10 Screening.ppt
- 2. Learning objectives By the end of this session, you should be able to: • Define and explain epidemiologic screening principles • Identify criteria to be fulfilled before a screening program is introduced. • Understand & calculate sensitivity, specificity, PPV and NPV of a screening test.
- 3. ‘The presumptive identification of unrecognized disease by application of rapid tests or examinations, or other procedures that can be applied rapidly.’ ‘The examination of asymptomatic people in order to classify them as likely or unlikely to have the disease of interest.’ Early detection of disease (earlier than would usually occur in clinical practice) in the hope of modifying prognosis b/c those who have a positive result from the screening test are made to go further evaluation What is screening?
- 4. Screening sort out apparently well persons who probably have a disease from those probably do not have a disease Q: When should we do screening? Q: what are the aims of screening?
- 5. Exposure Stage of susceptibility Stage of Subclinical disease Stage of clinical disease Stage of recovery, disability or death Natural course: stages of progression
- 6. When? After sub-clinical disease (changes have occurred), but Before symptoms are manifest.
- 7. To reverse, halt, or slow the progression of disease more effectively than would probably normally happen To alter the natural course of disease for a better outcome for individuals affected. To reduce morbidity & mortality through early detection & treatment (prevention) To protect the society from contagious d/s • Assumptions – Early detection before development of symptoms will lead to a more favorable prognosis. – Treatment begun before the disease becomes clinically manifest will be more effective than later treatment … Aims of screening
- 8. To protect an institution • Rational allocation of resource To make preliminary identification of cases in epidemiological studies • Selection of healthy individuals: employment, military… • study on natural history of disease… aims…
- 9. Strategies of screening 1. Population approach – Apply methods to total population eg HIV testing Advantage- Inclusive of everyone and Ethically appropriate Disadvantage- Costs 2. Risk group approach: Advantages – It could be appropriate to individuals – Could produce subject motivation – Could have favorable benefits to cost ratio Disadvantages – It may be difficult in identifying high risk individuals – There may be misclassification of individuals – Unwanted labeling of individuals could bring anxiety 9
- 10. How to establish a screening program? Mechanism: CRITERIA called Modified Wilson criteria The Wilson criteria for screening emphasize the important features of any screening program, as follows: the condition should be an important health problem the natural history of the condition should be understood there should be a recognizable latent or early symptomatic stage there should be a test that is easy to perform and interpret, acceptable, accurate, reliable, sensitive and specific there should be an accepted treatment recognized for the disease treatment should be more effective if started early there should be a policy on who should be treated diagnosis and treatment should be cost-effective case-finding should be a continuous process
- 11. Criteria for introducing a screening program CONDITION /problem PROGRAM TREATMENT /intervention TEST/Dx
- 12. 1. The condition, i.e. health problem Does the significance of the disease warrant its consideration as a community problem?? Importance (prevalent, serious, predispose to other d/s) – Prevalence of pre-clinical disease should be high – Disease must be serious: congenital hypothyroidism, breast cancer Is the natural history of the disease known? – It should have a recognizable early or latent stage (asymptomatic) – Natural history should be known – Long period between 1st sign and overt disease
- 13. Is the screening test – Simple (not sophisticated) – Cheap – Precise, validated – Safe, Suitable & acceptable to population (impose minimal discomfort on patient) – Agreed diagnostic test(s) – Sensitive and specific – Reliable – Facility should be available – There should be confirmatory test which is accurate, relatively cheap and easy to perform 2. The test or diagnosis
- 14. Should be available, acceptable & Effective Of the disease at its earlier stages more effective than treatment begun after the development of symptoms? • If treatment makes no difference there is no need for screening – Cervical cancer (PAP smear): good prognosis – Lung cancer: bad prognosis • Presence of evidence-based policies on whom to treat (i.e. when the intervention is appropriate) Treatment during the detectable preclinical phase must provide the patient better prognosis 3. The treatment
- 15. Is there a mechanism for follow-up of individuals with positive screening results to ensure thorough diagnostic testing? Is there a schedules for the interval to repeat a screening? Intervention – Is it acceptable to public & professionals – Are facilities & staff available (ensure continuity-ongoing) – Benefits outweigh risks: cost-benefit and cost-effectiveness – Is the overall costs (cost of detection & treatment) reasonable Is there a counselling program for people who got Psychological/ Physical Harm? 4. The program, i.e. testing
- 16. Examples of screening Programs • Cancers: breast, cervix, colon, prostate, lung • Congenital : congenital displacement of hip • Cardiovascular d/s: aortic aneurysm • Which screening program might be appropriate to introduce to Ethiopia?
