Title: Clinical Epidemiology: Thyroid disease and test results
1Clinical EpidemiologyThyroid disease and test
results
- Wiley D. Jenkins, PhD, MPH
- Research Assistant Professor
- Southern Illinois University School of Medicine
- Department of Family and Community Medicine
2Who I am
- My name is Wiley D. Jenkins and I am currently
Research Assistant Professor at the SIU-SOM
Department of Family and Community Medicine.
Prior to this I spent 13 years in the state
health department laboratory. - I received my MPH-Epidemiology from Tulane
University in 2002. This was followed by my PhD
in Health policy from the University of Illinois
at Chicago in 2007. - Much of my research and work experience has
concerned laboratory testing, STDs and the
quality of laboratory data.
3Learning objectives
- To understand the concepts of test sensitivity,
specificity, positive predictive value and
negative predictive value. - To understand how these factors effect the
utility of individual tests when diagnosing a
condition. - To understand how these factors are manipulated
by targeting screening tests to specific
populations.
4Performance objectives
- To be able to calculate the sensitivity,
specificity, positive predictive value and
negative predictive value for a given test. - To be able to determine if a tests result is
useful given its calculated values. - To be able to show how screening guidelines
should be adjusted to increase positive and
negative predictive values to maximize result
usefulness.
5There is always uncertainty
- Our common language incorporates uncertainty.
- Usually implies error bars
- Physics tells us that in an infinite universe,
anything is possible. Some things are just more
or less likely. - Heisenberg uncertainty principle
- statement that locating a particle in a small
region of space makes the momentum of the
particle uncertain and conversely, that
measuring the momentum of a particle precisely
makes the position uncertain - As a matter of practicality, some things are
essentially 100 or always something.
HOWEVER, its important to know when this is not
the case, and that is not always obvious.
6Quick review of terms
- Sensitivity the ability of a test to correctly
identify those who have a condition - Specificity the ability of a test to correctly
identify those who do not have a condition - Positive predictive value the number of
individuals who have a condition from all those
who test positive - Negative predictive value - the number of
individuals who do not have a condition from all
those who test negative
7The 2 x 2 table
- Youll use this a lot later in life
8Sensitivity
- 90 sensitivity implies that of all those who
have the disease, 10 will not be identified by
the test. If prevalence is 20 of the population
9Specificity
- 75 specificity implies that of all those who do
not have the disease, 25 will not be identified
by the test. If prevalence is 20 of the
population
10Positive/negative predictive value
- We complete the remaining marginals and find
- PPV for our example test is 180/380 47
- NPV is 600/620 97.
- What do we draw from this about the usefulness of
the test?
11Time for a clinical example
- 27-year-old woman
- 10 lb weight loss in past two months, not trying
- Some difficulty sleeping
- Never had anything like this before
- No signs/symptoms of depression
- Meds Oral contraceptive pills
- 1-cm, firm, smooth nodule in right lobe of
thyroid - BMI 20
- Skin slightly dry
- Remainder of physical examination normal
- What do you think?
- What should we do?
12Lab tests and results
13What next?
- Order more tests?
- Schedule for surgery?
- Prescribe medication, therapy, hamburgers?
- 1st, lets see what the tests are really telling
us.
14Thyroid stimulating hormone
- Our patient has a (low) normal TSH
- Sensitivity 92
- Specificity 94
- Are these good values?
- Assume prevalence for thyroid disease of 4 in
large populations - Calculate PPV and NPV for TSH
- Do we care more about the PPV or NPV for this
scenario?
15TSH 2 x 2 table
- Complete the table and calculate the PPV and NPV
assuming sens 92, spec 94 and prevalence
4
16TSH 2 x 2 table - completed
- We find
- PPV 37/95 31
- NPV 902/905 100
- Which do we care about and what conclusions do we
draw?
17Free T4
- Our patient has an elevated Free T4
- Sensitivity 82
- Specificity 94
- Assume prevalence for thyroid disease of 4 in
large populations - Calculate PPV and NPV for Free T4
- Do we care more about the PPV or NPV for this
scenario?
18Free T4 table
- Complete the table and calculate the PPV and NPV
assuming sens 82, spec 94 and prevalence
4
19Free T4 table - completed
- We find
- PPV 33/91 36
- NPV 902/909 99
- Which do we care about and what conclusions do we
draw?
