Screening for Disease PDF

SCREENING FOR DISEASE Dr. Babiker Mohamed Ali Rahamtalla 1 1  Introduction  Epidemiologist and others who study disease find that the pattern of disease in hospitals is quite different from that in a community.  That is, a far l...

SCREENING FOR DISEASE Dr. Babiker Mohamed Ali Rahamtalla 1 1  Introduction  Epidemiologist and others who study disease find that the pattern of disease in hospitals is quite different from that in a community.  That is, a far larger proportion of disease (e.g., diabetes, hypertension) is hidden from view in the community than is evident to physicians or to the general public.  The analogy of an iceberg, only the tip of which is seen, is widely used to describe disease in the community.  The concept of the "iceberg phenomenon of disease" gives a better idea of the progress of a disease from its sub-clinical stages to overt or apparent disease than the familiar spectrum of disease.  The submerged portion of the iceberg represents the hidden mass of disease (e.g., sub-clinical cases, carriers, undiagnosed cases).  The floating tip represents what the physician sees in his practice.  The hidden part of the iceberg thus constitutes the mass of unrecognized disease in the community, and its detection and control is a challenge to modern techniques in preventive medicine. 2  Iceberg of disease 3  Concept of Screening  The active search for disease among apparently healthy people is a fundamental aspect of prevention.  This is embodied in screening, which has been defined as "the search for unrecognized disease or defect by means of rapidly applied tests, examinations or other procedures in apparently healthy individuals."  Historically, the annual health examinations were meant for the early detection of "hidden" disease.  To bring such examinations within the reach of large masses of people with minimal expenditures of time and money, a number of alternative approaches have come into use.  They are based primarily on conserving the physician-time for diagnosis and treatment and having technicians to administer simple, inexpensive laboratory tests and 4 operate other measuring devices.  Concept of Screening  This is the genesis of screening programmes.  The original screening programmes were for individual diseases such as tuberculosis, syphilis or selected groups such as antenatal mothers, school children and occupational groups.  Over the years, the screening tests have steadily grown in number.  Screening is considered a preventive care function, and some consider it a logical extension of health care.  Screening differs from periodic health examinations in the following respects: 1. capable of wide application 2. relatively inexpensive, and 3. requires little physician-time.  In fact the physician is not required to administer the test, but only to interpret it. 5  Screening and Diagnostic Tests  A screening test is not intended to be a diagnostic test.  It is only an initial examination.  Those who are found to have positive test results are referred to a physician for further diagnostic work-up and treatment.  However, the criteria are not hard and fast.  There are some tests which are used both for screening and diagnosis, e.g., test for anaemia and glucose tolerance test.  Screening and diagnosis are not competing, and different criteria apply to each. 6  Screening and Diagnostic Tests Contrasted Screening test Diagnostic test 1. Done on apparently healthy Done on those with indications or sick. 2. Applied to groups Applied to single patients, all diseases are considered. 3. Test results are arbitrary and final Diagnosis is not final but modified in light of new evidence, diagnosis is the sum of all evidence. 4. Based on one criterion or cut-off point Based on evaluation of a number of symptoms, signs (e.g., diabetes) and laboratory findings. 5. Less accurate More accurate. 6. Less expensive More expensive. 7. Not a basis for treatment Used as a basis for treatment. 8.The initiative comesfrom the investigator or The initiative comes from a patient with a· agency providing care. complaint.  Concept of Lead Time  There is nothing to be gained in screening for diseases whose onset is quite obvious.  Detection programmes should be restricted to those conditions in which there is considerable time lag between disease onset and the usual time of diagnosis.  In this period, there are usually a number of critical points which determine both the severity of the disease and the success of any treatment in reversing the disease process.  There is clearly little value in detecting disease in advance of the usual time of diagnosis unless such detection precedes the final critical point beyond which treatment would be unsuccessful and/or permanent damage would be done. 8  Concept of Lead Time  Detection programmes should, therefore, concentrate on those conditions where the time lag between the disease's onset and its final critical point is sufficiently long to be suitable for population screening.  "Lead time" is the advantage gained by screening, i.e., the period between diagnosis by early detection and diagnosis by other means.  The benefits of the programme must be seen in terms of its outcomes.  