand has strengthened against the US Dollar in recent years, conducting trials here is not as cheap as it once was, but generally the per patient fees are less than in first world countries. As mentioned before, standard of care varies widely and where protocol specified first world care is required, this may lead to some extra costs for the sponsor. We are also obliged to compensate participants for their out of pocket expenses for participating and a guideline fee of R150 is recommended.

Although the country has 11 official languages, the language of business in South Africa is English. Patient documents usually need to be translated into Afrikaans as well. Depending on the disease under study, geographical region involved and the type of population being recruited, translations into other local languages such as isiZulu or Setswana may be required.

Licenses and Permits

The MCC approval letter also acts as an import license. Investigational drug may not be imported until the letter has been received and copies should be included with each shipment.

Investigational drug should be stored and dispensed by a pharmacist or an investigator who is in possession of a valid dispensing license.

Special permits are required for the import and export of biological substances, human tissues, cultures and micro-organisms and copies should be enclosed with each shipment.

A permit is also required for the temporary or permanent importation of listed electro-medical products such as ECG machines and infusion pumps.

SAGCP

South Africa has its own Good Clinical Practice guideline which conforms to ICH-GCP in most aspects. There are some differences and a locally based CRO will be able to guide you through the differences.

Local safety reporting requirements differ from other countries and special listings may need to be generated to meet South African requirements. Only SUSARs occurring in South Africa require expedited reporting to the MCC. All other safety reporting, including all unexpected suspected adverse reactions, is done in a line-listing format every 6 months.

Trials are listed on the South African National Clinical Trials Register (SANCTR), an online website similar to clinicaltrials.gov.

This is a post by Nicola Main, B.Pharm., Danitha Oudegeest, B.Cur., Sarita Bierman, R.N., and Chrissie Marais, B.Sc.  Nicola, Danitha, and Sarita are Clinical Research Associates and Chrissie is a Project Manager.  All are based in Cato Research’s Johannesburg, South Africa office.