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ISLAMIC MEDICAL EDUCATION RESOURCES-04

0610-DISEASE SCREENING

Lecture for 2nd Year Master of Health Policy Student at Universiti Brunei Darussalam on Saturday 28th October 2006 by Professor Omar Hasan Kasule Sr.

Learning Objectives

  • Screening: definition, types, benefits
  • Methods of screening
  • Evaluation of screening

 

Key Words and Terms

  • Screening, breast cancer screening
  • Screening, cervical cancer screening
  • Genetic screening
  • Lead time bias
  • Length bias
  • Selection bias
  • Mammography
  • Mass screening
  • Multi-phasic screening
  • Neonatal screening
  • Pap smear
  • Pre-natal screening
  • Vision screening

 


OUTLINE

1.0 DEFINITION, OBJECTIVES, ORGANIZATION, and BENEFITS

A. Definition of Screening

B. Objectives of the Screening Program

C. Screening Procedures

D. Benefits & Disadvantages of Screening Programs

E. Examples of Screening Programs

 

2.0 CHARACTERISTICS OF DISEASE & SCREENING TESTS

A. Suitable Disease

B. Worth-While Screening Test/Procedure

C. Process Parameters of Screening Procedures

D. Outcome Parameters of A Screening Program

E. Biases in the Interpretation of Screening Results

 

3.0 EPIDEMIOLOGIC EVALUATION OF SCREENING PROGRAMS

A. Factors of Screening Program Effectiveness

B. Process Evaluation

C. Outcome Evaluation

D. Evaluation of Specific Screening Programs

E. Improving Screening Programs

 

4.0 COST BENEFIT ANALYSIS OF SCREENING PROGRAMS

A. Financial Costs

B. Human Costs

C. Benefits

D. Hazards of Screening:

E. Recommended Screening Schedules

 

5.0 ETHICAL ISSUES

A. Benefit Vs Harm

B. Efficacy

C. Adverse Social Consequences

D. False Positive and False Negative Results

E. Others


UNIT SYNOPSIS

1.0 DEFINITION, OBJECTIVES, ORGANIZATION, and BENEFITS

Screening, a type of secondary prevention, is identification of unrecognized disease by the application of tests, examinations or other procedures which can be applied easily. Screening can be described as routine or episodic/adhoc, individual or mass, selective or comprehensive. Its effectiveness is assessed by morbidity, mortality, survival, and quality of life. Its objectives are achieved through early detection and treatment of disease. Its benefits may be public (infectious disease), private (insurance screening), and individual (early treatment and reassurance). Its disadvantages are longer morbidity for untreatable screen-detected cases, over-treatment of borderline cases, false reassurance of false negatives, unnecessary treatment of false positives, risks and costs of the screening tests.  The most successful screening programs are breast and cervical cancer. Breast cancer screening is by mammography screening every 1-2 years is recommended in women above 50 years. There is no proof that BSE and mammography are useful in women below 50 years of age. Mammography for women below 50 years is done only if there is a family history of breast cancer. Cervical cancer screening is by use of the PAP smear test is very popular and is recommended for women above 20 years every 3 years.

 

2.0 CHARACTERISTICS OF DISEASE & SCREENING TESTS

A disease suitable for screening must be definable clearly, with known natural history and a relatively long detectable pre-clinical phase, common (high prevalence), serious, and effectively treatable if detected early. The screening test must be simple, cheap and cost-effective, acceptable, safe, and perform optimally (high sensitivity, high specificity, low false positive, suitable cut-off level, and reliability).

 

3.0 EPIDEMIOLOGIC EVALUATION OF SCREENING PROGRAMS

Process parameters of screening program effectiveness are accuracy, validity, reliability, and predictive value. The outcome parameters of a screening program are health outcomes (reduction of morbidity, reduction of mortality, survival, and improvement in the quality of life) or economic outcomes. Correct interpretation of the outcome measures requires consideration of lead-time bias, length bias, selection bias, over diagnosis bias, and over-treatment bias. The effectiveness of the screening program is affected by the test used, the attendance or coverage, the screening interval, and success of referral for diagnostic confirmation. Outcome assessment can be by pre and post screening comparisons of the same population or comparison of morbidity and /or mortality in the screened and non-screened using the case control or random allocation designs. Apparent lack of benefit from a screening program could be due to two the disease having no detectable pre-clinical phase or an ineffective intervention. Screening programs can be improved by selective screening (by age, gender, and high risk), optimal screening frequency, multi-phase screening, and sequential screening.

