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  <head>
    <title>066-01 Foundations</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Evidence-based medicine foundations">
      <outline text="Orientation and question framing">
        <outline text="Research plus expertise, values, biology, context">
          <outline text="Not obeying a hierarchy without judgement"/>
        </outline>
        <outline text="Methods before results"/>
        <outline text="Absence of evidence is not evidence of no effect"/>
        <outline text="Treatment: population, intervention, comparator, outcomes"/>
        <outline text="Diagnosis: condition, test, reference, setting"/>
        <outline text="Prioritise patient-experienced outcomes"/>
        <outline text="Biomarkers and composites may mislead">
          <outline text="Surrogate must reliably change clinical outcome"/>
        </outline>
      </outline>
      <outline text="Study designs">
        <outline text="Randomisation balances prognostic factors on average"/>
        <outline text="Concealment prevents prediction before enrolment"/>
        <outline text="Blinding reduces differential care and assessment"/>
        <outline text="Intention-to-treat preserves randomisation">
          <outline text="Per-protocol loses it, vulnerable to selection"/>
        </outline>
        <outline text="Crossover, cluster, factorial, pragmatic trials"/>
        <outline text="Case-control: efficient for rare disease">
          <outline text="Vulnerable to selection and recall"/>
        </outline>
        <outline text="Meta-analysis adds precision, not unbiasedness">
          <outline text="Pooling incomparable studies misleads precisely"/>
        </outline>
      </outline>
      <outline text="Random error and estimation">
        <outline text="Confidence interval expresses precision">
          <outline text="Ninety-five per cent of repeated intervals"/>
        </outline>
        <outline text="P value assumes the null model is true">
          <outline text="Not probability the null is true"/>
        </outline>
        <outline text="Significance depends on sample size"/>
        <outline text="Number needed to treat varies with baseline risk"/>
        <outline text="Non-significance is not equivalence">
          <outline text="Non-inferiority needs prespecified margins"/>
        </outline>
      </outline>
      <outline text="Bias within studies">
        <outline text="Selection: groups differ in prognosis"/>
        <outline text="Performance: unequal co-interventions"/>
        <outline text="Detection: outcome measurement differs"/>
        <outline text="Attrition and selective reporting"/>
        <outline text="Random error lowers precision, systematic shifts"/>
        <outline text="Recall and interviewer bias"/>
        <outline text="Confounding creates non-causal association">
          <outline text="Adjustment cannot remove unmeasured confounding"/>
          <outline text="Adjusting mediator or collider adds bias"/>
        </outline>
      </outline>
      <outline text="Causation">
        <outline text="Temporality, consistency, dose-response, mechanism">
          <outline text="No checklist proves causation"/>
        </outline>
        <outline text="Randomisation best supports intervention causality"/>
        <outline text="Triangulation across differently biased designs"/>
        <outline text="Biomarker correlation does not prove targeting helps"/>
        <outline text="Reverse causation from early disease"/>
        <outline text="Immortal time favours the exposed"/>
      </outline>
      <outline text="Diagnostic evidence">
        <outline text="Representative patients, complete verification"/>
        <outline text="Partial verification, incorporation, review bias"/>
        <outline text="Sensitivity and specificity vary with spectrum"/>
        <outline text="Predictive values vary with prevalence"/>
        <outline text="Area under curve measures discrimination only">
          <outline text="Adds little if management does not change"/>
        </outline>
        <outline text="Prediction models need external validation">
          <outline text="Calibration compares predicted with observed"/>
        </outline>
      </outline>
      <outline text="Prognosis and survival">
        <outline text="Inception cohort, follow-up, objective outcomes"/>
        <outline text="Kaplan-Meier assumes comparable censored risk"/>
        <outline text="Hazard ratio is not a risk ratio"/>
        <outline text="Ignoring competing events overestimates incidence"/>
        <outline text="Group prognosis is not individual destiny"/>
      </outline>
      <outline text="Harms and pharmacovigilance">
        <outline text="Trials too small or short for rare harms"/>
        <outline text="Spontaneous reports cannot give incidence">
          <outline text="Reporting and denominator unknown"/>
        </outline>
        <outline text="Temporality, dechallenge, rechallenge, dose"/>
        <outline text="Channeling: high-risk patients get one drug">
          <outline text="New-user and active-comparator designs"/>
        </outline>
      </outline>
      <outline text="Applicability and research integrity">
        <outline text="Does the patient resemble participants"/>
        <outline text="Exclusion raises uncertainty, not ineffectiveness"/>
        <outline text="Absolute effects depend on baseline risk"/>
        <outline text="Guidelines add values and may lag"/>
        <outline text="Credible subgroups: prespecified, tested interaction"/>
        <outline text="Positive novel studies more likely published"/>
        <outline text="Multiple analyses inflate false positives"/>
        <outline text="Disclosed conflict does not void sound methods"/>
      </outline>
      <outline text="From evidence to decision">
        <outline text="Certainty is not size of benefit"/>
        <outline text="Absolute natural frequencies, same denominator"/>
        <outline text="Include harms, burden, and no intervention"/>
        <outline text="Shared decision-making on what matters"/>
        <outline text="Weak evidence, high urgency: time-limited trial">
          <outline text="Document assumptions and stopping rules"/>
        </outline>
        <outline text="Act, measure, learn, and revise"/>
      </outline>
    </outline>
  </body>
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