BREAKOUT SESSION

Clinical and Translational Research in Global Health and Emergency Care: A Research Agenda Michael S. Runyon, MD, Hendry R. Sawe, MD, Adam C. Levine, MD, MPH, Amelia Pousson, MD, MPH, Darlene R. House, MD, MS, Pooja Agrawal, MD, MPH, Maxwell Osei-Ampofo, MD, Scott G. Weiner, MD, MPH, and Katherine Douglass, MD, MPH

Abstract As policy-makers increasingly recognize emergency care to be a global health priority, the need for highquality clinical and translational research in this area continues to grow. As part of the proceedings of the 2013 Academic Emergency Medicine consensus conference, this article discusses the importance of: 1) including clinical and translational research in the initial emergency care development plan, 2) defining the burden of acute disease and the barriers to conducting research in resource-limited settings, 3) assessing the appropriateness and effectiveness of local and global acute care guidelines within the local context, 4) studying the local research infrastructure needs to understand the best methods to build a sustainable research infrastructure, and 5) studying the long-term effects of clinical research programs on health care systems. ACADEMIC EMERGENCY MEDICINE 2013; 20:1272–1277 © 2013 by the Society for Academic Emergency Medicine

A

s policy-makers increasingly recognize emergency care to be a global health priority, the need for high-quality clinical and translational research in emergency care continues to grow. Often, when developing emergency care programs in resource-limited settings, the inclination is to focus on clinical and educational services given the relative lack of resources and personnel. However, clinical and translational research must also be seen as critical to the successful development of a sustainable emergency care infrastructure.1

IMPORTANCE OF CLINICAL AND TRANSLATIONAL RESEARCH IN GLOBAL HEALTH AND EMERGENCY CARE Concurrent development of a research infrastructure within the emergency care system will serve to enhance care delivery and sustainability. As the initial focus is on improving emergency care, it is important to recognize that research is necessary to inform clinical care delivery. Just as the adult literature does not always translate to children, treatments or care delivery paradigms

From the Department of Emergency Medicine, Carolinas Medical Center (MSR), Charlotte, NC; the Department of Emergency Medicine, Muhimbili University of Health and Allied Sciences (HRS), Dar Es Salaam, Tanzania; the Department of Emergency Medicine, Brown University (ACL), Providence, RI; the Department of Emergency Medicine, George Washington University (AP, KD), Washington, DC; the Department of Emergency Medicine, Indiana University (DRH), Indianapolis, IN; the Department of Emergency Medicine, Yale School of Medicine (PA), New Haven, CT; the Department of Emergency Medicine, Tufts University School of Medicine (SGW), Boston, MA; and the Emergency Medicine Department, Komfo Anokye Teaching Hospital (MO), Kumasi, Ghana. Received July 15, 2013; revision received August 28, 2013; accepted August 29, 2013. This article reports on a breakout session of the May 2013 Academic Emergency Medicine consensus conference in Atlanta, GA: “Global Health and Emergency Care: A Research Agenda.” Breakout session participants: Pooja Agrawal, Charlene Irvin Babcock, Michelle H. Biros, Elizabeth DeVos, Katherine Douglass, Stephen Dunlop, Karen Ekernas, Marna Greenberg, Melanie Hogg, Darlene R. House, Rebecca Kornas, Elizabeth Krebs, Anita Kust, Adam C. Levine, Catherine Lynch, Ian B. K. Martin, C. Nee-Kofe Mould-Millman, Margaret Murray, Maxwell Osei-Ampofo, Ronald Pirrallo, Amelia Pousson, Michael S. Runyon, Jennifer Reifel Saltzberg, Hendry R. Sawe, Joseph Walline, Michael Weigner, and Scott G. Weiner. The authors have no relevant financial information or potential conflicts of interest to disclose. Supervising Editor: Mark Hauswald, MD. Address for correspondence and reprints: Michael S. Runyon, MD; e-mail: [email protected]

