אבחנה וסריקה diagnostic and screening tests ד"ר רונית קלדרון-מרגלית.
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Transcript of אבחנה וסריקה diagnostic and screening tests ד"ר רונית קלדרון-מרגלית.
אבחנה וסריקה diagnostic and screening tests
ד"ר רונית קלדרון-מרגלית
Screening vs. Diagnosisscreening
negative positive
diagnosis
No disease
Havedisease
treatment
Clean separation of normal from abnormal people. Assay for reduced glutathione in male relatives of patients with glucose 6-phosphate dehydrogenase
deficiency
Separating normal from abnormal when few of the patients are abnormal. Hypothetical distribution of
serum calciums in normal and hyperparathyroid people in the general population (prevalence of
normal/prevalence of hyperparathyroid 200/1)
Change in normal function with age. BUN people aged 20-29 and 80 or older
The relationship between normal and the risk of disease. The risk for men having gouty arthritis at various levels of serum
uric acid
Increasing risk through the normal range. Serum cholesterol and the risk of coronary heart disease in
men aged 30-39.
Percentage distribution of serum cholesterol levels (mmol/L) in men aged 50-62 who did or did not subsequently develop coronary heart disease
Increasing number of procedures per patient at the Ohio State University Hospitals, Columbus, Ohio
Percentage of persons expected to be normal for a number of test, each using x ± 2s normal range
Number of different tests Persons expected to be normal for all tests undertaken (%)
1 2 3 4 5 6 7 8 9 10 11 12
95.45 91.11 86.96 83.00 79.23 75.62 72.18 68.90 65.76 62.77 59.91 57.19
התבחין: תוקף ומהימנותValidity and reliability
A high reliability mean that in repeated measurements the results fall very close to each other; conversely, a low reliability means that they are scattered. Validity determines how close the mean of repeated measurements is to the true value. A low validity will produce more problems when interpreting results than a low reliability
Different combinations of high and low precision/reliability and validity
תוקף נמדד ע"י מידת הדיוק של התבחין: – עד כמה התבחין רגיש sensitivityרגישות - •
לזהות את החולים – עד כמה התבחין סגולי specificityסגוליות - •
בזיהוי הבריאים
עבור השימוש הקליני:
positive predictive value– ערך ניבוי חיובי
negative predictive value– ערך ניבוי שלילי
הערכת תוקף
Disease
PresentAbsent
Test
AbnormalTrue positive
False positive
NormalFalse negative
True negative
Disease
PresentAbsent
Test
AbnormalTrue positive
a
False positive
c
NormalFalse negative
b
True negative
d
Disease
PresentAbsent
Test
AbnormalTrue positive
a
False positive
c
NormalFalse negative
b
True negative
d
Sensitivity = a/(a+b)
Disease
PresentAbsent
Test
AbnormalTrue positive
a
False positive
c
NormalFalse negative
b
True negative
d
Specificity = d/(c+d)
Disease
PresentAbsent
Test
AbnormalTrue positive
a
False positive
c
NormalFalse negative
b
True negative
d
Accuracy = (a+d)/(a+b+c+d)
Disease
PresentAbsent
Test
AbnormalTrue positive
a
False positive
c
NormalFalse negative
b
True negative
d
Positive predictive value = the probability of an individual with an abnormal result to have the disease = a/(a+c)
Disease
PresentAbsent
Test
AbnormalTrue positive
a
False positive
c
NormalFalse negative
b
True negative
d
Negative predictive value = the probability of an individual with a normal result to be free of disease = d/(b+d)
MINo MI
CK test results
Positive
(>80IU)
215248463
Negative(<80 IU)
1518221837
23020702300
The sensitivity, specificity and predictive values of the CK test in myocardial infarction
among general hospital admissions
MINo MI
CK test results
Positive
(>80IU)
215248463
Negative(<80 IU)
1518221837
23020702300
The sensitivity, specificity and predictive values of the CK test in myocardial infarction
among general hospital admissions
Prevalence = pretest likelihood of disease =prior probability of disease = 230/2300=10%
MINo MI
CK test results
Positive
(>80IU)
215248463
Negative(<80 IU)
1518221837
23020702300
The sensitivity, specificity and predictive values of the CK test in myocardial infarction
among general hospital admissions
Sensitivity= TP rate =215/230=93%
MINo MI
CK test results
Positive
(>80IU)
215248463
Negative(<80 IU)
1518221837
23020702300
The sensitivity, specificity and predictive values of the CK test in myocardial infarction
among general hospital admissions
Specificity= TN rate =1822/2070= 88%
