2013-04-17: The Promise, Current State, And Future of Personalized Medicine
The promise, current state, andfuture of personalized medicineJeffrey M. Otto, PhD MBA National Director, CHI’s Center for Translational Research April 17, 2013
Overview§ Intro to personalized medicine § Short look at the early days, circa2000-2001 § Review of current state § Discussion of the gap between the initialpromise and the current state § The CTR’s approach § Summary and conclusion
Definitions§ Personalized medicine: the tailoring of medical treatment tothe individual characteristics of each patient in order to classifyindividuals into subpopulations that differ in their susceptibilityto a particular disease or their response to a speciﬁc treatment. Preventative or therapeutic interventions can then beconcentrated on those who will beneﬁt, sparing expense and sideeffects for those who will not. § Biomarkers: An indicator or pattern in a patient that reﬂectsnormal biologic processes, disease processes, or the effect ofmedical treatment. § Translational Research: Translational research transformsscientiﬁc discoveries arising from laboratory, clinical, orpopulation studies into clinical applications to reduce diseaseincidence, morbidity, and mortality.
Personalized Medicine 101The Promise § Better diagnoses and earlier interventions § More efﬁcient drug development § More effective therapies The Challenges § Intellectual property § Regulatory oversight § Reimbursement Retrieved 03/28/2013 fromhttp://www.personalizedmedicinecoalition.org/about/about-personalized-medicine
The ClassicPersonalized Medicine ParadigmToxic Not Toxic Eﬀec%ve Not Eﬀec%ve The standard approach to medicine does not distinguish between individuals…. …although individuals within a population are often very different. Biomarkers can be used to stratify patients… …and to select a safer, more efﬁcacious treatment for the individual.
Personalized medicine is akin to shoemanufacturing:Like shoes at a department store, manydifferent drugs are available. Althoughseveral drugs may be available to treata particular disease, all drugs are notsafe or effective for all people.Similar to sizing for a shoe,molecular diagnostic testsinform the selection of theappropriate drug.Although the selected drugwas not createdspecifically for you, it ismore likely to work for you.
Biomarkers currently usedin clinical medicine§ Electrocardiogram § PET brain image § Bone densitometricmeasurement § Serum chemistries § Auto-antigens in blood § Pulmonary function test § X-ray § MRI
Examples of -Omic Biomarkers§ DNA variation q SNPs, rearrangements,CNVs § DNA methylation § Chromosomalrearrangements § microRNA § RNA expression § Protein panels
The beginning of “irrationalexuberance” in personalized medicine
June 11, 2001 "We strongly believe that pharmacogenomics will shortly transform the way drugs are developed, marketed, and prescribed. I think youre going to see the beneﬁts of this appearing within a ﬁve-‐year %meframe," Gerald F. Vovis SVP & Chief Technology Oﬃcer of Genaissance Pharmaceu%cals
The Challenge of “chasing the tail”§ Statistically signiﬁcantresults are easier toachieve betweenpopulations at the leftand right ends of thediagram, but are notnecessarily meaningfulfrom a health economicsperspective Treatment efficacyFrequencyinpopulation
Genomic medicine milestones1953: Structure of DNA elucidated by Watson & Crick 1950 19601956: 1st discovery of a gene%c basis for selec%ve toxicity (primaquine – an%malarial drug) 19701977: DNA sequencing technology developed by Fred Sanger 1977: Discovery of CYP450 metabolic enzymes -‐ varia%on in these enzymes signiﬁcantly inﬂuence the eﬀec%ve dose of a drug 19801994: EGFR TKI cla19901990: The Human Genome Project is launched 20001998: HHER2+ m1998: 1sHercep-‐Milestones Research Drugs Diagnos?c Drug + CDx Regulatory
