Association and Causation

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Association Basics - Spotting Connections

  • Association: Statistical relationship between two or more variables/events; they occur together more or less often than expected by chance.
  • Types of Association:
    • Spurious/Artifactual: False association due to chance or bias (e.g., selection bias, measurement bias).
    • Indirect: Statistical association due to a common factor (confounder) linking exposure and outcome.
    • Direct/Causal: Exposure directly leads to outcome.
      • One-to-one: Factor A → Disease X.
      • Multifactorial: Factor A + Factor B → Disease X.
  • Strength of Association: Measured by Relative Risk (RR), Odds Ratio (OR).
    • RR/OR = 1: No association.
    • RR/OR > 1: Positive association (risk factor).
    • RR/OR < 1: Negative association (protective factor).

⭐ Spurious association can arise from Berksonian bias, where hospital admission rates differ for exposed/unexposed or cases/controls, leading to a distorted association observed only in hospital settings.

Bradford Hill Criteria - Causation's Commandments

Bradford Hill Criteria for Causation Framework for assessing if an observed association is likely causal. Fulfilling more criteria strengthens causal inference; not all are required. 📌 Mnemonic: "BTS CAPS CE".

  • Strength of Association: Strong association (e.g., high RR/OR) is more indicative of causality.
  • Consistency: Association observed repeatedly by different researchers, in diverse populations, settings, and times.
  • Specificity: Exposure linked to a specific disease, not multiple outcomes. (Often the weakest criterion).
  • Temporality: Exposure must precede disease onset. (This is the absolutely essential criterion).
  • Biological Gradient (Dose-Response): Increased exposure (dose) correlates with increased risk or severity of disease.
  • Plausibility: A biologically sensible mechanism can explain the association.
  • Coherence: Association aligns with existing knowledge of the disease's natural history and biology.
  • Experimental Evidence: Findings from controlled experiments (e.g., RCTs, animal studies) support the causal link.
  • Analogy: Similar causal relationships are known for related exposures or diseases.

⭐ Temporality is the sine qua non for causation: the cause must precede the effect. Without this, an association cannot be deemed causal.

Bias & Confounding - Tricky Twins

  • Bias: Systematic error in study design, conduct, or analysis; distorts true association. Not reduced by ↑ sample size.
    • Selection Bias: Groups differ systematically.
      • E.g., Berkson's (hospital-based), Neyman (incidence-prevalence), Healthy worker effect.
    • Information (Measurement) Bias: Errors in measuring exposure/outcome.
      • E.g., Recall bias (cases recall more), Interviewer bias (systematic questioning differences).
    • Control: Blinding, randomization, standardized protocols.
  • Confounding: A third variable (confounder) distorts the exposure-outcome link.
    • Confounder:
      1. Associated with exposure.
      2. Independent risk factor for outcome.
      3. Not on causal pathway.
    • Control:
      • Design: Randomization, restriction, matching.
      • Analysis: Stratification, multivariate analysis.

⭐ Randomization is the gold standard for controlling confounding, especially for unknown confounders.

Diagrams illustrating confounding, mediation, and biasoka

Study Designs & Causality - Evidence Ladder

  • Hierarchy of Evidence (↑ Causal Inference Strength):
    • Case reports/series, Ecological (hypothesis generation)
    • Cross-sectional (Snapshot, prevalence)
    • Case-Control (Retrospective, Odds Ratio)
    • Cohort (Prospective/Retrospective, Relative Risk, Incidence)
    • Randomized Controlled Trial (RCT - Intervention, experimental)
    • Systematic Review & Meta-analysis (Highest, pooled evidence)
  • Evidence pyramid for epidemiological studies

⭐ RCTs provide the strongest evidence for causality among primary study designs due to minimized confounding through randomization.

  • Bradford Hill criteria are key for assessing causality, not just association.
  • Strength of association (e.g., high RR/OR) is a strong criterion, but not definitive.
  • Temporality (cause precedes effect) is the only essential criterion for causality.
  • Dose-response relationship (↑ exposure → ↑ risk) strengthens causal inference.
  • Consistency of findings across diverse studies and populations is crucial.
  • Specificity (one cause → one effect) is weak for chronic diseases.
  • Biological plausibility and coherence with existing knowledge support causality.

Practice Questions: Association and Causation

Test your understanding with these related questions

Which type of study determines the odds ratio?

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Flashcards: Association and Causation

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_____ studies are useful for measuring odds ratio (OR)

TAP TO REVEAL ANSWER

_____ studies are useful for measuring odds ratio (OR)

Case-control

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