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Emergency Medicine Australasia (2014) 26, 8–13
doi: 10.1111/1742-6723.12178
RESEARCH
Past, present and future of emergency care research Jeffrey A Kline1,2 Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA, and 2Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana, USA 1
The title of this work reflects the thematic change under way in emergency research. Whereas medicine implies a discipline, care implies the human transfer of knowledge, drugs, procedures and compassion. The public demands pragmatic clinical care. Citizens who vote and pay taxes, and those who voluntarily donate money for research, increasingly use layperson medical information to evaluate our collective return on investment in medical research. Our patients are demanding research with less concern on ‘how it works’ and more focus on ‘does it work for people like me’.
Historical perspective of emergency research Box 1 summarises a few influential time periods and events in emergency care research over the past three decades. Twenty-five years ago, early emergency researchers who submitted grant applications that proposed applied research had almost no chance of being funded by national peer-reviewed agencies, including the major funding agencies in Australia (the National Health and Medical Research Council), New Zealand (the Health Research Council), UK (Medical Research Council) and in the United States (the National Institutes for Health, NIH). Using the old parlance of these agencies, almost all grant applications that sought to determine if a new idea had potential to work clinically were ‘triaged’, meaning they were not even discussed for possible funding. Many young investigators in emergency medicine resorted to contacting their local sales representative responsible for marketing the drug or device most relevant to their research. This led to many unrestricted grants that allowed preliminary data for innovative ideas that might economically benefit the sponsor. Most of these projects remained preliminary.
In 1994, the Research Committee of the Society for Academic Emergency Medicine (SAEM) recognised the need for emergency care researchers to make a presence on national review committees, including the NIH. However, the committee members collectively knew that many emergency physicians needed much more basic knowledge to get started, including a set of guidelines on how to do research. The next year, the committee members published a series of papers intended to function as a field guide for would-be emergency researchers. Thus, 20 years ago, thought leaders in emergency research literally had to write papers in peer review to tell academicians how to embark on research in emergency medicine. In the mid-1990s, the world had fewer than 35 researchers in emergency medicine who were principal investigators on grants awarded by National agencies. Many countries, including England, France and New Zealand, had one to two full professors of emergency medicine. However, determining the exact number of NIH- or equivalent National Health MinistryFunded investigators by querying national research databases (e.g. NIH RePORTER) has always been a methodological challenge. Within these available databases, which are the only reasonable way to search and collate such data, emergency researchers were often obfuscated to discovery on searches looking for the word ‘emergency’. This problem can be explained by the fact that principal investigators had appointments in academic EDs that were divisions of other departments (such as internal medicine or surgery) and their awards were listed in those departments. With that caveat, the search by department ‘emergency medicine’ in RePORTER yields 109 funded projects (as of 19 November 2013), to approximately 40 unique investigators. With this datum, together with my own experience and interactions as an
Jeffrey A Kline, MD, Vice Chair of Research, Professor. © 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
Research
Box 1. Major forces of change and time periods in emergency care • 1980s: Recognition of emergency medicine as a unique specialty by the American Board of Medical Specialties. Early research focused heavily on cardiac arrest and whether or not buffered lidocaine hurt less than non-buffered lidocaine. Emergency medicine academic departments began to be staffed by graduates of emergency medicine residencies. • Early 1990s: Development of funding sources unique to emergency medicine, first by the Emergency Medicine Foundation, then the Society for Academic Emergency Medicine. The requirement to be an emergency researcher is to graduate from a residency and be willing to make less money and take an academic job. • Late 1990s: Pharmaceutical and device manufacturers became less willing to fund investigator-initiated research. • 1995: The Macy Foundation conference from 1994, held in Williamsburg, VA, anticipates a huge deficit in emergency medicine researchers and resolves that ‘ACEP and SAEM should quickly convene a conference to develop an agenda for research in emergency medicine and to define strategic options for implementing that agenda’.4 • 1998: Harold Varmus, NIH director, speaks at an SAEM meeting in Washington, DC, and acknowledges that treatments initiated in the ED profoundly affect outcome. He uses an example of thrombolytic treatment for stroke that he saw on the television programme ‘ER’ as an example. • Early 2000s: Emergency researchers gained exposure within national funding agencies, including individual research awards and service on review panels. • 2000s: Protocolised care is demonstrated to improve outcomes for several emergent conditions, increasing awareness of the importance of emergency medicine in longitudinal outcomes; Programmes offering masters of clinical investigation become more common as do emergency medicine research fellowships. The requirement to be an emergency researcher shifts towards requiring formal research training. • 2006: In its report, Hospital-Based Emergency Care: At the Breaking Point, the US Institute of Medicine implicates more strongly the need for emergency care researchers. • 2009: Primarily in response to the IOM report, the NIH convenes a roundtable of stakeholders to discuss the future of research emergency care to determine the priorities and needs for emergency care in the future; publications emanating from the meetings call for enhanced research training programmes.5 • 2010: Protected research time for emergency practitioners who have not done formal training becomes extremely rare in academic programmes. SAEM initiates a process to approve emergency research fellowships. The NIH designates $50 million to support five K12 training programmes. A nearly perfect score is awarded to a programme focusing on qualitative research. • 2010s: The Affordable Care Act creates the Patient Centered and Outcomes Research Institute (PCORI), representing a forum more open to qualitative methods, shared decision-making, protocols comparing diagnostic methods, processes of care and treatments, using outcomes decided in part by patients. • 2020s: Consumerism will drive research, requiring researchers to enhance the PCORI-driven initiatives. Innovations, including video-informed consent, will reduce the barriers to enrolment. Large accountable care organisations will set up boilerplate indemnification agreements to enhance multicentre research. The impact of printed journals continues to decline, leaving only a few major journals received in the mail by anyone. Researchers will become increasingly motivated to report their findings at CME conferences; websites that offer updated, transparent and continuous peer review for medical research; and public forums to bring their work directly to their audience. • Late 2020s: In a lag far longer than predicted, researchers finally begin to leverage electronic data records to conduct massive retrospective studies, using techniques similar to propensity matching to compare costs and outcomes of protocols, care processes, treatments and healthcare systems.
