Prehospital Emergency Care
ISSN: 1090-3127 (Print) 1545-0066 (Online) Journal homepage: http://www.tandfonline.com/loi/ipec20
Research in Prehospital Care: Overcoming the Barriers to Success E. Brooke Lerner PhD, Tasmeen Weik DrPH, MPH & Elizabeth A. Edgerton MD, MPH To cite this article: E. Brooke Lerner PhD, Tasmeen Weik DrPH, MPH & Elizabeth A. Edgerton MD, MPH (2015): Research in Prehospital Care: Overcoming the Barriers to Success, Prehospital Emergency Care, DOI: 10.3109/10903127.2014.980480 To link to this article: http://dx.doi.org/10.3109/10903127.2014.980480
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Date: 17 November 2015, At: 21:23
RESEARCH IN PREHOSPITAL CARE: OVERCOMING THE BARRIERS TO SUCCESS E. Brooke Lerner, PhD, Tasmeen Weik, DrPH, MPH, Elizabeth A. Edgerton, MD, MPH
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ABSTRACT
ery prehospital study. Communities should engage in studies that align with their values and resources. Investigators need to develop honest relationships where issues can be openly discussed and the community can collaborate on prehospital research. Learning from those who have overcome challenges may be a key to expanding the quality and quantity of EMS research. Key words: emergency medical services; pediatrics
Objective. The objective of this project was to determine how investigators conduct clinical trials in the prehospital setting and to suggest how emergency medical services (EMS) systems can develop the capacity to conduct prehospital clinical research. Methods. A representative sample of U.S.-based study sites was selected from all studies registered on clinicaltrials.gov since the year 2000, where prehospital care providers conducted study-related activities in the prehospital setting. The site principal investigator and the research coordinator or EMS liaison were invited to participate in a structured discussion. A single interviewer conducted each discussion following a structured guide that generically asked for barriers and enablers to the sites’ research success and then reviewed commonly identified prehospital research barriers. Notes were taken during each discussion and reviewed for common themes. Themes were reviewed by the project team and sent for comment to all participants. Results. Discussions were held with 25 principal investigators, 9 coordinators, and 7 EMS liaisons. A total of 27 communities were represented in the discussions from 22 different states. The communities had a range of research experience from one prehospital trial to multiple trials. Key barriers were funding, ethics approval, data collection, protocol training and compliance, randomizing and blinding interventions, obtaining patient outcomes, adequate study staffing, and partnering with EMS agencies. Conclusion. This project identified many challenges to EMS research, but they were not insurmountable. Not every community can conduct ev-
PREHOSPITAL EMERGENCY CARE 2015;Early Online:1–6
INTRODUCTION The scientific literature base for prehospital emergency care is limited.1,2 This is likely due to two factors: the relatively young age of the specialty, and the challenges of conducting research in an uncontrolled environment. It is difficult to pinpoint an exact moment in time when modern prehospital care began, but likely the best starting point was the 1966 publication of Accidental Death and Disability: The Neglected Disease of Modern Society.3 In 1965, there were essentially no research publications related to prehospital emergency care, but that number has steadily grown over the years.4 Simultaneously the recognition of prehospital care as a medical specialty has been increasing, and in 2010 emergency medical services (EMS) was given physician subspecialty certification approval.5 There are many challenges to using standard research methods in the uncontrolled and unpredictable prehospital environment. These challenges include identifying funding for EMS research, engaging EMS agency participation, obtaining ethics approval, training EMS providers in research procedures, collecting data in the EMS setting, and collecting outcome information from the receiving facilities.2,11–15 Arguably one of the biggest challenges is that most patients consider themselves to have time-sensitive emergent conditions and in many cases are considered incapable of providing informed consent for research participation, either because they are incapacitated or because they are so concerned about receiving treatment that care providers offering a research option may be considered coercive. Prior to 1993, some investigators used a process of deferred consent when enrolling patients who could not provide consent and for whom no legally authorized representative was available.6 This meant that researchers enrolled patients into studies and then asked for their consent post-enrollment, after the study intervention had already been initiated. This practice was determined to be unethical and banned by the federal Office for the Protection of Research Risks in
Received August 28, 2014 from the Department of Emergency Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (EBL), Office of Populations Affairs, Office of the Assistant Secretary for Health, Department of Health and Human Services, Washington, DC (TW), and Emergency Medical Services for Children, Health Resources and Services Administration, Washington, DC (EAE). Revision received October 14, 2014; accepted for publication October 21, 2014. This study was supported through contract S2012.100SC with the National Highway Traffic Safety Administration. The views expressed in this publication are solely the opinions of the authors and do not necessarily reflect the official policies of the U.S. Department of Health and Human Services or the Health Resources and Services Administration, nor does mention of the department or agency names imply endorsement by the U.S. Government. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. Address correspondence to E. Brooke Lerner, PhD, Department of Emergency Medicine, Medical College of Wisconsin, Froedtert Hospital, 9200 W. Wisconsin Ave., Milwaukee, WI 53226, USA. E-mail: [email protected] doi: 10.3109/10903127.2014.980480
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1993, essentially making it impossible to conduct any emergency medical services research that might pose greater than minimal risk to the subject unless the patient provided informed consent.7 This significantly inhibited the growth of prehospital and resuscitation science, so in 1996, federal rule 21 CFR 50.24 was released allowing for an exception from informed consent for emergency research.8 In early 2000, several authors demonstrated that there had been a severe decrease in resuscitationrelated research publications in the United States.9,10 These authors and others suggested that the new ethical requirements outlined in 21CFR 50.24 were too onerous and were inhibiting prehospital and resuscitation research. Anecdotally, since those publications were released in 2000, there has been a surge in the number of randomized clinical trials conducted in the prehospital setting. Limited information has been published on how investigators have been able to overcome what had seemed to be insurmountable barriers created by the new ethics requirements as well as the general issues with attempting to conduct research in the prehospital setting. The objective of this project was to determine how investigators conduct clinical trials in the prehospital setting and to suggest how EMS systems and the communities they serve can develop the capacity to conduct successful prehospital clinical research.
