QI vs Research: QI vs Research: Where do we Where do we

draw the line?draw the line?Sandra L. Alfano, Pharm.D. FASHPSandra L. Alfano, Pharm.D. FASHP

Chair, Human Investigation Chair, Human Investigation Committee-ICommittee-I

Yale University School of MedicineYale University School of MedicineOctober 23, 2008October 23, 2008

Session ObjectivesSession Objectives

Provide guidance on when a project Provide guidance on when a project meets criteria as QI or researchmeets criteria as QI or research

Present a bioethical perspective Present a bioethical perspective examining issues involved with QI examining issues involved with QI and researchand research

Provide a researcher’s perspective Provide a researcher’s perspective on both conducting QI and researchon both conducting QI and research

SpeakersSpeakers Sandra L. Alfano, Pharm.D., FASHPSandra L. Alfano, Pharm.D., FASHP

Chair, Human Investigation CommitteeChair, Human Investigation CommitteeYale University School of MedicineYale University School of Medicine

Nancy Neveloff Dubler, LL.B.Nancy Neveloff Dubler, LL.B.Professor of Bioethics, Albert Einstein College of MedicineProfessor of Bioethics, Albert Einstein College of MedicineDirector, Division of Bioethics, Montefiore Medical CenterDirector, Division of Bioethics, Montefiore Medical Center

Harlan Krumholz, MD, SMHarlan Krumholz, MD, SMProfessor of Medicine and Epidemiology and Public Health Professor of Medicine and Epidemiology and Public Health Yale UniversityYale University

AudienceAudience

Researchers and research personnelResearchers and research personnel Quality improvement personnelQuality improvement personnel IRB staff, regulatory perspectiveIRB staff, regulatory perspective

Some that do a little of bothSome that do a little of both

ContinuumContinuum

Pronovost/OHRP/JHU Case Pronovost/OHRP/JHU Case TimelineTimeline

NEJM PublicationNEJM Publication Dramatic effective results to Dramatic effective results to

decrease infection ratedecrease infection rate Letter of complaint to OHRPLetter of complaint to OHRP

Allegations of lack of prior Allegations of lack of prior IRB review, and lack of IRB review, and lack of informed consent on the part informed consent on the part of the patientsof the patients

JHU responds to OHRPJHU responds to OHRP Insists study was exemptInsists study was exempt

OHRP responds to JHUOHRP responds to JHU Asks for corrective actionsAsks for corrective actions

JHU responds that PI has JHU responds that PI has suspended all activitiessuspended all activities

December 28, 2006December 28, 2006

Prompts OHRP compliance Prompts OHRP compliance investigationinvestigation

March 30, 2007March 30, 2007

July 19, 2007July 19, 2007

September 25, 2007September 25, 2007

Timeline continuedTimeline continued OHRP to JHUOHRP to JHU

Atul Gawande, NY Atul Gawande, NY TimesTimes ““A Lifesaving A Lifesaving

Checklist”Checklist”

OHRP listserve OHRP listserve responseresponse Clarifies that JHU Clarifies that JHU

suspended study, suspended study, not OHRPnot OHRP

November 6, 2007November 6, 2007

December 30, December 30, 2007 2007

January 15, 2008January 15, 2008

Timeline continuedTimeline continued OHRP response to JHU: 2-14-08OHRP response to JHU: 2-14-08

Now refers to the ‘Initiative activities’Now refers to the ‘Initiative activities’ Notes the intervention was done for clinical purposesNotes the intervention was done for clinical purposes The only data released are de-identified, so therefore The only data released are de-identified, so therefore

project has evolved to be no longer engaged in human project has evolved to be no longer engaged in human subjects researchsubjects research

2 NEJM editorials: 2-21-082 NEJM editorials: 2-21-08 Miller and Emanuel:Miller and Emanuel:

Not exempt, as it was a prospective studyNot exempt, as it was a prospective study Should have been reviewed by IRB via full or expedited Should have been reviewed by IRB via full or expedited

reviewreview Baily:Baily:

Sophisticated IRB had difficulty with interpretation of Sophisticated IRB had difficulty with interpretation of regulations is a bad sign in itselfregulations is a bad sign in itself

Project was a combo of QI and research on organizationsProject was a combo of QI and research on organizations

