clinical research in central oregon archie bleyer, md schs what’s available to you, to our...

Clinical Research in Central OregonClinical Research in Central Oregon

Archie BleyerArchie Bleyer, MD, MD

SCHSSCHS

What’s What’s Available Available to to You,You, to Our to Our Community, Community, and and WhyWhy Tim BeardTim Beard, MD, MD

BMCBMC

ObjectivesObjectives

1)1) Understand why clinical research is Understand why clinical research is crucial to Central Oregoncrucial to Central Oregon

2)2) Realize the breadth of clinical trials open Realize the breadth of clinical trials open to entry at our healthcare facilitiesto entry at our healthcare facilities

3)3) Discover what the IRB is and how it helps Discover what the IRB is and how it helps assure that our clinical trials are optimalassure that our clinical trials are optimal

4)4) Anticipate our Clinical Research CenterAnticipate our Clinical Research Center



1)1) Understand why clinical research is crucial Understand why clinical research is crucial to Central Oregonto Central Oregon

Brings Brings Cutting-EdgeCutting-Edge Healthcare to Healthcare to Central Oregon SoonerCentral Oregon Sooner

Extraordinary Care close to HomeExtraordinary Care close to HomeThe “Latest and Greatest”The “Latest and Greatest”

ExamplesExamples

1)1)Ortho / Neuro / Surgical DevicesOrtho / Neuro / Surgical Devices

2)2)Cancer Chemotherapies: Oxaliplatin, …Cancer Chemotherapies: Oxaliplatin, …

3)3)Anti-thrombosis TreatmentsAnti-thrombosis Treatments

4)4)Post-Op Therapy: AlvimopanPost-Op Therapy: Alvimopan

*Diagnosis, Therapy, Prevention*Diagnosis, Therapy, Prevention

*

Research to standard of care exemplified

Phase 3 trials at BMC and SCMC Results Methylnaltrexone?

P&T committee Our study 3 groups of patients $4000 per patient hospital

savings

Factor Xa Inhibitors

Sentinal lymph node surgery Colectomy Spiral CT for coronary and lung imaging Respiratory support for premature

infants Thorascopic ablation for atrial

fibrillation Oral therapy for pulmonary

hypertension

100 %100 %

80 %80 %

60 %60 %

100 %100 %

80 %80 %

60 %60 %

Benefit*Benefit* Safety*Safety*

Progress vs. Safety in Progress vs. Safety in Clinical TrialsClinical Trials

**Personal and SocietalPersonal and Societal

100 %100 %

80 %80 %

60 %60 %

100 %100 %

80 %80 %

60 %60 %

**Personal and SocietalPersonal and Societal


Benefit*Benefit* Safety*Safety*

100 %100 %

80 %80 %

60 %60 %

100 %100 %

80 %80 %

60 %60 %


BenefitBenefit SafetySafety

Clinical Trials Provide Best BalanceClinical Trials Provide Best BalanceRaise Benefit & Safety SimultaneouslyRaise Benefit & Safety Simultaneously

Patient Management BaseBy Expanding Patient ManagementBy Expanding Patient Managementand Raising the Fulcrumand Raising the Fulcrum

Levels of Review of Levels of Review of NCI-Sponsored Clinical TrialsNCI-Sponsored Clinical Trials

CTSUCTSU

Protocol CommitteeProtocol Committee

Institutional Research AdministrationInstitutional Research Administration

ConceptConceptIdeaIdea ProtocolProtocol AccrualsAccruals ResultsResults

InvestigatorInvestigator

CRC and IRB CRC and IRB

Institutional LeadershipInstitutional Leadership

State of the Science

Assessment

State of the Science

Assessment

Cancer Therapy Evaluation Program and Division of Cancer Prevention*Cancer Therapy Evaluation Program and Division of Cancer Prevention*

Modified by A Bleyer from R Comis, ASCO 2002

Data Safety Monitoring BoardData Safety Monitoring BoardIRBIRB

NCI PIONCI PIO

Multidisciplinary Input and Support of Multidisciplinary Input and Support of Cancer Clinical TrialsCancer Clinical Trials

SurgerySurgery

Research LaboratoryResearch

Laboratory

RadiotherapyRadiotherapy

PharmacyPharmacy

Palliative Care

Palliative Care

Medical Specialties

Medical Specialties

Lab. Med. Lab. Med.

NursingNursing

Diagnostic Imaging

Diagnostic Imaging

PathologyPathology

ChemotherapyChemotherapy

ClinicalTrial

ClinicalTrial

BloodbankingBloodbankingSupportive

CareSupportive

Care

Medical SpecialtiesMedical Specialties Input and Support of Input and Support of Cancer Clinical TrialsCancer Clinical Trials

InfectiousDisease

InfectiousDisease

PsychiatryPsychiatry

NeurologyNeurology

NephrologyNephrology

Derma-tologyDerma-tology

ImmunologyImmunology

CardiologyCardiology

RheumatologyRheumatology

PulmonologyPulmonologyEndocrinologyEndocrinology

ClinicalTrial

ClinicalTrial

ENTENT

Gastro-enterology

Gastro-enterology

OphthalmologyOphthalmology

BenefitBenefit SafetySafety

Highly-Peer Reviewed Clinical TrialsHighly-Peer Reviewed Clinical TrialsRaise Benefit & Safety SimultaneouslyRaise Benefit & Safety Simultaneously

