1. Diagnostic studies
Adrian Boyle

2. Diagnostic studies: objectives
Sensitivity
Specificity
Positive and negative predictive values
Accuracy
Likelihood ratios
Receiver Operator Curves

3. Diagnostic studies: design
Cross sectional comparison to a gold standard
Cohort study
RCT
That’s the way we’ve always done it

4. Basics Gold standard +ve Gold standard -ve Test +ve A B A+B -ve C D
A+C
B+D

5. Basics Sensitivity A/A+C True positive SNNOUT
How good is this test at picking up disease?
SNNOUT
A SeNsitive test which is Negative effectively rules OUT a diagnosis

6. Specificity D/B+D True negative SpPin
How good is this test at excluding the well?
SpPin
A SPecific test which is Positive rules a case IN

7. Basics PPV A/A+B Post +ve test prob
If a patient has a +ve test what is the probablity that they have the disease

8. Basics NPV D/C+D Post test prob of –ve test
If a patient has a negative test, the probablity that they do not have the condition

9. Advanced Accuracy A+D/A+B+C+D
What proportion of all tests have given the correct result?

10. Exercise: D-dimer in pleuritic chest pain and SOB with active cancer
CTPA +ve
CTPA -ve
D-dimer > 500
198
502
700
D-dimer < 500 2
298
300
200
800
1000

11. Example
Sensitivity
Specificity
PPV
NPV
99%
38%
28%

12. Example: D-dimer in patients with a cough
CTPA +ve
CTPA -ve
D-dimer > 500 9
691
700
D-dimer < 500 1
299
300 10
990
1000

13. Example
Sensitivity
Specificity
PPV
NPV
90%
38%
1.2%
99%

14. Advanced Receiver (Relative) Operator Curves for continuous data
Plot the Sensitivity (y axis) against the false positive rate, 1-Specificity (x-axis)
A good test has the greatest area under the curve
These curves are used to decide where to make the cut-off

15. ROC curves

16. Advanced Likelihood ratio of a positive test (LR+ve)
Sensitivity / 1-Specificity
How much more likely is a positive result to be found in a patient with, as opposed to without, the condition?
1 to an infinitely big number

17. Advanced Likelihood ratio of a negative test
1-Sensitivity/ Specificity
How much more likely is a negative test in a patient with, as opposed to without, the target disorder
1 to an infinitely small number

18. Example (Fictitious)
A 55 year old man presents with headache. You are concerned about temporal arteritis You know that the prevalence of TA in this age group with headache is 5%. (PRETEST PROBALITY) The LR+ve of an ESR >60 is 6.9 for diagnosing TA

20. Specific things to look for
95% Confidence intervals especially lower limit
Sensitivity 94% (95% CI %)
Sensitivity 92% (95% CI 89-95%)

21. Example 2
0.05 x 6.9 = 0.345
If this man has a raised ESR then his chances of having temporal arteritis are 34%

22. Example 3 The LR-ve of an ESR in this condition is 0.6
If this man has a normal ESR, then his chances of having TA are 3%

24. Use of LR
A positive LR test > 5.0 is pretty useful at diagnosing something
A negative LR <0.02 s pretty good at ruling something out

25. Particular biases : spectrum
BNP story
Is there any selection in this group who might have systematic differences to my patients?
Case Control Design leads to Spectrum Bias

26. Particular biases : work-up bias
(Verification bias)
Patients with suspected coronary artery disease and positive exercise tests were more likely to undergo coronary angiography (the reference standard) than those with negative exercise tests.

27. Other biases
Incorporation bias
Test is also part of the gold standard

28. STARD
STAndards for the Reporting of Diagnostic Accuracy studies

29. Biases to be aware of Spectrum bias
is the study population exaggerated into yes / no groups
Partial verification bias
Gold standard applied inconsistently to confirm negative results
Incorporation bias
Test is also part of the gold standard

30. Quick list for appraising a paper
Identify aims
Identify study design
Identify population, exposure and outcome
Consider the gold standard
Consider the measurement
What biases (work up, expectation) are there?
What is the result and what does it mean

31. Useful resources BMJ debate paper about test characteristics

32. Any questions?