Timeline continuedTimeline continued

QI Panel presentation to SACHRP: QI Panel presentation to SACHRP: March 27, 2008March 27, 2008

OHRP letter to Pronovost: July 30, OHRP letter to Pronovost: July 30, 20082008 Posted prominently on OHRP websitePosted prominently on OHRP websitehttp://www.hhs.gov/ohrp/policy/correspond/http://www.hhs.gov/ohrp/policy/correspond/

Pronovost20080730.htmlPronovost20080730.html

Regulatory research Regulatory research definitionsdefinitions

ResearchResearch: a systematic investigation : a systematic investigation designed to develop or contribute to designed to develop or contribute to generalizable knowledgegeneralizable knowledge

Human SubjectHuman Subject: a : a livingliving individual individual about whom an investigator about whom an investigator conducting research obtains conducting research obtains data through interaction or intervention data through interaction or intervention

with the individual, or with the individual, or identifiable private informationidentifiable private information

Regulatory research Regulatory research definitionsdefinitions

Engagement in ResearchEngagement in Research: An institution : An institution becomes “engaged’ in human subjects becomes “engaged’ in human subjects research when its employees or agents research when its employees or agents intervene or interact with living intervene or interact with living individuals for research purposes, or individuals for research purposes, or obtain individually identifiable private obtain individually identifiable private information for research purposes information for research purposes

If engaged in federally funded research, If engaged in federally funded research, must file a Federalwide Assurance (FWA) must file a Federalwide Assurance (FWA) with HHSwith HHS

Regulatory research Regulatory research definitionsdefinitions

Exempt: Research activities in which the only Exempt: Research activities in which the only involvement of human subjects will be in one or involvement of human subjects will be in one or more of the more of the stipulated categoriesstipulated categories are exempt are exempt from this policy (Common Rule, 45CFR46)from this policy (Common Rule, 45CFR46)

Expedited review procedures are allowed for Expedited review procedures are allowed for certain kinds of research involving no more certain kinds of research involving no more than minimal risk, and for minor changes in than minimal risk, and for minor changes in approved research. In such cases, the review is approved research. In such cases, the review is conducted by the IRB Chair, or by one or more conducted by the IRB Chair, or by one or more experienced reviewers designated by the Chair experienced reviewers designated by the Chair from among IRB membersfrom among IRB members

A complicating wrinkleA complicating wrinkle

HIPAAHIPAA: Health Insurance Portability : Health Insurance Portability and Accountability Actand Accountability Act Establishes security and privacy Establishes security and privacy

standards for the use and disclosure of standards for the use and disclosure of ‘protected health information’ (PHI)‘protected health information’ (PHI)

Not well designed to deal with research Not well designed to deal with research issuesissues

Uses different definitions regarding Uses different definitions regarding personal information (PHI versus personal information (PHI versus identifiable private information)identifiable private information)

Belmont PrinciplesBelmont Principles

Respect for PersonsRespect for Persons Autonomy, therefore voluntariness Autonomy, therefore voluntariness

requirementrequirement Informed consent for research Informed consent for research

participationparticipation BeneficenceBeneficence

Risk:Benefit analysisRisk:Benefit analysis JusticeJustice

Fair distribution of burdens and benefitsFair distribution of burdens and benefits

Lessons learnedLessons learned

Was it research? If so, ‘Exempt’ Was it research? If so, ‘Exempt’ versus ‘Expedited’ review?versus ‘Expedited’ review?

Funding source and FWA engagement Funding source and FWA engagement issuesissues

Informed consent? If so, from whom?Informed consent? If so, from whom?

Publication/dissemination of resultsPublication/dissemination of results

Pronovost publicationPronovost publication

The studyThe study Our studyOur study Study interventionStudy intervention ResearchersResearchers Study hypothesisStudy hypothesis Study periodStudy period Objective of the Objective of the

studystudy Study designStudy design

1414

11

1414

22

11

55

11

33

Was it research? If so, Was it research? If so, ‘Exempt’ versus ‘Expedited’ ‘Exempt’ versus ‘Expedited’

review?review? Researchers seemed to think it was Researchers seemed to think it was

researchresearch Be careful of terminologyBe careful of terminology Baily (NEJM 2008) argues that it was Baily (NEJM 2008) argues that it was

QI, coupled with organizational QI, coupled with organizational research, not human subjects research, not human subjects researchresearch

