Uses of Screening Test

Four Main Uses of Screening

a. Case Detection (Prescriptive Screening)

• Defined as the presumptive identification of unrecognized disease, which does NOT arise from a patient's request.
• People are screened primarily for their own benefit.
• Examples of diseases sought: bacteriuria in pregnancy, breast cancer, cervical cancer, deafness in children, diabetes mellitus, iron deficiency anaemia, PKU (phenylketonuria), pulmonary tuberculosis, haemolytic disease of the newborn.
• Example: neonatal screening.
• Since disease detection is initiated by medical/public health personnel, they have a special obligation to ensure appropriate early treatment is started.

b. Control of Disease (Prospective Screening)

• People are examined for the benefit of others (not just themselves).
• Examples: screening of immigrants for tuberculosis and syphilis to protect the home population; screening for streptococcal infection to prevent rheumatic fever.
• The screening programme, by leading to early diagnosis, allows more effective treatment and reduces the spread of infectious disease and/or mortality.

c. Research Purposes

• Screening may be performed to obtain more basic knowledge about the natural history of diseases (especially chronic diseases like cancer, hypertension, where natural history is not fully known).
• Initial screening provides a prevalence estimate; subsequent screening provides an incidence figure.
• When done for research purposes, the investigator should inform study participants that no follow-up therapy will be available.

d. Educational Opportunities

• Apart from benefits to individuals and public health information, screening programmes (e.g., screening for diabetes) provide:
  • Opportunities for creating public awareness
  • Educating health professionals

Key Distinction: Screening vs. Diagnostic Test

Types of Screening (Bonus)

1. Mass screening - Screening of a whole population or sub-group, offered to all irrespective of individual risk (e.g., tuberculosis).
2. High-risk/Selective screening - Applied to high-risk groups defined by epidemiological research; most productive approach. Also includes screening for risk factors (e.g., serum cholesterol for CHD risk).
3. Multiphasic screening - Application of two or more screening tests in combination to a large number of people at one time (includes questionnaire, clinical exam, blood/urine tests, lung function, audiometry, visual acuity assessment).

Types of Screening

a. Mass Screening

• Screening of a whole population or a sub-group (e.g., all adults).
• Offered to all individuals, irrespective of the particular risk any individual may run of contracting the disease in question.
• Classic example: screening for tuberculosis.
• Mass screening received enthusiastic support in the past. However, when subjected to critical review, there appeared to be little justification for its use in many instances.
• Key point: Indiscriminate mass screening 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.

b. High-Risk or Selective Screening

• Screening is most productive when applied selectively to high-risk groups, defined on the basis of epidemiological research.
• Example: Cancer cervix tends to occur less often in upper social groups, so screening the lower social groups increases the yield of new cases.
• Family aggregation of disease (diabetes, hypertension, breast cancer) - by screening other family members and close relatives, additional cases can be detected.
• Epidemiologists have extended this concept to screening for "risk factors" which antedate actual disease development:
  • Example: Elevated serum cholesterol - associated with high risk of coronary heart disease.
  • Risk factors of a pathophysiological nature (serum cholesterol, blood pressure) are amenable to effective interventions - preventive measures can be applied before disease occurs.
• Also economically advantageous - resources are used efficiently when tests are applied selectively to high-risk individuals.

c. Multiphasic Screening

• Defined as the application of two or more screening tests in combination to a large number of people at one time, rather than carrying out separate tests for single diseases.
• The procedure may include:
  • Health questionnaire
  • Clinical examination
  • Chemical and haematological tests on blood and urine specimens
  • Lung function assessment
  • Audiometry
  • Measurement of visual acuity
• All these can be performed rapidly with appropriate staffing, organization, and equipment.
• Multiphasic screening has enjoyed considerable popularity, BUT evidence from randomized controlled studies in UK and USA showed it has NOT demonstrated any benefit in terms of mortality and morbidity reduction.
• It has instead increased the cost of health services without any observable benefit.
• Furthermore, most of the tests currently used in multiphasic screening have not been validated.
• These observations have cast doubts on the utility of multiphasic screening.

