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Epidemiology and measures of disease

Calculate and interpret common measures of disease frequency, association, diagnostic accuracy and intervention effect while recognising bias, confounding, uncertainty and population context.

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01Core principlesThe concepts and mechanisms needed to understand the subject.

Point prevalence is existing cases divided by the population at a specified moment. Period prevalence includes anyone who had the condition during a stated interval. Prevalence rises when incidence rises, survival lengthens or case ascertainment improves, and falls when recovery, death or out-migration removes cases. It is valuable for workload planning: the number needing asthma review today depends on prevalence, not only this year’s new diagnoses.

Cumulative incidence, or risk, is new cases during a period divided by the disease-free population at the start, assuming sufficient follow-up. Example: among 800 initially unaffected people, 32 develop disease over one year; one-year risk is 32/800 = 0.04 or 4%. Incidence rate uses person-time. If observation totals 620 person-years and 31 new events occur, the rate is 31/620 = 0.05 per person-year, often reported as 5 per 100 person-years.

An attack rate is a cumulative incidence used in outbreaks. If 45 of 180 wedding guests develop gastroenteritis, the attack rate is 25%. Food-specific attack rates compare those who ate and did not eat an item. Secondary attack rate measures spread among susceptible contacts of primary cases. Define who counts as exposed, susceptible and a case, and align the observation window with the plausible incubation period.

Mortality rate measures deaths in a population over time. Case fatality proportion measures the proportion of identified cases who die from the condition over a specified period and reflects disease severity, case definition and ascertainment. Survival is conditional on diagnosis and follow-up. Apparent improvement in survival can occur through lead-time bias when screening advances diagnosis without changing time of death, or length bias when slower disease is more likely to be detected.

Measures of association compare groups. In a cohort, if 24 of 300 exposed people and 9 of 300 unexposed people develop disease, risks are 8% and 3%; risk ratio is 0.08/0.03 = 2.67, risk difference is 5 percentage points, and attributable fraction among exposed is (2.67−1)/2.67 = 62.5%. Relative measures describe strength; absolute measures show population and clinical impact.

Odds are probability divided by one minus probability. A case-control study begins with outcome status, so disease risks cannot usually be calculated directly from sampled cases and controls; use the exposure odds ratio. For a two-by-two table, odds ratio equals ad/bc. When disease is rare, odds and risk are close. With common outcomes, describing an odds ratio as a risk ratio exaggerates the apparent effect.

Intervention effects require a time horizon and baseline risk. Suppose an event occurs in 18 of 300 controls and 9 of 300 treated participants. Control risk is 6%, treatment risk 3%, relative risk 0.5, relative risk reduction 50%, and absolute risk reduction 3 percentage points. NNT is 1/0.03 = 33.3, conventionally rounded up to 34 for that follow-up period. State the population and duration because NNT changes with baseline risk.

For harm, absolute risk increase is intervention risk minus control risk and number needed to harm is its reciprocal. Benefits and harms may have different denominators, severities and times. A composite outcome can be driven by a less important frequent component. Intention-to-treat analysis preserves randomisation and estimates effect of assignment, while per-protocol analysis answers a different question and can introduce selection bias.

A diagnostic two-by-two table compares the index test with an appropriate reference classification. Sensitivity = TP/(TP+FN); specificity = TN/(TN+FP). Positive predictive value = TP/(TP+FP); negative predictive value = TN/(TN+FN). Sensitivity and specificity can vary with spectrum and thresholds; predictive values vary with prevalence. Verify that participants received the same reference process independent of index result to avoid verification bias.

Worked numbers show prevalence effect. A test has 90% sensitivity and 90% specificity. In 1,000 people with 10% prevalence, expect 90 true positives, 10 false negatives, 90 false positives and 810 true negatives; PPV is 90/180 = 50%. At 1% prevalence, expect about 9 true positives and 99 false positives among 1,000; PPV falls to roughly 8.3%. The test characteristics did not change, but the meaning of a positive result did.

Likelihood ratios update odds. LR+ = sensitivity/(1−specificity), and LR− = (1−sensitivity)/specificity. With sensitivity 0.90 and specificity 0.90, LR+ is 9 and LR− is 0.11. Convert pre-test probability to odds, multiply by the likelihood ratio, then convert odds back to probability. Nomograms or validated tools reduce arithmetic error, but a precise output remains wrong if the pre-test estimate or study population is unsuitable.

