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Mary Elizabeth Jones, 1 Irene Petersen, 1 Kate Walters, 1 Cini Bhanu, 1 Jill Manthorpe, 2 Rosalind Raine, 3 Naaheed Mukadam, 4 Claudia Cooper 4 1Department of Primary Care and Population Health, University College London, London, UK; 2NIHR Health and Social Care Workforce Research Unit, King’s College London, London, UK; 3Epidemiology and Public Health, University College London, London, UK; 4Division of Psychiatry, University College London, London, UKCorrespondence: Claudia CooperDivision of Psychiatry, University College London, 6th Floor, Maple House, Tottenham Court Road, London W1T 7BN, UKTel +44 7759703235Email claudia.cooper@ucl.ac.ukPurpose: To test hypotheses that minority ethnic people with dementia in the UK receive fewer anti-dementia drugs and more psychotropic and anticholinergic drugs associated with harms.Patients and Methods: We analyzed UK primary care electronic health records from The Health Improvement Network (THIN) database (2014– 2016), comparing psychotropic drug prescribing initiation and duration between people with dementia from White, Black, and Asian ethnic groups. We repeated analyses in people (aged 50+) without dementia, to explore whether any differences found reflected prescribing patterns in the general older population, or were specific to dementia.Results: We included 53,718 people with and 1,648,889 people without dementia. Among people with dementia, compared to White ethnic groups, Asian people were less likely to be prescribed anti-dementia drugs when they were potentially indicated (adjusted prevalence rate ratio 0.86 (95% Confidence Interval 0.76– 0.98)), and received them for on average 15 days/year less. Compared to White groups, Asian and Black individuals with dementia were no more likely to take an antipsychotic drug, but those that had were prescribed them for 17 and 27 days/year more, respectively (190.8 (179.6– 199.1) and 200.7 (191.1– 206.5) days). Black people were less likely to be prescribed anxiolytics/hypnotics (0.60 (0.44– 0.8)), but the duration these drugs were prescribed was similar across ethnic groups. Asian people were more likely to be prescribed anticholinergic drugs (1.43 (1.19– 1.73)), in analyses unadjusted for cardiovascular comorbidities. Among people without dementia, those in the Asian and Black ethnic groups were less likely to be prescribed psychotropic drugs, relative to people from White groups.Conclusion: Among people with dementia, Asian groups received less potentially beneficial symptomatic treatments, and Asian and Black groups were prescribed antipsychotic drugs for longer than White ethnic groups. Our findings may indicate care inequalities.Keywords: ethnicity, prevalence rate ratio, medication, prescription duration

PURPOSE: To improve the precision of prescription duration estimates when using the reverse waiting time distribution (rWTD).METHODS: For each patient we uniformly sampled multiple random index dates within a sampling window of length δ . For each index date, we identified the last preceding prescription redemption, if any, within distance δ . Based on all pairs of last prescription and index date, we estimated prescription durations using the rWTD with robust variance estimation. In simulation studies with increasing misspecification we investigated bias, root mean square error (RMSE) and coverage probability of the rWTD using multiple index dates (1, 5, 10, and 20). We applied the method to Danish data on warfarin prescriptions from 2013 to 2014 stratifying by and adjusting for sex and age. RESULTS: In simulation scenarios without misspecification, the relative bias was negligible (-0.04% to 0.01%) and nominal coverage probabilities almost retained (93.8%-95.4%). RMSE decreased with the number of random index dates (e.g., from 1.3 with 1 index date to 0.6 days with 5). With misspecification, the relative bias was higher irrespective of the number of index dates. Precision increased with the number of index dates, and hence coverage probabilities decreased. When estimating durations of warfarin prescriptions in Denmark, precision increased with number of index dates, in particular in strata with few patients (e.g., men 90+ years: width of 95% confidence interval was 16.2 days with 5 index dates versus 35.4 with 1).CONCLUSIONS: Increasing the number of random index dates used with the rWTD improved precision without affecting bias.

OBJECTIVES: 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.

Kristina Laugesen,1 Henrik Støvring,2 Jesper Hallas,3 Anton Pottegård,3 Jens Otto Lunde Jørgensen,4 Henrik Toft Sørensen,1 Irene Petersen1,5 1Department of Clinical Epidemiology, Aarhus University Hospital, 2Department of Public Health, Aarhus University, Aarhus, 3Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, 4Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; 5Department of Primary Care and Population Health, University College London, London,UK Purpose: Glucocorticoids are widely used medications. In many pharmacoepidemiological studies, duration of individual prescriptions and definition of treatment episodes are important issues. However, many data sources lack this information. We aimed to estimate duration of individual prescriptions for oral glucocorticoids and to describe continuous treatment episodes using the parametric waiting time distribution.Methods: We used Danish nationwide registries to identify all prescriptions for oral glucocorticoids during 1996–2014. We applied the parametric waiting time distribution to estimate duration of individual prescriptions each year by estimating the 80th, 90th, 95th and 99th percentiles for the interarrival distribution. These corresponded to the time since last prescription during which 80%, 90%, 95% and 99% of users presented a new prescription for redemption. We used the Kaplan–Meier survival function to estimate length of first continuous treatment episodes by assigning estimated prescription duration to each prescription and thereby create treatment episodes from overlapping prescriptions.Results: We identified 5,691,985 prescriptions issued to 854,429 individuals of whom 351,202 (41%) only redeemed 1 prescription in the whole study period. The 80th percentile for prescription duration ranged from 87 to 120 days, the 90th percentile from 116 to 150 days, the 95th percentile from 147 to 181 days, and the 99th percentile from 228 to 259 days during 1996–2014. Based on the 80th, 90th, 95th and 99th percentiles of prescription duration, the median length of continuous treatment was 113, 141, 170 and 243 days, respectively.Conclusion: Our method and results may provide an important framework for future pharmacoepidemiological studies. The choice of which percentile of the interarrival distribution to apply as prescription duration has an impact on the level of misclassification. Use of the 80th percentile provides a measure of drug exposure that is specific, while the 99th percentile provides a sensitive measure. Keywords: glucocorticoids, pharmacoepidemiology, prescription duration, parametric waiting time distribution