METHODOLOGY Prospective studies conducted in the prehospital setting were identified by searching clinicaltrials.gov using the individual search terms “emergency medical services,” “prehospital,” “emergency exception to informed consent,” and “heart arrest.” Each study identified by the search was reviewed. Studies were included if they were initiated after the year 2000, had at least one study site in the United States, and had required prehospital care providers to conduct studyrelated activities in the prehospital setting. If an identified study had not completed enrollment, then it needed to have been enrolling participants for at least one year. To verify that the search strategy was effective, we compared the identified studies to a list of major EMS studies known to the project team (e.g., all of the studies conducted by the Resuscitation Outcomes Consortium). All of those studies were identified plus additional lesser-known studies, so the search strategy was considered comprehensive. A list of United States study sites was compiled for each identified study using the sites listed for the study in their clinicaltrial.gov entries. Due to resource constraints a subset of the identified sites were then selected for contact. All study sites that participated in a study that included pediatric patients were contacted and from the remaining sites one site was randomly se-
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lected from each represented state. The list of selected sites was then reviewed to ensure that it included at least one site that had conducted a self-funded study, a site for an industry-sponsored study, a site with a federally funded study, a site from a multicenter trial, a site from a single-center trial, a nonurban site, an urban site, a site with a municipal fire service, a site with a municipal third service, and a site with a commercial EMS service. A total of 39 study sites were selected and contacted to participate in a discussion about their prehospital research efforts (Figure 1). The site principal investigator for each selected study site was contacted to discuss his or her prehospital research experiences. Contact was made with the principal investigators using information that was provided on clinical trials.gov, on any study publications, through the project team’s personal contacts, or through an Internet search. After the site principal investigator was contacted, he or she was asked for permission to also contact either the EMS liaison or the study coordinator for the site in order to obtain a second perspective on local barriers and enablers to prehospital research. The position that was requested was determined by random assignment prior to contacting the site principal investigator. We attempted to contact each principal investigator twice by email. If there was no response and we could find a telephone number, at least one attempt was made to contact the principal investigator by phone. A standardized discussion guide was developed based on previously published articles that described the barriers to clinical research in the prehospital setting.2,4,11–24 Participants were also asked if there were benefits of research to either the EMS agency or the community they serve and if so to describe them. The guide was sent to participants prior to the discussion and they were told that we wanted to learn about the barriers they encountered during their research and how they overcame them. The discussions were open-ended and there was a great deal of flexibility in the flow of the discussion. A single project team member (EBL) conducted all of the discussions and asked probing questions as needed. The discussions were limited to an hour in length or however long the participant was willing to discuss their experiences; in some cases this was 30 minutes and in others it was 2 hours. In some cases topics on the guide were skipped to save time or due to the circumstances of the study and site that were being discussed. The discussions were not recorded but in-depth notes were taken during each discussion. These notes were reviewed by the team member who conducted the interviews to identify and categorize general themes. This process was then reviewed and verified by the entire project team. A draft version of the project’s findings was sent to all participants for review and comment.
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FIGURE 1. Number of clinical trial sites that were identified and participated in discussions.
