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Drug Safety
Journal Prestige (SJR): 1.447
Citation Impact (citeScore): 3
Number of Followers: 177  
 
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ISSN (Print) 0114-5916 - ISSN (Online) 1179-1942
Published by Adis Homepage  [21 journals]
  • Sex Differences in Adverse Drug Reactions of Metformin: A Longitudinal
           Survey Study
    • Abstract: Introduction In general, women more often experience metformin-associated adverse drug reactions (ADRs) than men. Objectives We aimed to assess whether sex differences in reported ADRs for metformin are observed at different times after initiation, and to explore their concurrence with sex differences in the dose of metformin over time. This may guide future studies in assessing the involved mechanisms of sex differences in metformin-associated ADRs and may guide sex-specific management of ADRs in clinical practice. Methods This study has a longitudinal design using data about patients initiating metformin collected by the Dutch National Pharmacovigilance Center Lareb through their Intensive Monitoring program. Patients were asked to complete a web-based questionnaire six times after initiation (i.e., at 2 weeks, 6 weeks and at 3, 6, 9, and 12 months). The outcome variables were the proportion of patients reporting any ADR (primary) and the dose of metformin (secondary). Sex differences in the proportions of ADRs and in the dose were tested at each assessment using Pearson Chi-Squared tests and Wilcoxon rank-sum tests, respectively. Using Bonferroni adjustment for multiple testing, a p value < 0.01 was considered statistically significant. Results The number of included patients was 1712 (40.9% women). Women reported an ADR more often than men, which was statistically significant at the assessment at 2 weeks (34% vs 25%, p < 0.001), and 6 weeks (37% vs 28%, p = 0.001) after initiation. In general, women were reported to be prescribed a lower dose than men, which became statistically significant at the 9-month assessment (p < 0.01). Conclusions Sex differences in reported ADRs were seen in the first weeks after metformin initiation, whereas statistically significant differences in self-reported prescribed dosing were observed after several months. Patients, in particular women, might benefit from being prescribed lower metformin doses at treatment initiation.
      PubDate: 2020-02-11
       
  • Benzodiazepine Use and Risk of Acute Angle-Closure Glaucoma: A
           Population-Based Case-Crossover Study
    • Abstract: Introduction Theoretically, benzodiazepines (BZDs) can narrow the iridocorneal angle and induce acute angle-closure glaucoma (AACG). However, little evidence exists regarding this association. Objective The objective of this study was to assess whether the use of BZDs is associated with the risk of AACG. Methods We conducted a population-based case-crossover study using the nationwide claims database of the National Health Insurance Service in Korea. Patients with newly diagnosed AACG—between 1 January 2013 and 31 December 2016—who had received at least one BZD prescription prior to AACG diagnosis were enrolled. The date of AACG diagnosis was set as the index date. We assessed BZD use by each patient during a 30-day case period prior to the index date and three consecutive control periods that preceded this date. We used conditional logistic regression that adjusted for concomitant medications to determine the odds ratio for the use of BZDs in the case period compared with that in the control period in patients with incident AACG. Results Of the 11,093 patients with incident AACG, 6709 received a prescription for BZD prior to diagnosis. BZD use was associated with an increased risk of AACG [adjusted odds ratio (aOR) = 1.40; 95% confidence interval (CI) 1.27–1.54]. AACG risk was similar for short-acting (aOR = 1.40, 95% CI 1.24–1.57) and long-acting BZDs (aOR = 1.33, 95% CI 1.18–1.50). Conclusion We found that BZD use was associated with AACG risk in the Korean population. Clinicians should carefully monitor the occurrence of visual disturbance in BZD-treated patients.
      PubDate: 2020-02-07
       
