Drug Safety Information Research Articles

Patients' Knowledge of Key Messaging in Drug Safety Communications for Zolpidem and Eszopiclone: A National Survey.

Drug Safety Communications (DSCs) are used by the Food and Drug Administration (FDA) to inform health care providers, patients, caregivers, and the general public about safety issues related to FDA-approved drugs. To assess patient knowledge of the messaging contained in DSCs related to the sleep aids zolpidem and eszopiclone, we conducted a large, cross-sectional patient survey of 1,982 commercially insured patients selected by stratified random sampling from the Optum Research Database who had filled at least two prescriptions for either zolpidem or eszopiclone between July 1, 2012 and June 30, 2013. Among the 594 respondents (32.7% response rate), two-thirds reported hearing generally about drug safety information prior to starting a new drug, with the remaining one-third "rarely" or "never" hearing such information. Providers and pharmacists were primary sources of drug safety information. Two-thirds of zolpidem users and half of eszopiclone users reported having heard about the related DSC messages, ability to accurately identify the major factual messages was limited (overall median 2 correct out of 5, with men and those reporting higher educational level scoring higher [2/5 vs. 1/5, p=0.001]). Respondents reacted to new drug safety information about their sleep aids by reporting that they would want to learn about alternative ways to help them sleep (70%) and seek out more information about the safety of their specific sleeping pill (59-78%). Opportunities may exist for the FDA to work with providers and pharmacies to help ensure the DSC information is more widely received and is more fully understood by those taking the affected medications.

Factors that influence the intention to use mobile phone caller tunes for patient reporting of adverse drug reactions: a qualitative study.

Background:Patient reporting of adverse drug reactions (ADRs) is low in low- and middle-income countries, in part because of poor awareness to report. With the increase in mobile subscription, mobile phones can be used as a platform to disseminate information on ADRs. The aim of this study was to qualitatively assess the potential of using mobile phone caller tunes (the message or sound the caller hears before the receiver answers the call) to encourage patient reporting of ADRs.Methods:A total of 38 key informant interviews and 12 focus group discussions (57 participants in groups of 4–5) were conducted in Accra, Ghana. The transcripts were analysed using key constructs of the Technology Acceptance Model (TAM) including perceived usefulness, perceived ease of use, and behavioural intention to use caller tunes for patient reporting of ADRs.Results:Respondents mentioned lack of knowledge on reporting ADRs, and their willingness to use mobile phone caller tunes to promote patient reporting of ADRs. Many respondents pointed out how ADRs usually led to discontinuity in medication use, usually without consultation with health professionals. Caller tunes were regarded an innovative, accessible and convenient platform to disseminate information on ADRs. Most respondents intended to use caller tunes with drug safety information to promote ADR reporting, particularly to help their friends and family members. Simplicity of the message, use of songs or messages in local languages and price of downloading the caller tunes were important considerations.Conclusion:There is a need for the creation and testing of caller tunes on ADRs in Ghana to promote patient or consumer reporting of ADRs. Further studies are needed to assess factors that could influence the creation and use of caller tunes to disseminate information on drug safety.

Use of drug safety information in Japanese facilities

Use of drug safety information in Japanese facilities

The usefulness of listening social media for pharmacovigilance purposes: a systematic review

ABSTRACTIntroduction: Social media mining could be a possible strategy to retrieve drug safety information. The mining of social media is a complex process under progressive evolution, falling into three broad categories: listening (safety data reporting), engaging (follow-up), and broadcasting (risk communication). This systematic review is aimed at evaluating the usefulness and quality of proto-signals by social media listening.Areas covered: In this systematic search, performed according to MOOSE and PRISMA statements, we selected studies, published in MEDLINE, EMBASE, and Google Scholar until 31 December 2017, that listened at least one social media to identify proto-adverse drug events and proto-signals.Expert opinion: The selected 38 studies identified serious and unexpected proto-adverse drug events characterized by poorer information quality as compared with spontaneous reporting databases. This feature allows rarely the evaluation of causal relationships. Proto-signals identified by social media listening had the potential of anticipating pre-specified known signals in only six studies. Moreover, the personal perception of patients reported in social media could be used to implement effective risk communication strategies. However, signal detection in social media cannot be currently recommended for routine pharmacovigilance, due to logistic and technical issues.