RESULTS A total of 1,862 entries were identified in clinicaltrials.gov based on the search strategy. Of those, 26 studies met the inclusion criteria. There were 64 different study sites listed for those 26 studies that were in the United States. Of those, 39 were contacted for discussions. Discussions were held with 25 principal investigators, 9 coordinators, and 7 EMS liaisons (Figure 1). Eleven principal investigators did not respond to participation requests. Three principal investigators refused to participate, two of whom referred us to their research coordinators, both of whom participated. Five principal investigators participated but their coordinators or liaisons did not, two of whom never responded to discussion requests and three of whom responded but were not available. Five principal investigators stated that they served as either the research coordinator or the EMS liaison and no secondary discussant was identified. One principal
investigator was not able to effectively start the study and only three patients were enrolled, so no follow-up discussant was requested. A total of 27 EMS systems from 22 different states were represented in the discussions (Table 1). These EMS systems had a range of research experience from only one prehospital clinical trial to multiple trials. Funding for the trial included federal, industry, and local sources. The RAMPART trial was the only trial to include children, and was conducted in 15 of the represented communities.25 A summary of the themes that emerged during these discussions was developed. Specific issues that were identified were 1) obtaining ethics approval, 2) obtaining funding, 3) recruiting EMS agencies to participate in research, 4) collecting data and maintaining protocol compliance, 5) training EMS providers to enroll patients in research, and 6) collecting outcome data from receiving facilities. All of the respondents stated that they believed that EMS research benefited the community beyond simply the study that was being con-
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TABLE 1. Description of the 27 participating EMS systems
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Count
Discussants PI only PI and coordinator PI and EMS liaison Coordinator only EMS agency type Municipal fire Municipal or hospital third service Commercial Combination Number of IRB that had to approve the study within a specific community 1 2 3 4 5–10 >10 Not available Used exception from informed consent (i.e., federal rule 21 CFR 50.24) Yes No Not approved by IRB Type of community consultation (n = 24) Phone survey Social media advertisements and phone survey Focus groups/meetings Booth at community events Focus groups and community events Not available State approval required Yes No Funding Federal Industry Local Multiple studies with multiple funding sources Study type Multisite Single site Multi- and single-center studies Study status Complete data collection Ended before meeting sample size expectations Never initiated enrollment Multiple studies at multiple stages
11 8 6 2 13 6 2 6
4 7 4 2 4 4 2
24 1 2 6 1 7 1 2 7 9 16 18 4 2 3
23 2 2 19 1 2 5
ducted. Appendix 1 (available online) provides a list of the issues and solutions that were identified regarding EMS research. Table 2 lists the specific benefits of research to both the EMS agencies and the communities they serve.
DISCUSSION At face value the findings from this project may seem obvious and to mirror the barriers to EMS research that have been identified previously. However, what
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this project found was that these barriers are not insurmountable and that the issues related to them are deeper and more nuanced than those simple descriptions. For example, while ethics approval is an issue, the issues are related to the staffing that is needed to maintain multiple approvals and the time and resources required to meet the community consultation and notification requirements. In all but two sites these issues were able to be overcome, primarily by conducting studies that were adequately funded to provide the staff and other resources that were needed to meet ethics requirements. Interestingly, none of the participants advocated for a change in 21CFR 50.24; in fact, several stated that it gave them a sense of protection and comfort when enrolling patients without their consent. The change that they would advocate for is to develop more consistency between institutional review boards (IRB) as to what community consultation and public disclosure entail, since many reported significant variability between IRBs and even within the same IRB between projects. Further, many investigators had taken steps within their communities to develop processes for streamlining the need for multiple approvals, such as developing local agreements for IRB deferrals between hospitals (i.e., an IRB does not review a study but instead defers oversight to another IRB. These solutions were all community specific and developed through the efforts of the community stakeholders. There has yet to be a universal solution that will address this issue for all communities. Two sites were not able to obtain IRB approval. At one of these sites it was likely due to a lack of administrative support for conducting research using 21CFR 50.24, and at the other institution the investigator was a student, creating what was likely discomfort with having an inexperienced investigator lead the institution’s first project to use 21CFR 50.24. Both of these examples highlight a very important theme that was echoed by all participants. Relationship building and maintenance is the cornerstone to conducting prehospital research. The principal investigator needs to form strong relationships with providers and administrators across the full continuum of care. In many cases the investigator will be the first to propose using 21CFR 50.24 and many will consider the activities related to prehospital research to be politically risky. Therefore, all must trust the principal investigator to lead them through conducting the project ethically and safely. It is important to note that discussants emphasized that this includes hospital administrators as well as the staff who can be gatekeepers to medical record information as well as to the subjects and their families. Most participants advocated making investments in building relationships between the research team and the hospital staff they will interact with on a day-to-day basis. This ranged from developing informational binders that were carried to the site and included approval let-
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TABLE 2. Benefits of participating in EMS research to the community and the EMS agency
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• Encouraged better protocol adherence among EMS providers. • Lead to improved patient care, which ultimately leads to improved patient outcomes. Many sites could provide exact estimates of the number of additional lives that were being saved because of a particular study. This included sites showing a doubling of cardiac arrest survival rates. • Provided needed clinical training and improved the EMS agency’s quality improvement processes. • Provided agencies with state of the art equipment and supplies that they would not have otherwise. • Allowed them to rapidly incorporate cutting-edge interventions into their protocols as soon as the findings of the study were known, because providers were already trained and had the equipment. • Gave providers and agencies “bragging rights” and pride in the cutting-edge care that they give their patients and the positive effect they are having on EMS globally, especially when national guidelines are changed based on their work. • Assisted EMS agencies and unions with contract negotiations, because the community feels their participation is important and valuable.