  • Quality of Reporting on the Evaluation of Risk Minimization Programs: A
           Systematic Review
    • Abstract: Introduction Risk minimization programs are interventions mandated by regulatory agencies to ensure that benefits of pharmaceutical products outweigh risks. Many regulatory agencies require programs be evaluated for effectiveness; however, the quality of evidence has limited the ability to definitively determine if programs improve drug safety. Objective The aim of this systematic review was to assess and describe the current status of reporting on the effectiveness of pharmaceutical risk management programs. Methods Peer-reviewed articles published between January 2012 and December 2018 were selected from three online databases (MEDLINE, PubMed, Embase). Eligible studies reported on effectiveness evaluations of mandated risk minimization measures (beyond labeling) and were written in English. Two reviewers independently examined 2744 titles of articles and 52 full articles were included. Forty-eight sources of gray literature from conference abstract presentations and publicly available regulatory documents were also included. Results Key opportunities for improvement in reporting included the provision of information regarding (1) selection, design, and testing of risk minimization measures, (2) implementation of programs, (3) process and outcome metrics, including the extent to which programs reached the intended audience, were integrated into the target healthcare settings, or were sustained over time, and (4) burden of the program on the healthcare system and implications for patient access. Conclusions Gaps in reporting of risk minimization program evaluation studies were identified. Addressing gaps will help build the evidence base regarding risk minimization initiatives, as well as ensure that programs are maximally effective and minimally burdensome on the healthcare system, and do not unduly interfere with patient access to the medicine.
      PubDate: 2020-02-04
       
  • Investigating Overlap in Signals from EVDAS, FAERS, and VigiBase ®
    • Abstract: Introduction The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and VigiBase® are two established databases for safety monitoring of medicinal products, recently complemented with the EudraVigilance Data Analysis System (EVDAS). Objective Signals of disproportionate reporting (SDRs) can characterize the reporting profile of a drug, accounting for the distribution of all drugs and all events in the database. This study aims to quantify the redundancy among the three databases when characterized by two disproportionality-based analyses (DPA). Methods SDRs for 100 selected products were identified with two sets of thresholds (standard EudraVigilance SDR criteria for all vs Bayesian approach for FAERS and VigiBase®). Per product and database, the presence or absence of SDRs was determined and compared. Adverse events were considered at three levels: MedDRA® Preferred Term (PT), High Level Term (HLT), and HLT combined with Standardized MedDRA® Query (SMQ). Redundancy was measured in terms of recall (SDRs in EVDAS divided by SDRs from any database) and overlap (SDRs in EVDAS and at least one other database, divided by SDRs in EVDAS). Covariates with potential impact on results were explored with linear regression models. Results The median overlap between EVDAS and FAERS or VigiBase® was 85.0% at the PT level, 94.5% at the HLT level, and 97.7% at the HLT or SMQ level. The corresponding median recall of signals in EVDAS as a percentage of all signals generated in all three databases was 59.4%, 74.1%, and 87.9% at the PT, HLT, and HLT or SMQ levels, respectively. The overlap difference is partially explained by the relative number of EU cases in EudraVigilance and the ratio of EVDAS cases and FAERS cases, presumably due to differences in marketing authorizations, or market penetration in different regions. Products with few cases in EVDAS (< 1500) also display limited recall of signals relative to FAERs/VigiBase®. Time-on-market does not predict signal redundancy between the three databases. The choice of the DPA has an expected but somewhat small effect on redundancy. Conclusions Organizations typically consider regulatory expectations, operating performance (e.g., positive predictive value), and procedural complexity when selecting databases for signal management. As SDRs can be seen as a proxy of general reporting characteristics identifiable in a systematic screening process, our results indicate that, for most products, these characteristics are largely similar in each of the databases.
      PubDate: 2020-02-04
       
  • The Role of Unit-Dose Child-Resistant Packaging in Unintentional Childhood
           Exposures to Buprenorphine–Naloxone Tablets
    • PubDate: 2020-02-01
       