Criteria for Screening (Bonus - commonly asked alongside types)

1. The Disease

1. Should be an important health problem (high prevalence)
2. Should have a recognizable latent or early asymptomatic stage
3. Natural history should be adequately understood
4. A test should be able to detect disease prior to onset of signs/symptoms
5. Facilities available for confirmation of diagnosis
6. Effective treatment exists
7. Agreed-on policy on whom to treat (e.g., borderline cases)
8. Good evidence that early detection reduces morbidity and mortality
9. Expected benefits exceed the risks and costs

2. The Screening Test

• Acceptability - must be acceptable to the target population; painful, discomforting or embarrassing tests (e.g., rectal/vaginal examinations) are not likely to be accepted in mass campaigns
• Repeatability (Reliability/Precision/Reproducibility) - must give consistent results when repeated under the same conditions; depends on observer variation, biological/subject variation, and technical errors
• Validity - must accurately measure what it purports to measure
• Besides: yield, simplicity, safety, rapidity, ease of administration, and cost

Concept of "Lead Time"

Definition

The Model for Early Detection (Fig. 1)

• Line A = Usual outcome of disease (without screening)
• Line B = Outcome when disease is detected at the earliest possible moment (with screening)
• Benefits of the programme = B - A

Key Concepts Explained

When is screening worthwhile?

• There is nothing to be gained in screening for diseases whose onset is quite obvious.
• Detection programmes should be restricted to conditions where there is a considerable time lag between disease onset and the usual time of diagnosis.
• During this period, there are a number of critical points which determine both the severity of the disease and the success of treatment in reversing the disease process.

The "Final Critical Point" concept

• There is 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
• Detection programmes should therefore concentrate on conditions where the time lag between disease onset and its final critical point is sufficiently long to be suitable for population screening.

Benefits must justify costs

• The benefits of the screening programme (B - A) must be seen in terms of its outcomes.
• The complexities and costs of any detection programme must be viewed against the benefits accruing from it.

Aims and Objectives of Screening (linked concept)

1. Sort out from a large group of apparently healthy persons those likely to have the disease or at increased risk
2. Bring those who are "apparently abnormal" under medical supervision and treatment
3. The hope is that earlier diagnosis and subsequent treatment favourably alters the natural history of the disease in a significant proportion of those who test positive

Summary (Exam Point)

Lead time = the period of time by which the diagnosis is advanced (brought forward) through screening, compared to when the disease would have been clinically diagnosed without screening.

Lead Time Bias

Definition

"Lead time bias occurs because screening identifies a case before it would have presented clinically, thereby creating the perception that a patient lived longer after diagnosis simply by moving the date of diagnosis earlier rather than the date of death later."

• Harrison's Principles of Internal Medicine, 22e

The Core Problem

• Lead time = the period between detection by screening and the usual time of clinical diagnosis.
• When a disease is detected earlier by screening, the clock of "survival after diagnosis" starts earlier.
• If the treatment is NOT effective, the patient still dies at the same time - but because diagnosis was made earlier, survival from diagnosis appears longer.
• This creates the false impression that screening improved survival, when in reality it only moved the start date of counting.

Diagram 1 - Lead Time Bias (from Campbell Walsh Wein Urology)

• In the ineffective screening scenario, survival appears 3x longer (15 vs 5 years), but the patient dies at the same age (75). The extra 10 years is pure lead time bias - it is the lead time being counted as "survival."
• Only in effective screening is there a genuine prolongation of life.

Diagram 2 - Lead Time Bias (from Symptom to Diagnosis)

• Unscreened patient: Short pre-diagnosis time, shorter post-diagnosis survival, but same total survival
• Screened patient, early treatment NOT effective: Longer post-diagnosis survival (appears better) - but total survival is identical to unscreened
• Screened patient, early treatment effective: Genuinely longer total survival - this is real benefit, not bias

How Lead Time Bias Distorts Results

Classic Real-World Example

• Over 30 years, increased use of abdominal CT detected more asymptomatic renal masses
• 5-year survival improved: 50% → 75%
• BUT the mortality rate from kidney cancer remained stable
• Conclusion: the apparent survival improvement is lead time bias, not true benefit

How to Avoid / Correct for Lead Time Bias

1. Use mortality (not survival) as the primary endpoint - measure disease-specific deaths per 100,000 population, not survival from diagnosis
2. Use all-cause mortality or disease-specific mortality in randomized controlled trials
3. Randomized controlled trials (RCTs) with mortality outcomes are the gold standard for evaluating screening efficacy
4. Mathematical correction: Estimate the lead time and subtract it from the screened group's survival

"It is critical that disease incidence or mortality is the primary endpoint rather than length of disease survival... because lead time bias and length time bias can create the appearance of an improvement in disease survival from a screening test when there is no actual effect."

• Harrison's Principles of Internal Medicine, 22e

Lead Time Bias vs Length Time Bias (Comparison)

Park's SPM Connection