It is also necessary for the complexities and costs of any detection programme to be viewed against the benefits accruing therefrom. 9  Aims and Objectives  The basic purpose of screening is to sort out from a large group of apparently healthy persons those likely to have the disease or at increased risk of the disease under study, to bring those who are "apparently abnormal" under medical supervision and treatment.  Screening is carried out in the hope that earlier diagnosis and subsequent treatment.  Favourably alters the natural history of the disease in a significant proportion of those who are identified as "positive" 10  Explanation of Terms  Screening Strictly speaking, screening is testing for infection ordisease in populations or in individuals who are not seeking health care; for example, serological testing for AIDS virus in blood donors, neonatal screening, premarital screening for syphilis.  Case-finding This is use of clinical and/or laboratory tests to detect disease in individuals seeking health care for other reasons; for example, the use of VDRL test to detect syphilis in pregnant women. Other diseases include pulmonary tuberculosis in chest symptomatics, hypertension, cervical cancer, breast cancer, diabetes mellitus, etc.  Diagnostic tests Use of clinical and/or laboratory procedures to confirm or refute the existence of disease or true abnormality in patients with signs and symptoms presumed to be caused by the disease; for example, VDRL testing of patients with lesions suggestive of secondary syphilis; endocervical culture for N. gonorrhoea. 11  Explanation of Terms  The distinction between screening, case-finding or diagnosis should be clear-cut.  Often, however, it is blurred by the multiplicity of tests used and the haphazard nature of diagnostic decision-making.  Thus the same test may be used in different contexts for both screening and diagnosis.  Each step may involve multiple tests as in the case of syphilis.  In evaluating a test, then, one must consider whether it is for screening or diagnosis, alone or in conjunction with other tests 12  Uses of Screening  Four main uses have been described:  Case detection  This is also known as "prescriptive screening".  It is defined as the presumptive identification of unrecognized disease, which does not arise from a patient's request, e.g., neonatal screening.  In other words, people are screened primarily for their own benefit.  Specific diseases sought by this method have included bacteriuria in pregnancy, breast cancer, cervical cancer, deafness in children, diabetes mellitus, iron deficiency anaemia, PKU, pulmonary tuberculosis, haemolytic disease of the newborn, etc.  Since disease detection is initiated by medical and public health personnel, they are under special obligation to make sure that appropriate treatment is started early. 13  Uses of Screening  Control of disease  This is also known as "prospective screening".  People are examined for the benefit of others, e.g., screening of immigrants from infectious diseases such as tuberculosis and syphilis to protect the home population; and screening for streptococcal infection to prevent rheumatic fever.  The screening programme may, by leading to early diagnosis permit more effective treatment and reduce the spread of infectious disease and/or mortality from the disease. 14  Uses of Screening  Research purposes Screening may sometimes be performed for research purposes. For example, there are many chronic diseases whose natural history is not fully known (e.g., cancer, hypertension). Screening may aid in obtaining more basic knowledge about the natural history of such diseases, as for example, initial screening provides a prevalence estimate and subsequent screening, an incidence figure. Where screening is done for research purposes, the investigator should inform the study participants that no follow-up therapy will be available.  Educational opportunities Apart from possible benefits to the individual and the acquisition of information of public health relevance, screening programmes (as for example, screening for diabetes) provide opportunities for creating public awareness and for educating health professionals.Screening may sometimes be performed for research purposes. 15  Types of Screening Three types of screening have been described: 1. Mass screening 2. High-risk or selective screening 3. Multiphasic screening. 16  Types of Screening  Mass screening  Mass screening simply means the screening of a whole population or a sub-group, as for example, all adults.  It is offered to all, irrespective of the particular risk individual may run of contracting the disease in question (e.g., tuberculosis).  Mass screening for disease received enthusiastic support in the past.  However, when a number of mass screening procedures were subjected to critical review, there appeared to be little justification for their use in many instances.  Indiscriminate mass screening, therefore; is not a useful preventive measure unless it is backed up by suitable treatment that will reduce the duration of illness or alter its final outcome. 