  • Medical Devices: Classification and Analysis of Faults Leading to Harms
    • Abstract: Introduction Harms from medical devices are important, but have been much less well studied than adverse drug reactions. Information provided to device users is of variable quality. Objective Our aim was to define “medical device fault” and “adverse effect of a medical device”; to establish whether medical device faults arise in design, manufacture, or use; and to consider ways of mitigating the adverse effects of medical devices. Methods We analysed 100 consecutive faults reported by the US Food and Drug Administration (FDA) and 50 faults reported by the UK Medicines and Healthcare products Regulatory Agency (MHRA), and classified faults according to the point at which they occurred. Results Nearly 70% of reported faults related to devices that entered the body. Over 70% arose at the design stage, a quarter of the faults were associated with manufacture, and less than 5% were primarily caused by faulty use. Conclusion We defined a medical device fault as an unintended failure in the design, manufacture, or use of a medical device that leads to, or has the potential to lead to, harm to the patient, and an adverse effect of a medical device as an unintended and appreciably harmful effect, caused by a medical device, which demonstrates a hazard of the device and may warrant preventive measures, or a change in the mode of use, or withdrawal of the device. Most faults that generate warnings arise from problems at the design stage, some arise at the manufacturing stage, and a few in usage. Careful assessment of the design of safety-critical devices in the light of previous problems may help to prevent repetition of errors. It would be helpful if, in addition to user manuals, manufacturers were required to produce Summaries of Device Characteristics (SDCs, “labels”) that contained a systematically presented set of information about a product.
      PubDate: 2020-02-01
       
  • Exposure to Infliximab During Pregnancy: Post-Marketing Experience
    • Abstract: Background Women of childbearing potential are often treated with monoclonal antibodies to control chronic and debilitating inflammatory diseases. Remicade® (innovator infliximab [IFX]) may cross the placenta after the first trimester of pregnancy. Hence, evidence is needed to optimize treatment while carefully weighing benefits and risks to the mother and child. Here, we report on birth and infant outcomes (up to 2 years) following gestational exposure to IFX based on a summary of cumulative pregnancy reports in women exposed to IFX during pregnancy from the Janssen global safety database. Methods Prospective and medically confirmed safety data on IFX-exposed pregnancies from Janssen’s global safety surveillance database since authorization in 1998 are summarized. Descriptive statistics were used to summarize pregnancy and infant outcomes overall, by disease and timing of exposure. Results As of 23 August 2018, 1850 maternally IFX-exposed pregnancies with known outcomes were identified from the safety database. Of the 1850 pregnancies (mean age 29.7 years), 1526 (82.5%) resulted in live births. When reported, most women had Crohn’s disease (67.7%) or ulcerative colitis (18.4%), and 82.8% of live births were exposed to IFX in the first trimester. Spontaneous abortion/intrauterine death/ectopic pregnancy/molar pregnancy (12.1%), preterm births (9.2%), low birth weight infants (3.6%), congenital anomalies (2.0%), and infant infections (1.2%) were documented. The type of congenital anomalies and frequency of serious infant infections observed were consistent with the general population. Frequencies of congenital anomalies and other adverse outcomes were similar in women exposed to IFX in the first trimester and those exposed in the third trimester. More preterm births (13–18.8%) and infant complications (8.7–12.5%) were reported with concomitant immunosuppressant use. Conclusions The observed prevalence of adverse pregnancy and infant outcomes including congenital anomalies following exposure to IFX did not exceed estimates reported for the general population and no unexpected patterns were observed.
      PubDate: 2020-02-01
       
  • A Post-Authorization Safety Study of Quetiapine as Antidepressant
           Treatment in Sweden: Nested Case–Control Analyses of Select Outcomes
    • Abstract: Introduction This post-authorization safety study (PASS) was a commitment to the European Medicines Agency. Objective This PASS investigated quetiapine as antidepressant treatment in Swedish registers with regard to the risk for all-cause mortality, self-harm and suicide, acute myocardial infarction, stroke, diabetes mellitus, extrapyramidal disorders, and somnolence. Methods Users of quetiapine and antidepressants (2011‒2014) who had changed treatment in the past year were included. Conditional logistic regression models were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) for each outcome in nested case–control studies for quetiapine as combination therapy and monotherapy, monotherapy with antidepressants, and no medication, versus the use of combinations of antidepressants (reference group). Results Overall, 7421 quetiapine users and 281,303 antidepressant users were included. For quetiapine in combination, risks were increased for all-cause mortality [adjusted OR (aOR) 1.31, 95% CI 1.12–1.54] compared with combinations of antidepressants; however, when stratified by age, only patients ≥ 65 years of age had an increased mortality, and, in a post hoc analysis excluding patients with Parkinson’s disease, no mortality increase remained. Furthermore, the risk for self-harm and suicide was increased (aOR 1.53, 95% CI 1.31–1.79), but when stratified by age, the risk increase was found only among patients aged 18–64 years. Risks were also increased for stroke among patients ≥ 65 years of age (aOR 1.47, 95% CI 1.01–2.12), for extrapyramidal disorder (aOR 6.15, 95% CI 3.57–10.58), and for somnolence (aOR 2.41, 95% CI 1.42–4.11). Conclusion Risks for all-cause mortality, self-harm and suicide, and stroke in older patients may be higher among patients treated with quetiapine and antidepressant combination therapy.
      PubDate: 2020-02-01
       
