Follow-Up on the Use of Machine Learning in Clinical Quality Assurance: Can We Detect Adverse Event Under-Reporting in Oncology Trials?
(Source: Drug Safety)
Source: Drug Safety - December 13, 2019 Category: Drugs & Pharmacology Source Type: research

Insight into the Severity of Adverse Drug Reactions as Experienced by Patients
(Source: Drug Safety)
Source: Drug Safety - December 13, 2019 Category: Drugs & Pharmacology Source Type: research

Drug-Induced Hypophosphatemia: Current Insights
AbstractPhosphate is actively involved in many important biochemical pathways, such as energy and nucleic acid metabolism, cellular signaling, and bone formation. Hypophosphatemia, defined as serum phosphate levels below 2.5  mg/dL (0.81 mmol/L), is frequently observed in the course of treatment with commonly used drugs, such as diuretics, bisphosphonates, antibiotics, insulin, and antacids. Furthermore, this undesired effect may complicate the use of several novel medications, including teriparatide, denosumab, paren teral iron, and antiviral and antineoplastic agents. This review addresses drug-associated hypop...
Source: Drug Safety - November 27, 2019 Category: Drugs & Pharmacology Source Type: research

Fatal Toxicity Indices for Medicine-Related Deaths in New Zealand, 2008 –2013
ConclusionNew Zealand prescribers should be aware of the high relative risk of death associated with methadone and clozapine; that clomipramine, dosulepin and doxepin were identified as the most dangerous antidepressants; and that zopiclone carries a similar fatal risk to benzodiazepines. Varying results were found between the FTIs calculated, making comparisons, particularly between populations, difficult. (Source: Drug Safety)
Source: Drug Safety - November 20, 2019 Category: Drugs & Pharmacology Source Type: research

The Role of Unit-Dose Child-Resistant Packaging in Unintentional Childhood Exposures to Buprenorphine –Naloxone Tablets
(Source: Drug Safety)
Source: Drug Safety - November 20, 2019 Category: Drugs & Pharmacology Source Type: research

Prenatal Exposure to Macrolides and Risk of Congenital Malformations: A Meta-Analysis
ConclusionsOur study suggests a weak association between prenatal use of macrolides and congenital malformations, limited to exposure in early pregnancy, and musculoskeletal and digestive systems. In addition to studies with a larger control of confounding, risk –benefit research is needed to determine the usefulness of macrolides during pregnancy. (Source: Drug Safety)
Source: Drug Safety - November 12, 2019 Category: Drugs & Pharmacology Source Type: research

Rheumatology Common Toxicity Criteria (RCTC): An Update Reflecting Real-World Use
ConclusionThe RCTC 2.0 performed as intended, although some inaccuracies and omissions were found. We provide a corrected version, RCTC 2.1, and also recommend further revision of the RCTC within OMERACT guidances to include AEs that have been reported in rheumatology clinical trials since RCTC 2.0 was published. Ideally, a revised RCTC 3.0 would not only facilitate standardized assessment and reporting of AEs, but would also expand and encourage accurate comparison of the safety profiles of treatments for rheumatic/autoimmune diseases. (Source: Drug Safety)
Source: Drug Safety - November 6, 2019 Category: Drugs & Pharmacology Source Type: research

Effectiveness of Risk Minimization Measures for Fentanyl Buccal Tablet (FENTORA) in Canada: A Mixed-Methods Evaluation Using Surveys, Medical Chart Records and Web Surveillance
ConclusionsThe 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. (Source: Drug Safety)
Source: Drug Safety - November 5, 2019 Category: Drugs & Pharmacology Source Type: research

Medical Devices: Classification and Analysis of Faults Leading to Harms
ConclusionWe 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-...
Source: Drug Safety - November 5, 2019 Category: Drugs & Pharmacology Source Type: research

Acknowledgement to Referees
(Source: Drug Safety)
Source: Drug Safety - November 4, 2019 Category: Drugs & Pharmacology Source Type: research

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
ConclusionsThe 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 RegistrationClinicalTrials.gov identifier: NCT02973321. (Source: Drug Safety)
Source: Drug Safety - November 2, 2019 Category: Drugs & Pharmacology Source Type: research

Exposure to Infliximab During Pregnancy: Post-Marketing Experience
ConclusionsThe 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. (Source: Drug Safety)
Source: Drug Safety - November 1, 2019 Category: Drugs & Pharmacology Source Type: research

