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The Biotechnology Centre, University of Yaounde 1, Cameroon.
The Road to Building a Clinical Research Laboratory in Central Africa
Among the hierarchy of evidence for medical practice and public health interventions, randomized clinical trials are at the top. These trials are primarily used to provide evidence for the implementation of one intervention against another in what is also known as comparative effectiveness research. There is an unprecedented increase in technologies for global health today. Smaller, more performing and point of care devices are being developed every day. Increasingly new drugs, diagnostics and vaccines for diseases across the global health spectrum are expected to enter the market in the foreseeable future; with the product development pipeline richer for some of the target diseases than for others (see http://www.ott.nih.gov/productpipeline/default.aspx). Although infectious diseases still dominate the developing world today, predictions show that by 2025, non-communicable diseases will champion the lead. As opposed to the developed world where infrastructure, systems, enabling environments, funding resources etc. are better developed and available, countries in the south, mostly sub-Saharan Africa are not tenacious enough to embrace challenge of participation and contribute to global health because of their under-representativeness in trials of global health importance. Few scientists in sub-Saharan Africa, especially central Africa, initiate trials of global health importance to support the implementation of health interventions within their particular contexts. Trials for global health, especially in HIV predominate in South Africa, with few investigators initiating such trials in other sub-Saharan countries. In order for these countries to improve the provision and delivery of quality health care, critical gaps need to be closed. Of prime importance is the building of sustainable clinical research infrastructure and human capacity for global health intervention research. The following paragraphs show the experience of the establishment of a small clinical research laboratory in Cameroon located in Central Africa and the building of a team with the capabilities required for high quality clinical research in global health.
The man and the mindset
The Biotechnology Centre is a specialized Centre under the University of Yaoundé 1 created by presidential decree with the mandate of performing biotechnological research in Agriculture and animal sciences and the popularization of sciences within the region. The animal biotechnology section is composed of six research groups specialized in immunology, public health research biotechnologies, molecular parasitology and vector research, molecular epidemiology of tuberculosis, metabolomics and diabetes research, health economics, food microbiology and quality control and a small research clinic under development. The clinical research laboratory in question is located in the laboratory for public health research biotechnologies, the group being headed by Prof Wilfred Mbacham, a Harvard Tropical Public Health professor. Ten years ago, the clinical research laboratory barely existed for the name of it. Old non-functional basic equipment, no research protocols, little human resource commitment and other factors characterized what could rightly be termed the inexistence of an appropriate clinical research laboratory. But it required the strength of the mind and the motivation to see where others only look, to write when others sleep, to plan when others fight, and to use common sense, patience, perseverance, personal sacrifice and previous relations to acquire, manage and invest little funding to achieve big results. These are the qualities of leadership, and the building of the scientist as the manager; two qualities that are extremely important for a successful career as a clinical research laboratory director. Therefore, it is important to think quite early on what kind of laboratory capacity one desires to have in the future, what type of research to be carried out, and for the case of laboratories that support global health services to follow a set of well-designed criteria for quality and sustainability.
The infrastructure and maintenance
Most scientists will agree that in Africa and SSA in particular, acquiring lab infrastructure is a big challenge. It is common to see laboratories which are not equipped, or are half equipped. Even the equipped may face the acute problem of ongoing maintenance. In the early years of the development of our laboratories, it was the desire for the lab to have a maintenance officer, but this could only be someone who was carefully chosen with the deliberate aim of training the individual in biomedical equipment maintenance ‘on the job’. As risky as this may be, it paid off. Early contributions in the development of our laboratories came from the International Atomic Energy Agency which aimed at empowering disease endemic countries with the safe use of radioactivity for public benefit; and the Gates Malaria Partnership postdoctoral fellowship administered by the London School of Hygiene and Tropical medicine to Wilfred Mbacham. Due to electric current surges, some equipment often shuts off, even with the establishment of systems for controlling thunderbolts which are frequent in countries that lie in the equatorial regions of Africa. In 80% of the times that these events happen, the equipment was repaired onsite. Spectrophotometers and Thermocyclers have been rescued many times due to the prompt intervention of a locally trained technician. Arguably, this may not represent the most appropriate scenario, but the most cost-effective and safe. Obtaining and renewing maintenance contracts for equipment in Africa usually remains a dream, not only because of the cost but also because of the logistics of having to move heavy equipment from place to place without a clear picture of the likely outcome. The challenge still remains though, for the training of biomedical engineers with the capability of maintenance of valuable clinical and research equipment for proper functioning of the laboratory.
The systems and sustainability
A clinical research laboratory is only as good as the systems that maintain it. Through the good will of the tropical disease research empowerment arm of the WHO/TDR, the next step in developing the laboratory was the implementation of the whole concept and practice of guidelines of good clinical laboratory practice otherwise known as GCLP. This concept specifies best practices in the clinical diagnostic and research laboratories in terms of personnel and records, organization, equipment and reagents, samples and quality management systems, etc. Some of the critical elements addressed in these guidelines are a clear line of communication in the laboratory, responsibility, record keeping and inventory control, equipment logs and preventive maintenance, logic of pre-analytic, analytic and post-analytic processes, training and re-training, staff delegation, internal quality control, proficiency testing etc. The slogan here is ‘if it is not written, it was not done’. Good documentation practices underlie effective implementation of GCLP and key to the production of high quality data in clinical research laboratories. A key aspect to the implementation of such a system is the development and establishment of standard operating procedures for all activities that take place in the laboratory. Some of these SOPs are project specific while others are generic and are frequently used in the laboratory across different clinical research projects. We undertook to produce more than 170 SOPs on various aspects of the clinical projects or routine activities happening in our lab. This laborious process required a complete overhaul of our laboratory system with the mentorship of an expert from the TDR. In the research laboratory, this helped to facilitate work and increased self-confidence. At our clinical sites where hospitals are located, it enabled patients and research participants to be even more compliant.
