Implications of the Implications of the Privacy Rule for Privacy Rule for Trialists Trialists and Academic Researchand Academic Research

Robert M Robert M CaliffCaliff MDMD

Vice Chancellor for Clinical ResearchVice Chancellor for Clinical Research

Duke University Medical CenterDuke University Medical Center

HIPAA Privacy Rule HIPAA Privacy Rule

Because of the paralyzing effect of the Because of the paralyzing effect of the interpretation of HIPAA (and other associated interpretation of HIPAA (and other associated regulatory issues) it is likely that thousands to regulatory issues) it is likely that thousands to tens of thousands of Americans are dying or tens of thousands of Americans are dying or becoming disabled needlesslybecoming disabled needlessly

But, that’s just my opinion and I can’t prove it!But, that’s just my opinion and I can’t prove it!

“Academic”“Academic”

�� Of theoretical interest but of no practical Of theoretical interest but of no practical importanceimportance

�� Pertaining to an effort to understand Pertaining to an effort to understand

Implications of HIPAA Privacy RuleImplications of HIPAA Privacy Rule�� Current issuesCurrent issues

Finding research subjectsFinding research subjects

Getting consent appropriatelyGetting consent appropriately

Following research subjects over timeFollowing research subjects over time

Finding lost research subjectsFinding lost research subjects

�� The futureThe future

We are creating an aura around clinical research which is We are creating an aura around clinical research which is demoralizing, expensive and out of touch with modern demoralizing, expensive and out of touch with modern views of the integration of clinical research and clinical views of the integration of clinical research and clinical practicepractice

This aura is contributing to the exodus of clinical research This aura is contributing to the exodus of clinical research from the US and likely to the continued decline of US from the US and likely to the continued decline of US health outcomes relative to the rest of the worldhealth outcomes relative to the rest of the world

“I skate to where the puck is going to be, not to where it has been.”

Wayne Gretsky(the Puck Stops Here!)

“I skate to where the puck is going to be, not to where it has been.”

Wayne Gretsky(the Puck Stops Here!)

Current SituationCurrent Situation——Clinical Investigators Clinical Investigators DemoralizedDemoralized

�� 5.5% annual decrease in US investigators filing 5.5% annual decrease in US investigators filing 1572 form with FDA 1572 form with FDA

�� At same time growth occurring elsewhereAt same time growth occurring elsewhere

Central and Eastern Europe 16% annual increaseCentral and Eastern Europe 16% annual increase

Asia 45% annual increaseAsia 45% annual increase

Ken GetzKen Getz

Applied Clinical Trials 9/2007Applied Clinical Trials 9/2007

Demoralization of Clinical Researchers in the USDemoralization of Clinical Researchers in the US

"The regulatory climate has become so "The regulatory climate has become so oppressive in the recent past that two out of oppressive in the recent past that two out of three principal investigators who have worked three principal investigators who have worked with us for 20with us for 20--some years said they don't want some years said they don't want the responsibility anymore," warned the responsibility anymore," warned MaloyMaloy. . "They don't have time for it. They're busy "They don't have time for it. They're busy seeing patients in their practice." seeing patients in their practice."

Ken GetzKen GetzApplied Clinical Trials 9.2007Applied Clinical Trials 9.2007

Current SituationCurrent Situation——US Losing its Leadership RoleUS Losing its Leadership Role

�� Turnover rates doubled between 1990 and 2000Turnover rates doubled between 1990 and 2000

�� Half of first time researchers will not participate Half of first time researchers will not participate againagain

�� Women only 12% of researchers filing 1572s Women only 12% of researchers filing 1572s

�� GCP violations increased multiple foldGCP violations increased multiple fold

Ken Getz

ACT 9.2007

Current SituationCurrent Situation——More Difficult to Screen for More Difficult to Screen for PatientsPatients

�� Global Stroke TrialGlobal Stroke Trial

All European sites provided detailed screening logs All European sites provided detailed screening logs so that generalizability of study could be determinedso that generalizability of study could be determined

Only 5 of 15 US sites provided data and these data Only 5 of 15 US sites provided data and these data were incompletewere incomplete

KompanjeKompanje and Maas, Critical Care Med 2006and Maas, Critical Care Med 2006

Current SituationCurrent Situation——Skewed Access to PopulationsSkewed Access to Populations

�� Unstable angina registry that spanned privacy Unstable angina registry that spanned privacy rule implementationrule implementation

Consenting subjects: older, whiter, more marriedConsenting subjects: older, whiter, more married

DramticallyDramtically lower mortality in consenting subjectslower mortality in consenting subjects

Armstrong, Arch Armstrong, Arch IntInt Med, 2006Med, 2006

�� Stroke registryStroke registry

36% of subjects participated with passive effort and 36% of subjects participated with passive effort and just over 50% with $500k active effortjust over 50% with $500k active effort

Biased sample with lower mortality and disabilityBiased sample with lower mortality and disability

Clinical Trials ExampleClinical Trials Example

�� Industry sponsored international Industry sponsored international megatrialsmegatrials

�� Up to 4% of people lost to Up to 4% of people lost to followupfollowup at the end at the end of studyof study

�� This can swing the result of a trial (This can swing the result of a trial (espesp in in common chronic diseases)common chronic diseases)

�� What can be done to find patients?What can be done to find patients?

