12/12/2009Dr. Salwa Tayel1 Comunicación y Gerencia

12/12/2009Dr. Salwa Tayel2 Screening Family and Community Medicine Department King Saud University

Learning Objectives: 1.D efine screening and mention its purpose. 2.L ist WHO criteria for screening 3.C alculate and interpret measures of the validity of a screening test: ---Sensitivity ---Specificity 4.C alculate and interpret measures of the performance (yield) of a screening test: ---Predictive value positive (PV+) --- Predictive value negative (PV-)

Screening for Disease Control l Screening: The application of a disease- detection test in asymptomatic apparently healthy individuals. l Purpose: To classify individuals with respect to their likelihood of having a particular disease. l Screening procedure itself does NOT formally diagnose illness.

12/12/2009 Dr. Salwa Tayel5 Screening tools Questionnaire, inventory,…. Examination: blood pressure, weight, height Investigation: Lab, x-ray,…

Susceptible Host Subclinical Disease Clinical Disease Stage of Recovery, Disability, or Death Point of Exposure Screening Onset of symptoms Diagnosis required Natural History of Disease Detectable subclinical disease

12/12/2009Dr. Salwa Tayel7 Early Intervention in the Natural History of Disease HEALTH OUTCOMES Cure Control Disability Death Disease Onset SymptomsDiagnosisTherapy Care Seeking Good Health Early detection through Screening

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Examination of asymptomatic people likely l Classification as unlikely ….. to have a disease screening

“ Unlikely”referred to next screening cycle l “Likely”further testing for diagnosis yes no referred to next treatment screening cycle

12/12/2009Dr. Salwa Tayel11 Flow diagram for a screening program Population Test -veTest +ve UnaffectedAffected Intervention Diagnostic procedures Screening test Re-screen

Screening for Disease Control Screening Objective: To lower morbidity and mortality of the disease in a population (control, rather than elimination of disease).

Comparison between screening and diagnostic tests Diagnostic tests Screening tests Done to those with suggestive signs or symptoms Done to those who are apparently healthy or asymptomatic Applied to a single person Applied to a group of individuals Results are based on the evaluation of a number of symptoms, signs and investigations Results are based on one criterion Results are conclusive and finalResults are not conclusive More accurateLess accurate More expensiveLess expensive Basis for treatmentNot a basis for treatment

WHO criteria for screening: 1)The disease should be important public health problem (relates to cost effectiveness, and prognosis). 2)There should be an effective and acceptable treatment for the condition if identified in an early stage. 3)Facilities for the confirmation of the diagnosis and treatment should be available.

WHO criteria for screening: 4)There should be a latent stage of the disease (long and detectable pre- symptomatic stage). 4) There should be a latent stage of the disease (long and detectable pre- symptomatic stage). 5) There should be a suitable screening test or examination that can detect the condition 6) The test should be acceptable to the population.

7) Natural history of disease should be adequately understood. 8) There should be an agreed upon policy on whom to treat.

9) The total cost of finding a case should be economically balanced in relation to medical expenditure as a whole. 10) Case finding should be a continuous process, not just a “once and for all” project.

Diseases for which screening has been recommended Cervical cancer l Breast cancer l Ovarian cancer l Colorectal cancer l Skin cancer l Diabetes l Hypertension

Conditions for which screening programmes have been proved successful l Rhesus haemolytic disease of newborns: screening of at risk mothers is carried out and their sensitization is prevented by post-partum anti-D antiserum. l Phenyl ketonurea in infants: A condition leading to mental retardation - may be easily screened for and mental retardation prevented by prescribing a diet low in phenylalanine. l Hypertension in middle aged men : Risk of stroke may be reduced by preventive or prophylactic measures

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Characteristics of a screening test: Validity (Sensitivity, Specificity) Reliability (repeatability/precision) Yield (performance): Predictive values of the test.

Validity of Screening Tests How good is the screening test compared with the confirmatory diagnostic test (Gold Standard test)? l The test will correctly classify a diseased person as likely to have the condition (“sensitivity”). l The test will correctly classify a non- diseased person as unlikely to have the condition (“specificity”).

12/12/ Results of screening test compared to gold standard Total Gold standard Screening test NegativePositive PS(FP)(TP)Positive NS(TN)(FN)Negative GTTHTDTotal

Validity of Screening Tests a d c b True Disease Status + - Results of Screening Test + - a = true positive b = false positive c = false negative d = true negative

Validity of Screening Tests a d c b True Disease Status + - Results of Screening Test + - Sensitivity: The probability of testing positive if the disease is truly present Sensitivity = a / (a + c)

Validity of Screening Tests a d c b True Disease Status + - Results of Screening Test + - Specificity: The probability of screening negative if the disease is truly absent Specificity = d / (b + d)

12/12/ Results of screening 100 men for prostate cancer using (PSA) Total Gold standard (Prostatic biopsy) Screening test (PSA) No cancer Cancer 10 7 (FP) 3 (TP) Positive (TN) 2 (FN) Negative Total

12/12/2009Dr. Salwa Tayel28 Adverse effects of screening  Stress and anxiety caused by a false positive screening results.  Unnecessary investigation and treatment of false positive results  Prolonging knowledge of an illness if nothing can be done about it.  A false sense of security caused by false negatives, which may even delay final diagnosis.  Overuse/waste of medical resources.

