Développement d’une approche de régulation des essais cliniques dans un contexte de pays en développement : le cas du Mali

Le Mali est devenu un milieu attractif pour les essais cliniques. Cependant, le cadre de réglementation pour leur surveillance y est très limité. Le pays manque de l’expertise, de l’infrastructure et des ressources nécessaires pour mettre en œuvre pleinement la régulation. Ceci représente un risque pour la sécurité des sujets de recherche et l’intégrité des résultats scientifiques. Il ne permet pas non plus de s’aligner sur les normes internationales en vigueur, telles que la déclaration d’Helsinki, les directives éthiques internationales du Conseil des organisations internationales des sciences médicales (CIOMS) ou les réglementations de pays industrialisés comme les États-Unis, le Canada ou l’Union Européenne. Pour améliorer la situation, la présente étude vise à comprendre les enjeux de la régulation des essais cliniques au Mali afin de suggérer des pistes de solutions et des recommandations. L’étude a été réalisée à l’aide de méthodes qualitatives, soit l’examen de documents officiels et des entrevues semi-dirigées avec les principaux acteurs impliqués dans les essais cliniques. La théorie néo-institutionnelle a servi de toile de fond à l’analyse des données. L’approche néo-institutionnelle consiste à expliquer l’influence de l’environnement sur les organisations. Selon cette approche, l’environnement s’assimile à des champs organisationnels incluant les connexions locales ou non, les liens horizontaux et verticaux, les influences culturelles et politiques ainsi que les échanges techniques. Les résultats présentés dans un premier article montrent l’existence de nombreux enjeux reflétant la carence du système de régulation au Mali. La coexistence de quatre scénarios d’approbation des essais cliniques illustre bien l’inconsistance des mécanismes. Tout comme l’absence d’inspection, l’inconsistance des mécanismes traduit également l’intervention limitée des pouvoirs publics dans la surveillance réglementaire. Ces enjeux résultent d’une double influence subie par les autorités réglementaires et les comités d’éthique. Ceux-ci sont, d’une part, influencés par l’environnement institutionnel sous pressions réglementaires, cognitives et normatives. D’autre part, les pouvoirs publics subissent l’influence des chercheurs qui opèrent comme des entrepreneurs institutionnels en occupant un rôle central dans le champ de la régulation. Dans un second article, l’étude propose une analyse détaillée des facteurs influençant la régulation des essais cliniques. Ces facteurs sont synthétisés en cinq groupes répartis entre deux sphères d’influence. L’analyse montre combien ces facteurs influencent négativement la régulation, notamment : 1) la structuration inachevée du champ de régulation due à un faible degré d’interactions, une absence de structure de coordination, d’informations mutuelles et de conscience dans la constitution des interdépendances; et 2) les positions relatives des acteurs impliqués dans la construction du champ de régulation se manifestant par une faible autorité des pouvoirs publics et l’ascendance des groupes de recherche. Enfin, dans un troisième article nous proposons quelques mécanismes qui, s’ils sont mis en œuvre, pourraient améliorer la régulation des essais cliniques au Mali. Ces mécanismes sont présentés, en référence au cadre théorique, sous trois types de vecteurs d’influence, notamment réglementaires, normatifs et cognitifs-culturels. En guise de conclusion, l’étude envoie un signal fort pour la nécessité d’une régulation appropriée des essais cliniques au Mali. Elle montre que la plupart des problèmes de fond en matière de régulation relèvent d’un besoin de restructuration du champ organisationnel et de renforcement de la position des pouvoirs publics.Mali has become an attractive environment for clinical trials. However, the regulatory framework for oversight of these trials is very limited. The country lacks the expertise, infrastructure and resources to fully implement the regulation. This represents a risk to the safety of research participants and the integrity of scientific results. As such, regulation in Mali does not meet international standards such as the Helsinki Declaration or the International Ethical Guidelines of the Council for International Organizations of Medical Sciences (CIOMS), or regulations of industrialized countries like the United States, Canada, or the European Union. To help address this situation, this study examines issues in the regulation of clinical trials in Mali in order to suggest possible solutions and provide recommendations. The study was carried out using qualitative methods; we reviewed official documents and conducted interviews with key stakeholders involved in clinical trials. Neo-institutional theory served as the framework with which to analyse the data. The focus of the neo-institutional approach is to explain the influence of the institutional environment on organizations. According to this approach, the institutional environment is composed of organizational fields such as local and non-local connections, vertical and horizontal ties, cultural and political influences, and technical exchanges. The results presented in the first article show that there are many issues that reflect the weakness of the regulatory system in Mali. The coexistence of four scenarios for approving clinical trials illustrates the inconsistency of current mechanisms. As well as the absence of inspection, there is also limited intervention on the part of the government in regulatory oversight. These issues arise from a double influence on the regulatory authorities and ethics committees. First, they are influenced by an institutional environment that is subject to regulatory, cognitive and normative pressures. Second, researchers operate as institutional entrepreneurs by occupying a central role in the field of regulation, and so influence the oversight bodies. In a second article, our study provides a detailed analysis of the factors influencing the regulation of clinical trials, synthesized into five groups that are divided into two spheres of influence. The analysis shows how these factors negatively influence regulation, specifically: 1) there is an incomplete structuring of the regulatory field due to a low degree of interaction, a lack of coordination structure, mutual information and consciousness in the constitution of interdependencies, and 2) the relative positions of the actors involved in the construction of the regulatory field manifests in a weak authority of the government and the domination of research groups. Finally, in a third article we propose some mechanisms that, if implemented, could improve the regulation of clinical trials in Mali. These mechanisms are presented, with reference to the theoretical framework, as three channels of influence, namely regulatory, normative and cultural-cognitive. In conclusion, the study sends a strong signal for the need for appropriate regulation of clinical trials in Mali. It shows that the most fundamental problems in regulation result from a need for restructuring of the organizational field and a strengthening the position of governmen

