Suchergebnisse

BACKGROUND: Non-commercial clinical research plays an increasingly essential role for global health. Multiple partners join in international consortia that operate under the limited timeframe of a specific funding period. One organisation (the sponsor) designs and carries out the trial in collaboration with research partners, and is ultimately responsible for the trial's scientific, ethical, regulatory and legal aspects, while another organization, generally in the North (the funder), provides the external funding and sets funding conditions. Even if external funding mechanisms are key for most non-commercial research, the dependence on an external funder's policies may heavily influence the choices of a sponsor. In addition, the competition for accessing the available external funds is great, and non-commercial sponsors may not be in a position to discuss or refuse standard conditions set by a funder. To see whether the current definitions adequately address the intricacies of sponsorship in externally-funded trials, we looked at how a "sponsor" of clinical trials is defined in selected international guidelines, with particular focus on international Good Clinical Practices codes, and in selected European and African regulations/legislations. DISCUSSION: Our limited analysis suggests that the sponsors definition from the 1995 WHO Good Clinical Practices code has been integrated as such into many legislations, guidelines and regulations, and that it is not adequate to cover today's reality of funding arrangements in global health, where the legal responsibility and the funding source are de facto split. In agreement with other groups, we suggest that the international Good Clinical Practices codes should be updated to reflect the reality of non-commercial clinical research. In particular, they should explicitly include the distinction between commercial and non-commercial sponsors, and provide guidance to non-commercial sponsors for negotiating with external funding agencies and other research counterparts. Non-commercial sponsors of clinical trials should surely invest in the development of adequate legal, administrative and management skills. By acknowledging their role and specificities, and by providing them with adapted guidance, the international Good Clinical Practices codes would provide valuable guidance and support to non-commercial clinical research, whose relevance for global health is increasingly evident.

Alleviating acute and chronic pain is a moral imperative for health professionals and health systems, and it requires adequate access to and use of essential opioid analgesics. However, this is still a neglected issue in global health, with striking inequalities in opioids availability between high and low- and middle-income countries. Countries most affected by lack of access are those with a fragile political situation and weak regulatory and healthcare systems. The main threats to accessibility, availability and affordability are situated at different levels: legislation and policy, financing, knowledge and cultural behavior, erroneous beliefs, and training and education. Among these threats, the lack of (adequate) training and education seems to be a cross-cutting issue. Exploring the current body of knowledge about training and educational activities related to use of opioid analgesics and palliative care, is helpful to understand gaps and to delineate priorities for setting up adequate interventions. When applied to West and Central Africa, this exercise reveals that there is little information (easily) available in the public domain. The African Palliative Care Association (APCA) appears to be the leading provider of capacity building activities in this region for key stakeholders, including national authorities, healthcare professionals and the general population; it is also very active in publishing and communicating about these issues. However, apart from APCA, there is little information on training programs' contents and long-term outcomes. Furthermore, trainings rarely target important stakeholders such as lawmakers, regulators, supply officers and the lay public (i.e., patients, caregivers, community leaders and members of the society as a whole). Hence, it is urgent to fill the existing gaps in training and educational activities to improve access to essential opioid analgesics in West and Central Africa, involving different stakeholders at the national and regional level. Furthermore, such ...

The Good Clinical Practices (GCP) codes of the WHO and the International Conference of Harmonization set international standards for clinical research. But critics argue that they were written without consideration for the challenges faced in low and middle income countries (LMICs). Based on our field experience in LMICs, we developed a non-exhaustive set of recommendations for the improvement of GCP. These cover 3 domains: ethical, legal and operational, and 8 specific issues: the double ethical review of 'externally sponsored' trials; the informed consent procedure in minors and in illiterate people; post-trial access to newly-developed products for the trial communities; the role of communities as key research actors; the definition of sponsor; and the guidance for contractual agreements, laboratory quality management systems, and quality assurance of investigational medicinal products. Issues not covered in our analysis include among others biobanking, standard of care, and study designs. The international GCP codes de facto guide national legislators and funding agencies, so the current shortcomings may weaken the regulatory oversight of international research. In addition, activities neglected by GCP are less likely to be implemented or funded. If GCP are meant to serve the interests of global society, a comprehensive revision is needed. The revised guidelines should be strongly rooted in ethics, sensitive to different sociocultural perspectives, and allow consideration for trial-specific and context-specific challenges. This can be only achieved if all stakeholders, including researchers, sponsors, regulators, ethical reviewers and patients' representatives from LMICs, as well as non-commercial researchers and sponsors from affluent countries, are transparently involved in the revision process. We hope that our limited analysis would foster advocacy for a broad and inclusive revision of the international GCP codes, to make them at the same time 'global', 'context centred' and 'patient centred'.