What if they “withdrew consent”?What if they “withdrew consent”?

What if they have died?What if they have died?

BureaucracyBureaucracy

�� The only thing that saves us from the bureaucracy is The only thing that saves us from the bureaucracy is inefficiency. An efficient bureaucracy is the greatest threat inefficiency. An efficient bureaucracy is the greatest threat to libertyto liberty

Eugene McCarthyEugene McCarthy (1916 (1916 -- ), ), Time magazine, Feb. 12, Time magazine, Feb. 12, 19791979

�� Bureaucracy defends the status quo long past the time Bureaucracy defends the status quo long past the time when the quo has lost its statuswhen the quo has lost its status

Laurence J. PeterLaurence J. Peter (1919 (1919 -- 1988) 1988)

�� Any sufficiently advanced bureaucracy is indistinguishable Any sufficiently advanced bureaucracy is indistinguishable from molasses. from molasses.

—— UnknownUnknown

GeneralizabilityGeneralizability

ValidityValidity

GoalGoal

XX

Life Expectancy Around the WorldLife Expectancy Around the World

Country Country Life expectancyLife expectancy

MenMen WomenWomen

AngolaAngola 37.937.9 42.042.0

CambodiaCambodia 51.951.9 57.157.1

ChinaChina 69.669.6 72.772.7

USUS 74.674.6 79.879.8

CubaCuba 75.075.0 79.379.3

UKUK 75.875.8 80.580.5

CanadaCanada 77.277.2 82.382.3

JapanJapan 78.478.4 85.385.3

The Cycle of Quality: Generating Evidence to The Cycle of Quality: Generating Evidence to Inform PolicyInform Policy

Califf RM et al, Califf RM et al, Health Affairs, 2007Health Affairs, 2007

Measurement and

Education

Measurement Measurement

andand

EducationEducation

Early Translational

Steps

Early Translational

Steps

ClinicalTrials

ClinicalTrials

ClinicalPractice

Guidelines

ClinicalPractice

Guidelines

PerformanceMeasures

PerformanceMeasures

OutcomesOutcomes

Discovery ScienceDiscovery Science

DataStandards

DataData

StandardsStandardsNetwork

Information

NetworkNetwork

InformationInformation

EmpiricalEthics

EmpiricalEmpirical

EthicsEthics

Prioritiesand Processes

PrioritiesPriorities

and Processesand Processes

InclusivenessInclusivenessInclusiveness

Use forFeedback

on Priorities

Use forUse for

FeedbackFeedback

on Prioritieson Priorities

Conflict-of-interestManagement

ConflictConflict--ofof--interestinterest

ManagementManagementEvaluation of Speed

and Fluency

Evaluation of SpeedEvaluation of Speed

and Fluencyand Fluency

Pay forPerformance

Pay forPay for

PerformancePerformance

Transparencyto Consumers

TransparencyTransparency

to Consumersto Consumers

FDACritical Path

FDAFDA

Critical PathCritical Path

NIH RoadmapNIH RoadmapNIH Roadmap1

2 3

4

5

6

7

8

910

11

12

Goals for CRUSADE: Goals for CRUSADE: Improve Adherence to ACC/AHA Guidelines forImprove Adherence to ACC/AHA Guidelines forPatients with Unstable Angina/NonPatients with Unstable Angina/Non--STEMISTEMI

�� AspirinAspirin

ClopidogrelClopidogrel

�� Beta BlockerBeta Blocker

�� Heparin (Heparin (UFH or LMWHUFH or LMWH))

�� GP IIbGP IIb--IIIa InhibitorIIIa Inhibitor

All receiving All receiving cathcath/PCI/PCI

�� AspirinAspirin

�� ClopidogrelClopidogrel

�� Beta BlockerBeta Blocker

�� ACE Inhibitor ACE Inhibitor

�� StatinStatin/Lipid Lowering/Lipid Lowering

�� Smoking CessationSmoking Cessation

�� Cardiac RehabilitationCardiac Rehabilitation

Acute TherapiesAcute TherapiesAcute Therapies Discharge TherapiesDischarge TherapiesDischarge Therapies

Circulation, JACC 2002 - ACC/AHA Guidelines updateCirculation, JACC 2002 Circulation, JACC 2002 -- ACC/AHA Guidelines updateACC/AHA Guidelines update

Evaluating the Process of Care• An adherence score is applied to each patient. incorporating the components of process of care.• The score from each patient then combined for all patients at each hospital. Typical scores ranged from 50 to 95%.• All 400 hospital adherence scores then ranked in quartiles - best to worst.