 

4.0 COST BENEFIT ANALYSIS OF SCREENING PROGRAMS

Cost benefit analysis is used to decide on program initiation or continuation. The costs include cost of screening, the cost diagnosis and treatment, patient costs such as lost earnings, human emotional and other costs. QUALY is used as a summary measure of benefits.

 

5.0 ETHICAL ISSUES

Ethico-legal considerations in screening programs are: the benefit of screening must outweigh the harm, the efficacy of screening must be proved in a proper trial, confidentiality must be maintained, and informed consent must be obtained.

 


1.0 DEFINITION, OBJECTIVES, ORGANIZATION, and BENEFITS

A. DEFINITION OF SCREENING

Screening is a type of secondary prevention involving identification of apparently healthy persons are at risk for further diagnostic or therapeutic interventions. It must be emphasized that screening by itself is not diagnostic. The World Health Organisation defines screening as presumptive identification of unrecognized disease or defect by the application of tests, examinations or other procedures which can be applied easily (WHO 1968). Screening can be looked at in two ways. Screening for pre-clinical disease is part of routine practice of preventive medicine for example BP measurement and x-rays. It can be extended to become mass screening of the whole population. Mass screening is population screening. Screening can be mass screening involving the whole population. It may be regular routine screening or episodic and adhoc. It may be selective or comprehensive. Screening is usually associated with chronic disease. It can also be used in infectious disease. Comprehensive cancer screening program. The players in screening programs are: public health departments, managed care organizations, community based coalitions for specific diseases, and workplace coalitions.

 

B. OBJECTIVES OF THE SCREENING PROGRAM

A screening program aims at achieving 3 major objectives: decrease of morbidity, decrease of mortality, and improving the quality of life. The effectiveness of the screening program is assessed on how well the above objectives are achieved. The objectives are achieved through early detection and treatment of disease. Downstaging is detection of disease at an earlier stage when it is curable. Downstaging of cervical cancer can be done by nurses and non-medical health workers who can use a simple speculum for visual inspection. Oral inspection is used to downstage oral cancer. BSE is downstaging breast cancer.

 

C. SCREENING PROCEDURES

Screening test/procedures can be simple or complex. Screening is occurring all the time in the clinical setting though the caregivers and the patients may not be consciously aware of it. Simple clinical questions are to identify those at risk eg maternal age for Down’s syndrome. Special tests are used for example clinical examination (breast exam), laboratory (serum AFP), and radiological (mammogram).

 

The target population must be identified. The population may be defined as a community or an institution (school, factory, and neighborhood). Mass screening covers the whole target population. Selective screening covers only defined segments of the target population. Risk stratification may be employed in selecting individuals to screen. The publicity for the program must ensure high coverage and uptake retention. Adequate resources must be deployed to ensure success of the program. Quality control procedures must be instituted from the beginning. An efficient referral system must be set up. All personnel must be trained. The program must be evaluated.

 

D. BENEFITS and DISADVANTAGES OF THE SCREENING PROGRAMS

A screening program may have public, private, and individual benefits. These benefits sometimes interact or even are contrary to one another. TB screening has a public benefit in that cases of infectious disease are identified and are treated so that they pose no further danger to the public. Screening may have a private benefit. HIV screening by insurance companies has no public benefit because the companies do not disclose the results to the public or the person screened. However the information is useful in their decisions to insure persons and what premiums to charge. Screening may have a direct benefit to the individual. It improves prognosis and enables earlier treatment with less radical therapy. Screening for childhood diseases and their subsequent treatment is beneficial to the child. Screening is reassurance for those with negative results

 

DISADVANTAGES OF SCREENING

There are several disadvantages associated with screening. Screen –detected cases whose disease can not be cures suffer from a longer period of morbidity. Borderline lesions may be overtreated when if left alone they would not progress to serious disease. False negatives is false reassurance that will discourage them from seeking care when early symptoms appear. False positives live with anxiety longer than necessary. False positives undergo unnecessary medical intervention. Screening tests have their own risks and costs.

 

E. EXAMPLES OF SCREENING PROGRAMS

Breast cancer screening is by mammography screening every 1-2 years is recommended in women above 50 years. There is no proof that BSE and mammography are useful in women below 50 years of age. Mammography for women below 50 years is done only if there is a family history of breast cancer. Screening mammography has a false negative rate of 10-20%.