The reporting of safety among drug systematic reviews was poor before the implementation of the PRISMA harms checklist

ObjectivesTo examine, through a cross-sectional survey, how well safety information was reported among drug systematic reviews predating PRISMA harms checklist and explore factors associated with better reporting. Study Design and SettingWe searched PubMed to identify all systematic reviews published in the Cochrane Database of Systematic Review or the core clinical journals in 2015, one year before the PRISMA harms checklist was published. We randomly selected, in a 1:1 ratio, Cochrane and non-Cochrane systematic reviews assessing drug effects (including both efficacy and safety). We used the PRISMA harms checklist published in 2016 to assess the quality of reporting of drug safety information. Multivariable linear regression analyses were used to explore the association of six prespecified variables with more complete reporting of PRISMA harms items. ResultsWe included 120 systematic reviews, including 60 Cochrane and 60 non-Cochrane reviews. Scores on the PRISMA harms checklist (23 items) were low (median 4, [first, third quartile: 2, 6]), with no difference between Cochrane and non-Cochrane reviews (4.5 [2, 7] vs. 4 [2.5, 5]; P = 0.29). Among all eligible reviews, only one item (i.e., state conclusions in coherence with the review findings) was reported adequately (proportion of adherence 81.6%); proportion of reporting for other items ranged from 1.7% to 68.3%. The four essential reporting items from PRISMA harms checklist were also poorly complied (proportion of adherence ranged from 1.7% to 9.2%). Multivariable linear regression analyses found no significant associations between any study characteristic and reporting on the PRISMA harms, likely because of limited variability in scores across studies. ConclusionsThe reporting of safety information was poor both for Cochrane and non-Cochrane drug systematic reviews predating PRISMA harms checklist. The findings suggested a strong need to use the PRISMA harms checklist for reporting safety among drug systematic reviews.

Adverse drug reactions in hospitalized paediatric patients in a tertiary care center in Kerala, India

Background: Drug safety information about children is scarcely available. This study aims to describe the ADRs in hospitalized paediatric patients under 12 years of age in paediatrics wards of DM WIMS Hospital, Wayanad, Kerala, a tertiary care center in southern part of India.Methods: A retrospective study based on data collected as per the ongoing pharmacovigilance program of India (PvPI) was conducted for twelve months period in order to study the ADRs in hospitalized paediatric patients under 12 years of age with at least one medication prescribed. The study was conducted in paediatrics wards of DM WIMS Hospital, Wayanad. WHO-UMC scale and Naranjo´s Algorithm was used to evaluate causality, the modified Hartwig and Siegel assessment scale was used to establish severity and the Schumock and Thornton criteria was used to determine preventability.Results: Forty-two children (42) who experienced 55 ADRs were included in the study. The frequency was higher in children under 1 year of age (47.62%). Emergence of ADRs was higher in male patients (59.52%), in those used three or more medicines together (71.43%) and in those with systemic antibiotics (58.18%).Conclusions: Being the first study from Kerala in paediatric patients, it is an important contribution to drug safety profile in children from this region of India. ADRs frequency and other descriptive characteristics are provided for the enrolled children under 12 years of age. ADRs are an additional burden of morbidity and risk, particularly in those who used several medicines, including antibiotics.

Review of the Methods to Obtain Paediatric Drug Safety Information: Spontaneous Reporting and Healthcare Databases, Active Surveillance Programmes, Systematic Reviews and Meta-analyses.

