QI vs Research: Where do we draw the line

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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

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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 researchers perspective on both
  conducting QI and research

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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

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Audience

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

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Continuum
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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

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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

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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

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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/Pronovos
  t20080730.html

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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

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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

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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

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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)

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Belmont Principles

• Respect for Persons
• Autonomy, therefore voluntariness requirement
• Informed consent for research participation
• Beneficence
• RiskBenefit analysis
• Justice
• Fair distribution of burdens and benefits

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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
  dont 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)

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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

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Workgroup

• Email ysmhic_at_yale.edu
• Or sandra.alfano_at_yale.edu

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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

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Quality Improvement and ResearchThe permeable
barrier

• Bellin E, Dubler NN, The Quality
  ImprovementResearch 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

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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.

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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

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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

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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 patients health status

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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.

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Ethical JustificationResearch

• 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 participationmost conclude do not
• Therefore, potential human subjects in research
  are morally free to consent to or to refuse
  participation .

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Ethical JustificationQuality 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

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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

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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,
  evaluaterepeatimplement
• 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

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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

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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.

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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 participationmost conclude do not.

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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

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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

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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)

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Informed participation

• Clear statements by the health care institution
  about QIobligation to participate in minimal
  risk QI projects for the immediate benefit to
  some patients and the long-term benefits for all
• Oversight structure for QIreview before
• Structure for accountabilityimplementation of
  positive findings after data are collected and
  analyzed
• Feedback and Information for patients/participants
  .

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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
Research
Both Research and QI
Quality Improvement
Investigator elects to not proceed
IRB submission
Informed consent
QI project registration
Informed participation
Draft
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EXAMPLE Registration Form
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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.

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Quality Improvement Research Ethical
Considerations Harlan M. Krumholz MD Yale
School of Medicine New Haven, CT
October 23, 2008
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Out of the ashes of Nuremberg
Margaret Bourke-White
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rose a trial with particular relevance to
medical research.
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rose a trial with particular relevance to
medical research.
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Nuremberg Code is the articulation of our ethical
obligations to study subjects.
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The voluntary consent of the human subject is
absolutely essential.
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Having principles isnt enough
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There was this simple ideaGawande, The New
Yorker, 12/10/2007
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Intervention

• 1. Wash their hands with soap.
• 2. Clean the patients 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.

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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.

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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.
  

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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

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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.

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The results were published in NEJM
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And the results were very good.
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Timeline
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Pronovost became a celebrity.
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What was the ethical obligation?
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Questions were raised by OHRP.
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OHRP sends another letter in July 08.
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They clarified what was being done.
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What determines what we need to do to protect
subjects?

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

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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."

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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
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Treatment of STEMI
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Primary PCI for STEMI is a remarkable
intervention.
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The D2B standard in 1999was 90 30 minutes
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Around the turn of the century,performance was
stable.
84
Several key strategies were identified.
85
D2B Alliance is a vehicle to disseminate
knowledge and promote improvement.
www.d2balliance.org
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More than 1,000 hospitalsjoined the effort.
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The use of strategies changedin D2B Alliance
hospitals

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

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NCDR Cath PCI Registry lt 90 minutes
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Was shortening LOS for patients after CABG an
intervention?
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What is research?
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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

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What is quality improvement?

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

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Is QI without evaluation (research) ethical?
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Baily Organizational research not human subjects
research
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Improving the effectiveness of care is part of
the research agenda.
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Is it about language?