Evaluating the Process of Care• An adherence score is applied to each patient. incorporating the components of process of care.• The score from each patient then combined for all patients at each hospital. Typical scores ranged from 50 to 95%.• All 400 hospital adherence scores then ranked in quartiles - best to worst.

Overall Adherence Score Trends Over Overall Adherence Score Trends Over TimeTime

68.1%

69.6%

71.0%

72.3%73.0%

73.6%

75.2%

77.9% 78.0%

79.3%

60%

70%

80%

Q1 '02 Q4 '02 Q3 '03 Q2 '04

Link Between Overall ACC/AHA Guidelines Adherence and MortalityLink Between Overall ACC/AHA Link Between Overall ACC/AHA Guidelines Adherence and MortalityGuidelines Adherence and Mortality

Peterson et al, ACC 2004Peterson et al, ACC 2004

5.95

5.16 4.97

4.16

5.074.63

4.17

6.33

0

1

2

3

4

5

6

7

<=25% 25 - 50% 50 - 75% >=75%

Hospital Composite Quality Quartiles

% I

n-H

osp

Mo

rtali

ty

Adjusted Unadjusted

5.95

5.16 4.97

4.16

5.074.63

4.17

6.33

0

1

2

3

4

5

6

7

<=25% 25 - 50% 50 - 75% >=75%

Hospital Composite Quality Quartiles

% I

n-H

osp

Mo

rtali

ty

Adjusted Unadjusted

Every 10% Every 10% ↑↑↑↑↑↑↑↑ in guidelines adherence in guidelines adherence →→→→→→→→ 11% 11% ↓↓↓↓↓↓↓↓ in in

mortalitymortality

STS: National Randomized Trial in STS: National Randomized Trial in Quality Improvement in Bypass Quality Improvement in Bypass SurgerySurgery

�� The Society of Thoracic SurgeonsThe Society of Thoracic Surgeons

T. Bruce Ferguson Jr. PI; Mary T. Bruce Ferguson Jr. PI; Mary EikenEiken, RN, MS; Meghan , RN, MS; Meghan Carey, MS; Fred L. Grover, MD; Carey, MS; Fred L. Grover, MD;

�� The Duke Clinical Research InstituteThe Duke Clinical Research Institute

Eric D. Peterson, MD, MPH, CoEric D. Peterson, MD, MPH, Co--PI; Elizabeth R. DeLong, PI; Elizabeth R. DeLong, PhD; Laura P. Coombs, PhD; PhD; Laura P. Coombs, PhD;

�� The Quality Assurance FoundationsThe Quality Assurance Foundations: Iowa, Colorado : Iowa, Colorado Minnesota, AlabamaMinnesota, Alabama

�� Supported by AHRQ ROSupported by AHRQ RO--1 HS 104031 HS 10403

RandomizationRandomization

All Sites

N=399

Intervention #2:

IMA Use in

Elderly

N=120

Intervention #1:

Preop ß-blockade

N=124

Control:

No Intervention

N=115

Regional QI:

Both Interventions

N=40

Science and Technology

Science and Technology

Improved Outcomes

Improved Outcomes

Common database

Common database

OutcomesOutcomes

GapsGaps

Trials and Outcomes ProjectsTrials and Outcomes ProjectsTrials and Outcomes Projects

Society of Thoracic Surgeons ModelSociety of Thoracic Surgeons Model

Educationand

Feedback

EducationEducation

andand

FeedbackFeedback

National Consortium For

Clinical Databases (NC2D)

National Consortium For

Clinical Databases (NC2D)

Applicability of HIPAA and the Common Rule Applicability of HIPAA and the Common Rule

to the STS Databasesto the STS Databases

Data to link to for QI purposes

Data to link to for QI purposes

Data to link to for research purposes

Data to link to for research purposes

NOT RESEARCHNOT RESEARCH

HUMAN SUBJECTS

RESEARCH

HUMAN SUBJECTS

RESEARCHNOT HUMAN

SUBJECTS RESEARCH

NOT HUMAN

SUBJECTS RESEARCH

STS Data w/ direct patient identifiers used for QI

STS Data w/ direct patient identifiers used for QI

STS Data w/ direct patient identifiers forms a research

repository

STS Data w/ direct patient identifiers forms a research

repository

Data with identifiers used for specific research study

Data with identifiers used for specific research study

Common Rule: Waiver of consentHIPPA: Waiver of authorizationApproach IRB with research repository protocol

