Integrating Clinical Research into Epidemic Response The Ebola Experience (2017) / Chapter Skim
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5 Strengthening Capacity for Response and Research
5 Strengthening Capacity for Response and Research
Pages 155-198
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From page 155... ...
. As a result of the globalization of clinical trials and accompanying external investment, developing countries have increased their capacity and resources for conducting research, and increasingly they have also tried to ensure the research agenda is relevant to the health challenges they face (Lang and Siribaddana, 2012)
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, the Canadian International Development Research Centre, the UK Medical Research Council, the Wellcome Trust, the Pasteur Institutes, the European Developing Country Clinical Trials Partnership, and the Special Programme for Research and Training in Tropical Disease at the WHO, among many others around the world. Despite these efforts, the majority of African countries, including
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, said, "The state of the health workforce and health systems of the affected countries hampers the ability of these countries to respond to the Ebola outbreak -- but these countries are hardly alone in having inadequate training, support and numbers of health workers, especially in the rural areas where this outbreak took hold" (Pablos-Mendez, 2014)
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. CAPACITY CHALLENGES TO CONDUCTING CLINICAL RESEARCH The highly regulated nature of clinical trials, as well as the scientific and ethical mandates established to ensure that their risks to participants are minimized and the expected benefits are sufficient to justify going forward, can make trials time consuming and expensive to conduct (DiMasi et al., 2016)
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For example, inexperience with independent scientific and ethics review of proposed research and limited legal experience in evaluating and negotiating research contracts put the countries at a strategic disadvantage, whether actual or just potential. In order to conduct high-quality research in a timely manner in a resourcepoor setting during an emerging epidemic, the following challenges experienced during the Ebola outbreak must be addressed if there is to be a more efficient, rapid, and effective research response: • poor surveillance and a lack of experience with outbreak investiga tions in the three countries • a lack of clinical experience with Ebola-infected patients in West Africa • a lack of health care personnel and basic and health infrastructure • a small pool of clinical research experts and research infrastructure in countries • limited prior experience in the conduct of clinical research • overwhelmed, understaffed, and poorly supported ethics review boards • limited experience with contract negotiations and large program project management Each of these challenges can be addressed by strengthening in-country capacity.
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report called for the development of sustainable surveillance capacity for emerging infectious diseases rather than the buildup of surveillance when a new threat occurs and then its dismantling when the threat disappears (IOM and NRC, 2009)
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. A retrospective serosurvey of 672 serum samples collected at the Lassa Diagnostic Laboratory at Kenema Government Hospital, Sierra Leone, between 2007 and 2014, primarily from Sierra Leone, identified 35 samples (5.2 percent)
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There is reason to be concerned about whether a sustainable surveillance system within countries at a similar level of core capacity as Guinea, Liberia, and Sierra Leone can be established, although there is some appreciation of the need and an attempt to do so by the European Union
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. The WHO meanwhile is working to strengthen the surveillance systems of the Ebola-affected countries; efforts include • providing technical support to the West African Health Organiza tion for the establishment of the West African Regional CDC and its network of national coordinating institutions; • supporting nine West African countries which will participate in the World Bank's West Africa Regional Diseases Surveillance Sys tems Enhancement (REDISSE)
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Conclusion 5-1 In order to better respond to future outbreaks and recognize an emerging epidemic in time to effectively mount a response, including conduct of clinical trials, it is critical that surveillance, out break investigation, and diagnostic capacity be strengthened in low and middle-income countries. The mandate to ensure compliance with IHR 2005 core capacity for surveillance, reporting, and initial response rests with the WHO; however, two-thirds of countries have not yet reached the minimal required standards, which represents a major gap in global readiness.