1272

ISSN 1069-6563 PII ISSN 1069-6563583

© 2013 by the Society for Academic Emergency Medicine doi: 10.1111/acem.12268

ACADEMIC EMERGENCY MEDICINE • December 2013, Vol. 20, No. 12 • www.aemj.org

generally accepted as effective in one region or population may prove harmful in another.2 For example, pediatric resuscitation according to Pediatric Advanced Life Support guidelines proved harmful when resuscitating febrile children in East Africa.2 Setting-specific research prevents inappropriate extrapolation of treatments across disparate populations and provides evidence for practice guidelines to improve patient care. An active and productive research program will also engage local care providers, not only those working in emergency departments, but also across disciplines and departments. Implementation of research can combat the “brain drain” that plagues developing countries as physicians leave for positions in more industrialized countries to further their careers.3–5 In some instances, research has enticed physicians to return from positions abroad to participate in research in their home countries.5,6 Emergency care research provides academic and professional development opportunities that will improve career satisfaction and enhance the identity of providers who focus on emergency care as they learn to independently design, conduct, and report clinical trials. Research also promotes multidisciplinary collaboration. Because emergency care involves clinical aspects of all specialties, it follows that research on emergency conditions should be a collaborative venture engaging other departments and specialties in investigations aimed at optimizing care delivery. Such interdepartmental cooperation will facilitate the conduct of high-impact studies, as well as the dissemination and acceptance of study results. Furthermore, embarking on a shared research agenda can assist in establishing and maintaining productive communication between departments. This collegiality will provide a wider perspective on addressing various operational challenges, increase academic productivity, and improve the acceptance of care providers who view emergency medicine as a specialty. In addition, collaboration between departments facilitates optimal clinical care through interdepartmental teamwork. Research will also lead to greater access to advanced care and associated resources that may not otherwise be available to clinicians. Research protocols and funding often bring in equipment and supplies, which are often left behind in the department after the investigation is complete. These resources, such as lab kits, medications, and ultrasound equipment, can be reallocated for clinical use and ultimately lead to enhanced patient care. A productive research infrastructure also brings funding. This funding can be allocated in a variety of ways, including physical infrastructure enhancements, ongoing clinical training for providers, procurement of additional supplies and equipment, and hiring of additional staff. The money can be applied in ways that fulfill the specific needs of the department in the context of the population it serves. This funding is also a tangible demonstration of the value of emergency care and the return on investment for political and financial stakeholders, which hopefully will prompt those stakeholders to provide further funding and investment. Therefore, there must be a concurrent creation and integration of a clinical and translational research strategy. The parallel development of each of these

1273

interwoven system components will serve to enhance the other independently and simultaneously. DEFINING THE BURDEN OF ACUTE DISEASE IN RESOURCE-LIMITED SETTINGS Before initiating any new research project, it is important to consider the local environment and burden of disease. A rigorous needs assessment should be conducted, and in doing so it is critically important to consider the needs of the local institution first and foremost in setting research priorities.7 The delivery of optimal emergency care depends on an accurate understanding of the local burden of disease and barriers to care. For example, care delivery in the developing world has long focused on diagnosis and treatment of communicable diseases. This is understandable considering the relatively high rates of human immunodeficiency virus, malaria, tuberculosis, and diarrheal diseases in these settings.8 However, over the past several decades, developing countries have also seen a significant increase in acute complications and death from noncommunicable diseases.9–11 Whereas diabetes mellitus, hypertension, and other cardiovascular diseases have traditionally been associated with highincome countries, they are an increasing source of morbidity and mortality in the developing world.12 Injuries, most notably road traffic crashes, have become another major source of death and disability across the developing world.13,14 Associated factors include rapid urbanization, increasing numbers of motorized vehicles, and inadequate road networks and infrastructure.14 The problem is compounded by a lack of organized trauma systems to care for these patients.15 In addition, despite the surge in emergency conditions related to noncommunicable diseases and injuries, there remains a significant gap in the diagnostic and management resources that are available in developing countries.10,16 It is imperative to incorporate these considerations into the clinical and translational research plan. CHALLENGES TO CONDUCTING RESEARCH IN RESOURCE-LIMITED SETTINGS While there are a wide variety of barriers to conducting emergency care research in a resource-limited setting, they can mostly be grouped into one of three categories: funding barriers, logistic barriers, and ethical barriers. Lack of time and funding have been described as the most significant barriers to conducting emergency care research, and this is especially true in resource-limited settings, where physician salaries are generally smaller and patient loads higher than in high-income countries.17 Moreover, obtaining grant funding for projects in developing countries can be far more difficult than obtaining funding for similar projects in developed countries. Funding issues are discussed in more detail in this issue.18 Once funding has been obtained, multiple logistic challenges must be overcome to conduct emergency care research in a resource-limited setting. Lack of physical infrastructure, including electricity, water, quiet areas for informed consent, computers, printers, copiers, Internet

