Valproate utilisation trends among women of childbearing potential in Ireland between 2014 and 2019: A drug utilisation study using interrupted time series

Abstract

Purpose: This study aimed to examine trends in valproate use among women of childbearing potential (WCBP) aged 16-44 years in Ireland following two European-directed regulatory interventions in December 2014 and April 2018.

Methods: This was a repeated cross-sectional study using monthly national pharmacy claims data, to examine trend changes in the prevalence of valproate use among WCBP pre and post two separate regulatory events in December 2014 and April 2018. Annual population estimates from the Central Statistics Office were used to calculate the prevalence rate per 1000 eligible women. Segmented regression analysis of interrupted time series with negative binomial regression was used to examine rates for WCBP aged 16-44 years, and by 10-year age groups. Prevalence ratios (PR) are presented with 95% confidence intervals (CIs).

Results: Among WCBP aged 16-44 years, there was no statistically significant change in the month-to-month prevalence ratio in the post- compared to pre-December 2014 intervention period. A significant decline was, however, observed in the post-, compared to pre-April 2018 intervention period (PR = 0.998, [95% CIs: 0.996, 1.000]; p = 0.029). Among those aged 16-24 years, a significant decreasing trend in the month-to-month prevalence ratio was found in the post- compared to pre-December 2014 intervention period (PR = 0.991, [95% CIs: 0.984, 0.998];p <0.01). A marginal effect was observed in the post- compared to pre-April 2018 intervention period for those aged 25-34 years (PR = 0.996, [95% CIs: 0.992, 1.000]; p = 0.048).

Conclusion: Although no evidence of change was observed following the December 2014 intervention period, a significant decline in the prevalence ratio of valproate use was observed after the 2018 intervention, which may reflect the introduction of the most recent contraindication measures.

Keywords: European medicines agency; interrupted time series; pregnancy prevention programme; sodium valproate; teratogenicity.

FIGURE 1

Timeline for segmented regression analysis according to the first and second EMA regulatory interventions. DHPC, direct healthcare professional communication; EMA, European Medicines Agency

FIGURE 2

Prevalence per 1000 WCBP aged 16–44 years of valproate use overall (GMS, DPS, and LTI) and by community drug scheme between 2014 and 2019, and a time series interruption where the 2014 and 2018 European Medicines Agency regulatory intervention is indicated by the vertical black line. DPS, drugs payment scheme; GMS, general medical services; LTI, long‐term illness

FIGURE 3

Overall (GMS, DPS, and LTI) prevalence per 1000 of women of childbearing potential using valproate (by 10‐year age groups) between 2014 and 2019, and a time series interruption where the 2014 and 2018 European Medicines Agency regulatory intervention is indicated by the vertical black line. DPS, drugs payment scheme; GMS, general medical services; LTI, long‐term illness