Comparative Effectiveness Research Shalini Kulasingam, PhD University of Minnesota

Comparative Comparative Effectiveness Effectiveness

ResearchResearch

Shalini Kulasingam, PhDShalini Kulasingam, PhD

University of MinnesotaUniversity of Minnesota

OverviewOverview Learning objectivesLearning objectives Background: why do we need a “special type” of Background: why do we need a “special type” of

research agenda?research agenda? Definition: comparative effectiveness researchDefinition: comparative effectiveness research What areas/conditions have been prioritized for What areas/conditions have been prioritized for

study?study? Role of nursing?Role of nursing? Methods for conducting comparative effectiveness Methods for conducting comparative effectiveness

researchresearch ExamplesExamples

RCTsRCTs Observational studiesObservational studies Simulation modelingSimulation modeling

FundingFunding

Learning ObjectivesLearning Objectives

Why there is a need for CER?Why there is a need for CER? Priority CER topicsPriority CER topics Study designs for conducting CERStudy designs for conducting CER Examples of CER studies Examples of CER studies

BackgroundBackground

Health care expenditures were $2.4 trillion in 2008 and are projected to grow by an average of 6.2 percent per year for the next 10 years, more than triple the projected rate of overall gross domestic product (GDP) growth (Sisko et al., 2009)

The Congressional Budget Office (CBO) projects that under current law, health care will consume more than 30 percent of GDP by 2035 (CBO, 2008).

IOM report, 2009


Regional variations in treatment patterns and cost growth provide deeper insight into the need for more informed medical decision making. Patients in the highest-spending regions

of the country receive 60 percent more health services than those in the lowest-spending regions, yet this additional care is not associated with improved outcomes (Fisher et al., 2003).

BackgroundBackground RResearch suggests that physicians inhigher-spending areas are more likely than

physicians inother regions to recommend costly interventions thathave not been definitively shown to be effective

(Fisher etal., 2009).

Nationwide, the Institute of Medicine (IOM) hasestimated that less than half of all treatments

deliveredtoday are supported by evidence (IOM, 2007).


A recent review of practice guidelines developed by the American College of Cardiology and the American Heart Association found that relatively few recommendations were based on high-quality evidence—randomized controlled trials, for instance—and many were based solely on expert opinion, individual case studies, or standard of care (Tricoci et al., 2009).

What is comparative What is comparative effectiveness research?effectiveness research?

Comparative effectiveness research (CER) is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care. The purpose of CER is to assist consumers, clinicians, purchasers, and policy makers to make informed decisions that will improvehealth care at both the individual and population levels.

CER Summary and CER Summary and Investment in ResearchInvestment in Research

How good is the How good is the intervention/treatment/test?intervention/treatment/test?

In what patients?In what patients? Under what circumstances?Under what circumstances? American Recovery and Reinvestment American Recovery and Reinvestment

Act of 2009Act of 2009 $1.1 billion “down payment” to support CER$1.1 billion “down payment” to support CER $400 million given to the NIH$400 million given to the NIH $300 million given to the AHRQ$300 million given to the AHRQ $400 million to Health and Human Services$400 million to Health and Human Services

What are the priority areas What are the priority areas for research?for research?

The American Recovery and Reinvestment Act of 2009 called on the Institute of Medicine to recommend a list of priority topics to be the initial focus of a new national investment in comparative effectiveness research. The IOM’s recommendations are contained in the report, Initial National Priorities for Comparative Effectiveness Research.


