Download The Value and Performance of 20/20`s Blood Test

PAULA’s Test
Early Detection of Lung Cancer
Webinar #2 Technical Concepts
January 26 2013
Training Overview
• Sales Presentation – Elevator Pitch
• Sales Collateral Folder
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Physician Overview
Sample Result
Validation Whitepapers I & II
New LC Screening Guidelines
NCI Press Release of NLST Study
NCCN Guidelines and High Risk Population
• Technical Description of PAULA’s Test
• Technical Performance
• Operational Details
– Requisition form, Consent Form, Shipping, etc.
Slide 2
Elevator Pitch
Q: “What do you have for me today?”
I have a blood test for lung cancer for your high risk patients. It
can help find lung cancer in asymptomatic patients in the early
stage of development. When caught early, the tumor is removed
before it spreads, and the patient is spared treatment from
advanced disease and has a good chance of surviving long term.
It is for your patients at “High Risk” with a minimum of 20
pack/years smoking history, age 50 and over.
Q: “How does it work?” or “What does it look at?”
The test is a panel of 4 cancer markers (tumor antigens)
associated with the presence of lung cancer.
Slide 3
Initial Discussion
In a typical discussion about the test, several basic subjects are
usually discussed:
• Which markers the test is looking at.
• The Technical Performance
– Sensitivity/ Specificity
– Sub types of Lung Cancer
– Ability to detect disease by Stage
• Testing Logistics
Once the basic questions and answers have been asked and
answered, it is important to quickly move to the process of
qualifying whether the doctor is interested in moving ahead.
Slide 4
Initial Conversation
By asking the right questions you can help the provider
acknowledge the problem and need for a practical solution.
The Doctor Asks:
You Ask:
“Who do I use it on?”
“Tell me about your high risk patient
population?”
“What is your Sensitivity?”
“What do you do now to find LC?”
“How is this better than just sending
patients directly to a CT?”
“How do you feel about the new lung
cancer screening guidelines?”
Slide 5
Technical Questions
You will be asked these questions:
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What is your test looking at?
Who is paying for the test?
What is your sensitivity/specificity?
What is your false positive rate?
What do I do with a high score?
What if the CT does not show anything?
What types of Lung Cancer do you pick up?
How early do you pick up lung cancer when it is present?
Will it pick up other cancers?
Can I use it on younger patients? Non-smokers, pot smokers?
How many lung cancers have you found?
How many tests will I need to run before I find one LC?
Slide 6
Moving Ahead
After the basic information is presented it is important to advance
the sales process toward a conclusion. Here are some key questions
to ask.
Getting patients tested:
“It is important to make sure that the patients that should get tested are
identified. What could you do to make sure the right patients get tested?”
Plan to get started:
“We want to show success by finding a patient that would have gone undetected.
We will probably need to get 50-100 tests done. Would you to try this for 4
weeks to see if we can find that patient?” (would need a min. 2 per day)
Follow-up steps, “The plan is for you and I to review your progress in 4
weeks to see what happened to the patients that were tested.”
Slide 7
Sales Collateral
Sales Collateral Folder
• Left Side
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Physician Overview
Sample Result report
Validation Studies
Patient Brochure
• Right Side
– Summary of LC Screening Guidelines
– NCCN Guidelines and patient risk levels
– Summary of NLST National Lung Screening Trial
Slide 8
LC Screening Guidelines
Important Facts
• Based on results of a large NCI study called NLST (National Lung Screening
Trial) with 53,000 patients. SEE THE DOCUMENT IN SALES FOLDER.
• Originally designed to compare X-ray to Low Dose CT for Dx of LC.
• Guidelines adopted from recommendations of the NLST.
• Published by American Lung Assn, American Cancer Society, ASCO, CHEST,
NCCN, and others.
• Recommendations have been controversial and has mixed endorsements.
Slide 9
Following Guidelines
Guidelines call for:
• Low Dose CT for 100% of high risk patients yearly for 3
years.
RISK STATUS
AGE
High Risk
Moderate Risk
55-74 y
>= 50 y
Asymptomatic highrisk patient
SMOKING HISTORY
>= 30 pack year
>= 20 pack year
LD CT
CT Scan
Positive Finding in
24% of patients
Slide 10
So, what’s the problem?
Key Objections:
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Not covered by insurance.
