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Background: We sought to develop and test an objective scorecard-based system for assessing and categorizing available research sites in Lassa fever-affected countries based on their preparedness and capability to host Lassa fever vaccine clinical trials.
Methods: We mapped available clinical research sites through interrogation of online clinical trial registries and relevant disease-based consortia. A structured online questionnaire was used to assess the capability of clinical trial sites to conduct Lassa fever vaccine clinical trials. We developed a new scoring template by allocating scores to questionnaire parameters based on perceived importance to the conduct of clinical trials as described in the WHO/TDR Global Competency Framework for Clinical Research. Cutoff points of 75% and 50% were used to categorize sites into categories A, B, or C.
Results: This study identified 44 clinical trial sites in 8 Lassa fever-affected countries. Out of these, 35 sites were characterized based on their capacity to hold Lassa fever vaccine clinical trials. A total of 14 sites in 4 countries were identified as ready to host Lassa fever vaccine trials immediately or with little support.
Conclusion: It is feasible to hold Lassa fever vaccine trials in affected countries based on the outcome of the survey. However, the findings are to be validated through sites' visits. This experience with a standardized and objective method of the site assessment is encouraging, and the site selection method used can serve as an orientation to sponsors and researchers planning clinical trials in the region.
Improving Risk Assessment in Clinical Trials: Toward a Systematic Risk-Based Monitoring Approach
(2021)
Regulatory authorities have encouraged the usage of a risk-based monitoring (RBM) system in clinical trials before trial initiation for detection of potential risks and inclusion of a mitigation plan in the monitoring strategy. Several RBM tools were developed after the International Council for Harmonization gave sponsors the flexibility to initiate an approach to enhance quality management in a clinical trial. However, various studies have demonstrated the need for improvement of the available RBM tools as each does not provide a comprehensive overview of the characteristics, focus, and application. This research lays out a rationale for a risk methodology assessment (RMA) within the RBM system. The core purpose of RMA is to deliver a scientifically based evaluation and decision of any potential risk in a clinical trial. Thereby, a monitoring plan can be developed to elude prior identified risk outcome. To demonstrate RMA’s theoretical approach in practice, a Shiny web application (R Foundation for Statistical Computing) was designed to describe the assessment process of risk analysis and visualization tools that eventually aid in focusing monitoring activities. RMA focuses on the identification of an individual risk and visualizes its weight on the trial. The scoring algorithm of the presented approach computes the assessment of the individual risk in a radar plot and computes the overall score of the trial. Moreover, RMA’s novelty lies in its ability to decrease biased decision making during risk assessment by categorizing risk influence and detectability; a characteristic pivotal to serve RBM in assessing risks, and in contributing to a better understanding in the monitoring technique necessary for developing a functional monitoring plan. Future research should focus on validating the power of RMAs to demonstrate its efficiency. This would facilitate the process of characterizing the strengths and weaknesses of RMA in practice.
Background
The business of clinical research has changed in the past two decades, shifting from industrialised Western countries to so-called emerging markets such as Eastern Europe, Latin America and Africa. An appraisal of the trends could identify associated factors that may have implications for the local populations and their endemic diseases.
Objectives
To identify potential reasons why emerging countries have become attractive places for international sponsors to conduct their clinical trials.
Methods
Using ClinicalTrials.gov, the Pan African Clinical Trials Registry, the National Health Research Database and the Nigeria Clinical Trials Registry, trend data on clinical research development were determined for two emerging African markets, Nigeria and South Africa (SA), from 2010 to 2018. Also, health data on the two countries from the fact sheets of health statistics of the World Health Organization were compared, as well as regulatory and ethical conditions. Available data were analysed using descriptive statistics and trend analysis.
Results
The impact of globalisation is evident from the upward trend in clinical trials in SA before 2010, and the clear downward trend thereafter. One reason for this change could be the alignment of SA’s regulatory and ethical frameworks with the Western world. In contrast,
the upward trend is only just beginning in Nigeria, with the introduction of ethical/regulatory frameworks, and supportive institutions making the business of clinical research more attractive on an international level. Although the number of international and local sponsors increased in Nigeria from 2010 to 2018, only the latter increased in SA, with the former decreasing over the same period. Overall, there is a mismatch between country-specific diseases and the drugs being tested, to the extent that leprosy, which is endemic in Nigeria, and tuberculosis in SA were not in the list of top 10 study areas in either country.