 

Cervical cancer screening is by use of the PAP smear test is very popular and is recommended for women above 20 years every 3 years. A positive PAP smear test may regress during follow up. Other screening tests are colposcopy, cervicography, Schiller’s test using Lugol’s iodine, the acetic acid test, and the HPV DNA test.

 

Colon cancer screening uses sigmoidoscopy and fecal occult blod tests (FOBT). There are three main FOBTs: guaiac, immunochemical, and hemeporphyrin tests. The guaiac (hemooccult) test is the only reliable test for colon cancer. Other tests are still being investigated. FOBTs must be applied regularly since bleeding is intermittent. Red meat and anti-inflammatory drugs may confuse FCBTs. Molecular screening for colon cancer is being evaluated.

 

Prostate cancer screening is by digital rectal examination (DRE), serum PSA assessment, and ultrasonography.

 

2.0 CHARACTERISTICS OF DISEASE & SCREENING TESTS

A. SUITABLE DISEASE

A disease suitable for screening must have certain characteristics. It must be definable clearly. Its natural history must be known with a relatively long detectable pre-clinical phase. It must be sufficiently common (known prevalence). It must be serious with a heavy burden of suffering. It must have effective treatment if detected early. Pre-symptomatic treatment must be able to make a difference. Treatment facilities must be available.

 

B. WORTH-WHILE SCREENING TEST/PROCEDURE

The screening test must be simple, cheap and cost-effective, acceptable, safe, and perform optimally (high sensitivity, high specificity, low false positive, suitable cut-off level, and reliability): False negative tests are falsely reassuring and may be a reason for delay of treatment. False positive tests lead to anxiety and unnecessary diagnostic and therapeutic procedures. The test must be ethical (the test and the subsequent diagnostic and intervention procedures must be ethical).

 

C. PROCESS PARAMETERS OF SCREENING PROCEDURES

The following parameters are process measures that measure how effective the program is: accuracy, validity, reliability, and predictive value. They can be defined by reference to the figure below They are process measures that measure how effective the program is.

Figure #: Showing screening parameters

           

Test result +

Test result -

Disease +

A

B

Disease -

C

D

                           

The accuracy of the screening test can be established by comparing findings of the test and clinical or diagnostic confirmatory tests.

True positive(TP) =                 a

 True negative(TN )=              d. 

False negative(FN) =              b.

False positive(FP) =                c.

 

The validity of the screening test is assessed by its sensitivity and specificity.

 

Sensitivity, measured as a/(a+b), is the ability to pick up preclinical disease.

 

Specificity, measured as d/(c+d), is ability to classify non-diseased people correctly.

 

The predictive value of a positive test (PV+), measured as a/(a+c), is the proportion of people with a positive test who actually have the disease. A high value of PV+ indicates good cost-benefit and a low value of PV+ indicates low cost benefit.

 

The predictive value of a negative test (PV-), measured as d/(b+d), is the proportion of people with a negative test who do not have the disease. Values of PV- closer to 1.0 indicates that the test is reassuring.

 

D. OUTCOME PARAMETERS OF A SCREENING PROGRAM

The outcome of a screening program is assessed based health outcomes (reduction of morbidity, reduction of mortality, and improvement in the quality of life) or economic outcomes. Correct interpretation of the outcome measures requires understanding of the natural history of the disease especially its time line.

 

The natural history of the disease is intimately related to screening parameters. The time-line below shows various events in disease evolution. Disease onset is at T1. At T2 disease is detectable by screening. The screening test is done at T3. Clinical disease onset is at T4.  It is possible to compute and interpret various time interval measurements. The delay time is T3-T2. The lead time is T4-T3. Total pre-clinical disease is T4-T1. The total pre-clinical detectable disease phase is T4-T2.

