Strengthening regulatory systems and ethical research review
By end of 2018, EDCTP had supported projects to develop these capabilities in 24 sub-Saharan countries, with a view to create enabling environments for high-quality research. This includes investment in activities to train ethics and regulatory staff, coordinate between ethics and regulatory bodies, harmonise regional approaches, and development of online tools to improve efficiency of ethical review processes.
Improved efficiency of national ethics committees in providing research ethics oversight.
Improved compliance of legal frameworks for national ethics committees and national regulatory authorities with international standards.
More efficient turnaround times of study protocols and effective pharmacovigilance reporting.
Higher qualified staff of national ethics committees and national regulatory authorities in research ethics and ethics evaluation.
Increased public awareness of research ethics review and regulatory oversight of clinical trials.
Establishment of new national ethics committees where these do not exist.
EDCTP's contribution towards ethics and regulatory activities in Africa
Ethical review of clinical research protocols in Uganda
Clinical research is important and ought to be of high quality and relevance such that research participants are not exposed to unnecessary harm or inconvenience. Their safety, rights, interests and values should be protected. A transparent and efficient clinical research regulatory system enhances human research protection. Clinical research regulation and ethics review should not impede but facilitate research progress and aim for the right balance.
Clinical research oversight in Uganda is done by the National Drug Authority (NDA), the Uganda National Council for Science and Technology (UNCST), the Uganda National Health Research Organisation (UNHRO), the Office of the President (OoP) and accredited research ethics committees.
The Consortium for Clinical Research Regulation and Ethics Capacity Development in Uganda (CREDU) is implemented by the NDA, UNCST, UNHRO, the Infectious Diseases Institute of the Makerere University and the Mbale Regional Referral Hospital. The project objectives are to:
- Strengthen the capacity of national regulatory agencies (UNCST, UNHRO, NDA, OoP) for the review and approval of clinical research;
- Establish a coordinated framework for clinical research management in Uganda;
- Improve the quality of ethical review of clinical research by research ethics committees and national regulatory authorities;
- Increase opportunities for information sharing, dialogue, knowledge translation and networking among researchers, regulatory officials, research ethics committees and the wider community within Uganda and abroad.
Ms Badanga Nazziwa, CREDU’s project coordinator: “The individual capacities of staff at the agencies have been improved through ethics and regulatory training, mentorship and placements at more advanced institutions. Staff members of the National Drug Authority visited the more advanced Japan Pharmaceutical and Medical Devices Agency (PMDA) in Tokyo. A one-week Good Research Regulatory Practice Course has been developed for professionals on research ethics committees and staff of the regulatory agencies.”
Currently, Uganda has a clear regulatory framework and an extensive infrastructure in the field of research ethics. A notable effort has been made in the past years to build a coherent framework for ethics and health research regulation. However, there are still several challenges with respect to the quality of scientific and ethical review of health research protocols, the regulatory burden imposed by several time-consuming layers of approvals, and a lack of streamlining of operational practices between the different regulatory agencies. This creates an impediment to research progress. A second challenge is posed by the limited opportunities for sharing information, dialogue, translation of knowledge and networking among researchers, regulatory officials, research ethics committees, and the wider community within Uganda.
Ms Winfred Badanga Nazziwa of the Uganda National Council for Science and Technology: “It is important to ensure that systems for ethics review and regulation of health research protect the safety, rights and welfare of research participants and at the same time do not impede health research progress. Achieving this balance requires capacity building for the research ethics committees and agencies responsible for health research oversight and regulation”.
“At the institutional level, systems and standard work processes have been improved, including office and ICT infrastructure support for research ethics committees and regulatory agencies. An important aspect of this was the development of an electronic Clinical Research Information Management System (CRIMS) within the agencies, and across the research ethics committees to facilitate communication in the review, approval and monitoring of clinical research protocols. The CRIMS is a tool intended to streamline review processes by the research ethics committees and regulatory agencies in Uganda while enabling investigators to track the progress of the review process.”