Treatment strategies for atrial fibrillation Treatment for hearing loss Primary prevention versus clinical

treatments in preventing falls in older adults

Biologics for inflammatory diseases Upper endoscopy for patients with

gastroesophageal reflux disease Dissemination and translation of

techniques for use of CER by cliniciansIOM, 2009


Comprehensive care programs for people with chronic disease

Interventions for MRSA Strategies to reduce health care

associated infections Management of prostate cancer Registry for lower back pain Detection and management of

dementia in a community settingIOM, 2009


Management of behavioral disorders associated with dementia

School-based interventions for treating obesity in children

Interventions to reduce hypertension, obesity etc. in urban poor and Native American populations

Management strategies for ductal carcinoma in-situ

Use of imaging technologies for cancer Genetic and biomarkers for cancerIOM, 2009


Prevention of dental caries in childrenPrevention of dental caries in children Treatment strategies for children with ADHDTreatment strategies for children with ADHD Management of serious emotional conditions Management of serious emotional conditions

in children and adultsin children and adults Interventions to reduce health disparitiesInterventions to reduce health disparities Literacy sensitive disease managementLiteracy sensitive disease management Interventions to reduce adverse birth Interventions to reduce adverse birth

outcomes in women especially African outcomes in women especially African American womenAmerican women

Prevention of unintended pregnanciesPrevention of unintended pregnanciesIOM, 2009

Role of NursingRole of Nursing Statement by MaryJean Schumann, Chief Statement by MaryJean Schumann, Chief

Program Officer, ANA, 2009Program Officer, ANA, 2009Perspective is based on two types of nurses the registered nurse providing direct care the advanced practice registered nurse

Certified Registered Nurse-Anesthetists (CRNAs) who provide critical anesthesia services;

Clinical Nurse Specialists (CNSs) who provide acute care expertise for complex patients;

Certified Nurse-Midwives (CNMs) who provide health care to women across the lifespan;

Nurse Practitioners (NPs) who deliver a wide range of primary care services.

Role of NursingRole of Nursing

“Nursing’s holistic view – attention to the whole person – makes nurses particularly effective in advancing these priorities. Nurses, with their expertise in health promotion, disease prevention, and health literacy, can contribute to changing the current sickness care system into a true health care system.”

MaryJean Schumann,, ANA,. 2009MaryJean Schumann,, ANA,. 2009

Setting priorities based on Setting priorities based on ANA- related work and dataANA- related work and data

National Quality Forum National Priorities and Goals

Six Priority areas: What are the most effective tools and systems to

engage patients in their care? What are the most effective models for care

coordination? How do we reduce 30-day readmission rates? How is palliative care best provided? “How do we eliminate unnecessary or risky care? “Improve health by ensuring that patients receive

the most effective preventive services recommended by the U.S. Preventive Services Task Force. “ “

MaryJean Schumann,, ANA,. 2009MaryJean Schumann,, ANA,. 2009

Setting priorities based on Setting priorities based on ANA related work and dataANA related work and data

CER priorities based on quality indicators developed by ANA

1998, ANA established the National Database of Nursing Quality Indicators® (NDNQI®), the only national database that provides nursing data and patient outcomes at the unit level where care occurs.

Data are collected on structure, process and outcome measures in approximately 1400 hospitals of all sizes, in all 50 states and the District of Columbia.

Data is collected on 17 measures, 11 of which have been endorsed by the National Quality Forum. MaryJean Schumann,, ANA,. 2009MaryJean Schumann,, ANA,. 2009

Area NOT recommended for Area NOT recommended for further researchfurther research

A Cochrane review concluded that “appropriately trained nurses can produce as high quality care as primary care doctors and achieve as good health outcomes for patients.” It was noted that the research available is limited and some may call for further comparative studies. There are, however, no other professionals who have been subjected to the depth of study that NPs and CNMs have, and we question the need to expend limited resources on additional studies comparing professional groups, though we stand ready to play a role in the design and conduct of such studies should they be deemed necessary.

