Empirical validation of the reverse parametric waiting time distribution and standard methods to estimate prescription durations for warfarin.

PURPOSE: In many prescription databases, the duration of treatment for the single prescription is not recorded. This study aimed to validate 2 different types of approaches for estimating prescription durations, using the oral anticoagulant warfarin as a case. METHODS: The approaches undergoing empirical validation covered assumptions of a fixed daily intake of either 0.5 or 1.0 defined daily dose (DDD), as well as estimates based on the reverse parametric waiting time distribution (rWTD), with different sets of covariates. We converted estimates of prescription duration to daily dose and compared them to prescribed daily dose as recorded in a clinical registry (using Bland-Altman plots). Methods were compared based on their average prediction error (logarithmic scale) and their limit of agreement ratio (ratio of mean error ± 1.96 SD after transformation to original scale). RESULTS: Estimates of daily doses were underestimated by 19% or overestimated by 62% when assumptions of 0.5 or 1.0 DDD were applied. The limit of agreement ratio was 6.721 for both assumptions. The rWTD-based approaches performed better when using the estimated mean value of the inter-arrival density, yielding on average negligible bias (relative difference of 0 to 2%) and with limit of agreement ratios decreasing upon additional covariate adjustment (from 6.857 with no adjustment to 4.036 with the fully adjusted model). CONCLUSIONS: Comparing the different methods, the rWTD algorithm performed best and led to unbiased estimates of prescribed doses and thus prescription durations and reduced misclassification on the individual level upon inclusion of covariates.

Use of Tic-Suppressing Medication and Other Psychotropic Drugs in Children and Adolescents with Newly Diagnosed Tic Disorders in Denmark.

Objective: Only few psychotropic drugs are approved to treat tic disorders. The aim was to describe use of tic-suppressing medication and other psychotropic drugs in children with tics. Methods: Using nationwide registries, we identified children receiving a tic diagnosis in Denmark during 2006-2017 and extracted data on tic-suppressing medication and other psychotropic drugs. Results: Antipsychotics were used by 12%. Use of tic-suppressing medication increased with age and varied according to sex. Over time less children with tics were medicated (from 44% to 38% in the total use of psychotropic drugs) mainly due to decreased use of antipsychotics (from 18% to 6.4%). In recent years, use of aripiprazole exceeded that of risperidone (38% vs. 35%), although risperidone was most often first choice (34%) followed by aripiprazole (22%). Most children stayed on their initial treatment. Attention-deficit/hyperactivity disorder medication (27%) was the most common additional psychotropic drug class used. Regional variations were found in the treatment of tics. Hospital specialists were mainly responsible for treatment. Conclusions: Most children with tics do not use tic-suppressing or other psychotropic drugs. The use of aripiprazole superseded risperidone, however risperidone remains the most common first-choice treatment. Treatment was mainly handled by specialists, which is reassuring given the lack of national guidelines, however, regional variations merit further attention as do the variation in treatment between young girls and boys.