QI vs Research: Where do we draw the line?

1. QI vs Research: Where do we draw the line? Sandra L. Alfano, Pharm.D. FASHP Chair, Human Investigation Committee-I Yale University School of Medicine October 23, 2008

2. Session Objectives • Provide guidance on when a project meets criteria as QI or research • Present a bioethical perspective examining issues involved with QI and research • Provide a researcher’s perspective on both conducting QI and research

3. Speakers • Sandra L. Alfano, Pharm.D., FASHP Chair, Human Investigation Committee Yale University School of Medicine • Nancy Neveloff Dubler, LL.B. Professor of Bioethics, Albert Einstein College of Medicine Director, Division of Bioethics, Montefiore Medical Center • Harlan Krumholz, MD, SM Professor of Medicine and Epidemiology and Public Health Yale University

4. Audience • Researchers and research personnel • Quality improvement personnel • IRB staff, regulatory perspective • Some that do a little of both

5. Continuum

7. NEJM Publication Dramatic effective results to decrease infection rate Letter of complaint to OHRP Allegations of lack of prior IRB review, and lack of informed consent on the part of the patients JHU responds to OHRP Insists study was exempt OHRP responds to JHU Asks for corrective actions JHU responds that PI has suspended all activities December 28, 2006 Prompts OHRP compliance investigation March 30, 2007 July 19, 2007 September 25, 2007 Pronovost/OHRP/JHU Case Timeline

8. OHRP to JHU Atul Gawande, NY Times “A Lifesaving Checklist” OHRP listserve response Clarifies that JHU suspended study, not OHRP November 6, 2007 December 30, 2007 January 15, 2008 Timeline continued

9. Timeline continued • OHRP response to JHU: 2-14-08 • Now refers to the ‘Initiative activities’ • Notes the intervention was done for clinical purposes • The only data released are de-identified, so therefore project has evolved to be no longer engaged in human subjects research 2 NEJM editorials: 2-21-08 • Miller and Emanuel: • Not exempt, as it was a prospective study • Should have been reviewed by IRB via full or expedited review • Baily: • Sophisticated IRB had difficulty with interpretation of regulations is a bad sign in itself • Project was a combo of QI and research on organizations

10. Timeline continued • QI Panel presentation to SACHRP: March 27, 2008 • OHRP letter to Pronovost: July 30, 2008 • Posted prominently on OHRP website http://www.hhs.gov/ohrp/policy/correspond/Pronovost20080730.html

11. Regulatory research definitions • Research: a systematic investigation designed to develop or contribute to generalizable knowledge • Human Subject: a living individual about whom an investigator conducting research obtains • data through interaction or intervention with the individual, or • identifiable private information

12. Regulatory research definitions • Engagement in Research: An institution becomes “engaged’ in human subjects research when its employees or agents intervene or interact with living individuals for research purposes, or obtain individually identifiable private information for research purposes • If engaged in federally funded research, must file a Federalwide Assurance (FWA) with HHS

13. Regulatory research definitions • Exempt: Research activities in which the only involvement of human subjects will be in one or more of the stipulated categories are exempt from this policy (Common Rule, 45CFR46) • Expedited review procedures are allowed for certain kinds of research involving no more than minimal risk, and for minor changes in approved research. In such cases, the review is conducted by the IRB Chair, or by one or more experienced reviewers designated by the Chair from among IRB members

14. A complicating wrinkle • HIPAA: Health Insurance Portability and Accountability Act • Establishes security and privacy standards for the use and disclosure of ‘protected health information’ (PHI) • Not well designed to deal with research issues • Uses different definitions regarding personal information (PHI versus identifiable private information)

15. Belmont Principles • Respect for Persons • Autonomy, therefore voluntariness requirement • Informed consent for research participation • Beneficence • Risk:Benefit analysis • Justice • Fair distribution of burdens and benefits

16. Lessons learned • Was it research? If so, ‘Exempt’ versus ‘Expedited’ review? • Funding source and FWA engagement issues • Informed consent? If so, from whom? • Publication/dissemination of results

17. The study Our study Study intervention Researchers Study hypothesis Study period Objective of the study Study design 14 1 14 2 1 5 1 3 Pronovost publication

18. Was it research? If so, ‘Exempt’ versus ‘Expedited’ review? • Researchers seemed to think it was research • Be careful of terminology • Baily (NEJM 2008) argues that it was QI, coupled with organizational research, not human subjects research • If not human subjects research, Common Rule does not apply