MaryJean Schumann, ANA. 2009MaryJean Schumann, ANA. 2009

Study Designs for CERStudy Designs for CER

Synthesis of existing dataSynthesis of existing data Analysis of observational dataAnalysis of observational data Randomized controlled trialsRandomized controlled trials

Study DesignStudy Design

Synthesis of existing dataSynthesis of existing data Systematic reviewSystematic review Meta-analysisMeta-analysis Decision modelingDecision modeling


Observational dataObservational data Administrative claimsAdministrative claims Electronic medical recordsElectronic medical records Registries Registries Case control or cohort studiesCase control or cohort studies


Randomized controlled trialRandomized controlled trial Luce et al. Annals Internal Medicine, 2009Luce et al. Annals Internal Medicine, 2009 How to change RCTs for comparative How to change RCTs for comparative

effectiveness researcheffectiveness research Analytic and operational efficiencyAnalytic and operational efficiency

Reduce costs of running a trial, and be able to Reduce costs of running a trial, and be able to up date trials on an ongoing basis, dropping up date trials on an ongoing basis, dropping tests/drugs/interventions that are not tests/drugs/interventions that are not promisingpromising

Accomplish this using Bayesian approachesAccomplish this using Bayesian approaches Pragmatic clinical trialPragmatic clinical trial

Study DesignStudy Design Pragmatic RCTPragmatic RCT

CER objective is to provide information to help CER objective is to provide information to help patients, consumers, clinicians, and payers make patients, consumers, clinicians, and payers make informed decisions.informed decisions.

Trials tend to exclude relevant patient Trials tend to exclude relevant patient populations, commonly used comparators, long populations, commonly used comparators, long term outcomes, and non-expert providersterm outcomes, and non-expert providers

Clinically effective comparatorsClinically effective comparators Study patients with common co-morbid conditionsStudy patients with common co-morbid conditions Diverse study patientsDiverse study patients Providers from community settingsProviders from community settings Provider and patient chosen outcomesProvider and patient chosen outcomes

Potential Sequence for Potential Sequence for Identifying and Proposing Identifying and Proposing

CER CER IOM list of priority topics lists those IOM list of priority topics lists those

that are most likely to get funded that are most likely to get funded IOM report notes that systematic IOM report notes that systematic

reviews and meta-analyses provide reviews and meta-analyses provide information on areas for further information on areas for further study.study.

Question: can you use take a topic Question: can you use take a topic from the IOM priority list and from the IOM priority list and identify a study for grant purposes?identify a study for grant purposes?

Examples of CER StudiesExamples of CER Studies

Detection of dementia in a community Detection of dementia in a community settingsetting Systematic reviewSystematic review Decision modelingDecision modeling Pragmatic trialPragmatic trial

Patient fallsPatient falls Systematic reviewSystematic review Patient record reviewPatient record review Randomized controlled trial – with Randomized controlled trial – with

pragmatic aspectspragmatic aspects

Detection of Detection of dementia in a dementia in a

community settingcommunity setting

The original CMS-The original CMS-sponsored TAsponsored TA

Aim: Assess the benefits of FDG-PET Aim: Assess the benefits of FDG-PET scanning in patients with dementia, with scanning in patients with dementia, with mild cognitive impairment (MCI) and in mild cognitive impairment (MCI) and in asymptomatic patients with a family asymptomatic patients with a family history of AD, subsequent to the standard history of AD, subsequent to the standard evaluation as described in the American evaluation as described in the American Academy of Neurology (AAN) guidelines. Academy of Neurology (AAN) guidelines.

CMS requested that the AHRQ identify an CMS requested that the AHRQ identify an Evidence Practice Center to perform a Evidence Practice Center to perform a Technology Assessment (TA)Technology Assessment (TA)

Duke EPC assigned the TA in 2001Duke EPC assigned the TA in 2001

Methods of the original Methods of the original TATA

Literature reviewLiterature review Decision model to provide an Decision model to provide an

understanding of the decisional understanding of the decisional contextcontext

http://www.cms.hhs.gov/coverage/download/id64.pdfhttp://www.cms.hhs.gov/coverage/download/id64.pdf