active researcher, I estimate that globally, between 100 to 150 emergency clinician researchers are principal investigators funded by national agencies today, supported by approximately 30–50 million dollars in direct cost funding per year. Although this 10-fold growth over 20 years is impressive, on a per-patient basis, the current absolute amount of funding trifles in proportion to funding for heart disease, cancers or most subspecialties in internal medicine.
In the United States, over 100 million patients are seen each year in an ED, and about half of all hospital admissions come through an ED. In the United States, we spend approximately 25 cents per patient visit on research in emergency medicine, compared with $23 000 per patient living with HIV in the United States. This lack of funding impairs emergency care research. Greater still, the compressed time frame, chaos and uncertainty patients with life-threatening processes
© 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
9
JA Kline
experience in the ED amplify the difficulty of highquality, important research in the ED setting.
Why is it so hard to do high-impact research? Consider the improbable intersection of forces required to conduct powerful patient-focused research. Research starts with an important new good idea, conceived by a person with the ability to explain it clearly, and the wherewithal to plan and persist in its execution. The investigator needs an enabling environment, including patient access and then enough time, human resources and money to do the work. Then the project needs some good luck along the way. In the ED, the cost of orchestrating these forces into a functioning protocol depends on timing, as shown in Figure 1. Figure 1 depicts how the ED directs undifferentiated complaints into diagnostic categories, which in turn determine treatment. As we approach the treatment threshold, the cost, risk and reward of research increase in parallel. I emphasise this is on a per-patient basis. In the outpatient setting, obtaining informed consent and following cohorts of at-risk patients are generally less expensive per patient than research conducted in the ED. Thus, population-based cohort studies relevant to understanding the biology of patients in the
Triage and initial management
Pre-hospital
01:00
Treatment
Diagnosis
02:00
00:00
ED require large numbers and assiduous follow up to make a collectively large impact. The diagnostic process carries a pivotal role because it dictates the treatment plan, launches protocol, and decides who gets consulted and where the patient goes. In the ED, diagnostic studies are generally more cost-feasible than interventional studies, simply because testing new diagnostic protocols often can be opportunistic, meaning they compare a new test or algorithm with standard care processes, perhaps supplemented by electronic medical record or telephone follow up.1 The problem with these non-interventional studies is they provide only a ‘what-if’ look at how a new diagnostic test could perform. Peer reviewers and consumers of research can be expected to turn up their demand for randomised controlled trial designs that compare the real outcomes and cost of different methods of diagnosis. Ironically, at the same time, in an attempt to protect patients, laws and regulations in the United States and other westernised countries have impaired this type of research in diagnosis. Twenty years ago, institutional review boards (IRBs) routinely approved informed consent documents that warned patients of the possibility that participation could increase their cost of care. At present, IRBs routinely mandate that the research budget pay for tests and treatments for all uninsured patients, and for patients with insurance that might not cover the research. The research budget must
03:00
Disposition
Admission
04:00 05:00
Trauma Infection/ Sepsis
Home phase of illness
Transport by emergency services or private vehicle
Vital signs, chief complaint, initial clinician contact, laboratory and imaging studies
Thrombotic/ Ischaemic Relapsing chronic
Drugs Devices Protocols Consultation Admission location
Outcome
Psychiatric Minor
Figure 1. Diagram of the phases where patient-focused emergency research generally occurs. The plot below the phases provides the author’s estimate of the relative cost and impact of research at each phase on a per-patient basis. ( ), Relative cost of research; ( ), relative impact of research. The horizontal time line shows hours.