Patient Compliance to get test done.
24% of patients receive a positive finding.
Of these, 96.4% may be False Positives.
Often will lead to unnecessary additional workups and risks, including
over-diagnoses, radiation exposure from repeat CT, invasive
procedures such as biopsies.
Asymptomatic highrisk patient
LD CT
CT Scan
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96% False
Positives
Not Covered By
Ins
Risk of invasive
biopsies and
additional CT
scans
Positive Finding in
24% of patients
Slide 11
Who is Objecting?
Panel Says No to Medicare Coverage for Lung
Cancer Screening
Zosia Chustecka May 01, 2014
After a day's deliberation, an advisory panel voted last night against recommending national Medicare
coverage for annual screening for lung cancer with low-dose computed tomography (CT) in high-risk
individuals.
"We have the benefit of the USPSTF recommendation which conducted an independent two-year
evidence review resulting in a B grade for a population 55 to 80 with a heavy smoking history," FentonAmbrose told MEDCAC. "The threshold of evidence has been met to support Medicare coverage for
lung cancer screening within the USPSTF population."
MEDCAC committee members disagreed, noting that questions remain regarding the application of the
available evidence to the Medicare population and the likelihood that community-based screening
would replicate the positive results of the National Lung Screening Trial without the safeguards of a
rigorous randomized controlled trial. MEDCAC members also raised concerns about the ability to
accurately identify high risk individuals in practice, patient adherence to lung cancer screening
programs, the definition of a positive finding, as well as the potential impact of incidental findings on
scans that may lead to unnecessary invasive procedures and adverse events.
Slide 12
Who Else is Objecting?
Evidence Lacking to Support or Oppose Low-dose CT Screening for
Lung Cancer, Says AAFP
Inability to Make Harms/Benefits Comparison Precludes Definitive Recommendation
January 13, 2014 04:50 pm Cindy Borgmeyer – Citing a paucity of high-quality evidence on which to
base a comparison of relative harms and benefits, the AAFP today released an "I" recommendation
regarding the routine use of low-dose CT scans in screening high-risk, older smokers for lung cancer.
The Academy's action puts it at odds with a recommendation issued last
month(www.uspreventiveservicestaskforce.org) by the U.S. Preventive Services Task Force (USPSTF).
Specifically, the new AAFP recommendation states: "The AAFP concludes that the evidence is
insufficient to recommend for or against screening for lung cancer with low-dose computed
tomography (LDCT) in persons at high risk for lung cancer based on age and smoking history."
The USPSTF, on the other hand, "recommends annual screening for lung cancer with low-dose
computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history
and currently smoke or have quit within the past 15 years."
Slide 13
Alternate Approach: PAULA’s Test
PAULA’s Test:
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Is positioned before sending patients to CT
A simple test, requiring 1 tube of blood drawn at the office.
Covered by most insurance plans and minimal cost to patients.
Meant to stratify out those at elevated risk for lung cancer.
Provides a simple result of actionable information.
Asymptomatic
high-risk smoker
Early Diagnosis of Lung
Cancer
PAULA’s Test
CT Scan
Slide 14
Confidential
Technical Performance
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How are Diagnostics Measured?
What is Sensitivity?
What is Specificity?
What is a False Positive?
What is the impact of a false positive?
How & Why did we decide where to set the point
on the AUC Curve?
• What is more important: True positive or False
Positive?
Slide 15
How are Diagnostics Measured?
The following terms are fundamental to understanding the utility
of clinical tests:
True positive:
False positive:
True negative:
False negative:
the patient has the disease and the test is positive.
the patient does not have the disease but the test is positive.
the patient does not have the disease and the test is negative
False negative: the patient has the disease but the test is negative.
Source: http://ceaccp.oxfordjournals.org/content/8/6/221.full.pdf+html
Clinical tests: sensitivity and specificity by Abdul Ghaaliq Lalkhen MB ChB FRCA and Anthony McCluskey BSc MB ChB FRCA
Slide 16
How are Diagnostics Measured?
When evaluating a clinical test, the terms sensitivity and specificity are most
commonly used.
Source: http://ceaccp.oxfordjournals.org/content/8/6/221.full.pdf+html
Clinical tests: sensitivity and specificity by Abdul Ghaaliq Lalkhen MB ChB FRCA and Anthony McCluskey BSc MB ChB FRCA
Slide 17
Sensitivity
What is “Sensitivity”?
