Screening and Diagnostic Tests Overview

Screening and Diagnostic Tests

• Screening is identifying people who have (or are likely to have) a specific condition. This allows for treatment decisions.
• Screening is particularly important when early detection benefits prevention or treatment.
• Diagnostic tests are used on symptomatic or screened people to determine if they have a specific disease.

Types of Prevention

• Primary prevention: Avoiding the onset of a disease. (e.g., Polio vaccine)
• Secondary prevention: Minimizing outcomes through early detection and treatment. (e.g., Mammography)
• Tertiary prevention: Reducing disability and complications of advanced disease. (e.g., HAART)

Goals of Screening

• Immediate goal: Determine if a person is likely or unlikely to have a disease.
• Ultimate goal: Reduce morbidity and mortality from the disease.

Requirements for Effective Screening

• Suitable disease: The disease must have a sufficient burden (consequences if left untreated), a suitable detectable preclinical period, and a reasonable cost. Rare diseases may also need to be considered.
• Accurate test: The test must be reliable (consistent results), valid ("correct"), sensitive (detecting true positives), and specific (identifying true negatives).
• Effective treatment: Treatment must be available, effective, & cost-effective and/or favorable to prevent further progression of the disease.
• Benefits outweigh harms: Benefits of screening must outweigh the harms (including adverse events from invasive procedures, adverse treatment effects, and psychological effect from false positives).
• Reasonable cost: The costs of screening, diagnosis, and treatment should be reasonable.
• Screening in low- and middle-income countries: Screening requires considerations of healthcare systems, follow-up resources, and adequate diagnostic testing.

Test Properties

• Basic facts: People can be sick or well (sad/happy face). A test can be positive or negative (ie. diseases or not having a disease).
• Visual overview: There are four possible test outcomes (true positive, true negative, false positive, false negative).
• Sensitivity: The probability of detecting a true positive case of a disease. (e.g. 70% sensitivity means 70% chance of being reported positive if the disease is truly present).
• Specificity: The probability of detecting a true negative case of a disease. (e.g.,70% specificity means 70% chance of being reported negative if the disease is truly absent).
• Sensitivity and Specificity: Are independent of prevalence.
• Sensitivity and Specificity calculations: The calculation uses a 2 x 2 table with true positives (TP), True negative (TN), False positive (FP), and false negative (FN). Sensitivity = TP / (TP+FN). Specificity = TN / (TN+FP).
• Trade-offs in sensitivity and specificity: Increasing sensitivity decreases specificity and vice-versa making it important to consider the overall trade-offs or the cut-off point selection.
• ROC curves: Used to find the best cut-point for a given screening test. Plot true positive rate against 1-specificity.
• AUC: ROC curve Area Under Curve value; Represents the probability of a correctly classified case). Higher AUC, the better.
• Positive predictive value (PPV): The proportion of people with positive screening results who truly have the condition. Increases with prevalence.
• Negative predictive value (NPV): The proportion of people with negative screening tests who truly do not have the condition. Decreases with prevalence.

Population Perspective

• Relationship with prevalence: PPV and NPV are affected by the prevalence of a particular disease is within a target population.

Lead Time

• Definition: The time between when the disease would have been detected without screening and when the screen detects the disease.
• Impact: Screenings for disease can cause people to survive longer with the disease (with a diagnosed disease), without really impacting a disease survival rate fundamentally. Lead time has little effect on overall survival rates.

Length Time

• Bias: Diseases that develop rapidly are easier to detect through screening (better diagnostic rate). While diseases that develop slowly might lead to apparent improvement in survival, not reflecting an actual change in survival (worse diagnostic rate).

Overdiagnosis

• Pseudo-disease: People who test positive but the disease is not causing any real harm (usually asymptomatic and/or indolent).
• Serendipity: True diagnosis without screening but no difference in future prognostics.

Key Questions for Screening

• Possible gains from screening: (Mortality reduction, availability of cost-effective treatment)
• Possible decreases from screening: (Transmission of disease, behavioral changes, quality of life)
• Cost & Quality of life

Types of Biases

• Lead time bias: Diagnosis is made earlier in a screened group.
• Length time bias: Aggressive diseases are more easily detected, whereas slow-growing diseases tend to have longer lead times.
• Overdiagnosis bias: Finding disease when it doesn't affect survival or require treatment.

Timeline for Screening

• Natural history of disease: Describes the course of a disease from its onset to its resolution or death.

• Lead time: Time between the time diagnosis would have been made without screening to when the screening detects the disease.