1. HOW TO READ AN ARTICLE ABOUT A DIAGNOSTIC TEST Chitkara MB, Boykan R, Messina C Stony Brook Long Island Children’s Hospital

2. WHAT IS EVIDENCE - BASED MEDICINE (EBM)? The translation of medical research into clinical practice Integration of best research evidence with clinical experience and patient values Knowing how to use clinical literature to ensure optimal patient care EBM is about USING, not doing, research

3. MOVE PAST THE P VALUE We are looking for CLINICAL SIGNIFICANCE STATISCAL SIGNIFICANCE (p ≤ 0.05) is nice…but not always feasible

4. GOALS FOR EBM CURRICULUM Present a general approach to use clinical reading time more effectively Demonstrate techniques that boil down EBM into simple, usable concepts We want you to GET IT

5. HOW TO PRACTICE EBM? Step 1: Frame your patient care question Step 2: Search and find the evidence Step 3: Validate the evidence Step 4: Evaluate the evidence Step 5: Apply the evidence

6. C ASE S CENARIO You are doing an elective in the Pediatric GI clinic. An 8 year old male presents with complaints of recurrent epigastric chest pain and dyspepsia. He is otherwise well-appearing. You are concerned about H. Pylori infection, but you are reluctant to recommend endoscopy in this otherwise well child. You ask your attending about other non-invasive options, and she tells you to look it up and present your findings at their Journal Club this afternoon.

7. A NSWERABLE C LINICAL Q UESTION (PICO) Patient – In a child w/ symptomatic GERD Intervention – Can stool antigen testing be used Comparison – In place of invasive procedures Outcome - To detect the presence or absence of H. Pylori infection?

8. SEARCH AND YOU WILL FIND You use your lunch break to hit the library. Your PUBMED/MeSH database search yields a promising article. Prospective study of 103 children undergoing endoscopy for recurrent abdominal pain (Iranikhah A et al. Iran J Pediatr, Apr 2013; 23(2):138-142).

9. EBM BIG THREE QUESTIONS Is this study VALID? What are the RESULTS? Are the results APPLICABLE to my patient?

10. DIAGNOSTIC TEST – VALIDITY PRIMARY GUIDES Was the “gold standard” applied to all patients? Was there an independent, blind comparison to reference standard? Was the diagnostic test evaluated in an appropriate spectrum of patients (like those in whom we would use it in practice)?

11. DIAGNOSTIC TEST: VALIDITY SECONDARY GUIDES Work-up or Verification Bias: Did the results of the test being evaluated influence the decision to perform the reference standard? Were the methods for performing the test described in sufficient detail to permit replication?

12. DIAGNOSTIC TEST: RESULTS Do the authors present Likelihood Ratios? If not, is the data needed to calculate the Likelihood Ratios included? How do I calculate a Likelihood Ratio?

13. DIAGNOSTIC TEST: RESULTS Start with Sensitivity and Specificity Sensitivity: The ability of the test to detect diseased people from a diseased population Specificity: The ability of a test to detect healthy people from a healthy population

14. DIAGNOSTIC TEST: RESULTS Likelihood Ratios indicate by how much a given diagnostic test result will raise or lower the pretest probability of the target disorder LR (+) The probability that the patient has a true positive test, rather than a false positive LR (-) The probability that the patient has a true negative test and not a false negative

15. DIAGNOSTIC TEST: RESULTS

16. Stool Antigen Tests for H. Pylori in Children Disease Present Disease Absent Totals Test pos 35439 Test neg 65864 4162103 Sen: 35/41 = 85.4% Spec: 58/62 = 93.5% LR+: 35/41 ÷ 4/62=13 LR-: 6/41 ÷58/62=0.16 Pre-test probability for this study = 40% Iranikhah A et al. Iran J Pediatr, Apr 2013; 23(2):138-142

17. H OW ARE L IKELIHOOD RATIOS USED Know your Pre-Test Probability (PTP) Varies from patient to patient PTP may be considered disease prevalence for your population Check first few sentences of article introduction to see if authors describe their disease prevalence Might have to use personal clinical judgment Exerts a major influence on the diagnostic process

18. T HE F AGAN N OMOGRAM TP 40%

19. DIAGNOSTIC TEST: RESULTS LR = 1: post-test probability is exactly the same as pre-test probability LR > 1 increases the probability that the target disorder is present LR < 1 decreases the probability that the target disorder is present LR = 8 means that it is 8 times more likely that a positive test is a true positive than a false positive.

20. LIKELIHOOD RATIOS LR > 10 or < 0.1 generate large changes from pre-test to post-test probability LR = 5 - 10 or 0.1 - 0.2 generate moderate shifts pre-test to post-test LR = 2 – 5 or 0.5 – 0.2 generate small, but sometimes important changes in probability LR = 1 – 2 or 0.5 – 1 are rarely important shifts

21. D IAGNOSTIC T EST L IKELIHOOD R ATIO VS P REDICTIVE V ALUE Prevalence = all study pts with disease / all pts in study Likelihood Ratio is prevalence- in dependent Predictive Value is wholly prevalence- de pendent Prevalence is often higher in studies compared to routine practice due to selection bias.

22. DIAGNOSTIC TEST – APPLICABILITY Test Properties may change with a different mix of disease severity or a different distribution of competing conditions When patients with the target disorder all have severe disease, the LR’s will move away from a value of 1 (sensitivity increases) When patients without the target disorder have competing conditions that mimic the test results of patients who do have the target disorder, the LRs move toward one, and the test appears less useful

23. DIAGNOSTIC TEST – APPLICABILITY Test Threshold – probabilities below which a clinician would dismiss a diagnosis and order no further tests Treatment Threshold – probabilities above which a clinician would consider the diagnosis confirmed, and would stop testing

24. DIAGNOSTIC TEST – APPLICABILITY When the probability of the target disorder falls between the test and treatment thresholds, further testing is mandated Once test and treatment thresholds are determined, the post-test probabilities have direct treatment implications

25. C LINICAL B OTTOM L INE What are the desires and expectations of my patient? Will this test result in better outcomes? Will this test change my management of my patients?

26. P RACTICE C ASE R EFERENCES Case 1: Poehling KA et al. Accuracy and Impact of a Point-of-Care Rapid Influenza Test in Young Children with Respiratory Illnesses. Arch Ped Adol Med, July 2006; 160 Case 2: Janguoo A et al. Is urinary 5- hydroxyindoleacetic acid helpful for early diagnosis of acute appendicitis? Am J Emerg Med, 2012; 30:540-544. Case 3: Gaydos CA et al. Performance of the Abbott RealTime CT/NG for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae. J Clin Micro, 2010; 48(9):3236-3243.

27. EBM R EFERENCES /R ESOURCES Jaeschke R, Guyatt G, Sackett DL. User’s Guide to the Medical Literature. How to use an Article About a Diagnostic Test. A. Are the Results of the Study Valid? JAMA, 1994; 271(5):389-391. Jaeschke R, Guyatt G, Sackett DL. User’s Guide to the Medical Literature. How to use an Article About a Diagnostic Test. B. What Are the Results and Will They Help Me in Caring for My Patients? JAMA, 1994; 271(9):703-707. Iranikhah A, Ghadir MR, Sarkeshikian S, Saneian H, Heiari A, Mahvari M. Stool Antigen Tests for the Detection of Helicobacter Pylori in Children. Iran J Pediatr, 2013; 23(2):138-142.