Conference Material > Abstract
Gotham D, Martin M, Barber M, Kazounis E, Batts C, et al.
MSF Scientific Day International 2024. 16 May 2024; DOI:10.57740/aMphKRQ
INTRODUCTION
Clinical trials are a cornerstone of medical innovation. Nonetheless, little information on the cost of conducting clinical trials is available, especially for clinical trials in the global south. This lack of data and transparency hinders the creation of reliable cost estimates and adequate funding of clinical trials in resource- limited settings. Following the recent adoption of the Médecins Sans Frontières (MSF) Clinical Trial Transparency Policy, we present a detailed cost report for TB-PRACTECAL.
METHODS
TB-PRACTECAL was an open-label, phase 2–3, multicentre randomised trial of all-oral regimens for the treatment of drug- resistant tuberculosis. Trial planning began in 2013 and work on publications continued into 2023. The trial took place in six sites across Belarus, South Africa, and Uzbekistan, and enrolled 552 patients. We analysed accounting data for the TB-PRACTECAL project, comprehensively including different costs, presented into 27 categories, by site, and by year, and at the per-patient level.
RESULTS
Total costs for TB-PRACTECAL were €33.9 million, of which 26% were at central level (costs incurred by the UK clinical trial team including trial planning, management, quality assurance, and analysis of results), while 72% were at the trial site level (across all six sites) and 2% were uncategorisable. At trial sites, the largest cost category was staff (43%), followed by external diagnostic services (11%), medicines (9%), other medical consumables (7%), external non-medical services (6%), and transport and travel (6%). Among medicines, the costliest were bedaquiline (46% of medicine costs), linezolid (16%), imipenem/ cilastatin (10%), and delamanid (9%). The mean cost per patient enrolled was €61,460 across the whole trial (including trial management overhead). When only site-level costs were considered, per-patient costs ranged between €19,998 and €45,942 across the six sites.
CONCLUSION
The costs of TB-PRACTECAL were similar to previously reported estimates for comparable clinical trials. However, TB- PRACTECAL included additional costs that would not typically be incurred in a commercial trial, such as investments in clinical research infrastructure and purchase of investigative medical products. To our knowledge, this is the first time MSF, or any other entity, published and analysed the disaggregated costs of a specific clinical trial. These data could help generate reliable predictions for future clinical trials and support planning and involvement, particularly in low-resource settings. Additionally, this study highlights the role of clinical trial cost disclosure in supporting both practical and policy discussions around the development of a more equitable system of biomedical R&D and fairer medicine pricing. Additionally, we developed a financial reporting template to facilitate future reporting of clinical trial cost by MSF and other entities investing in research.
Clinical trials are a cornerstone of medical innovation. Nonetheless, little information on the cost of conducting clinical trials is available, especially for clinical trials in the global south. This lack of data and transparency hinders the creation of reliable cost estimates and adequate funding of clinical trials in resource- limited settings. Following the recent adoption of the Médecins Sans Frontières (MSF) Clinical Trial Transparency Policy, we present a detailed cost report for TB-PRACTECAL.
METHODS
TB-PRACTECAL was an open-label, phase 2–3, multicentre randomised trial of all-oral regimens for the treatment of drug- resistant tuberculosis. Trial planning began in 2013 and work on publications continued into 2023. The trial took place in six sites across Belarus, South Africa, and Uzbekistan, and enrolled 552 patients. We analysed accounting data for the TB-PRACTECAL project, comprehensively including different costs, presented into 27 categories, by site, and by year, and at the per-patient level.
RESULTS
Total costs for TB-PRACTECAL were €33.9 million, of which 26% were at central level (costs incurred by the UK clinical trial team including trial planning, management, quality assurance, and analysis of results), while 72% were at the trial site level (across all six sites) and 2% were uncategorisable. At trial sites, the largest cost category was staff (43%), followed by external diagnostic services (11%), medicines (9%), other medical consumables (7%), external non-medical services (6%), and transport and travel (6%). Among medicines, the costliest were bedaquiline (46% of medicine costs), linezolid (16%), imipenem/ cilastatin (10%), and delamanid (9%). The mean cost per patient enrolled was €61,460 across the whole trial (including trial management overhead). When only site-level costs were considered, per-patient costs ranged between €19,998 and €45,942 across the six sites.
