Supplemental Material for The Impact of the COVID-19 Pandemic and the iPLEDGE REMS Update on Isotretinoin Prescription Delays and Interruptions: An Interrupted Time Series Analysis

eMethod 1: Cohort determination, data collection, definitions of outcomes, and analysis.

eTable I. Patient demographics, isotretinoin treatment information, and reasons for iPLEDGE-related delays and interruptions for patients with acne on isotretinoin stratified by time period.

eTable II. ITSA results for the monthly percentage of prescriptions with either iPLEDGE-Related Delays or Interruptions for all patients with acne on isotretinoin, stratified by iPLEDGE Category, and the difference between iPLEDGE Category.

eFigure 1. Interrupted Time Series Analysis (ITSA) for the monthly percentage of isotretinoin prescriptions with iPLEDGE-related delays for all patients with acne on isotretinoin from January 2018 to October 2023. The first vertical dashed line (March 16, 2020) indicates the onset of the COVID-19 Pandemic, with a 2.6% immediate increase in iPLEDGE-related delays (p<0.001) (shown by the orange vertical line) which had a stable trend during the pandemic time period (a 0.08% decrease per month, p=0.397). The second vertical dashed line (December 13, 2021) marks the transition to the new iPLEDGE system, showing a 5.0% immediate increase in monthly iPLEDGE-related delays (p<0.001) represented by the vertical blue dashed line which was sustained through the post-update period as shown by the post-iPLEDGE Update trend line in red (a 0.07% decrease per month, p=0.476).

eFigure 2. ITSA for the monthly percentage of isotretinoin prescriptions with iPLEDGE-related delays stratified by iPLEDGE category from January 2018 to October 2023. The first vertical dashed line (March 16, 2020) indicates the start of the COVID-19 pandemic, with a 4.0% immediate increase in monthly iPLEDGE-related delays for patients who can become pregnant (p<0.001) followed by a 0.1% per month decrease in iPLEDGE-related delays over the pandemic time period (p=0.027). For patients who cannot become pregnant, there was a 1.3% immediate increase in monthly iPLEDGE-related delays at the start of the pandemic (p=0.024) followed by a 0.1% decrease per month (p=0.024) throughout the pandemic time period. The second vertical dashed line (December 13, 2021) marks the iPLEDGE update, with patients who can become pregnant having a 6.0% immediate increase in monthly iPLEDGE-related delays (p<0.001) which persisted through the end of the post-update period as shown by the red trend line (a 0.1% decrease per month, p=0.133). Patients who cannot become pregnant had a 3.9% immediate increase in monthly iPLEDGE-related delays after the iPLEDGE update (p<0.001) without a significant change in the trend through the end of the post-update period, shown by the dashed blue trend line (a 0.12% per month decrease, p=0.053).

e方法1：队列确定、数据收集、结局定义及分析。
e表I：按时间段分层，对异维A酸治疗痤疮患者的患者人口统计学、异维A酸治疗信息以及iPLEDGE相关延迟和中断的原因进行描述。
e表II：对于所有接受异维A酸治疗的痤疮患者，按iPLEDGE类别分层，分析每月处方中出现iPLEDGE相关延迟或中断的处方比例，以及iPLEDGE类别之间的差异。
e图1：从2018年1月至2023年10月，对所有接受异维A酸治疗的痤疮患者的每月异维A酸处方中与iPLEDGE相关的延迟比例进行中断时间序列分析（ITSA）。第一条垂直虚线（2020年3月16日）表示COVID-19大流行的开始，iPLEDGE相关延迟在短时间内立即上升2.6%（p<0.001），并在大流行期间呈现稳定趋势（每月下降0.08%，p=0.397）。第二条垂直虚线（2021年12月13日）标志着新iPLEDGE系统的过渡，每月iPLEDGE相关延迟在短时间内立即上升5.0%（p<0.001），通过红色趋势线（每月下降0.07%，p=0.476）在更新后的期间内保持稳定。
e图2：从2018年1月至2023年10月，按iPLEDGE类别分层，对异维A酸处方中与iPLEDGE相关的延迟比例进行中断时间序列分析（ITSA）。第一条垂直虚线（2020年3月16日）表示COVID-19大流行的开始，对于可能怀孕的患者，每月iPLEDGE相关延迟在短时间内立即上升4.0%（p<0.001），随后在大流行期间每月下降0.1%（p=0.027）。对于不能怀孕的患者，在大流行开始时，每月iPLEDGE相关延迟在短时间内立即上升1.3%（p=0.024），随后在大流行期间每月下降0.1%（p=0.024）。第二条垂直虚线（2021年12月13日）标志着iPLEDGE更新，对于可能怀孕的患者，每月iPLEDGE相关延迟在短时间内立即上升6.0%（p<0.001），并持续到更新后的结束，如红色趋势线所示（每月下降0.1%，p=0.133）。对于不能怀孕的患者，在iPLEDGE更新后，每月iPLEDGE相关延迟在短时间内立即上升3.9%（p<0.001），在整个更新后的期间内趋势没有显著变化，如蓝色虚线所示（每月下降0.12%，p=0.053）。