Defining clinical trial quality from the perspective of resource-limited settings: a qualitative study based on interviews with investigators, sponsors, and monitors conducting clinical trials in sub-Saharan Africa

In recent decades, the quality management of clinical trials has been criticised for being inefficient and ineffective. This has led to a waste of clinical trial investment and has made it particularly difficult to conduct clinical trials in settings with limited resources. The lack of a universally accepted comprehensive definition of clinical trial quality was suggested as one of the possible causes of inadequate quality management. However, resource-limited countries were not considered in the attempt to create such a definition. In our study, we developed a quality concept based on qualitative interviews from the perspective of investigators, sponsors, and monitors with experience in conducting clinical trials in sub-Saharan Africa. The analysis of these stakeholders' definitions of clinical trial quality has produced a Clinical Trial Quality Concept that includes quality promoting factors (i.e., Context adaptation; Infrastructure; Partnership; Operational excellence; Quality system) in addition to conventional scientific and ethical factors. The results thus support the need for a multidimensional quality concept to reflect clinical trial quality more comprehensively. We recommend the term "Comprehensive Quality Management (CQM)" for this concept. CQM has the potential to serve as a basis for the current revision of quality management principles in international clinical trial guidelines. Furthermore, the sub-Saharan African perspective has highlighted additional considerations compared to the existing comprehensive INQUIRE clinical trial quality framework. Therefore, we propose including the following three points relevant to resource-limited settings in the framework: 1) Communicating potential infrastructural disadvantages to funders, sponsors, and auditors. 2) Preventing potential exploitation of research populations and workforce in low- and middle-income countries by following existing ethical frameworks. 3) Including "Context adaptation" as an additional framework category (i.e., promoting factor)

Defining clinical trial quality from the perspective of resource-limited settings: A qualitative study based on interviews with investigators, sponsors, and monitors conducting clinical trials in sub-Saharan Africa

Background Increasing clinical trial cost and complexity, as well as a high waste of clinical trial investment over the past decades, have changed the way clinical trial quality is managed. Recent evidence has highlighted that the lack of a clear clinical trial quality definition may have contributed to previous inefficiencies. This study aims to support the understanding of what clinical trial quality entails from the perspective of resource-limited settings. Methodology/Principal findings We conducted 46 semi-structured interviews involving investigators, sponsors, and monitors with experience in conducting clinical trials in 27 countries in sub-Saharan Africa. The questionnaire addressed the overall meaning of clinical trial quality and a conclusive clinical trial quality definition, as well as specific aspects of resource-limited settings across the clinical trial process. We held the interviews either in person, via Skype or by phone. They were recorded and transcribed verbatim, and we performed the analysis using The Framework Method. The analysis of clinical trial quality definitions resulted in 11 elements, which were summarised into a clinical trial quality concept consisting of two components: 1) clinical trial quality building factors (Scientific factors and Moral factors) and 2) promoting factors (Context adaptation; Infrastructure; Partnership; Operational excellence; Quality system). 12 resource-limited settings specific themes were identified. These themes were all categorised under the promoting factors "Context adaptation", "Infrastructure", and "Partnership". Conclusions/Significance We found that in order to enable comprehensive clinical trial quality management, clinical trial quality should be defined by a multidimensional concept that includes not only scientific and ethical, but also quality-promoting factors. Such a concept is of general relevance and not limited to clinical trials in resource-limited settings, where it naturally carries particular weight. In addition, from the perspective of sub-Saharan Africa, we identified specific categories that appear to be critical for the conduct of clinical trials in resource-limited settings, and we propose respective changes to a particular existing clinical trial quality framework (i.e., INQUIRE)

Phenomics data processing: A plot-level model for repeated measurements to extract the timing of key stages and quantities at defined time points

Decision-making in breeding increasingly depends on the ability to capture and predict crop responses to changing environmental factors. Advances in crop modeling as well as high-throughput eld phenotyping (HTFP) hold promise to provide such insights. Processing HTFP data is an interdisciplinary task that requires broad knowledge on experimental design, measurement techniques, feature extraction, dynamic trait modeling, and prediction of genotypic values using statistical models. To get an overview of sources of variation in HTFP, we develop a general plot-level model for repeated measurements. Based on this model, we propose a seamless step-wise procedure that allows for carry on of estimated means and variances from stage to stage. The process builds on the extraction of three intermediate trait categories; (1) timing of key stages, (2) quantities at de ned time points or periods, and (3) dose-response curves. In a rst stage, these intermediate traits are extracted from low-level traits’ time series (e.g., canopy height) using P-splines and the quarter of maximum elongation rate method (QMER), as well as nal height percentiles. In a second and third stage, extracted traits are further processed using a stage-wise linear mixed model analysis. Using a wheat canopy growth simulation to generate canopy height time series, we demonstrate the suitability of the stage-wise process for traits of the rst two above-mentioned categories. Results indicate that, for the rst stage, the P-spline/QMER method was more robust than the percentile method. In the subsequent two-stage linear mixed model processing, weighting the second and third stage with error variance estimates from the previous stages improved the root mean squared error. We conclude that processing phenomics data in stages represents a feasible approach if estimated means and variances are carried forward from one processing stage to the next. P-splines in combination with the QMER method are suitable tools to extract timing of key stages and quantities at de ned time points from HTFP data

