QI vs Research: Where do we draw the line

Slide 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

Slide 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

Slide 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

Slide 4:Audience

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

Slide 5:Continuum

Slide 7:Pronovost/OHRP/JHU Case Timeline

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

Slide 8:Timeline continued

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

Slide 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

Slide 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

Slide 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

Slide 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

Slide 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

Slide 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)

Slide 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

Slide 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

Slide 17:Pronovost publication

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

Slide 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

Slide 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

Slide 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

Slide 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

Slide 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

Slide 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

Slide 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

Slide 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)

Slide 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

Slide 27:Workgroup

Email ysmhic@yale.edu Or sandra.alfano@yale.edu

Slide 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

Slide 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

Slide 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.

Slide 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]

Slide 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

Slide 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

Slide 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.

Slide 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 .

Slide 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]

Slide 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

Slide 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

Slide 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

Slide 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.

Slide 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 is not 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.

Slide 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]

Slide 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

Slide 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)

Slide 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.

Slide 47:EXAMPLE: Registration Form

Slide 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.

Slide 49:Quality Improvement Research: Ethical Considerations Harlan M. Krumholz MD Yale School of Medicine New Haven, CT

October 23, 2008

Slide 50:Margaret Bourke-White, a great American photographer who established herself as an industrial photographer at a very young age. She also photographed other, non-industrial scenes, such as the one on the left of a bombed Nuremberg in 1945. Margaret Bourke-White, a great American photographer who established herself as an industrial photographer at a very young age. She also photographed other, non-industrial scenes, such as the one on the left of a bombed Nuremberg in 1945.

Slide 51:The Doctors Trial considered the fate of twenty-three German physicians who either participated in the Nazi program to euthanize persons deemed "unworthy of life" (the mentally ill, mentally retarded, or physically disabled) or who conducted experiments on concentration camp prisoners without their consent. The Doctors Trial lasted 140 days. Eighty-five witnesses testified and almost 1,500 documents were introduced. Sixteen of the doctors charged were found guilty. Seven were executed. The Doctors Trial considered the fate of twenty-three German physicians who either participated in the Nazi program to euthanize persons deemed "unworthy of life" (the mentally ill, mentally retarded, or physically disabled) or who conducted experiments on concentration camp prisoners without their consent. The Doctors Trial lasted 140 days. Eighty-five witnesses testified and almost 1,500 documents were introduced. Sixteen of the doctors charged were found guilty. Seven were executed.

Slide 52:Brigadier General Telford Taylor offers the opening statement for the prosecution. Brigadier General Telford Taylor offers the opening statement for the prosecution.

Slide 53:Brigadier General Telford Taylor offers the opening statement for the prosecution. Brigadier General Telford Taylor offers the opening statement for the prosecution.

Slide 54:Brigadier General Telford Taylor offers the opening statement for the prosecution. Brigadier General Telford Taylor offers the opening statement for the prosecution.

