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
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
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
Audience

Researchers and research personnel
Quality improvement personnel
IRB staff, regulatory perspective

Some that do a little of both


Continuum
Pronovost/OHRP/JHU Case
Timeline

NEJM Publication




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Prompts OHRP compliance investigation

March 30, 2007

July 19, 2007

September 25, 2007
Insists study was exempt
OHRP responds to JHU


Allegations of lack of prior IRB review,
and lack of informed consent on the
part of the patients
JHU responds to OHRP

December 28, 2006
Dramatic effective results to decrease
infection rate
Letter of complaint to OHRP


Asks for corrective actions
JHU responds that PI has suspended
all activities
Timeline continued

OHRP to JHU

November 6, 2007

Atul Gawande, NY
Times

December 30, 2007

January 15, 2008


“A Lifesaving Checklist”
OHRP listserve response

Clarifies that JHU
suspended study, not
OHRP
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
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
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

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
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
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)

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
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
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
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
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
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
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
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
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
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
Publication/dissemination of results



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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)
Conclusions



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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
Workgroup

Email ysmhic@yale.edu

Or sandra.alfano@yale.edu
A Process of Quality Improvement:
Informed Participation and
Institutional Process
Yale University
October 23, 2008
Nancy Neveloff Dubler
Senior Associate
Montefiore-Einstein Center for Bioethics
Montefiore Medical Center
Professor Emerita
The Albert Einstein College of Medicine
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

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
Quality Improvement

“The group defined QI as the systematic, dataguided 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]
Disease Management

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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
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
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.
Ethical Justification:
Research



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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 .
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]
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
Elements of QI



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

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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
Similarities Between QI and
Research




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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
Ethical Requirements for
Protection of Human Participants
in QI Activities:
Social or scientific value of the individual QI project;

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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.
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.
Moral Imperative for Patients,
Providers and Institutions
Three moral imperatives:
1. Medical professionals must conduct QI;
[do no harm]
2. Individual health care organizations must support QI;
[obligation from moral agency]
3. Active patients must participate in QI.
[Responsibilities from possible immediate benefit to self
and responsibilities from benefits to others]
Ethical Protections for
Patient/Participants in QI

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Social or scientific value
Scientific validity
Fair participant selection
Favorable risk-benefit ratio: minimal risk
Respect for participants
Informed consent/informed participation
Independent review
Provisions in research for altering or waiving
the requirement of Informed Consent:
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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)
Informed participation:
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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.
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
IRB
submission
Both Research and QI
Informed
consent
Quality Improvement
QI project
registration
Informed
participation
EXAMPLE: Registration Form
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.
Quality Improvement
Research: Ethical
Considerations
Harlan M. Krumholz MD
Yale School of Medicine
New Haven, CT
October 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 was
this simple
idea…
Gawande, The New
Yorker, 12/10/2007
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.
Grant Number: 5UC1HS014246-02
Project 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.
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.
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;
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.
The results were published in
NEJM
And the results were very good.
Timeline
Pronovost became a celebrity.
What was
the ethical
obligation?
Questions
were
raised by
OHRP.
OHRP
sends
another
letter in
July ‘08.
They
clarified
what was
being done.
What determines what we need
to do to protect subjects?
intent (mens rea)
intervention?
rigor?
publication?
funding?
timing?
safety?
feasibility?
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."
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
Treatment of STEMI
Primary PCI for STEMI is a
remarkable intervention.
The D2B standard in 1999
was 90 ± 30 minutes
0
20
40
60
80
100
120
Around the turn of the century,
performance was stable.
Jan 99
Jul 00
Jan 02
Month
Jul 03
Several key strategies were identified.
D2B Alliance is a vehicle to disseminate
knowledge and promote improvement.
www.d2balliance.org
More than 1,000 hospitals
joined the effort.
The use of strategies changed
in D2B Alliance hospitals
Recommended Strategy*
Baseline
Follow-up
EM activation
Single call
Cath team < 30 min
Prompt data feedback
Activate from PH ECG
D2B Team
52%
31%
81%
61%
33%
64%
60%
37%
89%
79%
41%
85%
* All differences are significant P< 0.001
87
NCDR Cath PCI Registry
% < 90 minutes
Was shortening LOS for patients after CABG
an intervention?
What is
research?
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

What is quality improvement?

Systematic, data-guided activities designed to
bring about immediate improvements in health
care delivery in a particular setting
Is QI without
evaluation (research) ethical?
Baily: Organizational research not
human subjects research
Improving the
effectiveness of
care is part of
the research
agenda.
Is it about language?