CONCLUSION
The costs of TB-PRACTECAL were similar to previously reported estimates for comparable clinical trials. However, TB- PRACTECAL included additional costs that would not typically be incurred in a commercial trial, such as investments in clinical research infrastructure and purchase of investigative medical products. To our knowledge, this is the first time MSF, or any other entity, published and analysed the disaggregated costs of a specific clinical trial. These data could help generate reliable predictions for future clinical trials and support planning and involvement, particularly in low-resource settings. Additionally, this study highlights the role of clinical trial cost disclosure in supporting both practical and policy discussions around the development of a more equitable system of biomedical R&D and fairer medicine pricing. Additionally, we developed a financial reporting template to facilitate future reporting of clinical trial cost by MSF and other entities investing in research.
Conference Material > Video
Gotham D
MSF Scientific Day International 2024. 16 May 2024; DOI:10.57740/ZRiHGQ
Journal Article > ProtocolFull Text
BMJ Open. 23 August 2023; Volume 13 (Issue 8); e071544.; DOI:10.1136/bmjopen-2022-071544
Bahati D, Sy H, Kalhor A, Marchal B
BMJ Open. 23 August 2023; Volume 13 (Issue 8); e071544.; DOI:10.1136/bmjopen-2022-071544
INTRODUCTION
In humanitarian settings, aid agencies are constantly challenged by difficult decisions such as when and how to terminate aid without harming the aid recipients, local institutions, staff members and the organisation. Despite important efforts devoted to responsibly leaving a setting, hurtful exits are still common in contemporary relief aid. Moreover, debates on how humanitarian aid agencies exit are limited, with no previous comprehensive evidence synthesis on the concept of ‘responsible exit’. The objective of this scoping review is to map evidence and knowledge gaps, to identify and describe concepts, theories and existing frameworks related to ‘responsible exit’ of humanitarian aid agencies.
METHODS AND ANALYSIS
Our search uses searches of several bibliographic databases (CAB Direct (including Global Health), Web of Science, PubMed and Google Scholar) as well as manual searches of specific journals and retrieval of grey literature through searches of organisational websites and direct contact with experts and organisations. Reference tracking will be used to identify additional sources. Searches will cover papers available up to the dates of the searches (December 2022 to January 2023), with no date restrictions applied to the literature search. To be included, published or unpublished papers must explicitly discuss the exit of humanitarian aid agencies from humanitarian settings and be accessible. We will exclude all exits related to military, local and governmental humanitarian operations, education, development, employment, and business sectors. Only papers written in English and French will be considered. Three reviewers will conduct the selection process against the predefined criteria. Data will be extracted in an iterative process following pre-established items and the results will be presented in a Preferred Reporting Items for Systematic Reviews Extension for Scoping Reviews flow chart, tables and/or graphs, and descriptive formats.
ETHICS AND DISSEMINATION
Being a review, conducted on publicly available information, no ethical approval is required. The results will be disseminated through publication in an open access journal, scientific conferences, workshops, and via humanitarian aid agencies to facilitate further research and possible practical translations of generated knowledge.
In humanitarian settings, aid agencies are constantly challenged by difficult decisions such as when and how to terminate aid without harming the aid recipients, local institutions, staff members and the organisation. Despite important efforts devoted to responsibly leaving a setting, hurtful exits are still common in contemporary relief aid. Moreover, debates on how humanitarian aid agencies exit are limited, with no previous comprehensive evidence synthesis on the concept of ‘responsible exit’. The objective of this scoping review is to map evidence and knowledge gaps, to identify and describe concepts, theories and existing frameworks related to ‘responsible exit’ of humanitarian aid agencies.