17  Types of Screening  High-risk or selective screening Screening will be most productive if applied selectively to high- risk groups, the groups defined on the basis of epidemiological research. For example, since cancer cervix tends to occur relatively less often in the upper social groups, screening for cancer cervix in the lower social groups could increase the yield of new cases. One population sub-group where certain diseases (e.g., diabetes, hypertension, breast cancer) tend to be aggregated in the family. By screening the other members of the family (and close relatives), the physician can detect additional cases. 18  Types of Screening  High-risk or selective screening ( cont…)  Epidemiologists have extended the concept of screening for disease to screening for "risk factors", as these factors apparently antedate the development of actual disease.  For example, elevated serum cholesterol is associated with a high risk of developing coronary heart disease.  Risk factors, particularly those of a patho-physiological nature such as serum cholesterol and blood pressure are amenable to effective interventions.  In this way, preventive measures can be applied before the disease occurs.  Besides effectiveness, economical use of resources will also occur if the screening tests are selectively applied to individuals in high-risk group. 19  Types of Screening  Multiphasic screening  It has been defined as the application of two or more screening tests in combination to a large number of people at one time than to carry out separate screening tests for single diseases.  The procedure may also include a health questionnaire, clinical examination and a range of measurements and investigations (e.g., chemical and haematological tests on blood and urine specimens, lung function assessment, audiometry and measurement of visual acuity) - all of which can be performed rapidly with the appropriate staffing organization and equipment. 20  Types of Screening  Multiphasic screening (cont….)  Multiphasic screening has enjoyed considerable popularity, and evidence from randomized controlled studies in UK and USA suggested that multiphasic screening has not shown any benefit accruing to the population in terms of mortality and morbidity reduction.  On the other hand, it has increased the cost of health services without any observable benefit.  Furthermore, in multiphasic screening, as currently practised, most of the tests have not been validated.  These observations have cast doubts on the utility of multiphasic screening 21  Criteria for Screening Before a screening programme is initiated, a decision must be made whether it is worthwhile, which requires ethical, scientific, and, if possible financial justification. The criteria for screening are based on two considerations: 1. the DISEASE to be screened, and 2. the TEST to be applied 22  Disease  The disease to be screened should fulfil the following  criteria before it is considered suitable for screening: the condition sought should be an important health problem (in general, prevalence should be high); there should be a recognizable latent or early asymptomatic stage; the natural history of the condition, including development from latent to declared disease, should be adequately understood (so that we can know at what stage the process ceases to be reversible); there is a test that can detect the disease prior to the onset of signs and symptoms; 23  Disease facilities should be available for confirmation of the diagnosis; there is an effective treatment; there should be an agreed-on policy concerning whom to treat as patients (e.g., lower ranges of blood pressure; border-line diabetes); there is good evidence that early detection and treatment reduces morbidity and mortality; the expected benefits (e.g., the number of lives saved) of early detection exceed the risks and costs.  When the these criteria are satisfied, then only, it would be appropriate to consider a suitable screening test. 24  Screening Test The test must satisfy the criteria of acceptability, repeatability and validity, besides others such as yield, simplicity, safety, rapidity, ease of administration and cost. Tests most likely to fulfil one condition may however, be least likely to fulfil another - for example, tests with greater accuracy may be more expensive and time consuming. The choice of the test must therefore often be based on compromise. 25  Screening Test  Acceptability Since a high rate of cooperation is necessary, it is important that the test should be acceptable to the people at whom it is aimed. In general, tests that are painful, discomforting or embarrassing (e.g., rectal or vaginal examinations) are not likely to be acceptable to the population in mass campaigns.  Repeatability An attribute of an ideal screening test or any measurement (e.g., height, weight) is its repeatability (sometimes called reliability, precision or reproducibility). That is, the test must give consistent results when repeated more than once on the same individual or material, under the same conditions. The repeatability of the test depends upon three major factors, namely observer variation, biological (or subject) variation and errors relating to technical methods. For example, the measurement of blood pressure is poorly reproducible because it is subjected to all these three major factors. 