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ISLAMIC MEDICAL EDUCATION RESOURCES 04

0308-DISEASE SCREENING

CONTINUING MEDICAL EDUCATION LECTURE at the Institute of Medical Research Kuala Lumpur 29th August 2003 By Professor Dr Omar Hasan Kasule, Sr. MB ChB (MUK), MPH, DrPH (Harvard) Deputy Dean for Research, Faculty of Medicine, UIA PO Box 141  Kuantan Pahang MALAYSIA Tel 609 513 2797 Fax 609 513 3615. E-M omarkasule@yahoo.com

Learning Objectives

Definition, objectives, organization, and benefits

Characteristics of the disease & screening tests / procedures

Epidemiological evaluation of screening programs

Cost benefit analysis of screening programs

Ethical issues

 

Key Words and Terms

Lead time bias

Length bias

Selection bias

Mammography

Mass screening

Multi-phasic screening

Pap smear

PRE-TEST

 

1. The following statements are true about diseases suitable for screening

The natural history of the disease must be known

The disease must have a long pre-clinical detectable phase

The disease need not be a serious one

The disease must have effective treatment

It does not matter whether the disease is rare or is very prevalent

 

2. The following statements are true about good screening tests

The screening test must be simple

It does not matter whether the test is acceptable to the screened population or not

The test need not be safe as long as the disease screened for is a serious disease

The test must be cheap

The test selected must minimizes false positives and false negatives

 

3. The following statements are true about breast cancer screening

Breast self-examination is completely useless in screening for breast cancer

The risks of radiation exposure in mammographic screening are more than the benefits of screening

Women with more than 1 first degree relative who had cancer are at higher risk and should be screened more often

Breast biopsy is a suitable preliminary screening test for breast cancer

Mammographic screening should start at the age of 15

 

4. The following statements are true about cervical cancer screening

Vaginal smears are more reliable than pap smears of the cervix

Data from various countries of the world has shown that cervical cancer screening is beneficial in decreasing mortality

Women at high risk for cervical cancer should be offered surgical biopsy from the beginning because pap smears would delay the diagnosis

Each screening program should be evaluated for effectiveness

Detection of disease at an earlier stage is beneficial because earlier treatment gives better results

 

INTRODUCTION

DEFINITION

Secondary prevention

Identification of unrecognized disease by easy tests, examinations or procedures

 

CLASSIFICATION

Routine or episodic/adhoc

Simple or complex

Individual or mass (primary care as a form of mass screening)

Selective or comprehensive

 

ORGANIZATION

Target population: community or institution (school, factory etc)

Coverage: mass vs. selective

Publicity to ensure high coverage and uptake retention

Adequate resources

Quality control procedures

Efficient referral system

Training personnel

Program evaluation

 

EFFECTIVENESS

Morbidity

Mortality

Survival

Quality of life

 

OBJECTIVES

Concept of downstaging

Early detection

Early treatment


BENEFITS vs DISADVANTAGES

 

BENEFITS

Prevention of disease, disability, and handicap

Number of cancers detected

Quality adjusted life years (QUALY)

Healthy years equivalent (HYE)

Alleviation of patient concerns by early diagnosis

Genetic counseling

Access to services

Decrease of health service expenditure by early detection and treatment

 

BENEFICIARIES

Public (infectious disease)

Private (insurance)

Individual (early treatment and reassurance)

 

DISADVANTAGES

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.

 

EXAMPLES OF CANCER SCREENING I

 

BREAST CANCER SCREENING

Mammography has false negative rate of 10-20%

Mammography screening every 1-2 years is recommended above 50 years

Mammography not useful below 50 years of age

Mammography below 50 years done only if there is a family history

 

CERVICAL CANCER SCREENING

PAP smear test is very popular

PAP may regress on follow-up

PAP recommended for women above 20 years every 3 years

Other tests

Colposcopy

Cervicography

Schiller’s test using Lugol’s iodine

Acetic acid test

HPV DNA test.

