This document summarizes the steps involved in critically appraising a diagnostic study. It discusses formulating a clinical question using PICO (Patient, Intervention, Comparison, Outcome), searching for evidence, and assessing the validity and results of included studies. Key points addressed include evaluating a diagnostic test compared to a gold standard, calculating measures of diagnostic accuracy like sensitivity and specificity, and interpreting likelihood ratios and predictive values. The document uses an example of using ferritin levels to diagnose iron deficiency anemia in elderly patients to demonstrate these concepts.
These annotated slides will help you interpret an OR or RR in clinical terms. Please download these slides and view them in PowerPoint so you can view the annotations describing each slide.
"Hierarchies of Evidence" is an important but problematic concept for medical professionals to understand as it underpins their capacity to be effective practitioners and researchers.
RECENT ADVANCES IN DIAGNOSIS OF TUBERCULOSISANGAN KARMAKAR
TRADITIONAL TESTS AND RECENT DIAGNOSTIC MODALITIES FOR TUBERCULOSIS WITH EMPHASIS TO MOLECULAR DETECTION TECHNIQUES, DRUG SENSITIVITY ASSESMENT IN INDIAN PERSPECTIVE
Study designs, Epidemiological study design, Types of studiesDr Lipilekha Patnaik
Study design, Epidemiological study designA study design is a specific plan or protocol
for conducting the study, which allows the investigator to translate the conceptual hypothesis into an operational one.
These annotated slides will help you interpret an OR or RR in clinical terms. Please download these slides and view them in PowerPoint so you can view the annotations describing each slide.
"Hierarchies of Evidence" is an important but problematic concept for medical professionals to understand as it underpins their capacity to be effective practitioners and researchers.
RECENT ADVANCES IN DIAGNOSIS OF TUBERCULOSISANGAN KARMAKAR
TRADITIONAL TESTS AND RECENT DIAGNOSTIC MODALITIES FOR TUBERCULOSIS WITH EMPHASIS TO MOLECULAR DETECTION TECHNIQUES, DRUG SENSITIVITY ASSESMENT IN INDIAN PERSPECTIVE
Study designs, Epidemiological study design, Types of studiesDr Lipilekha Patnaik
Study design, Epidemiological study designA study design is a specific plan or protocol
for conducting the study, which allows the investigator to translate the conceptual hypothesis into an operational one.
Critical appraisal is the process of carefully and systematically analyze the research paper to judge its trustworthiness, its value and relevance in a particular context. (Amanda Burls 2009)
A critical review must identify the strengths and limitations in a research paper and this should be carried out in a systematic manner.
The Critical Appraisal helps in developing the necessary skills to make sense of scientific evidence, based on validity, results and relevance.
Epidemiological method to determine utility of a diagnostic testBhoj Raj Singh
The usefulness of diagnostic tests, that is their ability to detect a person with disease or exclude a person without disease, is usually described by terms such as sensitivity, specificity, positive predictive value and negative predictive value (NPV). Many clinicians are frequently unclear about the practical application of these terms (1). The traditional method for teaching these concepts is based on the 2 × 2 table (Table 1). A 2 × 2 table shows results after both a diagnostic test and a definitive test (gold standard) have been performed on a pre-determined population consisting of people with the disease and those without the disease. The definitions of sensitivity, specificity, positive predictive value and NPV as expressed by letters are provided in Table 1. While 2 × 2 tables allow the calculations of sensitivity, specificity and predictive values, many clinicians find it too abstract and it is difficult to apply what it tries to teach into clinical practice as patients do not present as ‘having disease’ and ‘not having disease’. The use of the 2 × 2 table to teach these concepts also frequently creates the erroneous impression that the positive and NPVs calculated from such tables could be generalized to other populations without regard being paid to different disease prevalence. New ways of teaching these concepts have therefore been suggested.
Description of various ultrasound features of benign and suspicious thyroid nodules with multiple ultrasound systems for risk stratification of malignancy.