- 17. Quality of Screening Programs?
- 18. Accuracy of a screening test Measurement error Discrepancy b/n the numbers we use to represent the thing we are measuring & the actual value of the thing we are measuring Ex: your true wt is 60 Kg, but a scale this morning read 62 kg; the discrepancy (i.e. 2kg) is due to the measuring instrument & is called measurement error (measurement error of 2) • The two determining property of measure are 1. Validity 2. Reliability
- 19. Validity • The extent to which a test measures what it is supposed to measure. • (does it truly measure what it sets out to measure?: • Sensitivity and Specificity Ex: a devise for measuring sperm motility that actually measures sperm count is not valid
- 20. Reliability • Does it give consistent results? i.e. does it give the same measurement each time?: • Repeatability or precision • Refers to the degree to which results obtained can be replicated. • Lack of reliability can be due to • The measurement & measuring instrument • Instability of the attribute (characteristic) being measured (Intra-subject variation) • The observers (Inter-observer) 20
- 21. Q: “Gold standard” ?
- 22. Gold standard” • Confirmatory test • Is the best available information, which is the basis for evaluation of the performance of a screening (second diagnostic) test which is usually is cheaper, easier, or safer.
- 23. What can be calculated to check the accuracy of a screening test against Gold standard” 1. SENSITIVITY of the screening test (validity) 2. SPECIFICITY of the screening test (validity) 3. POSITIVE PREDICTIVE VALUE of the screening test (Yield) 4. NEGATIVE PREDICTIVE VALUE of the screening test
- 24. Validity of a categorical test: four possible relationships b/t a diagnostic test & actual presence of disease Screening Test result Disease status or Diagnostic test or Reference Test (Gold standard) Positive Negative Positive True + (a) False + (b) Negative False - (c) True - (d)
- 25. Sensitivity Ability of a test to correctly identify those with the disease Sensitivity = a a + c Probability of a positive test in people with the disease Disease +ve a + c Test Posit. Negat. a c Screening Pos Neg Positive Negative Confirmatory test Gold standard a + b c + d a + c b + d a b c d
- 26. Specificity Ability of a test to correctly identify those without the disease Specificity = d b + d Probability of a negative test in people without the disease Disease -ve b + d Test Posit. Negat. b d Screening Pos Neg Positive Negative Confirmatory test Gold standard a + b c + d a + c b + d a b c d
- 27. Screening test results Disease status (Gold standard) Diseased Not Diseased Total Positive 18 49 67 Negative 2 931 933 Total 20 980 1000 Sensitivity = ____ Specificity = _____ Example 27
- 28. Specificity and sensitivity • Increased sensitivity decreases the specificity –Leads to more false positives – people wrongly diagnosed as having the disease – unnecessary panic among people & Health workers –Unnecessary exposure for treatment –Unnecessary wastage of resource (human, time, drug, etc) –Unnecessary stress on the health system –Wrong negative implication external relation 28
- 29. Specificity and sensitivity • Increased specificity decreases the sensitivity –Leads to more false negatives – people wrongly diagnosed as not having the disease – delay in diagnosis –Negative implication on prognosis of disease –Unnecessary wastage of resource (human, time, drug, etc) for sever disease –Unnecessary stress on the health system 29
- 30. Specificity and sensitivity There is a need to weigh consequences of leaving cases undetected (false negatives) against erroneously classifying healthy persons as diseased (false positives) 30
- 31. Issues.. • Sensitivity should be increased at the expense of specificity when: – Consequence of missing a case is a problem – Disease is serious and definitive treatment exists – Disease easily spreads (eg. syphilis, HIV) – Subsequent diagnosis and treatment have minimal costs and risk (eg further series of blood pressure reading for BP) 32
- 32. Cont… • Specificity should be increased over sensitivity when –having the disease results in stigmatization/ discrimination 34
- 33. POSITIVE predictive value (Yield) = is the probability of having a disease in a person with a positive (abnormal) test result or when the test reads positive. = proportion of screening test positives who are truly positive = +PV= a/(a+b) Test result DISEASE STATUS (Gold standard) PRESENT ABSENT + TP (a) FP (b) _ FN (c) TN (d)
- 34. Positive Predictive Value (PVP) 37 a+b Ill Not ill Test positive PVP = a / (a+b) a b Positive Negative Screening Pos Neg Confirmatory test Gold standard a + b c + d a + c b + d a b c d
- 35. NEGATIVE predictive value The probability that an individual free of disease will test negative by the test = is the probability of not having the disease in a person with a negative result or when the result is negative (normal) = proportion of screening test negatives who are truly negative = -PV= d/(c+d) Test result DISEASE STATUS (Gold standard) PRESENT ABSENT + TP (a) FP (b) _ FN (c) TN (d)
- 36. Negative Predictive Value (PVN) 39 c+d Ill Not ill Test Negative PVN = d / (c+d) c d Positive Negative Screening Pos Neg Confirmatory test Gold standard a + b c + d a + c b + d a b c d
- 37. Relationship between PPV, NPV Sensitivity & Specificity • Lower PPV: more likely to be the result of poor specificity than poor sensitivity • Lower NPV: more likely to be the result of poor sensitivity than poor specificity 40
- 38. Issues…. • The more specific the test the greater the PPV • PPV can also be increased if prevalence of preclinical disease is high in screened population. – Can accomplish this by targeting high risk group • The more sensitive the test the greater the NPV 41
- 39. • The usefulness of a test depends not only on its sensitivity and specificity, but also on the prevalence of the condition tested for in the population. • As prevalence of disease increases…..the predictive value of a positive test also increases • As prevalence of disease decreases….the predictive value of a negative test increases Issues….