Bias is systematic deviation. Selection bias occurs when inclusion or follow-up differs with exposure and outcome. Information bias arises from measurement or classification; non-differential misclassification often dilutes association but not invariably. Recall bias particularly threatens retrospective self-report. Confounding is a mixing of effects by a factor associated with exposure and independently with outcome, outside the causal pathway. Restriction, randomisation, matching, stratification and multivariable adjustment address different parts of the problem.

Chance and precision matter. A confidence interval describes values compatible with data under model assumptions, not the probability that a fixed true value lies within this realised interval. A p value is the probability of results at least as extreme under a specified null model, not the probability that the null hypothesis is true. Statistical significance does not establish clinical importance, validity or causality. Inspect effect size, interval, missing data, multiplicity and design.

Key points

  • Incidence measures new events among people at risk over time; cumulative incidence uses a starting population at risk, whereas incidence rate uses person-time.
  • Prevalence is the proportion with a condition at a point or during a period and depends on both incidence and duration; it is useful for service need but not usually causal sequence.
  • Risk ratio compares risks, rate ratio compares incidence rates, and odds ratio compares odds; the odds ratio approximates the risk ratio only when the outcome is uncommon.
  • Absolute risk reduction equals control risk minus intervention risk; number needed to treat is the reciprocal of absolute risk reduction when risk is expressed as a proportion.
  • Sensitivity is true positives divided by all with disease; specificity is true negatives divided by all without disease; predictive values also depend strongly on prevalence.
  • Positive likelihood ratio is sensitivity divided by one minus specificity; negative likelihood ratio is one minus sensitivity divided by specificity.
  • Random error affects precision and is expressed with confidence intervals; bias is systematic error and is not cured merely by increasing sample size.
  • Association does not establish causation: ask about selection, measurement, confounding, reverse causation, chance, temporality, plausibility and applicability.
02Mechanisms and patternsImportant relationships and how to distinguish them.
Wrong denominator

Counts, risks and rates become misleading when the denominator includes people not at risk or uses a different time window.

Prevalence-incidence confusion

A cross-sectional prevalence difference may reflect disease duration or survival rather than a difference in new disease occurrence.

Relative-effect inflation

A large relative reduction can correspond to a small absolute benefit when baseline risk is low.

Predictive-value shift

The same sensitivity and specificity produce different positive and negative predictive values when prevalence changes.

Systematic bias

Selection, measurement or analytic errors can move an estimate consistently away from truth and remain after a larger sample.

Confounding pathway

A third factor related to exposure and outcome can create or hide association unless design or analysis handles it appropriately.

03Interpreting evidenceInformation, measurements and their limitations.
Reasoning sequence

Consider the information, its meaning and its limitations before deciding what follows.