Knowledge of drugs safety collected during the pre-marketing phase is inevitably limited because the randomized clinical trials (RCTs) are rarely designed to evaluate safety. The small and selective groups of enrolled individuals and the limited duration of trials may hamper the ability to characterize fully the safety profiles of drugs. Additionally, information about rare adverse drug reactions (ADRs) in special groups is often incomplete or not available for most of the drugs commonly used in the daily clinical practice. In the paediatric setting several highimpact safety issues have emerged. Hence, in recent years, there has been a call for improved post-marketing pharmacoepidemiological studies, in which cohorts of patients are monitored for sufficient time in order to determine the precise risk-benefit ratio. In this review, we discuss the current available strategies enhancing the post-marketing monitoring activities of the drugs in the paediatric setting and define criteria whereby they can provide valuable information to improve the management of therapy in daily clinical practice including both safety and efficacy aspects. The strategies we cover include the signal detection using international pharmacovigilance and/or healthcare databases, the promotion of active surveillance initiatives which can generate complete, informative data sets for the signal detection and systematic review/meta-analysis. Together, these methods provide a comprehensive picture of causality and risk improving the management of therapy in a paediatric setting and they should be considered as a unique tool to be integrated with post-marketing activities.

Potential negative impact of informing patients about medication side effects: a systematic review.

Background Pharmacovigilance, as it is carried out primarily by healthcare professionals is more focused on being very objective in nature. Acknowledging the importance of the subjective experience of patients in pharmacovigilance was underpinned by its unique ability to bring about a more holistic understanding through the deep information unraveled by the patients. Medication safety-related information has to be shared with patients to allow them to be actively involved in their therapy andpharmacovigilance. Despite the advantages of sharing information, it stands to reasons whether sharing information related to possible side effects would negatively affect patients and impinge upon their treatment plan and process. Aimof the Review The purpose of this systematic review was to critically assess the potential negative impact of informing patients about medication side effects by written and/or oral information on medication compliance, occurrence/development of suspected side effects and clinical outcomes. Method A comprehensive search was conducted in PubMed, and Cochrane library to identify potential records between the year 1975 and 2017; then titles, abstracts, and full texts were screened using the inclusion criteria to filter out irrelevant studies. The data extraction, and the results were narratively synthesized and presented in tables. Results A total of 2012 articles were screened for inclusion, 32 full-text articles were assessed for eligibility and finally resulting in the inclusion of 17 randomized control studies which met the set criteria. Findings unraveled that the educational intervention did not result in increased occurrence/reporting of side effects in most of the evaluated studies; except 4 studies, and no significant impact on compliance to medications and negative clinical outcome was observed. Apprehension of negative events to medications were observed in two of the four studies which evaluated these parameters. Conclusion The present review did not find enough evidence to support the over concerns on the potential negative impact of sharing of information on the adverse effects to patients, though the influence could manifest as nocebo-effect. The various components and methods employed for this information sharing process can influence the potential impact of this activity. These concerns about the undesirable effects should not deter the active involvement of patients in pharmacovigilance activities. There is a definite need to have more studies in this area, where much of concern still does exist among the various stakeholders of drug safety information.

What is the quality of drug safety information for patients: An analysis of REMS educational materials.

BackgroundPoor‐quality patient drug information has been identified as a major cause of preventable medication errors in the United States. The US Food and Drug Administration (FDA) has the authority to require marketing authorization holders of medicinal products to implement risk evaluation and mitigation strategies (REMS) to ensure that the benefits of a drug or biological product outweigh its risks. Aside from medication guides, no research has been conducted to assess the quality of patient‐targeted REMS materials, including whether, and to what extent, patients find these materials understandable and actionable.PurposeTo describe the readability, understandability, and actionability of patient educational materials in currently approved REMS programs, and to highlight opportunities for improving both the quality and effectiveness of these important drug safety tools.MethodsSeventy‐seven REMS programs were identified from the FDA REMS database. We excluded medication guides (MGs) from our analysis because of the fact that there is a mandatory MG template. Based on this, we identified a total of 27 (non‐MG) REMS patient materials on the FDA REMS website for analysis purposes. The materials were tested for readability using the Lexile Measure, the Gunning Fog Index, and Flesch Kincaid and then assessed using the Patient Education Materials Assessment Tool for printable materials, for understandability and actionability.ResultsTwenty‐three of 77 (30%) REMS programs used educational materials to communicate serious risks to patients, yielding a total of 27 REMS patient materials for analysis. The median readability score for these materials was at a ninth‐grade reading level or higher. While most (89%) of these patient education materials met established criteria for being understandable, less than half (49%) were deemed actionable.DiscussionCurrently approved REMS patient materials fell short in terms of recommended reading level, and over half did not meet recommended standards for actionability. Developers of these materials should apply plain language principles when design these materials to improve their readability and to assess both understandability and actionability in order to increase the effectiveness when distributed to patients.

