EPIDEMIOLOGY III. Screening

Transcription

1 EPIDEMILGY III. Screening

2 Prevention Primary prevention strategies intend to avoid the development of a disease Secondary prevention strategies attempt to diagnose and treat an existing disease in its early stages (no signs and symptomps) before it results in significant morbidity The aim of terrtiary prevention is to reduce the negative impact of established disease by restoring function and reducing disease-related complications Quaternary prevention describes the set of health activities that mitigate or avoid the consequences of unnecessary or excessive interventions in the health system

3 Prevention Doctor s side Prevention levels [6] Disease absent present absent Primary prevention (illness absent disease absent) Secondary prevention (illness absent disease present) Patient s side Illness present Quaternary prevention (illness present disease absent) Tertiary prevention (illness present disease present)

4 Screening...the identification of unrecognized disease or defect by the application of tests, examinations or other procedures......sort out apparently well persons who probably have disease from those who probably do not....not intended to be diagnostic...

5 Different kinds of testing in medicine Diagnostic - specifically looking for a suspected condition which is tested for and confirmed or excluded Case-finding - usually in an investigation of exposed people, to sort the exposed and ill from the exposed and well. (E.g. test people who were in contact with a case of tuberculosis, or check b.p. of patient who is overweight) pportunistic case-finding - A test is offered to an individual without symptoms of the disease when they present to a health care practitioner for reasons unrelated to that disease. Screening - usually no specific exposure or indication that the individual has disease. (E.g. routine mammography testing in middle-aged females)

6 Secondary prevention (screening) The World Health rganization (WH) defines screening as the presumptive identification of unrecognised disease or defects by means of tests, examinations or other procedures that can be applied rapidly. Screening is intended for all people, in an identified target population, who do not have symptoms of the disease or condition being screened for. The process can identify: a pre-disease abnormality; early disease; or disease risk markers.

7 Types of screening Mass screening, no selection of population (e.g., checking all infants for hearing problems) Selective screening (e.g., by age and sex: mammograms for women aged over 40) Multiphased screening (a series of tests, as family doctors do at annual health exams)

8 Population-based screening A test is offered systematically to all individuals in the defined target group within a framework of agreed policy, protocols, quality management, monitoring and evaluation. It is an organised integrated process where all activities along the screening pathway are planned, coordinated, monitored and evaluated through a quality improvement framework.

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10 WH - Principles of Screening 1. The condition should be an important health problem. 2. There should be a treatment for the condition. 3. Facilities for diagnosis and treatment should be available. 4. There should be a latent stage of the disease. 5. There should be a test or examination for the condition. 6. The test should be acceptable to the population. 7. The natural history of the disease should be adequately understood. 8. There should be an agreed 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.

11 Characteristics of a good screening test Valid (highly sensitive and specific, see later) Simple, accomplished easily and quickly Reliable (gives consistent results; no random errors) Yield (number of cases identified per thousand screened) Cost benefit (compare costs avoided due to early detection of the disease against cost of the screening. Does the test merely uncover more disease that is expensive to treat without appreciable advantage?) Applicable and acceptable (discomfort, hassle, cost of obtaining test) Follow-up services (plan needed to deal with positive results)

12 Ethics in screening Informed consent obtained? Implications of positive result? Number and implications of false positives? Ditto for false negatives? Labeling and stigmatization

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14 Remember this slide?

15 Cases Pre-detectable preclinical clinical old

16 What is the prevalence of the condition?

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19 What is used as a reference test or gold standard 1. Most definitive diagnostic procedure e.g. microscopic examination of a tissue specimen 2. Best available laboratory test e.g. polymerase chain reaction (PCR) for HIV virus 3. Comprehensive clinical evaluation e.g. clinical assessment of arthritis

20 SENSITIVITY (example: blood in stool) Sensitivity tells us how well a positive test detects the agent to be screened. It is defined as the fraction of the sample with positive test outcome. Its counterpart is the false negative rate, defined as the fraction of the sample who test negative. Sensitivity and false negative rate add up to one.

21 SPECIFICITY (if the outcome is specific for colon cancer) Specificity tells us how well a negative test detects non-disease (non-colon cancer). It is defined as the fraction of the nondiseased who test negative. Its counterpart is the false positive rate, defined as the fraction of the non-diseased who test positive. Specificity and the false positive rate add up to one.