  1. 01
    Numerator-denominator audit
    Why
    Confirm the measure’s population, event and time basis.
    Interpretation and limitations
    State who can enter each count, who is at risk, start and stop times and whether repeat events are permitted.
  2. 02
    Two-by-two table
    Why
    Calculate associations or test accuracy transparently.
    Interpretation and limitations
    Label disease, exposure and test axes before filling cells; reversing an axis swaps quantities and can invalidate the answer.
  3. 03
    Confidence interval review
    Why
    Judge precision and compatibility with clinically important effects.
    Interpretation and limitations
    Consider width, scale and null value together; absence of statistical significance is not proof of equivalence.
  4. 04
    Bias and confounding assessment
    Why
    Evaluate whether design or conduct explains the observed association.
    Interpretation and limitations
    Trace selection, measurement, missingness, causal timing and adjustment rather than using a generic checklist alone.
  5. 05
    Applicability comparison
    Why
    Decide whether study effects fit the target patient or population.
    Interpretation and limitations
    Compare baseline risk, eligibility, setting, intervention fidelity, outcome importance and follow-up duration.
04Applied reasoningWorked examples connecting principles to decisions.
01Worked example: screening test tableCalculate accuracy and explain prevalenceAmong 1,000 people, 100 truly have disease. A test is positive in 90 with disease and 90 without disease.
  1. 1Construct the table: true positive 90, false negative 10, false positive 90 and true negative 810; verify all four cells sum to 1,000.
  2. 2Calculate sensitivity 90/(90+10)=90% and specificity 810/(810+90)=90%; these condition on disease status.
  3. 3Calculate the final predictive answers: PPV 90/(90+90)=50% and NPV 810/(810+10)=98.8%, rounded to one decimal place.
  4. 4Verify interpretation: half of positive results are false positives in this 10%-prevalence population; recalculate rather than carrying PPV unchanged into a lower-prevalence setting.
02Intervention effectMove from event counts to NNTEvents occur in 18 of 300 controls and 9 of 300 treated people over one year.
  1. 1Calculate control and treatment risks as 6% and 3%.
  2. 2Derive relative risk 0.50 and absolute risk reduction 0.03, keeping the one-year horizon.
  3. 3Calculate 1/0.03=33.3 and round up to an NNT of 34, then report population, outcome and duration.
03Outbreak frequencyDefine an attack rate before comparing foodsMultiple guests develop a compatible illness after a shared event.
  1. 1Create a case definition with person, clinical features, place and time and identify all attendees at risk.
  2. 2Calculate overall and food-specific attack rates using exposed and unexposed denominators.
  3. 3Compare ratios or differences, inspect timing and dose-response, and verify hypotheses with environmental and microbiological evidence.
04Critical appraisalSeparate chance, bias and causalityAn observational study reports a strong association and a narrow confidence interval.
  1. 1Check temporality, selection, measurement, missing data and whether a plausible confounder explains the result.
  2. 2Interpret effect size and interval rather than p value alone, and distinguish precision from freedom from bias.
  3. 3Compare the study population and exposure with the target setting before estimating absolute impact or changing practice.
05Checking understandingVerify the reasoning, revisit uncertainties and apply feedback.
  • Use a written data dictionary so case, denominator, exposure and time definitions remain stable across repeated measurements.
  • Plot counts and rates over time with denominator and data-completeness checks before attributing change to an intervention.
  • Report absolute and relative effects together, with confidence intervals, follow-up duration and adverse outcomes.
  • Review missing data, loss to follow-up and differential ascertainment because each can change the direction of an estimate.
  • Recalculate predictive values or post-test probabilities when target prevalence differs materially from the source study.
  • Pre-specify primary outcomes and analyses where possible, and label exploratory subgroup findings to reduce selective interpretation.
06Special situationsVariants, exceptions and circumstances that change the usual approach.

Person-time handles unequal follow-up

Incidence rates allow each participant to contribute observed time, but depend on defensible counting and censoring assumptions.

Survival can improve without benefit

Earlier diagnosis creates lead time, and preferential detection of slower disease creates length bias.

Odds ratios are non-collapsible

Adjusted and unadjusted odds ratios can differ even without ordinary confounding, so interpretation needs care when outcomes are common.

NNT is contextual

Baseline risk, outcome definition, follow-up duration and competing events determine the absolute benefit and its reciprocal.

Precision is not validity

A huge dataset can estimate a biased quantity very precisely when coding, selection or confounding is flawed.

Ecological data concern groups

An association between area-level exposure and outcome cannot automatically be assigned to individuals within those areas.

07Common pitfallsFrequent interpretation and management errors.
  1. 01

    Do not divide new cases by a population that includes people who already had the condition when risk began.

  2. 02

    Do not report an incidence rate without person-time units.

  3. 03

    Do not describe an odds ratio as a risk ratio when the outcome is common.

  4. 04

    Do not calculate NNT from relative risk reduction; use the reciprocal of absolute risk reduction.

  5. 05

    Do not treat sensitivity, specificity and predictive value as interchangeable.

  6. 06

    Do not assume a narrow confidence interval excludes systematic bias.

  7. 07

    Do not interpret a p value as the probability that the null hypothesis is true.

  8. 08

    Do not infer individual causation directly from an area-level association.

Practice

Two practice questions

Question 1 of 20 correct
Primary care and public healthOriginal SBA

Number needed to treat

Over one year, an outcome occurs in 12% of a control group and 8% of an intervention group. Assuming a causal effect, what is the number needed to treat to prevent one outcome over one year?

Sources and review status5 sources · checked 7 Sept 2026 · clinical review pending
Sources

Sources and review status

National guidance is shown before implementation-dependent detail. Apply principles in context and verify current guidance when a decision affects care. Source check completed 7 Sept 2026; clinical approval remains outstanding.

Authoring stateComplete draftClinical stateAwaiting reviewJurisdictionUnited Kingdom