How to Identify Organizational High-Alert Medications.

High-alert medications may cause significant patient harm when used in error. Hospital-specific safety data should be used to customize high-alert medication lists to fit the local context. The aim of this study was to identify organizational high-alert medications by evaluating university hospital's data on adverse drug reaction (ADR) and medication error (ME). The Anatomical Therapeutic Chemical (ATC) codes and top active substances in ADR (n = 401) and ME (n = 11,668) reports of Helsinki University Hospital from 2015-2016 were analyzed and compared with hospitals' drug consumption and the Institute for Safe Medication Practices' (ISMP) list of high-alert medications. The top ATC groups and active substances in ADR and ME reports were not similar. The most numerous ATC groups were L, antineoplastic and immunomodulating agents (30%) in ADRs and N, nervous system (26%) in MEs. According to ADR and ME reports, several high-alert medications from Institute for Safe Medication Practices' lists, such as antineoplastic agents, antithrombotics, opioids, and insulins, should be considered high-alert medications also in Helsinki University Hospital. Although no ADR reports of amphotericin B existed, it had the highest number of MEs causing severe/moderate harm or unexpected reactions relative to its consumption. To identify organizational high-alert medications, both drug safety information and medication safety information should be used. Adverse drug reaction and ME data are needed to recognize high-alert medications, but these should also be combined with a literature search and local expert opinions.

Diclofenac in the treatment of pain in patients with rheumatic diseases.

Diclofenac, a phenylacetic acid derivative, is a drug demonstrating high efficacy after oral administration in the treatment of pain and physical disability in rheumatic diseases. In view of the adverse effects associated with using diclofenac, it is necessary to consider all known drug safety information before the drug is selected for therapy and the dosage regimen is set for individual patients. Selecting an oral dosage form with specific properties determined by excipients is a method to improve the availability of the drug substance and, at the same time, minimize adverse drug reactions. An alternative to tablet or capsule dosage forms is diclofenac application to the skin. The proven efficacy of this method is further improved through the use of transdermal penetration enhancers and vehicle ingredients which provide dosage forms with specific physical properties.

Interest in a Mobile App for Two-Way Risk Communication: A Survey Study Among European Healthcare Professionals and Patients.

IntroductionPreviously, an app has been developed for healthcare professionals (HCPs) and patients to report adverse drug reactions (ADRs) to national medicines agencies and to receive drug safety information.ObjectiveThis study aimed to assess (1) European HCPs’ and patients’ interest in an app for this two-way risk communication; (2) their preferences and perceptions towards specific app characteristics; and (3) which HCPs and patients are particularly interested in the app. In addition, these aspects were studied specifically for the countries where such an app was already available, i.e. Croatia, The Netherlands, and The UK.MethodsEuropean HCPs and patients were asked to complete a web-based survey developed in the context of the Web-Recognizing Adverse Drug Reactions (Web-RADR) project. Data on app interest and preferences and perceptions towards app characteristics were analysed descriptively. Logistic regression analyses were conducted to assess the association of HCP characteristics and patient characteristics on the level of interest in the app (i.e. very interested vs. not/somewhat interested).ResultsIn total, 399 HCPs and 656 patients completed the survey. About half of the patients (48%; ranging from 38% from The Netherlands to 54% from The UK), and 61% of the HCPs (ranging from 42% from The Netherlands to 54% from The UK) were very interested in the app. A faster means of reporting ADRs and easier access to the reporting form were the main perceived benefits. HCPs and patients who already use a health app were particularly interested in the app (HCPs: odds ratio [OR] 3.52; 95% confidence interval [CI] 1.96–6.30, patients: OR 1.64; 95% CI 1.19–2.27).ConclusionsAn app is positively perceived by HCPs and patients for reporting ADRs quickly and for receiving drug safety information from national medicines agencies. In particular, HCPs and patients who already use other health apps were interested in the app.Electronic supplementary materialThe online version of this article (10.1007/s40264-018-0648-0) contains supplementary material, which is available to authorized users.

