Table 1

Key concepts and methods to establish the reliability32 and validity33 34 of SPADE

ConceptMethodValidity and reliability
Symptom-disease pairTest an association that is clinically plausible, linking a presenting symptom (chief complaint) and specific disease.28 Face validity and biological plausibility of the target symptom-disease dyad
Bidirectional analysisUse both look-back and look-forward methods to assess the same symptom-disease association.21 25 Convergent construct validity of the symptom-disease dyad
Baseline comparisons (observed to expected)Compare event frequency or rate of return with baseline or expected level (look back—OR25; look forward—HR21) or matched control population.23 Strength of measured association relative to internal or external control
Temporal profilesPlot temporal profile or trend (look back—time before index event25; look forward—time after index event21).Temporality and biological plausibility/gradient based on disease natural history
Positive control comparisonsTest a similar association that is clinically plausible (look back—linked symptom19 25; look forward—linked disease35).Coherence of the symptom-disease dyad or alternative form reliability
Negative control comparisonsTest an association that is not clinically plausible (look back—unlinked symptom25; look forward—unlinked disease21 22).Discriminant construct validity (specificity) of the symptom-disease dyad
Subgroup analysesTest for clinically plausible subgroup associations (eg, dizziness linked to missed ischaemic but not haemorrhagic stroke; headache linked to both25).Face validity and biological plausibility/gradient of the measured associations
Associated diagnostic process failuresCorrelate specific outcomes with known process failures (eg, missed stroke linked to improper use of CT rather than MRI51).Coherence of the identified associations and construct validity
Triangulation of findingsUse alternative methods (eg, chart review, surveys, root cause analyses) to confirm the diagnostic error association.26 Convergent construct validity, coherence of the measured associations
Impact analysisMonitor the impact of interventions designed to reduce error or harms on the measure (‘flattening the hump’).Predictive (criterion) validity and measure responsiveness
Reproducibility of analytical resultsRepeat the analysis in multiple data sets21–23 or using resampling methods (eg, bootstrapping or split-halves).Consistency of the measured associations or resampling73 reliability
Reproducibility of SPADE approachRepeat the approach across other analogous symptom-disease dyads (eg, chest pain-myocardial infarction,24 fever-meningitis/sepsis36).Analogy34 of the approach to related problems
  • HR, hazard ratio; OR, odds ratio; SPADE, Symptom-Disease Pair Analysis of Diagnostic Error.