METHODS AND ANALYSIS
Our search uses searches of several bibliographic databases (CAB Direct (including Global Health), Web of Science, PubMed and Google Scholar) as well as manual searches of specific journals and retrieval of grey literature through searches of organisational websites and direct contact with experts and organisations. Reference tracking will be used to identify additional sources. Searches will cover papers available up to the dates of the searches (December 2022 to January 2023), with no date restrictions applied to the literature search. To be included, published or unpublished papers must explicitly discuss the exit of humanitarian aid agencies from humanitarian settings and be accessible. We will exclude all exits related to military, local and governmental humanitarian operations, education, development, employment, and business sectors. Only papers written in English and French will be considered. Three reviewers will conduct the selection process against the predefined criteria. Data will be extracted in an iterative process following pre-established items and the results will be presented in a Preferred Reporting Items for Systematic Reviews Extension for Scoping Reviews flow chart, tables and/or graphs, and descriptive formats.
ETHICS AND DISSEMINATION
Being a review, conducted on publicly available information, no ethical approval is required. The results will be disseminated through publication in an open access journal, scientific conferences, workshops, and via humanitarian aid agencies to facilitate further research and possible practical translations of generated knowledge.
Journal Article > ReviewFull Text
Wellcome Open Res. 14 August 2023; Volume 8; 343.; DOI:10.12688/wellcomeopenres.19490.1
Sheather J, Littler K, Singh JA, Wright K
Wellcome Open Res. 14 August 2023; Volume 8; 343.; DOI:10.12688/wellcomeopenres.19490.1
Anthropogenic climate change is unequivocal, and many of its physical health impacts have been identified, although further research is required into the mental health and wellbeing effects of climate change. There is a lack of understanding of the importance of ethics in policy-responses to health and climate change which is also linked to the lack of specific action-guiding ethical resources for researchers and practitioners. There is a marked paucity of ethically-informed health input into economic policy-responses to climate change—an area of important future work. The interaction between health, climate change and ethics is technically and theoretically complex and work in this area is fragmentary, unfocussed, and underdeveloped. Research and reflection on climate and health is fragmented and plagued by disciplinary silos and exponentially increasing literature means that the field cannot be synthesised using conventional methods. Reviewing the literature in these fields is therefore methodologically challenging. Although many of the normative challenges in responding to climate change have been identified, available theoretical approaches are insufficiently robust, and this may be linked to the lack of action-guiding support for practitioners. There is a lack of ethical reflection on research into climate change responses. Low-HDI (Human Development Index) countries are under-represented in research and publication both in the health-impacts of climate change, and normative reflection on health and climate change policy. There is a noticeable lack of ethical commentary on a range of key topics in the environmental health literature including population, pollution, transport, energy, food, and water use. Serious work is required to synthesise the principles governing policy responses to health and climate change, particularly in relation to value conflicts between the human and non-human world and the challenges presented by questions of intergenerational justice.
Journal Article > CommentaryFull Text
PLOS Glob Public Health. 18 January 2023; Volume 3 (Issue 1); e0001418.; DOI:10.1371/journal.pgph.0001418
Hodson DZ, Etoundi YM, Parikh S, Boum Y
PLOS Glob Public Health. 18 January 2023; Volume 3 (Issue 1); e0001418.; DOI:10.1371/journal.pgph.0001418
Interest in “global health” among schools of medicine, public health, and other health disciplines in high-income countries (HIC) continues to rise. Persistent power imbalances, racism, and maintenance of colonialism/neocolonialism plague global health efforts, including global health scholarship. Scholarly projects conducted in low- and middle-income countries (LMIC) by trainees at these schools in HIC often exacerbate these problems. Drawing on published literature and shared experiences, we review key inequalities within each phase of research, from design through implementation and analysis/dissemination, and make concrete and practical recommendations to improve equity at each stage. Key problems facing global health scholarship include HIC-centric nature of global health organizations, paucity of funding directly available for LMIC investigators and trainees, misplaced emphasis on HIC selected issues rather than local solutions to local problems, the dominance of English language in the scientific literature, and exploitation of LMIC team members. Four key principles lie at the foundation of all our recommendations: 1) seek locally derived and relevant solutions to global health issues, 2) create paired collaborations between HIC and LMIC institutions at all levels of training, 3) provide funding for both HIC and LMIC team members, 4) assign clear roles and responsibilities to value, leverage, and share the strengths of all team members. When funding for global health research is predicated upon more ethical and equitable collaborations, the nature of global health collaborations will evolve to be more ethical and equitable. Therefore, we propose the Douala Equity Checklist as a 20-item tool HIC and LMIC institutions can use throughout the conduct of global health projects to ensure more equitable collaborations.