1274

access, and phones/airtime can be important impediments to conducting a research study.19 The busy and chaotic work settings of clinics and hospitals in resourcelimited areas also make research more difficult.19 Remote locations with long transport times can lead to supply chain difficulties, such as lack of capacity to fix broken research equipment or the inability to keep a steady supply of study drugs and supplies available, as well as difficulty monitoring data collection or even communicating with field sites.19 Security for the research team may also be an important issue, especially in disaster and humanitarian research and emergency care research in postconflict countries. Finally, disease burden can vary significantly throughout the year, especially for infectious diseases, making the timing of the study as important as the location. Time should be spent observing or working in the clinical environment where the proposed research will take place to have a realistic understanding of the physical impediments to conducting research in that setting. Lack of an established research infrastructure, including institutional review boards, dedicated research staff, and research mentors, can be another important challenge.17 Some of this can be overcome through appropriate collaboration, where emergency medicine colleagues in developed countries with significant research experience help their colleagues in less-developed regions by reviewing study designs, providing statistical support, or editing manuscripts prior to submission.17 A lack of journals in which to publish global emergency care research can also limit the dissemination of research findings.17 The number of journals publishing global emergency care research continues to grow, but more journals are needed.20 In the short term, this can be partially resolved if organizations commit to including an international research track during their conferences where researchers from different countries can present their findings.17 Ethical issues represent a final set of challenges to conducting global emergency care research. Most experts agree, for instance, that decisions about what to study should involve the local community and/or local medical staff and hospital leadership and not simply be imposed by researchers parachuting in from abroad.17,21–23 In practice, international researchers should work with local partners prior to the start of a study to create written guidelines that lay out the terms of the research collaboration and ensure fair distribution of the benefits and rewards of the research.23 Ethical issues are also discussed in more detail elsewhere in this issue.24 Understanding these challenges is integral to designing a high-quality research study in a resource-limited setting. To be successful, the initial clinical or translational research plan should take into account the local burden of acute disease and the barriers to conducting research in resource-limited settings. ASSESSING THE APPROPRIATENESS AND EFFECTIVENESS OF LOCAL AND GLOBAL ACUTE CARE GUIDELINES WITHIN THE LOCAL CONTEXT Acute care guidelines exist in varying formats around the globe. These range from locally adapted versions of

Runyon et al. • CLINICAL AND TRANSLATIONAL RESEARCH AGENDA

resources, such as the World Health Organization’s guidelines on Integrated Management of Childhood Illness,25 and Integrated Management of Adolescent and Adult Illness,26 to formal paradigmatic strategies such as the American College of Surgeons’ Advanced Trauma Life Support program.27 Informal guidelines also exist at both the global and the local levels. A challenge to the clinician is that development of these guidelines is often driven by expert consensus and they are intended to be broadly applicable across a variety of settings. As such, the recommendations are often not rigorously assessed to ensure their appropriateness in the context of the local medical culture and available resources. This knowledge gap is an important target for clinical and translational research efforts in developing emergency care systems. As demonstrated by the “Fluid Expansion As Supportive Therapy” trial and the multicountry evaluation of the Integrated Management of Childhood Illness materials, it is clear that high-quality in-context assessment to address the appropriateness and the effectiveness of both formal and informal acute care guidelines is feasible and informative.2,28–30 The majority of other studies in this domain focus on the evaluation of disease-specific guidelines (e.g., chronic obstructive pulmonary disease, pneumonia, human immunodeficiency virus, and sepsis) as they pertain to resource-limited settings, but with little dedicated research focused on patient-oriented effectiveness outcomes in the unique setting of acute and emergency care and resuscitation.31–34 Even less work has focused on the challenging issue of transforming guidelines into accepted clinical practice—a critical intermediary step for well-researched guidelines to actually affect clinical care. Additionally, the majority of studies investigating guideline appropriateness and effectiveness have addressed infectious disease in low- and middle-income countries, despite the aforementioned increasing and well-documented burden of noncommunicable disease and injury.8,35 Therefore, another important focus of the clinical and translational research plan must be to assess the appropriateness and effectiveness of local and global acute care guidelines within the local context. STUDYING THE LOCAL RESEARCH INFRASTRUCTURE NEEDS TO UNDERSTAND THE BEST METHODS TO BUILD A SUSTAINABLE RESEARCH INFRASTRUCTURE When simultaneously developing research infrastructure along with clinical capacity, it can be challenging to independently evaluate effects and outcomes in the system when so many things are happening at the same time. In regard to evaluation and measurement of a developing research system, it makes sense to evaluate the effectiveness of the research program itself, as well as the outcomes and effects of the research that is being carried out. Eventually, research will serve to improve and inform clinical practice, which is the ultimate goal of clinical and translational research.36 Integrating a research mission from the outset has been recognized as a key step to enable professional development and academic growth of emergency care practitioners.1,37,38

