![Page 1: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/1.jpg)
The promise, current state, and future of personalized medicine
Jeffrey M. Otto, PhD MBA National Director, CHI’s Center for Translational Research
April 17, 2013
![Page 2: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/2.jpg)
Overview
§ Intro to personalized medicine § Short look at the early days, circa
2000-2001 § Review of current state § Discussion of the gap between the initial
promise and the current state § The CTR’s approach § Summary and conclusion
![Page 3: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/3.jpg)
Definitions
§ Personalized medicine: the tailoring of medical treatment to the individual characteristics of each patient in order to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment. Preventative or therapeutic interventions can then be concentrated on those who will benefit, sparing expense and side effects for those who will not.
§ Biomarkers: An indicator or pattern in a patient that reflects normal biologic processes, disease processes, or the effect of medical treatment.
§ Translational Research: Translational research transforms scientific discoveries arising from laboratory, clinical, or population studies into clinical applications to reduce disease incidence, morbidity, and mortality.
![Page 4: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/4.jpg)
Personalized Medicine 101
The Promise § Better diagnoses and earlier interventions § More efficient drug development § More effective therapies The Challenges § Intellectual property § Regulatory oversight § Reimbursement Retrieved 03/28/2013 from http://www.personalizedmedicinecoalition.org/about/about-personalized-medicine
![Page 5: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/5.jpg)
The Classic Personalized Medicine Paradigm
Toxic 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.
![Page 6: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/6.jpg)
Personalized medicine is akin to shoe manufacturing:
Like shoes at a department store, many different drugs are available. Although several drugs may be available to treat a particular disease, all drugs are not safe or effective for all people.
Similar to sizing for a shoe, molecular diagnostic tests inform the selection of the appropriate drug.
Although the selected drug was not created specifically for you, it is more likely to work for you.
![Page 7: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/7.jpg)
Biomarkers currently used in clinical medicine
§ Electrocardiogram § PET brain image § Bone densitometric
measurement § Serum chemistries
§ Auto-antigens in blood § Pulmonary function test § X-ray § MRI
![Page 8: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/8.jpg)
Examples of -Omic Biomarkers
§ DNA variation q SNPs, rearrangements,
CNVs § DNA methylation § Chromosomal
rearrangements § microRNA § RNA expression § Protein panels
![Page 9: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/9.jpg)
The beginning of “irrational exuberance” in personalized medicine
![Page 10: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/10.jpg)
June 11, 2001 "We strongly believe that pharmacogenomics will shortly transform the way drugs are developed, marketed, and prescribed. I think you're going to see the benefits of this appearing within a five-‐year %meframe,"
Gerald F. Vovis SVP & Chief Technology Officer of Genaissance Pharmaceu%cals
![Page 11: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/11.jpg)
The Challenge of “chasing the tail”
§ Statistically significant results are easier to achieve between populations at the left and right ends of the diagram, but are not necessarily meaningful from a health economics perspective
Treatment efficacy
Freq
uenc
y in
pop
ulat
ion
![Page 12: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/12.jpg)
Genomic medicine milestones
1953: Structure of DNA elucidated by Watson & Crick
1950 1960
1956: 1st discovery of a gene%c basis for selec%ve toxicity (primaquine – an%malarial drug)
1970
1977: 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
1980
1994: EGFR TKI class discovered
1990
1990: The Human Genome Project is launched
2000 2010
1998: Hercep%n approved by FDA for HER2+ metasta%c breast cancer
1998: 1st CDx developed by Dako – Hercep-‐Test
2003: The Human Genome Project is completed
2004: Targeted therapies approved in colorectal and NSC lung cancer
2007: FDA updated Coumadin label to recommend gene%c tes%ng for dosage administra%on
2011: 1st simultaneous approval for drug (Zelboraf) & CDx for melanoma with BRAF V600E muta%on
2011: Simultaneous approval for Xalkori & CDx for NSCLC with abnormal ALK gene
Milestones Research
Drugs
Diagnos?c
Drug + CDx
Regulatory
Milestones Research
Drugs
Diagnos?c
Drug + CDx
Regulatory
![Page 13: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/13.jpg)
Overview of Targeted Cancer Therapies
Manchana, T., Ittiwut, C., Mutirangura, A., & Kavanagh, J. J. (2010). Targeted therapies for rare gynaecological cancers. Lancet Oncol, 11(7), 685-693. doi: http://dx.doi.org/10.1016/S1470-2045(09)70368-7
![Page 14: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/14.jpg)
Why so few success stories?
§ Genomic era of medicine is less than 15 yrs old
§ Technology is not sufficient on its own
§ Biomarkers are not necessarily “fit for purpose”
§ Test needs to work within the existing healthcare workflow
§ Stakeholder alignment § Is the patient the customer?
Cartoon: Agres, Ted. (2009) The hunt for personalization. Retrieved 03/08/2013 from http://www.dddmag.com/articles/2009/06/hunt-personalization
![Page 15: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/15.jpg)
Catholic Health Initiatives & The Center for Translational Research
![Page 16: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/16.jpg)
CHI: 5th Largest Hospital Network in US
Strength 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 care
16
![Page 17: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/17.jpg)
CIRI Overview
Center 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
![Page 18: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/18.jpg)
Executive Summary: The CHI/CIRI Research “Onion”
18
CCR
CTR
CHCI
CIRI Hospitals
Government
Academia
Industry Lab
Pharmacy
Radiology
Tumor Registry
Pathology
![Page 19: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/19.jpg)
Cloud-based Informatics: Network Strength
Research Datamart
CCR CTR
Research Data
Analysis
19
![Page 20: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/20.jpg)
Cloud-based informatics: Patient Data & Sample Annotation
Hospita
l 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 Warehouse
Biospecimen Variables
Tissue Report
Anesthesia Ischemic Time Time to Freeze
Tumor Staging Diagnosis % Tumor
% Necrosis
Image Data Demographics
MRI PET/CT Scan Image Report
Age Race
Gene Expression Profiling
Genotype/ Sequence Data
Affy Human Genome Expression Array
EGFR KRAS
Follow Up Data Treatment
Treatment Outcome Recurrence
Disease Status
Drugs Radiation Response
Pre-‐Acquisi%on Variables
Post-‐Acquisi%on Variables
*Admission/Discharge/Transfer
TRANSLATIONAL INFORMATICS
![Page 21: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/21.jpg)
Bench to Bedside Translational Research
CTR
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
![Page 22: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/22.jpg)
Study Design: An Integrated Approach
FFPE Sample
EHR data
Biosta%s%cal Analysis
Predic%ve Signature
Gene%c
Epigene%c
Environmental
22
![Page 23: 2013-04-17: The Promise, Current State, And Future of Personalized Medicine](https://reader034.vdocuments.us/reader034/viewer/2022051816/54473a04afaf9f65178b47d2/html5/thumbnails/23.jpg)
Thank You