New Discoveries and Updates on Cutaneous Adverse Drug Reactions Presented at the 24th World Congress of Dermatology, Milan, Italy, 2019
(Source: Drug Safety)
Source: Drug Safety - October 31, 2019 Category: Drugs & Pharmacology Source Type: research

Benefit-Risk Assessment of Alogliptin for the Treatment of Type 2 Diabetes Mellitus
AbstractThe dipeptidyl peptidase-4 inhibitor (DPP-4i) alogliptin is an oral, antidiabetic treatment that is approved in many countries to treat patients with type 2 diabetes mellitus (T2DM), including the USA, Europe, and Japan. Alogliptin is efficacious both as monotherapy and as add-on/combination therapy with other commonly prescribed T2DM treatments, such as metformin and pioglitazone. Overall, alogliptin is well-tolerated in patients with T2DM, including older patients, those with renal and/or hepatic impairment, and those at high risk of cardiovascular events. There is a low risk of hypoglycemia, weight gain, acute p...
Source: Drug Safety - October 25, 2019 Category: Drugs & Pharmacology Source Type: research

Complementing Observational Signals with Literature-Derived Distributed Representations for Post-Marketing Drug Surveillance
ConclusionsResults from this study support the hypothesis that knowledge extracted from the literature can enhance the performance of SRS-based methods (and vice versa). Across reference sets, using literature and SRS information together performed better than using either source alone, providing strong support for the complementary nature of these approaches to post-marketing drug surveillance. (Source: Drug Safety)
Source: Drug Safety - October 23, 2019 Category: Drugs & Pharmacology Source Type: research

Healthcare Database Networks for Drug Regulatory Policies: International Workshop on the Canadian, US and Spanish Experience and Future Steps for Italy
(Source: Drug Safety)
Source: Drug Safety - October 22, 2019 Category: Drugs & Pharmacology Source Type: research

Occurrences and Outcomes of Immune Checkpoint Inhibitors-Induced Vitiligo in Cancer Patients: A Retrospective Cohort Study
ConclusionsThis 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 evaluatin...
Source: Drug Safety - October 19, 2019 Category: Drugs & Pharmacology Source Type: research

Comparing Acute Kidney Injury Reports Among Antibiotics: A Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS)
ConclusionThis study found 14 classes of antibiotics having significant reporting associations with AKI. Among the antibiotics evaluated in this study, colistin had the highest AKI ROR and moxifloxacin had the lowest. (Source: Drug Safety)
Source: Drug Safety - October 18, 2019 Category: Drugs & Pharmacology Source Type: research

Description of the Risk Management of Medication Errors for Centrally Authorised Products in the European Union
ConclusionsMedication error safety concerns were listed for almost a quarter of centrally authorised products approved during the study period. Further research is needed to evaluate the effectiveness and continued need for additional risk minimisation measures for medication errors. (Source: Drug Safety)
Source: Drug Safety - October 16, 2019 Category: Drugs & Pharmacology Source Type: research

Exploratory Study of Signals for Asthma Drugs in Children, Using the EudraVigilance Database of Spontaneous Reports
ConclusionsThe majority of signals regarding asthma therapy in children were already known, but we also identified new signals. We showed that signals can be masked if age stratification is not conducted. Further exploration is needed to investigate the risk and causality of the newly found signals. (Source: Drug Safety)
Source: Drug Safety - October 15, 2019 Category: Drugs & Pharmacology Source Type: research

Application of Augmented Intelligence for Pharmacovigilance Case Seriousness Determination
ConclusionsThe results of this study indicate that a neural network approach can provide an accurate and scalable solution for potentially augmenting pharmacovigilance practitioner determination of adverse event seriousness in spontaneous, solicited, and medical literature reports. (Source: Drug Safety)
Source: Drug Safety - October 11, 2019 Category: Drugs & Pharmacology Source Type: research