Direct inferenceDirect inference

Test

Decreasedmortality

Delayedprogression

Indirect inference: causal Indirect inference: causal pathwaypathway

Test True +

False +False -

AdverseEvent

True -

Decreasedmortality

DelayedprogressionTreat

Model: Part 1Model: Part 1

AD, treatAD, treat

AD, no treatAD, no treat

No AD, treatNo AD, treat

No AD, treatNo AD, treat##

TrueposTrueposADAD

prevADprevADFalseposFalseposNoADNoAD

No PET/Rx No PET/Rx

FalsenegFalsenegADAD

prevADprevAD

TruenegTruenegNoADNoAD

##

No PET/NoRxNo PET/NoRx

TrueposTruepos

senssens

FalsenegFalseneg

##

ADAD

prevADprevAD

FalseposFalsepos

##

TruenegTrueneg

specspec

NoADNoAD

##

PETPET

Mild dementiaMild dementiaAD, treatAD, treat

AD, no treatAD, no treat

No AD, no treatNo AD, no treat

No AD, no treatNo AD, no treat

Test performanceTest performance

AD by AD by

clinical clinical evaluationevaluation

No AD by No AD by clinical clinical evaluationevaluation

Test +Test + True +True + False +False +

Test -Test - False -False - True -True -

Sensitivity = True +/AD

Specificity = True - /No AD

ROC curve of PET test accuracy based on the literature review

Tree results: mild Tree results: mild dementiadementia

True +True +

(%)(%)False False

++

(%)(%)

False –False –

(%)(%)True –True –

(%)(%)CorrecCorrec

tt

(%) (%)

No No PET/ PET/ RxRx

5656 4444 00 00 5656

PET/ PET/ Rx+Rx+

4949 66 77 3838 8787

No No PET/ PET/ no Rxno Rx

00 00 5656 4444 4444

Dead

ModerateDementia

Asymptomatic

MCI

MildDementia

Severe Dementia

Model: Part 2Model: Part 2

Illustrative patient Illustrative patient historyhistory

Year

Asy MCI MiD MoD SeD D1




Markov results: mild Markov results: mild dementiadementia

QALYQALY LELE SDFLESDFLE

No PET/ No PET/ RxRx

4.104.10 7.897.89 4.024.02

PET/ PET/

Rx+Rx+4.094.09 7.887.88 4.004.00

No PET/ No PET/ no Rxno Rx

4.024.02 7.827.82 3.863.86

Primary conclusionPrimary conclusion

PET could improve the overall PET could improve the overall accuracy compared to accuracy of accuracy compared to accuracy of an exam based on AAN guidelines. an exam based on AAN guidelines.

Treatment based on an AAN-Treatment based on an AAN-recommended examination leads to recommended examination leads to better health outcomes than better health outcomes than treatment based on PET results treatment based on PET results

How can this make How can this make sense?sense?

While net accuracy with PET may be better, While net accuracy with PET may be better, this is because there are many fewer false this is because there are many fewer false positives but a few more false negativespositives but a few more false negatives

Incorrectly not treating (due to a false negative Incorrectly not treating (due to a false negative result a patient misses an opportunity for a Rx result a patient misses an opportunity for a Rx benefit) is worse than incorrectly treating (the benefit) is worse than incorrectly treating (the patient unnecessarily receives medication, patient unnecessarily receives medication, however the Rx is relatively benign, may be however the Rx is relatively benign, may be beneficial even if they don’t have AD, and the beneficial even if they don’t have AD, and the personal downside is that their cognitive personal downside is that their cognitive impairment/disability is not correctly labeled)impairment/disability is not correctly labeled)

When testing is When testing is preferredpreferred

1. If a new treatment becomes 1. If a new treatment becomes available that is not only more available that is not only more effective than AChEIs but is also effective than AChEIs but is also associated with a risk of severe associated with a risk of severe adverse effects. adverse effects.


