Clinical Research in the Emergency Department

1. Clinical Research in the Emergency Department Jim Quinn MD MS Associate Professor of Surgery/Emergency Medicine Research Director Emergency Medicine

2. Overview • Goals for research in academic emergency medicine • Problems/solutions for researchers in emergency medicine • Problems/solutions for research implementation • The new clinical research unit in the ED at Stanford

3. Academic Emergency Medicine • Outstanding residency and clinical operations • Research lags behind educational and clinical performance • Excellence in education, clinical operation and research will lead to departmental status at the university • Departmental status will lead to more academic and fiscal freedom

4. Improving ResearchHow Do We Get There • Obstacles • Too busy • No training in research • Too few mentors/role models • No interest

5. Improving ResearchHow Do We Get There • Solutions 1) Recruit researchers 2) Develop researchers - Personal and academic investment • Expose EM residents to advantages of academic career • Funding through grants and career development awards

6. Research During Residency • Train residents to appreciate research efforts, critically evaluate a study • Study design, methodology, statistics • Exposure to opportunities for an academic career • Some will decide to do research fellowships and pursue academic medicine

7. Research During Residency • Start early (1st year) • Develop own idea • Develop that idea with a faculty mentor • avoid doing research for them • find mentors with common interest • Research curriculum and support to facilitate project development • Research Director- support and direction

8. Research CurriculumStructure and Support to Develop Your Idea • Curriculum (tried and tested) • 12 hours – 6 sessions with core reading and homework designed to develop your project • Textbook • “Designing Clinical Research” - Hulley and Cummings • small paperback readable • Help identify mentors and sources of data

9. The Five Page ProtocolGoal for the Research Curriculum • Concise protocol • More concise than an NIH submission, but often sufficient for small intramural grants • Discipline approach to planning the study • Provide the materials and answers for IRB submission • Completed by the end of first year • Implement in years 2 and 3

10. OrganizationThe Five Page Protocol • Page One - Title, Specific objectives, significance • Pages 2-5 • Overview of design (RCT, observational cohort/ cross sectional, case/control) • Study subjects: selection criteria, exclusions, accessible populations, plans for sampling and recruitment • Measurement – predictor and outcome variables • Statistical issues – sample size, proposed analysis • Quality control and data management • Timetable • Ethical considerations

11. Research Development • Residents • EMF: Resident Research Grants - $5,000 • EMF, SAEM: Research Fellowships - $75,000 • T and F awards from NIH Faculty • Career development awards SAEM, EMF, K awards from NIH

12. What is a Career Development Award ? • Funding to protect your time so that you can develop your research skills • Research may be: • Clinical • Basic Science

13. NIH Awards for Individuals with a Health-Professional Doctorate Institutional Training Grants (T32) Senior Fellowships (F33) Short-Term Training Grant (T35) PostdoctoralFellowships (F32) Independent Investigator Medical School Internship/Residency Specialty Career Enhancement Award Stem Cells (K18) Scientist Development Program (K12) Midcareer Investigator in Patient-Oriented Research (K24) Mentored Clinical Scientist Development Award (K08) Mentored Patient-Oriented Research CDA (K23)

14. Benefits of a Career Development Award ? • Protected time • Extra Training • Step towards independence • New relationships

15. Myth: NIH Grants/Study Sections • Emergency medicine proposals, especially clinical research, will not be evaluated fairly, nor will they be funded consistently, until the NIH has a study section devoted to emergency medicine. • NIH grants are rare and hard to get

16. What is Important to Study Section Members? • Study section members don’t care what department the investigator is in. • Study section members care about: • The match between the proposed work and the goals of the program • The quality of the proposal • Investigator’s track record and preliminary data • The institutional research environment

17. Selected NIH Panel Recommendations • “The NIH must ensure fair and effective reviews of extramural grant applications for support of clinical research: panels that review clinical research • (a) must include experienced clinical investigators and • (b) at least 30-50% of the applications reviewed by these panels must be for clinical research.”

18. Selected NIH Panel Recommendations • “The NIH should improve the quality of training for clinical researchers by requiring grantee organizations to provide formal training experiences in clinical research and careful mentoring by experienced clinical investigators.”

21. Does NIH Fund EM Research? • A search of currently funded federal grants using the CRISP database and key words “Emergency” yielded 204 new grants in the years 2000-2002. • Accurate numbers of grants submitted by specialty are difficult to find and interpret. No separate statistics are maintained for Emergency Medicine.