  • Development and First Use of the Patient’s Qualitative Assessment of
           Treatment (PQAT) Questionnaire in Type 2 Diabetes Mellitus to Explore
           Individualised Benefit–Harm of Drugs Received During Clinical Studies
    • Abstract: Introduction Individualised benefit–harm assessments can help identify patient-perceived benefits and harms of a treatment, and associated trade-offs that may influence patients’ willingness to use a treatment. This research presents the first use of a patient-reported outcome measure designed to assess patient-perceived benefits and disadvantages of drugs received during clinical studies. Methods The Patient’s Qualitative Assessment of Treatment (PQAT) was developed in English and cognitively tested with US (n = 4) and Canadian (n = 3) patients with type 1 and type 2 diabetes mellitus (T2DM). The revised version of the PQAT comprises three qualitative open-ended questions focused on the benefits and disadvantages of treatment and reasons why patients would choose to continue/discontinue treatment. A final quantitative question asks patients to evaluate the balance between benefits and disadvantages using a 7-point scale. The revised version of the questionnaire was administered as an exploratory endpoint in a phase II clinical trial for a new injectable treatment for T2DM. Qualitative data were analysed using thematic analysis, and relationships between qualitative and quantitative data were identified. Results Patient-reported benefits of treatment administered during the clinical trial included clinical markers of efficacy and subjective markers. Disadvantages reported by patients were mainly related to drug adverse effects or to the mode of administration. Of the 57 patients completing the PQAT, 70.2% reported being willing to continue treatment, with 59.6% reporting that the benefits outweighed the disadvantages. The reported benefits of feeling better and improved energy levels were more likely to be associated with a more positive ratio (70% and 71.4%, respectively), while the disadvantages of fatigue, headaches, and stomach pain were associated with a negative ratio and patients not being willing to continue the treatment. Conclusions The PQAT is a unique patient-reported outcome tool designed to aid understanding patients’ real experience of benefits and disadvantages of a treatment. It combines the richness of qualitative data with quantitative data—information valuable for various stakeholders to make well-informed treatment decisions. Trial Registration ClinicalTrials.gov identifier: NCT02973321.
      PubDate: 2020-02-01
       
  • Occurrences and Outcomes of Immune Checkpoint Inhibitors-Induced Vitiligo
           in Cancer Patients: A Retrospective Cohort Study
    • Abstract: Background The use of immune checkpoint inhibitors (ICI) in melanoma and non-small cell lung cancer patients is associated with the onset of vitiligo. However, previous studies have suggested conflicting results on the conditions of occurrence of ICI-induced vitiligo. Objective The aim of this study was to describe the occurrences and outcomes of several cases of ICI-induced vitiligo. Methods A retrospective study was carried out using the French Pharmacovigilance Database (FPD) between the beginning of the commercialization of ICI in France and 1 January 2019, selecting for analysis the vitiligo reactions of patients due to treatment with ICI. Results Among the 95 case patients identified in the FPD, the median times to onset of vitiligo after the start of pembrolizumab, nivolumab and ipilimumab therapies were 5.4, 5.0, and 3.8 months, respectively. Furthermore, 37 patients (45%) discontinued ICI treatment due to disease progression. The median follow-up time of all patients was 33 months (interquartile range 2–56). Conclusions This study provided an overall picture of ICI-induced vitiligo in daily medical practice on a large number of pharmacovigilance observations of case patients. Among the observations of ICI-induced vitiligo, the diagnosed cancer was melanoma for almost all patients. Most patients in the study experienced other associated adverse drug reactions (ADRs), such as colitis, pruritus, hypothyroidism, hyperthyroidism, thyroiditis, pancreatitis, and gastritis. Furthermore, our data suggest that the resolution of pembrolizumab- or nivolumab-induced vitiligo could be a marker of disease progression. Future studies evaluating vitiligo outcomes are warranted.
      PubDate: 2020-02-01
       