10
© 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
Research
then pay exorbitant ‘research prices’, which for imaging studies, in particular, often exceed that which insurers pay, because hospitals price them to profit from industry-funded trials. In countries where national healthcare agencies are willing to pay for clinically available diagnostic studies as part of a clinical trial, the amount of money that the investigator has to raise to conduct a diagnostic study is often considerably less than in the United States. The Affordable Care Act in the United States in theory could provide some remedy because it contains language requiring that insurers must pay for approved procedures.2 However, the act does not specify any mechanism or government agency to police this requirement when beneficiaries are denied coverage of hospital charges attributed to a research protocol. In short, research designed to truly change how we diagnose disease in the ED will cost more unless we see a relaxation in the administrative burden. Figure 1 indicates the largest per-patient step in cost for research that tests new treatments, especially for high-risk conditions, such as trauma, suicidality, ischaemic vital organs or sepsis. Treatment initiated in the ED has amplified importance, because of its timing in the course of disease. This effect is conceptually equivalent to aiming a rifle (the treatment) at a target 100 yards away (patient outcome). Minute changes in the angle of the barrel, or a small tremor, can be the difference between hitting the bullseye and missing the entire target. Protocolised care for patients with trauma, sepsis, myocardial infarction and stroke all show the value of time-urgent interventions. Unfortunately, these studies carry astounding costs to perform. As we hope and plan for future emergency research to find new treatments and treatment paradigms that will reduce death, disability, suffering and cost, researchers must understand the hidden and uncompensated costs and complexities of treatment studies. To better define these challenges, in preparation for the present editorial, I and my colleagues involved in the multicentre randomised trial of Tenecteplase Or Placebo, Cardiopulmonary Outcomes At Three months (TOPCOAT) published the methods and initial findings in this Journal.3 Textbooks on clinical trials have included chapters that qualitatively acknowledge some of the uncompensated costs of clinical trials, but to my knowledge, no publication has quantified these costs for a high-stakes intervention study that enrolled primarily ED patients.3 TOPCOAT randomised patients with severe submassive pulmonary embolism to placebo or tenecteplase, and followed their outcomes. Each patient knew he or she had a tangible risk of death from his/her
disease. Their participation offered either a bolus of saltwater or a treatment that could literally dissolve the immediate threat to their wellness, or put them at risk for devastating bleeding in the hours subsequent to signing the consent form.3 I believe TOPCOAT contains several elements that will drive future emergency investigator-initiated research, including the multicentre design, alternative sources of funding and its composite, quality of life end-points, constructed with patient input. However, what TOPCOAT teaches us about current and future impediments to research includes: 1. National funding agencies are averse to clinical trials that impose substantial risk to patients, and as a result, investigators wanting to conduct trials that could lead to death or disability had better plan on alternative sources of funding beyond the NIH. Despite the contraction in private equity for research, we were able to find a corporate partner to fund TOPCOAT because the design and outcomes aligned with the scientific and business interests of Genentech Inc. (South San Francisco, CA, USA). 2. The enormous scope and exhausting administrative burden of subcontracting other hospitals for a multicentre, high-risk trial. Almost no important, interventional study of a life-threatening disease can be done without a multicentre approach. The ‘indemnification language’ for participating hospitals and investigators poses one of the most formidable administrative obstacles. Indemnification refers to the wording in the research agreement or contract that decides who will pay in the event that something goes wrong, primarily if a patient is injured as a result of participation. These payments are not just for the medical care, but also for legal costs for a lawsuit, and who will pay for a settlement or jury verdict. Depending on the lawyers involved and the setting, indemnification might extend to cover issues, such as lost market share by hospitals in the event of bad publicity, or covering legal costs of investigators in the event they are sued as individuals. 3. The hidden opportunity cost of enrolling and following patients exemplified by screening costs. To enroll 83 patients with complete data, TOPCOAT investigators and their teams had to approach 640 patients, their families and healthcare team members to begin the informed consent process. In about 10% of cases, immediate exclusions were found within 30–45 min after initial identification. In at least 50% of cases, one or more members of the research team had to engage the patient, the medical record, the patients’
© 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
11
JA Kline
family and the medical care team. For every patient enrolled, we spent approximately 6 h in uncompensated time while we attempted to enroll other patients, who ultimately declined or otherwise were found to be ineligible. We estimate that, for the entire study had $313 000 in uncompensated screening costs. Once a patient was deemed fully eligible, he/she was asked to read and initial in his/her own hand, 10 pages of an informed consent document (replete with warnings and descriptions of bodily and financial risk), and then print and sign their name and date twice at the end. This seemingly menial task can be Herculean for an exhausted, exasperated and frightened person being asked to participate in a research study. Thus, as we forge forward, current and future investigators must acknowledge the cost and hard work that needs to be done. These narratives describing the difficulties with diagnostic and therapeutic research underscore how the effort puts at risk the personal time and effort from the principal investigator, or so-called opportunity cost. For this reason, public benefit from emergency care research will spring from the motivation, resilience, desire and fire in the belly of properly trained and institutionally supported individual emergency researchers. This statement stands in contrast to the zeitgeist of most ‘transforming research’ initiatives being discussed and vaguely implemented at medical schools around the world, which, without exception, are purporting the importance of breaking down walls to encourage teambased research. A key example of this effort can be seen in the development of vascular medicine centres that consolidate the turfs of cardiology, nephrology, heart and vascular surgeons, and interventional radiologists. In this regard, I believe thought leaders have confused successful systems of care delivery and marketing with successful systems of research. The workhorse of research has, and always will be, individual researchers. Groups of people are well suited to producing accurate normative results, such as guessing the weight of a cow. A paradigm-busting, out-of-the-box, transformative research idea, which is prosecuted to its finality, comes from individuals who have training, confidence, and access to resources and patients to do the work. What about the benefit of collaboration without regard to turf, ideology or department status, but to bring the best minds together? That has been an absolute requirement for any researcher who has demonstrated successful funding year after year and has produced a work product that is favourably reviewed at journal clubs 12
around the world. Trans-departmental collaboration has and always will require one person who has the conviction to go knocking on doors of researchers outside of emergency medicine. The past teaches us that if an investigator has an idea of real merit, can articulate his or her position, and shows unshakable dedication, he or she will walk away with a new collaborator. The development of these research warriors requires three interlocking concepts: a society that values knowledge creation enough to pay for research training; physicians and scientists willing to spend the time and effort to gain emergency care-specific research training; and the programmes for them to get the training. The first part comes from voters and patients; the second part comes from education leaders who influence young minds as they train to be practitioners of emergency care; and the third part comes from advocacy groups, agencies and governments. The Emergency Care K12 Training Programs and the SAEM’s mechanism to review and approve emergency research fellowships in the United States are important examples of how emergency care training programmes are being created in the United States.