In order to improve the quality of ethical review of clinical research protocols by the research ethics committees and the national regulatory agencies, the accreditation system for the committees has been strengthened. Ms Badanga Nazziwa: “Accredited committees have been facilitated to develop clear policies and standard operating procedures which are easily accessible to researchers. This has strengthened the administrative capacity of the research ethics committees, in terms of staffing, infrastructure and logistics to facilitate their review operations. In addition, course materials for training directors and administrators of regional referral hospitals were developed. A course on research ethics and clinical trial management was delivered to directors and administrators of regional referral hospitals”.
The Clinical Research Information Management System implemented by the project will support the national regulatory agencies and the research ethics committees in their oversight of clinical research conducted in the country. Ms Badanga Nazziwa: “The CRIMS platform is a tool to assist agencies and committees in managing research-related records and interact with investigators more effectively. This will further improve the human research protection system in Uganda”.
Ms. Winfred Badanga Nazziwa
Project at a glance
Project: Consortium for clinical research regulation and ethics capacity development in Uganda (CREDU)
Project lead: Ms. Winfred Badanga Nazziwa, Uganda National Council for Science and Technology (UNCST), Uganda
Year funded: 2017
EDCTP funding: €0.3 M
Photo: Training on Research Ethics and Clinical Trial Management for Directors and Administrators of Regional Referral Hospitals at Mt Elgon Hotel Mbale, Eastern Uganda (February 2018).
Photo: The CRIMS platform (www.crims.ug).
Ethics review network in West Africa
The REECAO project is a research ethics network for West Africa based on North-South collaboration. The activities of REECAO (Renforcement de l’Ethique des Essais Cliniques en Afrique de l’Ouest) are supported by the Ministries of Health of Mali, Ghana and Guinea, the institutional review boards, and the Catholic University of Lyon, France, which contributes its experience in ethics training. The project is coordinated by Dr Karim Traoré of the Ministère de la Santé et de l’Hygiène Publique in Mali.
Dr Kaoré: “The network is coordinated by the Ministry of Health of Mali through the National Ethics Committee. A steering committee has been set up at the kick-off meeting including the coordinator of the network and the local coordinators of each country. This committee constitutes the governance structure of the network. In each country, the local coordinator and the national ethics committee of the country coordinate all the activities of the network in collaboration with the network coordinator. In Ghana, the activities are coordinated by the Institutional Ethics Committee of the Noguchi Memorial Institute of Medical Research. Each coordinator is the leader of a specific work package. All the institutional ethics committees in the three countries are involved in the training activities and the ethical debate during the case study meetings. Each local coordinator creates and maintains collaboration between institutional ethics committees and the national ethics committee or between the institutional ethics committees.”
West Africa has seen a strong increase in clinical trials in the last ten years. The need to conduct more clinical trials on malaria, TB, HIV and neglected infectious diseases and the recent epidemic of Ebola virus disease posed new challenges for ethical oversight and protection of clinical trial volunteers.
As in other regions of sub-Saharan Africa, many volunteers in clinical trials belong to poor rural populations, are often illiterate, have urgent health care needs, and sometimes have very different sociocultural views. These are all important factors that limit their understanding of complex aspects of clinical research. To better protect these populations, it is crucial to strengthen the governance, operation, effectiveness and sustainability of ethics committees. Additionally, language barriers in relation to multicentre clinical trials and the need to prepare for emergency research during epidemics indicated the need for a regional ethics network.
REECAO is to reinforce ethics oversight of clinical trials in Mali, Ghana, and Guinea. The project aims to achieve this by:
- establishing a joint ‘ethical watch’ through North-South and South-South collaboration;
- creating and implementing standardised procedures for protocol submission and evaluation;
- training a critical mass of trainers for ethics review;
- reinforcing the governance of ethics committees.
Dr Traoré: “REECAO is implementing a joint training program for national ethics committee and institutional review board members in Mali, Ghana and Guinea on ethical issues related to clinical trials and biotechnologies/nanotechnologies in humans. The objective of the training is to develop a critical mass of trainers in ethics for each institutional ethics committee and national ethics committee to maintain a continuous and autonomous training of ethic committee members. REECAO is also developing an online submission platform with standardised guidelines for protocol submission and review procedures within the network.”
REECAO already delivered its first results. It has set up the network, organised two sessions to discuss case studies and two training sessions for trainers (one in English and one in French). Six training modules were developed, the hotline to assist research ethics committee members and the database for ethics professionals have been set up.