2.If testing could be demonstrated to 2.If testing could be demonstrated to be a better reference standard than be a better reference standard than an examination based on AAN an examination based on AAN guidelines. (i.e., testing would need guidelines. (i.e., testing would need to better distinguish patients who to better distinguish patients who respond to therapy than is possible respond to therapy than is possible with a standard examination.) with a standard examination.)


3.If the results have demonstrable 3.If the results have demonstrable benefits beyond informing AChEI benefits beyond informing AChEI use. use. This “value of knowing” could have This “value of knowing” could have

both positive and negative components.both positive and negative components.

A research agenda in A research agenda in service to decision-service to decision-

makingmakingDesigns:Designs: Minimize biasMinimize bias Maximize generalizabilityMaximize generalizability Why not a trial?Why not a trial?

In particular, why not a pragmatic clinical In particular, why not a pragmatic clinical trial?trial?

Kulasingam et al. Am J Alzheimers Dis Other Demen. 2006

Design of a pragmatic Design of a pragmatic clinical trialclinical trial

Matched Communities

R

PET reimbursed

PET not reimbursed

Medicare claims (primary outcome = resource use from index date to 3 months)

Patients identified,

1 page evaluation completed*

* Medicare claims at the community-level for individuals with relevant ICD codes will be examined (see Methods)


DesignDesign: A demonstration project in which matched : A demonstration project in which matched communities are randomly assigned to have FDG-PET communities are randomly assigned to have FDG-PET reimbursed by Medicare or not.reimbursed by Medicare or not.

AllocationAllocation: Communities are allocated to intervention : Communities are allocated to intervention or control by concealed randomization.or control by concealed randomization.

BlindingBlinding: Blinded outcome assessors/data collectors, : Blinded outcome assessors/data collectors, biostatisticians.biostatisticians.

Follow-up periodFollow-up period: 3 years: 3 years SettingSetting: Communities in which state-of-the-science : Communities in which state-of-the-science

FDG-PET is reasonably available for various Medicare-FDG-PET is reasonably available for various Medicare-covered clinical applications. covered clinical applications.

PatientsPatients: Patients will be enrolled based on (a) age ≥ : Patients will be enrolled based on (a) age ≥ 65, (b) free-living, (c) presenting without prior specific 65, (b) free-living, (c) presenting without prior specific workup for a complaint of memory deficit, and (d) the workup for a complaint of memory deficit, and (d) the physician specifies that some degree of workup is physician specifies that some degree of workup is planned.planned.


InterventionIntervention: All participating communities will : All participating communities will have a general education program regarding the have a general education program regarding the diagnosis and evaluation of cognitive diagnosis and evaluation of cognitive impairment, and will be informed how to enroll impairment, and will be informed how to enroll patients into the study. To ensure comparable patients into the study. To ensure comparable patient identification in all communities, patient identification in all communities, providers will be compensated on completion of a providers will be compensated on completion of a basic evaluation form for an eligible patient. basic evaluation form for an eligible patient. Communities randomized to have FDG-PET Communities randomized to have FDG-PET reimbursed will have payment coordinated by the reimbursed will have payment coordinated by the regional Medicare carrier. Communities regional Medicare carrier. Communities randomized to not have FDG-PET reimbursed by randomized to not have FDG-PET reimbursed by Medicare will not have restrictions on FDG-PET Medicare will not have restrictions on FDG-PET if covered under other payment arrangements.if covered under other payment arrangements.