 

OVARIAN CANCER SCREENING

Pelvic examination is of limited value

CA-125 is a but non-specific

Trans vaginal ultrasonography

CAT and MRI

Monoclonal antibodies

 

ENDOMETRIAL CANCER SCREENING

Cytology of endometrial samples

 

NEUROBLASTOMA SCREENING

Vinyl mandelic acid

Homovanillic acid

 

COLON CANCER SCREENING

Sigmoidoscopy

Fecal occult blod tests (FOBT)

Types of FOBTs

Guaiac (hemooccult): only reliable test?

Immunochemical

Hemeporphyrin tests

Others under investigation

 

FOBTs must be regular because of intermittent bleeding

Red meat and anti-inflammatory drugs may confuse FOBTs

Molecular screening – being evaluated

 

EXAMPLES OF CANCER SCREENING II

 

ORAL CANCER SCREENING

Visual inspection

Exfoliative cytology

 

ESOPHAGEAL CANCER SCREENING

Barium screening: Barret’s esophagus. 

Screening for H.pylori infection (RR 3.6 – 6.0)

Esophageal balloon cytology

 

LIVER CANCER SCREENING

Alpha fetal protein

HBV

 

LUNG CANCER SCREENING

Cytology

Sputum analysis

Chest X-ray

Newer approaches

Immunostaining of sputum

Fluorescent bronchoscopy

 

PROSTATE CANCER SCREENING

Digital rectal examination (DRE)

Serum PSA assessment

Ultrasonography

 

BLADDER CANCER SCREENING

Urinary cytology

 

TESTICULAR CANCER SCREENING

Physical examination

 

MELANOMA SCREENING

Skin examination is cheap and reliable

Punch biopsy

Molecular screening

 

SCREENING FOR SKIN CANCER

Mass screening not logical since 2/3 of cancers arise de novo

Screening better directed to high-risk groups

 

NPC SCREENING

EBV serology and follow up of the positives.

 

OTHER EXAMPLES OF SCREENING

 

CARDIOVASCULAR SCREENING

Screening for high blood pressure

 

GENETIC SCREENING

Screening for what?

Chromosomal abnormalities

Single gene disorders

Multifactorial disorders

 

Targets of screening

Neonates

Older children

Pregnant women.

 

SCREENING FOR CONGENITAL HIP DISLOCATION

 

SCREENING FOR SHOULDER DISLOCATION

 

SUITABLE DISEASES AND TESTS

 

DISEASE SUITABLE FOR SCREENING

Definable clearly

Known natural history

Relatively long detectable pre-clinical phase

Common (high prevalence)

Serious

Effectively treatable if detected early.

 

SUITABLE SCREENING TEST

Simple / easy

Cheap and cost-effective

Acceptable

Safe

Optimal performance

High sensitivity

High specificity

Low false positive

Suitable cut-off level

Reliable.

 


PROCESS EVALUATION

PROCESS PARAMETERS

Validity

Sensitivity

Specificity

Reliability

Predictive value

 

DEFINITION OF THE PARAMETERS

 

           

Test result +

Test result -

Disease +

A

B

Disease -

C

D

                           

True

True positive (TP) = a

True negative (TN) = d

 

False

False negative (FN) = b

False positive (FP) = c

 

Sensitivity and specificity

Sensitivity = a/a+b = ability to pick up preclinical disease

Specificity = d/c+d = ability to classify non-diseased people correctly

Sensitivity is inversely related to specificity

Trade-off between sensitivity and specificity

 

Reliability = ability of the test to give the same result on repeated applications

 

Predictive value of a positive test (PV+)

PV+ = a/(a+c)

PV+ = proportion of people with a positive test actually diseased

High value of PV+ indicates good cost-benefit

Low value of PV+ indicates low cost benefit.

The higher the sensitivity the higher the PV+

The higher the prevalence, the higher the PV+ (so screen high risk groups)

 

Predictive value of a negative test (PV-)

PV- = d/(b+d)

PV- = proportion of people with a negative test not diseased

Values of PV- closer to 1.0 indicates that the test is reassuring.