145 Hospitals145 Hospitals0 Entries0 Entries

226 Hospitals226 Hospitals1.0 (0.5-1.4)1.0 (0.5-1.4) %% on Trialon Trial

123 Hospitals123 Hospitals4.9 (3.5-9.7)4.9 (3.5-9.7) % on Trial% on Trial

494 hospitals with 174,062 patients 494 hospitals with 174,062 patients with non–ST-segment with non–ST-segment

Acute Coronary Syndrome (ACS)Acute Coronary Syndrome (ACS)

Majumdar SR, Roe MT, Peterson ED, Chen AY, Gibler WB, Armstrong PW Majumdar SR, Roe MT, Peterson ED, Chen AY, Gibler WB, Armstrong PW Arch Intern Med.Arch Intern Med. 2008;168(6):657-62 2008;168(6):657-62

5.9

4.4

3.5

Low High

Better Outcomes for Patients Treated at Better Outcomes for Patients Treated at Hospitals That Participate in Clinical TrialsHospitals That Participate in Clinical Trials

Clinical Trial Participation

In-hospital mortality

(%)

P = .003

Intermediate


145 Hospitals145 Hospitals0 Entries0 Entries

226 Hospitals226 Hospitals1.0 (0.5-1.4)1.0 (0.5-1.4) %% on Trialon Trial

123 Hospitals123 Hospitals4.9 (3.5-9.7)4.9 (3.5-9.7) % on Trial% on Trial

494 hospitals with 174,062 patients 494 hospitals with 174,062 patients with non–ST-segment with non–ST-segment

Acute Coronary Syndrome (ACS)Acute Coronary Syndrome (ACS)

SCMC-BSCMC-B


5.9

4.4

3.5

Low HighClinical Trial Participation


(%)

P = .003

Intermediate

Better Outcomes for Patients Treated at Better Outcomes for Patients Treated at Hospitals That Participate in Clinical TrialsHospitals That Participate in Clinical Trials

SCMC-BSCMC-B


Correlation Between Clinical Trial Correlation Between Clinical Trial Participation and Hospital OutcomesParticipation and Hospital Outcomes

ExampleExample: Non-ST segment myocardial infarction: Non-ST segment myocardial infarction(NSTEMI)(NSTEMI)

0

2

4

6

0 2 4 6 8 10

% of NSTEMI Patients In ACS Clinical Trials


(%)

Cost of treating patients in clinical trials Cost of treating patients in clinical trials just slightly higherjust slightly higher**

Clinical trials appear not to drive up cost of Clinical trials appear not to drive up cost of treatment**treatment**

99% of the time, the extra costs are paid by the 99% of the time, the extra costs are paid by the sponsor (federal, private) and sponsor (federal, private) and notnot the patient the patient

Negligible and Acceptable Financial Cost Negligible and Acceptable Financial Cost to Patients of Participating to Patients of Participating

in Clinical Trialsin Clinical Trials

*www.cancer.gov/clinicaltrials/conducting/developments/notcostly0603, **…/notcostly0103



2)2) Realize the breadth of clinical trials open to Realize the breadth of clinical trials open to entry at our healthcare facilitiesentry at our healthcare facilities

and how I and my patients and how I and my patients

can participatecan participate

Oncology Cardiology Orthopedic Surgery Neurosurgery Neonatology Surgery Neurology Psychology Nephrology Infectious Disease Immunology

Sleep Disorders Pulmonology Trauma Sports Medicine Rheumatology Patient Monitoring Equip. Pediatrics/Adol. Med. Acupuncture Other Integrative Med. Patient Satisfaction Rural Health

Sponsored National Institutes of Health (NIH)

National Cancer Institute (NCI) National Heart, Lung and Blood Institute

Universities (OHSU, Portland State)Private/Corporate Enterprises

Pharmaceutical Industry Medical (Human) Device Industry Other Healthcare Systems (e.g. US Oncology)

Investigator-Initiated (N = 8) IRB Approved

SCHS IRB Western IRB

SCHS Trials April 2009 - March 2010 11 healthcare organizations921 Central Oregonians currently on trials

180 patients entered past year 42 trials open for new subjects 25 trials closed to entry, in follow-up

BMC Trials 31 trials open for new subjects313 Central Oregonians currently on trials

89 patients entered past year Total Number of Patients on Trials:

1,234

What it takes Time Ancillary help Certified Physician Investigator Meetings

Phase I Phase II Phase III Phase IV

What is it Is this research?

How to do it? What do you need? Facility Collaboration

Michel BoileauMichel Boileau, MD, MD SELECTSELECT

Bill MartinBill Martin, MD, MD E5202E5202

Linyee ChangLinyee Chang, MD, MD AXXENTAXXENT

Russ OmizoRuss Omizo, MD, MD PRIMAPRIMA Steve KornfeldSteve Kornfeld, ,

MDMD S0925S0925 ……

Robert BooneRobert Boone, , MDMD STARSTAR ASSUREASSURE TAILORxTAILORx IBCSG 24-02IBCSG 24-02 MA.27MA.27 JMA.17JMA.17 S0226S0226 …… …… …… ……

Our Researchers and Their ResearchOur Researchers and Their ResearchOncologyOncology

Bruce McClellanBruce McClellan, , MDMD AFIBAFIB COMM AFIBCOMM AFIB OASISOASIS LUNARLUNAR ……