MeasuresMeasures: Measures will consist of (a) a simple (i.e., 1 : Measures will consist of (a) a simple (i.e., 1 page) form completed on the date of presentation (index page) form completed on the date of presentation (index date) by the patient’s provider regarding basic date) by the patient’s provider regarding basic demographic and clinical features, diagnosis/further demographic and clinical features, diagnosis/further diagnostic plan, treatment plan, and prognosis; and (b) diagnostic plan, treatment plan, and prognosis; and (b) resource utilization related to initial evaluation and resource utilization related to initial evaluation and management of individuals with CI, as assessed via management of individuals with CI, as assessed via linked Medicare claims files. Cumulative resource costs linked Medicare claims files. Cumulative resource costs from the index date to three-months (short-term) will from the index date to three-months (short-term) will serve as the primary outcome measure for purposes of serve as the primary outcome measure for purposes of sample size calculation. Additional measures will sample size calculation. Additional measures will include resource counts (e.g., imaging studies, specialty include resource counts (e.g., imaging studies, specialty referrals, laboratory testing, and so on), FDG-PET referrals, laboratory testing, and so on), FDG-PET diffusion (in terms of proportion of candidates who have diffusion (in terms of proportion of candidates who have had a FDG-PET), as well as trajectory of resource use had a FDG-PET), as well as trajectory of resource use over time.over time.

Review of StepsReview of Steps

Priority topicPriority topic Literature review/decision modeling Literature review/decision modeling

to identify areas for further researchto identify areas for further research Proposed pragmatic clinical trialProposed pragmatic clinical trial

Patient FallsPatient Falls

Potential Areas of Potential Areas of ResearchResearch

“Patient falls are one example of how our quality work informs a CER priority. As an outcome of interest, falls are of critical importance, highlighted by CMS’ decision to include falls on the list of Hospital Acquired Conditions for which they no longer pay. There are many validated fall assessment tools, but there has not, to date, been any comparative research on the tools to determine which is more effective in determining fall risk assessment and which interventions are most effective for preventing falls.” MaryJane Schumann, ANA, 2009

FallsFalls Coussement J et al. American Geriatrics Society, 2008Coussement J et al. American Geriatrics Society, 2008 Interventions for Preventing Falls in Acute- and Interventions for Preventing Falls in Acute- and

Chronic-Care Hospitals: A Systematic Review and Chronic-Care Hospitals: A Systematic Review and Meta-Analysis Meta-Analysis

Goal: To determine the characteristics and the Goal: To determine the characteristics and the effectiveness of hospital fall prevention programs effectiveness of hospital fall prevention programs

Results: Review showed that most studies were Results: Review showed that most studies were conducted on conducted on long-stay long-stay (mean length of stay (LOS) (mean length of stay (LOS) >1.5 years) and >1.5 years) and rehabilitation unitsrehabilitation units (mean LOS 36.9 (mean LOS 36.9 days). days).

Results: For analysis of the number of falls, one Results: For analysis of the number of falls, one unifactorial and two multifactorial studies showed a unifactorial and two multifactorial studies showed a significant reduction of 30% to 49% in the significant reduction of 30% to 49% in the intervention group, with the greatest effect obtained intervention group, with the greatest effect obtained in the unifactorial study that assessed a in the unifactorial study that assessed a pharmacological intervention. pharmacological intervention.

FallsFalls Lakatos BE et al. Psychosomatics, 2009 Objective: to determine the prevalence of diagnosed

and undiagnosed delirium in patients who fell during their hospital stay.

Study design: Retrospective chart review Methods: Falls were categorized by their severity

(i.e., minor, moderate, and major). Demographic information, patient outcomes, and diagnostic criteria for delirium (per DSM–IV) were collected on the day of admission, the day of the fall, and the 2 days preceding the patient’s fall

Results: Falls in the general hospital were associated with delirium (both diagnosed and undiagnosed), advanced age, and specific surgical procedures

FallsFalls Vass et al. Reducing Falls in In-patient Elderly, Trials,

2009 Summary of an RCT that aims to reduce falls in an

elderly in-patient population in an acute care setting. Background: More than half of all in-patient falls in

elderly people in acute care settings occur at the bedside, during transfers or whilst getting up to go to the toilet. In the majority of cases these falls are un-witnessed.

