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Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate past president, Israeli Society of Hypertension, Sheba Medical Center, Tel Hashomer Tel Aviv University

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Page 1: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Guidelines & Personalized MedicineFriends or Enemies

Prof. Yehonatan Sharabi, MD, FAHA

Director, Hypertension Unit

Immediate past president, Israeli Society of Hypertension,

Sheba Medical Center, Tel Hashomer

Tel Aviv University

Page 2: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Figure 4

The Lancet 2018 392, 2052-2090DOI: (10.1016/S0140-6736(18)31694-5)

Leading 20 causes of YLLs globally in 2016 and 2040 by rank order

Page 3: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Figure 4

The Lancet 2018 392, 2052-2090DOI: (10.1016/S0140-6736(18)31694-5) Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC

BY 4.0 license Terms and Conditions

Page 4: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Figure 6

The Lancet 2018 392, 2052-2090DOI: (10.1016/S0140-6736(18)31694-5)

Page 5: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Figure 6

The Lancet 2018 392, 2052-2090DOI: (10.1016/S0140-6736(18)31694-5) Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC

BY 4.0 license Terms and Conditions

WHO: “high blood pressure – No 1 contributor for preventable death worldwide”

Page 6: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Mills KT, Circulation, 2016:

We are doing better but can do much better…

1995 2015

Awareness 58% 67%

Treatment 44% 55%

Control 18% 28%

Page 7: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Why?

Page 8: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Eyal Zimlichman MD, MSc8

Page 9: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Solution: structured protocols?

• Protocol based treatment

– ACS

– Decompensated HF

– Pneumonia

• Chronic conditions?

Page 10: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Clinical Practice Guidelines

12

“Clinical practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances.”Purposes:

• standardization of medical care

• Reduce discrepancies

• Improve outcome

• Reduce costs

* Institute of Medicine. Guidelines for clinical practice. 1990

Page 11: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

2018 ESC/ESH Guidelines for the managementof arterial hypertension

• 89 pages

• 33 tables

• 629 references

Page 12: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

The quest to clinically significant treatment:

Penicillin to pneumonia…

• Tilghman CR, Finland M,Arch Intern Med, 1937

• Observation

• N= dozens – hundreds

• Effect on mortality: -85%

Page 13: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

The quest for statistically significant treatments…

Page 14: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

𝑥

𝑁≫ 𝑃𝑣𝑎𝑙𝑢𝑒

The quest to P<0.05…

N P

The quest for statistically significant treatments…

Page 15: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

The quest for statistically significant treatments…

• Large clinical trials THOUSANDS

• Examples:• PROGRESS N=6105

• ADVANCE N=11000

• HYVET N=3845

• LIFE N=9193

• SCOPE N=4964

• ASCOT N=19257

• ACCOMPLISH N=10995

Page 16: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

The quest for statistically significant treatments…

• Metanalyses of HUNDREDS OF THOUSANDS

• Examples from ESH guidelines on how to treat your patient:

• Thomopoulos et al N=247,006

• Emdin et al N=100,354

• Ettehad et al N=613,815

Published in highly ranked journals

Page 17: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Small step to mankind, Giant leap to CV…

Page 18: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

ARB’s CV outcome

BMJ. 2011; 342: d2234.

Page 19: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

ARB’s CV outcome

BMJ. 2011; 342: d2234.

Page 20: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

The quest for statistically significant treatments…

• Databases – MILLIONS !!

Page 21: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Old school statistics applied on huge populations

Where is my patient? An average of all?

Page 22: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Patients differ from each other

• Variability is the law of life, and as no two faces are the same, so no two bodies are alike, and no two individuals react alike and behave alike ...

• If it were not for the great variability among individuals, medicine might as well be a science and not an art

Sir William Osler

Page 23: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

34 y/o black female 52 y/o Caucasian male

Patients differ from each other

Page 24: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate
Page 25: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Meta-regression analyses assessing the relationship between the hypertension cure rate

after PTRA and mean age, publication year.

Trinquart L et al. Hypertension 2010;56:525-532

Copyright © American Heart Association

Page 26: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

PERSONALIZED MEDICINE

Personalized medicine is a model that proposes the customization of healthcare, with decisions and practices being tailored to the individual patient.

Page 27: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Basic data analytics: focus on one factor

• LIFE study – LVH

• PROGRESS – post CVA

• RENAAL - CKD

Page 28: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Advanced data analytics: multiple factors modeling

Page 29: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Modeling in medicine: current generation – scoring systems

• Atrial fibrillation and anticoagulants

– From yes/no to ChadsVasc score

• Statins in primary prevention

– From LDL levels to ESC/AHA risk score

Page 30: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Future modeling: BIG DATA

Big data is a broad term for data sets so large or complex that traditional data processing applications are inadequate.

Page 31: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Big data enables machine learning

Machine Learning and Prediction in Medicine

Chen et al, NEJM, June 2017:

• Machine-learning methods are particularly suited to predictions based on existing data

• Machine-learning algorithms can improve the accuracy of prediction over the use of conventional regression models by capturing complex, nonlinear relationships in the data

Page 32: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

• Genomics

• Epigenomics

• Pharmacogenomics

• Proteomics

• Metabolomics

• Microbiotomics

• Omics, Omics, Omics…

Page 33: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

35Wearable into Health Predictor

MACHINE LEARNINGSMARTPHONESENSORS & DEVICES STORAGE

24/7 Continuous - not sample diagnostic

MicrosoftJawboneGoogleSamsung

BandManage

Page 34: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

RCT Vs Big Data analytics

Page 35: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate
Page 36: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

38ר איל צימליכמן"ד

Children’s Hospital, BostonSCAMPS – Standardized Clinical Assessment and Management Plan

Guidelines – next generation

Page 37: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Guidelines & Personalized Medicinecan be friends

• Guidelines, with its limitations, provides framework

• Guidelines should be followed NOT religiously

• Physicians should be comfortable to personalize treatment

• Clinical experience

• Experts guidance

• Common sense

• Modern technology would assist us in the near future

Page 38: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

Overview of the

meeting

Patient Centered Meeting is about translating the wealth of data to clinical practice

Case based learning

Different pateint prototypes from real world

A journey from the very beginning, through the management of a chronic disease to complex challenging cases

Motivational interview – how to make it happen

Page 39: Guidelines & Personalized Medicine Friends or Enemies · Guidelines & Personalized Medicine Friends or Enemies Prof. Yehonatan Sharabi, MD, FAHA Director, Hypertension Unit Immediate

THANK YOU AND WELCOME TO PCM !