Description of different ultrasound features of carpal tunnel syndrome before and after carpal tunnel release including Doppler imaging and elastography
Doppler ultrasound of visceral arteriesSamir Haffar
Doppler ultrasound of different diseases of visceral arteries including arterial stenosis and occlusion, arterial aneurysm, artrial pseudoaneurysm, arterio-venous fistula, artrial dissection, and abdominal vascular compression syndromes
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Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
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2 Case Reports of Gastric Ultrasound
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
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MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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1. Critical appraisal of a diagnostic study
Samir Haffar M.D.
Assistant Professor of Gastroenterology
2. The amount of medical literature
0
500000
1000000
1500000
2000000
2500000
Biomedical MEDLINE Trials Diagnostic
MedicalArticlesperYear
5,000
per day
1,800
per day
95 per
day
55 per
day
Glasziou P, Del Mar C. Evidence based practice workbook.
Blackwell Publishing, 2nd edition, 2007.
3. Question type Which study design will
best answer my question?
Intervention • RCT
Aetiology & risk factors • Cohort or case control
Diagnosis • Cross-sectional
Prognosis & incidence • Cohort study
Prevalence • Cross-sectional
In each case, SR of all available studies
better than individual study
4. 1- Ask
2- Acquire
4- Apply
Patient
dilemma
Principles
of EBP
Evidence alone does not decide
Combine with other knowledge & values
3- Appraise
Hierarchy
of evidence
5 A
5- Assess
5. Structure for a study of diagnostic test
Suspected target
condition
Guyatt G et all. Users‟ guides to medical literature: manual for EBP.
McGraw-Hill, New York, USA, 2nd edition, 2008.
Accuracy of diagnostic test compared to gold standard
Gold standard test
Positive
Negative
Diagnostic test
Positive
Negative
7. Clinical history
• 75-year-old woman with community-acquired pneumonia
She responds nicely to appropriate antibiotics
Hg:10 g/dL – MCV 80 – Blood smear: hypochromia
Otherwise well – No incriminating medications
• Hg 10.5 g/dL 6 months ago – Ferritin 40 μg/L
Never investigated before
• How to interpret ferritin result?
How precise & accurate ferritin in diagnosis of IDA*?
* IDA: Iron Deficiency Anemia
8. Key components of your clinical question
Concept of PICO
P
I
C
O
Patient Elderly patient with IDA
Intervention Bone marrow aspirates
Comparaison Ferritin
Outcome Accuracy (Sn – Sp – PPV – NPV – LR)
* IDA: Iron Deficiency Anemia
9. Formulation of the relevant question
In an elderly woman with hypochromic microcytic
anemia, can a low serum ferritin level diagnose iron
deficiency anemia?
12. PubMed translation of query into search terms
PICO Element Search terms for PubMed
* MeSH: Medical Subject Headings in PubMed
I Bone marrow aspirates “bone marrow examination” [MeSH term]
C Ferritin “ferritins” [MeSH term]
O Accuracy “sensitivity” [MeSH term]
“diagnosis” [MeSH term]
P Elderly
Iron deficiency anemia
Limits to [aged: + 65 years]
“iron deficiency anemia” [MeSH term]
15. Terms used to search a diagnostic test in PubMed
Target condition
Name of the test
“Diagnosis”
OR
“Sensitivity”
AND
AND
Iron deficiency anemia
Ferritins
Clinical Queries
Category: diagnosis
20. Key components of your clinical question
PICO
P Target condition Elderly patient with IDA
I Gold standard test Bone marrow aspirates
C Comparaison Ferritin Positive ≤ 45 μg/L
Negative > 45 μg/L
O Accuracy Sn – Sp – PPV – NPV – LR – CIs
IDA: Iron Deficiency Anemia
21. Validity of study design of diagnostic study
Blind comparison with the gold standard test
Gold standard test performed in all patients
Diagnostic test evaluated in appropriate
spectrum of patients
If no → Stop here
22. Test evaluated in large spectrum of patients
Story of CEA
• CEA in advanced CRC & healthy controls1
35 of 36 pts with advanced CRC had elevated CEA (98% )
Almost all healthy controls had low levels of CEA
CEA might be a useful screening tool for CRC
• CEA in early-stage CRC & other GI disorders2
Test unable to differentiate early cancer from other disorders
1 Thomson DM et all. Proc Natl Acad Sci U S A 1969 ; 64 : 161.
2 Bates SE. Ann Intern Med 1991 ; 115 : 623.
Spectrum Bias
23. Accuracy of dichotomous diagnostic test
Only 2 results
• Sensibility (Sn)
• Specificity (Sp)
• Positive Predictive Value (PPV)
• Negative Predictive Value (NPV)
• Likelihood Ratios (LRs)
• Diagnostic Odds Ratio (OR)
Newman TB & Kohn MA. Evidence-based diagnosis.