ters, to providing in-services on the study to staff, to simply providing food as a thank you for their assistance. Arguably, EMS research should be seen as community participatory research where researchers work with the community being studied to conduct the trial. This is because with few exceptions it impossible for an EMS researcher to perform study enrollment themselves. They have to rely on EMS providers to perform many study-related activities in addition to their regular job, which is to provide life-saving care. The full continuum of care providers within the community will need to work together to conduct a study in the prehospital setting. As such these communities need to be consulted prior to initiating a trial, and they need to have the right to say no to an investigation. It is unclear how often a community says no to a proposed EMS-based study. During this project two sites were not able to proceed past the IRB stage, but there were other examples where investigators were not able to initiate specific studies in specific communities. In some cases this was because of the study topic, but in most cases this was described as being due to the resources that would be required to participate in the project. This is a very practical consideration since EMS research is expensive and even funded studies do not always have the resources to cover all of the costs associated with provider training and quality improvement. Some EMS agencies saw these activities as the “cost of doing business,” but it is important for both the investigator and the EMS agency to identify the true costs of a study and who will provide those resources. Further, many investigators described the importance of learning from communities who have successfully conducted EMS research. Most commonly they described the importance of giving IRBs access to IRB members at other institutions that have overseen EMS studies. However, this was much deeper than simply sharing information on the ethics approval process. In many cases investigators described the need to learn from each other’s experiences so that studies can be implemented efficiently without repeating the same mistakes.
CONCLUSION This project identified many challenges to EMS research, but these challenges were not found to be insurmountable. Not every community can conduct every study, and communities need to have the ability to engage in studies that align with their values and resources. Investigators need to develop honest relationships where these issues can be discussed openly and the community can come together to successfully collaborate on important and life-saving research. Learning from those who have overcome challenges may be a key to expanding the quality and quantity of EMS research.
References 1. Brice JH, Garrison HG, Evans AT. Study design and outcomes in out-of-hospital emergency medicine research: a ten-year analysis. Prehosp Emerg Care. Apr-Jun 2000;4(2):144–50. 2. Sayre MR, Gausche-Hill M. Conducting randomized trials in the prehospital setting. Prehosp Emerg Care. Apr-Jun 2002; 6(2 Suppl):S38–47. 3. Accidental Death and Disability: The Neglected Disease of Modern Society. Washington, DC: National Academy of Sciences, National Research Council; 1966. 4. Sayre MR, White LJ, Brown LH, McHenry SD. National EMS Research Agenda. Prehosp Emerg Care. Jul-Sep 2002; 6(3 Suppl):S1–43. 5. American Board of Emergency Medicine. EMS Approved as an Emergency Medicine Subspecialty. www.abem.org/PUBLIC/portal/alias rainbow/lang enUS/tabID 4128/DesktopDefault.aspx. Accessed May 7, 2013. 6. Salzman JG, Frascone RJ, Godding BK, Provo TA, Gertner E. Implementing emergency research requiring exception from informed consent, community consultation, and public disclosure. Ann Emerg Med. Oct 2007;50(4):448–55, 455 e441–4. 7. Office for Protection from Research Risks. Informed Consent – Legally Effective and Prospectively Obtained: OPRR Reports. Publ no 93-3. Washington, DC: The Committee; 1993. 8. U.S. Department of Health and Human Services. Protection of Human Subjects: Informed Consent and Waiver of Informed Consent Requirements in Certain Emergency Circumstances. In: 21 CFR 50; 45 CFR 46; 1996. 9. Nichol G, Huszti E, Rokosh J, Dumbrell A, McGowan J, Becker L. Impact of informed consent requirements on cardiac arrest research in the United States: exception from consent or from research? Resuscitation. Jul 2004;62(1):3–23.
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6 10. Hiller KM, Haukoos JS, Heard K, Tashkin JS, Paradis NA. Impact of the Final Rule on the rate of clinical cardiac arrest research in the United States. Acad Emerg Med. Nov 2005;12(11):1091–8. 11. Gausche-Hill M, Lewis RJ, Gunter CS, Henderson DP, Haynes BE, Stratton SJ. Design and implementation of a controlled trial of pediatric endotracheal intubation in the out-of-hospital setting. Ann Emerg Med. Oct 2000;36(4):356–65. 12. Lerner EB, Mosesso V Jr, Zak C. Implementation of research in the out-of-hospital setting. Prehosp Emerg Care. Apr-Jun 2002;6(2 Suppl):S24–27. 13. Maio RF, Garrison HG, Spaite DW, et al. Emergency medical services outcomes project I (EMSOP I): prioritizing conditions for outcomes research. Ann Emerg Med. Apr 1999;33(4):423–32. 14. Pepe PE. Out-of-hospital resuscitation research: rationale and strategies for controlled clinical trials. Ann Emerg Med. Jan 1993;22(1):17–23. 15. Spaite DW, Criss EA, Valenzuela TD, Guisto J. Emergency medical service systems research: problems of the past, challenges of the future. Ann Emerg Med. Aug 1995;26(2):146–52. 16. Brice JH, Friend KD, Delbridge TR. Accuracy of EMS-recorded patient demographic data. Prehosp Emerg Care. Apr-Jun 2008;12(2):187–91. 17. Institute of Medicine Committee on the Future of Emergency Care in the United States Health System. Emergency Medical Systems (EMS): At the Crossroads. Washington, DC: The National Academies Press, 2006. Available at: http://www.iom.edu/Reports/2006/Emergency-MedicalServices-At-the-Crossroads.aspx. 18. EMSC National Resource Center, Children’s National Medical Center. Gap Analysis of EMS Related Research. Report to the Federal Interagency Committee on EMS. 2009. Available at: www.childrensnational.org/emsc.