What can be predicted? As it always has, the availability of funds and the priorities of funding entities will drive the direction and scope of future research in emergency care. Box 1 shows where we have been and where we are headed. We will see continued rise of patient involvement in the design of clinical research. Funding from the nongovernmental Patient Centererd Outcomes Research Institute organisation will continue to grow, and governmental funding agencies will feel pressure from elected officials, who in turn are voted into office by a constituency that demands their health ministries and agencies produce clinically relevant research. The global cache of well-trained, consistently funded emergency researchers will increase from approximately 100 today to 500 by the year 2025. Almost all successful emergency researchers will obtain titles and appointments in other departments where their research is most relevant. Money will flow to those of you who provide new data on outcomes that inform how hospitals can best provide high-quality care at the lowest cost. Not-for-profit hospital systems, which despite their exhortations of impending revenue loss, will continue to post 5–10% profit margins and will have no other options but to invest in research. These mega-systems
© 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
Research
will invest in research that examines outcomes that distinguish them from their competitors and improve patient satisfaction. Industry funding will remain a relatively small source of investigator-initiated research, but companies will occasionally fund important homegrown projects that suit their business goals. Smaller foundations, such as the Emergency Medicine Foundation of the American College of Emergency Physicians® and SAEM, will continue to serve as important incubators for new researchers. The cost of screening patients for research studies will decrease as natural language processing methods are used in systemised electronic health record databases to identify eligible patients, with electronic alerts sent to research team members. Less burdensome methods of informed consent will prevail, including consent obtained and recorded by video, enabling remote enrollment in smaller hospitals, connected legally and electronically to a hospital network with a flagship academic hospital. Publicly available, large databases, such as the Healthcare Cost and Utilization Project National Inpatient sample and National Emergency Department sample, will be inexpensively mined and subjected to propensity-matching methodology to test the role of new treatments. The sheer size of these databases will provide as much power as randomised trials for inferences about hard end-points such as mortality, and economic end-points, such as intermediate cost of medical care. The key areas of research that will lead to pioneering findings and deep results will incorporate elements of shared decision-making and patient participation, and measure end-points that consider quality of life and patient perception of wellness. I would predict, in particular, that one topic that will gain particularly high level of attention from the public will be the role of emergency practitioners to empower patients and families to make end-of-life decisions in the ED setting.
In summary, funding for emergency care will determine what gets done, and I believe that the stronger the message of compassion and empathy that our research carries, the more likely it is to gain financial backing. In addition to conventional end-points of mortality or cure, research that makes patients feel better faster, empowers them in the medical decision-making process and liberates them from the hospital sooner, will see the highest levels of support.
Competing interests JAK is a member of the Editorial Board (International) of Emergency Medicine Australasia, owns stock in CP Diagnostics LLC, is a consultant for Daiichi, Donawa Lifesciences Consulting, and has received funding from the Agency for Healthcare Quality and the National Institutes for Health.
References 1.
Kline JA, Mitchell AM, Runyon MS, Jones AE, Webb WB. Electronic medical record review as a surrogate to telephone follow-up to establish outcome for diagnostic research studies in the emergency department. Acad. Emerg. Med. 2005; 12: 1127–232.
2.
Kline JA, Walthall JD. Patient Protection and Affordable Care Act of 2010: summary, analysis, and opportunities for advocacy for the academic emergency physician. Acad. Emerg. Med. 2010; 17: e69–e74.
3.
Kline JA, Hernandez-Nino J, Hogg MM et al. Rationale and methodology for a multicenter randomised trial of fibrinolysis for pulmonary embolism that includes quality of life outcomes. Emerg. Med. Australas. 2013; 25: 515–26.
4.
Macy J, Jr. The role of emergency medicine in the future of American medical care. Ann. Emerg. Med. 1995; 25: 230–3.
5.
Kaji AH, Lewis RJ, Beavers-May T et al. Summary of NIH Medical-Surgical Emergency Research Roundtable held on April 30 to May 1, 2009. Ann. Emerg. Med. 2010; 56: 522–37.
