Sequence symmetry analysis graphic adjustment for prescribing trends

BACKGROUND: Sequence symmetry analysis (SSA) is a signal detection method that can be used to assist with adverse drug event detection. It provides both a risk estimate and a data visualisation. Published methods provide results in the form of an adjusted sequence ratio, which adjusts for underlying market trends of medicine use, however no method for adjusting the visualisation is available. We aimed to develop and evaluate another method of adjustment for prescribing trends and apply it to the SSA visualisation. METHODS: The SSA method relies on incident prescriptions for pairs of medicines of interest. Smoothing curves were fitted to the frequency distributions of incident medicine use. When divided and normalised, these curves yielded a set of proportions related to differences in prescribing trends over follow-up. These were then used to adjust the unit counts for incident prescriptions in the SAA visualisation and to calculate the sequence ratio. Curve fitting was also used to identify the proportional relationship between sequences over time for SSA and is presented as a supplementary visualisation to the SSA. We compared the sensitivity and specificity of our method with that from the SSA method of Tsiropolous et al. RESULTS: Curve-fit adjusted SSA visualisations yielded adjusted sequence ratios very close to those of Tsiropolous, with a p-value of 0.999 for the two sample Kolmogorov-Smirnov test. Results for sensitivity and specificity derived from adjusted sequence ratios were also practically the same. The curve-fit method graphically indicates the proportionality of the sequence and provides a useful supplement of net differences between the two sides of the SSA visualisation. Additionally, we found that incident prescriptions for patients common to both distributions are best precluded from adjustment calculations, leaving only incident prescriptions for patients unique to one or other distribution. This improved the accuracy of SSA in some atypical instances with negligible affect on accuracy elsewhere. CONCLUSIONS: Our curve-fit method is equivalent to current methods in the literature for adjusting prescribing trends in SAA, with the advantage of providing adjustment incorporated in the SAA visualisation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12874-019-0781-1) contains supplementary material, which is available to authorized users.