 

E. BIASES IN THE INTERPRETATION OF SCREENING RESULTS

Correct interpretation of the screening results requires appreciation of lead-time bias, length bias, selection bias, over diagnosis bias, and overtreatment bias. Lead time is amount of time by which the diagnosis is early. Earlier diagnosis of disease does not change the natural history of the disease but could give an apparent picture of better survival for screen-detected cases. The earlier detection of disease leads to a longer period of morbidity. This may not be accompanied by any change in survival had the disease been detected clinically. Some screen-detected cases may not develop into clinical disease because they are biologically different. Their detection causes morbidity, worry and anxiety. It leads to further diagnostic work-up and therapeutic procedures that could be risky but are yet unnecessary. Length bias could give a false picture of better survival in screen-detected cases because prevalent cases with slower-growing lesions are detected by screening more than incident cases with rapidly-growing lesions that are more easily detected clinically. Selection bias occurs when cases with a good prognosis are more likely to be screened than those with a bad prognosis. Overdiagnosis bias or overtreatment arise when lesions that are histologically malignant are treated whereas they would have never progressed to invasive disease.

 

3.0 EPIDEMIOLOGIC EVALUATION OF SCREENING PROGRAMS

A. FACTORS OF SCREENING PROGRAM EFFECTIVENESS

The effectiveness of the screening program is affected by the test used, the attendance or coverage, the screening interval, and success of referral for diagnostic confirmation. Effects of a single screen are different from those of repeated screening. After a single screen, incidence increases dramatically due to detection of pre-clinical cases. The incidence then falls to below pre-screen levels and gradually build up to the pre-screen levels (see figure below). Care must be taken in interpreting this data because death may be just postponed if the early treatment following screening removes tumor bulk but does not eradicate disease. Some cases die of competing causes of death during the period of postponement. Repeated screening results in lower average disease-specific death rates and increase in the number of years of life gained.

 

B. PROCESS EVALUATION

The various parameters of accuracy, validity, and predictability give an indication on the test.  Other process measures that can be used are the number referred for screening, the number who received at least one screening, the number who receib=ved multiple screenings, the number screened as a proportion of the target population, number found positive, number of pre-clinical cases detected, number of cases confirmed, number referred for diagnostic work-up, total cost of the program, cost per case detected by screening.

 

C. OUTCOME EVALUATION

It is easy to tell whether screening has benefited an individual if his or her disease is discovered early and is treated. Longer survival of screen-detected cases compared to normally-detected cases is a useful outcome measure. It is not easy to tell whether a screening program has made a difference in morbidity and mortality for the general population. Controversy is over whether risk and costs borne by the individual are commensurate with the benefit that is measurable only for the whole population. Selection bias, over-diagnosis bias, length bias, and lead-time bias complicate the interpretation of morbidity and mortality data. Selection bias occurs in the form of referral bias or volunteer bias. It is the situation in which the screened population does not have the same characteristics as the unscreened. For example volunteers are healthier and more health-conscious than non-volunteers. Over diagnosis bias arises due to higher diagnostic enthusiasm due to the screening program. Length bias, a type of prognostic bias, is a situation in which screen-detected cases have grow more slowly and are easy to detect by screening and have a better prognosis. Lead-time bias arises when screen-detected cases appear to have improved survival when actually screening made no difference to the time of death but increased the time they were under observation. Lead-time bias could be the reason for false 5-year survival rates.

 

Outcome measures are decrease in mortality, decrease of case fatality, decrease in site-specific mortality, increase in the proportion of early diagnosis, stage distribution of screening-detected cases, decrease in complications, decrease in recurrence, and improved quality of life. Three approaches are available for assessing outcome. The outcome in the screened population could be compared to data in the same population before the screening program or could be compared to data of similar populations in an ecologic study. This is fraught with a lot of interpretive complications because of confounding bias. A case control study could be set up in which morbidity and mortality are compared among screened and non-screened individuals. This may however not assess the whole program because there are parameters in the general population that affect outcome but may not be measured by the case control study. The best approach is to select a study population and randomize subjects to the screening or non-screening groups. Morbidity and mortality are then compared after a suitable duration of the study.

 

4.0 COST BENEFIT ANALYSIS OF SCREENING PROGRAMS

A. FINANCIAL COSTS

This includes the cost of screening and the cost of further diagnostic work-up and treatment of screen-detected cases. There are also financial costs to the screened subjects themselves because they have to leave work and go for screening. The cost are relatively higher if they screen negative. False positive and false negative screens are an additional cost. Rehabilitation of detected cases is an additional health cost. Death is a cost to the family and the estate.