© 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
13
Emergency Medicine Australasia (2014) 26, 8–13
doi: 10.1111/1742-6723.12178
RESEARCH
Past, present and future of emergency care research Jeffrey A Kline1,2 Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA, and 2Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana, USA 1
The title of this work reflects the thematic change under way in emergency research. Whereas medicine implies a discipline, care implies the human transfer of knowledge, drugs, procedures and compassion. The public demands pragmatic clinical care. Citizens who vote and pay taxes, and those who voluntarily donate money for research, increasingly use layperson medical information to evaluate our collective return on investment in medical research. Our patients are demanding research with less concern on ‘how it works’ and more focus on ‘does it work for people like me’.
Historical perspective of emergency research Box 1 summarises a few influential time periods and events in emergency care research over the past three decades. Twenty-five years ago, early emergency researchers who submitted grant applications that proposed applied research had almost no chance of being funded by national peer-reviewed agencies, including the major funding agencies in Australia (the National Health and Medical Research Council), New Zealand (the Health Research Council), UK (Medical Research Council) and in the United States (the National Institutes for Health, NIH). Using the old parlance of these agencies, almost all grant applications that sought to determine if a new idea had potential to work clinically were ‘triaged’, meaning they were not even discussed for possible funding. Many young investigators in emergency medicine resorted to contacting their local sales representative responsible for marketing the drug or device most relevant to their research. This led to many unrestricted grants that allowed preliminary data for innovative ideas that might economically benefit the sponsor. Most of these projects remained preliminary.
In 1994, the Research Committee of the Society for Academic Emergency Medicine (SAEM) recognised the need for emergency care researchers to make a presence on national review committees, including the NIH. However, the committee members collectively knew that many emergency physicians needed much more basic knowledge to get started, including a set of guidelines on how to do research. The next year, the committee members published a series of papers intended to function as a field guide for would-be emergency researchers. Thus, 20 years ago, thought leaders in emergency research literally had to write papers in peer review to tell academicians how to embark on research in emergency medicine. In the mid-1990s, the world had fewer than 35 researchers in emergency medicine who were principal investigators on grants awarded by National agencies. Many countries, including England, France and New Zealand, had one to two full professors of emergency medicine. However, determining the exact number of NIH- or equivalent National Health MinistryFunded investigators by querying national research databases (e.g. NIH RePORTER) has always been a methodological challenge. Within these available databases, which are the only reasonable way to search and collate such data, emergency researchers were often obfuscated to discovery on searches looking for the word ‘emergency’. This problem can be explained by the fact that principal investigators had appointments in academic EDs that were divisions of other departments (such as internal medicine or surgery) and their awards were listed in those departments. With that caveat, the search by department ‘emergency medicine’ in RePORTER yields 109 funded projects (as of 19 November 2013), to approximately 40 unique investigators. With this datum, together with my own experience and interactions as an
Jeffrey A Kline, MD, Vice Chair of Research, Professor. © 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
Research
Box 1. Major forces of change and time periods in emergency care • 1980s: Recognition of emergency medicine as a unique specialty by the American Board of Medical Specialties. Early research focused heavily on cardiac arrest and whether or not buffered lidocaine hurt less than non-buffered lidocaine. Emergency medicine academic departments began to be staffed by graduates of emergency medicine residencies. • Early 1990s: Development of funding sources unique to emergency medicine, first by the Emergency Medicine Foundation, then the Society for Academic Emergency Medicine. The requirement to be an emergency researcher is to graduate from a residency and be willing to make less money and take an academic job. • Late 1990s: Pharmaceutical and device manufacturers became less willing to fund investigator-initiated research. • 1995: The Macy Foundation conference from 1994, held in Williamsburg, VA, anticipates a huge deficit in emergency medicine researchers and resolves that ‘ACEP and SAEM should quickly convene a conference to develop an agenda for research in emergency medicine and to define strategic options for implementing that agenda’.4 • 1998: Harold Varmus, NIH director, speaks at an SAEM meeting in Washington, DC, and acknowledges that treatments initiated in the ED profoundly affect outcome. He uses an example of thrombolytic treatment for stroke that he saw on the television programme ‘ER’ as an example. • Early 2000s: Emergency researchers gained exposure within national funding agencies, including individual research awards and service on review panels. • 2000s: Protocolised care is demonstrated to improve outcomes for several emergent conditions, increasing awareness of the importance of emergency medicine in longitudinal outcomes; Programmes offering masters of clinical investigation become more common as do emergency medicine research fellowships. The requirement to be an emergency researcher shifts towards requiring formal research training. • 2006: In its report, Hospital-Based Emergency Care: At the Breaking Point, the US Institute of Medicine implicates more strongly the need for emergency care researchers. • 2009: Primarily in response to the IOM report, the NIH convenes a roundtable of stakeholders to discuss the future of research emergency care to determine the priorities and needs for emergency care in the future; publications emanating from the meetings call for enhanced research training programmes.5 • 2010: Protected research time for emergency practitioners who have not done formal training becomes extremely rare in academic programmes. SAEM initiates a process to approve emergency research fellowships. The NIH designates $50 million to support five K12 training programmes. A nearly perfect score is awarded to a programme focusing on qualitative research. • 2010s: The Affordable Care Act creates the Patient Centered and Outcomes Research Institute (PCORI), representing a forum more open to qualitative methods, shared decision-making, protocols comparing diagnostic methods, processes of care and treatments, using outcomes decided in part by patients. • 2020s: Consumerism will drive research, requiring researchers to enhance the PCORI-driven initiatives. Innovations, including video-informed consent, will reduce the barriers to enrolment. Large accountable care organisations will set up boilerplate indemnification agreements to enhance multicentre research. The impact of printed journals continues to decline, leaving only a few major journals received in the mail by anyone. Researchers will become increasingly motivated to report their findings at CME conferences; websites that offer updated, transparent and continuous peer review for medical research; and public forums to bring their work directly to their audience. • Late 2020s: In a lag far longer than predicted, researchers finally begin to leverage electronic data records to conduct massive retrospective studies, using techniques similar to propensity matching to compare costs and outcomes of protocols, care processes, treatments and healthcare systems.