Michael WidmerMichael Widmer, , MDMD ASCENDASCEND LGVXLGVX LGVYLGVY RED-HFRED-HF

John BlizzardJohn Blizzard, MD, MD MEND CABGMEND CABG

Tim HanlonTim Hanlon, MD, MD EXCEEDEXCEED

James LaughlinJames Laughlin, MD, MD VITALVITAL

Jason WollmuthJason Wollmuth, , MDMD SATURNSATURN

Chris HatlestadChris Hatlestad, MD, MD TACT2TACT2

Our Researchers and Their ResearchOur Researchers and Their ResearchHeartHeart

Our Researchers and Their ResearchOur Researchers and Their ResearchOrthopedic Surgery / Physical TherapyOrthopedic Surgery / Physical Therapy

Knute BuehlerKnute Buehler, MD, MD CECTCECT EXETEREXETER ……

James VerheydenJames Verheyden, MD, MD ASCENSION MCP, PIPASCENSION MCP, PIP

Scott JacobsenScott Jacobsen, MD, MD AEQUALISAEQUALIS

Michael CoeMichael Coe, MD, MD AVANTAAVANTA

David StewartDavid Stewart, MD, MD ALVIMOPAMALVIMOPAM

Cara WaltherCara Walther, MD, MD KNEEBOUNDKNEEBOUND

Viviane UgaldeViviane Ugalde, MD, MD SQUAT TESTSQUAT TEST

Brett GingoldBrett Gingold, MD, MD OP1 ImplantOP1 Implant

Kathleen MooreKathleen Moore, , MDMD OP1 PuttyOP1 Putty

Anthony HinzAnthony Hinz, MD, MD GEMGEM

Robert ThomasRobert Thomas, MD, MD LFITLFIT

Raymond TienRaymond Tien, MD, PhD, MD, PhD SAPPHIRESAPPHIRE NEUROFORMNEUROFORM

Mark BelzaMark Belza, MD, MD CERVDISCCERVDISC TILFTILF

Our Researchers and Their ResearchOur Researchers and Their ResearchNeurosurgeryNeurosurgery

Brad WardBrad Ward, MD, MD COASTCOAST KAVIARKAVIAR

Kent YundtKent Yundt, MD, MD OP1PuttyOP1Putty

Stephen ArcherStephen Archer, MD, MD BOLDBOLD

Susan GormanSusan Gorman, MD, MD MWEndometAblationMWEndometAblation AdianaAdiana

Linda LeffelLinda Leffel, MD, MD BreastImplantBreastImplant

David DedrickDavid Dedrick, MD, MD RestlessLegsRestlessLegs

Patrick McCarthyPatrick McCarthy, MD, MD AGREEAGREE EndureEndure

Francis McCabeFrancis McCabe, MD, MD WELCH ALLYNWELCH ALLYN

Brian O’HollarenBrian O’Hollaren, , MDMD ALVIMOPAMALVIMOPAM

Todd TornayTodd Tornay, MD, MD ED DxED Dx

Teresa ChianelloTeresa Chianello, , PhDPhD MUPSMUPS

Travis MonchampTravis Monchamp, , MDMD SanofiiAventisEFCSanofiiAventisEFC

Lyle FagnonLyle Fagnon, MD, MD CLEMENTECLEMENTE

Our Researchers and Their ResearchOur Researchers and Their ResearchOther SpecialtiesOther Specialties

Our Researchers and Their ResearchOur Researchers and Their ResearchBend Memorial ClinicBend Memorial Clinic

Tim BeardTim Beard, MD, MD MNTXHerniaMNTXHernia MNTXColecMNTXColec PozenPozen Adolor cystectomyAdolor cystectomy BRI DVTBRI DVT Pozen EndoPozen Endo I3 POII3 POI

Darren KowalskiDarren Kowalski, , MDMD LAPCOLONLAPCOLON

Bill SchmidtBill Schmidt, MD, MD GSK MagritGSK Magrit EclipseEclipse Pfizer BreastPfizer Breast Clovis PancreaticClovis Pancreatic

Ted BraichTed Braich, MD, MD ACORNACORN

Gavin NobleGavin Noble, MD, MD BorealisBorealis AspectAspect


(continued)(continued) Mike FeldmanMike Feldman, MD, MD

Mitsubishi KRM Mitsubishi KRM Luitpold anemiaLuitpold anemia

Matt LasalaMatt Lasala, MD, MD Genentech StageGenentech Stage Roche Emerge 6Roche Emerge 6 Genentech SundialGenentech Sundial Roche Emerge 8Roche Emerge 8 BRI COPD BRI COPD

Adam WilliamsAdam Williams, MD, MD Forest COPD Forest COPD

Greg BorstadGreg Borstad, MD, MD Takeda GoutTakeda Gout Lilly BCDOLilly BCDO Abbott RAAbbott RA

Rich KochRich Koch, MD, MD Lilly TabyLilly Taby IELCAPIELCAP

Mike HarrisMike Harris, MD, MD ICON/BMSICON/BMS

Rob MatthewsRob Matthews, MD, MD NIAONNIAON


(continued)(continued) Jon LutzJon Lutz, MD, MD

WESTNILEWESTNILE

Mary CarrollMary Carroll, MD, MD Takeda SYR-322 Takeda SYR-322 Trial Net DMTrial Net DM Lilly GBDALilly GBDA Lilly IOQCLilly IOQC