Conclusions
The globalisation trend is evident in the clinical trials business, but cannot be generalised to all emerging countries. Timing and intensity vary from country to country relative to factors that advance the existing profit-orientated business models of the sponsors. Furthermore, various diseases have been localised, which entails a diversely increasing need for research.
Background: The globalization of clinical research should also benefit the population in developing markets. In this context, the approval of tested medicines and the associated expansion of medical care beyond clinical studies would be desirable as a possible long-term benefit.
Objectives: This study was designed to compare the development of the number of clinical trials with the number of marketing authorizations of medicines on the African continent. To contrast these 2 parameters, the data were analyzed using the model of an ecological study.
Methods: To reflect the broad spectrum of African developing countries with diverse levels of development, the data collection was based on 2 geographically selected sample countries each from Central, North, East, West, and Southern Africa. Based on the ClinicalTrials.gov registry, the first step was to collect trends data on the development of the clinical trials in the 10 selected countries of the country list of the African Region published by the World Health Organization for the period 2015 to 2018. Subsequently, data on the current number of marketing authorizations of medicines in the selected sample countries were identified using the online registries of the national authorities. The data were utilized in comparative analyses.
Results: Eight out of 10 model countries showed an increase in the number of clinical trials, with the exceptions of Cameroon and Libya, which showed an overall decline in research activity over the entire time. In direct comparison with drug registrations, the numbers indicate a similar development. The only exception here is Nigeria, a country with a solid performance in clinical research and yet a decrease in medicine registrations since 2015.
Conclusions: The expected increase in the development of clinical research as result of the globalization trend can basically be observed in most of the model countries. However, this increase does not guarantee an improvement in the number of medicine registrations. Although this is evident in some of the selected model countries, it cannot be projected to the entire African region. This may be linked to the diverse development of the individual countries due to the different political situations and the varying degrees of clinical research infrastructure.
Monitoring of clinical trials is a fundamental process required by regulatory agencies. It assures the compliance of a center to the required regulations and the trial protocol. Traditionally, monitoring teams relied on extensive on-site visits and source data verification. However, this is costly, and the outcome is limited. Thus, central statistical monitoring (CSM) is an additional approach recently embraced by the International Council for Harmonisation (ICH) to detect problematic or erroneous data by using visualizations and statistical control measures. Existing implementations have been primarily focused on detecting inlier and outlier data. Other approaches include principal component analysis and distribution of the data. Here we focus on the utilization of comparisons of centers to the Grand mean for different model types and assumptions for common data types, such as binomial, ordinal, and continuous response variables. We implement the usage of multiple comparisons of single centers to the Grand mean of all centers. This approach is also available for various non-normal data types that are abundant in clinical trials. Further, using confidence intervals, an assessment of equivalence to the Grand mean can be applied. In a Monte Carlo simulation study, the applied statistical approaches have been investigated for their ability to control type I error and the assessment of their respective power for balanced and unbalanced designs which are common in registry data and clinical trials. Data from the German Multiple Sclerosis Registry (GMSR) including proportions of missing data, adverse events and disease severity scores were used to verify the results on Real-World-Data (RWD).
Economic and political/governmental infrastructural factors are major contributors to the economic development/growth of all sectors of a country, such as in the area of healthcare systems and clinical research, including the pharmaceutical industry. But what is the interaction between economic, and political/governmental infrastructural factors and the development of healthcare systems, especially, the performance of the pharmaceutical industry? Information from selected articles of a literature search of PubMed and by using Google Advanced Search led to the generation of five categories of infrastructural factors, and were filled with data from 41 African Countries using the World Health Organization data repository. Median changes over time were given and tested by Wilcoxon signed-rank test and Friedman test, respectively. Analysis of factors related to availability of healthcare facilities showed that physicians and pharmacies were significant increased, with insignificantly decreased number of hospital beds. Healthcare Financing by the Government showed notable differences. Private health spending decreased significantly unlike Gross National Income. Analysis of infrastructural factors showed that stable supply of electricity and the associated use of the Internet improved significantly. The low level of data on the expansion of paved road networks suggests less developed medical services in remote rural areas. Healthcare systems in African countries improved over the last two decades, but differences between the individual countries still prevail and some of the countries cannot yet offer an attractive sales market for the products of pharmaceutical companies.