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19. Foltin GL, Dayan P, Tunik M, et al. Priorities for pediatric prehospital research. Pediatr Emerg Care. Oct 2010;26(10):773–7. 20. Leonard JC, Scharff DP, Koors V, et al. A qualitative assessment of factors that influence emergency medical services partnerships in prehospital research. Acad Emerg Med. Feb 2012;19(2):161–73. 21. Osterwalder JJ. Insufficient quality of research on prehospital medical emergency care – where are the major problems and solutions? Swiss Med Wkly. Jul 10 2004;134(27-28):389–94. 22. Schmidt TA, Nelson M, Daya M, DeIorio NM, Griffiths D, Rosteck P. Emergency medical service providers’ attitudes and experiences regarding enrolling patients in clinical research trials. Prehosp Emerg Care. Apr-Jun 2009;13(2):160–8. 23. Seidel JS, Henderson D, Tittle S, et al. Priorities for research in emergency medical services for children: results of a consensus conference. Ann Emerg Med. Feb 1999;33(2):206–10. 24. Spaite DW, Maio R, Garrison HG, et al. Emergency Medical Services Outcomes Project (EMSOP) II: developing the foundation and conceptual models for out-of-hospital outcomes research. Ann Emerg Med. Jun 2001;37(6):657–63. 25. Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. Feb 16 2012;366(7):591–600.
SUPPLEMENTAL MATERIALS AVAILABLE ONLINE Appendix 1— Issues and Solutions for Conducting EMS Research
ISSN: 1090-3127 (Print) 1545-0066 (Online) Journal homepage: http://www.tandfonline.com/loi/ipec20
Research in Prehospital Care: Overcoming the Barriers to Success E. Brooke Lerner PhD, Tasmeen Weik DrPH, MPH & Elizabeth A. Edgerton MD, MPH To cite this article: E. Brooke Lerner PhD, Tasmeen Weik DrPH, MPH & Elizabeth A. Edgerton MD, MPH (2015): Research in Prehospital Care: Overcoming the Barriers to Success, Prehospital Emergency Care, DOI: 10.3109/10903127.2014.980480 To link to this article: http://dx.doi.org/10.3109/10903127.2014.980480
View supplementary material
Published online: 18 May 2015.
Submit your article to this journal
Article views: 101
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipec20 Download by: [Universite Laval]
Date: 17 November 2015, At: 21:23
RESEARCH IN PREHOSPITAL CARE: OVERCOMING THE BARRIERS TO SUCCESS E. Brooke Lerner, PhD, Tasmeen Weik, DrPH, MPH, Elizabeth A. Edgerton, MD, MPH
Downloaded by [Universite Laval] at 21:23 17 November 2015
ABSTRACT
ery prehospital study. Communities should engage in studies that align with their values and resources. Investigators need to develop honest relationships where issues can be openly discussed and the community can collaborate on prehospital research. Learning from those who have overcome challenges may be a key to expanding the quality and quantity of EMS research. Key words: emergency medical services; pediatrics
Objective. The objective of this project was to determine how investigators conduct clinical trials in the prehospital setting and to suggest how emergency medical services (EMS) systems can develop the capacity to conduct prehospital clinical research. Methods. A representative sample of U.S.-based study sites was selected from all studies registered on clinicaltrials.gov since the year 2000, where prehospital care providers conducted study-related activities in the prehospital setting. The site principal investigator and the research coordinator or EMS liaison were invited to participate in a structured discussion. A single interviewer conducted each discussion following a structured guide that generically asked for barriers and enablers to the sites’ research success and then reviewed commonly identified prehospital research barriers. Notes were taken during each discussion and reviewed for common themes. Themes were reviewed by the project team and sent for comment to all participants. Results. Discussions were held with 25 principal investigators, 9 coordinators, and 7 EMS liaisons. A total of 27 communities were represented in the discussions from 22 different states. The communities had a range of research experience from one prehospital trial to multiple trials. Key barriers were funding, ethics approval, data collection, protocol training and compliance, randomizing and blinding interventions, obtaining patient outcomes, adequate study staffing, and partnering with EMS agencies. Conclusion. This project identified many challenges to EMS research, but they were not insurmountable. Not every community can conduct ev-
PREHOSPITAL EMERGENCY CARE 2015;Early Online:1–6
INTRODUCTION The scientific literature base for prehospital emergency care is limited.1,2 This is likely due to two factors: the relatively young age of the specialty, and the challenges of conducting research in an uncontrolled environment. It is difficult to pinpoint an exact moment in time when modern prehospital care began, but likely the best starting point was the 1966 publication of Accidental Death and Disability: The Neglected Disease of Modern Society.3 In 1965, there were essentially no research publications related to prehospital emergency care, but that number has steadily grown over the years.4 Simultaneously the recognition of prehospital care as a medical specialty has been increasing, and in 2010 emergency medical services (EMS) was given physician subspecialty certification approval.5 There are many challenges to using standard research methods in the uncontrolled and unpredictable prehospital environment. These challenges include identifying funding for EMS research, engaging EMS agency participation, obtaining ethics approval, training EMS providers in research procedures, collecting data in the EMS setting, and collecting outcome information from the receiving facilities.2,11–15 Arguably one of the biggest challenges is that most patients consider themselves to have time-sensitive emergent conditions and in many cases are considered incapable of providing informed consent for research participation, either because they are incapacitated or because they are so concerned about receiving treatment that care providers offering a research option may be considered coercive. Prior to 1993, some investigators used a process of deferred consent when enrolling patients who could not provide consent and for whom no legally authorized representative was available.6 This meant that researchers enrolled patients into studies and then asked for their consent post-enrollment, after the study intervention had already been initiated. This practice was determined to be unethical and banned by the federal Office for the Protection of Research Risks in