Background: New patient monitoring technologies have the potential to offer advances in fall prevention. Bedside sensor equipment can alert staff, not in the immediate vicinity, to a potential problem and avert a fall. However no studies utilizing this assistive technology have demonstrated a significant reduction in falls rates in a randomized controlled trial setting.

RCT for fall preventionRCT for fall prevention The research design is an individual patient

randomized controlled trial of bedside chair and bed pressure sensors, incorporating a radio-paging alerting mode to alert staff to patients rising from their bed or chair, across five acute elderly care wards in NottinghamUniversity Hospitals NHS Trust.

Participants will be randomized to bedside chair and bed sensors or to usual care (without the use of sensors). The primary outcome is the number of bedside inpatient falls.

RCT – proposed data RCT – proposed data collectioncollection

Data Data collectioncollection

BaselineBaseline DischargeDischarge

DemographicsDemographics XX

Previous falls/med. Previous falls/med. Hx.Hx.

XX

Cognitive AbilityCognitive Ability XX XX

Quality of LifeQuality of Life XX XX

Activities of Daily Activities of Daily LivingLiving

XX XX

Discharge Discharge DestinationDestination

XX XX

Length of stayLength of stay XX XX

Fear of falling Fear of falling questionnairequestionnaire

XX XX

Total # of in-Total # of in-patient fallspatient falls

XX XX

Vass et al. Trials, 2009

Review of StepsReview of Steps

Priority topicPriority topic Meta-analysis and chart review Meta-analysis and chart review

study to identify gapsstudy to identify gaps Proposed clinical trialProposed clinical trial

Pragmatic aspects are community Pragmatic aspects are community settingsetting

Range of outcomesRange of outcomes

ConclusionsConclusions CER is new focus of funding at the NIH and CER is new focus of funding at the NIH and

AHRQAHRQ List of priority topics (IOM)List of priority topics (IOM) Evidence reports and meta-analyses can Evidence reports and meta-analyses can

provide information on gaps in knowledge provide information on gaps in knowledge base that require further study (AHRQ)base that require further study (AHRQ)

Search grants.gov for RFAs or other Search grants.gov for RFAs or other announcements re: new funding opportunitiesannouncements re: new funding opportunities

Lots of potential colleagues/collaborators at Lots of potential colleagues/collaborators at the U MNthe U MN School of Public HealthSchool of Public Health School of MedicineSchool of Medicine School of DentistrySchool of Dentistry

Funding and Funding and AcknowledgementsAcknowledgements Shalini Kulasingam is supported by NCI grant K07-Shalini Kulasingam is supported by NCI grant K07-

CA113773CA113773 Previously funded by:Previously funded by:

Grants: Merck, CSL-Australia, SP-MSD, CDC, NIH, mtmGrants: Merck, CSL-Australia, SP-MSD, CDC, NIH, mtm Consultant: SP-MSD, CSL – New Zealand, MedtronicConsultant: SP-MSD, CSL – New Zealand, Medtronic

CollaboratorsCollaborators Evan Myers, Duke UniversityEvan Myers, Duke University George Sawaya, University of California, San FranciscoGeorge Sawaya, University of California, San Francisco Joy Melnikow, University of California, DavisJoy Melnikow, University of California, Davis Mark Schiffman, Philip Castle, NCIMark Schiffman, Philip Castle, NCI Eduardo Franco, Raghu Rajan, McGill UniversityEduardo Franco, Raghu Rajan, McGill University Laura Koutsky and Akhila Balasubramanian, University of Laura Koutsky and Akhila Balasubramanian, University of

WashingtonWashington Patti Gravitt, Johns Hopkins UniversityPatti Gravitt, Johns Hopkins University Levi Downs, Rahel Ghebre, Ruby Nguyen, Karen Kuntz, Levi Downs, Rahel Ghebre, Ruby Nguyen, Karen Kuntz,

University of MinnesotaUniversity of Minnesota

Documents

Comparative Effectiveness Research Shalini Kulasingam, PhD University of Minnesota