Currently Viewing:
The American Journal of Managed Care November 2019
Population Health Screenings for the Prevention of Chronic Disease Progression
Maren S. Fragala, PhD; Dov Shiffman, PhD; and Charles E. Birse, PhD
Comprehensive Health Management Pharmacist-Delivered Model: Impact on Healthcare Utilization and Costs
Leticia R. Moczygemba, PhD, PharmD; Ahmed M. Alshehri, PhD; L. David Harlow III, PharmD; Kenneth A. Lawson, PhD; Debra A. Antoon, BSPharm; Shanna M. McDaniel, MA; and Gary R. Matzke, PharmD
One Size Does Not Always Fit All in Value Assessment
Anirban Basu, PhD; Richard Grieve, PhD; Daryl Pritchard, PhD; and Warren Stevens, PhD
Value Assessment and Heterogeneity: Another Side to the Story
Steven D. Pearson, MD, MSc
From the Editorial Board: Joshua J. Ofman, MD, MSHS
Joshua J. Ofman, MD, MSHS
Multimodality Cancer Care and Implications for Episode-Based Payments in Cancer
Suhas Gondi, BA; Alexi A. Wright, MD, MPH; Mary Beth Landrum, PhD; Jose Zubizarreta, PhD; Michael E. Chernew, PhD; and Nancy L. Keating, MD, MPH
Medicare Advantage Plan Representatives’ Perspectives on Pay for Success
Emily A. Gadbois, PhD; Shayla Durfey, BS; David J. Meyers, MPH; Joan F. Brazier, MS; Brendan O’Connor, BA; Ellen McCreedy, PhD; Terrie Fox Wetle, PhD; and Kali S. Thomas, PhD
Cost Analysis of COPD Exacerbations and Cardiovascular Events in SUMMIT
Richard H. Stanford, PharmD, MS; Anna D. Coutinho, PhD; Michael Eaddy, PharmD, PhD; Binglin Yue, MS; and Michael Bogart, PharmD
CKD Quality Improvement Intervention With PCMH Integration: Health Plan Results
Joseph A. Vassalotti, MD; Rachel DeVinney, MPH, CHES; Stacey Lukasik, BA; Sandra McNaney, BS; Elizabeth Montgomery, BS; Cindy Voss, MA; and Daniel Winn, MD
Importance of Reasons for Stocking Adult Vaccines
David W. Hutton, PhD; Angela Rose, MPH; Dianne C. Singer, MPH; Carolyn B. Bridges, MD; David Kim, MD; Jamison Pike, PhD; and Lisa A. Prosser, PhD
Currently Reading
Prescribing Trend of Pioglitazone After Safety Warning Release in Korea
Han Eol Jeong, MPH; Sung-Il Cho, MD, ScD; In-Sun Oh, BA; Yeon-Hee Baek, BA; and Ju-Young Shin, PhD

Prescribing Trend of Pioglitazone After Safety Warning Release in Korea

Han Eol Jeong, MPH; Sung-Il Cho, MD, ScD; In-Sun Oh, BA; Yeon-Hee Baek, BA; and Ju-Young Shin, PhD
The pioglitazone safety warning issued in South Korea, which recommended prescribing with careful attention among those with high risk of bladder cancer, led to a moderate decrease in pioglitazone users.
ABSTRACT

Objectives:
This study was conducted to determine the number of pioglitazone users before and after the issue of the pioglitazone safety warning (intervention) by South Korea’s Ministry of Food and Drug Safety on June 10, 2011.

Study Design: A quasi-experimental interrupted time series study was conducted to examine the number of pioglitazone and other antidiabetic drug users between 2009 and 2015.

Methods: We used the National Health Insurance Service–National Sample Cohort database to estimate the number of pioglitazone and other antidiabetic drug users between 2009 and 2015. Relative and absolute changes in the number of drug users were calculated with 95% CIs. Monthly numbers of drug users were presented according to the maximum likelihood estimation method, and a segmented regression analysis was performed to evaluate the effect of the intervention. A Durbin-Watson statistic and Dickey-Fuller test were used to assess autocorrelation and seasonality, respectively.

Results: A total of 80,724 patients with diabetes, including 12,249 pioglitazone users, were investigated. The relative change in pioglitazone users was –8.13% (95% CI, –8.41% to –7.86%). The intervention was associated with an immediate decrease of 177 pioglitazone users per 1000 patients with diabetes (P <.05). Without this intervention, the predicted proportion of pioglitazone users would be 90 per 1000 patients with diabetes, which is 1.5-fold higher than the actually observed rate of 60 per 1000 patients with diabetes.

Conclusions: This intervention led to a moderate decrease in pioglitazone users. Until further evidence is available, caution should be exercised when prescribing pioglitazone to patients with high potential risk of bladder cancer and alternative treatments should be considered.