If not human subjects research, If not human subjects research, Common Rule does not applyCommon Rule does not apply

Trouble with the exempt Trouble with the exempt versus expedited review versus expedited review

questionquestion Miller and Emanuel (NEJM 2008) Miller and Emanuel (NEJM 2008)

argue for expedited reviewargue for expedited review This assumes the project is ‘human This assumes the project is ‘human

subjects research’, and the Common subjects research’, and the Common Rule appliesRule applies

Exemption determination requires Exemption determination requires fitting one of the stipulated categoriesfitting one of the stipulated categories

Lessons learnedLessons learned

Was it research? If so, ‘Exempt’ Was it research? If so, ‘Exempt’ versus ‘Expedited’ review?versus ‘Expedited’ review?

Funding source and FWA engagement Funding source and FWA engagement issuesissues

Informed consent? If so, from whom?Informed consent? If so, from whom?

Publication/dissemination of resultsPublication/dissemination of results

Funding source and FWA Funding source and FWA engagement issuesengagement issues

When federally funded, must follow When federally funded, must follow Common Rule regulationsCommon Rule regulations

Pronovost study funded by AHRQPronovost study funded by AHRQ OHRP guidance about engagement OHRP guidance about engagement

in research would require an FWA in research would require an FWA and IRB of record for each and IRB of record for each institution involvedinstitution involved

Lessons learnedLessons learned

Was it research? If so, ‘Exempt’ Was it research? If so, ‘Exempt’ versus ‘Expedited’ review?versus ‘Expedited’ review?

Funding source and FWA engagement Funding source and FWA engagement issuesissues

Informed consent? If so, from whom?Informed consent? If so, from whom?

Publication/dissemination of resultsPublication/dissemination of results

Informed consent? If so, Informed consent? If so, from whom?from whom?

If it is human subjects research, If it is human subjects research, strong requirement to get voluntary strong requirement to get voluntary participation from subjects of the participation from subjects of the research, via informed consentresearch, via informed consent

Remember there were two groups Remember there were two groups involved: staff and patientsinvolved: staff and patients

If viewed as QI and organizational If viewed as QI and organizational research, no requirement for informed research, no requirement for informed consent from either patients or staffconsent from either patients or staff

Lessons learnedLessons learned

Was it research? If so, ‘Exempt’ Was it research? If so, ‘Exempt’ versus ‘Expedited’ review?versus ‘Expedited’ review?

Funding source and FWA engagement Funding source and FWA engagement issuesissues

Informed consent? If so, from whom?Informed consent? If so, from whom?

Publication/dissemination of resultsPublication/dissemination of results

Publication/dissemination Publication/dissemination of resultsof results

Research is designed to develop or contribute Research is designed to develop or contribute to generalizable knowledgeto generalizable knowledge

Many consider publication as a threshold for Many consider publication as a threshold for meeting the ‘generalizable’ definition of meeting the ‘generalizable’ definition of researchresearch

But it certainly seems counterproductive to But it certainly seems counterproductive to say it is OK to improve care (via QI) as long say it is OK to improve care (via QI) as long as you don’t tell anyone about it!as you don’t tell anyone about it!

Most now agree publication does not make a Most now agree publication does not make a project ‘research’ project ‘research’ per se per se (OHRP even (OHRP even recognizes this fact in its new guidance on recognizes this fact in its new guidance on Engagement in Research)Engagement in Research)

ConclusionsConclusions

Organizations wishing to conduct Organizations wishing to conduct Quality Improvement activities need Quality Improvement activities need to do so without inappropriate to do so without inappropriate regulatory burdenregulatory burden

Project design, and terminology used, Project design, and terminology used, must be carefully examinedmust be carefully examined

QI and research components should QI and research components should be carefully definedbe carefully defined

Publication of results is not a Publication of results is not a determinant of researchdeterminant of research

WorkgroupWorkgroup

Email Email ysmhic@yale.edu

Or sandra.alfano@yale.eduOr sandra.alfano@yale.edu

A Process of Quality A Process of Quality Improvement: Improvement:

Informed Participation and Informed Participation and Institutional ProcessInstitutional Process

Yale UniversityYale UniversityOctober 23, 2008October 23, 2008

Nancy Neveloff DublerNancy Neveloff DublerSenior AssociateSenior Associate

Montefiore-Einstein Center for BioethicsMontefiore-Einstein Center for BioethicsMontefiore Medical CenterMontefiore Medical Center

Professor EmeritaProfessor EmeritaThe Albert Einstein College of MedicineThe Albert Einstein College of Medicine

Quality Improvement and Quality Improvement and Research:Research:

The permeable barrierThe permeable barrierBellin E, Dubler NN, The Quality Improvement–Bellin E, Dubler NN, The Quality Improvement–

Research Divide and the Need for External Research Divide and the Need for External Oversight, Oversight, American Journal of Public HealthAmerican Journal of Public Health, , 2001, 91(9): 1512-1517.2001, 91(9): 1512-1517.