Common Rule: Waiver of consentHIPPA: Waiver of authorizationApproach IRB with research repository protocol

Common Rule: NAHIPPA: BA agreement in placeNo need to approach IRB

Common Rule: NAHIPPA: BA agreement in placeNo need to approach IRB

Common Rule: Waiver of consentHIPPA: Waiver of authorizationApproach IRB with new study protocol

Common Rule: Waiver of consentHIPPA: Waiver of authorizationApproach IRB with new study protocol

Common Rule: Not human subjects researchHIPPA: Limited dataset with a data use agreementApproach IRB for declaration of “Not human subjects”

Common Rule: Not human subjects researchHIPPA: Limited dataset with a data use agreementApproach IRB for declaration of “Not human subjects”

Limited data set used for research

Limited data set used for research

Most STS analyses includingthose performed for Access & Publications will be done withthis dataset

Most STS analyses includingthose performed for Access & Publications will be done withthis dataset

‘‘--omicsomics’ Technologies Can Help Predict ’ Technologies Can Help Predict Treatment Response.Treatment Response.

ResponderResponder Adverse eventAdverse event NonNon--responderresponder

CancerCancer

Exercise + Exercise + Diet ADiet A

Exercise +Exercise +Diet BDiet B

Exercise +Exercise +Diet +Diet +

MedicationMedication

DiabetesDiabetes Genetic & Genomic ProfilingGenetic & Genomic Profiling

In 20 Years… In 20 Years… (or a bit longer)(or a bit longer)

�� All people will haveAll people will have

An electronic health recordAn electronic health record

Biological samples stored to enable personal decisionsBiological samples stored to enable personal decisions

Digitized imagesDigitized images

�� Healthcare will be personalized or “mass customized” Healthcare will be personalized or “mass customized” using an individual’s images, samples and clinical datausing an individual’s images, samples and clinical data

�� The health of a community will be monitored using The health of a community will be monitored using aggregate recordsaggregate records

�� Clinical research will use these records to create Clinical research will use these records to create “learning health care” systems“learning health care” systems

3

In 20 years… (or a bit longer)In 20 years… (or a bit longer)

�� Clinical research will be seen as a learning Clinical research will be seen as a learning system built into health care deliverysystem built into health care delivery

�� Electronic health records will provide Electronic health records will provide inexpensive characterization and inexpensive characterization and followupfollowup

�� Disease specific registries will proved the deep Disease specific registries will proved the deep and more precise data needed for detailed and more precise data needed for detailed mechanistic and specialty based studies mechanistic and specialty based studies

�� Randomization will be seen as an important Randomization will be seen as an important tool inserted where appropriate into these tool inserted where appropriate into these ongoing data streamsongoing data streams

Competing Views of Globalization of Competing Views of Globalization of Clinical ResearchClinical Research

Networks of clinician Networks of clinician investigators linked by investigators linked by common interest in common interest in health, disease, health, disease, prevention, diagnostics prevention, diagnostics and therapeuticsand therapeutics

Research embedded into Research embedded into clinical practice to gain clinical practice to gain both validity and both validity and generalizabilitygeneralizability

Open to studies of high Open to studies of high quality regardless of quality regardless of source of fundingsource of funding

Multinational corporations Multinational corporations hiring investigators at the hiring investigators at the lowest cost to “work for lowest cost to “work for them” doing clinical trialsthem” doing clinical trials

Research separated from Research separated from clinical practice as much clinical practice as much as possible as possible

Separate government Separate government funded organizations to funded organizations to do evaluative studies and do evaluative studies and epidemiology using tax epidemiology using tax moneymoney

Clinical and Translational Science AwardsClinical and Translational Science Awards

Integration of Clinical Integration of Clinical Research NetworksResearch Networks

�� Link existing networks so Link existing networks so clinical studies and trials can clinical studies and trials can be conducted more effectivelybe conducted more effectively

�� Ensure that patients, Ensure that patients, physicians, and scientists physicians, and scientists form true “Communities of form true “Communities of Research”Research”

FDA PPP on Safe and Effective Clinical TrialsFDA PPP on Safe and Effective Clinical Trials

�� First meeting on October 11First meeting on October 11thth

�� Hope to raise funding to develop empirical Hope to raise funding to develop empirical base for FDA guidance on regulations for base for FDA guidance on regulations for clinical trialsclinical trials

�� Key playersKey players

FDA, industry, academia, patient advocates, nonFDA, industry, academia, patient advocates, non--academic clinical research professionalsacademic clinical research professionals