26  Screening Test  Repeatability: (cont…)  A. Observer variation  All observations are subjected to variation (or error).  These may be of two types:  a. Intra-observer variation: If a single observer takes two measurements (e.g., blood pressure, chest expansion) in the same subject, at the same time and each time, he obtained a different result, this is termed as intra-observer or within- observer variation. This is variation between repeated observations by the same observer on the same subject or material at the same time. Intra-observer variation may often be minimized by taking the average of several replicate measurements at the same time. 27  Screening Test  Repeatability: (cont…)  A. Observer variation  b. Inter-observer variation  This is variation between different observers on the same subject or material, also known as between-observer variation.  Inter-observer variation has occurred if one observer examines a blood-smear and finds malaria parasite, while a second observer examines the same slide and finds it normal.  Observational errors are common in the interpretation of X-rays, ECG tracings, readings of blood pressure and studies of histopathological specimens.  Observer errors can be minimized by: 1. standardization of procedures for obtaining measurements and classifications 2. intensive training of all the observers 3. making use of two or more observers for independent assessment, etc. It is probable that these errors can never be eliminated absolutely. 28  Screening Test  Repeatability: (cont…)  B. Biological (subject) variation  There is a biological variability associated with many physiological variables such as blood pressure, blood sugar, serum cholesterol, etc.  The fluctuation in the variate measured in the same individual may be due to:  (a) Changes in the parameters observed:  This is a frequent phenomena in clinical presentation.  For example, cervical smears taken from the same woman may be normal one day, and abnormal on another day.  Myocardial infarction may occur without pain.  Subject variation of blood pressure is a common phenomenon.  (b) Variations in the way patients perceive their symptoms and answer: 29  Screening Test  Repeatability: (cont…)  B. Biological (subject) variation  This is a common subject variation.  There may be errors in recollection of past events when a questionnaire is administered. When the subject is aware that he is being probed, he may not give correct replies.  In short, subject variation can be a potential source of error in epidemiological studies.  (c) Regression to the mean:  An important example of biological variability is regression to the mean.  There is a tendency for values at the extremes of a distribution, either very high or low, to regress towards the mean or average on repeat measurements. 30  Screening Test  Repeatability: (cont…)  B. Biological (subject) variation  Many features of disease states vary considerably over time, for example, the pain of rheumatoid arthritis, stool frequency in ulcerative colitis, blood pressure in hypertension or the blood glucose in diabetes.  This concept is particularly important to remember in evaluating the effects of a specific therapy on a variable such as the use of a specific drug to reduce blood pressure or serum cholesterol.  Whereas observer variation may be checked by repeat measurements at the same time, biological variation is tested by repeat measurements over time.  This is due to the fact that measurement is done only on a tiny sample of the normal distribution of the physiological variable. 31  Screening Test  Repeatability: (cont…)  C. Errors relaiing to technical methods  Lastly, repeatability may be affected by variations inherent in the method, e.g.: defective instruments, erroneous calibration, faulty reagents; or the test itself might be inappropriate or unreliable.  Where these errors are large, repeatability will be reduced, and a single test result may be unreliable. 32  Screening Test  Validity (accuracy)  The term validity refers to what extent the test accurately measures which it purports to measure. In other words, validity expresses the ability of a test to separate or distinguish those who have the disease from those who do not.  For example, g!ycosuria is a useful screening test for diabetes, but a more valid or accurate test is the glucose tolerance test.  Accuracy refers to the closeness with which measured values agree with "true" values. 33  Screening Test  Validity (accuracy) (cont…)  Validity has two components sensitivity and specificity.  When assessing the accuracy of a diagnostic test, one must consider both these components.  Both measurements are expressed as percentages.  Sensitivity and specificity are usually determined by applying the test to one group of persons having the disease, and to a reference group not having the disease.  