- 40. Example 1 Comparison of routine diagnosis of malaria and double read research slide Reference test: 100 fields read by 2 technicians Positive Negative Screening test: routine smear at 10 hospitals Positive 1555 988 Negative 514 1394
- 41. Example 1 - Results Sensitivity = 1555/2069 = 75.2% Specificity = 1394/2382 = 58.5% PPV = 1555/2543 = 61.1% NPP =73.1% Prev = 46.5% (Ref: BMJ 2004;329:1212-1215)
- 42. Strategies to Increase Yield • Select a test with high specificity –High sensitivity >> Low false negative - >> High NPV –High specificity >> Low false positive >> High PPV • Select disease with high prevalence of preclinical stage • Target high risk group for screening
- 43. Which test to choose • A sensitive test is preferable when – there is an important penalty for failing to detect a disease (e.g., when trying to detect a dangerous but treatable condition). – the probability of disease is relatively low and the purpose of the test is to discover possible cases. A sensitive test is, therefore, most helpful when the test result is negative. • A specific test is preferable when – the test result is positive, and are often used to confirm a diagnosis, which has been suggested by other data. A highly specific is preferable when false positive results might have negative (physical, emotional, or financial) consequences.
- 44. Sensitivity Sensitivity = True positives / Affected persons Persons testing positive (True positives) Persons testing negative (False negatives) Affected persons (Positive by gold standard) The sensitivity of a test in the ability of the test to identify correctly affected individuals Proportion of persons testing positive among affected individuals
- 45. What factors influence the sensitivity of a test? Characteristics of the affected persons? YES: Antigenic characteristics of the pathogen in the area (e.g., if the test was not prepared with antigens reflecting the population of pathogens in the area, it will not pick up infected persons in the area) Characteristics of the non-affected persons? NO: The sensitivity is estimated on a population of affected persons Prevalence of the disease? NO: The sensitivity is estimated on a population of affected persons Sensitivity is an INTRINSIC characteristic of the test
- 46. Specificity Specificity = True negatives / Non-affected persons Persons testing negative (True negatives) Persons testing positive (False positives) Non-affected persons (Negative by gold standard) The specificity of a test in the ability of the test to identify correctly non-affected individuals Proportion of person testing negative among non affected individuals
- 47. What factors influence the specificity of a test? Characteristics of the affected persons? NO: The specificity is estimated on a population of non affected Characteristics of the non-affected persons? YES: The diversity of antibodies to various other antigens in the population may affect cross reactivity (e.g., If malaria is endemic, polyclonal hyper gammaglobulinemia may increase the proportion of false positives) Prevalence of the disease? NO: The specificity is estimated on a population of non affected Specificity is an INTRINSIC characteristic of the test
- 48. Predictive value of a positive test Persons affected (True positives) Persons not affected (False positives) Persons testing positive (Positive by test) Predictive value of a positive test = True positives / Persons testing positive The predictive value of a positive test is the probability that an individual testing positive is truly affected Proportion of affected persons among those testing positive
- 49. What factors influence the predictive value positive of a test? • Sensitivity? YES: To some extend. • Specificity? YES: The more the test is specific, the more it will be negative for non affected persons. Thus, when the test is positive, it is probably truly positive (All non affected were correctly identified as testing negative). • Prevalence of the disease? YES: Low prevalence: The test will pick up more false positives YES: High prevalence: The test will pick up more true positives
- 50. Predictive value of a negative test Persons non affected (True negatives) Persons affected (False negatives) Persons testing negative (Negative by test) Predictive value of a negative test = True negatives / Persons testing negative The predictive value of a negative test is the probability that an individual testing negative is truly non-affected Proportion of non-affected persons among those testing negative
- 51. What factors influence the predictive value negative of a test? • Sensitivity? YES: The more the test is sensitive, the more it captures affected persons. Thus, when the test is negative, it is probably truly negative (all affected were captured among the positive). • Specificity? YES: But to a lesser extend. • Prevalence of the disease? YES: Low prevalence: The test will pick up more true negatives YES: High prevalence: The test will pick up more false negatives
- 52. To whom sensitivity, specificity and predictive values matters most? Sensitivity and specificity matter to laboratory specialists – Studied on panels of positives and negatives – Look into the intrinsic characteristics of the test: • Capacity to pick affected • Capacity to pick non affected Predictive values matter to clinicians and epidemiologists – Studied on homogeneous populations – Look into the performance of the test in real life: • What to make of a positive test • What to make of a negative test
- 53. Q: How do you evaluate a given screening program?