MSF Ethics Review Board > Publications
BMC Medical Ethics. 26 February 2015; Volume 16; 10.; DOI:10.1186/s12910-015-0002-3
Schopper D, Dawson A, Upshur R, Ahmad ASI, Jesani A, et al.
BMC Medical Ethics. 26 February 2015; Volume 16; 10.; DOI:10.1186/s12910-015-0002-3
BACKGROUND
Médecins Sans Frontières (MSF) is one of the world’s leading humanitarian medical organizations. The increased emphasis in MSF on research led to the creation of an ethics review board (ERB) in 2001. The ERB has
encouraged innovation in the review of proposals and the interaction between the ERB and the organization. This has led to some of the advances in ethics governance described in this paper.
DISCUSSION
We first update our previous work from 2009 describing ERB performance and then highlight five innovative practices:
• A new framework to guide ethics review
• The introduction of a policy exempting a posteriori analysis of routinely collected data
• The preapproval of “emergency” protocols
• General ethical approval of “routine surveys”
• Evaluating the impact of approved studies
The new framework encourages a conversation about ethical issues, rather than imposing quasi-legalistic rules, is more engaged with the specific MSF research context and gives greater prominence to certain values and
principles. Some of the innovations implemented by the ERB, such as review exemption or approval of generic protocols, may run counter to many standard operating procedures. We argue that much standard practice in research ethics review ought to be open to challenge and revision. Continued interaction between MSF researchers and independent ERB members has allowed for progressive innovations based on a trustful and respectful partnership between the ERB and the researchers. In the future, three areas merit particular attention. First, the impact of the new framework should be assessed. Second, the impact of research needs to be defined more precisely as a first step towards being meaningfully assessed, including changes of impact over time. Finally, the dialogue between the MSF ERB and the ethics committees in the study countries should be enhanced.
SUMMARY
We hope that the innovations in research ethics governance described may be relevant for other organisations carrying out research in fragile contexts and for ethics committees reviewing such research.
Médecins Sans Frontières (MSF) is one of the world’s leading humanitarian medical organizations. The increased emphasis in MSF on research led to the creation of an ethics review board (ERB) in 2001. The ERB has
encouraged innovation in the review of proposals and the interaction between the ERB and the organization. This has led to some of the advances in ethics governance described in this paper.
DISCUSSION
We first update our previous work from 2009 describing ERB performance and then highlight five innovative practices:
• A new framework to guide ethics review
• The introduction of a policy exempting a posteriori analysis of routinely collected data
• The preapproval of “emergency” protocols
• General ethical approval of “routine surveys”
• Evaluating the impact of approved studies
The new framework encourages a conversation about ethical issues, rather than imposing quasi-legalistic rules, is more engaged with the specific MSF research context and gives greater prominence to certain values and
principles. Some of the innovations implemented by the ERB, such as review exemption or approval of generic protocols, may run counter to many standard operating procedures. We argue that much standard practice in research ethics review ought to be open to challenge and revision. Continued interaction between MSF researchers and independent ERB members has allowed for progressive innovations based on a trustful and respectful partnership between the ERB and the researchers. In the future, three areas merit particular attention. First, the impact of the new framework should be assessed. Second, the impact of research needs to be defined more precisely as a first step towards being meaningfully assessed, including changes of impact over time. Finally, the dialogue between the MSF ERB and the ethics committees in the study countries should be enhanced.