ACADEMIC EMERGENCY MEDICINE • December 2013, Vol. 20, No. 12 • www.aemj.org

Institutional support can be measured to determine how effective that institution is in supporting the establishment of a research program. For example, does an effective ethics review board exist and function within the institution? Is there institutional support to assist persons interested in applying for external funding? Is there support staff to provide technical assistance, for example, in grant administration or statistical support? Availability of support staff, such as a research coordinator, has been shown to be associated with improved research productivity.37 Academic institutions and tertiary care centers would be expected to have more standard infrastructure for this kind of academic development. However, even smaller centers that are traditionally more focused on clinical care can be encouraged and supported to develop both research activities and research infrastructure to maintain these endeavors. As there is currently no widely accepted “standardized” method of research infrastructure development, it is important to study the local research infrastructure needs to understand the best methods to build a sustainable research infrastructure. STUDYING THE LONG-TERM EFFECTS OF CLINICAL RESEARCH PROGRAMS ON HEALTH CARE SYSTEMS It is possible to measure research productivity by means of certain academic metrics. For example, output metrics can include the number of research projects being conducted, the number of persons involved in research activities, the number of principal investigators from the local institution, the number of publications per year, and of those, the number of first authors from the local institution. It is important to additionally consider the financial investment by the institution to research activities, as well as the amount of external grant funding obtained.37 Academic credit is important in medicine throughout the world, and hopefully by means of achieving these measurable goals, downstream outcomes and effects on health will be achieved as well. All of these measurable outputs can be collected to demonstrate the functionality of a research program. Original clinical research studies are obviously also very important in building the capacity of a department to deliver effective clinical care relevant to the local patient population. Original inquiry in the form of new and novel clinical trials is of tremendous importance as contribution to general knowledge and academic productivity and the effects of such work may be felt across a given health care system. A recent paper published by Pariyo et al.39 describes the process as well as outputs, outcomes, and effects of general development of research infrastructure at an academic institution in sub-Saharan Africa. Investment in research at the institutional level has led to impressive results. With regard to clinical trials, it is noted that the scale-up of capability to perform clinical research has led to study outcomes with effects at the population level. Clinical research that is relevant to patient care, for example, in prevention of mother-to-child transmission of human immunodeficiency virus, was initiated at the institution level, yet has been found to be relevant on a broader scale and

1275

has a direct effect on morbidity and mortality.39 While it is often challenging to draw direct conclusions regarding the value of increasing institutional support for research capacity on patient care outcomes, the model described by Pariyo et al. presents a framework by which this kind of association can be drawn. It is also important to consider the potential for effective incorporation of clinical and translational research, as it can ultimately affect policy makers in various settings.7 Outputs of good clinical and translational research can inform decisions and play an important role in allocation of health care resources and prioritysetting. Therefore, another important consideration in the development of the clinical and translational research plan is study of the long-term effects of clinical research programs on health care systems. CONCLUSIONS This is an exciting time for emergency care providers. As systems develop, inclusion of a clinical and translational research plan should be viewed as integral to the development of a sustainable emergency care infrastructure. While several challenges exist in accomplishing this goal, the initial research agenda should include the following: Defining the burden of acute disease in various local contexts. Consideration of the barriers to conducting clinical research in resource limited settings and ways to overcome them. Assessing the appropriateness and effectiveness of local and global acute care guidelines within the local context. Studying local research infrastructure needs and understanding the best methods for building a sustainable research infrastructure. Studying the long-term effects of clinical research programs on health care systems.

