Clinical trials for identification of efficient and effective new diagnostic and treatment modalities are needed to address disproportionately high burden of communicable (e.g., HIV/AIDS, tuberculosis, and malaria) and non-communicable diseases (e.g., diabetes) in developing countries. However, gross under-representation in global clinical trial platforms contributes to sustained health inequity in these countries. We reviewed the literature on barriers facing clinical researchers in developing countries for conducting clinical trials in their countries. Literature indexed in PubMed, Embase, CINAHL and Web of Science, WHO Global Health Library were searched. Grey literature was also searched. Search key words included barriers, challenges, clinical trials and developing countries. Articles within the scope of this review were appraised by two reviewers. Ten studies, which are reported in 15 papers, were included in this review. Following critical review we identified five unifying themes for barriers. Barriers for conducting clinical trials included lack of financial and human capacity, ethical and regulatory system obstacles, lack of research environment, operational barriers and competing demands. There were substantial barriers at system, organization and individual level. We propose that to address this problem, instituting a system for wider implementation of local investigator-initiated trials is warranted. These trials are more applicable to local populations because they build on local healthcare knowledge. They are more demand-led, influence policy and responsive to a country’s needs because they are driven by a local or national agenda.

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Barriers for conducting clinical trials in developing countries- a systematic review

Background 
The costs, complexity, legal requirements and number of amendments associated with clinical trials are rising constantly, which negatively affects the efficient conduct of trials. In Sub-Saharan Africa, this situation is exacerbated by capacity and funding limitations, which further increase the workload of clinical trialists. At the same time, trials are critically important for improving public health in these settings. The aim of this study was to identify the internal factors that slow down clinical trials in Sub-Saharan Africa. Here, factors are limited to those that exclusively relate to clinical trial teams and sponsors. These factors may be influenced independently of external conditions and may significantly increase trial efficiency if addressed by the respective teams.


Methods 
We conducted sixty key informant interviews with clinical trial staff working in different positions in two clinical research centres in Kenya, Ghana, Burkina Faso and Senegal. The study covered English- and French-speaking, and Eastern and Western parts of Sub-Saharan Africa. We performed thematic analysis of the interview transcripts.


Results 
We found various internal factors associated with slowing down clinical trials; these were summarised into two broad themes, “planning” and “site organisation”. These themes were consistently mentioned across positions and countries. “Planning” factors related to budget feasibility, clear project ideas, realistic deadlines, understanding of trial processes, adaptation to the local context and involvement of site staff in planning. “Site organisation” factors covered staff turnover, employment conditions, career paths, workload, delegation and management.


Conclusions 
We found that internal factors slowing down clinical trials are of high importance to trial staff. Our data suggest that adequate and coherent planning, careful assessment of the setting, clear task allocation and management capacity strengthening may help to overcome the identified internal factors and allow clinical trials to proceed more efficiently.

/pdf/you-can-save-time-if-a-qualitative-study-on-internal-factors-sto3cxwuyj.pdf

"You can save time if…"—A qualitative study on internal factors slowing down clinical trials in Sub-Saharan Africa

Clinical research is important in establishing the effects of health-care interventions. Vaccine clinical trials are to examine the effectiveness and safety of vaccines for the prevention of diseases. Africa has a high burden of infectious diseases such as malaria, tuberculosis, HIV/AIDS, and Ebola virus disease. Here we report a database surveillance study of vaccine-related clinical trials conducted in Africa. An objective is to address and profile vaccine clinical trials conducted in Africa. Data were extracted from the WHO International Clinical Trials Registry Platform on 22 July 2018 and updated on 05 September 2019. We found that 61% of the 377 clinical trials were registered prospectively and 35% registered retrospectively. About 72% of the trials were single-country studies and within the country, most trials (86%) were single-center studies. The proportion of trials involving multiple African countries was 11% and that of trials involving countries outside of Africa was 16%. The biggest funder of the vaccine trials (34%) was industry, followed by governments (25%) and universities (21%). The most studied diseases were malaria (20%), HIV/AIDS (15%), tuberculosis (7%), and Ebola virus disease (6%). Most of the vaccine trials were conducted in adults (42%). The trials ranged from phase I to phase IV, with most of the trials being in phase I (18%) and phase III (18%). The conduct of vaccine clinical trials in Africa seeks to address the disease epidemics faced by the continent. There is a need for more investments from governmental bodies toward vaccine research in Africa. Further, African country collaborations are needed in efforts to find African solutions to the current infectious disease threats faced by the continent.