Cambridge University Press, Cambridge, UK, 1st edition, 2009.
CIs
If no → Stop here
24. Diagnosis of IDA in elderly patients
2 x 2 table
Gold standard test
Bone marrow aspirates Row totals
Disease present Disease absent
Diagnostic test
Ferritin
Positive
Negative
Column totals
25. Gold standard test
Bone marrow aspirates
Row totalsDisease present Disease absent
Diagnostic test
Ferritin
Positive
≤ 45 μg/L
70 15 85
Negative
> 45 μg/L
15 135 150
Column totals 85 150 235
Diagnosis of IDA in elderly patients
Guyatt G et all. Am J Med 1990;88:205.
26. Sensitivity
Percent of diseased individuals with positive test
Gold standard test
Bone marrow aspirates
Row totalsDisease present Disease absent
Diagnostic test
Ferritin
Positive
≤ 45 μg/L
a
Negative
> 45 μg/L
b
Column totals (a + b)
Denominator = Column totals
Sn
a
a + c
=
27. Sensitivity
Percent of diseased individuals with positive test
Gold standard test
Bone marrow aspirates
Row totalsDisease present Disease absent
Diagnostic test
Ferritin
Positive
≤ 45 μg/L
70
Negative
> 45 μg/L
15
Column totals 85
=
Denominator = Column totals
Sn
70
70 + 15
= 0.82
28. Sensitivity
• Mnemonic for sensitivity is “PID”
“Positive In Disease”
or Pelvic Inflammatory Disease
• SnNOUT
Highly Sensitive test, when Negative, rules OUT disease
Urine pregnancy test very sensitive for ectopic pergnancy
Negative urine pregnancy test rules out ectopic pregnancy
29. Gold standard test
Bone marrow aspirates
Row totalsDisease present Disease absent
Diagnostic test
Ferritin
Positive
≤ 45 μg/L
b
Negative
> 45 μg/L
d
Column totals b + d
Specificity
Percent of non-diseased individuals with negative test
Denominator = Column totals
Sp
d
b + d
=
30. Specificity
Percent of non-diseased individuals with negative test
Gold standard test
Bone marrow aspirates
Row totalsDisease present Disease absent
Diagnostic test
Ferritin
Positive
≤ 45 μg/L
15
Negative
> 45 μg/L
135
Column totals 150
=
Denominator = Column totals
Sp
135
135 + 15
= 0.9
31. Specificity
• Mnemonic for specificity is “NIH”
Negative In Health
or National Institutes of Health
• SpPIN
Perfectly Specific test, when Positive, rules disease IN
“Pathognomonic” findings
Visualization of head lice for that infestation
32. Limitations of sensitivity & specificity
• Sn & Sp work backwards from clinical practice:
Evaluate patients with known disease
Data about presence or absence of certain dg test results
• Patients present with symptoms & diagnostic test results
Work forwards to determine likelihood of the disease
PPV & NPV provide these data
33. Positive predictive value
Percent of positive tests that are truly positive
Gold standard test
Bone marrow aspirates
Row totalsDisease present Disease absent
Diagnostic test
Ferritin
Positive
≤ 45 μg/L
a b a + b
Negative
> 45 μg/L
Column totals
Denominator = Row totals
PPV
a
a + b
=
34. Positive predictive value
Percent of positive tests that are truly positive
Gold standard test
Bone marrow aspirates
Row totalsDisease present Disease absent
Diagnostic test
Ferritin
Positive
≤ 45 μg/L
70 15 85
Negative
> 45 μg/L
Column totals
=
Denominator = Row totals
PPV
70
85
= 82 %
35. Negative predictive value
Percent of negative tests that are truly negative
Gold standard test
Bone marrow aspirates
Row totalsDisease present Disease absent
Diagnostic test
Ferritin
Positive
≤ 45 μg/L
Negative
> 45 μg/L