PURPOSE: A pervasive problem in registry-based pharmacoepidemiological studies is what exposure duration to assign to individual prescriptions. The parametric waiting time distribution (WTD) has been proposed as a method to estimate such durations. However, when prescription durations vary due to seasonal stockpiling, WTD estimates will vary with choice of index date. To counter this, we propose using random index dates.METHODS: Within a calendar period of a given length, δ, we randomly sample individual index dates. We include the last prescription redemption prior to the index date in the analysis. Only redemptions within distance δ of the index date are included. In a simulation study with varying types and degrees of stockpiling at the end of the year, we investigated bias and precision of the reverse WTD with fixed and random index dates, respectively. In addition, we applied the new method to estimate durations of Norwegian warfarin prescriptions in 2014.RESULTS: In simulation settings with stockpiling, the reverse WTD with random index dates had low relative biases (-0.65% to 6.64%) and high coverage probabilities (92.0% to 95.3%), although when stockpiling was pronounced, coverage probabilities decreased (2.7% to 85.8%). Using a fixed index date was inferior. The estimated duration of warfarin prescriptions in Norway using random index dates was 131 (130; 132) days.CONCLUSIONS: In the presence of seasonal stockpiling, the WTD with random index dates provides estimates of prescription durations, which are more stable, less biased and with better coverage when compared to using a fixed index date.

Purpose To test hypotheses that minority ethnic people with dementia in the UK receive fewer anti-dementia drugs and more psychotropic and anticholinergic drugs associated with harms. Patients and Methods We analyzed UK primary care electronic health records from The Health Improvement Network (THIN) database (2014–2016), comparing psychotropic drug prescribing initiation and duration between people with dementia from White, Black, and Asian ethnic groups. We repeated analyses in people (aged 50+) without dementia, to explore whether any differences found reflected prescribing patterns in the general older population, or were specific to dementia. Results We included 53,718 people with and 1,648,889 people without dementia. Among people with dementia, compared to White ethnic groups, Asian people were less likely to be prescribed anti-dementia drugs when they were potentially indicated (adjusted prevalence rate ratio 0.86 (95% Confidence Interval 0.76–0.98)), and received them for on average 15 days/year less. Compared to White groups, Asian and Black individuals with dementia were no more likely to take an antipsychotic drug, but those that had were prescribed them for 17 and 27 days/year more, respectively (190.8 (179.6–199.1) and 200.7 (191.1–206.5) days). Black people were less likely to be prescribed anxiolytics/hypnotics (0.60 (0.44–0.8)), but the duration these drugs were prescribed was similar across ethnic groups. Asian people were more likely to be prescribed anticholinergic drugs (1.43 (1.19–1.73)), in analyses unadjusted for cardiovascular comorbidities. Among people without dementia, those in the Asian and Black ethnic groups were less likely to be prescribed psychotropic drugs, relative to people from White groups. Conclusion Among people with dementia, Asian groups received less potentially beneficial symptomatic treatments, and Asian and Black groups were prescribed antipsychotic drugs for longer than White ethnic groups. Our findings may indicate care inequalities.

Kristina Laugesen,1 Henrik Støvring,2 Jesper Hallas,3 Anton Pottegård,3 Jens Otto Lunde Jørgensen,4 Henrik Toft Sørensen,1 Irene Petersen1,5 1Department of Clinical Epidemiology, Aarhus University Hospital, 2Department of Public Health, Aarhus University, Aarhus, 3Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, 4Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; 5Department of Primary Care and Population Health, University College London, London,UK Purpose: Glucocorticoids are widely used medications. In many pharmacoepidemiological studies, duration of individual prescriptions and definition of treatment episodes are important issues. However, many data sources lack this information. We aimed to estimate duration of individual prescriptions for oral glucocorticoids and to describe continuous treatment episodes using the parametric waiting time distribution.Methods: We used Danish nationwide registries to identify all prescriptions for oral glucocorticoids during 1996–2014. We applied the parametric waiting time distribution to estimate duration of individual prescriptions each year by estimating the 80th, 90th, 95th and 99th percentiles for the interarrival distribution. These corresponded to the time since last prescription during which 80%, 90%, 95% and 99% of users presented a new prescription for redemption. We used the Kaplan–Meier survival function to estimate length of first continuous treatment episodes by assigning estimated prescription duration to each prescription and thereby create treatment episodes from overlapping prescriptions.Results: We identified 5,691,985 prescriptions issued to 854,429 individuals of whom 351,202 (41%) only redeemed 1 prescription in the whole study period. The 80th percentile for prescription duration ranged from 87 to 120 days, the 90th percentile from 116 to 150 days, the 95th percentile from 147 to 181 days, and the 99th percentile from 228 to 259 days during 1996–2014. Based on the 80th, 90th, 95th and 99th percentiles of prescription duration, the median length of continuous treatment was 113, 141, 170 and 243 days, respectively.Conclusion: Our method and results may provide an important framework for future pharmacoepidemiological studies. The choice of which percentile of the interarrival distribution to apply as prescription duration has an impact on the level of misclassification. Use of the 80th percentile provides a measure of drug exposure that is specific, while the 99th percentile provides a sensitive measure. Keywords: glucocorticoids, pharmacoepidemiology, prescription duration, parametric waiting time distribution