Karen OppenheimerKaren Oppenheimer, ,

MDMD Daiichi EngageDaiichi Engage

Total: Total: 54 54 MD & MD/PhD MD & MD/PhD

Principal Principal InvestigatorsInvestigators

Total: Total: 54 54 MD & MD/PhD MD & MD/PhD

Principal Principal InvestigatorsInvestigators

SCHSSCHS

Noura SallNoura Sall, , MS, CCRCMS, CCRC Andrea AndrusAndrea Andrus, , CCRC, RDCSCCRC, RDCS

Aimee SolesAimee Soles, , CRA CRA

Cardiovascular Services, SCHSCardiovascular Services, SCHS Meredith DawsonMeredith Dawson, CCRC, CCRC

The Center for Orthopedic and Neurosurgical The Center for Orthopedic and Neurosurgical Care and ResearchCare and Research

Megan BooneMegan Boone, , CRACRA

Kristi SterryKristi Sterry, , CCRPCCRP

Cancer Center, SCHSCancer Center, SCHS

Research CoordinatorsResearch Coordinators

Research Coordinators Research Coordinators (continued)(continued)

Karla LichterKarla Lichter, , MS, CCRCMS, CCRC Pamela GogenolaPamela Gogenola, , CCRCCCRC

Joanne SmithJoanne Smith, , CCRCCCRC Christine ReedChristine Reed, , BS, BS, CCRCCCRC

Aaron PrattAaron Pratt, , BS, CRCBS, CRC

Jennifer McCormickJennifer McCormick, MA CRC, MA CRC

Molly JohnsonMolly JohnsonDanielle QuinlinDanielle QuinlinAnne BerginAnne BerginJoanne SmithJoanne SmithBend Memorial ClinicBend Memorial Clinic

Research Coordinators Research Coordinators (continued)(continued)

TBATBAAdvanced Specialty CareAdvanced Specialty Care

Sara McCarthySara McCarthyNW EndocrinologyNW Endocrinology

Total: Total: 1717 Research Coordinators Research CoordinatorsTotal: Total: 1717 Research Coordinators Research Coordinators

Research Coordinators Research Coordinators Ex OfficioEx Officio

Karen DoolanKaren Doolan, , RN, NP, CRARN, NP, CRA Teddy RichardsonTeddy Richardson, , RNRN, , CRACRA

Heart Institute of the CascadesHeart Institute of the Cascades Deb RogersDeb Rogers , , RN, NP, CRARN, NP, CRA

The Center for Orthoppedic and The Center for Orthoppedic and Neurosurgery Care and ResearchNeurosurgery Care and Research

Janice McDanielJanice McDaniel , , CCRPCCRP

SCHS Cancer CenterSCHS Cancer Center

History and EthicsHistory and Ethics Nuremburg Code Nuremburg Code (WWII)(WWII) Wichita Jury Case (1953)Wichita Jury Case (1953) Milgram “Obedience to Authority” (1963)Milgram “Obedience to Authority” (1963) Declaration of Helsinki Declaration of Helsinki (1964)(1964) Beecher Report (1966)Beecher Report (1966) PHS Tuskegee Syphilis PHS Tuskegee Syphilis (1932-1971)(1932-1971) Humphrey “Tea Room Trade” (1970)Humphrey “Tea Room Trade” (1970) Zimbardo “Simulated Prison” (1973)Zimbardo “Simulated Prison” (1973) Belmont Report Belmont Report (1979)(1979)

Respect for Respect for PersonsPersons

BeneficenceBeneficenceJusticeJustice

Respect for Respect for PersonsPersons

BeneficenceBeneficenceJusticeJustice

Legally mandated Legally mandated to assure thatto assure that

1)1) The conduct of all The conduct of all researchresearch activities involving activities involving humans or specimens from humans within the humans or specimens from humans within the SCHS is SCHS is in compliance within compliance with

• International (ICH)International (ICH)• Federal (DHHS, FDA, etc.)Federal (DHHS, FDA, etc.)• StateState• LocalLocal

regulationsregulations45CFR46

21CFR50

21CFR56

SCHS Insitututional Review Board SCHS Insitututional Review Board (IRB)(IRB)

2.2. The The rights and welfarerights and welfare of our people willing to participate in clinical of our people willing to participate in clinical research are protectedresearch are protected

3.3. The The risksrisks, discomforts and inconveniences of the research is justified , discomforts and inconveniences of the research is justified relative torelative to potential individual and societal potential individual and societal benefitbenefit

4.4. All subjects are fully All subjects are fully informed and freely consentinformed and freely consent

5.5. AllAll human subject research human subject research and research proposals at SCHS is reviewed and research proposals at SCHS is reviewed and approvedand approved

6.6. IRB includes scientists and community membersIRB includes scientists and community members

SCHS Insitututional Review Board SCHS Insitututional Review Board (IRB)(IRB)

SCHS IRBSCHS IRB

FoundedFounded: : 19881988 Studies approvedStudies approved: : 330+330+ since 1994 since 1994 Prior ChairsPrior Chairs

Michel BoileauMichel Boileau, MD, MD Bruce BrundageBruce Brundage, MD, MD Derek GillespieDerek Gillespie, PharmD, PharmD Mary Jane KuharMary Jane Kuhar, MD, MD

Robert BooneRobert Boone, MD, MD Steve MeyerSteve Meyer, MD, MD Allen MerrittAllen Merritt, MD, MD