Factors influencing the utilization of research findings by health policy-makers in a developing country: the selection of Mali's essential medicines

BACKGROUND: Research findings are increasingly being recognized as an important input in the formation of health policy. There is concern that research findings are not being utilized by health policy-makers to the extent that they could be. The factors influencing the utilization of various types of research by health policy-makers are beginning to emerge in the literature, however there is still little known about these factors in developing countries. The object of this study was to explore these factors by examining the policy-making process for a pharmaceutical policy common in developing countries; an essential medicines list. METHODS: A study of the selection and updating of Mali's national essential medicines list was undertaken using qualitative methods. In-depth semi-structured interviews and a natural group discussion were held with national policy-makers, most specifically members of the national commission that selects and updates the country's list. The resulting text was analyzed using a phenomenological approach. A document analysis was also performed. RESULTS: Several factors emerged from the textual data that appear to be influencing the utilization of health research findings for these policy-makers. These factors include: access to information, relevance of the research, use of research perceived as a time consuming process, trust in the research, authority of those who presented their view, competency in research methods, priority of research in the policy process, and accountability. CONCLUSION: Improving the transfer of research to policy will require effort on the part of researchers, policy-makers, and third parties. This will include: collaboration between researchers and policy-makers, increased production and dissemination of relevant and useful research, and continued and improved technical support from networks and multi-national organizations. Policy-makers from developing countries will then be better equipped to make informed decisions concerning their health policy issues

Assessment of the impact of market regulation in Mali on the price of essential medicines provided through the private sector

Objective In 1998, the government of Mali adopted a national pharmaceutical policy aimed at promoting a supply system for generic essential medicines that would guarantee equal access for all citizens. Distribution and delivery is a shared responsibility of both public and private sectors (wholesalers and pharmacies). To influence private sector behaviour, the national policy uses a combination of government regulation and market forces. In 2006, the government issued a decree fixing maximum prices in the private sector for 107 prescription drugs from the national list of 426 essential medicines. The current study assessed the impact of this intervention on the evolution of market prices (wholesale and retail), and the subsequent availability and public access to essential medicines in Mali.Methods A cross-sectional descriptive survey was conducted in February and May 2006, and January 2009, with 16 wholesalers and 30 private drugstores in Bamako, Mali.Results The overall availability of essential medicines at private wholesalers (p = 1) and pharmacies (p = 0.53) was identical before and after the enforcement of the 2006 decree fixing maximum drug prices. Contrary to concerns expressed by wholesalers and pharmacies, and the other stakeholders, the decree did not impact negatively on availability of essential medicines. In fact, median wholesale prices in 2009 were 25.6% less than those fixed by the decree. In private pharmacies, retail prices were only 3% more expensive than the recommended prices, compared with being 25.5% more expensive prior to enforcement of the decree.Conclusions The study shows that prices of essential medicines in Mali have evolved favourably towards the prices recommended by the government decree. Further, the study contributes to mounting evidence that market regulation by governments does not necessarily negatively affect drug availability; in fact, given the reduction in prices, the study shows that Malians arguably have better access to more affordable essential medicines.Essential medicines Pharmaceutical Market regulation Monitoring Pharmacy Private sector Mali