• • • • •

References 1. Biros MH, Barsan WG, Lewis RJ, Sanders AB. Supporting emergency medicine research: developing the infrastructure. Acad Emerg Med. 1998; 5:177–84. 2. Maitland K, Kiguli S, Opoka RO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med. 2011; 364:2483–95. 3. Hagopian A, Thompson MJ, Fordyce M, Johnson KE, Hart LG. The migration of physicians from subSaharan Africa to the United States of America: measures of the African brain drain. Hum Resour Health. 2004; 2:17. 4. Wright D, Flis N, Gupta M. The ‘Brain Drain’ of physicians: historical antecedents to an ethical debate, c. 1960-79. Philos Ethics Humanit Med. 2008; 3:24. 5. Dodani S, LaPorte RE. Brain drain from developing countries: how can brain drain be converted into wisdom gain? J R Soc Med. 2005; 98:487–91. 6. Cyranoski D. Chinese biology. A great leap forward. Nature. 2001; 410:10–2. 7. Kolars JC, Cahill K, Donkor P, et al. Perspective: partnering for medical education in sub-Saharan

1276

8.

9.

10.

11.

12.

13.

14. 15.

16.

17.

18.

19.

20.

21.

22.

23. 24.

Africa: seeking the evidence for effective collaborations. Acad Med. 2012; 87:216–20. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012; 380:2095–128. Cooper RS, Osotimehin B, Kaufman JS, Forrester T. Disease burden in sub-Saharan Africa: what should we conclude in the absence of data? Lancet. 1998; 351:208–10. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. 2006; 367:1747–57. Boutayeb A. The double burden of communicable and non-communicable diseases in developing countries. Trans R Soc Trop Med Hyg. 2006; 100:191–9. Bertrand E, Muna WF, Diouf SM, et al. Cardiovascular emergencies in Subsaharan Africa. Arch Mal Coeur Vaiss. 2006; 99:1159–65. Lagarde E. Road traffic injury is an escalating burden in Africa and deserves proportionate research efforts. PLOS Med. 2007; 4:e170. Mock C. Injury in the developing world. West J Med. 2001; 175:372–4. Kobusingye OC, Hyder AA, Bishai D, Hicks ER, Mock C, Joshipura M. Emergency medical systems in low- and middle-income countries: recommendations for action. Bull World Health Organ. 2005; 83:626–31. Miranda JJ, Kinra S, Casas JP. Davey Smith G, Ebrahim S. Non-communicable diseases in low- and middle-income countries: context, determinants and health policy. Trop Med Int Health. 2008; 13:1225–34. Alagappan K, Schafermeyer R, Holliman CJ, et al. International emergency medicine and the role for academic emergency medicine. Acad Emerg Med. 2007; 14:451–6. Vu A, Duber HC, Sasser S, et al. Emergency care research funding in the global health context: trends, priorities, and future directions. Acad Emerg Med. 2013; 20:1259–63. Tinto H, Noor RA, Wanga CL, et al. Good clinical practice in resource-limited settings: translating theory into practice. Am J Trop Med Hyg. 2013; 88:608–13. Levine AC, Goel A, Keay CR, et al. International emergency medicine: a review of the literature from 2006. Acad Emerg Med. 2007; 14:1190–3. Molyneux E, Mathanga D, Witte D, Molyneux M. Practical issues in relation to clinical trials in children in low-income countries: experience from the front line. Arch Dis Child. 2012; 97:848–51. Emanuel EJ, Wendler D, Killen J, Grady C. What makes clinical research in developing countries ethical? The benchmarks of ethical research. J Infect Dis. 2004; 189:930–7. Costello A, Zumla A. Moving to research partnerships in developing countries. BMJ. 2000; 321:827–9. Hirshon JM, Hansoti B, Hauswald M, et al. Ethics in acute care research: a global perspective and

Runyon et al. • CLINICAL AND TRANSLATIONAL RESEARCH AGENDA

25.