Psoriasis After Exposure to Angiotensin-Converting Enzyme Inhibitors: French Pharmacovigilance Data and Review of the Literature
AbstractIntroductionAngiotensin-converting enzyme inhibitors (ACEIs) can induce or aggravate psoriasis. This risk is not specified in the Summary of Product Characteristics (SmPC) of some drugs of this class, such as captopril or enalapril. We aimed to investigate the association between psoriasis and ACEI exposure.MethodsWe analyzed spontaneous reports recorded in the French national Pharmacovigilance Database (FPVD) from 1985 to 31 December 2018. The association between psoriasis and ACEI exposure was assessed using the case/non-case method. We also reviewed literature reports.ResultsOne hundred reports of psoriasis afte...
Source: Drug Safety - October 9, 2019 Category: Drugs & Pharmacology Source Type: research

Adverse Events Associated with Cumulative Corticosteroid Use in Patients with Castration-Resistant Prostate Cancer: An Administrative Claims Analysis
This study evaluated the impact of cumulative corticosteroid exposure on the risk of developing specific adverse events in men with CRPC.MethodsData were obtained from administrative claims databases. Adult chemotherapy-na ïve men who initiated CRPC treatment following surgical or medical castration were selected. Patients were grouped into four cohorts based on cumulative corticosteroid dose: no exposure, low exposure (  2.0 g). Time to each adverse event was assessed using Kaplan–Meier analyses and time-dependent Cox proportional hazard models, adjusting for baseline characteristics.ResultsOverall,...
Source: Drug Safety - October 5, 2019 Category: Drugs & Pharmacology Source Type: research

Reported Severe Hypersensitivity Reactions after Intravenous Iron Administration in the European Economic Area (EEA) Before and After Implementation of Risk Minimization Measures
ConclusionsFuture research is needed to investigate whether the wide variability in reporting rates for severe HSRs associated with these intravenous iron products are due to potential differences in the safety profiles of these substances. (Source: Drug Safety)
Source: Drug Safety - October 3, 2019 Category: Drugs & Pharmacology Source Type: research

Data-Driven Identification of Adverse Event Reporting Patterns for Japan in VigiBase, the WHO Global Database of Individual Case Safety Reports
ConclusionAnalysis of Japanese adverse event reporting patterns in a global context has revealed key features that may reflect possible  pharmaco-ethnic vulnerabilities in the Japanese, as well as differences in adverse event reporting and clinical practice. This knowledge is essential in the global collaboration of signal detection afforded by the WHO Programme for International Drug Monitoring. (Source: Drug Safety)
Source: Drug Safety - September 26, 2019 Category: Drugs & Pharmacology Source Type: research

Measuring the Effectiveness of Safety Warnings on the Risk of Stroke in Older Antipsychotic Users: A Nationwide Cohort Study in Two Large Electronic Medical Records Databases in the United Kingdom and Italy
ConclusionAntipsychotic safety warnings were followed by a reduction in stroke incidence among older antipsychotic users in the UK, but not Italy. (Source: Drug Safety)
Source: Drug Safety - September 25, 2019 Category: Drugs & Pharmacology Source Type: research

Authors ’ Reply to Ravi Jandhyala’s Comment on “Patient Registries: An Underused Resource for Medicines Evaluation: Operational Proposals for Increasing the Use of Patient Registries in Regulatory Assessments”
(Source: Drug Safety)
Source: Drug Safety - September 24, 2019 Category: Drugs & Pharmacology Source Type: research

Comment on: “Patient Registries: An Underused Resource for Medicines Evaluation: Operational Proposals for Increasing the Use of Patient Registries in Regulatory Assessments”
(Source: Drug Safety)
Source: Drug Safety - September 24, 2019 Category: Drugs & Pharmacology Source Type: research

Comparative Effectiveness and Safety of Direct Oral Anticoagulants: Overview of Systematic Reviews
AbstractDirect oral anticoagulants are now recommended by major guidelines as first-choice agents for both stroke prevention in non-valvular atrial fibrillation and treatment/prevention of venous thromboembolism in non-cancer patients. Although there are no published head-to-head trials comparing different direct oral anticoagulants, a growing body of evidence from indirect comparisons and observational studies is suggesting that each direct oral anticoagulant may have a specific risk profile. This review aims to (1) synthesize and critically assess the latest evidence in comparative effectiveness and safety research in th...
Source: Drug Safety - September 24, 2019 Category: Drugs & Pharmacology Source Type: research

19th ISoP Annual Meeting “New Opportunities for New Generations” Bogotá, Colombia, 26–29 October, 2019
(Source: Drug Safety)
Source: Drug Safety - September 11, 2019 Category: Drugs & Pharmacology Source Type: research