Use of large data setsUse of large data sets RandomizationRandomization Eschew IRB reviewEschew IRB review Need for Oversight not for IRB ReviewNeed for Oversight not for IRB Review

IntentIntent Ability/authority to implement resultsAbility/authority to implement results Irrespective of source and quality of data and of Irrespective of source and quality of data and of

technique, including randomizationtechnique, including randomization

ResearchResearch

45 CFR 46.102 (d):45 CFR 46.102 (d):

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

Quality ImprovementQuality Improvement

““The group defined QI as the systematic, The group defined QI as the systematic, data-guided activities designed to bring data-guided activities designed to bring about immediate improvements in health about immediate improvements in health care delivery in a particular setting”. care delivery in a particular setting”.

[The Ethics of Using Quality [The Ethics of Using Quality Improvement Methods in Health Care, Improvement Methods in Health Care, Lynn et al, Annals, May 2007, Vol.146, Lynn et al, Annals, May 2007, Vol.146, No.9, 666-674]No.9, 666-674]

Disease ManagementDisease Management Improve over-all quality of lifeImprove over-all quality of life Reduce morbidity and mortalityReduce morbidity and mortality Ensure that patients receive evidence based Ensure that patients receive evidence based

interventions for their particular chronic interventions for their particular chronic illnessesillnesses

Improve patient and family comprehensionImprove patient and family comprehension Reduce in-patient admissions and reduce length-Reduce in-patient admissions and reduce length-

of-stayof-stay Reduce ER visitsReduce ER visits Ensure that new evidence-based interventions Ensure that new evidence-based interventions

are incorporated into practice at all levels of careare incorporated into practice at all levels of care Reduce CostsReduce Costs

Key components of Key components of disease managementdisease management

Patient identification, assessment and Patient identification, assessment and stratification;stratification;

Continued physician compliance with Continued physician compliance with new evidence based interventions;new evidence based interventions;

Education and empowerment of Education and empowerment of patient and family members;patient and family members;

Ongoing monitoring of patient’s Ongoing monitoring of patient’s health statushealth status

Three QI InterventionsThree QI Interventions

Design: each patient given a cell phone and Design: each patient given a cell phone and called when medication is due: vs. Patients called when medication is due: vs. Patients not given cell phones vs. Patients on DOTnot given cell phones vs. Patients on DOT

Design: Clinical Looking Glass: Replicate of Design: Clinical Looking Glass: Replicate of the clinical activities: How many patients, the clinical activities: How many patients, which services, which physicians, have which services, which physicians, have higher than acceptable viral loads in higher than acceptable viral loads in HIV/AIDS?HIV/AIDS?

Smart scale: patient weighs every morning Smart scale: patient weighs every morning and discusses with nurse.and discusses with nurse.

Ethical Justification:Ethical Justification:ResearchResearch

Research is not morally mandatory for institutions;Research is not morally mandatory for institutions; Participation in research is not morally mandatory for Participation in research is not morally mandatory for

human subjects; Research is important to advance human subjects; Research is important to advance medical science but participation is morally gratuitous medical science but participation is morally gratuitous because most research is not necessary for the survival because most research is not necessary for the survival of society;of society;

The principle of Justice might require the prior The principle of Justice might require the prior beneficiaries of research to repay the benefit that they beneficiaries of research to repay the benefit that they gained;gained;

So vital social interest and justice might require So vital social interest and justice might require participation—most conclude do not;participation—most conclude do not;

Therefore, potential human subjects in research are Therefore, potential human subjects in research are morally free to consent to or to refuse participationmorally free to consent to or to refuse participation . .