The sensitivity of a clinical test refers to the ability of the test to correctly identify
those patients with the disease.
Sensitivity = True positives
True positives + False negatives
A test with 100% sensitivity correctly identifies all patients with the disease. A test
with 80% sensitivity detects 80% of patients with the disease (true positives) but 20%
with the disease go undetected (false negatives). A high sensitivity is clearly important
where the test is used to identify a serious but treatable disease (e.g. cervical cancer).
Source: http://ceaccp.oxfordjournals.org/content/8/6/221.full.pdf+html
Clinical tests: sensitivity and specificity by Abdul Ghaaliq Lalkhen MB ChB FRCA and Anthony McCluskey BSc MB ChB FRCA
Slide 18
Specificity
What is “Specificity”?
The specificity of a clinical test refers to the ability of the test to correctly identify
those patients without the disease.
Specificity = True negatives
(True negatives + False positives)
Therefore, a test with 100% specificity correctly identifies all patients without the
disease. A test with 80% specificity correctly reports 80% of patients without the
disease as test negative (true negatives) but 20% patients without the disease are
incorrectly identified as test positive (false positives).
Source: http://ceaccp.oxfordjournals.org/content/8/6/221.full.pdf+html
Clinical tests: sensitivity and specificity by Abdul Ghaaliq Lalkhen MB ChB FRCA and Anthony McCluskey BSc MB ChB FRCA
Slide 19
Getting Technical
The following slides begin the technical discussion of the PAULA’s
Test. While we expect you to be prepared to present the
technical information relating to the test, we strongly advise
Representatives to focus on the approach to early detection,
changing survival rates for lung cancer. PAULA’s Test can provide
significant clinical utility to they physician that is motivated to
change the rates of death due to lung cancer in his patient
population.
The discussion of the technical material can be challenging for
even technical experts. Be aware that some physicians may
engage in an intellectual technical debate but may not likely
have a true interest in using the test.
Slide 20
Makeup of the Panel
“The tumor antigens have individually and collectively been
shown by dozens of outside investigators around the world to
distinguish early lung cancer from risk-matched controls. The
combination of “established” biomarkers with more innovative
analytes such as autoantibodies coupled with advanced
statistical treatment provides an optimal panel for screening
divers
Source: Clinical Performance of a Multiplex Biomarker Blood Test for the Early Detection of Lung
Cancer e, asymptomatic patient populations.
Slide 21
Components of Panel
A panel of 4 biomarkers (3 tumor antigens & 1 auto-antibody)
• CEA
• CA-125
• CYFRA
• NY-ESO1 (Auto Antibody)
Slide 22
Confidential
Technical Performance of Paula’s Test
• What is the sensitivity of Paula’s Test?
• What is Specificity of Paula’s Test?
• What is the False Positive Rate?
74%
80%
20%
Slide 23
Four markers = Panel
“The whole is greater than the sum of
the parts…”
Slide 24
Types of LC found
Q: What types of lung cancer to you “detect”?
(the answer can be found in the document “Clinical Performance of Multiplex…”
The relevant comment is that the vast majority of lung cancers are from
Adenocarcinoma, Squamous Cell and Brocholoalveolar carcinomas.
Slide 25
How Early can you detect?
Q: How early are you able to “detect”?
(the answer can be found in the document “Clinical Performance of Multiplex…”
A: We are able to see high scores in early stage (stage 1).
Follow up Question:
Q: Is it possible to detect the cancer before it is visible on a CT?
A: Theoretically, Yes. A lot depends on how the CT was run by the radiologist. If
the CT slice interval is wide enough, you could have a small tumor fall in between
the CT slices. This is something that you should discuss with the radiologist.
Slide 26
Other Cancers?
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What about Small Cell LC?
What about other rare types of LC?
Can it find cancer in other parts of the body?
Can test be used in detecting LC in never smokers
Slide 27
Technical Objections
“Sensitivity is too low.”
• Compared to What?
– What are you doing now?
– How many LC’s have you typically found early?
– Other common cancer screens?
• Is going from 0% to 74% enough of an improvement to get
you testing?
J Med Screen. 2000;7(2):105-10.
The sensitivity, specificity, and positive predictive value of screening mammography and symptomatic status.