‘I Could Not Bear It’. Perceptions of Chronic Pain among Somali Pastoralists in Ethiopia. A Qualitative Study

Background Pain is a major public health problem in the Global South, particularly among marginalized communities, such as Somali pastoralists. Yet, the topic of chronic pain has not yet been comprehensively studied in Sub-Saharan Africa, specifically in the Somali region of Ethiopia. Therefore, this study aims to explore the perceptions and notions of chronic pain among Somali pastoralists in this context. Methods This study used an explorative qualitative design. We performed semi-structured, face-to-face interviews with 20 purposively selected female and male Somali pastoralists with chronic pain. For data analysis, we applied the Framework Method by Gale et al. and explained patterns drawing on the Enactive Approach to Pain proposed by Stilwell and Harman. Findings Six different themes emerged: (1) “Pain as a symptom of harsh daily life”, (2) “Pain descriptions and dimensions”, (3) “Temporality of pain”, (4) “Pain-related stigma and stoicism” (5) “Mediating role of spirituality”, and (6) “Impact of pain on daily life activities”. Conclusions Somali pastoralists described their chronic pain as a multicausal and relational experience. Pastoralists (especially women) commonly refrained from communicating their pain and represented aspects of social stigma and stoicism. The mediating role of spirituality aided pastoralists to make sense of their pain and to ease its impact on their harsh daily life. The findings of this study can contribute to raise awareness of chronic pain issues among pastoralists. They highlight the need for policymakers to prioritize the improvement of pastoralist-specific pain management. Necessary resources and skills should be available within health care facilities. Pain management should be accessible, affordable and culturally acceptable for this population

Opportunities and challenges for decentralised clinical trials in sub-Saharan Africa: a qualitative study

IntroductionDigital health has gained traction in research and development, and clinical decision support systems. The COVID-19 pandemic accelerated the adoption of decentralised clinical trials (DCTs) as a mitigation and efficiency improvement strategy. We assessed the opportunities and challenges of a digital transformation in clinical research in sub-Saharan Africa from different stakeholders’ perspectives.MethodsA qualitative study, including 40 in-depth semi structured interviews, was conducted with investigators of three leading research institutions in sub-Saharan Africa and Switzerland, contract research organisations and sponsors managing clinical trials in sub-Saharan Africa. A thematic approach was used for the analysis.ResultsInterviewees perceived DCTs as an opportunity for trial efficiency improvement, quality improvement and reducing the burden of people participating in clinical trials. However, to gain and maintain an optimal quality of clinical trials, a transition period is necessary to tackle contextual challenges before DCTs are being implemented. The main challenges are categorised into four themes: (1) usability and practicability of the technology; (2) paradigm shift and trial data quality; (3) ethical and regulatory hurdles and (4) contextual factors (site-specific research environment and sociocultural aspects).ConclusionThe transformation from a site to a patient-centric model with an increased responsibility of participants should be context adapted. The transformation requires substantial investment, training of the various stakeholders and an efficient communication. Additionally, commitment of sponsors, investigators, ethics and regulatory authorities and the buy-in of the communities are essential for this change

"I could not bear it": Perceptions of chronic pain among Somali pastoralists in Ethiopia. A qualitative study.

BackgroundPain is a major public health problem in the Global South, particularly among marginalized communities, such as Somali pastoralists. Yet, the topic of chronic pain has not yet been comprehensively studied in Sub-Saharan Africa, specifically in the Somali region of Ethiopia. Therefore, this study aims to explore the perceptions and notions of chronic pain among Somali pastoralists in this context.MethodsThis study used an explorative qualitative design. We performed semi-structured, face-to-face interviews with 20 purposively selected female and male Somali pastoralists with chronic pain. For data analysis, we applied the Framework Method by Gale et al. and explained patterns drawing on the Enactive Approach to Pain proposed by Stilwell and Harman.FindingsSix different themes emerged: (1) "Pain as a symptom of harsh daily life", (2) "Pain descriptions and dimensions", (3) "Temporality of pain", (4) "Pain-related stigma and stoicism" (5) "Mediating role of spirituality", and (6) "Impact of pain on daily life activities".ConclusionsSomali pastoralists described their chronic pain as a multicausal and relational experience. Pastoralists (especially women) commonly refrained from communicating their pain and represented aspects of social stigma and stoicism. The mediating role of spirituality aided pastoralists to make sense of their pain and to ease its impact on their harsh daily life. The findings of this study can contribute to raise awareness of chronic pain issues among pastoralists. They highlight the need for policymakers to prioritize the improvement of pastoralist-specific pain management. Necessary resources and skills should be available within health care facilities. Pain management should be accessible, affordable and culturally acceptable for this population