Sensitivity and specificity, together with "predictive accuracy" are inherent properties of a screening test. 34  Evaluation of a Screening Test Sensitivity The term sensitivity was introduced by Yerushalmy in 1940s as a statistical index of diagnostic accuracy. It has been defined as the ability of a test to identify correctly all those who have the disease, that is "true- positive". A 90 per cent sensitivity means that 90 per cent of the diseased people screened by the test will give a "true- positive" result and the remaining 10 per cent a "false- negative" result. 35  Evaluation of a Screening Test  Specificity  It is defined as the ability of a test to identify correctly those who do not have the disease, that is, "true-negatives".  A 90 per cent specificity means that 90 per cent of the non-diseased persons will give "true-negative" result, 10 per cent of non-diseased people screened by the test will be wrongly classified as "diseased" when they are not.  In dealing with diagnostic tests that yield a quantitative result {e.g., blood sugar, blood pressure) the situation is different.  There will be overlapping of the distributions of an attribute for diseased and non-diseased persons.  False positives and false negatives comprise the area of the overlap. 36  Evaluation of a Screening Test  Specificity (cont…)  When the distributions overlap, it is not possible to correctly assign individuals with these values to either the normal or the diseased group on the basis of screening alone.  For example, if we decide to use the 2-hour post-prandial blood glucose level of 180 mg/100 ml as an index of the presence of diabetes mellitus, the sensitivity and specificity are 50 and 99.8 per cent respectivel.  In other words, sensitivity is low, but specificity very high.  Sensitivity and specificity are inversely related.  That is, sensitivity may be increased only at the expense of specificity and vice versa.  An ideal screening test should be 100 per cent sensitive and 100 per cent specific.  In practice, this seldom occurs. 37  Evaluation of a Screening Test  Predictive accuracy In addition to sensitivity and specificity, the performance of a screening test is measured by its "predictive value" which reflects the diagnostic power of the test. The predictive accuracy depends upon sensitivity, specificity and disease prevalence. The "predictive value of a positive test" indicates the probability that a patient with a positive test result has, in fact, the disease in question. The more prevalent a disease is in a given population, the more accurate will be the predictive value of a positive screening test. The predictive value of a positive result falls as disease prevalence declines. 38  Evaluation of a Screening Test  False negatives and positives  Whereas the epidemiologist thinks in terms of sensitivity and specificity, the clinician thinks in terms of false negatives and false positives.  False-negatives: The term "false-negative" means that patients who actually have the disease are told that they do not have the disease. It amounts to giving them a "false reassurance". The patient with a "false-negative" test result might ignore the development of signs and symptoms and may postpone the treatment. This could be detrimental if the disease in question is a serious one and the screening test is unlikely to be repeated within a short period of time. A screening test which is very sensitive has few "false negatives". The lower the sensitivity, the larger will be the number of false negatives. 39  Evaluation of a Screening Test  False negatives and positives (cont)  False-positives: The term "false-positive" means that patients who do not have the disease are told that they have the disease. In this case, normal healthy people may be subjected to further diagnostic tests, at some inconvenience, discomfort, anxiety and expense - until their freedom from disease is established. A screening test with a high specificity will have few false positives. False-positives not only burden the diagnostic facilities, but they also bring discredit to screening programmes. In fact, no screening test is perfect, i.e., 100 per cent sensitive and 100 per cent specific. 40  Evaluation of a Screening Test  Yield  "Yield" is the amount of previously unrecognized disease that is diagnosed as a result of the screening effort.  It depends upon many factors, viz. sensitivity and specificity of the test, prevalence of the disease, the participation of the individuals in the detection programme.  For example, by limiting a diabetes screening programme to persons over 40  years, we can increase the yield of the screening test. High-risk populations are usually selected for screening, thus increasing yield.  Combination of tests  Two or more tests can be used in combination to enhance the specificity or sensitivity of screening.  For example, syphilis screening affords an example whereby all screenees are first evaluated by an RPR test.  This test has high sensitivity, yet will yield false positives. However, all those positive to RPR are then submitted to FTA-ABS, which is a more specific test, and the resultant positives now 41 truly have syphilis.  Evaluation of a Screening Test  The problem of the borderline  The question arises which of the two qualities (sensitivity or specificity) is more important in screening? No categorical answer can be given.  In screening for disease, a prior decision is made about the cut-off point, on the basis of which individuals are classified as "normal" or "diseased".  