active researcher, I estimate that globally, between 100 to 150 emergency clinician researchers are principal investigators funded by national agencies today, supported by approximately 30–50 million dollars in direct cost funding per year. Although this 10-fold growth over 20 years is impressive, on a per-patient basis, the current absolute amount of funding trifles in proportion to funding for heart disease, cancers or most subspecialties in internal medicine.
In the United States, over 100 million patients are seen each year in an ED, and about half of all hospital admissions come through an ED. In the United States, we spend approximately 25 cents per patient visit on research in emergency medicine, compared with $23 000 per patient living with HIV in the United States. This lack of funding impairs emergency care research. Greater still, the compressed time frame, chaos and uncertainty patients with life-threatening processes
© 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
9
JA Kline
experience in the ED amplify the difficulty of highquality, important research in the ED setting.
Why is it so hard to do high-impact research? Consider the improbable intersection of forces required to conduct powerful patient-focused research. Research starts with an important new good idea, conceived by a person with the ability to explain it clearly, and the wherewithal to plan and persist in its execution. The investigator needs an enabling environment, including patient access and then enough time, human resources and money to do the work. Then the project needs some good luck along the way. In the ED, the cost of orchestrating these forces into a functioning protocol depends on timing, as shown in Figure 1. Figure 1 depicts how the ED directs undifferentiated complaints into diagnostic categories, which in turn determine treatment. As we approach the treatment threshold, the cost, risk and reward of research increase in parallel. I emphasise this is on a per-patient basis. In the outpatient setting, obtaining informed consent and following cohorts of at-risk patients are generally less expensive per patient than research conducted in the ED. Thus, population-based cohort studies relevant to understanding the biology of patients in the
Triage and initial management
Pre-hospital
01:00
Treatment
Diagnosis
02:00
00:00
ED require large numbers and assiduous follow up to make a collectively large impact. The diagnostic process carries a pivotal role because it dictates the treatment plan, launches protocol, and decides who gets consulted and where the patient goes. In the ED, diagnostic studies are generally more cost-feasible than interventional studies, simply because testing new diagnostic protocols often can be opportunistic, meaning they compare a new test or algorithm with standard care processes, perhaps supplemented by electronic medical record or telephone follow up.1 The problem with these non-interventional studies is they provide only a ‘what-if’ look at how a new diagnostic test could perform. Peer reviewers and consumers of research can be expected to turn up their demand for randomised controlled trial designs that compare the real outcomes and cost of different methods of diagnosis. Ironically, at the same time, in an attempt to protect patients, laws and regulations in the United States and other westernised countries have impaired this type of research in diagnosis. Twenty years ago, institutional review boards (IRBs) routinely approved informed consent documents that warned patients of the possibility that participation could increase their cost of care. At present, IRBs routinely mandate that the research budget pay for tests and treatments for all uninsured patients, and for patients with insurance that might not cover the research. The research budget must
03:00
Disposition
Admission
04:00 05:00
Trauma Infection/ Sepsis
Home phase of illness
Transport by emergency services or private vehicle
Vital signs, chief complaint, initial clinician contact, laboratory and imaging studies
Thrombotic/ Ischaemic Relapsing chronic
Drugs Devices Protocols Consultation Admission location
Outcome
Psychiatric Minor
Figure 1. Diagram of the phases where patient-focused emergency research generally occurs. The plot below the phases provides the author’s estimate of the relative cost and impact of research at each phase on a per-patient basis. ( ), Relative cost of research; ( ), relative impact of research. The horizontal time line shows hours.