20So
- We have
- A symptomatic woman on OCPs with a thyroid nodule
- A normal TSH
- An elevated Total T4
- An elevated Free T4
- What next?
- Scintigraphy?
- Fine Needle Aspiration Biopsy?
- Excisional Biopsy?
21Fine needle aspiration biopsy
- Indeterminate result
- 15-20 false positive rate (assume 20 for
calculations to follow) - 3 false negative rate
- If we assume a 4 prevalence of thyroid cancer,
calculate the sensitivity and specificity of the
biopsy. - Calculate the positive and negative predictive
value.
22The FNAB 2 x 2 table
- What do we know?
- Prevalence 4
- False positive rate 20
- False negative rate 3
23The FNAB 2 x 2 table
- False positives FP rate x all negatives 0.20
x 960 192 - False negatives FN rate x all positives .03 x
40 1
24The FNAB 2 x 2 table - completed
- We find
- PPV 39/231 17
- NPV 768/769 100
- Which do we care about and what conclusions do we
draw?
25Clinical course
- The patient was referred to a surgeon for
excisional biopsy. - Nodule was removed, was a benign colloid goiter,
no malignancy and no evidence of Hashimotos or
other disease.
26Lab results
27How do laboratory tests contribute to medical
errors?
- Are not always right
- May result in unnecessary further testing
- May result in unnecessary surgery
- With attendant complications
- If we assume that tests are correct 95 of the
time, what is the likelihood that, in a battery
of 20 tests, one will be a false result? - So, for every Chem 20 you order (or other battery
of 20 tests), 1 will be either a FALSE POSITIVE
or a FALSE NEGATIVE. - Need to know how to work with sensitivity and
specificity in order to know what to believe.
28Time for a population example
- Why, because we like you! (M I C)
- Seriously though, population-level studies are
translated into clinical guidelines. - In 2006, the number of reported cases of
Chlamydia trachomatis (Ct) in the US exceeded
1,000,000 for the 1st time. - The great majority of cases (70 in women) are
entirely asymptomatic. - Upwards of 40 of untreated Ct progress to PID
followed by chronic pelvic pain, ectopic
pregnancy and infertility. - How do we address this?
29Chlamydia trachomatis screening
- Diagnostic companies have spent considerable
money developing rapid and accurate tests for the
detection of Ct. - Current tests offer
- 95 sensitivity
- 98 specificity
- So, do we just test everyone? Lets see.
(150,000,000 women) x (10/test) need for
other alternative. - Who has Ct?
- 0.35 all Americans
- 0.52 women
- 0.17 men
- 1.76 Black women
- 0.24 White women
- 2.9 women aged 15-19
- 2.8 women aged 20-24
30The Ct 2 x 2 table - completed
- For the general population (0.35) we find
- PPV 33/233 14
- NPV 9765/9767 100
31The Ct 2 x 2 table - completed
- For all women (0.52) we find
- PPV 49/248 20
- NPV 9749/9752 100
32The Ct 2 x 2 table - completed
- For all women aged 16-24 (2.9) we find
- PPV 276/470 59
- NPV 9516/9530 100
33Utility of targeted testing
- By purposefully targeting our testing to at-risk
populations, we increase the PPV of the test and
better allocate resources. - General population
- Prevalence 0.35 PPV 14
- All women
- Prevalence 0.52 PPV 20
- Women aged 16-24
- Prevalence 2.9 PPV 59
- Females admitted into juvenile detention
centers?? - Prevalence 12-20 PPV gt90!
- Other risk factors important.
- This works for clinical guidelines for screening,
such as mammography, prostate exams, cholesterol
34Take away items
- Not a good practice to order tests just because
we can or for fishing expeditions. - Costs can quickly become quite significant (e.g.
compare HC expenditure for US versus other
industrialized countries and resultant health
outcomes). - Utility of the results is directly impacted by
the population/person to which they are given. - Multiple tests increase the likelihood of a
correct diagnosis. - E.g. Ct in 16-24, PPV 59
- Additional test on just these positives (e.g. 59
prevalence) with same sens/spec results in PPV of
99! - In the absence (always) of the ultimate test,
use multiple results to arrive at the best
conclusion.
35Questions or comments?? Contact info Wiley D.
Jenkins, PhD, MPH wjenkins_at_siumed.edu 217-545-8717