Figure 2.

Method for establishing a symptom-disease pair using dizziness-stroke as the exemplar. Envisioned is a ‘symptom’ and ‘disease’ visit occurring as clinical events unfold in the natural history of a disease, as illustrated in figure 1. (A) The ‘look-back’ approach is used to take a single disease known to cause harm (eg, stroke) and identify a number of high-risk symptoms that may be missed (eg, dizziness/vertigo). In this sense, the ‘look-back’ approach (case-control design) can be thought of as hypothesis generating. In the exemplar, stroke is chosen as the disease outcome. Various symptomatic clinical presentations at earlier visits are examined as exposure risk factors, some of which are found to occur with higher-than-expected odds in the period leading up to the stroke admission. (B) The ‘look-forward’ approach is used to take a single symptom known to be misdiagnosed (eg, dizziness/vertigo) and identify a number of dangerous diseases that may be missed (eg, stroke). In this sense, the ‘look-forward’ approach (cohort design) can be thought of as hypothesis testing. In the exemplar, dizziness is chosen as the exposure risk factor, and various diseases are examined as potential outcomes, some of which are found to occur with higher-than-expected risk in the period following the dizziness discharge.