Making Patient-focused Information Provision a Reality: One Company's Approach

In recent years, as the market has seen the appearance of innovative medical products with novel mechanisms of action, adverse reactions that cannot be expected from the approved product label are being detected in the postmarketing phase. It is increasingly important to undertake timely product label updates and other drug safety measures through the monitoring, early detection, and reporting of adverse reactions. In 2013, the risk management plan (RMP) system was introduced in Japan. An RMP documents efforts to ensure the safety of a medical product, and sharing the RMP with stakeholders results in enhanced postmarketing safety measures. Healthcare providers have already started to utilize RMPs, but issues with perception and utilization remain. The industry, regulators, and academia are also working together to facilitate the use of RMPs. With the implementation of the RMP requirement, pharmaceutical companies are seeking to improve safety assurance by enhancing their drug safety functions, including the collection, assessment, and dissemination of drug safety information. Chugai Pharmaceutical is starting a completely new approach to patient-focused information provision, exemplified by the "PMS & SAFETY DB Tools," designed to give healthcare providers quick access to its extensive database of real-world drug safety information. This paper introduces Chugai Pharmaceutical's new efforts to manage adverse reactions and raises issues for future consideration.

Frequent discussion of insomnia and weight gain with glucocorticoid therapy: an analysis of Twitter posts

In recent years, social media websites have been suggested as a novel, vast source of data which may be useful for deriving drug safety information. Despite this, there are few published reports of drug safety profiles derived in this way. The aims of this study were to detect and quantify glucocorticoid-related adverse events using a computerised system for automated detection of suspected adverse drug reactions (ADR) from narrative text in Twitter, and to compare the frequency of specific ADR mentions within Twitter to the frequency and patterns of spontaneous ADR reporting to a national drug regulatory body. Of 159,297 tweets mentioning either prednisolone or prednisone between 1st October 2012 and 30th June 2015, 20,206 tweets were deemed to contain information resembling an ADR. The top AE MedDRA® Preferred Terms were ‘insomnia’ and ‘weight increased’, both recognised non-serious but common side effects. These were proportionally over-reported in Twitter when compared to spontaneous reports in the UK regulator’s ADR reporting scheme. Serious glucocorticoid related AEs were reported less frequently. Pharmacovigilance using Twitter data has the potential to be a valuable, supplementary source of drug safety information. In particular, it can illustrate which drug side effects patients discuss most commonly, potentially because of important impacts on quality of life. This information could help clinicians to inform patients about frequent and relevant non-serious side effects as well as more serious side effects.

Clozapine-Induced Gastrointestinal Hypomotility: A 22-Year Bi-National Pharmacovigilance Study of Serious or Fatal ‘Slow Gut’ Reactions, and Comparison with International Drug Safety Advice