c d c + d
Column totals
Denominator = Row totals
NPP
d
c + d
=
36. Negative predictive value
Percent of negative tests that are truly negative
Gold standard test
Bone marrow aspirates
Row totalsDisease present Disease absent
Diagnostic test
Ferritin
Positive
≤ 45 μg/L
Negative
> 45 μg/L
15 135 150
Column totals
Denominator = Row totals
NPV
135
15 + 135
= = 90 %
37. Limitations of Sn/Sp & PPV/NPV
• Sensitivity & specificity
Calculated around a cutoff point (45 μg/L for ferritin)
Work where evaluated test has only 2 results (unusual)
• PPV & NPV
Vary widely depending on disease‟s prevalence
Work where evaluated test has only 2 results (unusual)
Likelihood ratios (LRs) overcome these weaknesses
38. Incidence & prevalence
• Incidence:
Proportion of patients in the at-risk population who
get the disease over a period of time (e.g.: 1 year)
• Prevalence:
Proportion of patients in the at-risk population who
have the disease at one point in time
Prevalence = Pre-test probability
39. Relationship between incidence & prevalence
Detels R et al. Oxford textbook of public health.
Oxford University Press, Oxford, 4th edition, 2002.
40. Gold standard test
Bone marrow aspirates
Row totalsDisease present Disease absent
Diagnostic test
Ferritin
Positive
≤ 45 μg/L
a b
Negative
> 45 μg/L
c d
Column totals a + c a + b + c + d
Diagnosis of IDA in the elderly
Prevalence
=Prevalence
a + c
a + b + c + d
=
Cases
Total population
41. Gold standard test
Bone marrow aspirates
Row totalsDisease present Disease absent
Diagnostic test
Ferritin
Positive
≤ 45 μg/L
Negative
> 45 μg/L
Column totals 85 150 235
Diagnosis of IDA in the elderly
Prevalence
Prevalence = 0.36=
85
235
42. LRs & weaknesses of Sn, Sp, PPV & NPV
• Weaknesses of Sn & Sp
LRs calculated for multiple ranges of dg test results
LRs more useful to evaluate tests with > 2 results
• Weaknesses of PPV & NPV
LRs don‟t change with different disease‟s prevalence
LRs more useful to evaluate tests with > 2 results
43. Likelihood ratio (LR)
• Different way to interpret accuracy of a diagnostic test
• How much likelihood of disease changes given a test result
• Not important to comprehend formulae to calculate LR
• If LRs are not provided, you need to compute your own
44. LR for a positive test
LR + = 0.82 / (1 – 0.9 ) = 8.24
LR + = Sensitivity / (1 – Specificity)
Corresponds to clinically “ruling in disease”
Probability that the patient has true positive,
rather than false positive test
45. LR for a negative test
LR – = (1 – 0.82 ) / 0.9 = 0.2
LR – = (1 – Sensitivity ) / specificity
Corresponds to clinically “ruling out disease”
Probability that the patient has true negative
rather than false negative test
46. Interpretation of LRs
Measure of changes in disease probability
• Test result with LR > 1.0
Increase the likelihood of disease
The higher the LR is, the closer you are to confirm dg
• Test result with LR very close to 1.0
Little impact on estimates of likelihood of disease
• Test result with LR < 1.0
Decrease the likelihood of disease
The lower the LR is, the closer you are to rule out dg
47. Interpretation of LRs
• LR > 10 Rule in a diagnosis
• LR < 0.1 Rule out a diagnosis
• LR 0.5 – 2 Little effect on post-test probability
As a general rule of thumb
48. Bayes nomogram
LR convert pre-test probability to post-test probability
Evid Based Med 2001 ; 6 : 164 – 166.