  • Effectiveness of Risk Minimization Measures for Fentanyl Buccal Tablet
           (FENTORA) in Canada: A Mixed-Methods Evaluation Using Surveys, Medical
           Chart Records and Web Surveillance
    • Abstract: Background Fentanyl buccal tablet (FBT), a potent opioid, was approved in Canada in 2013 for breakthrough pain in opioid-tolerant adult cancer patients. Additional risk minimization measures (aRMMs), consisting of communications to patients and healthcare providers (HCPs), were implemented from November 2014 through September 2015. Objectives The aim of this study was to assess the effectiveness of FBT aRMMs as measured by prescriber knowledge, understanding, and behavior regarding key safety concerns (off-label use, use in non-opioid-tolerant patients, misuse/abuse/diversion, and drug–drug interaction) and to evaluate illicit FBT use. Methods The study included three components: (1) a knowledge and understanding (KAU) survey of FBT prescribers conducted in two waves: November 2016–February 2017 and April–September 2018; (2) a retrospective prescription study of medical records of patients treated with FBT by a subgroup of prescribers from the KAU survey; and (3) Web surveillance of illicit FBT use in Canada using the search term FENTORA (May 2014–September 2018). The aRMMs were considered effective if the lower bound of the 95% confidence interval indicated that at least 65% of respondents met or partly met the knowledge objective for each key safety concern. Results KAU survey: Of 46 eligible HCPs, 97.8% met or partly met the knowledge objective on use in breakthrough pain cancer patients, 97.8% on use in opioid-tolerant patients, 89.1% on dose and titration, 100% on abuse/addiction, and 58.7% on drug–drug interaction. Retrospective prescription study: Of 22 FBT-treated patients identified from 14 HCPs, 45.5% had cancer, 50.0% recorded a breakthrough pain indication, and 36.4% reported opioid tolerance; however, only 13.6% of patients were prescribed FBT according to the approved indication. Web surveillance: Of 932 FBT posts in Canada, only 40 (4.3%) mentioned illicit use. Conclusions The aRMMs as measured by the prescriber KAU were effective for most key safety messages; however, not all key messages of the aRMMs were stringently followed in routine practice.
      PubDate: 2020-02-01
       
  • Medical Devices: Definition, Classification, and Regulatory Implications
    • Abstract: Abstract We propose the following definition of a medical device: “A contrivance designed and manufactured for use in healthcare, and not solely medicinal or nutritional.” Current regulatory classifications of medical devices are complex and designed primarily for regulators. We propose a simpler classification, based on (1) the site of application of the device, (2) the time scale of its use, and (3) whether it has an external power source. The regulation of medical devices is less well developed than the regulation of medicinal products, which it could follow more closely. In particular, devices that incorporate medicines should be required to meet the same regulatory standards as medicinal products. This would remove the anomaly that some delivery systems that incorporate medicines are classified as devices while other similar systems that deliver the same medicines are classified as medicinal products. Some improvements might also result from more widespread use of registries, such as those used for prosthetic joint replacements. Registries would allow both a prospective examination of the performance of high-risk devices and a retrospective analysis when signals from other sources of information suggest problems. Those who apply for a marketing authorization for a new device should have to assure regulators of its quality of manufacture, safety, and efficacy before licensing. Even the most straightforward device should be shown to be useable in practice. Trials on patients, or at least simulations of use in the real world, should be practicable for most devices.
      PubDate: 2020-02-01
       