Received August 28, 2014 from the Department of Emergency Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (EBL), Office of Populations Affairs, Office of the Assistant Secretary for Health, Department of Health and Human Services, Washington, DC (TW), and Emergency Medical Services for Children, Health Resources and Services Administration, Washington, DC (EAE). Revision received October 14, 2014; accepted for publication October 21, 2014. This study was supported through contract S2012.100SC with the National Highway Traffic Safety Administration. The views expressed in this publication are solely the opinions of the authors and do not necessarily reflect the official policies of the U.S. Department of Health and Human Services or the Health Resources and Services Administration, nor does mention of the department or agency names imply endorsement by the U.S. Government. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. Address correspondence to E. Brooke Lerner, PhD, Department of Emergency Medicine, Medical College of Wisconsin, Froedtert Hospital, 9200 W. Wisconsin Ave., Milwaukee, WI 53226, USA. E-mail: [email protected] doi: 10.3109/10903127.2014.980480
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1993, essentially making it impossible to conduct any emergency medical services research that might pose greater than minimal risk to the subject unless the patient provided informed consent.7 This significantly inhibited the growth of prehospital and resuscitation science, so in 1996, federal rule 21 CFR 50.24 was released allowing for an exception from informed consent for emergency research.8 In early 2000, several authors demonstrated that there had been a severe decrease in resuscitationrelated research publications in the United States.9,10 These authors and others suggested that the new ethical requirements outlined in 21CFR 50.24 were too onerous and were inhibiting prehospital and resuscitation research. Anecdotally, since those publications were released in 2000, there has been a surge in the number of randomized clinical trials conducted in the prehospital setting. Limited information has been published on how investigators have been able to overcome what had seemed to be insurmountable barriers created by the new ethics requirements as well as the general issues with attempting to conduct research in the prehospital setting. The objective of this project was to determine how investigators conduct clinical trials in the prehospital setting and to suggest how EMS systems and the communities they serve can develop the capacity to conduct successful prehospital clinical research.
METHODOLOGY Prospective studies conducted in the prehospital setting were identified by searching clinicaltrials.gov using the individual search terms “emergency medical services,” “prehospital,” “emergency exception to informed consent,” and “heart arrest.” Each study identified by the search was reviewed. Studies were included if they were initiated after the year 2000, had at least one study site in the United States, and had required prehospital care providers to conduct studyrelated activities in the prehospital setting. If an identified study had not completed enrollment, then it needed to have been enrolling participants for at least one year. To verify that the search strategy was effective, we compared the identified studies to a list of major EMS studies known to the project team (e.g., all of the studies conducted by the Resuscitation Outcomes Consortium). All of those studies were identified plus additional lesser-known studies, so the search strategy was considered comprehensive. A list of United States study sites was compiled for each identified study using the sites listed for the study in their clinicaltrial.gov entries. Due to resource constraints a subset of the identified sites were then selected for contact. All study sites that participated in a study that included pediatric patients were contacted and from the remaining sites one site was randomly se-
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lected from each represented state. The list of selected sites was then reviewed to ensure that it included at least one site that had conducted a self-funded study, a site for an industry-sponsored study, a site with a federally funded study, a site from a multicenter trial, a site from a single-center trial, a nonurban site, an urban site, a site with a municipal fire service, a site with a municipal third service, and a site with a commercial EMS service. A total of 39 study sites were selected and contacted to participate in a discussion about their prehospital research efforts (Figure 1). The site principal investigator for each selected study site was contacted to discuss his or her prehospital research experiences. Contact was made with the principal investigators using information that was provided on clinical trials.gov, on any study publications, through the project team’s personal contacts, or through an Internet search. After the site principal investigator was contacted, he or she was asked for permission to also contact either the EMS liaison or the study coordinator for the site in order to obtain a second perspective on local barriers and enablers to prehospital research. The position that was requested was determined by random assignment prior to contacting the site principal investigator. We attempted to contact each principal investigator twice by email. If there was no response and we could find a telephone number, at least one attempt was made to contact the principal investigator by phone. A standardized discussion guide was developed based on previously published articles that described the barriers to clinical research in the prehospital setting.2,4,11–24 Participants were also asked if there were benefits of research to either the EMS agency or the community they serve and if so to describe them. The guide was sent to participants prior to the discussion and they were told that we wanted to learn about the barriers they encountered during their research and how they overcame them. The discussions were open-ended and there was a great deal of flexibility in the flow of the discussion. A single project team member (EBL) conducted all of the discussions and asked probing questions as needed. The discussions were limited to an hour in length or however long the participant was willing to discuss their experiences; in some cases this was 30 minutes and in others it was 2 hours. In some cases topics on the guide were skipped to save time or due to the circumstances of the study and site that were being discussed. The discussions were not recorded but in-depth notes were taken during each discussion. These notes were reviewed by the team member who conducted the interviews to identify and categorize general themes. This process was then reviewed and verified by the entire project team. A draft version of the project’s findings was sent to all participants for review and comment.