49. Pre-test probability/prevalence
• Definition Likelihood of disease before dg test result
• Estimation History
Physical examination
Clinical experience
Prevalence studies More accurate
• Order dg test: Very low → No diagnostic test
Intermediate? → Diagnostic test
Very high → No diagnostic test
Not accurate
50. Example of a low pre-test probability
• a 24-year-old female
• Occasional pain anterior chest wall not related to effort
• Physical findings unremarkable
• Probability of having a heart attack quite low
• Pre-test probability of heart attack to 0.1%
51. Example of a high pre-test probability
• Prevalence of HP in PU in some countries ≈ 100%
• These patients automatically treated for HP after
identification of peptic ulcer without testing for HP
52. What level of pretest probability is intermediate?
• Would it be 25 or 75% likelihood of disease?
• Use clinical judgment:
– Cost
– Accuracy
– Side effects of diagnostic test
– Consequences of “missed” diagnosis
Lower threshold to order tests if fatal consequences
– Patient’s preferences
Negative test reassure anxious patients
53. Estimating pre-test probability
• It is often difficult to know whether the pre-test
probability you assign is correct
• Often, you must make a guess, which seems rather
arbitrary given the complex calculations that ensue
Pines J & Everett W. Evidence-Based emergency care.
Blackwell Publishing, Oxford, UK, 1st edition, 2008.
Assigning pre-test probability is both an art & a science
54. Likelihood ratio
Measure of changes in disease probability
• Definition
How much likelihood of disease change given a test result
• Estimation
Result(s) of study(ies) you reviewed
LR varies depending on test result LR for a positive test
LR for a negative test
55. Post-test probability
• Definition
Likelihood of disease after a diagnostic test result
• Estimation
Using Bayes nomogram
For those who are numero-phobic
Manual computation
For those who are up to challenge of manual computation
56. Probability of diagnosis
Guyatt G et all. Users‟ guides to medical literature: manual for EBP.
McGraw-Hill, New York, USA, 2nd edition, 2008.
After arriving at a post-test probability of disease
You may make a clinical decision
57. Use of likelihood ratio
75-year-old female with pneumonia
Hemoglobin level: 10 g/dL
MCV: 80
Ferritin level: 40 μg/L
*IDA: iron deficiency anemia
Pre-test probability of IDA*: 36%
LR for + & – test: 8.2 – 0.2
Post-test probability: ?
58. Fagan nomogram
Post-test probability for a positive test
Pre-test probability 36%
LR + 8.2
Post-test probability 82 %
Certainly high enough for us to
want investigate her anemia
Corresponds to “SpPin”
http://araw.mede.uic.edu/
59. Fagan nomogram
Post-test probability for a negative test
Pre-test probability 36%
LR – 0.2
Post-test probability 10 %
Certainly low enough for us to
exclude other causes of anemia
Corresponds to SnNout
http://araw.mede.uic.edu/
61. Statistical significance
• Confidence Interval
Reported around each measure of diagnostic accuracy:
Sn – Sp – PPV – NPV – LRs – diagnostic OR
• Interpretation of CI in absence of „line of no difference‟
Interpret results in same way at lower & higher end of CI?
62. Calculation of CI
P Proportion of patients with etiology of interest
N Number of patients in the sample
Formula inaccurate if number of cases is 5 or fewer
Guyatt G et all. Users‟ guides to the medical literature.
Manual for evidence-based clinical practice. McGraw-Hill, 2nd edition, 2008.
63. Interpretation of 95% CI
When the data sampling is repeated many
times, the 95% CI calculated from each sample
will, on average, contain the “true” value of the
proportion in 95% of the samples
CI width smaller with increasing sample size
68. 95% CIs around accuracy measures
Cut-off value 45 μg/L
Accuracy Results (95% CIs) Comments
Sensitivity 82% (74 – 90) Good sensitivity
Specificity 90% (85 – 95) Good specificity
PPV 82% (74 – 90) Good PPV
NPV 90% (85 – 95) Good NPV
Prevalence 36% (30 – 42) –
LR+ 8.24 (5.04 - 13.44) Moderate changes
LR– 0.2 (0.12 - 0.31) Moderate changes
Diagnostic OR 42 Good diagnostic OR
69. Accuracy of tests & number of results
• Dichotomous test (only 2 results)
Sensibility & Specificity
PPV & NPV
LR + & –
Diagnostic OR
• Multilevel test (> 2 results)
Receiver Operating Characteristic (ROC)
LR associated with each possible result or interval
Make continuous test dichotomous: fixed cut-off value
CIs
70. Diagnosis of IDA in elderly patients
Gold standard test
Bone marrow aspirates Sn Sp
Disease + Disease –
Dg test
Ferritin (μg/L)
≤ 18 47 2 0.55
(47/85)
0.98
(148/150)
≤ 45 70 15 0.82
(70/85)
0.90
(135/150)
≤ 100 77 42 0.90
(77/85)
0.72
(108/150)
Column totals 85 150
Guyatt G et all. Diagnosis of iron deficiency anemia in the elderly.