Ethical Justification:Ethical Justification:Quality ImprovementQuality Improvement

Medical professionals are morally required to Medical professionals are morally required to engage in QI in order to revere the basic ethic engage in QI in order to revere the basic ethic of medicine [do no harm];of medicine [do no harm];

Individual health care organizations are Individual health care organizations are morally required to engage in QI –an morally required to engage in QI –an obligation derived from organizational ethics obligation derived from organizational ethics and the notion or institutional moral agency;and the notion or institutional moral agency;

Patients are morally required to participate in Patients are morally required to participate in QI [Responsibilities from possible immediate QI [Responsibilities from possible immediate benefit to self and responsibilities from benefit to self and responsibilities from benefits to others]benefits to others]

Ethical Justifications for Ethical Justifications for Disease ManagementDisease Management

Health and wellbeing of chronically ill Health and wellbeing of chronically ill populationspopulations

Quality of care across the continuumQuality of care across the continuum Lowering or reducing costs of Lowering or reducing costs of

hospitalizationhospitalization Helping the health care system to Helping the health care system to

“affordability”“affordability” Assisting patients and families in the Assisting patients and families in the

communitycommunity

Elements of QIElements of QI QI: systemic, data-guided and efficientQI: systemic, data-guided and efficient QI: may inadvertently cause harm, waste scarce QI: may inadvertently cause harm, waste scarce

resources or affect some patients unfairlyresources or affect some patients unfairly QI: distinguished from research:QI: distinguished from research: QI: hypothesis, plan, pilot, test, evaluate—repeat—QI: hypothesis, plan, pilot, test, evaluate—repeat—

implementimplement [Research: hypothesis, gather data, analyze, discuss][Research: hypothesis, gather data, analyze, discuss]

QI: uses experience to identify promising improvements, QI: uses experience to identify promising improvements, implements change on a small scale and monitors effectsimplements change on a small scale and monitors effects

QI: may review aggregate data impose evidence based QI: may review aggregate data impose evidence based methodsmethods

QI: is in intrinsic part of good clinical careQI: is in intrinsic part of good clinical care

Similarities Between QI Similarities Between QI and Researchand Research

Involve human participantsInvolve human participants Are concerned with inquiryAre concerned with inquiry Are processes in which empirical or Are processes in which empirical or

systematic inquiry generates a question systematic inquiry generates a question that data collection is designed to answerthat data collection is designed to answer

Propose a set of outcome measures that Propose a set of outcome measures that will support proposalwill support proposal

Testing solutionsTesting solutions Involve critical evaluation of dataInvolve critical evaluation of data

Ethical Requirements Ethical Requirements for Protection of Human for Protection of Human

Participants in QI Participants in QI Activities:Activities: Social or scientific value of the individual QI project;Social or scientific value of the individual QI project;

Scientific validity in design and methodology;Scientific validity in design and methodology; Fair participant selection that does not overly burden one Fair participant selection that does not overly burden one

population nor stigmatize any population;population nor stigmatize any population; Favorable risk-benefit ratio: basically minimal risk or less Favorable risk-benefit ratio: basically minimal risk or less

than minimal risk;than minimal risk; Respect for participantsRespect for participants Informed participation or occasionally in QI efforts that Informed participation or occasionally in QI efforts that

require individual actions, informed consent;require individual actions, informed consent; Independent review by an institutional office authorized to Independent review by an institutional office authorized to

approve or disapprove QI projects, to register these approve or disapprove QI projects, to register these projects, to gather data on completion, to evaluate results projects, to gather data on completion, to evaluate results and see to the implementation of new systems.and see to the implementation of new systems.

Moral Obligation: Moral Obligation: Research and QIResearch and QI

Participation is morally imperative only if Participation is morally imperative only if research or QI is so characterized;research or QI is so characterized;

Research is important to advance medical Research is important to advance medical science but participation is science but participation is morally morally gratuitous gratuitous because most research isbecause most research is not not necessary for the survival of society;necessary for the survival of society;

Justice requires prior beneficiaries to repay;Justice requires prior beneficiaries to repay;

So So vital social interestvital social interest and and justicejustice might might require participation—most conclude do require participation—most conclude do not. not.

