Journal Article > ResearchFull Text
PLOS Glob Public Health. 23 April 2025; Volume 5 (Issue 4); e0003759.; DOI:10.1371/journal.pgph.0003759
Gotham D, Martin M, Barber MJ, Kazounis E, Batts C, et al.
PLOS Glob Public Health. 23 April 2025; Volume 5 (Issue 4); e0003759.; DOI:10.1371/journal.pgph.0003759
Clinical trials are considered to be the largest contributor to pharmaceutical development costs. However, public disclosure of the costs of individual clinical trials is rare. Médecins Sans Frontières (MSF) sponsored a phase 2b-3 randomised controlled trial (TB-PRACTECAL), which identified a new treatment regimen for drug-resistant TB. We aimed to analyse the costs of undertaking a pivotal clinical trial conducted in relatively low-resource health settings and to demonstrate the feasibility of reporting clinical trial costs. TB-PRACTECAL trial costs were analysed using MSF accounting documents. Costs were broken down by cost category, year, and trial site. Total costs for TB-PRACTECAL were €33.9 million and the average cost per patient was €61,460. Twenty-six percent of total costs represented central activities (e.g. trial planning, trial management) and 72% represented trial site activities, with 2% uncategorizable. Within trial site costs, personnel costs were the largest cost (43%) followed by external diagnostic services (11%), medicines (9%), and other medical consumables (7%). Cost variation across trial sites was driven by different varying levels of pre-existing trial infrastructure. A review of previous studies yielded a wide range of cost estimates for clinical trials (ranging US$7–221 million/trial for pharmaceutical phase 2 and 3 trials). Nearly all previous estimates derive from industry reporting that is neither standardized nor auditable; to our knowledge, this is the first published comprehensive analysis of direct expenditures of a specific clinical trial including detailed cost breakdowns. The €34 million cost of TB-PRACTECAL included investments in developing clinical trial infrastructure, the complexity of managing six sites across three health systems, and medical expenditures that are not typical of standard clinical trials. Greater transparency in drug development costs can inform medicine pricing negotiations and is a key element in the design and implementation of more equitable systems of biomedical research and development.
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 > Slide Presentation
Gotham D, Martin M, Barber M, Kazounis E, Batts C, et al.
MSF Scientific Day International 2024. 16 May 2024; DOI:10.57740/asasBXQ
Journal Article > ResearchFull Text
Epidemiol Infect. 11 October 2013; Volume 142 (Issue 8); DOI:10.1017/S0950268813002562
Grandesso F, Allan M, Jean-Simon PSJ, Boncy J, Blake A, et al.
Epidemiol Infect. 11 October 2013; Volume 142 (Issue 8); DOI:10.1017/S0950268813002562
SUMMARY Two community-based density case-control studies were performed to assess risk factors for cholera transmission during inter-peak periods of the ongoing epidemic in two Haitian urban settings, Gonaives and Carrefour. The strongest associations were: close contact with cholera patients (sharing latrines, visiting cholera patients, helping someone with diarrhoea), eating food from street vendors and washing dishes with untreated water. Protective factors were: drinking chlorinated water, receiving prevention messages via television, church or training sessions, and high household socioeconomic level. These findings suggest that, in addition to contaminated water, factors related to direct and indirect inter-human contact play an important role in cholera transmission during inter-peak periods. In order to reduce cholera transmission in Haiti intensive preventive measures such as hygiene promotion and awareness campaigns should be implemented during inter-peak lulls, when prevention activities are typically scaled back.
Journal Article > ResearchAbstract Only
Prehosp Disaster Med. 15 January 2014; Volume 29 (Issue 1); 21-26.; DOI:10.1017/S1049023X13009278
Teicher CL, Alberti KP, Porten K, Elder G, Baron E, et al.
Prehosp Disaster Med. 15 January 2014; Volume 29 (Issue 1); 21-26.; DOI:10.1017/S1049023X13009278
INTRODUCTION
During January 2010, a 7.0 magnitude earthquake struck Haiti, resulting in death and destruction for hundreds of thousands of people. This study describes the types of orthopedic procedures performed, the options for patient follow-up, and limitations in obtaining outcomes data in an emergency setting.
PROBLEM
There is not a large body of data that describes larger orthopedic cohorts, especially those focusing on internal fixation surgeries in resource-poor settings in postdisaster regions. This article describes 248 injuries and over 300 procedures carried out in the Médecins Sans Frontières-Orthopedic Centre Paris orthopedic program.