Am J Med 1990 ; 88 : 205.
71. Receiver Operating Characteristic (ROC)
• Plot of test sensitivity on the y axis versus its FPR
(or 1 – specificity) on the x axis
• Each discrete point on graph called operating point
• Curve illustrates how sensitivity & FPR vary together
74. Empirical ROC/ Diagnosis of IDA in elderly
Connect all the points obtained
at all the possible cutoff levels:
- 3 values of FPR & sensibility
- 2 endpoints on curve: 0,0 & 1,1
75. Empirical ROC curve/Area under the curve
Summation of areas of trapezoids formed by
connecting points on ROC curve
AUC ROC = 0.91
76. Useful properties of ROC curve
Accuracy of binary diagnostic test for a cut-point value
AUC provides an overall measure of a test‟s accuracy
Slope of tangent at cut-point gives LR for that value
Determination of cut-off point to distinguish D + & D –
Comparison of different tests for dg of a target disorder
78. Area under the ROC curve in IDA
If we select 2 patients at random one with IDA & one without
Probability is 0.91 that patient with IDA will have abnormal ferritin
79. Accuracy of diagnostic test using AUC of ROC
Value Accuracy
0.90 - 1.00 Excellent
0.80 - 0.90 Good
0.70 - 0.80 Fair
0.60 - 0.70 Poor
Pines JM & Everett WW. Evidence-Based emergency care: diagnostic testing & clinical decision
rules. Blackwell‟s publishing – West Sussex – UK – 2008.
The higher AUC the better the overall performance of the test
80. Slope of tangent at cut-point gives LR
Steeper tangent for cutoff of 18 than it is for cutoff of 45
81. Peat JK. Health science research. Allen & Unwin, Australia, 1st edition, 2001.
Cut-off point discriminates between
subjects with or without disease
Indicated by the point on curve that
is far away from chance diagonal
Determination of cut-off point
to distinguish D + & D –
82. Diagnosis of IDA AUC of the ROC
Seurm ferritin 0.91
Transferrin saturation 0.79
MCV 0.78
RCP 0.72
* RCP: Red Cell Protoporphyrin
Guyatt GH et al. J Gen Intern Med 1992 ; 7 : 145 – 153.
Comparing different tests for target disorder
83. Likelihood Ratio Line
If you have sufficient observations, you can go
beyond the multiple cut approach & construct LR
line describing the relation between the test result
& LR across the entire range of test values
84. LR line for serum ferritin in dg of IDA
Guyatt GH et al. J Gen Intern Med 1992 ; 7 : 145 – 153.
Systematic review – 55 eligible studies – 2,579 patients
Completely smooth curve (No difference in LRs between categories)
Need help of a statistician
85. Critical appraisal of an article on dg test
Glasziou P et al. BMJ 2004 ; 328 : 39 – 41.
86. Furberg BD & Furberg CD. Evaluating clinical research.
Springer Science & Business Media – First Edition – New York – 2007.
87. Appraising a diagnostic study – 1
a. Blind comparison with gold standard test Yes
b. Gold standard test performed in all patients Yes
c. Diag test done in appropriate spectrum of pts Yes
Are the results valid (study design)?
Straus C et al. Evidence-based medicine: How to practice & teach & EBM.
