Precision prevention and tailored screening public

Precision Prevention and Tailored
Screening: who gains and who loses?
Graham Colditz, MD, DrPH
April 26, 2018
Department of Surgery
Division of Public Health Sciences

Disclosures
I have no conflicts of interest
• Talk – slides at
http://bit.ly/precision-prevention-gainers-losers

Goals
• Identify overarching issues
• Identify trade-offs
• Gap between evidence and implementation
• Benefits, harms, and measures of success
• Time horizon or “Are we there yet”?

Goals - Implementation Science in “Precision”
settings
Ensure that knowledge and materials produced by
health research actually lead to improved population
health:
1. Reaching intended audience
2. Adapted to local circumstances
3. Implemented effectively, safely, equitably, and in a timely manner
that keeps patient at forefront of decision making

Key Terms
Precision medicine – uses information about a person’s genes,
environment, and lifestyle to prevent, detect, diagnose, and treat disease
• Allows for more accurate prediction of which treatment and prevention strategies
for a particular disease will work in which groups of people
Precision prevention – tailored approach that considers genetic
variants, mechanisms, and environmental and lifestyle factors to reduce the
risk of disease
• Mainly related to reducing the risk of cancer
Tailored screening – tailored approach based on level of risk
classified by lifestyle/~omics/or other biomarkers to maximize
benefits and reduce harms.

Criteria for evaluation of screening program
Scientific
• Validity and reliability of test
• Natural history of disease
• Effective treatment available
Ethics
• Does treatment prolong life (lead time, length bias)
• Is program acceptable to target population?
Economics
• Can we afford false positives
• Can we afford follow-up of positive patients
• Is program cost effective?
Wilson J, Jungner G. 1968.
Screening for Disease.
Geneva, Switz.:World Health Organ.

Precision prevention and tailored screening –
50 years later
The right intervention
In the right person
At the right time in disease process (life)
Why precision approaches?
Maximizes benefit
Reduces harm
Increases efficiency

Overlapping relative
frequency distributions
in affected and
unaffected individuals
Wald et al. BMJ 1999

Wald et al. BMJ 1999

High risk vs population strategy
Lynch syndrome
Identify all families – prevent 7,000 cases of CRC per year in
USA
Population wide screening
Increase US population-wide screening from 60% to 80%
reduce CRC incidence by over 30,000 cases per year

Integrated breast risk prediction: lifestyle score,
mammographic breast density, polygene score
• Lifestyle = age, age at menopause, age at first birth, biopsy
confirmed benign breast disease, family history, current use
of estrogen or estrogen plus progestin therapy, current BMI,
height, current alcohol
• Mammographic breast density
• Polygene score – 147 SNPs

0
2
4
6
8
10
12
14
16
18
20
<4.0 4.0-4.9 5.0-5.9 6.0-6.9 7.0-7.9 8.0-8.9 9.0-9.9 10.0-11.9 12.0-14.9 15.0-19.9 ≥ 20.0
Percent
18 year score 2
case control
33% cases arise from
14% of total population
Case
noncase
16% 10% 12% 10% 8% 7% 7% 8% 8% 7% 7%
Plot of case non case distribution by predicted 18yr risk score

Precision, high risk / tailored vs population approach
• What are our outcomes using this approach?

Precision, high-risk / tailored vs population approach
What are our outcomes using this approach?
Some ideas
• Intervene / screen high-risk
• Offer second level intervention on intermediate risk
• Reassure low risk
• Offer lower frequency, lower cost approaches to lower risk
population
• Increased costs?
• Fewer adverse events from screening?

Framework for
precision prevention
and tailored
screening for
cancer
Figure 1.
http://cebp.aacrjournals.org/content/cebp/23/12/2713.full.pdf
Rebbeck CEBP 2014
$
Prevention and
Screening
Guidelines

Institute of Medicine
Crossing the quality chasm
A new health system for the 21st Century,
National Academy Press
2001
Name guidelines not fully implemented?

Does precision prevention and tailored screening
increase cost efficiency?
Name examples please?
What is evidence?

Getting the right intervention to the right individual
at the right time in life
List challenges?

List challenges?
Ease of use
Comprehension
Language
Concepts of disease and prevention
– health literacy of end user
Purpose and benefits clear?
Risks in context?

Are we studying how to get the precision intervention
to the end user?
Is it
Understandable?
Engaging?
Actionable?

Technology
Social setting/cultural belief structures
Time frame

Does precision classification improve enough over
cheaper and broader (more accessible) classifier to
impact health outcomes?

Does precision classification improve enough over
cheaper and broader (more accessible) classifier to
impact health outcomes?
• Population satisfaction with practice (acceptability)
• System more effective?
• (benefits outweigh risks at population level)
• System more cost-effective?
• Have we avoided exacerbating disparities &
maximized health equity?

Can we define and measure benefits? Name a few…

Can we define and measure benefits? Name a few…
Health system level?
At the provider level?
At the patient level?
At the community level?

Can we define and measure harms, and their time
course?

Key questions across applications of precision
prevention and tailored screening
1. Can we clearly define benefits of precision approach
vs population approach?
2. Can we communicate the benefits of this approach?
3. Does precision approach increase cost efficiency?
4. Are we studying the end user in sufficient detail?
5. Does precision classification improve enough over
cheaper and broader classifier?
6. Can we measure benefits?
7. Can we measure harms?

Thank you
Graham Colditz
colditzg@wustl.edu

Precision prevention and tailored screening public

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