BACKGROUND: Ensuring individual free and informed decision‐making for research participation is challenging. It is thought that preliminarily informing communities through 'community sensitization' procedures may improve individual decision‐making. This study set out to assess the relevance of community sensitization for individual decision‐making in research participation in rural Gambia. METHODS: This anthropological mixed‐methods study triangulated qualitative methods and quantitative survey methods in the context of an observational study and a clinical trial on malaria carried out by the Medical Research Council Unit Gambia. RESULTS/DISCUSSION: Although 38.7% of the respondents were present during sensitization sessions, 91.1% of the respondents were inclined to participate in the trial when surveyed after the sensitization and prior to the informed consent process. This difference can be explained by the informal transmission of information within the community after the community sensitization, expectations such as the benefits of participation based on previous research experiences, and the positive reputation of the research institute. Commonly mentioned barriers to participation were blood sampling and the potential disapproval of the household head. CONCLUSION: Community sensitization is effective in providing first‐hand, reliable information to communities as the information is cascaded to those who could not attend the sessions. However, further research is needed to assess how the informal spread of information further shapes people's expectations, how the process engages with existing social relations and hierarchies (e.g. local political power structures; permissions of heads of households) and how this influences or changes individual consent.

Implementing an Ebola vaccine trial in a remote area in the Democratic Republic of the Congo (DRC), and being confronted with a dysfunctional health care system and acute unmet health needs of participants, ethical considerations were made regarding the ancillary care obligations of the sponsor and researchers. Spurred by the occurrence of non-related (serious) adverse events (NR-SAEs), the Universities of Antwerp and Kinshasa jointly developed an algorithm, accompanied by an algorithm policy. The algorithm consists of a set of consecutive questions with binary response options, leading to structured, non-arbitrary and consistent support and management for each NR-SAE. It is the result of dialogue and collaboration between the sponsor (University of Antwerp) and the principal investigator (University of Kinshasa), consultation of literature, and input of research ethics and social sciences experts. The characteristics of the project and its budgetary framework were taken into account, as well as the local socioeconomic and healthcare situation. The algorithm and related policy have been approved by the relevant ethics committee (EC), so field implementation will begin when the study activities resume in November 2021. Lessons learnt will be shared with the relevant stakeholders within and outside DRC. If NR-SAEs are not covered by a functioning social welfare system, sponsors and researchers should develop a feasible, standardised and transparent approach to the provision of ancillary care. National legislation and contextualised requirements are therefore needed, particularly in low/middle-income countries, to guide researchers and sponsors in this process. Protocols, particularly of clinical trials conducted in areas with 'access to care' constraints, should include adequate ancillary care arrangements. Furthermore, it is essential that local ECs systematically require ancillary care provisions to enhance the well-being and protection of the rights of research participants. This project was funded by the ...

There is little published information on the epidemiology of neurological disorders in rural Central Africa, although the burden is considered to be substantial. This study aimed to investigate the pattern, etiology, and outcome of neurological disorders in children > 5 years and adults admitted to the rural hospital of Mosango, province of Kwilu, Democratic Republic of Congo, with a focus on severe and treatable infections of the central nervous system (CNS). From September 2012 to January 2015, 351 consecutive patients hospitalized for recent and/or ongoing neurological disorder were prospectively evaluated by a neurologist, subjected to a set of reference diagnostic tests in blood or cerebrospinal fluid, and followed-up for 3–6 months after discharge. No neuroimaging was available. Severe headache (199, 56.7%), gait/walking disorders (97, 27.6%), epileptic seizure (87, 24.8%), and focal neurological deficit (86, 24.5%) were the predominant presentations, often in combination. Infections of the CNS were documented in 63 (17.9%) patients and mainly included bacterial meningitis and unspecified meningoencephalitis (33, 9.4%), second-stage human African trypanosomiasis (10, 2.8%), and human immunodeficiency virus (HIV)-related neurological disorders (10, 2.8%). Other focal/systemic infections with neurological manifestations were diagnosed in an additional 60 (17.1%) cases. The leading noncommunicable conditions were epilepsy (61, 17.3%), psychiatric disorders (56, 16.0%), and cerebrovascular accident (23, 6.6%). Overall fatality rate was 8.2% (29/351), but up to 23.8% for CNS infections. Sequelae were observed in 76 (21.6%) patients. Clinical presentations and etiologies of neurological disorders were very diverse in this rural Central African setting and caused considerable mortality and morbidity.