https://www.tandfonline.com/doi/pdf/10.1080/21645515.2019.1693720

Description of vaccine clinical trials in Africa: a narrative review

BACKGROUND The geographic representation of investigators and participants in heart failure (HF) randomized clinical trials (RCTs) may not reflect the global burden of disease. AIMS We assessed the geographic diversity of RCT leaders and explored associations with geographic representation of enrolled participants among impactful HF RCTs. METHODS AND RESULTS We searched MEDLINE, EMBASE, and CINAHL for HF RCTs published in journals with impact factor ≥10 between January 2000 and June 2020. We used the Jonckheere-Terpstra test to assess temporal trends and multivariable logistic regression models to explore associations between predictors and outcomes. There were 414 eligible RCTs. Only 80 of 828 trial leaders (9.7%; 95% CI: 7.8% to 11.8%), and 453 of 4656 collaborators (9.7%; 95% CI: 8.8% to 10.6%) were from outside Europe and North America, with no change in temporal trends and greater disparities in large RCTs. The adjusted odds of trial leadership outside Europe and North America were lower with industry funding (aOR: 0.33; 95% CI: 0.15 to 0.75; P = 0.008). Among 157,416 participants in whom geography was reported, only 14.5% (95% CI: 14.3% to 14.7%) were enrolled outside Europe and North America, but odds of enrolment were ten-fold greater with trial leadership outside Europe and North America (aOR: 10.0; 95% CI 5.6-19.0; P < 0.001). CONCLUSIONS Regions disproportionately burdened with HF are under-represented in HF trial leadership, collaboration, and enrolment. RCT leadership outside Europe and North America is independently associated with participant enrolment in under-represented regions. Increasing research capacity outside Europe and North America could enhance trial diversity and generalizability.

http://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcab058/40393778/qcab058.pdf

Global Representation of Heart Failure Clinical Trial Leaders, Collaborators, and Enrolled Participants: A Bibliometric Review 2000-2020.

Clinical trial study failures cause significant disruptions to supply chain operations, which lead to operational inefficiencies and financial losses. In this paper, a framework to construct a Bayesian belief network (BBN) by leveraging subject matter expertise and probabilistic elicitation methods to quantify the probability of a disruption to a clinical supply chain is presented. The effect of varying input factors on a disruption probability is studied, and new metrics are developed to evaluate the significance of a disruption. This framework allows practitioners to assess the probability of disruptions to their network, thus enabling targeted strategies to be developed and implemented.

A Framework for Assessing Disruptions in a Clinical Supply Chain Using Bayesian Belief Networks

International public health and infectious diseases research has expanded to become a global enterprise transcending national and continental borders in organized networks addressing high-impact diseases. In conducting multicountry clinical trials, sponsors and investigators have to ensure that they meet regulatory requirements in all countries in which the clinical trials will be conducted. Some of these requirements include review and approval by national drug regulatory authorities and recognized research ethics committees. A limiting factor to the efficient conduct of multicountry clinical trials is the regulatory environment in each collaborating country, with significant differences determined by various factors including the laws and the procedures used in each country. The long regulatory processes in resource-limited countries may hinder the efficient implementation of multisite clinical trials, delaying research important to the health of populations in these countries and costing millions of dollars a year.

Christina L Blanchard-Horan

Papers

Regulatory challenges associated with conducting multicountry clinical trials in resource-limited settings.