Prevalence has no effect on PV-

 

 

 

OUTCOME EVALUATION

 

OUTCOME PARAMETERS

Health outcomes

Reduction of morbidity

Reduction of mortality

Survival

Improvement in the quality of life

 

Economic outcomes

 

CONSIDERATIONS IN INTERPRETATION OF OUTCOME

lead-time bias

length bias

selection bias

Over diagnosis bias

Over-treatment bias.

 

FACTORS OF PROGRAM EFFECTIVENESS

Test used

Attendance or coverage

Screening interval

Success of referral for diagnostic confirmation.

 

METHODS OF OUTCOME ASSESSMENT

Morbidity/mortality Pre vs. post screening

Morbidity/mortality screened vs unscreened

Case control design

Random allocation study

 

 

PROGRAM EVALUATION

 

CAUSES OF APPARENT LACK OF BENEFIT

Disease has no detectable pre-clinical phase

Ineffective intervention.

 

IMPROVEMENT OF SCREENING PROGRAMS

Selective screening: by age, gender, and high risk

Optimal screening frequency

Multi-phase screening

Sequential screening.

 

COST BENEFIT ANALYSIS

Purpose: decision on program initiation / continuation

Costs

Cost of screening

Cost diagnosis

Cost of treatment

Patient costs (lost earnings, emotional, transport, bills)

Benefits: QUALY is used as a summary measure of benefits.

 

 

 

ETHICO-LEGAL CONSIDERATIONS

Benefit vs. harm

 

Efficacy of screening proved in a proper trial?

 

Confidentiality

 

Informed consent

 

RECOMMENDED SCREENING

Breast cancer

Annual breast examination for women >=40

Mammography every 1-2 years for women 50-75 years

 

Cervical cancer

Papanicolaou testing every 3 years for women of all ages who are sexually active

 

Colon cancer

FOBT & colonoscopy for age >=50 or have family h/o of colon cancer or h/o polyposis

 

Oral and testicular cancer

Screening for those with specific risk factors

  

Congenital Conditions

Amniocentesis for karyotyping for women >=35

Alpha feto-protein levels should be measured at weeks 16-18

Routine ultrasound examination is not recommended

 

Perinatal conditions

Auscultation for routine cases & electronic monitoring for high risk mothers

Ultrasound for high risk of IUGR

BP monitoring for pre-ecclampsia.

 

Hematological conditions

Hb in pregnant mothers and infants

Hemoglobinopathy analysis newborns (African, mediterranean, and south-east Asian)

Rh compatibility at first pre-natal visit by testing for ABO and Rh status

 

Infectious Diseases

Periodic dipstick urine testing for diabetic patients and pregnant women

HBV in 3rd trimester of pregnancy

HIV for multiple sexual partners or iv drug users

Rubella

Tuberculin testing for those at high risk

 

Metabolic and genetic diseases

Routine testing for hyperglycemia in high risk groups and pregnant women

Periodic height and weight determinations for obesity

Routine x-rays for osteoporosis not recommended

Phenylketonuria testing of all newborns

Newborns screening for hypothyroidism

 

Cerebrovascular disease and coronary heart disease

Risk factor screening: diet, exercise, smoking, & hypertension

Periodic serum cholesterol

Vision

Routine screening in the pre-school period at ages 3 or 4.

Glaucoma screening is done only for people aged 65 and over

 

Hearing impairment

Children at high risk screened before the age of 3 years

 

SCREENING NOT RECOMMENDED

 

Lung, ovarian, pancreatic, and prostate cancer

Routine screening not recommended

 

Alcohol and drug abuse

Routine biochemical screening is not recommended

 

Dementia

Routine screening of asymptomatic persons is not recommended

 

Depression and suicide

Routine screening is not recommended

 

Low back injury

No recommended routine screening for low back injury.

Professor Omar Hasan Kasule Sr. August 2003