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  <head>
    <title>066-02 Causal inference, effect interpretation, diagnostic evidence, and patient-level application</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Causal inference, effects, diagnosis, and application">
      <outline text="Four questions and focused framing">
        <outline text="Valid, how large, applicable, worth the burden"/>
        <outline text="Prestige, p value, or guideline answers none alone"/>
        <outline text="Treatment question includes a time horizon"/>
        <outline text="Harm: timing, dose, latency, competing causes"/>
        <outline text="Vague questions invite surrogate answers"/>
      </outline>
      <outline text="Trial conduct and reporting">
        <outline text="Conceal sequence so recruiters cannot manipulate"/>
        <outline text="Objective outcomes not automatically immune to bias"/>
        <outline text="Loss to follow-up can destroy balance"/>
        <outline text="Per-protocol answers an adherence-conditioned question"/>
        <outline text="Check registry and protocol for post-hoc changes">
          <outline text="Early stopping locks in chance effects"/>
        </outline>
        <outline text="Funding alone is not grounds for rejection"/>
        <outline text="Small trials may be imbalanced">
          <outline text="Baseline significance test is not the solution"/>
        </outline>
        <outline text="Cluster correlation ignored narrows intervals"/>
      </outline>
      <outline text="Observational studies and causal diagrams">
        <outline text="Essential for prognosis, rare harm, long latency"/>
        <outline text="Confounder influences exposure and outcome"/>
        <outline text="Adjustment cannot erase unmeasured confounders"/>
        <outline text="Channeling: sicker patients get one drug">
          <outline text="New-user active-comparator design aligns start"/>
        </outline>
        <outline text="Mediator adjustment removes part of the effect"/>
        <outline text="Collider conditioning creates false association">
          <outline text="Selection into hospital or study as collider"/>
        </outline>
        <outline text="Adjust by causal question, not availability"/>
      </outline>
      <outline text="Bias and missing data">
        <outline text="Selection depends on exposure and prognosis"/>
        <outline text="Recall: cases reconstruct exposure differently"/>
        <outline text="Misclassification dilutes or exaggerates"/>
        <outline text="Complete-case analysis assumes ignorable missingness">
          <outline text="Reasons and sensitivity analysis needed"/>
        </outline>
      </outline>
      <outline text="Effect measures and uncertainty">
        <outline text="Odds ratio approximates risk only when rare"/>
        <outline text="Hazard ratio is an instantaneous rate ratio"/>
        <outline text="Number needed to treat keeps population and time"/>
        <outline text="Interval width reflects information">
          <outline text="Narrow around trivial effect is unimportant"/>
        </outline>
        <outline text="Non-inferiority needs a justified margin">
          <outline text="Non-adherence biases toward similarity"/>
        </outline>
        <outline text="P value measures surprise under a null model"/>
        <outline text="Multiplicity inflates false positives">
          <outline text="Strict correction can hide a true signal"/>
        </outline>
        <outline text="Bayesian prior and model must be transparent"/>
      </outline>
      <outline text="Composite, competing, and surrogate outcomes">
        <outline text="Composite may be driven by least important part"/>
        <outline text="Competing death prevents later events">
          <outline text="Kaplan-Meier censoring overestimates incidence"/>
        </outline>
        <outline text="Surrogate must predict patient-important effects">
          <outline text="Non-causal marker, off-target harm, timing"/>
        </outline>
        <outline text="Disease improvement with worse mortality"/>
      </outline>
      <outline text="Diagnostic and prediction evidence">
        <outline text="Blinded reading, independent verification"/>
        <outline text="Partial verification inflates accuracy"/>
        <outline text="Incorporation: index test within reference"/>
        <outline text="Referral-centre results may not transfer"/>
        <outline text="Good ranking can coexist with overprediction"/>
        <outline text="Internal validation estimates optimism"/>
        <outline text="External validation tests transport"/>
      </outline>
      <outline text="Heterogeneity and systematic reviews">
        <outline text="Credible effect modification criteria"/>
        <outline text="Do not cut continuous modifiers arbitrarily"/>
        <outline text="Meta-analysis cannot repair biased studies"/>
        <outline text="Random effects do not unify questions"/>
        <outline text="Prediction interval for a new setting"/>
        <outline text="Funnel asymmetry has causes besides publication"/>
        <outline text="Test robustness with low-bias studies only"/>
      </outline>
      <outline text="Harms and external validity">
        <outline text="Registries give denominators but confounding"/>
        <outline text="Spontaneous reports find signals, not incidence"/>
        <outline text="Deliberate rechallenge may be unethical"/>
        <outline text="Exclusion creates uncertainty, not contraindication"/>
        <outline text="Relative effects may transport better"/>
        <outline text="Cost, travel, caregiver burden shape effectiveness"/>
      </outline>
      <outline text="Certainty, decision, and time-limited trials">
        <outline text="Certainty is separate from magnitude"/>
        <outline text="Natural frequencies with and without treatment">
          <outline text="Relative framing alone can manipulate"/>
        </outline>
        <outline text="Decision table at the patient&#x27;s baseline risk"/>
        <outline text="Weak evidence, high urgency: clinicians still act">
          <outline text="Target, timeframe, monitoring, stopping rule"/>
        </outline>
        <outline text="Regression to the mean mimics improvement">
          <outline text="One patient&#x27;s response is not population proof"/>
        </outline>
        <outline text="Record evidence, limits, assumptions, triggers"/>
        <outline text="Transparency of judgement raises safety"/>
      </outline>
    </outline>
  </body>
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