19. Trouble with the exempt versus expedited review question • Miller and Emanuel (NEJM 2008) argue for expedited review • This assumes the project is ‘human subjects research’, and the Common Rule applies • Exemption determination requires fitting one of the stipulated categories

20. Lessons learned • Was it research? If so, ‘Exempt’ versus ‘Expedited’ review? • Funding source and FWA engagement issues • Informed consent? If so, from whom? • Publication/dissemination of results

21. Funding source and FWA engagement issues • When federally funded, must follow Common Rule regulations • Pronovost study funded by AHRQ • OHRP guidance about engagement in research would require an FWA and IRB of record for each institution involved

22. Lessons learned • Was it research? If so, ‘Exempt’ versus ‘Expedited’ review? • Funding source and FWA engagement issues • Informed consent? If so, from whom? • Publication/dissemination of results

23. Informed consent? If so, from whom? • If it is human subjects research, strong requirement to get voluntary participation from subjects of the research, via informed consent • Remember there were two groups involved: staff and patients • If viewed as QI and organizational research, no requirement for informed consent from either patients or staff

24. Lessons learned • Was it research? If so, ‘Exempt’ versus ‘Expedited’ review? • Funding source and FWA engagement issues • Informed consent? If so, from whom? • Publication/dissemination of results

25. Publication/dissemination of results • Research is designed to develop or contribute to generalizable knowledge • Many consider publication as a threshold for meeting the ‘generalizable’ definition of research • But it certainly seems counterproductive to say it is OK to improve care (via QI) as long as you don’t tell anyone about it! • Most now agree publication does not make a project ‘research’ per se (OHRP even recognizes this fact in its new guidance on Engagement in Research)

26. Conclusions • Organizations wishing to conduct Quality Improvement activities need to do so without inappropriate regulatory burden • Project design, and terminology used, must be carefully examined • QI and research components should be carefully defined • Publication of results is not a determinant of research

27. Workgroup • Email ysmhic@yale.edu • Or sandra.alfano@yale.edu

28. A Process of Quality Improvement: Informed Participation and Institutional ProcessYale UniversityOctober 23, 2008 Nancy Neveloff Dubler Senior Associate Montefiore-Einstein Center for Bioethics Montefiore Medical Center Professor Emerita The Albert Einstein College of Medicine

29. Quality Improvement and Research:The permeable barrier Bellin E, Dubler NN, The Quality Improvement–Research Divide and the Need for External Oversight, American Journal of Public Health, 2001, 91(9): 1512-1517. • Use of large data sets • Randomization • Eschew IRB review • Need for Oversight not for IRB Review • Intent • Ability/authority to implement results • Irrespective of source and quality of data and of technique, including randomization

30. Research 45 CFR 46.102 (d): Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Activities which meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program which is considered research for other purposes. For example, some demonstration and service programs may include research activities.

31. Quality Improvement • “The group defined QI as the systematic, data-guided activities designed to bring about immediate improvements in health care delivery in a particular setting”. • [The Ethics of Using Quality Improvement Methods in Health Care, Lynn et al, Annals, May 2007, Vol.146, No.9, 666-674]

32. Disease Management • Improve over-all quality of life • Reduce morbidity and mortality • Ensure that patients receive evidence based interventions for their particular chronic illnesses • Improve patient and family comprehension • Reduce in-patient admissions and reduce length-of-stay • Reduce ER visits • Ensure that new evidence-based interventions are incorporated into practice at all levels of care • Reduce Costs

33. Key components of disease management • Patient identification, assessment and stratification; • Continued physician compliance with new evidence based interventions; • Education and empowerment of patient and family members; • Ongoing monitoring of patient’s health status

34. Three QI Interventions Design: each patient given a cell phone and called when medication is due: vs. Patients not given cell phones vs. Patients on DOT Design: Clinical Looking Glass: Replicate of the clinical activities: How many patients, which services, which physicians, have higher than acceptable viral loads in HIV/AIDS? Smart scale: patient weighs every morning and discusses with nurse.

35. Ethical Justification:Research • Research is not morally mandatory for institutions; • Participation in research is not morally mandatory for human subjects; Research is important to advance medical science but participation is morally gratuitous because most research is not necessary for the survival of society; • The principle of Justice might require the prior beneficiaries of research to repay the benefit that they gained; • So vital social interest and justice might require participation—most conclude do not; • Therefore, potential human subjects in research are morally free to consent to or to refuse participation .