MINo MI
CK test results
Positive
(>80IU)
215248463
Negative(<80 IU)
1518221837
23020702300
The sensitivity, specificity and predictive values of the CK test in myocardial infarction
among general hospital admissions
Positive Predictive Value= ppv=predictive value of a positive test=posttest likelihood or posterior probability of disease= 215 / 463 = 46%
MINo MI
CK test results
Positive
(>80IU)
215248463
Negative(<80 IU)
1518221837
23020702300
The sensitivity, specificity and predictive values of the CK test in myocardial infarction
among general hospital admissions
Negative Predictive Value= npv=predictive value of a negative test=posttest likelihood or posterior probability of no disease= 1822 / 1837 =99%
MINo MI
CK test results
Positive
(>80IU)
21516231
Negative(<80 IU)
15114129
230130360
The sensitivity, specificity and predictive values of the CK test in myocardial infarction
among general hospital admissions
MINo MI
CK test results
Positive
(>80IU)
21516231
Negative(<80 IU)
15114129
230130360
The sensitivity, specificity and predictive values of the CK test in myocardial infarction
among general hospital admissions
Prevalence = pretest likelihood of disease =prior probability of disease = 230/360=64%
MINo MI
CK test results
Positive
(>80IU)
21516231
Negative(<80 IU)
15114129
230130360
The sensitivity, specificity and predictive values of the CK test in myocardial infarction
among general hospital admissions
Sensitivity= TP rate =215/230=93%
MINo MI
CK test results
Positive
(>80IU)
21516231
Negative(<80 IU)
15114129
230130360
The sensitivity, specificity and predictive values of the CK test in myocardial infarction
among general hospital admissions
Specificity= TN rate =114/130= 88%
MINo MI
CK test results
Positive
(>80IU)
21516231
Negative(<80 IU)
15114129
230130360
The sensitivity, specificity and predictive values of the CK test in myocardial infarction
among general hospital admissions
Positive Predictive Value= ppv=predictive value of a positive test=posttest likelihood or posterior probability of disease= 215 / 231 = 93%
MINo MI
CK test results
Positive
(>80IU)
21516231
Negative(<80 IU)
15114129
230130360
The sensitivity, specificity and predictive values of the CK test in myocardial infarction
among coronary care unit admissions
negative Predictive Value= npv=predictive value of a negative test=posttest likelihood or posterior probability of no disease= 114 / 129 = 88%
Positive predictive value according to sensitivity, specificity, and prevalence of
disease
Effect of prevalence on predictive value: positive predictive value of prostatic acid phosphatase for
prostatic cancer (sensitivity=70%, specificity=90%) in various clinical settings
Setting Prevalence Positive predictive value
cases/100,000 %
General population 35 0.4
Men, age 75 or greater 500 5.6
Clinically suspicious
prostatic nodule 50,000 93.0
בעוד שרגישות וסגוליות הן מאפיינים של •הבדיקה,
ערכי הניבוי החיובי והשלילי תלויים גם במרכיב האוכלוסייה - בהמצאות המחלה באוכלוסיה
הנבדקת
The relation between sensitivity and specificity
רגישות גבוהה
• Don’t want to miss cases:– Severe disease– Effective treatment
• Don’t want to falsely label people as ill:– Fatal, no effective treatment– Emotional burden, stigma
סגוליות גבוהה
ROC curves for serum creatinine phosphokinase as used to detect myocardial infarction (hypothetical data)
Copyright restrictions may apply.
Ullrich, C. et al. JAMA 2005;294:924-930.
Receiver Operating Characteristic Curves for Reticulocyte Hemoglobin Content and Hemoglobin for the Detection of Iron Deficiency at Initial Screening
Hb=11.0
26.7
Triple test: serum α-fetoprotein, unconjugated
estriol, and human chorionic gonadotropin in
the 2nd trimester. Quadruple test: Triple test+
inhibin A. Combined test: serum pregnancy-associated
plasma protein A, free β subunit of human
gonadotropin, and nuchal translucency in the 1st
trimester. Integrated test: Combined
test+ Quadruple test
From Nelson textbook, based on Wald NJ, et al. NEJM 1999; 341:461–7From Nelson textbook, based on Wald NJ, et al. NEJM 1999; 341:461–7
Screening for Down’s syndrome
Usefulness of exercise ECG in 3 patients: sensitivity 60%, specificity 91%
A. 90% clinical probability
Coronary Disease
+ - T
+ 540 9 549 PPV 98%
Exercise - 360 91 451 NPV 20%
ECG
T 900 100 1000
Usefulness of exercise ECG in 3 patients: sensitivity 60%, specificity 91% cont.