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In the former, 0.11 percent of the general population died, versus 8.07 percent of health care workers, while in Sierra Leone the corresponding figures were 0.06 percent of the general population and 6.85 percent of the health care workers, with nurses and nursing aides accounting for more than half of these losses. Given the relative paucity of physicians and nurses or midwives in the three countries at the onset of the outbreak, these numbers translated into a 10 percent reduction in the number of doctors in Liberia; an 8 percent reduction in nurses and midwives, and a 5 percent and 7 percent reduction, respectively, in Sierra Leone; and 2 percent and 1 percent for doctors and nurses in Guinea (Evans et al., 2015)
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. While it is difficult to quantify, the internal brain drain of health care workers from local treatment centers providing routine health care to NGOs during the 2014–2015 Ebola outbreak -- or, at a later date, to provide skilled local professional and administrative staff to international research projects -- would be expected to contribute to an already weakening health care system performance and to adversely affect the environment in which clinical research could be safely conducted (Anderson and Beresford, 2016)
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Through their logistical support, humanitarian organizations contributed greatly to the launch of clinical trials during the Ebola outbreak. Trials were launched out of Ebola treatment units (ETUs)
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. The role of humanitarian organizations in the Ebola outbreak and their crucial contributions to the clinical trials conducted should not be understated.
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Additionally, in Sierra Leone, WHO responders did not have transportation available to them in order to monitor the spread of the virus despite a recently purchased fleet of vehicles that sat, unavailable, at UN headquarters in Freetown, Sierra Leone, fostering mistrust. "One WHO official suggested Sierra Leonean responders requesting motorbikes for travel to villages buy bicycles instead" (Associated Press, 2015a)
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Conclusion 5-3 Researchers conducting clinical trials during epidemics in low-resource settings will require substantial logistical support from organizations that build and operate treatment centers (including inter national humanitarian organizations and national health systems) , and these organizations should be included in strategic planning for clinical research activities during the inter-epidemic period.
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. This report was updated recently by an independent evaluation sponsored by the West African Health Organization (WAHO)
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For example, local researchers had limited or no experience in developing collaborative arrangements with international partners, with obtaining approval from local and international authorities, and with negotiating the legal aspects of clinical trial agreements and other legal documents such as clinical trial agreements, material transfer agreements,2 data sharing, and post-trial benefits. In addition to these responsibilities, local researchers were also under pressure to identify suitable research study locations, obtain funding, recruit research staff, conduct training on how to work safely in the context of containment, and ensure that research did not impair clinical care.
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. With little empirical evidence on Ebola prevention, treatment, or management to guide clinical care, those responding to the Ebola outbreak in West Africa lacked standardized clinical protocols for patient care contributing to the variability of care across ETUs.
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Overwhelmed Ethics Review Boards4 Among the many technical capabilities required for assessing clinical research proposals is the availability of a trained and independent research ethics committee and the administrative support necessary for its members to work efficiently in the country where the trial will be conducted. The Declaration of Helsinki addresses the role of ethics committees in the 3 Memoranda of Understanding: Documents whereby parties entering into a partnership agree to an intended common purpose or set of goals.
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. While Guinean, Liberian, and Sierra Leonean ethics review committees are all included in the National Institute of Allergy and Infectious Diseases–operated ClinRegs database of country-specific clinical research regulatory information, there is no accompanying assessment of their functional capacities (NIH, 2016)
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. 5 Testimony of several participants at the Public Workshop of the Committee on Clinical Trials During the 2014–2015 Ebola Outbreak.