22. Research Options • Basic Science • Translational Research • Clinical Research • Large database • Retrospective reviews • Clinical trials/Prospective cohorts

23. Myth: Large Databases • Large administrative databases contain large amounts of clinically useful information.

24. Large Databases • In general, large databases are collected: • For non-research purposes (e.g., claims and billing databases) • With no specific research question in mind (e.g., trauma center databases)

25. Large Databases • Large databases often lack the specific outcome and risk stratification variables needed for a particular study, requiring assumptions and approximations to be made. • Large databases often have a substantial proportion of missing or incorrect data which may reflect recording bias or other sources of bias.

26. Large Databases • Even small biases, together with a large sample size, may yield results with impressively small p values that are, nonetheless, artifacts. • Without independent methods for checking the accuracy and completeness of the data, these biases may be difficult to detect.

27. Clinical Trials • Prospective trials • Designed to answer specific questions • More likely to answer the question correctly

28. Problems Implementing Clinical Research • Where did all the patients go? “ The best way to eliminate disease is to study it” • Nobody cares • IRB/HIPAA issues • Department too busy, too many protocols

29. “Tragedy of the Commons” • A “Metaphor” to describe the sub-optimal use of a collectively shared resource “best strategies for individuals conflict with the common good”

30. Clinical Research Unit Goal – “conduct efficient and effect research in the chaotic environment of the ED for the common good” - Comprehensive database of all ED patients • Real time data infrastructure • Real time notification and enrollment • Research director, research coordinator, volunteers • Research committee to oversee all projects to ensure adequate resources

31. Clinical Research UnitReal Time Data Infrastructure • HIPPA complaint ED Research database • Hosted by SOM: secure, redundancy • Allows for instant notification directly from database • Web based enrollment • Eventually paperless • https://emerg-med.stanford.edu/

32. Clinical Research UnitResearch Coordinator and Volunteers • Volunteers • Undergrads and med students • Help screen and enroll patients - Deal with paper flow • Coordinator • oversees volunteers: schedules • patient follow-up • resource for data and chart acquisition for ED studies.

33. Clinical Research UnitResearch Committee • Meets monthly – 30-60 minute meetings after faculty meeting 2nd Wednesday • Open meetings • Oversees and approves all protocols in ED • Consists of research director, resident representation, at least 2 volunteer faculty members

34. Clinical Research UnitFunding and Resources • Coordinator – 50% time primarily from grant funding • New funding and studies could increase to 100% • Non-EM researchers/industry will have to pay to use our data infrastructure/research unit

35. Clinical Research UnitRegistering Protocols • Send e-mail with protocol to Dr.Quinn • Protocol will be reviewed at research committee for: • IRB approval • Funding Source • Resource Utilization • Benefit to EM • All external protocol will need to have an EM faculty as an investigator/supporter on the protocol

36. Next Step • Identify current projects utilizing ED patients/resources • Hire coordinator – Completed Dec/Jan • Volunteer recruitment - Ongoing • First committee meeting in December

37. Clinical Research UnitThe First Studies • Dog Bite Study - Requires prospective enrollment of patients and consent • NET-2 - Surveillance study to be part of large NINDS study, no consent

38. Are Prophylactic Antibiotics Beneficial in Dog Bites? • Controversial 1) Meta analysis- Ann Emerg Med – 1994 • Recommend treating 2) Cochrane Review 2004 • Recommend Not Treating 3) Current recommendation is to treat high risk wounds

39. Are Prophylactic Antibiotics Beneficial in Dog Bites? • Is it worth doing the study? • Over 1,000 patients needed in a multi-center trial at great cost to determine a 5% difference (less power on sub group analysis) • Is 5% an important difference?

40. Are Prophylactic Antibiotics Beneficial in Dog Bites?Value of Cost- Benefit Models The models done ahead of a trial can; 1) Clearly define important outcomes to measure 2) Help determine MCID for sample size 3) Sometimes provide the answer

41. Dog Bite: Cost – Benefit Model

42. Clinical Data

45. Willingness to Pay Data

46. Cost Data

49. Are Prophylactic Antibiotics Beneficial in Dog Bites?Value of Cost- Benefit Models • Model determined 1% difference may be important as far as cost • An RCT to determined this would not be reasonable But…. • The model is based on assumptions and best available data. • Sensitivity analysis can determine the errors associated with assumptions • Better model estimates will improve the accuracy of the results.

50. Are Prophylactic Antibiotics Beneficial in Dog Bites • Funding – NIAMS • Design Cost Benefit Analysis with Clinical Trial Data • Start Aug 2003 UCSF add Stanford November 2004, Study will run through June 2006 • Patient randomized to 3 days of Augmentin or Placebo • Goal 100 – 125 patients outcomes (the largest trial) - 37 patients with complete F/U to date • Goal is to define and measure accurately all outcomes (infections, side effects, hospitalizations etc.) in the model • Re-run the model and sensitivities to come up with the best recommendations.