METHODS
Surgeries described in this report were limited to orthopedic procedures carried out under general anesthesia for all surgical patients. Exclusion factors included simple fracture reduction, debridement, dressing changes, and removal of hardware. This data was collected using both prospective and retrospective methods; prospective inpatient data were collected using a data collection form designed promptly after the earthquake and retrospective data collection was performed in October 2010.
RESULTS
Of the 264 fractures, 204 were fractures of the major long bones (humerus, radius, femur, tibia). Of these 204 fractures of the major long bones, 34 (16.7%) were upper limb fractures and 170 (83.3%) were lower limb fractures. This cohort demonstrated a large number of open fractures of the lower limb and closed fractures of the upper limb. Fractures were treated according to their location and type. Of the 194 long bone fractures, the most common intervention was external fixation (36.5%) followed by traction (16.7%), nailing (15.1%), amputation (14.6%), and plating (9.9%).
CONCLUSION
The number of fractures described in this report represents one of the larger orthopedic cohorts of patients treated in a single center in the aftermath of the 2010 earthquake in Haiti. The emergent surgical care described was carried out in difficult conditions, both in the hospital and the greater community. While outcome and complication data were limited, the proportion of patients attending follow-up most likely exceeded expectations and may reflect the importance of the rehabilitation center. This data demonstrates the ability of surgical teams to perform highly-specialized surgeries in a disaster zone, and also reiterates the need for access to essential and emergency surgical programs, which are an essential part of public health in low- and medium-resource settings.
During January 2010, a 7.0 magnitude earthquake struck Haiti, resulting in death and destruction for hundreds of thousands of people. This study describes the types of orthopedic procedures performed, the options for patient follow-up, and limitations in obtaining outcomes data in an emergency setting.
PROBLEM
There is not a large body of data that describes larger orthopedic cohorts, especially those focusing on internal fixation surgeries in resource-poor settings in postdisaster regions. This article describes 248 injuries and over 300 procedures carried out in the Médecins Sans Frontières-Orthopedic Centre Paris orthopedic program.
METHODS
Surgeries described in this report were limited to orthopedic procedures carried out under general anesthesia for all surgical patients. Exclusion factors included simple fracture reduction, debridement, dressing changes, and removal of hardware. This data was collected using both prospective and retrospective methods; prospective inpatient data were collected using a data collection form designed promptly after the earthquake and retrospective data collection was performed in October 2010.
RESULTS
Of the 264 fractures, 204 were fractures of the major long bones (humerus, radius, femur, tibia). Of these 204 fractures of the major long bones, 34 (16.7%) were upper limb fractures and 170 (83.3%) were lower limb fractures. This cohort demonstrated a large number of open fractures of the lower limb and closed fractures of the upper limb. Fractures were treated according to their location and type. Of the 194 long bone fractures, the most common intervention was external fixation (36.5%) followed by traction (16.7%), nailing (15.1%), amputation (14.6%), and plating (9.9%).
CONCLUSION
The number of fractures described in this report represents one of the larger orthopedic cohorts of patients treated in a single center in the aftermath of the 2010 earthquake in Haiti. The emergent surgical care described was carried out in difficult conditions, both in the hospital and the greater community. While outcome and complication data were limited, the proportion of patients attending follow-up most likely exceeded expectations and may reflect the importance of the rehabilitation center. This data demonstrates the ability of surgical teams to perform highly-specialized surgeries in a disaster zone, and also reiterates the need for access to essential and emergency surgical programs, which are an essential part of public health in low- and medium-resource settings.
Journal Article > ResearchFull Text
PLOS One. 3 May 2013; Volume 8 (Issue 5); DOI:10.1371/journal.pone.0062767
Grellety E, Luquero FJ, Mambula C, Adamu HH, Elder G, et al.
PLOS One. 3 May 2013; Volume 8 (Issue 5); DOI:10.1371/journal.pone.0062767
The Sahel is subject to seasonal hungry periods with increasing rates of malnutrition. In Northern Nigeria, there is no surveillance system and surveys are rare. The objectives were to analyse possible observational bias in a sentinel surveillance system using repeated mixed longitudinal/cross-sectional data and estimate the extent of seasonal variation.
Journal Article > CommentaryFull Text
Bull World Health Organ. 28 October 2019; Volume 97 (Issue 12); 851-853.; DOI:10.2471/BLT.18.228585
Elder K, Saitta B, Ducomble T, Alia M, Close R, et al.
