World Health Organisation statistics continue to paint a tragic picture of a continent crippled by diseases such as malaria, tuberculosis and HIV/Aids. Yet drug development for these diseases remains concentrated in the developed world. The Drug Development and Discovery Centre (H3-D) has done much to change this status quo, and in 2014, with the capacity-building support of the Medicines for Malaria Venture (MMV), the Clinical Research Centre at UCT established one of the few ‘first-in-human’ clinical trial sites on African soil
First-in-human trials are the small Phase I clinical trials where drugs, which have so far been tested on several animal species, are for the first time tested on healthy human subjects. In Africa, established clinical sites to run these first-in-human trials are rare, in part, because of a lack of infrastructure and expertise to ensure clinical data management adheres to international regulatory requirements such as those of the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA).
When Professor Kelly Chibale, H3-D director and executive committee chair, developed the anti-malarial compound, MMV048, the university wanted to keep the production pipeline of the drug as close to home as possible. This was achieved when UCT’s Collaborating Centre for Optimising Antimalarial Therapy (CCOAT) led by Prof Karen Barnes was selected to conduct the MMV048 First-in-human clinical trial. This decision was taken by the non-profit research partnership between the MMV and the SA Department of Science and Technology's “Technology Innovation Agency” (TIA), who co-funded the development of MMV048 and provided most of the funding for its First-in-Human clinical trial. In 2013, the Novartis Institute for Biomedical Research partnered with UCT to help the university put the necessary systems in place to ensure its clinical, laboratory and data management systems would pass an FDA or EMA audit.
The software and computational requirements of this project were immense and, for the CCOAT team responsible for the clinical trial, this task was daunting. Fortunately, the Worldwide Antimalarial Resistance Network's (WWARN) scientific coordinator in UCT’s Division of Clinical Pharmacology, Lesley Workman, had recently attended a talk given by executive director of our Information and Communication Technology Services, (ICTS), Sakkie Janse van Rensburg, about eResearch and its role in scientific discovery. Workman and Barnes met with Janse van Rensburg to discuss a potential collaboration. This meeting took place in November 2013, before the eResearch Centre was officially established. Technical specialists Ashley Rustin and Timothy Carr were seconded from ICTS onto the project.
“The eResearch team’s involvement was critical for UCT to be able to take on these kinds of clinical trials,” says Barnes. “While individual research groups can upgrade and validate their own data management systems, as well as ensure their hardware and software are compliant, the regulatory authorities also require that the IT platform on which we work is compliant with international standards.”
The data management element is one of the greatest challenges in setting up clinical trials.
“No drug developer would sponsor an early drug development clinical trial unless it complies with stringent regulatory authority standards,” says Workman. “So the clinical data management software needed to be installed, operate and perform according to strict specifications.”
Novartis, worked with Barnes and her team to help get the systems in place. They first ran a series of workshops on clinical trial management, followed a few months later by a mock audit of the CCOAT and relevant UCT systems.
The amount of work undertaken in those months by both the CCOAT and the eResearch team was sizeable.
“Not only did the infrastructure need to be validated, but we needed standard operating procedures for every aspect of the infrastructure,” says Carr.
“What this meant in practice”, explains Rustin, “was a huge amount of paperwork. You need documentation to show the system was properly installed; you need documentation to show the system is performing and operating as it is supposed to. Then because we at ICTS were hosting the server we also needed to validate our platforms. All this documentation needed to be submitted to the Novartis auditor.”
The Novartis auditor was impressed with the standard of work achieved by the team and described the CCOAT clinical data management system as “on par, or even better than, some of the Phase I units in Europe and America.”
Within a few months the CCOAT was given the stamp of approval to successfully run first-in-human trials at Groote Schuur Hospital.
Today, the clinical trial ward in UCT’s Clinical Research Centre (CRC) is one of South Africa’s biggest early phase clinical trial sites, boasting a 24-bed ward in the historic Groote Schuur Hospital Old Main Building and a similar paediatric facility at Red Cross War Memorial Children’s Hospital. The CRC aims to support UCT Health Science Faculty staff in their conduct of high quality clinical research from an initial idea to the final report. The advantages of being able to run clinical trial data management in-house are significant. Previously, researchers had no option but to outsource data management, which can be extremely expensive and time-consuming. Now that the system is set up and running, not only do researchers have free access to this validated platform, but Novartis and others are exploring contracting some of their early drug development clinical trials to the university.