  • The Use of Long-Acting Insulin Analogs and the Risk of Colorectal Cancer
           Among Patients with Type 2 Diabetes: A Population-Based Cohort Study
    • Abstract: Introduction The association between long-acting insulin analogs and colorectal cancer is uncertain, with previous studies reporting discrepant findings. Objective To determine whether the use of long-acting insulin analogs is associated with an increased risk of colorectal cancer, when compared with use of intermediate-acting human insulins among patients with type 2 diabetes. Methods We conducted a population-based study using the United Kingdom Clinical Practice Research Datalink (CPRD). We identified patients newly treated with either a long-acting insulin analog or an intermediate-acting human insulin between September 1, 2002 and January 31, 2018, with follow-up until January 31, 2019. Each long-acting insulin analog user was propensity score-matched to one intermediate-acting human insulin user, and a lag of 1 year was imposed. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of colorectal cancer, comparing long-acting insulin analogs with intermediate-acting human insulin. Secondary analysis was conducted to assess whether there was a duration–response relationship. Results A total of 10,734 new long-acting insulin analog users were matched to 10,734 new intermediate-acting human insulin users. After a median follow-up of 2.8 years, the use of long-acting insulin analogs was not associated with an increased risk of colorectal cancer, compared with intermediate-acting human insulin (1.80 vs. 1.87 per 1000 person-years, respectively; HR 0.96, 95% CI 0.70–1.34). There was no evidence of a duration–response relationship. Conclusions The results of this population-based study indicate that use of long-acting insulin analogs is not associated with an overall increased risk of colorectal cancer.
      PubDate: 2020-02-01
       
  • New Discoveries and Updates on Cutaneous Adverse Drug Reactions Presented
           at the 24th World Congress of Dermatology, Milan, Italy, 2019
    • PubDate: 2020-02-01
       
  • Disproportionality Analysis for Pharmacovigilance Signal Detection in
           Small Databases or Subsets: Recommendations for Limiting False-Positive
           Associations
    • Abstract: Introduction Uncovering safety signals through the collection and assessment of individual case reports remains a core pharmacovigilance activity. Despite the widespread use of disproportionality analysis in signal detection, recommendations are lacking on the minimum size of databases or subsets of databases required to yield robust results. Objective This study aims to investigate the relationship between database size and robustness of disproportionality analysis, with regards to limiting spurious associations. Methods Three types of subsets were created from the global database VigiBase: random subsets (500 replicates each of 11 fixed subset sizes between 250 and 100,000 reports), country-specific subsets (all 131 countries available in the original VigiBase extract) and subsets based on the Anatomical Therapeutic Chemical classification. For each subset, a spuriousness rate was computed as the ratio between the number of drug–event combinations highlighted by disproportionality analysis in a permuted version of the subset and the corresponding number in the original subset. In the permuted data, all true reporting associations between drugs and adverse events were broken. Subsets with fewer than five original associations were excluded. Additionally, the set of disproportionately over-reported drug–event combinations in three specific countries at three different time points were clinically assessed for labelledness. These time points corresponded to database sizes of less than 10,000, 5000 and 1000 reports, respectively. All disproportionality analysis was based on the Information Component (IC), implemented as IC025 > 0. Results Spuriousness rates were below 0.15 for all 110 included countries regardless of subset size, with only seven countries (6%) exceeding the empirical threshold of 0.10 observed for large subsets. All 21 excluded countries had < 500 reports. For random subsets containing 3000–5000 or more reports, the higher end of observed spuriousness rates was close to 0.10. In the clinical assessment, the proportion of labelled or otherwise known drug–event combinations was very high (87–100%) across all countries and time points studied. Conclusions To mitigate the risk of highlighting spurious associations with disproportionality analysis, a minimum size of 500 reports is recommended for national databases. For databases or subsets that are not country-specific, our recommendation is 5000 reports. This study does not consider sensitivity, which is expected to be poor in smaller databases.
      PubDate: 2020-02-01
       