Bull World Health Organ. 28 October 2019; Volume 97 (Issue 12); 851-853.; DOI:10.2471/BLT.18.228585
Vaccination is an effective intervention to reduce disease, disability, death and health inequities worldwide. Over the last two decades, vaccines have become more accessible in low-income countries; however, significant gaps remain, particularly in humanitarian emergencies, where populations face increased risks of many diseases. In 2013, the World Health Organization (WHO) published "Vaccination in acute humanitarian emergencies: a framework for decision-making," to provide guidance on which vaccines to prioritize during emergencies. However, substantial obstacles, especially high prices for new vaccines, hinder implementation of this framework and of critical vaccination activities in emergency settings.
In response to these challenges, global health stakeholders held a series of consultations in 2016 and proposed a WHO-based mechanism, the Humanitarian Mechanism, for the rapid procurement of affordable vaccines during emergencies, to be used by nongovernmental organizations (NGOs), civil society organizations, United Nations (UN) agencies and governments. Here we present the background of the creation of the mechanism from the perspective of Médecins Sans Frontières (MSF), including a description of our past challenges in accessing affordable pneumococcal conjugate vaccine (PCV), a critical vaccine during many emergencies. We then describe how the mechanism has so far facilitated access to more affordable PCV and outline steps that could increase its potential for saving lives.
In response to these challenges, global health stakeholders held a series of consultations in 2016 and proposed a WHO-based mechanism, the Humanitarian Mechanism, for the rapid procurement of affordable vaccines during emergencies, to be used by nongovernmental organizations (NGOs), civil society organizations, United Nations (UN) agencies and governments. Here we present the background of the creation of the mechanism from the perspective of Médecins Sans Frontières (MSF), including a description of our past challenges in accessing affordable pneumococcal conjugate vaccine (PCV), a critical vaccine during many emergencies. We then describe how the mechanism has so far facilitated access to more affordable PCV and outline steps that could increase its potential for saving lives.
Journal Article > CommentaryFull Text
Surgery. 1 July 2015; Volume 158 (Issue 1); 33-36.; DOI:10.1016/j.surg.2015.04.006
Elder G, Murphy RA, Herard P, Dilworth K, Olson D, et al.
Surgery. 1 July 2015; Volume 158 (Issue 1); 33-36.; DOI:10.1016/j.surg.2015.04.006
Journal Article > CommentaryFull Text
Lancet. 5 July 2003; Volume 362 (Issue 9377); 74-75.; DOI:10.1016/S0140-6736(03)13813-5
Checchi F, Elder G, Schäfer M, Drouhin E, Legros D
Lancet. 5 July 2003; Volume 362 (Issue 9377); 74-75.; DOI:10.1016/S0140-6736(03)13813-5
Journal Article > CommentaryFull Text
BMJ Glob Health. 19 April 2022; Volume 7 (Issue 4); e007490.; DOI:10.1136/bmjgh-2021-007490
Perrin C, Athersuch K, Elder G, Martin M, Alsalhani A
BMJ Glob Health. 19 April 2022; Volume 7 (Issue 4); e007490.; DOI:10.1136/bmjgh-2021-007490
Two drugs with novel mechanisms of action, the diarylquinoline bedaquiline and the nitroimidazole delamanid—as well as pretomanid from the same class of drugs as delamanid—have recently become available to treat drug-resistant tuberculosis (DR-TB) after many decades of little innovation in the field of DR-TB treatment. Despite evidence of improved efficacy and reduced toxicity of multidrug regimens including the two agents, access to bedaquiline and delamanid has been limited in many settings with a high burden of DR-TB and consistently poor treatment outcomes. Aside from regulatory, logistic and cost barriers at country level, uptake of the novel agents was complicated by gaps in knowledge for optimal use in clinical practice after initial market approval. The main incentives of the current pharmaceutical research and development paradigm are structured around obtaining regulatory approval, which in turn requires efficacy and safety data generated by clinical trials. Recently completed and ongoing clinical trials did not answer critical questions of how to provide shorter, less toxic treatment DR-TB treatment regimens containing bedaquiline and delamanid and improve patient outcomes. Voluntary generation of evidence that is not part of this process—yet essential from a clinical or policy perspective—has been left to non-sponsor partners and researchers, often without collaborative efforts to improve post-regulatory approval access to life-saving drugs. Additionally, these efforts are currently not recognised in the value chain of the research and development process, and there are no incentives to make this critical research happen in a coordinated way.