Keith HarlessKeith Harless, MD, MD Christopher ClarkChristopher Clark, MD, MD John RaskJohn Rask, MD, MD Bryce YermanBryce Yerman, MD, MD Craig MillerCraig Miller, MD, MD Darius AzinDarius Azin, MD, MD Cherri McKenzieCherri McKenzie, RN, RN Dorothy BarrowDorothy Barrow, RN, RN

James HurleyJames Hurley, JD, JD Rick MartinRick Martin, BS, BS Ellen EismanEllen Eisman, PhD Alan BurkeAlan Burke, MSW, MSW Dave VialDave Vial, PharmD, PharmD Rose Dusen-SpeckRose Dusen-Speck, LPT, LPT Barton ClementsBarton Clements, EdD, EdD

Other Prior MembersOther Prior Members

SCHS IRBSCHS IRB

Jay CasbonJay Casbon, PhD, PhD, , CEO & Provost CEO & Provost emeritusemeritusOregon State University – Cascades Campus Oregon State University – Cascades Campus

Bryan GruetterBryan Gruetter, JD,, JD, AttorneyAttorney, , Gruetter LawGruetter Law Jana JaderborgJana Jaderborg, MD, MD, , Surgeon, Advanced Specialty CareSurgeon, Advanced Specialty Care Dana McClintockDana McClintock, MD, Bend Research Inc., MD, Bend Research Inc. Justin SanganiJustin Sangani, PharmD, Research Pharmacist, PharmD, Research Pharmacist Peggy Carey, Peggy Carey, RN, MPA, Cancer Program DirectorRN, MPA, Cancer Program Director

Other Prior MembersOther Prior Members(continued)(continued)

SCHS IRBSCHS IRB

SCHS IRB 2011SCHS IRB 2011

Archie BleyerArchie Bleyer, MD, , MD, ChairChair Bill DanaherBill Danaher, Spiritual Care, Spiritual Care Robert CutterRobert Cutter, , PharmD, PharmD, PharmacyPharmacy

SCHS MembersSCHS Members 8 Members8 Members

Katie RichardsKatie Richards, MD, , MD, Chair AlternateChair AlternateEmergency MedicineEmergency Medicine

James RitzenthalerJames Ritzenthaler, MD,, MD, Internist, Internist, Director, Volunteers in MedicineDirector, Volunteers in Medicine

David LyonDavid Lyon, PhD, , PhD, Vice President, Physical Vice President, Physical and Biological Sciences, Bend Research Inc.and Biological Sciences, Bend Research Inc.

Adam CarrollAdam Carroll, PhD, , PhD, Bend Research Inc.Bend Research Inc. Michael GibsonMichael Gibson, , BSBS, Patient Advocate, Patient Advocate

Community MembersCommunity Members

SCHS IRB 2011SCHS IRB 2011

SCHS CEO

VP Quality

DirectorDept. Quality Mgt.

ResearchInvestigators

SVP Medical Affairs

PresidentMedical Staff

SC-Bend

MDQA SC-Bend

MDQA PMH

MDQA SC-Rdmd

IRB Chair

IRBIRB

IRB Coordinator/

Secretary

Table of Organization

SCHS IRBSCHS IRB

C. Ken HouseC. Ken House

Lyn WalfordLyn Walford

FDA AuditFDA AuditMarch 2010March 2010

10 Consecutive Days10 Consecutive Days Nine Category 483 Nine Category 483

CitationsCitations





4)4) Anticipate our Clinical Research CenterAnticipate our Clinical Research Center

Enhanced recruitment All research sites work together Central database of research Central Oregon Clinical Research

Center (COCRC)

Central Oregon Clinical Research Website

launchpending

Clinical Research Associate Forum

Promotes Critical ThinkingPromotes Critical Thinkingo Attracts high quality physicians who demand Attracts high quality physicians who demand

a cutting-edge professional environment a cutting-edge professional environment while desiring Central Oregon quality of lifewhile desiring Central Oregon quality of life

Bruce Brundage, MD

and Jobs !and Jobs !

o Adds new $ to Central Oregon economyAdds new $ to Central Oregon economyo New healthcare technology companiesNew healthcare technology companieso Venture capital Venture capital (Bend Angel Fund $1.2m)(Bend Angel Fund $1.2m)o New jobsNew jobso New facilities (Juniper Ridge)New facilities (Juniper Ridge)

Prestige as major medical centerPrestige as major medical center

Patient RetentionPatient Retention

Patient RecruitmentPatient Recruitment

Healthcare Reform CompetitivenessHealthcare Reform Competitiveness

Grant CompetitivenessGrant Competitiveness

PhilanthropyPhilanthropy

Key CollaborationsKey Collaborations

Benefits for our community …Benefits for our community …

1)1) Why clinical research here is crucial Why clinical research here is crucial

2)2) Breadth of our clinical trialsBreadth of our clinical trials

3)3) Why and how of our IRB Why and how of our IRB

4)4) Central Oregon Clinical Research CenterCentral Oregon Clinical Research Center

ReviewReview

ableyerableyer@@stcharleshealthcare.orgstcharleshealthcare.org .... 541541--706706--69986998tbeardtbeard@@bmctotalcare.combmctotalcare.com ……….……….541-317-4310541-317-4310

ThankThankyouyou

Q/A SlidesQ/A Slides

2010 was a Good Year for Clinical 2010 was a Good Year for Clinical Research in Central Oregon / OregonResearch in Central Oregon / Oregon