SUMMARY
We hope that the innovations in research ethics governance described may be relevant for other organisations carrying out research in fragile contexts and for ethics committees reviewing such research.
Journal Article > CommentaryFull Text
PLOS Med. 6 September 2016; Volume 13 (Issue 9); e1002111.; DOI:10.1371/journal.pmed.1002111
Sheather J, Jobanputra K, Schopper D, Pringle J, Venis S, et al.
PLOS Med. 6 September 2016; Volume 13 (Issue 9); e1002111.; DOI:10.1371/journal.pmed.1002111
SUMMARY POINTS
• Humanitarian organisations often have to innovate to deliver health care and aid to populations in complex and volatile contexts.
• Innovation projects can involve ethical risks and have consequences for populations even if human participants are not directly involved. While high-level principles have been developed for humanitarian innovation, there is a lack of guidance for how these should be applied in practice.
• Médecins sans Frontières (MSF) has well-established research ethics frameworks, but application of such frameworks to innovation projects could stifle innovation by introducing regulation disproportionate to the risks involved. In addition, the dynamic processes of innovation do not fit within conventional ethics frameworks.
• MSF developed and is piloting an ethics framework for humanitarian innovation that is intended for self-guided use by innovators or project owners to enable them to identify and weigh the harms and benefits of such work and be attentive towards a plurality of ethical considerations.
• Humanitarian organisations often have to innovate to deliver health care and aid to populations in complex and volatile contexts.
• Innovation projects can involve ethical risks and have consequences for populations even if human participants are not directly involved. While high-level principles have been developed for humanitarian innovation, there is a lack of guidance for how these should be applied in practice.
• Médecins sans Frontières (MSF) has well-established research ethics frameworks, but application of such frameworks to innovation projects could stifle innovation by introducing regulation disproportionate to the risks involved. In addition, the dynamic processes of innovation do not fit within conventional ethics frameworks.
• MSF developed and is piloting an ethics framework for humanitarian innovation that is intended for self-guided use by innovators or project owners to enable them to identify and weigh the harms and benefits of such work and be attentive towards a plurality of ethical considerations.
MSF Ethics Review Board > Publications
PLOS Med. 28 July 2009; Volume 6 (Issue 7); e1000115.; DOI:10.1371/journal.pmed.1000115
Schopper D, Upshur R, Matthys F, Singh JA, Bandewar SS, et al.
PLOS Med. 28 July 2009; Volume 6 (Issue 7); e1000115.; DOI:10.1371/journal.pmed.1000115
MSF Ethics Review Board > Other guidance
MSF Ethics Review Board
1 November 2013
MSF Ethics Review Board > Publications
Public Health Ethics. 1 November 2016; Volume 10 (Issue 1); 49-61.; DOI:10.1093/phe/phw039
Schopper D, Ravinetto R, Schwartz L, Kamaara E, Sheel S, et al.
Public Health Ethics. 1 November 2016; Volume 10 (Issue 1); 49-61.; DOI:10.1093/phe/phw039
The Médecins Sans Frontières (MSF) ethics review board (ERB) has been solicited in an unprecedented way to provide advice and review research protocols in an 'emergency' mode during the recent Ebola epidemic. Twenty-seven Ebola-related study protocols were reviewed between March 2014 and August 2015, ranging from epidemiological research, to behavioural research, infectivity studies and clinical trials with investigational products at (very) early development stages. This article examines the MSF ERB's experience addressing issues related to both the process of review and substantive ethical issues in this context. These topics include lack of policies regarding blood sample collection and use, and engaging communities regarding their storage and future use; exclusion of pregnant women from clinical and vaccine trials; and the difficulty of implementing timely and high-quality qualitative/anthropological research to consider potential upfront harms. Having noticed different standards across ethics committees (ECs), we propose that when multiple ethics reviews of clinical and vaccine trials are carried out during a public health emergency they should be accompanied by transparent communication between the ECs involved. The MSF ERB experience should trigger a broader discussion on the 'optimal' ethics review in an emergency outbreak and what enduring structural changes are needed to improve the ethics review process.