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FIGURE 1. Number of clinical trial sites that were identified and participated in discussions.
RESULTS A total of 1,862 entries were identified in clinicaltrials.gov based on the search strategy. Of those, 26 studies met the inclusion criteria. There were 64 different study sites listed for those 26 studies that were in the United States. Of those, 39 were contacted for discussions. Discussions were held with 25 principal investigators, 9 coordinators, and 7 EMS liaisons (Figure 1). Eleven principal investigators did not respond to participation requests. Three principal investigators refused to participate, two of whom referred us to their research coordinators, both of whom participated. Five principal investigators participated but their coordinators or liaisons did not, two of whom never responded to discussion requests and three of whom responded but were not available. Five principal investigators stated that they served as either the research coordinator or the EMS liaison and no secondary discussant was identified. One principal
investigator was not able to effectively start the study and only three patients were enrolled, so no follow-up discussant was requested. A total of 27 EMS systems from 22 different states were represented in the discussions (Table 1). These EMS systems had a range of research experience from only one prehospital clinical trial to multiple trials. Funding for the trial included federal, industry, and local sources. The RAMPART trial was the only trial to include children, and was conducted in 15 of the represented communities.25 A summary of the themes that emerged during these discussions was developed. Specific issues that were identified were 1) obtaining ethics approval, 2) obtaining funding, 3) recruiting EMS agencies to participate in research, 4) collecting data and maintaining protocol compliance, 5) training EMS providers to enroll patients in research, and 6) collecting outcome data from receiving facilities. All of the respondents stated that they believed that EMS research benefited the community beyond simply the study that was being con-
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TABLE 1. Description of the 27 participating EMS systems
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Count
Discussants PI only PI and coordinator PI and EMS liaison Coordinator only EMS agency type Municipal fire Municipal or hospital third service Commercial Combination Number of IRB that had to approve the study within a specific community 1 2 3 4 5–10 >10 Not available Used exception from informed consent (i.e., federal rule 21 CFR 50.24) Yes No Not approved by IRB Type of community consultation (n = 24) Phone survey Social media advertisements and phone survey Focus groups/meetings Booth at community events Focus groups and community events Not available State approval required Yes No Funding Federal Industry Local Multiple studies with multiple funding sources Study type Multisite Single site Multi- and single-center studies Study status Complete data collection Ended before meeting sample size expectations Never initiated enrollment Multiple studies at multiple stages
11 8 6 2 13 6 2 6
4 7 4 2 4 4 2
24 1 2 6 1 7 1 2 7 9 16 18 4 2 3
23 2 2 19 1 2 5
ducted. Appendix 1 (available online) provides a list of the issues and solutions that were identified regarding EMS research. Table 2 lists the specific benefits of research to both the EMS agencies and the communities they serve.