We had to organize several SOP writing workshops, re-organization of our laboratory spaces to follow a logical flow that respects the principles of safety and critical for avoiding contamination of samples and promoting quality, and facilitation of the logical unidirectional workflow for routine analyses in clinical research. We had to label reagents prepared ourselves following GCLP labeling conventions, re-organize samples, develop and implement sample rejection and acceptance criteria, provide procedures for transportation, handling, storage and retrieval of biological samples. We further implemented GCLP procedures for inventory control of reagents and supplies and for preparing and ordering reagents and other products as needed by various clinical studies. In addition, we had to develop procedures for data handling, data querying, data archiving, cleaning, data entry, data compare and completely separate a dedicated clinical data management unit for the laboratory. The idea of a clinical laboratory is not much an issue of space as it is of organization.
We also engaged hospital laboratories in our trials sites in the whole process (which was not an easy thing to do with a different management structure) from development of SOPs to implementation and inspection of progress by the TDR GCLP team. This also included the development and implementation of internal and external quality systems. Validation of critical limits of normal physiological and pathological limits was an important part of the hospital laboratory GCLP training and implementation plan. This resulted in our sites using the Levey-Jennings plots and Westgard rules to validate clinical specimen data and to check the performance of their equipment and staff.
Proficiency testing was implemented as a regular activity to assess the performance of the hospital laboratory system against another laboratory operating as a reference facility. We committed to an ongoing training of peers and junior students on the processes and procedures in our clinical research lab. The TDR continues to help developing country scientists to develop and maintain such a system through a recognition program that is a critical step towards laboratory accreditation from accreditation bodies such as the College of American Pathologists. Guidelines of GCLP are provided by TDR and can be accessed online at http://www.who.int/tdr/publications/documents/gclp-web.pdf. A further place for continuous development of best practices and enhancement of capacity is online web platform of the Global Health Trials website. By logging into and updating your profile in the professional membership scheme after and taking eCourses for example, you can climb the professional ladder and help track your career progression.
Ideas and money, capacity in global health trials, sources and resources
Was it worthwhile? What was beautiful after all these procedures was the fact that investigator initiated trials (which had previously meant very laborious and difficult processes) could now be carried out with relative ease since the processes were understood from the beginning, and clear and transparent procedures for communication, delegation of responsibility, SOPs implemented greatly facilitated the work and motivated commitment. Through the implementation phase of the clinical trial, it was immediately evident how quality and reliable were generated, and how credible our results would be. It was easy to see how rigorous implementation of these procedures could lead to better clinical decisions in global health. It was worthwhile to embark after all.
Although we are yet to be what we wish to be in terms of our vision for clinical research in Central Africa, our past cannot match our present. An important lesson learnt during this procedure is that finances should not be a barrier to change. Procuring new equipment for different analyses does not automatically translate into better procedures. Identifying critical relevant questions and finding the best way to answer such questions is rather the key. It was a matter of mindset after all. Well refurbished and functional equipment operated and maintained following the principles of good clinical laboratory practice provides as valid results as a new one under the same operating conditions. Significant support for our activities in the laboratories come from proactivity and involvement in the European Union framework program support through EViMalaR Network.
The experience of the central African workshop and Global Health Trials
The reason for this paragraph is to highlight the continuous commitment to development of trial laboratories in Central Africa and in Cameroon in particular. Global Health Trials presently stands out as a platform to boost capacity of trial staff of all categories from field workers and coordinators to nurses through laboratory technicians, physicians, investigators and students on training in global health trials. It is important that it is global health, because the vision to prepare and build capacity to meet future challenges is bigger than addressing just one disease. Although there are disease specificities in terms of trials, there are nevertheless generic tools that are applicable across diseases and the basic principles of clinical research are the same. Therefore, the Global Health Trials platform provides the most appropriate avenue for such capacity building. Our relationship with the Global Health Trials was greatly facilitated by the gains we have recorded in the process of building our own clinical trial facility. We could not help but collaborate with the team to spread this knowledge, coordinate the effort to bring together all trial staff categories as we could reach within our means and to share experience and build a network. Such a network is expected in the long run to greatly facilitate the conduct of investigator driven trials in global health. Our commitment spans from organizing workshops, seminar series and we seek to provide mentorship support to individuals and laboratories across the sub-region. While we can adequately say we are blessed because we can speak both French and English languages and our country is relatively stable and known as the island of peace in troubled waters, we do not underestimate the task ahead. But we also do not minimize the tremendous effect of a better and healthy region resulting from mustard seed investments made today.
In this light, after launching the Central African Faculty of the Global Heal Trials in a Workshop in Nigeria, we organized a skills sharing workshop in Yaoundé, Cameroon in November, 2012. This free one day skills sharing and networking workshop brought together people beyond our expectation. It was overbooked and the momentum generated by the audience would have ripple effects in the near future. A fuller report of this workshop will be presented elsewhere within the global health trials web platform and will highlight our experience bringing together people of different backgrounds working for a common good in global health. Unlike the slogan for AIDS control ‘keep the promise, stop the spread’, we are fired to ‘keep the promise and also the spread’ of knowledge and skills to enhance global health trials capacity in Africa.
Acknowledgements
Funding agencies: IAEA, EvimalaR, Gates Malaria Partnership, The University of Yaoundé 1.