Diagnostic studies Adrian Boyle

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

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

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

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

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

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

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

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

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

Example Sensitivity Specificity PPV NPV 99% 38% 28%

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

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

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

ROC curves

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

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

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

Specific things to look for 95% Confidence intervals especially lower limit Sensitivity 94% (95% CI 65-100%) Sensitivity 92% (95% CI 89-95%)

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%

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%

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

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

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.

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

STARD STAndards for the Reporting of Diagnostic Accuracy studies

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

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

Useful resources BMJ debate paper about test characteristics http://bmj.bmjjournals.com/cgi/content/full/329/7459/209?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=snnout&andorexactfulltext=and&searchid=1115988869897_7738&stored_search=&FIRSTINDEX=0&sortspec=relevance&resourcetype=1

Any questions?