26.

27.

28.

29.

30.

31.

32.

33.

34.

35.

36. 37.

research agenda. Acad Emerg Med. 2013; 20:1251– 58. World Health Organization. Maternal, Newborn, Child and Adolescent Health. Integrated Management of Childhood Illness (IMCI). Available at: http://www.who.int/maternal_child_adolescent/topics/child/imci/en/. Accessed Sep 28, 2013. World Health Organization. Acute Care. Integrated Management of Adolescent and Adult Illness. Available at: http://whqlibdoc.who.int/hq/2004/WHO_CDS_IMAI_2004.1.pdf. Accessed Sep 28, 2013. American College of Surgeons. Advanced Trauma Life Support. Available at: http://www.facs.org/ trauma/atls/. Accessed Sep 28, 2013. Bryce J, Victora CG, Habicht JP, Vaughan JP, Black RE. The multi-country evaluation of the integrated management of childhood illness strategy: lessons for the evaluation of public health interventions. Am J Public Health. 2004; 94:406–15. Bryce J, Victora CG, Habicht JP, Black RE, Scherpbier RW. MCE-IMCI Technical Advisors. Programmatic pathways to child survival: results of a multicountry evaluation of Integrated Management of Childhood Illness. Health Policy Plan. 2005; 20(Suppl 1):i5–17. Gouws E, Bryce J, Habicht JP, et al. Improving antimicrobial use among health workers in firstlevel facilities: results from the multi-country evaluation of the Integrated Management of Childhood Illness strategy. Bull World Health Organ. 2004; 82:509–15. Desalu OO, Onyedum CC, Adeoti AO, et al. Guideline-based COPD management in a resource-limited setting–physicians’ understanding, adherence and barriers: a cross-sectional survey of internal and family medicine hospital-based physicians in Nigeria. Prim Care Respir J. 2013; 22:79–85. Graham SM, English M, Hazir T, Enarson P, Duke T. Challenges to improving case management of childhood pneumonia at health facilities in resource-limited settings. Bull World Health Organ. 2008; 86:349–55. Jacob ST, Lim M, Banura P, et al. Integrating sepsis management recommendations into clinical care guidelines for district hospitals in resource-limited settings: the necessity to augment new guidelines with future research. BMC Med. 2013; 11:107. Mahavanakul W, Nickerson EK, Srisomang P, et al. Feasibility of modified surviving sepsis campaign guidelines in a resource-restricted setting based on a cohort study of severe S. aureus sepsis [corrected]. PLOS One. 2012; 7:e29858. Lang TA, White NJ, Tran HT, et al. Clinical research in resource-limited settings: enhancing research capacity and working together to make trials less complicated. PLOS Negl Trop Dis. 2010; 4:e619. Woolf SH. The meaning of translational research and why it matters. JAMA. 2008; 299:211–3. Karras DJ, Kruus LK, Baumann BM, et al. Emergency medicine research directors and research programs: characteristics and factors associated with productivity. Acad Emerg Med. 2006; 13:637– 44.

ACADEMIC EMERGENCY MEDICINE • December 2013, Vol. 20, No. 12 • www.aemj.org

38. Aghababian RV, Barsan WG, Bickell WH, et al. Research directions in emergency medicine. Am J Emerg Med. 1996; 14:681–3. 39. Pariyo G, Serwadda D, Sewankambo NK, Groves S, Bollinger RC, Peters DH. A grander challenge: the

1277

case of how Makerere University College of Health Sciences (MakCHS) contributes to health outcomes in Africa. BMC Int Health Hum Rights. 2011; 11 (Suppl 1):S2.

Clinical and translational research in global health and emergency care: a research agenda.

As policy-makers increasingly recognize emergency care to be a global health priority, the need for high-quality clinical and translational research i...
221KB Sizes 0 Downloads 0 Views