Oregon SB316Oregon SB316 The Bulletin The Bulletin ArticlesArticles Investigator-Initiated Clinical TrialsInvestigator-Initiated Clinical Trials Clinical Research WebsiteClinical Research Website Central IRB ParticipationCentral IRB Participation Electronic IRB ManagementElectronic IRB Management Peggy CareyPeggy Carey, RN, MPA, RN, MPA David DiltsDavid Dilts, PhD, MBA, , PhD, MBA, OHSUOHSU FDA IRB AuditFDA IRB Audit Federal Affordable Care ActFederal Affordable Care Act Core Component of IDS, PHACore Component of IDS, PHA Triple Aim Triple Aim ala ala BerwickBerwick

2010 was a Good Year 2010 was a Good Year for Clinical Research for Clinical Research

in Central Oregonin Central Oregon

Oregon SB316Oregon SB316

The Bulletin The Bulletin ArticlesArticles

Investigator-Initiated Clinical TrialsInvestigator-Initiated Clinical Trials

Clinical Research WebsiteClinical Research Website

Central IRB ParticipationCentral IRB Participation

Electronic IRB ManagementElectronic IRB Management

2010 was a Good Year 2010 was a Good Year for Clinical Research for Clinical Research

in Central Oregonin Central Oregon

Regional CollaborationsRegional Collaborations

o COCC: Nursing School rotationsCOCC: Nursing School rotations

o OSU-Cascades: Health education researchOSU-Cascades: Health education research

o Portland State University: IRB RotationsPortland State University: IRB Rotations

o OHSU: OHSU: Medical student rotations and collaborative research Medical student rotations and collaborative research (cardiovascular surgery)(cardiovascular surgery)

o High Schools: High Schools: The Center, Emergency Dept.The Center, Emergency Dept.

Lack of Trial EffectLack of Trial Effect(Hawthorne Effect) (Halo Effect)(Hawthorne Effect) (Halo Effect)

Joffe, Weeks, et al, Dana Farber, BostonJoffe, Weeks, et al, Dana Farber, Boston Lancet, 1/23/04Lancet, 1/23/04 26 trials26 trials SummarySummary: Little evidence for the belief : Little evidence for the belief

that patients who enroll in clinical trials that patients who enroll in clinical trials live longer than those who do not live longer than those who do not

ClinicalTrial

ClinicalTrial

Halo EffectHalo Effect

Hawthorn Effect: Braunholtz DA et al, J Clin Epi 54:217-24, 2001

Quality of Life Benefit from Quality of Life Benefit from Clinical Trial ParticipationClinical Trial Participation

Multidisciplinary InputMultidisciplinary Input Center of Team Center of Team

AttentionAttention Special ConsiderationsSpecial Considerations Secondary GainSecondary Gain Follow-upFollow-up Altruistic Benefit Altruistic Benefit

Ave

rag

e N

o. A

ccru

als

per

Ye

ar

3551

3161

2588

1664

624

214

1365

834

553 500500

200 226

436

892

1661

2482

3284

3825

0

4000

0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85

3000

2000

1000

Age at Entry (Years)

U.S. Cancer Patients Entered on National Treatment Trialsby 5-year Age Intervals, 2001-2006

Number Patients on Trials

Average Annual Percent Change (AAPC) in 5-Year Relative Survival Rate, All Invasive Cancer excluding Kaposi Sarcoma

SEER 1985-1999

0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85Age at Diagnosis (Years)

0

0.5

1.0

1.5

2.0Survival Improvement

0.9 0.8

1.2

0.10.1 0.1

0.3 0.3

0.7 0.7

1.1

1.6

2.1

1.9

1.7

1.5

1.2

0.7

AAPC

Ave

rag

e N

o. A

ccru

als

per

Ye

ar

0

4000

0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85

3000

2000

1000

Number Patients

Age at Entry (Years)

p = 0.0000001

0

0.5

1.0

1.5

2.0

Survival Improvement

AAPC

Hurdles on the road to a clinical trial

Betsy CliffThe Bulletin

8/26/10s

Patients in medical research trialsWary patients evaluate pros and cons of participating in trial

Markian HawrylukThe Bulletin8/5/10s

MetricApr 2009 – Mar 2010

Clinical Trials Open for New Subjects 42

Investigator–Initiated Clinical Trials 4

Different Diseases or Medical Conditions 39

Healthcare Organizations 11

Trials Closed to Entry, in Follow-up 25

SCHS Clinical ResearchSCHS Clinical ResearchOur Clinical TrialsOur Clinical Trials

SCHS Clinical ResearchSCHS Clinical ResearchThe InvestigatorsThe Investigators

Their Organizations and Research SubjectsTheir Organizations and Research Subjects

MetricApril 2009 – March 2010

Principal Investigators35 MDs

&MD/PhDs

Clinical Research Associates 14 CRAs

New Clinical Trials Approved 21 of 23 submitted

Current Central Oregon Patients on clinical trials monitored by SCHS

921 total

4/09-3/10: 180 new

Promotes Critical Thinking in Promotes Critical Thinking in All Health Care ActivitiesAll Health Care Activities

o Makes us think “outside the box”Makes us think “outside the box”

o Opens our minds to new ideasOpens our minds to new ideas

o Promotes intellectual integrity Promotes intellectual integrity (antithesis of sloppy thinking)(antithesis of sloppy thinking)

o Encourages all caregivers to ask questions Encourages all caregivers to ask questions and not just accept the and not just accept the status quostatus quo