Moral Imperative for Moral Imperative for Patients, Providers and Patients, Providers and

InstitutionsInstitutionsThree moral imperatives:Three moral imperatives:

1.1. Medical professionals must Medical professionals must conductconduct QI; QI;

[do no harm][do no harm]

2.2. Individual health care organizations must Individual health care organizations must supportsupport QI; QI;

[obligation from moral agency][obligation from moral agency]

3.3. Active patients must Active patients must participateparticipate in QI. in QI.

[Responsibilities from possible immediate [Responsibilities from possible immediate benefit to self and responsibilities from benefit to self and responsibilities from benefits to others]benefits to others]

Ethical Protections for Ethical Protections for Patient/Participants in Patient/Participants in

QIQI Social or scientific valueSocial or scientific value Scientific validityScientific validity Fair participant selectionFair participant selection Favorable risk-benefit ratio: minimal Favorable risk-benefit ratio: minimal

riskrisk Respect for participantsRespect for participants Informed consent/informed Informed consent/informed

participationparticipation Independent reviewIndependent review

Provisions in research for altering Provisions in research for altering or waiving the requirement of or waiving the requirement of

Informed Consent:Informed Consent: Exceptions to Informed Consent: IRB may alter Exceptions to Informed Consent: IRB may alter

or waive:or waive: (1) The research involves no more than minimal (1) The research involves no more than minimal

risk to the subjects;risk to the subjects; (2) The waiver or alteration will not adversely (2) The waiver or alteration will not adversely

affect the rights and welfare of the subjects;affect the rights and welfare of the subjects; (3) The research could not practicably be carried (3) The research could not practicably be carried

out without the waiver or alteration; andout without the waiver or alteration; and (4) Whenever appropriate the subjects will be (4) Whenever appropriate the subjects will be

provided with additional pertinent information provided with additional pertinent information after participation.after participation.

§46.111 (d)§46.111 (d)

Informed participation:Informed participation:

Clear statements by the health care institution Clear statements by the health care institution about QI—obligation to participate in minimal about QI—obligation to participate in minimal risk QI projects for the immediate benefit to risk QI projects for the immediate benefit to some patients and the long-term benefits for some patients and the long-term benefits for all;all;

Oversight structure for QI—review before;Oversight structure for QI—review before; Structure for accountability—implementation Structure for accountability—implementation

of positive findings after data are collected and of positive findings after data are collected and analyzed;analyzed;

Feedback and Information for Feedback and Information for patients/participants.patients/participants.

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

Research Both Research and QI Quality Improvement

IRB submission

Informed consent

QI project registration

Informed participation

Liability issues

Legal Affairs

Draft

“Investigator” elects to not

proceed

EXAMPLE: Registration EXAMPLE: Registration FormForm

Conclusion:Conclusion:

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

Quality Quality Improvement Improvement

Research: Ethical Research: Ethical

ConsiderationsConsiderations Harlan M. Krumholz Harlan M. Krumholz

MD MD Yale School of Medicine Yale School of Medicine

New Haven, CTNew Haven, CTOctober 23, 2008

Out of the ashes of Nuremberg…

Margaret Bourke-White

…rose a trial with particular relevance to medical research.

…rose a trial with particular relevance to medical research.

Nuremberg Code is the articulation of our ethical obligations to study subjects.

The voluntary consent of the

human subject is absolutely essential.

Having principles isn’t enough…

There There was this was this simple simple idea…idea…

Gawande, The Gawande, The New Yorker, New Yorker, 12/10/200712/10/2007

InterventionIntervention

1. Wash their hands with soap.1. Wash their hands with soap.

2. Clean the patient’s skin with chlorhexidine.2. Clean the patient’s skin with chlorhexidine.

3. Put sterile drapes over the entire patient.3. Put sterile drapes over the entire patient.

4. Wear a sterile mask, hat, gown and gloves.4. Wear a sterile mask, hat, gown and gloves.

5. Put a sterile dressing over the catheter site.5. Put a sterile dressing over the catheter site.

Grant Number: Grant Number: 5UC1HS014246-025UC1HS014246-02

Project Title: Statewide Efforts Project Title: Statewide Efforts to Improve Care in Intensive to Improve Care in Intensive

Care UnitCare Unit

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

Statewide Efforts to Statewide Efforts to Improve Care in Improve Care in

Intensive Care UnitIntensive Care Unit To accomplish this, we will partner To accomplish this, we will partner

with the Michigan Hospital with the Michigan Hospital Association, whose has over 130 Association, whose has over 130 Michigan hospitals, to implement a Michigan hospitals, to implement a safety program and other safety program and other interventions in a cohort of interventions in a cohort of hospitals. hospitals.