RESULTS:
Sensitivity was lower for women with other symptoms (60.0%) than asymptomatic women (75.6%), or women
with significant symptoms (80.8%). Specificity was lower for women with significant symptoms (73.7%) than
asymptomatic women (94.9%), or women with other symptoms (95.4%).
http://www.ncbi.nlm.nih.gov/pubmed/11002452
Slide 28
Technical Objections
False Positive rate is too high:
• Compared to What?
• The New guidelines say go straight to CT. (96% false positive
rate).
• The impact of a high score (“false positive”) is simply sending
a patient for a CT. You could be doing that anyway.
• At 20% FP, the top 20% would go to CT; the other 80% could
be ruled out for CT’s.
• Other commonly used tests have false positive rates:
– PAP
– Mammogram: Specificity ranges from 73% to 95%
J Med Screen. 2000;7(2):105-10.
The sensitivity, specificity, and positive predictive value of screening mammography and symptomatic status.
Kavanagh AM1, Giles GG, Mitchell H, Cawson JN.
Slide 29
Summarizing Objections
There is no such thing as a perfect test.
In the world of diagnostic tests, there is always a tradeoff
between finding True Positives and minimizing False Positives?
You need to understand what is more important to the
individual doctor?
Most will favor finding True cancers vs avoiding false positives?
With guidance from our panel of physician advisors, we set the
cutoff at a point that would appeal to the majority of physicians.
Our advisors told us:
• It is important to maximize the number of true positives, but…
• Don’t exceed a 20% false positive rate.
Slide 30
“Number Needed to Test”
What is “NNT” or “NNS”?
The NNS represents the number of patients who must be enrolled in a screening program
over a given period of time (here normalized to 10 years) to prevent one death from the
disease in question. (The number of screening tests that would be required to prevent one
death would be up to 10 times higher, depending on the frequency of screening.) The NNS
reflects both the prevalence of the disease and the effectiveness of therapy, and has the
advantage of being easy to calculate and intuitively useful to clinicians and patients.
It does not, however, specifically account for the risks or the costs of screening.
Source:
Am Fam Physician 2001;63:513-22.) Screening for Cancer: Evaluating the Evidence
THOMAS J. GATES, M.D., Lancaster General Hospital, Lancaster, Pennsylvania
How does our NNS compare to other tests?
Slide 31
Other Common Tests
What is the NNS for other common tests?
Pap smear: NNS is 1,140
Mammography age<50: NNS ranges from 746 in 40-49
y/o down to 377 in 70-79 y/o
Sources:
Am Fam Physician 2001;63:513-22.) Screening for Cancer: Evaluating the Evidence
THOMAS J. GATES, M.D., Lancaster General Hospital, Lancaster, Pennsylvania
AJR Am J Roentgenol. 2012 Mar;198(3):723-8. doi: 10.2214/AJR.11.7146.
Mammography screening: a new estimate of number needed to screen to prevent one breast cancer death.
Slide 32
Final Question
Is running 100 tests to find 1 case of LC something you
are ready to do?
Slide 33
Relevant Subject Matters
Lung Cancer
in practice
LC Statistics,
treatment
& Costs
Insurance &
Reimburse
ment
LC
Screening &
Guidelines
CT's & Xrays,
providers,
EMR's &
Meaningful
Use
PAULA'S
Test
Early
Detection &
Diagnostics
Technical:
PPV,
Sensitivity,
False
Positives,
etc.
FDA &
Publications
Competitor
s & Other
Tests
Reporting
Results &
High Scores
Slide 34
End of Technical Training
Break for Questions
Slide 35
Getting Everyone involved
Who needs to help?
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Provider
Medical Assistants
Phlebotomists
Anyone else who knows which
patients are/were smoking.
Slide 36
Testing Operation Overview
Collection Method
• Requires our Collection Kit
– Insulated Box with Ice packs
– Requisition form, consent form, Fedex shipping label.
– 1 SST “tiger top” blood tube
• Requirements
– Tube must be spun
– Must remain refrigerated (not frozen)
– Must arrive within 72 hours from time of draw.
Slide 37
Operational Overview
Link to Operations Training PPT
Slide 38
Thank You
Happy Selling!
Barry Cohen
[email protected]
240-453-6339 ext. 103
Slide 39