In making this decision, the following factors are taken into consideration:  (a) Disease prevalence: When the prevalence is high in the community, the screening level is set at a lower level, which will increase sensitivity.  (b) The disease: If the disease is very lethal (e.g., cervical cancer, breast cancer) and early detection markedly improves prognosis, a greater degree of sensitivity, even at the expense of specificity, is desired. In these cases, subsequent diagnostic work-up can be relied on to rule out the disease in the false-positives.  That is, a proportion of false-positives is tolerable but not false-negatives. 42  Evaluation of a Screening Test  The problem of the borderline (cont…)  On the other hand, in a prevalent disease like diabetes for which treatment does not markedly alter outcome, specificity must be high and early cases may be missed, but false-positives should be limited; otherwise the health system will be overburdened with diagnostic demands on the positives, both true and false.  That is, high specificity is necessary when false-positive errors must be avoided.  A useful index in making this decision is the predictive value of a positive test.  This index measures the percentage of positive results that are true positives; it is a function of the sensitivity and specificity as well as the frequency of the disease.  There are various other points which must also be taken into account in screening.  First, people who participate in the screening programme may not be those who have most to gain from it, as for example, those at greatest risk of cancer of the cervix uteri are least likely to attend for cervical cytology.  Therefore screening must be applied selectively to those people most likely to benefit. Selection might be based on a person's age, sex, medical history, occupation, family history or other 43 factors.  Evaluation of a Screening Test  The problem of the borderline (cont…)  Secondly, tests with greater accuracy may be more expensive and time-consuming, and the choice of the test therefore often be based on compromise.  Thirdly, screening should not be developed in isolation; it should be integrated into the existing health services.  Lastly, the risks as well as the expected benefits must be explained to the people to be screened.  These risks include any possible complications of the examination procedures, and the possibility of false-positive and false-negative test results.  Regardless of the approach taken to screening tests, regular patient follow-up visits are important (not to leave the patients high and dry) if effective health and medical care are to result from the effort.  Garfield has stressed the need to meet demands for medical care by separating screenees into well, asymptomatic-sick, and sick groups.  This separation makes possible the optimal use of health care services. 44  Evaluation of Screening Programmes Evaluation of screening programmes Many screening tests were introduced in the past without subjecting them to rigid scrutiny. They were introduced because it was thought a good thing to detect and treat cases before they should reach an advanced stage. The modern view is that new screening programmes should be introduced only after proper evaluation. 45  Evaluation of Screening Programmes  Evaluation of screening programmes  (1) Randomized controlled trials: Ideally evaluation should be done by a randomized controlled trial in which one group (randomly selected) receives the screening test, and a control which receives no such test. Ideally RCT should be performed in the setting where the screening programme will be implemented, and should employ the same type of personnel, equipment and procedures that will be used in that programme. If the disease has a low frequency in the population, and a long incubation period (e.g., cancer) RCT may require following tens of thousands of people for 10-20 years with virtually perfect record keeping. The cost and logistics are often prohibitive. 46  Evaluation of Screening Programmes Evaluation of screening programmes (2) Uncontrolled trials: Sometimes, uncontrolled trials are used to see if people with disease detected through screening appear to live longer after diagnosis and treatment than patients who were not screened. One such example is uncontrolled studies of cervical cancer screening which indicated that deaths from that disease could be very much reduced if every woman was examined periodically. 47  Evaluation of Screening Programmes  Evaluation of screening programmes  (3) Other methods: There are also other methods of evaluation such as case control studies and comparison in trends between areas with different degrees of screening coverage. Thus it can be determined whether intervention by screening is any better than the conventional method of managing the disease. To conclude, the screening concept, filled with potential has been overburdened with problems, many of which remain unsolved. The construction of accurate tests that are both sensitive and specific is a key obstacle to the wide application of screening. Scientific and technical puzzles abound. 48  Thank you 49 49