Slide 56:There was this simple idea…Gawande, The New Yorker, 12/10/2007

The heavily-favored Cleveland Indians--whose .721 winning percentage (111-43) still stands as the American League record--were locked in a 2-2 tie with the New York Giants. The game was played at New York's Polo Grounds, where the wall in dead center field was listed at 483 feet from home plate (in other years, the distance was listed at anywhere from 475 to 505 feet, with no explanation for the changes). In the top of the eighth inning, Cleveland's first two batters, Larry Doby and Al Rosen, reached base, bringing up the hot-hitting Wertz. The Indians' first baseman would finish the day 4-for-5, including a double and a triple. The three-bagger had hit the right field wall and brought home both of Cleveland's runs in the first inning. This time, Wertz blasted a ball toward deep center field, threatening to break the game wide open. But Mays, the 23-year-old phenom, was off with the crack of the bat. After a long run, Mays hauled the ball in with a spectacular over-the-shoulder catch in front of the fence, then spun and threw the ball back to the infield. Doby tagged and advanced to third (a forgotten fact), but Rosen held at first, and they were stranded there. The Giants went on to win the game in extra innings, then complete a stunning upset by sweeping the demoralized Indians in four games.The heavily-favored Cleveland Indians--whose .721 winning percentage (111-43) still stands as the American League record--were locked in a 2-2 tie with the New York Giants. The game was played at New York's Polo Grounds, where the wall in dead center field was listed at 483 feet from home plate (in other years, the distance was listed at anywhere from 475 to 505 feet, with no explanation for the changes). In the top of the eighth inning, Cleveland's first two batters, Larry Doby and Al Rosen, reached base, bringing up the hot-hitting Wertz. The Indians' first baseman would finish the day 4-for-5, including a double and a triple. The three-bagger had hit the right field wall and brought home both of Cleveland's runs in the first inning. This time, Wertz blasted a ball toward deep center field, threatening to break the game wide open. But Mays, the 23-year-old phenom, was off with the crack of the bat. After a long run, Mays hauled the ball in with a spectacular over-the-shoulder catch in front of the fence, then spun and threw the ball back to the infield. Doby tagged and advanced to third (a forgotten fact), but Rosen held at first, and they were stranded there. The Giants went on to win the game in extra innings, then complete a stunning upset by sweeping the demoralized Indians in four games.

Slide 57:Intervention

1. Wash their hands with soap. 2. Clean the patient’s skin with chlorhexidine. 3. Put sterile drapes over the entire patient. 4. Wear a sterile mask, hat, gown and gloves. 5. Put a sterile dressing over the catheter site.

Slide 58:Grant Number: 5UC1HS014246-02Project Title: Statewide Efforts to Improve Care in Intensive Care Unit

We hypothesize that we can improve patient safety; improve safety culture; and reduce ICU mortality, blood stream infections, aspiration pneumonia and ICU length of stay.

Slide 59:Statewide Efforts to Improve Care in Intensive Care Unit

To accomplish this, we will partner with the Michigan Hospital Association, whose has over 130 Michigan hospitals, to implement a safety program and other interventions in a cohort of hospitals.

Slide 60:Statewide Efforts to Improve Care in Intensive Care Unit

Specific aims are to implement and evaluate: impact of the Comprehensive Unit-based Safety Program that includes the ICU Safety Reporting System; effect of an intervention to improve communication and staffing in ICUs;

Slide 61:Statewide Efforts to Improve Care in Intensive Care Unit

effect of an intervention to reduce/eliminate catheter related blood stream infections; effect of an intervention to improve the care of ventilated patients; and effect of an intervention to reduce mortality.

Slide 62:The results were published in NEJM

Slide 63:And the results were very good.

Slide 64:Timeline

Slide 65:Pronovost became a celebrity.

Slide 66:What was the ethical obligation?

Slide 67:Questions were raised by OHRP.

Slide 72:OHRP sends another letter in July ‘08.

Slide 73:Brigadier General Telford Taylor offers the opening statement for the prosecution. Brigadier General Telford Taylor offers the opening statement for the prosecution.

Slide 77:What determines what we need to do to protect subjects?

intent (mens rea) intervention? rigor? publication? funding? timing? safety? feasibility?

Slide 78:Exemption

"research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified."

Slide 79:Exemption

Nevertheless, the research could have been reviewed in an expedited fashion by the IRB chair alone, since it posed no more than "minimal risks" and fit within two categories for expedited review specified by the OHRP: "collection of data through noninvasive procedures (not including anesthesia or sedation) routinely employed in clinical practice" and "research including materials (data, documents, records, or specimens) that have been collected or will be collected solely for nonresearch purposes (such as medical treatment or diagnosis)." Miller and Emanuel NEJM

Slide 80:Treatment of STEMI

Slide 81:Primary PCI for STEMI is a remarkable intervention.

Slide 82:The D2B standard in 1999was 90 ± 30 minutes

Slide 83:Around the turn of the century,performance was stable.

Slide 84:Several key strategies were identified.