10
© 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
Research
then pay exorbitant ‘research prices’, which for imaging studies, in particular, often exceed that which insurers pay, because hospitals price them to profit from industry-funded trials. In countries where national healthcare agencies are willing to pay for clinically available diagnostic studies as part of a clinical trial, the amount of money that the investigator has to raise to conduct a diagnostic study is often considerably less than in the United States. The Affordable Care Act in the United States in theory could provide some remedy because it contains language requiring that insurers must pay for approved procedures.2 However, the act does not specify any mechanism or government agency to police this requirement when beneficiaries are denied coverage of hospital charges attributed to a research protocol. In short, research designed to truly change how we diagnose disease in the ED will cost more unless we see a relaxation in the administrative burden. Figure 1 indicates the largest per-patient step in cost for research that tests new treatments, especially for high-risk conditions, such as trauma, suicidality, ischaemic vital organs or sepsis. Treatment initiated in the ED has amplified importance, because of its timing in the course of disease. This effect is conceptually equivalent to aiming a rifle (the treatment) at a target 100 yards away (patient outcome). Minute changes in the angle of the barrel, or a small tremor, can be the difference between hitting the bullseye and missing the entire target. Protocolised care for patients with trauma, sepsis, myocardial infarction and stroke all show the value of time-urgent interventions. Unfortunately, these studies carry astounding costs to perform. As we hope and plan for future emergency research to find new treatments and treatment paradigms that will reduce death, disability, suffering and cost, researchers must understand the hidden and uncompensated costs and complexities of treatment studies. To better define these challenges, in preparation for the present editorial, I and my colleagues involved in the multicentre randomised trial of Tenecteplase Or Placebo, Cardiopulmonary Outcomes At Three months (TOPCOAT) published the methods and initial findings in this Journal.3 Textbooks on clinical trials have included chapters that qualitatively acknowledge some of the uncompensated costs of clinical trials, but to my knowledge, no publication has quantified these costs for a high-stakes intervention study that enrolled primarily ED patients.3 TOPCOAT randomised patients with severe submassive pulmonary embolism to placebo or tenecteplase, and followed their outcomes. Each patient knew he or she had a tangible risk of death from his/her
disease. Their participation offered either a bolus of saltwater or a treatment that could literally dissolve the immediate threat to their wellness, or put them at risk for devastating bleeding in the hours subsequent to signing the consent form.3 I believe TOPCOAT contains several elements that will drive future emergency investigator-initiated research, including the multicentre design, alternative sources of funding and its composite, quality of life end-points, constructed with patient input. However, what TOPCOAT teaches us about current and future impediments to research includes: 1. National funding agencies are averse to clinical trials that impose substantial risk to patients, and as a result, investigators wanting to conduct trials that could lead to death or disability had better plan on alternative sources of funding beyond the NIH. Despite the contraction in private equity for research, we were able to find a corporate partner to fund TOPCOAT because the design and outcomes aligned with the scientific and business interests of Genentech Inc. (South San Francisco, CA, USA). 2. The enormous scope and exhausting administrative burden of subcontracting other hospitals for a multicentre, high-risk trial. Almost no important, interventional study of a life-threatening disease can be done without a multicentre approach. The ‘indemnification language’ for participating hospitals and investigators poses one of the most formidable administrative obstacles. Indemnification refers to the wording in the research agreement or contract that decides who will pay in the event that something goes wrong, primarily if a patient is injured as a result of participation. These payments are not just for the medical care, but also for legal costs for a lawsuit, and who will pay for a settlement or jury verdict. Depending on the lawyers involved and the setting, indemnification might extend to cover issues, such as lost market share by hospitals in the event of bad publicity, or covering legal costs of investigators in the event they are sued as individuals. 3. The hidden opportunity cost of enrolling and following patients exemplified by screening costs. To enroll 83 patients with complete data, TOPCOAT investigators and their teams had to approach 640 patients, their families and healthcare team members to begin the informed consent process. In about 10% of cases, immediate exclusions were found within 30–45 min after initial identification. In at least 50% of cases, one or more members of the research team had to engage the patient, the medical record, the patients’
© 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
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JA Kline
family and the medical care team. For every patient enrolled, we spent approximately 6 h in uncompensated time while we attempted to enroll other patients, who ultimately declined or otherwise were found to be ineligible. We estimate that, for the entire study had $313 000 in uncompensated screening costs. Once a patient was deemed fully eligible, he/she was asked to read and initial in his/her own hand, 10 pages of an informed consent document (replete with warnings and descriptions of bodily and financial risk), and then print and sign their name and date twice at the end. This seemingly menial task can be Herculean for an exhausted, exasperated and frightened person being asked to participate in a research study. Thus, as we forge forward, current and future investigators must acknowledge the cost and hard work that needs to be done. These narratives describing the difficulties with diagnostic and therapeutic research underscore how the effort puts at risk the personal time and effort from the principal investigator, or so-called opportunity cost. For this reason, public benefit from emergency care research will spring from the motivation, resilience, desire and fire in the belly of properly trained and institutionally supported individual emergency researchers. This statement stands in contrast to the zeitgeist of most ‘transforming research’ initiatives being discussed and vaguely implemented at medical schools around the world, which, without exception, are purporting the importance of breaking down walls to encourage teambased research. A key example of this effort can be seen in the development of vascular medicine centres that consolidate the turfs of cardiology, nephrology, heart and vascular surgeons, and interventional radiologists. In this regard, I believe thought leaders have confused successful systems of care delivery and marketing with successful systems of research. The workhorse of research has, and always will be, individual researchers. Groups of people are well suited to producing accurate normative results, such as guessing the weight of a cow. A paradigm-busting, out-of-the-box, transformative research idea, which is prosecuted to its finality, comes from individuals who have training, confidence, and access to resources and patients to do the work. What about the benefit of collaboration without regard to turf, ideology or department status, but to bring the best minds together? That has been an absolute requirement for any researcher who has demonstrated successful funding year after year and has produced a work product that is favourably reviewed at journal clubs 12
around the world. Trans-departmental collaboration has and always will require one person who has the conviction to go knocking on doors of researchers outside of emergency medicine. The past teaches us that if an investigator has an idea of real merit, can articulate his or her position, and shows unshakable dedication, he or she will walk away with a new collaborator. The development of these research warriors requires three interlocking concepts: a society that values knowledge creation enough to pay for research training; physicians and scientists willing to spend the time and effort to gain emergency care-specific research training; and the programmes for them to get the training. The first part comes from voters and patients; the second part comes from education leaders who influence young minds as they train to be practitioners of emergency care; and the third part comes from advocacy groups, agencies and governments. The Emergency Care K12 Training Programs and the SAEM’s mechanism to review and approve emergency research fellowships in the United States are important examples of how emergency care training programmes are being created in the United States.