Elsevier – 3rd edition - 2009
88. b. Precision of the results Yes (narrow CI)
a. Accuracy: Sn, Sp, PPV, NPV, LR,dg OR Good
c. Dichotomizing continuous test scores:
Sn, Sp, LR+, LR–
Yes
Appraising a diagnostic study – 2
Are the valid results accurate?
Straus C et al. Evidence-based medicine: How to practice & teach & EBM.
Elsevier – 3rd edition – 2009.
90. Appraising a diagnostic study – 3
a. Test available & reproducible in my setting Yes
b. Generate sensible pre-test probability Yes (36%)
c. Post-test probability affects management Yes (82%)
d. Consequences of the test help our patient Yes
Can we apply valid accurate results to our patient
Straus C et al. Evidence-based medicine: How to practice & teach & EBM.
Elsevier – 3rd edition - 2009
91. Reproducibility
• Test results should not vary if repeated by:
Same observer Intra-rater reproducibility
Different observer Inter-rater reproducibility
Same or different locations
• Reproducibility measurement
Dichotomous results Kappa & its variants
Continuous results Within-subject standard deviation
Within-subject coefficient variation
Correlation coefficients
Bland-Altman plot
Newman TB & Kohn MA. Evidence-based diagnosis.
Cambridge University Press, Cambridge, UK, 1st edition, 2009.
92. Interpretation of different values of kappa
Kappa from Greek letter κ
Value of kappa Strength of agreement
0 – 0.20 Poor
0.21– 0.40 Fair
0.41– 0.60 Moderate
0.61– 0.80 Good
0.81–1.00 Very good
Perera R, Heneghan C & Badenoch D. Statistics toolkit.
Blackwell Publishing & BMJ Books, Oxford, 1st edition, 2008.
kappa score of 0.6 indicates good agreement
93. * Altman DG et al. Ann Intern Med 2001 ; 134 : 663 - 94.
Improving quality of reports
Diagnostic
accuracy study
STARD***
Standards for
Reporting of
Diagnostic Accuracy
Meta-analysis
Quality of
Reporting of
Meta-analyses
QUOROM**
RCTs
Consolidated
Standards of
Reporting Trials
CONSORT*
** Moher D et al. Lancet 1999 ; 354 : 1896 - 900.
*** Bossuyt PM et all. BMJ 2003; 326 : 41 – 44.
94. STARD
Standards for Reporting of Diagnostic Accuracy
• Date 2 days consensus meeting (sep16-17, 2000)
• Invited experts Researchers – editors – organizations
• Literature 33 checklists for diagnostic research
75 different items
• Aim Reduce extended list of potential items
• Results Checklist with 25 items based on evidence
Flow diagram
Bossuyt PM et all. BMJ 2003 ; 326 : 41 – 4.
95. Challenges of a diagnostic test study
• Conducting a high-quality diagnostic test study is very
challenging at every step of the way:
– Formulating the proposal
– Obtaining funding
– Carrying out the proposal
• To have an idea of the challenges involved
ACP Journal Club in 2003 published 86 RCTs &
only 7 diagnostic test studies
96. Accuracy of a diagnostic test -1
• Dichotomous test (only 2 results)
Sensibility (Sn) & Specificity (Sp)
Positive Predictive Value (PPV)
Negative Predictive Value (NPV)
Likelihood Ratios + & – (LRs)
Diagnostic Odds Ratio (OR)
• Multilevel test (> 2 results)
Receiver Operating Characteristic (ROC)
LR line
Newman TB & Kohn MA. Evidence-based diagnosis.
Cambridge University Press, Cambridge, UK, 1st edition, 2009.
CIs
97. Accuracy of a diagnostic test -2
Sensitivity Percent of diseased individuals who have + test
Specificity Percent of non-diseased who have negative test
PPV Percent of positive tests that are truly positive
NPV Percent of negative tests that are truly negative
Pre-test probability Likelihood of disease before dg test result
LRs Change of disease probability given a test result
Post-test probability Likelihood of disease after dg test result
ROC curve Accuracy of dg test with multiple levels
LR line Accuracy of dg test if large no. of observations
ERIC notebook in epidemiology. http://hrsd.durham.med.va.gov/eric/
98. Critical appraisal of a diagnostic study
Valid Blind comparison with gold standard test
Gold standard test performed in all patients
Dg test done in appropriate spectrum of pts
Test available & reproducible in my setting
Generate sensible pre-test probability
Post-test probability affects management
Consequences of test help my patient
Apply
Accurate Accuracy: Sn, Sp, PPV, NPV, LR, diagnostic OR
Precision of the results
Dichotomizing continuous test scores
Straus C et al. Evidence-based medicine: How to practice & teach & EBM.