There is little published information on the epidemiology of neurological disorders in rural Central Africa, although the burden is considered to be substantial. This study aimed to investigate the pattern, etiology, and outcome of neurological disorders in children> 5 years and adults admitted to the rural hospital of Mosango, province of Kwilu, Democratic Republic of Congo, with a focus on severe and treatable infections of the central nervous system (CNS). From September 2012 to January 2015, 351 consecutive patients hospitalized for recent and/or ongoing neurological disorder were prospectively evaluated by a neurologist, subjected to a set of reference diagnostic tests in blood or cerebrospinal fluid, and followed-up for 3-6 months after discharge. No neuroimaging was available. Severe headache (199, 56.7%), gait/walking disorders (97, 27.6%), epileptic seizure (87, 24.8%), and focal neurological deficit (86, 24.5%) were the predominant presentations, often in combination. Infections of the CNS were documented in 63 (17.9%) patients and mainly included bacterial meningitis and unspecified meningoencephalitis (33, 9.4%), second-stage human African trypanosomiasis (10, 2.8%), and human immunodeficiency virus (HIV)-related neurological disorders (10, 2.8%). Other focal/systemic infections with neurological manifestations were diagnosed in an additional 60 (17.1%) cases. The leading noncommunicable conditions were epilepsy (61, 17.3%), psychiatric disorders (56, 16.0%), and cerebrovascular accident (23, 6.6%). Overall fatality rate was 8.2% (29/351), but up to 23.8% for CNS infections. Sequelae were observed in 76 (21.6%) patients. Clinical presentations and etiologies of neurological disorders were very diverse in this rural Central African setting and caused considerable mortality and morbidity.

Traditional public health methods for detecting infectious disease transmission, such as contact tracing and molecular epidemiology, are time-consuming and costly. Information and communication technologies, such as global positioning systems, smartphones, and mobile phones, offer opportunities for novel approaches to identifying transmission hotspots. However, mapping the movements of potentially infected persons comes with ethical challenges. During an interdisciplinary meeting of researchers, ethicists, data security specialists, information and communication technology experts, epidemiologists, microbiologists, and others, we arrived at suggestions to mitigate the ethical concerns of movement mapping. These suggestions include a template Data Protection Impact Assessment that follows European Union General Data Protection Regulations. ; This work was supported by the European Research Council Proof of Concept "Enhanced Place Finding" (grant no. 727695).

Traditional public health methods for detecting infectious disease transmission, such as contact tracing and molecular epidemiology, are time-consuming and costly. Information and communication technologies, such as global positioning systems, smartphones, and mobile phones, offer opportunities for novel approaches to identifying transmission hotspots. However, mapping the movements of potentially infected persons comes with ethical challenges. During an interdisciplinary meeting of researchers, ethicists, data security specialists, information and communication technology experts, epidemiologists, microbiologists, and others, we arrived at suggestions to mitigate the ethical concerns of movement mapping. These suggestions include a template Data Protection Impact Assessment that follows European Union General Data Protection Regulations.

Traditional public health methods for detecting infectious disease transmission, such as contact tracing and molecular epidemiology, are time-consuming and costly. Information and communication technologies, such as global positioning systems, smartphones, and mobile phones, offer opportunities for novel approaches to identifying transmission hotspots. However, mapping the movements of potentially infected persons comes with ethical challenges. During an interdisciplinary meeting of researchers, ethicists, data security specialists, information and communication technology experts, epidemiologists, microbiologists, and others, we arrived at suggestions to mitigate the ethical concerns of movement mapping. These suggestions include a template Data Protection Impact Assessment that follows European Union General Data Protection Regulations.

BACKGROUND: In the wake of the recent outbreak of Ebola virus disease (EVD) in several African countries, the World Health Organization prioritized the evaluation of treatment with convalescent plasma derived from patients who have recovered from the disease. We evaluated the safety and efficacy of convalescent plasma for the treatment of EVD in Guinea. METHODS: In this nonrandomized, comparative study, 99 patients of various ages (including pregnant women) with confirmed EVD received two consecutive transfusions of 200 to 250 ml of ABO-compatible convalescent plasma, with each unit of plasma obtained from a separate convalescent donor. The transfusions were initiated on the day of diagnosis or up to 2 days later. The level of neutralizing antibodies against Ebola virus in the plasma was unknown at the time of administration. The control group was 418 patients who had been treated at the same center during the previous 5 months. The primary outcome was the risk of death during the period from 3 to 16 days after diagnosis with adjustments for age and the baseline cycle-threshold value on polymerase-chain-reaction assay; patients who had died before day 3 were excluded. The clinically important difference was defined as an absolute reduction in mortality of 20 percentage points in the convalescent-plasma group as compared with the control group. RESULTS: A total of 84 patients who were treated with plasma were included in the primary analysis. At baseline, the convalescent-plasma group had slightly higher cycle-threshold values and a shorter duration of symptoms than did the control group, along with a higher frequency of eye redness and difficulty in swallowing. From day 3 to day 16 after diagnosis, the risk of death was 31% in the convalescent-plasma group and 38% in the control group (risk difference, -7 percentage points; 95% confidence interval [CI], -18 to 4). The difference was reduced after adjustment for age and cycle-threshold value (adjusted risk difference, -3 percentage points; 95% CI, -13 to 8). No serious adverse reactions associated with the use of convalescent plasma were observed. CONCLUSIONS: The transfusion of up to 500 ml of convalescent plasma with unknown levels of neutralizing antibodies in 84 patients with confirmed EVD was not associated with a significant improvement in survival. (Funded by the European Union's Horizon 2020 Research and Innovation Program and others; ClinicalTrials.gov number, NCT02342171.).