- 54. Evaluation of screening programs • Feasibility of screening program is determined by – Acceptability of program by potential screens (quick and easily administered without much discomfort) – Cost effectiveness – Yield of cases: number of cases detected by screening program • Yield measured by predictive value positive (PVP) and negative (PVN) – Predictive value measures whether or not an individual actually has the disease, given the results of the screening test. 57
- 55. Evaluation of a screening program What proportion of tests are positive? What type of disease is being detected? What is the predictive value of the test? What is the cost per test? Do screen-detected cases have a better short term prognosis? The only proper evidence of effectiveness of a screening program is a reduction of total age-specific mortality or morbidity, ideally demonstrated by randomized trial.
- 56. Increasing Sensitivity and Specificity • Clinicians can improve the sensitivity or specificity of the diagnostic approach by using multiple tests • Using several tests in combination, i.e. in parallel, will significantly increase the sensitivity (while decreasing the specificity) • Conversely, using multiple tests in sequence, i.e. in serial significantly increases the specificity (while decreasing the sensitivity)
- 57. Different Strategies to Improve Screening by Combining 2 Independent Tests • IF, You want to be sure of your diagnosis – Prioritise a test with higher PPV and specificity – Reduce false positive • IF, You do not want to miss a potential case – Prioritise a test with higher NPV and sensitivity – Reduce false negative
- 58. Combination Testing • Serial Testing – A test is first applied to a group. All those with a positive result are retested. – E.g., Serological testing for syphilis • Parallel Testing – Two tests are applied together. All those with either or both tests are considered to be positive. 61
- 59. Two Stage Screening • Those who initially tested positive are called again for further testing – a more expensive, more invasive and less comfortable test • Designed to reduce the problem of false positives • Where as net sensitivity will decline in a two stage screening, net specificity will increase. • Why? Because we reduced false positives.
- 60. Volunteer bias Volunteers & non-volunteers are different in the basis of: 1) Volunteers tend to have better health and lower mortality rates than general population they are more likely to adhere to intervention (screening, medication, etc) 2) Those who volunteer are the “worried well” At higher risk of developing disease because of family history or life style characteristics May have an increased risk of mortality regardless of efficacy of screening program
- 61. Lead time bias Lead time is the interval between the diagnosis of a disease at screening and when it would have been detected due to development of symptoms • It represents the amount of time by which the diagnosis has been advanced as a result of screening • Depends on how soon the screening is performed • If not taken into account, screened groups may appear to survive longer than unscreened simply because diagnosis was made earlier in the course of disease (lead time bias)
- 62. Detected by screening Asymptomatic Pre-clinical Symptomatic Detected due to symptoms Lead time Screen based Symptom based Death 66
- 63. Length bias • Refers to the over representation among screen detected cases of those with a long preclinical phase of disease and thus a more favorable prognosis • Those with long preclinical phase are more readily detectable by screening than more rapidly progressing cases with a short preclinical phase. • Thus length bias could lead to erroneous conclusion that screening was beneficial • Yet observed difference is as a result of detection of less rapidly fatal cases through screening, while those more rapidly fatal are diagnosed after the development of symptoms
- 64. o o o o o o x x x x x X onset of disease process O time of death screening Rapidly Progressive Disease Slowly Progressive Disease 68 x