View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Springer - Publisher Connector Drugs - Real World Outcomes (2015) 2:335–344 DOI 10.1007/s40801-015-0042-5 SHORT COMMUNICATION Physician and Pharmacist Understanding of the Risk of Urinary Retention with Retigabine (Ezogabine): A REMS Assessment Survey 1,2 3 4 5,6 Lianna Ishihara • Melissa Beck • Sara Travis • Olusegun Akintayo • Neil Brickel5 Published online: 7 October 2015 Ó The Author(s) 2015. This article is published with open access at Springerlink.com Abstract RTG/EZG and to evaluate the effectiveness of the com- Background The Risk Evaluation and Mitigation Strategy munication plan. (REMS) for retigabine/ezogabine (RTG/EZG) required an Methods This was a US-based, cross-sectional, non-in- evaluation of the effectiveness of the communication plan terventional, observational survey, conducted from Febru- to communicate about the risks with use of RTG/EZG. ary to April 2013, of physicians who had prescribed RTG/ Objective GlaxoSmithKline conducted a survey to assess EZG in the past year, and pharmacists who had dispensed understanding of the risk of urinary retention (UR) with an antiepileptic drug within the past 3 months. Thirteen primary objective questions (five specific to UR risk) were included in the survey, which assessed healthcare profes- sionals’ (HCPs’) understanding of UR risk and symptoms of acute UR associated with RTG/EZG. The primary out- Electronic supplementary material The online version of this article (doi:10.1007/s40801-015-0042-5) contains supplementary come was the proportion of HCPs correctly answering each material, which is available to authorized users. question. For each question, a proportion of correct responses C80 % was considered to represent sufficient & Lianna Ishihara [email protected] understanding of associated risks. Results Of 1028 HCPs screened, 373 participated. Six Melissa Beck [email protected] of 13 questions (3/5 specific to UR risk) met the C80 % Sara Travis [email protected] Olusegun Akintayo Key Points [email protected] Neil Brickel Survey results demonstrated a mixed level of [email protected] understanding of aspects of UR risk associated with 1 Department of Epidemiology, GlaxoSmithKline, Uxbridge, retigabine/ezogabine (RTG/EZG) among Middlesex, UK prescribers. 2 Present Address: Lundbeck SAS, 37–45 Quai du President Pharmacists displayed a lower level of understanding Roosevelt, 92130 Issy-les-Moulineaux, France than prescribers, probably due to the short time that 3 Regulated Healthcare Market Research, Concentrics RTG/EZG had been available for prescription. Research LLC, Indianapolis, IN, USA 4 Project Operations, Concentrics Research LLC, Indianapolis, A key insight from the survey was that the questions IN, USA should be focused on the objective to assess specific 5 risks and evaluate effectiveness of the Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, Uxbridge, Middlesex, UK communication plan, and additional questions should not be included to avoid adding complexity. 6 Present Address: Apotex Inc., Toronto, Canada 336 L. Ishihara et al. threshold for correct responses in the physician cohort. (DEA), in line with the Controlled Substances Act, in order No questions achieved this threshold in the total phar- to determine the scheduling status. macist group; however, four questions scored C80 % As a condition of approval, the FDA required that GSK when stratified by pharmacists who had dispensed RTG/ assess this communication plan’s effectiveness. Accord- EZG. ingly, a survey was conducted among a sample of HCPs to Conclusions Results demonstrated a mixed level of evaluate knowledge of UR risk with RTG/EZG [10]. The understanding of aspects of UR risk associated with RTG/ survey focused on the risks described in the DHCP letter EZG, although some risk questions did not meet the 80 % for RTG/EZG, and assessed where HCPs prefer to seek threshold, especially among pharmacists. This is likely to information for RTG/EZG (e.g., DHCP letters, website, have been due to the short time that RTG/EZG has been product labeling). Here we report the results of this survey. available and its limited use. This study provides the first evaluation of the REMS communication plan on the risk of UR with RTG/EZG. 2 Methods 1 Introduction 2.1 Study Design Retigabine (RTG; international nonproprietary name)/ This was a cross-sectional, non-interventional, observa- ezogabine (EZG; US adopted name) is an antiepileptic tional survey of HCPs who prescribe RTG/EZG or dis- drug (AED) approved in the US (as POTIGATM, pense AEDs. The study did not include intervention; GlaxoSmithKline [GSK] and Valeant) for the adjunctive therefore, institutional review board approval was not