Bruce Brundage, MD

At least do some goodAt least do some good

Vincent DeVitaVincent DeVita, MD, MD

Primum non nocerePrimum non nocere

HippocratesHippocrates

make a habit of two things—to help, make a habit of two things—to help, or at least to do no harmor at least to do no harm

First, Do It Right !First, Do It Right !With cancer, the best chance With cancer, the best chance

is the first treatmentis the first treatment

St. Charles Health SystemSt. Charles Health System (SCHS) (SCHS) Institutional Review BoardInstitutional Review Board (IRB)(IRB)

IRB #00003908 FWA #00005956IRB #00003908 FWA #00005956

SCHS IRBSCHS IRB Years founded: Years founded: 19881988 Research studies (clinical trials) Research studies (clinical trials)

approved: approved: 330+ since 1994330+ since 1994 Monthly meetings: Monthly meetings: 6:30-8:00 am6:30-8:00 am Includes community volunteers Includes community volunteers

and scientific membersand scientific members Interim actions and daily surveillanceInterim actions and daily surveillance Plans for clinical research infrastructure Plans for clinical research infrastructure

support across Central Oregonsupport across Central Oregon

SCHS IRBSCHS IRB

C. Ken HouseC. Ken House, , Director, Quality ManagementDirector, Quality ManagementIRB ManagerIRB Manager

Lyn WalfordLyn Walford, , IRB Secretary/CoordinatorIRB Secretary/Coordinator

IRB Office StaffIRB Office Staff

Magnitude of the ConundrumMagnitude of the Conundrum

2. Adil Shamoo, Univ. Maryland School of Medicine, Natl. Human Research Protection Advisory Comm.

20,000,000 people enrolled as research 20,000,000 people enrolled as research subjects annually, increased 3x in 10 yearssubjects annually, increased 3x in 10 years

22

1. CenterWatch

~80,000 clinical trials conducted every ~80,000 clinical trials conducted every year in the U.S.year in the U.S.11

Average time spent by IRBs reviewing Average time spent by IRBs reviewing studies: 1-2 minutes eachstudies: 1-2 minutes each

Meetings

• Minutes: Votes for, against, abstention and reason not recorded; controverted [sic: controversial] discussions not summarized

• Diversity: Meeting convened without a non-scientific member

• Teleconferencing Participation: Lack of documentation of materials supplied to teleconferencing member

• Interim Convened Meetings: Lack of documentation of provision for and recording of materials provided at Interim convened meetings

• Suspension Reporting: A study’s accrual suspension was not reported to the FDA

Membership

• Membership rosters: Lack of documentation of scientific vs. non-scientific designation and of affiliate vs. non-affiliate and voting status

Category 483 Citations

FDA Audit Actions Completed, June 1 2010

Investigator Responsibilities

• Investigator Compliance: Compliance by Principal Investigator is not prospectively surveyed

Documentation

• Electronic Recording and Processing: Electronic method not CFR “part 11” compliant; March-April 2008 files missing

• Serious Adverse Events: Lack of documentation of scientific evaluation when expedited

• Initial Application and Continuing Review Process: Lack of documentation of application & continuing review processes, particularly of humanitarian devices; and of risk determination

• FDA Reporting: Suspended, terminated study not reported

• Informed Consent Forms: Discomforts for venipunctures and mammograms were not included

Category 483 Citations(continued)

FDA Audit Actions Completed, June 1 2010

Proposed SCHS Clinical Research Website

IRB Homepage

IRB Pages

Collaborations and Collaborations and Expanded OpportunitiesExpanded Opportunities

o National Institutes of HealthNational Institutes of Health

o Major Medical CentersMajor Medical Centers

o National: Harvard, Duke, UCSF, Stanford,National: Harvard, Duke, UCSF, Stanford,

o Regional: Seattle, Oregon Regional: Seattle, Oregon (Next Slide)(Next Slide)

o State of OregonState of Oregon

o US OncologyUS Oncology

Current Local Research Spectrum and Future Plans

Archie Bleyer, MDMedical AdvisorCancer Treatment CenterSCHS

Central Oregon Central Oregon Clinical ResearchClinical Research

Comprehensive services Comprehensive services to all clinical investigators to all clinical investigators (and potential clinical investigators) (and potential clinical investigators) in central Oregonin central Oregon

SCHS basedSCHS based

Provence of Provence of UniversityUniversity Hospitals Hospitals

Available to Available to CommunityCommunity Hospitals Hospitals

Provence of Provence of UniversityUniversity Hospitals Hospitals

Available to Available to CommunityCommunity Hospitals Hospitals

Modified from Watch Interviews Modified from Watch Interviews 9/12/069/12/06

Different Research Arenas Available to Different Research Arenas Available to Hospitals Offer Mix of Prestige and Hospitals Offer Mix of Prestige and

Profitability Profitability

Break-Even Break-Even (or unprofitable)(or unprofitable) ProfitableProfitable

PrestigiousPrestigious

Not PrestigiousNot Prestigious

Single Single SiteSite

Drug/DeviDrug/Devicece

ResearchResearch

Single Single SiteSite

Drug/DeviDrug/Devicece

ResearchResearch

““Hot” Hot” Research Research

Area Area du jourdu jour

““Hot” Hot” Research Research

Area Area du jourdu jour

Investigative Investigative Studies by Studies by PhysiciansPhysicians

Investigative Investigative Studies by Studies by PhysiciansPhysicians

Regionally Regionally Focused Focused ResearchResearch

Regionally Regionally Focused Focused ResearchResearch

No No Research Research ProgramProgram

No No Research Research ProgramProgram

Multi-SiteMulti-SiteDrug/Drug/DeviceDevice

ResearchResearch

Multi-SiteMulti-SiteDrug/Drug/DeviceDevice

ResearchResearch

Why Physicians Do ResearchWhy Physicians Do Research

CuriosityCuriosity

CompassionCompassion

DeterminationDetermination

Final Thoughts on Final Thoughts on Critical Role of Clinical ResearchCritical Role of Clinical Research