Am J Manag Care. 2019;25(11):e342-e348
Takeaway Points
  • To our knowledge, no study has been conducted in South Korea to evaluate the effect of the pioglitazone safety warning about its risk of bladder cancer that was released by South Korea’s Ministry of Food and Drug Safety on June 10, 2011.
  • For pioglitazone, the relative change in the proportion of drug users per 1000 patients with diabetes was –8.13% (95% CI, –8.41% to –7.86%) and the absolute change was –1.04 (95% CI, –1.40 to –0.68) percentage points per 1000 patients with diabetes.
  • The pioglitazone safety warning was associated with an immediate decrease of 177 pioglitazone users per 1000 patients with diabetes whereas, if the intervention had not been implemented, the proportion of pioglitazone users would have shown an increasing trend.
Pioglitazone is a drug of the thiazolidinedione (TZD) class used to treat type 2 diabetes.1 In June 2011, a French study suggested an increased risk of bladder cancer among patients treated with pioglitazone, resulting in the withdrawal of this drug by the French government. A study conducted in the United States reported similar findings.2 Following these results, the US FDA issued a drug safety communication, followed by warnings from both the European Medicines Agency and the Australian Therapeutic Goods Administration reporting similar concerns. On June 10, 2011, South Korea’s Ministry of Food and Drug Safety (MFDS) also released a safety warning (hereafter referred to as “the intervention”) stating that pioglitazone should be prescribed with caution.3

A pioglitazone withdrawal study in France investigating the impact of pioglitazone’s regulatory withdrawal on antidiabetic drug use found no adverse events among patients with diabetes.4 On the other hand, an Australian and British study on TZD utilization trends reported that safety warnings were associated with decreased use of the respective drugs, rosiglitazone and pioglitazone.5,6 Furthermore, Taiwan’s FDA communicated the possible risks of bladder cancer associated with pioglitazone, and this regulatory action had a positive impact of decreasing the use of pioglitazone among high-risk patients.7

The data reported in previous studies had limitations because they were analyzed over a relatively short period of time. Although the withdrawal study in France was conducted from 2010 to 2014, the drug withdrawal took place in January 2011, thus resulting in a prewithdrawal period of only 12 months.4 This short prewithdrawal period may affect the predicted number of drug users. Another study conducted in Spain examining the effect of rosiglitazone’s safety warning analyzed data collected over only 3 years (2006-2008), an even shorter period (safety warnings for rosiglitazone were released throughout 2007 and 2008).8 With such short observation periods, application of a time lag before or after an intervention may not be feasible. Furthermore, pioglitazone use following the MFDS’ safety warning has yet to be evaluated in Korea.

The current study was therefore conducted to explore the proportion of pioglitazone users before and after the intervention between 2009 and 2015. Furthermore, we evaluated the impact of the intervention on pioglitazone use by comparing the use of other antidiabetic drugs. If numbers of both pioglitazone users and users of other antidiabetic drugs decreased, a cause other than our intervention may be behind it. We hypothesized that with the intervention, the proportion of pioglitazone users would decrease and lead to an increase in the proportion of patients using other antidiabetic drugs, indicating that safety warnings are an effective regulatory measure to prevent use and thus potential adverse outcomes.

METHODS

Data

This study was conducted using the nationwide population-based National Health Insurance Service–National Sample Cohort (NHIS-NSC) database, which includes approximately 1 million individuals randomly selected from almost the entire Korean population, using national claims data from January 1, 2009, to December 31, 2015 (described in detail elsewhere).9 The NHIS-NSC database contains anonymized patient codes along with sociodemographic characteristics; medical care history; medical care institution types; International Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes; and drug prescription information (generic name, prescription date, duration, and dosage).

Study Design

The interrupted time series (ITS) study design, a type of quasi-experimental research, is widely used when evaluating the effectiveness of population-level health interventions implemented at a clearly defined point in time.10 The design generally involves constructing a time series of population-level rates for a particular quality improvement focus and statistically testing for variations in the outcome rate in the time periods before and after implementation of an intervention designed to alter the outcome.11 A segmented regression approach was used with an autoregressive integrated moving average approach to test the effect of the intervention on the outcome of interest by using an appropriately defined impact model, as there was no remaining residual autocorrelation.10,11

Study Subjects

Study subjects included all patients found in the NHIS-NSC database 18 years or older with a diagnosis of diabetes (ICD-10 codes E10-E14), in both inpatient and outpatient settings, who were prescribed any antidiabetic drug between January 2009 and December 2015. The periods before (January 1, 2009, to June 10, 2011) and after (June 11, 2011, to December 31, 2015) the intervention were defined as shown in eAppendix A (eAppendices available at ajmc.com).


 
Copyright AJMC 2006-2019 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
x
Welcome the the new and improved AJMC.com, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up