 

 

B. HUMAN COSTS

The human costs of screening programs include: (a) inappropriate reassurance for false negatives. (b) anxiety in the positives (c) false morbidity in the false positive (d) generation of true morbidity and problems eg SCD screening revealing illegitimacy (e) opportunity costs

 

C. BENEFITS

The benefits of screening programs include: (a) prevention of disease, disability, and handicap. This benefit is quantified by the number of cancers detected, Quality adjusted life years (QUALY) and healthy years equivalent (HYE). (b) patient concerns are alleviated by early diagnosis (c) genetic counseling is possible (d) service provision/access to services (e) decrease of health service expenditure by early detection and treatment.  For regular participants in screening programs two types of cancer can be detected: screen detected cancer and interval cancer that is detected in the routine way.

 

D. RECOMMENDED SCREENING SCHEDULES FOR DIFFERENT DISEASES IN ASYMPTOMATIC CASES

Cancers: Annual breast examination is recommended for all women 40 years and above. Mammography is recommended every 1-2 years for women 50-75 years. Papanicolaou testing is recommended every 3 years for women of all ages who are sexually active. FOBT and colonoscopy for colon cancer are recommended for those aged 50, or have a family history of colon cancer, or have a family history of polyposis. Routine screening is not recommended for lung cancer by sputum cytology, ovarian cancer, pancreatic cancer, or prostate cancer. Screening for oral cancer and testicular cancer is done for those with specific risk factors.

 

Congenital Conditions: Amniocentesis for karyotyping is offered to all women aged 35 years and higher. Alpha feto-protein levels should be measured at weeks 16-18. Routine ultrasound examination is not recommended

 

Perinatal conditions: For fetal distress, heart monitoring by auscultation is sufficient. Electronic monitoring is carried out only for women at very high risk. Ultrasound examination is carried out for women whose fetuses are at high risk for intra-uterine growth retardation. Blood pressure monitoring during pregnancy and labor is carried out for pre-ecclampsia.

 

Hematological conditions: Hemoglobin determination for anemia is carried out in pregnant women and infants in the first year of life. Hemoglobinopathy analysis is recommended for newborns of African, Mediterranean, and south-east Asian origin. Screening for Rh compatibility is carried out in the first pre-natal visit by testing for ABO and Rh status. Unsensitized women should be given Rh(D) immune globulin at 23-29 weeks of gestation.

 

Infectious Diseases: Periodic dipstick urine testing is recommended for diabetic patients and pregnant women. Culture for genital herpes infection is recommended for pregnant women with a history of infection or whose partners have had lesions. Pregnant women should have an endocervical culture for gonorrhea and chlamydial infections. Pregnancy women should be tested for HBV infection in the 3rd trimester.  Persons with multiple sexual partners or those who use intravenous drugs should be tested for HIV. Serological testing for rubella is recommended for all women in the child bearing age. Pregnantb women should be tested for syphilis at the first pre-natal visit. Persons at high risk of tuberculosis should undergo tuberculin testing.

 

Metabolic and genetic diseases: Routine testing for hyperglycemia is recommended in high risk groups and pregnant women at 24-28 weeks of gestation. Periodic height and weight determinations are recommended in children and adults to detect obesity. Routine x-rays for osteoporosis are not recommended. Phenylketonuria testing of all newborns is recommended. Newborns are screened for hypothyroidism in the first week of life.

 

Vascular diseases: Screening for cerebrovascular disease and coronary heart disease is based on screening for its risk factors (diet, exercise, smoking, and hypertension). Periodic testing for serum cholesterol is recommended in the middle aged. Regular measurement of blood pressure for hypertension is recommended for all persona aged 3 years and over. No routine screening for peripheral artery disease is recommended.

 

5.0 ETHICAL ISSUES

A. BENEFIT vs HARM

In general the benefit of screening must outweigh the harm.

 

B. EFFICACY

It is unethical to offer a screening program whose efficacy has not been proved in a proper trial. Definitive evidence of efficacy is available only for breast cancer and cervical cancer.

 

C. ADVERSE SOCIAL CONSEQUENCES

The results of genetic screening may have several adverse consequences such as stigmatization, discrimination, abortion, and psychological stress.

 

D. FALSE POSITIVE and FALSE NEGATIVE RESULTS

False positive results create unnecessary distress. False negative results create a false sense of security. True negative results may cause complacency. True positive results lead to worry and anxiety.

 

E. OTHERS

Screening programs may create an ethical issue by diverting resources away from other health programs. Failure to obtain informed consent is a serious ethical violation.

Professor Omar Hasan Kasule Sr. October 2006