DISCUSSION At face value the findings from this project may seem obvious and to mirror the barriers to EMS research that have been identified previously. However, what
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this project found was that these barriers are not insurmountable and that the issues related to them are deeper and more nuanced than those simple descriptions. For example, while ethics approval is an issue, the issues are related to the staffing that is needed to maintain multiple approvals and the time and resources required to meet the community consultation and notification requirements. In all but two sites these issues were able to be overcome, primarily by conducting studies that were adequately funded to provide the staff and other resources that were needed to meet ethics requirements. Interestingly, none of the participants advocated for a change in 21CFR 50.24; in fact, several stated that it gave them a sense of protection and comfort when enrolling patients without their consent. The change that they would advocate for is to develop more consistency between institutional review boards (IRB) as to what community consultation and public disclosure entail, since many reported significant variability between IRBs and even within the same IRB between projects. Further, many investigators had taken steps within their communities to develop processes for streamlining the need for multiple approvals, such as developing local agreements for IRB deferrals between hospitals (i.e., an IRB does not review a study but instead defers oversight to another IRB. These solutions were all community specific and developed through the efforts of the community stakeholders. There has yet to be a universal solution that will address this issue for all communities. Two sites were not able to obtain IRB approval. At one of these sites it was likely due to a lack of administrative support for conducting research using 21CFR 50.24, and at the other institution the investigator was a student, creating what was likely discomfort with having an inexperienced investigator lead the institution’s first project to use 21CFR 50.24. Both of these examples highlight a very important theme that was echoed by all participants. Relationship building and maintenance is the cornerstone to conducting prehospital research. The principal investigator needs to form strong relationships with providers and administrators across the full continuum of care. In many cases the investigator will be the first to propose using 21CFR 50.24 and many will consider the activities related to prehospital research to be politically risky. Therefore, all must trust the principal investigator to lead them through conducting the project ethically and safely. It is important to note that discussants emphasized that this includes hospital administrators as well as the staff who can be gatekeepers to medical record information as well as to the subjects and their families. Most participants advocated making investments in building relationships between the research team and the hospital staff they will interact with on a day-to-day basis. This ranged from developing informational binders that were carried to the site and included approval let-
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TABLE 2. Benefits of participating in EMS research to the community and the EMS agency
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• Encouraged better protocol adherence among EMS providers. • Lead to improved patient care, which ultimately leads to improved patient outcomes. Many sites could provide exact estimates of the number of additional lives that were being saved because of a particular study. This included sites showing a doubling of cardiac arrest survival rates. • Provided needed clinical training and improved the EMS agency’s quality improvement processes. • Provided agencies with state of the art equipment and supplies that they would not have otherwise. • Allowed them to rapidly incorporate cutting-edge interventions into their protocols as soon as the findings of the study were known, because providers were already trained and had the equipment. • Gave providers and agencies “bragging rights” and pride in the cutting-edge care that they give their patients and the positive effect they are having on EMS globally, especially when national guidelines are changed based on their work. • Assisted EMS agencies and unions with contract negotiations, because the community feels their participation is important and valuable.
ters, to providing in-services on the study to staff, to simply providing food as a thank you for their assistance. Arguably, EMS research should be seen as community participatory research where researchers work with the community being studied to conduct the trial. This is because with few exceptions it impossible for an EMS researcher to perform study enrollment themselves. They have to rely on EMS providers to perform many study-related activities in addition to their regular job, which is to provide life-saving care. The full continuum of care providers within the community will need to work together to conduct a study in the prehospital setting. As such these communities need to be consulted prior to initiating a trial, and they need to have the right to say no to an investigation. It is unclear how often a community says no to a proposed EMS-based study. During this project two sites were not able to proceed past the IRB stage, but there were other examples where investigators were not able to initiate specific studies in specific communities. In some cases this was because of the study topic, but in most cases this was described as being due to the resources that would be required to participate in the project. This is a very practical consideration since EMS research is expensive and even funded studies do not always have the resources to cover all of the costs associated with provider training and quality improvement. Some EMS agencies saw these activities as the “cost of doing business,” but it is important for both the investigator and the EMS agency to identify the true costs of a study and who will provide those resources. Further, many investigators described the importance of learning from communities who have successfully conducted EMS research. Most commonly they described the importance of giving IRBs access to IRB members at other institutions that have overseen EMS studies. However, this was much deeper than simply sharing information on the ethics approval process. In many cases investigators described the need to learn from each other’s experiences so that studies can be implemented efficiently without repeating the same mistakes.
CONCLUSION This project identified many challenges to EMS research, but these challenges were not found to be insurmountable. Not every community can conduct every study, and communities need to have the ability to engage in studies that align with their values and resources. Investigators need to develop honest relationships where these issues can be discussed openly and the community can come together to successfully collaborate on important and life-saving research. Learning from those who have overcome challenges may be a key to expanding the quality and quantity of EMS research.
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19. Foltin GL, Dayan P, Tunik M, et al. Priorities for pediatric prehospital research. Pediatr Emerg Care. Oct 2010;26(10):773–7. 20. Leonard JC, Scharff DP, Koors V, et al. A qualitative assessment of factors that influence emergency medical services partnerships in prehospital research. Acad Emerg Med. Feb 2012;19(2):161–73. 21. Osterwalder JJ. Insufficient quality of research on prehospital medical emergency care – where are the major problems and solutions? Swiss Med Wkly. Jul 10 2004;134(27-28):389–94. 22. Schmidt TA, Nelson M, Daya M, DeIorio NM, Griffiths D, Rosteck P. Emergency medical service providers’ attitudes and experiences regarding enrolling patients in clinical research trials. Prehosp Emerg Care. Apr-Jun 2009;13(2):160–8. 23. Seidel JS, Henderson D, Tittle S, et al. Priorities for research in emergency medical services for children: results of a consensus conference. Ann Emerg Med. Feb 1999;33(2):206–10. 24. Spaite DW, Maio R, Garrison HG, et al. Emergency Medical Services Outcomes Project (EMSOP) II: developing the foundation and conceptual models for out-of-hospital outcomes research. Ann Emerg Med. Jun 2001;37(6):657–63. 25. Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. Feb 16 2012;366(7):591–600.
SUPPLEMENTAL MATERIALS AVAILABLE ONLINE Appendix 1— Issues and Solutions for Conducting EMS Research