Exome sequences and multi-environment field trials elucidate the genetic basis of adaptation in barley

Broadening the genetic base of crops is crucial for developing varieties to respond to global agricultural challenges such as climate change. Here, we analysed a diverse panel of 371 domesticated lines of the model crop of barley to explore the genetics of crop adaptation. We first collected exome sequence data and phenotypes of key life history traits from contrasting multi-environment common garden trials. Then we applied refined statistical methods, including based on exomic haplotype states, for genotype-by-environment (G 7E) modelling. Sub-populations defined from exomic profiles were coincident with barley's biology, geography and history, and explained a high proportion of trial phenotypic variance. Clear G 7E interactions indicated adaptation profiles that varied for landraces and cultivars. Exploration of circadian clock-related genes, associated with the environmentally-adaptive days to heading trait (crucial for the crop's spread from the Fertile Crescent), illustrated complexities in G 7E effect directions, and the importance of latitudinally-based genic context in the expression of large effect alleles. Our analysis supports a gene-level scientific understanding of crop adaption and leads to practical opportunities for crop improvement, allowing the prioritisation of genomic regions and particular sets of lines for breeding efforts seeking to cope with climate change and other stresses

Constraint-based probabilistic learning of metabolic pathways from tomato volatiles

Clustering and correlation analysis techniques have become popular tools for the analysis of data produced by metabolomics experiments. The results obtained from these approaches provide an overview of the interactions between objects of interest. Often in these experiments, one is more interested in information about the nature of these relationships, e.g., cause-effect relationships, than in the actual strength of the interactions. Finding such relationships is of crucial importance as most biological processes can only be understood in this way. Bayesian networks allow representation of these cause-effect relationships among variables of interest in terms of whether and how they influence each other given that a third, possibly empty, group of variables is known. This technique also allows the incorporation of prior knowledge as established from the literature or from biologists. The representation as a directed graph of these relationship is highly intuitive and helps to understand these processes. This paper describes how constraint-based Bayesian networks can be applied to metabolomics data and can be used to uncover the important pathways which play a significant role in the ripening of fresh tomatoes. We also show here how this methods of reconstructing pathways is intuitive and performs better than classical techniques. Methods for learning Bayesian network models are powerful tools for the analysis of data of the magnitude as generated by metabolomics experiments. It allows one to model cause-effect relationships and helps in understanding the underlying processes

Waiting for “Good Care”. Biomedicine and the Elderly in North Sulawesi, Indonesia

Older persons in North Sulawesi (Indonesia) shared a long experience with biomedical health interventions during Soeharto’s New Order administration. These vertically and top-down structured development activities in health no longer fit current demographic, epidemiological, and social transformations in Indonesia. The rapidly aging communities, the sharp increase in non-communicable diseases, and aging impairments along with rapidly changing household assemblages call for a biomedical public health that ideally covers cure and care in equal shares. This understanding and vision of “good care” leads to a dynamic appropriation of biomedical services initiated by older persons. Here the monthly local health post sessions for elderly people occupy center stage of this appropriative process: a highly formalized and ritualized medical check-up based on the administration of drug which covers basic curative needs. In addition, the local cadres for aged persons play a significant role as intermediary and broker between an elderly patient, his/her caregiver(s), and the health professionals. Yet, except for the cadres’ home visits, the existing biomedical health system is not very concerned with eldercare (or social care) at household level—for ill older persons fully dependent on kin care truly a “missing link.” Biomedicine in turn increasingly attempts to appropriate elder health as its new market commodity. Thereby, the four fields of pharmaceuticalization, national health insurance scheme, biomedicalization as control and exercise of power in care, and commercialization of elder health support biomedicine in its pursuit of the hegemonic appropriation of older persons’ health and illness. However, dislocations and disjunctures due to the Covid-19 pandemic clearly reveal the structural vulnerability of this biomedical health system: Its sudden unreliability and unsustainability leads not only to a loss of trust in it, but also to a higher degree of vulnerability on the side of older persons in need of cure and care