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The West African Health Organization is presently working with COHRED to implement RHInnO Ethics in the national research ethics committees in 5 countries in West Africa in 2017, including Sierra Leone, Guinea, and Liberia. Nigeria already has 16 installations in place" (COHRED, 2016)
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Food and Drug Administration, the Ministry of Public Health and Hygiene of Guinea, the Liberian Medicines and Health Products Regulatory Authority, the Pharmacy Board of Sierra Leone, and the World Health Organization Department of Essential Medicines and Health Products (FDA, 2016)
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An additional benefit that is gained from close partnerships between international ethics and regulatory bodies during the inter-epidemic period is the establishment of a corps of ethics and regulatory experts knowledgeable about different regions or countries, their culture, and the context in which trials would be conducted. Limited Experience with Contract Negotiations While the clinical trials conducted during the Ebola outbreak moved at record speed once they were prioritized and through ethics reviews, the actual starts of the trials were unnecessarily slowed by bureaucratic barriers
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. As seen in Figure 5-1, most of the steps required to implement a clinical trial during the Ebola outbreak, such as designing the protocol and obtaining ethics committee approval, could be completed relatively quickly when the partners worked closely together (Lang, 2015)
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Those who agree to be available during outbreaks to provide surge capacity would review protocols and provide opinions and advice to local scientific and ethics review committees, which would retain control over and accountability for decisions about protocols. Potential sources of experts in ethics review and negotiation of clinical trial and material transfer agreements are schools of medicine and public health with extensive experience conducting clinical trials in low-resource settings; Public Interest Intellectual Property Advisors, a nongovernmental organization that provides pro bono legal advice to low- and middle-income countries regarding health research and contracts; and COHRED, through its program on fair research contracting (Musolino et al., 2015)
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; model clinical trial agreements and other contractual arrangements such as material transfer agreements, data sharing, and post-trial expectations; as well as logistical checklists. The numerous logistical tasks that need to be considered and addressed in advance of implementing clinical trials in a low-resource setting and responding to an outbreak are extensive and each task comes with a litany of steps and substeps that must be adapted to the individual situation and followed with precision.
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institutions received grants to partner with academic centers in two of the West African countries. The support will enable them to design training programs to increase expertise in Ebola, Lassa fever and other emerging viral diseases" (Fogarty International Center, 2016)
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Such observations are not new. In 2015, Daniel Bausch from the Tulane School of Public Health and Tropical Medicine in New Orleans, referring to research projects on Lassa and other hemorrhagic fever viruses in West Africa, noted that externally funded research projects "led to considerable upgrades in the laboratory infrastructure as well as advances in our understanding of Lassa fever, [but]
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With increased investments in health research strengthening in the three highly affected countries in West Africa focused on a few facilities and a few people, the divide in the quality and capacity of research facilities versus the quality and capacity of the health care and public health facilities is growing. In parallel, the striking limited capacity of health professional education, at least as observed in Liberia, constrains their ability to educate and train the next generation of health proessionals to provide competent health care; these individuals also rep f resent the national talent pool from which future health researchers and leaders will emerge.
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. Without new commitments from leadership in donor and recipient countries to invest in health systems, facilities, and staff in order to improve health care services and the health status of the population, it is likely that investments in health research systems will not produce the desired sustainable results and that those countries most at risk of emerging infectious disease outbreaks will be no more equipped to deal with the sudden clinical burden and the need to initiate critical research than Guinea, Liberia, and Sierra Leone were in 2014.
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, regional and interna tional development agencies, and foundations working in global health, should support national efforts by providing expertise and financing. Financing National Capacity Strengthening This committee's set of recommendations for actions to strengthen capacity for response and research is intended to provide the basis for cooperative initiatives and a rational partition of primary responsibility among national health authorities, the WHO, and other supranational and international partners involved in health care, public health, and research and development for therapeutics and vaccines, including the academic and private sectors; it is now up to these entities to seize the moment to engage and to invest the critical resources needed to strengthen capacity in low- and middle-income countries for the benefit of all in terms of creating national, regional, and global public goods.
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. Yet as we saw in the recent Ebola crisis in West Africa, there is currently no fast-disbursing financial mechanism to make available significant funds to resource-constrained countries early enough to help them fight an epidemic outbreak that is escalating.
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. In addition, the West African Health Organization will receive $20 million from IDA and $4 million in trust fund co-financing from the government of Canada to help improve disease surveillance infra structure, information sharing, and collaboration across the 15 [member]
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2016. Managing dangerous pathogens: Challenges in the wake of the recent West African Ebola outbreak.
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2011. Quality of clinical trials: A moving target.
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Presentation at the Public Workshop of the Committee on Clinical Trials During the 2014–2015 Ebola Outbreak. Washington, DC; June 13–15, 2016.
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Clinical Trials 13(1)
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2017. Clinical trials toolkit.
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Clinical Trials 13(1)
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2016. The Ebola outbreak: The challenge of establishing a clinical trial during an epidemic.
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2016. Implementing an Ebola vaccine study -- Sierra Leone.
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