treatment of partial-onset seizures in adults who have deemed necessary. responded inadequately to several treatments and for whom the benefits outweigh the risk of retinal abnor- 2.2 Sampling and Study Population malities and potential decline in visual acuity [1]. In clinical studies investigating the efficacy and safety of From a Concentrics Research market research partner’s RTG/EZG, an increased risk of urinary retention (UR) custom database of more than 668,000 geographically and was reported in patients receiving RTG/EZG compared therapeutically diverse US HCPs, approximately 14,000 with placebo [2–6]. eligible physicians and pharmacists were contacted from a RTG/EZG was approved in June 2011 with a US Food demographically representative population who prescribe and Drug Administration (FDA) requirement for a Risk RTG/EZG (neurologists, neurosurgeons, epileptologists), Evaluation and Mitigation Strategy (REMS) [7]. According or dispense AEDs (pharmacists). The original mailing list to the FDA Amendments Act of 2007, the FDA may require for the DHCP letter included prescribers, emergency room a drug manufacturer to submit a REMS, which is intended physicians and urologists, the HCPs most likely to come to manage known or potential serious risks associated with a into contact with RTG/EZG-treated patients who may have drug and to ensure that the benefits of the drug outweigh the UR symptoms. This survey focused only on recruiting risks [8, 9]. The REMS for RTG/EZG consisted of a com- potential prescribers and the overlap between the DHCP munication plan for healthcare professionals (HCPs), mailing list and the Concentrics database is not known. including prescribing physicians and dispensing pharma- cists, designed to disseminate information on the risk of UR 2.3 Survey Inclusion, Exclusion, and Withdrawal with RTG/EZG and highlight the importance of advising Criteria patients to seek immediate attention for symptoms of UR, including inability to urinate and/or pain with urination. The Inclusion criteria included practicing physicians who had communication plan had two elements: (i) a Dear Health- prescribed RTG/EZG within the past year, and practicing care Professional (DHCP) letter, disseminated within pharmacists who had filled a prescription for at least one 4 weeks of first retail availability (May 7, 2012) and AED within the past 3 months. Physicians and pharmacists annually for the following 2 years; and (ii) a REMS pro- currently employed by, or who were representatives of, a gram website available at the time of launch (April 16, pharmaceutical company or manufacturer of medicines or 2012; no longer active). The delay between the approval of healthcare products, or who were contributors to, or editors the new drug application (NDA; June, 2011) and retail of, published guideline committees for epilepsy or UR, were availability was caused by the requirement for RTG/EZG to ineligible. Additionally, HCPs who previously participated be reviewed by the US Drug Enforcement Administration in the pilot REMS study for RTG/EZG, or who were Understanding of Retigabine Urinary Retention Risk 337 employees of GSK or Concentrics Research, were excluded. 3.2 Demographics and Baseline Characteristics HCPs could withdraw from the study at any time. Physicians reported that their primary specialty was neu- 2.4 Screening and Baseline Assessments rology (64 %) or epileptology (36 %). Pharmacists repor- ted community/retail (55 %) or hospital/clinic (45 %) as HCPs were contacted initially by telephone, email, or fax their primary specialty. Most HCPs had been practicing with an invitation to participate in the study, conducted medicine/pharmacy and prescribing/dispensing AEDs for from February through April 2013. A standardized 5–35 years. screening questionnaire conducted by telephone assessed Prescribing physicians treated patients across all ages, eligibility, demographics, and interest in study participa- and most reported a total number of more than 1000 tion. After recruitment, HCPs’ understanding of the patients, more than 100 of whom had epilepsy. Sixty per- symptoms and risks of UR with RTG/EZG was evaluated cent of physicians had prescribed, and 41 % of pharmacists by means of an online survey or telephone interview. had filled prescriptions for AEDs to more than 50 patients Thirty closed-ended questions were asked to assess the monthly during the past year. Most pharmacists had not following: demographics and prescribing/dispensing his- dispensed (77 %) RTG/EZG or answered (83 %) patients’ tory of each HCP; understanding of RTG/EZG key safety questions about RTG/EZG in the past year. Of those who messages based on US prescribing information and prac- had done so, 44 % reported