Facteurs influençant la régulation des essais cliniques au Mali

Depuis 2005, le Mali participe à des activités de renforcement des autorités nationales de réglementation (ANR) initiées par l’OMS en vue d’une bonne régulation des essais cliniques. Malgré cette participation, il y a peu de régulation des essais et cette faiblesse s’explique en partie par un manque d’appropriation des mesures par les autorités nationales. Ainsi, il semble essentiel de comprendre quels facteurs influencent la régulation des essais cliniques, aspect encore peu étudié. En utilisant un cadre analytique basé sur la théorie néo-institutionnelle, cette étude qualitative à visée exploratoire, a été réalisée à partir d’entrevues semi-dirigées avec les ANR, les comités d’éthique, des chercheurs, des administrateurs, des praticiens hospitaliers et d’examens documentaires. Les résultats montrent que la configuration du champ organisationnel et la position des pouvoirs publics dans ce champ apparaissent essentiels à la compréhension des facteurs qui influencent la régulation des essais cliniques. La prépondérance des barrières à la régulation des essais, associée à l’incapacité des pouvoirs publics de renforcer la régulation et la faible structuration du champ organisationnel, plaident en faveur d’une réforme intégrale plutôt que pour l’adoption de mesures partielles comme, par exemple, les revues et inspections conjointes d’essais cliniques promues par l’OMS.Since 2005, Mali has participated in World Health Organization (WHO) training activities for national regulatory authorities (NRAs) to aid the proper regulation of clinical trials. Despite this participation, there is still very little regulation of trials, a weakness due in part to a lack of integration of oversight mechanism by national authorities. It is thus important to understand what factors actually influence the regulation of clinical trials in Mali. Using an analytical framework based on neo-institutional theory, this exploratory qualitative study involved semi-structured interviews with the Malian NRA, ethics committees, researchers, administrators and hospital practitioners, along with documentary analyses. The results show that the configuration of the organizational field and the position of authorities in this field are essential to understanding the factors that influence the regulation of clinical trials. The preponderance of regulatory barriers to clinical trials, coupled with the inability of the government to strengthen regulation and the weak organizational structure of the field, call for a comprehensive reform rather than partial measures such as, for example, joint reviews and inspections of clinical trials promoted by the WHO

Vaccine Licensure in the Absence of Human Efficacy Data

Clinical vaccine development and regulatory approval generally occurs in a linear, sequential manner: Phase 1: safety, immunogenicity; Phase 2: immunogenicity, safety, dose ranging, and preliminary efficacy; Phase 3: definitive efficacy, safety, lot consistency; and following regulatory approval, Phase 4: post-marketing safety and effectiveness. For candidate filovirus vaccines, where correlates of protection have not been identified, and phase 2 and 3 efficacy of disease prevention trials untenable, large and/or protracted, each trial may span decades, with full licensure expected only after several decades of development. Given the urgent unmet need for new Marburg virus and Ebola Sudan virus vaccines, the Sabin Vaccine Institute hosted a key stakeholder virtual meeting in May 2021 to explore the possibility of licensure by use of an “animal rule-like” licensure process, based on a risk/benefit assessment specific to regional needs and informed by epidemiology. This may be appropriate for diseases where there are no or limited treatment options, and those prone to sporadic outbreaks with high rates of transmission, morbidity, and mortality. The discussion focused on two contexts: licensure within the Ugandan regulatory environment, a high burden country where Ebola vaccine trials are ongoing, and licensure by the United States FDA—a well-resourced regulatory agency

Realising the potential of correlates of protection for vaccine development, licensure and use: short summary

On 27–29th of September 2022, Wellcome convened an international multi-stakeholder workshop to discuss the use of Correlates of Protection (CoP) to accelerate vaccine development, the hybrid format meeting was attended by 80 delegates including developers, manufacturers, regulators, public health officials and policy-makers from 17 countries, including 7 LMIC’s