B. 5% Clinical probability
+ - T
+ 30 86 116 PPV 26%
Exercise - 20 864 884 NPV 98%
ECG T 50 950 1000
Usefulness of exercise ECG in 3 patients: sensitivity 60%, specificity 91% cont.
C. 50% Clinical probability
+ - T
+ 300 45 345 PPV 87%
Exercise- 400 445 655 NPV 69%
ECG T 500 500 1000
רמות המניעה
מניעה ראשונית: פעולות שמטרתן למנוע •התפתחותה של מחלה
מניעה שניונית: התערבויות מוקדמות במהלך •המחלה שמטרתן ריפוי/שינוי מהלך המחלה.
מניעה שלישונית: התערבויות במהלך מחלה •קלינית שמטרתן שיקום/שיפור איכות החיים.
מהי סריקה?
רציונאל
אבחנה מוקדמת של מחלה תוביל לטיפול מוקדם •ולכן לעליה בסיכוי לריפוי והארכת חיים
Disease onset symptoms diagnosis
Clinical outcome, e.g.
death/disability
detection death
Natural course
screening
Time
הנחות יסוד
קיים שלב במהלך המחלה שבו טיפול יעיל •יותר מאשר לאחריו
עבור כל או רוב החולים ישנה תקופה •אסימפטומטית שבה ניתן לאבחן את המחלה
עבור רוב או כל החולים השלב הפרהקליני •יעבור להיות קליני בהיעדר טיפול
מהי סריקה?
איתור מוקדם של מחלה•
שלב א-סימפטומטי, פרהקליני•
שיפור התוצאים של המחלה•
מניעה שניונית•
Characteristics of a good screening test
•Simple
•Rapid
•Inexpensive
•Safe
•Acceptable
הערכה של תכניות סריקה
מדדים אופרטיבים:מס' האנשים שנסרקו•אחוז אוכלוסיית היעד שנסרק ומס' הפעמים שבוצעה •
סריקההמצאות המחלה הפרה-קלינית•עלות כוללת•עלות פר מקרה מאובחן•עלויות עבור מקרים שבעבר היו בלתי ידועים•אחוז החיוביים בסריקה שאובחנו וטופלו••PPV
תוצאים:
הפחתת תמותה באוכלוסיה הנסרקת•
) case fatality rateהפחתת שיעור הקטלניות (•בקרב הנסרקים
עליה בשיעור המקרים המאובחנים בשלב •מוקדם
הפחתת סיבוכים, השנויות, גרורות•
שפור איכות החיים בנסרקים•
הערכה של תכניות סריקה
Evaluation of screening programs
• Evaluation is subject to several sources of bias
Selection bias:• Individuals who are motivated enough to
participate in screening programs may have a different probability of disease than individuals who refuse participation (volunteers, people at risk…)
Lead time biasa perception of longer survival among screen detected
cases simply because the disease was detected earlier in its natural course
Length biasPreclinical
stageClinical stage
Length biasdetection of slower growing tumors that have an inherently
better prognosis than rapidly growing tumors that are usually detected following
clinical manifestations
Length bias
Length-time bias suggests that annual screening is more likely to detect slow-growing tumors, while fast-growing and potentially lethal tumors are less likely to be detected.
Overdiagnosis Bias
Evaluation of screening programs
• Outcome– Mortality:
• Cause specific mortality• All cause
– Survival– Morbidity– Quality of Life
lead time
&
length bias
שתי גישות לסריקה
אוכלוסייתית:Population
based approach
סיכון גבוה:High-riskapproach
Population based approach (mass screening)
• Screening test applied to the entire population, regardless of any a priory information on individual risk
• Test must be:– Inexpensive– Noninvasive
• Can be considered public health approach
High-risk approach(selective/targeted screening)
• The screening test is applied to a high risk group
• More cost-effective• Screening test can be:
– More expensive– More invasive/inconvenient
• Requires a clinical action to identify the high-risk group to be targeted
Case finding (opportunistic screening)
• Utilization of screening tests for detection of conditions unrelated to the patient’s complaints.
• Example: – FOB for a patient who came to the physician
complaining of pharyngitis.– Screening for depression
Multiphasic screening
• Screening for more than one disease
• The use of >2 screening tests together among a large group of people
• Example: pre-employment screening
• Cost-effective
• Limitations: multiple comparisons
Screening programs considerations
• Frequency: higher frequency less interval cancers higher sensitivity
• Population: higher risk higher PPV
נזקים אפשריים של מבחני סריקה
עלות
תופעות לוואי וסיבוכים
– תיוגlabelling effect
מאחר והאנשים הם לכאורה בריאים
כל תוצא שלילי בעקבות סריקה הוא יאטרוגני ולחלוטין ניתן למניעה