22 Where do we set the cut-off for a screening test? Consider: -The impact of high number of false positives: anxiety, cost of further testing -Importance of not missing a case: seriousness of disease, likelihood of re-screening

23 Validity measures of sreening tests TEST Result sensitivity - specificity Disease to be screened Disease N disease Total Positive a b a+b Negative c d c+d Total a+c b+d a+b+c+d Sensitivity = a/ (a+c) i.e. percentage (%) of true positives among patients indicated to be ill Specificity = d/ (b+d) i.e. percentage (%) of true negatives among patients indicated to be well

24 CHANGING THE THRESHLD FR A TEST When disease is defined by a threshold on a continuous test, the test characteristics can be altered by changing the threshold or cut-off point. Lowering the threshold improves sensitivity, but often at the price of lowered specificity (i.e. more false-positives). Raising the threshold improves specificity, but often at the price of lowered sensitivity (i.e. more false negatives). This can be especially important when the distribution of a characteristic is unimodal, such as blood pressure, cholesterol, weight, etc. (Because the gray area is so large).

25 Combination of screening tests Commonly done in medical practice Choices depend on cost, invasiveness, volume of test, presence and capability of lab infrastructure, urgency, etc. Can be done sequentially or simultaneously Sequential Testing (Two-Stage Screening) After the first (screening) test was conducted, those who tested positive were brought back for the second test to further reduce false positives Consequently, the overall process will increase specificity but with reduced sensitivity

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27 Combination of screening tests - Example Test 1 (blood sugar), assume: Disease prevalence = 5%, population = 10,000 Sensitivity = 70%, specificity = 80% Screen positives from the first test Diabetes No diabetes Total Positive Negative

28 Diabetes No diabetes Total Positive Negative Test 2 (glucose tolerance test) Sensitivity = 90% Specificity = 90% Diabetes No diabetes Total Positive Negative AFTER TW SCREENINGS: Net sensitivity = 315 / 500 = 63% New specificity = ( ) / 9500 =98%

29 Predictive value of sreening tests TEST Result positive - negative Disease to be screened Disease N disease Total Positive a b a+b Negative c d c+d Total a+c b+d a+b+c+d Positive predictive value = a/(a+b) i.e. percentage (%) of true positives among patients indicated to be positive (If a person tests positive, what is the probability that he or she has the disease?) Negative predictive value = d/(c+d) i.e. percentage (%) of true negatives among patients indicated to be negative (What is the probability that he or she does not have the disease?)

30 Disadvantages of screening Screening involves cost and use of medical resources on a majority of people who do not need treatment. Adverse effects of screening procedure (e.g. discomfort, radiation exposure, chemical exposure). Stress and anxiety caused by a false pozitive screening result. Unnecessary investigation and treatment of false positive results. Stress and anxiety caused by prolonging knowledge of an illness without any improvement in outcome. A false sense of security caused by false negatives, which may delay final diagnosis.

31 Problems of screening I. Lead time bias If the disease is diagnosed earlier with screening, the survival time since diagnosis is longer with screening, but life span may have not been prolonged Looking survival time since diagnosis, screening will show an increase what might be attributed success to a screening test that does nothing but advance diagnosis Comparing statistics of mortality due to a disease in a screened and unscreened population gives more meaningful information.

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33 Problems of screening II. Length (selection) bias If people with a higher risk of a disease are more likely to be screened (e.g. women with a family history of breast), then a screening test will look worse than it really is: negative outcomes among the screened population will be higher than for a random sample. If a test is more available to young and healthy people then fewer people in the screening population will have negative outcomes than for a random sample, and the test will seem to make a positive difference.

34 Horizontal line : duration of time in pre-clinical state Diagnosis : equivalent to placing a random vertical line. Intersection represents case diagnosed. Vertical line is more likely to intersect longer horizontal lines.

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36 Different nature of diseases S 0 : Disease free state : Does not have disease or has disease which cannot be detected by exam. S p : Pre-clinical state: Has disease but no signs or symptoms; capable of being detected by exam. Individual is asymptomatic. S c : Clinical state : diagnosis by usual care. S 0 S p S c : Progressive disease model (Breast cancer) S p S 0 S c : Progressive disease model : subgroup S p never goes on to clinical disease (Prostate cancer) S 0 S p S c : Non-progressive disease model (HPV, cervix cancer)

37 Effect of disease s prevalence Calculation Sensitivity Specifty PPV 1 PPV 10 NPV 1 NPV 10

38 Slides from: Sukon Kanchanaraksa, PhD Johns Hopkins University

39 Slides from: Sukon Kanchanaraksa, PhD Johns Hopkins University

40 Grade Definition A The USPSTF recommends the service. There is high certainty that the net benefit is substantial. B C D I State ment Suggestions for Practice ffer or provide this service. The USPSTF recommends the service. There is high ffer or provide this service. certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. The USPSTF recommends selectively offering or ffer or provide this service for providing this service to individual patients based on selected patients depending on professional judgment and patient preferences. There individual circumstances. is at least moderate certainty that the net benefit is small. The USPSTF recommends against the service. There Discourage the use of this service. is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. Read the clinical considerations section of USPSTF Recommendation Statement. If the service is offered, patients should understand the uncertainty about the balance of benefits and harms.

41 Check some of the USPSTF recommendations! org/uspstopics.htm#az