  • An Integrated Analysis of the Safety of Tofacitinib in Psoriatic Arthritis
           across Phase III and Long-Term Extension Studies with Comparison to
           Real-World Observational Data
    • Abstract: Introduction Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). Objective Our objective was to compare the incidence rates (IRs) of adverse events in tofacitinib clinical trials and real-world observational data for alternative treatments. Methods The tofacitinib “dose-comparison cohort” included months 0–12 of two phase III studies (tofacitinib 5 [n = 238] and 10 [n = 236] mg twice daily [BID]); the “all-tofacitinib comparison cohort” (n = 783) included two phase III and one ongoing long-term extension study (data cutoff May 2016). An “observational comparison cohort” (n = 5799) comprised patients initiating a conventional synthetic disease-modifying antirheumatic drug (DMARD), biologic DMARD, or apremilast in the US Truven MarketScan database from 2010 to 2015. IRs for serious infections (SIEs; requiring hospitalization), herpes zoster (HZ), malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC, and major adverse cardiovascular events (MACE) across cohorts were qualitatively compared. Results IRs (patients with events/100 patient-years) for SIEs were similar between the tofacitinib dose-comparison cohort (5 mg BID: 1.3; 10 mg BID: 2.0) and the observational comparison cohort (1.1–7.9; treatment dependent). The tofacitinib dose-comparison cohort had a higher rate of HZ (5 mg BID: 2.0; 10 mg BID: 2.7) than did the observational comparison cohort (0.8–2.0). IRs for NMSC were generally lower in the all-tofacitinib comparison cohort (0.5) than in the observational comparison cohort (0.4–6.0). IRs for MACE, malignancies excluding NMSC, and NMSC were similar between cohorts. Conclusion In patients with PsA, tofacitinib had a safety profile similar to that of other systemic therapies in real-world settings, except for the risk of HZ, a known risk of tofacitinib. Trial Registration ClinicalTrials.gov: NCT01877668; NCT01882439; NCT01976364.
      PubDate: 2020-01-31
       
  • Comment on “Evaluation of Potential Drug–Drug Interactions in Adults
           in the Intensive Care Unit: A Systematic Review and Meta-analysis”
    • PubDate: 2020-01-29
       
  • Authors’ Reply to Uysal and Colleagues’ Comment on: “Evaluation of
           Potential Drug–Drug Interactions in Adults in the Intensive Care Unit: A
           Systematic Review and Meta-Analysis”
    • PubDate: 2020-01-29
       
  • Adverse Events in Twitter-Development of a Benchmark Reference Dataset:
           Results from IMI WEB-RADR
    • Abstract: Introduction and Objective Social media has been suggested as a source for safety information, supplementing existing safety surveillance data sources. This article summarises the activities undertaken, and the associated challenges, to create a benchmark reference dataset that can be used to evaluate the performance of automated methods and systems for adverse event recognition. Methods A retrospective analysis of public English-language Twitter posts (Tweets) was performed. We sampled 57,473 Tweets out of 5,645,336 Tweets created between 1 March, 2012 and 1 March, 2015 that mentioned at least one of six medicinal products of interest (insulin glargine, levetiracetam, methylphenidate, sorafenib, terbinafine, zolpidem). Products, adverse events, indications, product-event combinations, and product-indication combinations were extracted and coded by two independent teams of safety reviewers. Results The benchmark reference dataset consisted of 1056 positive controls (“adverse event Tweets”) and 56,417 negative controls (“non-adverse event Tweets”). The 1056 adverse event Tweets contained 1396 product-event combinations referring to personal adverse event experiences, comprising 292 different MedDRA® Preferred Terms. The 1171 product-event combinations (83.9%) were confined to four MedDRA® System Organ Classes. The 195 Tweets (18.5%) contained indication information, comprising 25 different Preferred Terms. Conclusions A manually curated benchmark reference dataset based on Twitter data has been created and is made available to the research community to evaluate the performance of automated methods and systems for adverse event recognition in unstructured free-text information.
      PubDate: 2020-01-29
       
  • A New President’s Vision for International Pharmacovigilance
    • PubDate: 2020-01-14
       
 
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