IntroductionClozapine is the preferred antipsychotic for treatment-resistant schizophrenia, but has significant adverse effects, including gastrointestinal hypomotility or ‘slow gut’, which may result in severe constipation, ileus, bowel obstruction, and even death. These gastrointestinal effects remain inadequately recognized.MethodsWe reviewed all reports of serious clozapine-induced gastrointestinal hypomotility (CIGH) submitted to the Australian Therapeutic Goods Administration and New Zealand Pharmacovigilance Centre between 1992 and 2013. We extracted relevant demographic, clinical, and outcome data and derived a numerator from clozapine registries. We examined whether clozapine drug safety information in Australia, New Zealand, the US, and the UK was adequate and consistent with pharmacoepidemiologic evidence.ResultsA total of 43,132 people commenced clozapine over the study period. 160 were reported as having serious gastrointestinal hypomotility with clozapine the suspected cause (37/10,000 clozapine users). Of these, 66.3% were male, age range was 17–76 years, clozapine dose range 25–1000 mg/day (mean 439 mg/day) and median duration of clozapine treatment 2.5 years. Few had received laxatives. At least 29 patients died (7/10,000 clozapine users), a reported case fatality rate of 18%. The CIGH prevalence, while similar to other smaller studies, differs significantly from clozapine prescribing information issued by regulators and pharmaceutical companies, none of which mention CIGH, and which report serious gastrointestinal complications at rates of <1/10,000, almost a 40-fold difference.ConclusionThis is the largest study to date of serious CIGH. The reported prevalence of serious CIGH was 37/10,000, a likely underestimation of true prevalence. Current prescribing guidelines provide inadequate information on CIGH. This may be contributing to poor awareness and high associated morbidity and mortality. It is time regulators and manufacturers update their guidance.

国外安全性情報の収集・評価・報告とCIOMS報告書( 医薬品安全性情報の収集)

国外安全性情報の収集・評価・報告とCIOMS報告書( 医薬品安全性情報の収集)

化粧品安全性関連情報の収集について : フォーカスサービスを利用した文献情報の効率的収集法( 医薬品安全性情報の収集)

化粧品安全性関連情報の収集について : フォーカスサービスを利用した文献情報の効率的収集法( 医薬品安全性情報の収集)

受託安全確保業務 : GVP省令に基づく医薬品・医療機器等の情報収集について( 医薬品安全性情報の収集)

受託安全確保業務 : GVP省令に基づく医薬品・医療機器等の情報収集について( 医薬品安全性情報の収集)

Author Reply

Patients remain misinformed or underinformed about the indications and risks associated with testosterone replacement therapy (TRT), despite the Food and Drug Administration's Drug Safety Communications regarding testosterone products. 1 FDA Postmarket Drug Safety Information. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm161874.htm Google Scholar Most patients are unaware of the association between low serum testosterone, medical comorbidities, such as obesity, diabetes mellitus, and obstructive sleep apnea, and generally unhealthy lifestyles, characterized by stress, lack of physical exercise, poor sleep hygiene, and poor dietary intake. Thanks to modern lifestyles, a large proportion of the population already experiences the nonspecific symptoms associated with testosterone deficiency. Increased patient demand for serum testosterone evaluation, therefore, easily translates to an increase in the diagnosis of male hypogonadism.

Patient and Physician Perceptions of Drug Safety Information for Sleep Aids: A Qualitative Study.

The US Food and Drug Administration uses drug safety communications (DSCs) to release emerging information regarding post-market safety issues, but it is unclear the extent of awareness by patients and providers of these communications and their specific recommendations. We conducted semi-structured interviews with patients and physicians to evaluate their awareness and understanding of emerging drug safety information related to two sleep aids: zolpidem or eszopiclone. We conducted interviews with 40 patients and ten physicians recruited from a combination of insurer claims databases and online sources. We evaluated (1) sources of drug safety information; (2) discussions between patients and physicians about the two medications; (3) their knowledge of the DSC; and (4) preferences for learning about future drug safety information. Interviews were transcribed and analyzed thematically. Patients cited their physicians, pharmacy inserts, and the Internet as sources of drug safety information. Physicians often referred to medical journals and online medical sources. Most patients reported being aware of information contained in the DSC summaries they were read. Almost all patients and physicians reported discussing side effects during patient-provider conversations, but almost no patients mentioned that physicians had communicated with them key messaging from the DSCs at issue: the risk of next-morning impairment with zolpidem and the lower recommended initial dose for women. Some risks of medications are effectively communicated to patients and physicians; however, there is still a noticeable gap between information issued by the Food and Drug Administration and patient and physician awareness of this knowledge, as well as patients' decisions to act on this information. Disseminators of emerging drug safety information should explore ways of providing user-friendly resources to patients and healthcare professionals that can update them on new risks in a timely manner.