Dr Traoré: “The long-term expected impact is to have created a critical mass of trainers in ethics, implemented standardised procedures, established a network of national and institutional ethics committees, with the oversight functions of national ethics committees reinforced. There will also be the possibility to extend the network to other countries and existing networks”.
Dr Karim Traoré
Project at a glance
Project: Renforcement de l’Éthique des Essais Cliniques en Afrique de l’Ouest [Strengthening research ethics of clinical trials in West Africa]
Project lead: Dr Karim Traoré, Ministère de la Santé et de l’Hygiène Publique, Mali
Year funded: 2017
EDCTP funding: €0.3 M
Strengthening pharmacovigilance in Africa
Pharmacovigilance is the science and activities relating to the detection, assessment, understanding and prevention of adverse drug effects or any other drug-related problem. In sub-Saharan African countries the capacity for pharmacovigilance (a major responsibility of the national medicines regulatory authorities) is often weak due to several challenges.
These challenges manifest within a context of poverty-related diseases where drugs and vaccines for these diseases increasingly receive conditional approval by e.g. the European Medicines Authority or the WHO on the basis of the results from clinical trials with limited numbers of participants. As a consequence, there is not much data on less frequent adverse effects, or on safety in specific subgroups such as children, the elderly or pregnant women. While public health programmes often collect adverse event data, this is rarely shared systematically with national regulatory authorities. So, there is no central insight into the safety profiles of these products.
The Pharmacovigilance Africa project (PAVIA) aims to strengthen national pharmacovigilance systems in a collaborative effort with public health programmes and to develop medicine safety surveillance activities in the context of the introduction of new drugs for multidrug-resistant tuberculosis.
Professor Frank Cobelens, coordinator of the PAVIA project: “The consortium consists of thirteen partners from Europe and Africa. PAVIA will reinforce the cooperation between the regulatory authorities responsible for pharmacovigilance and the public health programmes responsible for the introduction of new drugs and vaccines for poverty-related diseases in Ethiopia, the Kingdom of Eswatini, Nigeria and Tanzania. In addition, there are several partners that provide highly complementary technical contributions. The University of Benin (Nigeria), for example, brings expertise in pharmacovigilance legislation and medicines regulation on the African continent, while the Amsterdam Institute for Global Health and Development (Netherlands) provides assistance in long-term financial sustainability, in addition to project coordination and expertise in TB drugs. Other partners contribute equally vital expertise.”
PAVIA will strengthen the pharmacovigilance surveillance system and the capacity of pharmacovigilance staff in four countries in sub-Saharan Africa, building on the tuberculosis program financed by USAID. Through a collaborative approach between pharmacovigilance, public health programmes and clinicians the coverage, accessibility and effectiveness of existing evidence-based interventions will be strengthened and the introduction of new interventions will be supported.
Prof. Cobelens: “We expect PAVIA’s legacy to be strengthened national pharmacovigilance systems that have a cadre of competent staff, show improved regulatory and legal embedding, are financially sustainable and have strong and effective collaborations with public health programmes. Ultimately, this leads to effective systems for ensuring the safety of new drugs and vaccines. And not only in the countries where the project was implemented but also in those that used the lessons learnt”.
Prof. Frank Cobelens
Project at a glance
Project: Pharmaco Vigilance Africa
Project lead: Prof. Frank Cobelens, AIGHD, the Netherlands
Year funded: 2018
EDCTP funding: €3 M
Total project funding: €12.8 M
“The project will first strengthen the pharmacovigilance systems based on new drugs for multidrug-resistant tuberculosis (MDR-TB) delivered by the national TB programmes. In each country, PAVIA establishes a “triangle” of cooperation between the national tuberculosis programme, the regulatory authority and a local medical research institute that provides clinical and scientific expertise. This “triangle” provides a channel for reporting and interpreting safety signals regarding MDR-TB, serves as a training ground for pharmacovigilance staff and clinicians, and provides a demonstration project for similar collaboration within other disease control programs.”
PAVIA aims to demonstrate the potential of the “triangle approach” and what conditions need to be met to improve reporting of adverse events for new drugs and regimens for MDR-TB to infom medical decision-making.