A research environment A research environment Sets a higher standard in all Sets a higher standard in all

that we dothat we do Makes us leaders instead of Makes us leaders instead of

followersfollowers It’s one of those tides that It’s one of those tides that

“floats all boats”“floats all boats”

1)1) DevicesDevices

2)2) DrugsDrugs

3)3) Health Insurance CoverageHealth Insurance Coverage

1)1) Oregon Law: SB316 Oregon Law: SB316

2)2) Affordable Care ActAffordable Care Act

Brings Brings Cutting-EdgeCutting-Edge Healthcare Healthcare** to to Central Oregon Central Oregon at at Lower CostLower Cost to to

Providers and PatientsProviders and Patients

Eliminates Eliminates UnnecessaryUnnecessary Treatment, Treatment, Diagnostic Tests, and Prevention Diagnostic Tests, and Prevention

Methods in Central Oregon SoonerMethods in Central Oregon Sooner

The “Ain’t Great” and The “Ain’t Great” and Potentially DangerousPotentially Dangerous

ExamplesExamples

1)1)Chelation – Coronary CalciumChelation – Coronary Calcium

2)2)Avastin (bevacizumab) for Breast CancerAvastin (bevacizumab) for Breast Cancer

For the patient…For the patient…

Clinical Trials Provide Access to Clinical Trials Provide Access to Potentially Better TherapiesPotentially Better Therapies

““Latest and Greatest” Latest and Greatest” HopeHope All we know about treating … All we know about treating …

has been learned through researchhas been learned through research

David Sandoval, MDMedical Director, Research Department

Bend Memorial Clinic

The New Drug Pipeline

In 2000, ~15,000 compounds in development

FDA approves ~70-80 new drugs per year

Process risky with failures >> successes

The average interval from 1st testing in humans to FDA approval is 10 years !

Before human testing, extensive laboratory and animal testing is performed to provide insights about the drug’s

Biological activity Toxicity Pharmacology (half life, etc) Basic side effects

<<1% of drugs that undergo pre-clinical testing go on to be tested in humans

To begin human testing, an “Investigational New Drug” application must be submitted to the FDA (IND)

All trials have a tacit FDA approval to “go ahead” (unless the FDA responds)

However, all trials MUST have active IRB approval before and while conducted, and in required follow-up

Clinical development has four phases if successful:

Phase I Phase II Phase III Phase IV May also have subphases A and B

IA IB IIA IIB …

Each phase involves a progressively larger population of subjects.

Focused on safety, with dose escalation to determine maximally tolerated dose (MTD)

Typically done in otherwise healthy volunteers or patients whose disease is refractory to available therapies

Human pharmcology assessement; ,may require admission to a “phase I unit”

Usually requires 25-100 subjects Takes up to one year Only about 70% of drugs complete this

phase

Focused on activity against disease (benefit) with continued safety (toxicity) assessmentr

Usually about 1000 subjects May take 1-2 years Only about 50-60% of drugs complete

this phase After completion: information about

activity, more on safety, and preliminary evidence about efficacy

Focus on efficacy Tests new therapy against current therapy,

with randomized comparison if possible Involves hundreds to several thousands of

subjects/patients Takes up to 2-4 years to complete About 80% of drugs which made it through

phase I and II complete this phase Some trials may be conducted

internationally

Study Designs: single blinded, double blinded, agent vs. placebo control, etc.

Also used when an already approved drug is seeking approval for a new indication or a new dosage form

Reason number for failures of phase III trials: inadequate ENROLLMENT

One third of participating sites fail to meet enrollment

Follow ethical principle of justice: “benefits and risks of research should be evenly distributed”

Remember: clinical trials are about patient care … the protocol must be followed

Advice for Staff Engaged in Clinical Research

Follow the 3 basic ethical principles Respect for persons/subjects:

Informed Consent. Remember “vulnerable” subject provisions

Beneficence: “desired knowledge” should be obtained in a way that maximizes benefits and minimizes risks

Justice: fairness in the selection of participants

After the new drug has been approved by the FDA

Usually requested by the FDA as a surveillance

Major litigation involving pharmaceutical products has occurred in marketed drugs

Excellent opportunity for new investigators

Works closely with CRAs (study monitors) Provides a well trained/qualified PI Assures/plans adequate enrollment of subjects Has a regulatory binder that includes:

1. Study protocol/amendments2. IRB approval/correspondence3. IRB approved informed consent4. Clinical brochure5. Sponsor letters6. CVs and licenses of PIs, sub-Is7. Safety reports

Investigator meeting. Make every effort to attend!

Informed consent: an continuous process; compliance with all elements required

Enrolling subjects participants: inclusion/exclusion; screening visit; randomization visit

Follow the protocol The PI is ultimately responsible for

determining causality and severity

clinical research in central oregon archie bleyer, md schs what’s available to you, to our...

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