Statewide Efforts to Statewide Efforts to Improve Care in Improve Care in

Intensive Care UnitIntensive Care UnitSpecific aims are to implement and Specific aims are to implement and

evaluate: evaluate: impact of the Comprehensive Unit-impact of the Comprehensive Unit-

based Safety Program that includes based Safety Program that includes the ICU Safety Reporting System; the ICU Safety Reporting System;

effect of an intervention to improve effect of an intervention to improve communication and staffing in ICUs; communication and staffing in ICUs;

Statewide Efforts to Statewide Efforts to Improve Care in Improve Care in

Intensive Care UnitIntensive Care Unit effect of an intervention to effect of an intervention to

reduce/eliminate catheter related reduce/eliminate catheter related blood stream infections; blood stream infections;

effect of an intervention to improve effect of an intervention to improve the care of ventilated patients; and the care of ventilated patients; and

effect of an intervention to reduce effect of an intervention to reduce mortality. mortality.

The results were The results were published in NEJMpublished in NEJM

And the results were very And the results were very good.good.

TimelineTimeline

Pronovost became a Pronovost became a celebrity.celebrity.

What What was the was the ethical ethical obligatiobligati

on?on?

QuestioQuestions were ns were raised raised

by by OHRP.OHRP.

OHRP OHRP sends sends

another another letter in letter in July ‘08.July ‘08.

They clarified what was being done.

What determines what What determines what we need we need

to do to protect subjects?to do to protect subjects?intent (mens rea)intent (mens rea)intervention?intervention?rigor?rigor?publication?publication?funding?funding?timing?timing?safety?safety?feasibility?feasibility?

ExemptionExemption

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

ExemptionExemption

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

Miller and Emanuel NEJM

Treatment of STEMITreatment of STEMI

Primary PCI for STEMI is Primary PCI for STEMI is a a

remarkable intervention.remarkable intervention.

The D2B standard in 1999The D2B standard in 1999was 90 was 90 ± 30 minutes± 30 minutes

Around the turn of the Around the turn of the century,century,

performance was stable.performance was stable.0

20

40

60

80

100

120

Door-

to-b

alloon tim

e (

min

ute

s)

Jan 99 Jul 00 Jan 02 Jul 03Month

020

40

60

80

100

120

Door-

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min

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Jan 99 Jul 00 Jan 02 Jul 03Month

Several key strategies were Several key strategies were identified.identified.

D2B AllianceD2B Alliance is a vehicle to is a vehicle to disseminate knowledge and disseminate knowledge and

promote improvement.promote improvement.

www.d2balliance.org

More than 1,000 hospitalsMore than 1,000 hospitalsjoined the effort.joined the effort.

87

The use of strategies changedThe use of strategies changedin in D2B AllianceD2B Alliance hospitals hospitals

Recommended Strategy*Recommended Strategy*BaselineBaseline Follow-upFollow-up

EM activationEM activation 52%52% 60%60%Single callSingle call 31%31% 37%37%Cath team < 30 minCath team < 30 min 81%81% 89%89%Prompt data feedbackPrompt data feedback 61%61% 79%79%Activate from PH ECGActivate from PH ECG 33%33% 41%41%D2B TeamD2B Team 64%64% 85%85%

* All differences are significant P* All differences are significant P<< 0.001 0.001

NCDR Cath PCI RegistryNCDR Cath PCI Registry% < 90 minutes % < 90 minutes

Was shortening LOS for patients Was shortening LOS for patients after CABG an intervention?after CABG an intervention?

What is What is researcresearc

h?h?

What is human research?What is human research?

A systematic investigation designed A systematic investigation designed to develop or contribute to to develop or contribute to generalizable knowledgegeneralizable knowledge Data through interaction or Data through interaction or

intervention with the individual, orintervention with the individual, or Identifiable private informationIdentifiable private information

What is quality What is quality improvement?improvement?

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

Is QI without Is QI without evaluation (research) evaluation (research)

ethical?ethical?

Baily: Organizational Baily: Organizational research not human research not human

subjects researchsubjects research

Improving Improving the the

effectiveneseffectiveness of care is s of care is part of the part of the research research agenda.agenda.

Is it about language?Is it about language?