What can be predicted? As it always has, the availability of funds and the priorities of funding entities will drive the direction and scope of future research in emergency care. Box 1 shows where we have been and where we are headed. We will see continued rise of patient involvement in the design of clinical research. Funding from the nongovernmental Patient Centererd Outcomes Research Institute organisation will continue to grow, and governmental funding agencies will feel pressure from elected officials, who in turn are voted into office by a constituency that demands their health ministries and agencies produce clinically relevant research. The global cache of well-trained, consistently funded emergency researchers will increase from approximately 100 today to 500 by the year 2025. Almost all successful emergency researchers will obtain titles and appointments in other departments where their research is most relevant. Money will flow to those of you who provide new data on outcomes that inform how hospitals can best provide high-quality care at the lowest cost. Not-for-profit hospital systems, which despite their exhortations of impending revenue loss, will continue to post 5–10% profit margins and will have no other options but to invest in research. These mega-systems
© 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
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will invest in research that examines outcomes that distinguish them from their competitors and improve patient satisfaction. Industry funding will remain a relatively small source of investigator-initiated research, but companies will occasionally fund important homegrown projects that suit their business goals. Smaller foundations, such as the Emergency Medicine Foundation of the American College of Emergency Physicians® and SAEM, will continue to serve as important incubators for new researchers. The cost of screening patients for research studies will decrease as natural language processing methods are used in systemised electronic health record databases to identify eligible patients, with electronic alerts sent to research team members. Less burdensome methods of informed consent will prevail, including consent obtained and recorded by video, enabling remote enrollment in smaller hospitals, connected legally and electronically to a hospital network with a flagship academic hospital. Publicly available, large databases, such as the Healthcare Cost and Utilization Project National Inpatient sample and National Emergency Department sample, will be inexpensively mined and subjected to propensity-matching methodology to test the role of new treatments. The sheer size of these databases will provide as much power as randomised trials for inferences about hard end-points such as mortality, and economic end-points, such as intermediate cost of medical care. The key areas of research that will lead to pioneering findings and deep results will incorporate elements of shared decision-making and patient participation, and measure end-points that consider quality of life and patient perception of wellness. I would predict, in particular, that one topic that will gain particularly high level of attention from the public will be the role of emergency practitioners to empower patients and families to make end-of-life decisions in the ED setting.
In summary, funding for emergency care will determine what gets done, and I believe that the stronger the message of compassion and empathy that our research carries, the more likely it is to gain financial backing. In addition to conventional end-points of mortality or cure, research that makes patients feel better faster, empowers them in the medical decision-making process and liberates them from the hospital sooner, will see the highest levels of support.
Competing interests JAK is a member of the Editorial Board (International) of Emergency Medicine Australasia, owns stock in CP Diagnostics LLC, is a consultant for Daiichi, Donawa Lifesciences Consulting, and has received funding from the Agency for Healthcare Quality and the National Institutes for Health.
References 1.
Kline JA, Mitchell AM, Runyon MS, Jones AE, Webb WB. Electronic medical record review as a surrogate to telephone follow-up to establish outcome for diagnostic research studies in the emergency department. Acad. Emerg. Med. 2005; 12: 1127–232.
2.
Kline JA, Walthall JD. Patient Protection and Affordable Care Act of 2010: summary, analysis, and opportunities for advocacy for the academic emergency physician. Acad. Emerg. Med. 2010; 17: e69–e74.
3.
Kline JA, Hernandez-Nino J, Hogg MM et al. Rationale and methodology for a multicenter randomised trial of fibrinolysis for pulmonary embolism that includes quality of life outcomes. Emerg. Med. Australas. 2013; 25: 515–26.
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Macy J, Jr. The role of emergency medicine in the future of American medical care. Ann. Emerg. Med. 1995; 25: 230–3.
5.
Kaji AH, Lewis RJ, Beavers-May T et al. Summary of NIH Medical-Surgical Emergency Research Roundtable held on April 30 to May 1, 2009. Ann. Emerg. Med. 2010; 56: 522–37.
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