Elsevier – 3rd edition – 2009.
Tests with just two results (positive or negative) are unusual.Denominator: مخرج
Proportion of persons with disease who have a positive testDenominator: مخرجThese numbers are not difficult to remember. The denominators for sn and sp are the column totals.
Proportion of persons with disease who have a positive testDenominator: مخرجThese numbers are not difficult to remember. The denominators for sn and sp are the column totals.
Pelvic Inflammatory Disease is a problem that requires clinician sensitivity.
Proportion of persons with disease who have a positive testDenominator: مخرجThese numbers are not difficult to remember. The denominators for sn and sp are the column totals.
Proportion of persons with disease who have a positive testDenominator: مخرجThese numbers are not difficult to remember. The denominators for sn and sp are the column totals.
The National Institutes of Health are very specific in their requirements on grant applications.Lice:
Row: صفProportion of persons with disease who have a positive testDenominator: مخرجThese numbers are not difficult to remember. The denominators for ppv and npv are the row totals.
Proportion of persons with disease who have a positive testDenominator: مخرجThese numbers are not difficult to remember. The denominators for ppv and npv are the row totals.
Proportion of persons with disease who have a positive testDenominator: مخرجThese numbers are not difficult to remember. The denominators for ppv and npv are the row totals.
Proportion of persons with disease who have a positive testDenominator: مخرجThese numbers are not difficult to remember. The denominators for ppv and npv are the row totals.
Sensitivity & specificity calculated around a cutoff point (45 μg/L for ferritin)Ferritin level 45 μg/L consistent with IDAFerritin level > 45 μg/L not consistent with IDAIntuitively, a patient with a ferritin level of 5 μg/L is more likely to have IDA than a patient with a ferritin level of 40 μg/Lthe sensitivity and specificity cannot differentiate between these two patients.When the prevalence decreases: PPV decreases & NPV increases.
Incidence: وقوعPrevalence: انتشار
Tests with just two results (positive or negative) are unusual.Denominator: مخرج
Tests with just two results (positive or negative) are unusual.Denominator: مخرج
LR = 10 means that it is 10 times more likely that a positive test is a true positive than a false positive.
Don’t become too engrossed with numbers. Sometimes it’s enough just to understand that LRs are a measure of changes indisease probability.
Nomogram: مخطط المعادلة
Low pre-test probability: Hospitalized patient who suddenly develops diarrhea? Stool tests for ova and parasites are routinely ordered to evaluate diarrhea, butthe pretest probability of a parasitic infection in a hospitalized patient with new-onset diarrhea approaches zero. In this situation, the pretest probability is so low that stool tests for ova and parasites should not be obtained.Intermediate pre-test probability: What level of pretest probability is intermediate & suggests the need for diagnostic tests? Would it be 25% likelihood of disease being present or 75% likelihood of disease being present? A physician must use clinical judgment here & consider cost, accuracy, side effects of diagnostic test, consequences of a “missed” diagnosis (i.e., if a missed diagnosis may have fatal consequences, then clinicians will have a lower threshold), & patientpreference (many patients may be particularly anxious that their symptoms represent the signs of a fatal disease).High pre-test probability: Patients with peptic ulcers are rarely tested for Helicobacter pylori in some countries (e.g., Armenia) because the prevalenceof H. pylori approaches 100%. These patients are automatically treated for H. pylori after identification of peptic ulcers without testing for H. pylori.
Nomogram: مخطط المعادلة
Nomogram: مخطط المعادلة
Slope: انحدارTangent: مماس
Slope: انحدارTangent: مماسSteep: حاد
Critical appraisal: Application of rules of scientific evidence to assess the validity of the results of a study. Validity: Extent to which an instrument accurately measures what we want it to measure.