36. Ethical Justification:Quality Improvement • Medical professionals are morally required to engage in QI in order to revere the basic ethic of medicine [do no harm]; • Individual health care organizations are morally required to engage in QI –an obligation derived from organizational ethics and the notion or institutional moral agency; • Patients are morally required to participate in QI [Responsibilities from possible immediate benefit to self and responsibilities from benefits to others]

37. Ethical Justifications for Disease Management • Health and wellbeing of chronically ill populations • Quality of care across the continuum • Lowering or reducing costs of hospitalization • Helping the health care system to “affordability” • Assisting patients and families in the community

38. Elements of QI • QI: systemic, data-guided and efficient • QI: may inadvertently cause harm, waste scarce resources or affect some patients unfairly • QI: distinguished from research: • QI: hypothesis, plan, pilot, test, evaluate—repeat—implement • [Research: hypothesis, gather data, analyze, discuss] • QI: uses experience to identify promising improvements, implements change on a small scale and monitors effects • QI: may review aggregate data impose evidence based methods • QI: is in intrinsic part of good clinical care

39. Similarities Between QI and Research • Involve human participants • Are concerned with inquiry • Are processes in which empirical or systematic inquiry generates a question that data collection is designed to answer • Propose a set of outcome measures that will support proposal • Testing solutions • Involve critical evaluation of data

40. Ethical Requirements for Protection of Human Participants in QI Activities: • Social or scientific value of the individual QI project; • Scientific validity in design and methodology; • Fair participant selection that does not overly burden one population nor stigmatize any population; • Favorable risk-benefit ratio: basically minimal risk or less than minimal risk; • Respect for participants • Informed participation or occasionally in QI efforts that require individual actions, informed consent; • Independent review by an institutional office authorized to approve or disapprove QI projects, to register these projects, to gather data on completion, to evaluate results and see to the implementation of new systems.

41. Moral Obligation: Research and QI Participation is morally imperative only if research or QI is so characterized; Research is important to advance medical science but participation is morally gratuitous because most research isnot necessary for the survival of society; Justice requires prior beneficiaries to repay; So vital social interest and justice might require participation—most conclude do not.

42. Moral Imperative for Patients, Providers and Institutions Three moral imperatives: • Medical professionals must conduct QI; [do no harm] • Individual health care organizations must support QI; [obligation from moral agency] • Active patients must participate in QI. [Responsibilities from possible immediate benefit to self and responsibilities from benefits to others]

43. Ethical Protections for Patient/Participants in QI • Social or scientific value • Scientific validity • Fair participant selection • Favorable risk-benefit ratio: minimal risk • Respect for participants • Informed consent/informed participation • Independent review

44. Provisions in research for altering or waiving the requirement of Informed Consent: • Exceptions to Informed Consent: IRB may alter or waive: • (1) The research involves no more than minimal risk to the subjects; • (2) The waiver or alteration will not adversely affect the rights and welfare of the subjects; • (3) The research could not practicably be carried out without the waiver or alteration; and • (4) Whenever appropriate the subjects will be provided with additional pertinent information after participation. • §46.111 (d)

45. Informed participation: • Clear statements by the health care institution about QI—obligation to participate in minimal risk QI projects for the immediate benefit to some patients and the long-term benefits for all; • Oversight structure for QI—review before; • Structure for accountability—implementation of positive findings after data are collected and analyzed; • Feedback and Information for patients/participants.

46. Oversight Structure “Investigator” is uncertain QI registration site surveillance IRB concerns or “QI rejections” Institutional referrals Quality Improvement Research Committee Performance Improvement, Bioethics, Legal Affairs, Risk Management, Bioethics, Administration, Interdisciplinary Providers Liability issues Legal Affairs “Investigator” elects to not proceed Research Both Research and QI Quality Improvement IRB submission Informed consent QI project registration Informed participation Draft

47. EXAMPLE: Registration Form

48. Conclusion: QI is morally mandatory for institutions physicians, and patients: It is part of the social contract of medicine that do no harm implies the need to improve as the skills and tools of improvement are developed. QI is not subject to review as research but is open, transparent and part of the culture of the medical center.

49. Quality Improvement Research: Ethical ConsiderationsHarlan M. Krumholz MD Yale School of Medicine New Haven, CT October 23, 2008

50. Out of the ashes of Nuremberg… Margaret Bourke-White