BACKGROUND: Prompt reperfusion treatment is essential for patients who have myocardial infarction with ST-segment elevation. Guidelines recommend that the interval between arrival at the hospital and intracoronary balloon inflation (door-to-balloon time) during primary percutaneous coronary intervention should be 90 minutes or less. However, few hospitals meet this objective. We sought to identify hospital strategies that were significantly associated with a faster door-to-balloon time. METHODS: We surveyed 365 hospitals to determine whether each of 28 specific strategies was in use. We used hierarchical generalized linear models and data on patients from the Centers for Medicare and Medicaid Services to determine the association between hospital strategies and the door-to-balloon time. RESULTS: In multivariate analysis, six strategies were significantly associated with a faster door-to-balloon time. These strategies included having emergency medicine physicians activate the catheterization laboratory (mean reduction in door-to-balloon time, 8.2 minutes), having a single call to a central page operator activate the laboratory (13.8 minutes), having the emergency department activate the catheterization laboratory while the patient is en route to the hospital (15.4 minutes), expecting staff to arrive in the catheterization laboratory within 20 minutes after being paged (vs. >30 minutes) (19.3 minutes), having an attending cardiologist always on site (14.6 minutes), and having staff in the emergency department and the catheterization laboratory use real-time data feedback (8.6 minutes). Despite the effectiveness of these strategies, only a minority of hospitals surveyed were using them. CONCLUSIONS: Several specific hospital strategies are associated with a significant reduction in the door-to-balloon time in the management of myocardial infarction with ST-segment elevation. N Engl J Med. 2006 Nov 30;355(22):2308-20. Epub 2006 Nov 13. BACKGROUND: Prompt reperfusion treatment is essential for patients who have myocardial infarction with ST-segment elevation. Guidelines recommend that the interval between arrival at the hospital and intracoronary balloon inflation (door-to-balloon time) during primary percutaneous coronary intervention should be 90 minutes or less. However, few hospitals meet this objective. We sought to identify hospital strategies that were significantly associated with a faster door-to-balloon time. METHODS: We surveyed 365 hospitals to determine whether each of 28 specific strategies was in use. We used hierarchical generalized linear models and data on patients from the Centers for Medicare and Medicaid Services to determine the association between hospital strategies and the door-to-balloon time. RESULTS: In multivariate analysis, six strategies were significantly associated with a faster door-to-balloon time. These strategies included having emergency medicine physicians activate the catheterization laboratory (mean reduction in door-to-balloon time, 8.2 minutes), having a single call to a central page operator activate the laboratory (13.8 minutes), having the emergency department activate the catheterization laboratory while the patient is en route to the hospital (15.4 minutes), expecting staff to arrive in the catheterization laboratory within 20 minutes after being paged (vs. >30 minutes) (19.3 minutes), having an attending cardiologist always on site (14.6 minutes), and having staff in the emergency department and the catheterization laboratory use real-time data feedback (8.6 minutes). Despite the effectiveness of these strategies, only a minority of hospitals surveyed were using them. CONCLUSIONS: Several specific hospital strategies are associated with a significant reduction in the door-to-balloon time in the management of myocardial infarction with ST-segment elevation. N Engl J Med. 2006 Nov 30;355(22):2308-20. Epub 2006 Nov 13.

Slide 85:D2B Alliance is a vehicle to disseminate knowledge and promote improvement.

www.d2balliance.org

Slide 86:More than 1,000 hospitalsjoined the effort.

Slide 87:The use of strategies changedin D2B Alliance hospitals

Recommended Strategy* Baseline Follow-up EM activation 52% 60% Single call 31% 37% Cath team < 30 min 81% 89% Prompt data feedback 61% 79% Activate from PH ECG 33% 41% D2B Team 64% 85% * All differences are significant P< 0.001

Slide 89:Was shortening LOS for patients after CABG an intervention?

Slide 90:What is research?

Slide 91:What is human research?

A systematic investigation designed to develop or contribute to generalizable knowledge Data through interaction or intervention with the individual, or Identifiable private information

Slide 92:What is quality improvement?

Systematic, data-guided activities designed to bring about immediate improvements in health care delivery in a particular setting

Slide 93:Is QI without evaluation (research) ethical?

Slide 94:Baily: Organizational research not human subjects research

Slide 95:Improving the effectiveness of care is part of the research agenda.

Slide 96:Is it about language?