Sensitivity: a / (a + c) Sensitivity = 90% Specificity: d / (b + d) Specificity = 95% Prevalence of disease =(a+c)/(a+b+c+d) =100/200=50%

Reliability of Screening Tests Reproducibility RELIABILITY (Reproducibility) Precision: The extent to which the screening test will produce the same or very similar results each time it is administered (repeated). --- A test must be reliable before it can be valid.

Reliability of Screening Tests Sources of variability that can affect the reproducibility of results of a screening test: 1. Biological variation (e.g. blood pressure) 2. Reliability of the instrument itself 3. Intra-observer variability (differences in repeated measurement by the same screener) 4.Inter-observer variability (inconsistency in the way different screeners apply or interpret test results)

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Yield (Performance) Yield is the amount of previously unrecognized disease that is diagnosed and brought to treatment as a result of screening. It is measured by: l Predictive Value Positive (PV+) l Predictive Value Negative (PV-)

Yield a d c b True Disease Status + - Results of Screening Test + - Predictive value positive (PV+): The probability that a person actually has the disease given that he or she tests positive. i.e. The ability to predict the presence of disease from test results. PV+ = a / (a + b)

Yield a d c b True Disease Status + - Results of Screening Test + - Predictive value negative (PV-): The probability that a person is truly disease free given that he or she tests negative. i.e. The ability to predict the absence of disease from test results. PV- = d / (c + d)

Calculate: PV+ =19/118=16% PV-= 1881/1882=99.999

Calculate: PV+=57/59=96.6% PV-=38/41=93% useful test

Sensitivity: a / (a + c)= 19/20 Sensitivity = 95% Specificity: d / (b + d)= 1881/1980 Specificity =95% Prevalence=20/2000*100=1%

Sensitivity: a / (a + c)= 57/60 Sensitivity = 95% Specificity: d / (b + d)= 38/40 Specificity =95% Prevalence= 60/100*100=60%

Prevalence (%) Sensitivity Specificity PV % 95% 1.8% 1.090% 95% 15.4% 5.090% 95% 48.6% % 95% 94.7% Factors affecting the yield of a screening test

Sensitivity:Specificity:Prevalence: PV+ is maximized when used in “high risk” populations since the prevalence of pre-clinical disease is higher than in the general population…. screening a total population for a relatively infrequent disease can be very wasteful of resources and may yield few previously undetected cases. Factors affecting the yield of a screening test

Characteristics of a suitable screening test: Validity – the extent to which the test distinguishes between persons with and without the disease: High validity requires: High Sensitivity High Specificity Reliability (High) Performance (Yield) Low cost, invasiveness, and discomfort Costs. 1. Costs of applying the test itself. 2. Costs of performing additional tests on people with false positives, in order to correct the test’s mistakes

12/12/2009Dr. Salwa Tayel43 Calculate: Sensitivity: Specificity: PV+: PV-: False Positive rate False Negative rate Disease prevalence

Comparison of mammography results with findings from surgical excisional biopsies in women without palpable breast masses Total Gold standard (Surgical biopsy) Screening test (Mammography) No cancer Cancer Positive Negative Total

12/12/ Bias in screening 1. (volunteer bias) Those who choose to participate are likely to be different from those who don’t. Volunteers tend to have: Better health Better health Lower mortality Lower mortality Likely to adhere to prescribed medical regimens Likely to adhere to prescribed medical regimens On the other hand…. The “worried well” (who have higher risk) may be more likely to participate.

12/12/ Lead Time Bias Survival will appear to be prolonged in screened people simply because survival is measured from an earlier point in the disease’s evolution.

12/12/ Lead time bias  Lead time: interval between the diagnosis of a disease at screening and the usual time of diagnosis (by symptoms) Diagnosis by screening Diagnosis via symptoms Lead Time

12/12/ Lead time bias  The apparently better survival for screened persons is because diagnosis is being made at an earlier point in the natural history of the disease.  There is no additional life is added but there may be added anxiety from knowing the disease earlier. Diagnosis by screening in 1994 Death in 2008 Survival = 14 years

12/12/ Lead time bias Diagnosisbyscreening in 1994 Usual time of diagnosis via symptoms in 1998 Lead Time 4 years Death in 2008 True Survival = 10 years Survival = 14 years

12/12/ Length bias Screening selectively identifies those with a long preclinical and clinical phase (i.e., those who would have a better prognosis regardless of the screening program) Screening selectively identifies those with a long preclinical and clinical phase (i.e., those who would have a better prognosis regardless of the screening program) If disease is slowly progressive at one stage, it is likely to be slowly progressive at others and hence, to have a better overall prognosis regardless of any effects of early treatment.

12/12/ Length bias O Biological onset of disease Screening Y Symptoms Begin D Death P Disease detectable via screening ODPY ODPY ODPY ODPY ODPY OPYD Time

12/12/ Over-diagnosis Enthusiasm for a new screening program may detect cancers that would never have become clinically apparent in a man’ lifetime. Enthusiasm for a new screening program may detect cancers that would never have become clinically apparent in a man’ lifetime. Un-necessary treatment of mild cases would result in unrealistically favorable outcomes in persons thought to have the disease This gives the appearance of an effective screening program.

12/12/ Prostate Cancer Incidence Rates by Stage, 1973–1995 Distant Unstaged Regional Localized

12/12/ Thank you Bibliotheca Alexandrina

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