Overview of Targeted Cancer TherapiesManchana, T., Ittiwut, C., Mutirangura, A., & Kavanagh, J. J. (2010). Targeted therapies for rare gynaecological cancers. LancetOncol, 11(7), 685-693. doi: http://dx.doi.org/10.1016/S1470-2045(09)70368-7
Why so few success stories?§ Genomic era of medicine isless than 15 yrs old § Technology is notsufﬁcient on its own § Biomarkers are notnecessarily “ﬁt forpurpose” § Test needs to work withinthe existing healthcareworkﬂow § Stakeholder alignment § Is the patient the customer? Cartoon: Agres, Ted. (2009) The hunt for personalization. Retrieved 03/08/2013 fromhttp://www.dddmag.com/articles/2009/06/hunt-personalization
Catholic Health Initiatives &The Center for Translational Research
CHI: 5th Largest Hospital Network in USStrength in Numbers§ 5th largest US network§ 81 acute care hospitals in 17 states§ 40 LTC facilities§ 86,000 employees§ 2,900 physicians and midlevel providers§ Diverse markets with 90% ranked #1 or #2§ $15B in assets, $9.8B in annual revenue§ FY 2012 – provided $715M+ in charity care16
CIRI OverviewCenter for Transla%onal Research (CTR) • Discovery Research Network na%onal biospecimen collec%on & repository with EHR connec%vity • Biomarker discovery, molecular diagnos%c development & valida%on Center for Clinical Research (CCR) • Ownership and management of • Research/clinical trial opera%ons: single site, mul%-‐site, mul%-‐therapeu%c • Research data warehouse connected to EHR and de-‐iden%ﬁed pa%ent data/outcomes Center for Healthcare Innova%on (CHCI) • Design and test innova%ons in care delivery • Co-‐develop new technology and methods to manage popula%on health 17 Personalized Medicine Clinical Opera%ons + EHR Research Environment Popula%on Health Management
Executive Summary:The CHI/CIRI Research “Onion”18 CCR CTR CHCI CIRI Hospitals Government Academia Industry Lab Pharmacy Radiology Tumor Registry Pathology
Cloud-based Informatics:Network StrengthResearch Datamart CCR CTR Research Data Analysis 19
Cloud-based informatics:Patient Data & Sample AnnotationHospital Network Digital Slide Images (QC) Staging – pTNM, cTNM Images Radiology Reports Genomic Data Blood Report Demographics Clinical History Epidemiology Drugs Interac%ons/Adverse Events Consent & IRB Approval Pre-‐Sampling Ischemic dura%on Chain of Custody Anesthesia outcomes Lab Radiology ADT* Tumor Registry Pharmacy Pathology Post-‐Sampling Time to freeze samples Type and %me of ﬁxa%ve Tissue QC ELECTRONIC HEALTH RECORD BIOREPOSITORY NETWORK Drug and Biomarker Discovery Protocol De-Identified Data WarehouseBiospecimenVariablesTissue ReportAnesthesiaIschemic TimeTime to FreezeTumor StagingDiagnosis% Tumor% NecrosisImage Data DemographicsMRIPET/CT ScanImage ReportAgeRaceGene ExpressionProfilingGenotype/Sequence DataAffy Human GenomeExpression ArrayEGFRKRASFollow Up Data TreatmentTreatment OutcomeRecurrenceDisease StatusDrugsRadiationResponse Pre-‐Acquisi%on Variables Post-‐Acquisi%on Variables *Admission/Discharge/Transfer TRANSLATIONAL INFORMATICS
Bench to Bedside Translational ResearchCTR CCR Beneﬁts to CHI Hospitals Clinical Trials Personalized Medicine Beneﬁts to Pa%ents Bener Drugs Bener Diagnos%cs Research Ques?ons Hypothesis Generated Hypothesis Tested Results: IP & Publica?ons Generated Beneﬁts Research Data 21 Key Opinion Leaders Physicians Academic Researchers CIRI Staﬀ Others 21
Study Design: An Integrated ApproachFFPE Sample EHR data Biosta%s%cal Analysis Predic%ve Signature Gene%c Epigene%c Environmental 22