Correction to: Patient Registries: An Underused Resource for Medicines Evaluation
The fourth sentence under the heading “1.1 Use of Patient Registries for Supporting Regulatory Assessments” in “1 Introduction” section should read as below. (Source: Drug Safety)
Source: Drug Safety - September 5, 2019 Category: Drugs & Pharmacology Source Type: research

Transparent Reporting on Research Using Unstructured Electronic Health Record Data to Generate ‘Real World’ Evidence of Comparative Effectiveness and Safety
AbstractResearch that makes secondary use of administrative and clinical healthcare databases is increasingly influential for regulatory, reimbursement, and other healthcare decision-making. Consequently, there are numerous guidance documents on reporting for studies that use ‘real-world’ data captured in administrative claims and electronic health record (EHR) databases. These guidance documents are intended to improve transparency, reproducibility, and the ability to evaluate validity and relevance of design and analysis decisions. However, existing guidance does n ot differentiate between structured and unst...
Source: Drug Safety - August 26, 2019 Category: Drugs & Pharmacology Source Type: research

Recommendations for the Use of Social Media in Pharmacovigilance: Lessons from IMI WEB-RADR
AbstractOver a period of 3  years, the European Union’s Innovative Medicines Initiative WEB-RADR project has explored the value of social media (i.e., information exchanged through the internet, typically via online social networks) for identifying adverse events as well as for safety signal detection. Many patients and cl inicians have taken to social media to discuss their positive and negative experiences of medications, creating a source of publicly available information that has the potential to provide insights into medicinal product safety concerns. The WEB-RADR project has developed a collaborative Engli...
Source: Drug Safety - August 24, 2019 Category: Drugs & Pharmacology Source Type: research

Prevalence and Nature of Medication Errors and Preventable Adverse Drug Events in Paediatric and Neonatal Intensive Care Settings: A Systematic Review
ConclusionsMedication errors occur frequently in critically ill children admitted to paediatric and neonatal intensive care units and may lead to patient harm. Important targets such as dosing errors and anti-infective medications were identified to guide the development of remedial interventions. (Source: Drug Safety)
Source: Drug Safety - August 13, 2019 Category: Drugs & Pharmacology Source Type: research

The  Association between Metformin Therapy and Lactic Acidosis
ConclusionsAlmost all cases of metformin-associated lactic acidosis reviewed presented with independent risk factors for lactic acidosis, supporting the suggestion that metformin plays a contributory role. The prescribed metformin dose, on average, exceeded the dosing recommendations by 1000  mg/day in patients with varying degrees of renal impairment but the predicted pre-admission plasma concentrations did not exceed the therapeutic range. (Source: Drug Safety)
Source: Drug Safety - August 1, 2019 Category: Drugs & Pharmacology Source Type: research

A Novel Approach to Visualize Risk Minimization Effectiveness: Peeping at the 2012 UK Proton Pump Inhibitor Label Change Using a Rapid Cycle Analysis Tool
ConclusionsThis pilot demonstrated a novel application of a visual, rapid analysis technique to assess RM effectiveness, and supported a hypothesis that prescribers altered some behaviors after the MHRA label change, such as channeling patients at risk of fracture or osteoporosis away from PPI use and potentially reducing fracture outcomes. Limitations include lack of confounding control and outcomes defined only by diagnosis code. Results demonstrate the potential to use large healthcare databases with chronographs to rapidly assess RM effectiveness, similar to signal detection in pharmacovigilance, and may help design mo...
Source: Drug Safety - July 31, 2019 Category: Drugs & Pharmacology Source Type: research

Non-Vitamin K Antagonist Oral Anticoagulants and Angioedema: A Cohort and Case-Crossover Study
ConclusionsOur estimates were inconsistent with substantial short-term relative increases in the rate of angioedema associated with oral anticoagulant therapy. (Source: Drug Safety)
Source: Drug Safety - July 18, 2019 Category: Drugs & Pharmacology Source Type: research

Multimodal Analysis of FDA Drug Safety Communications: Lessons from Zolpidem
AbstractBecause clinical trials conducted for US Food and Drug Administration (FDA) approval occur in carefully monitored settings and often have strict inclusion criteria for participation, new information about drug safety is commonly discovered once a medication is FDA approved and used by larger numbers of patients. The FDA issues Drug Safety Communications when new information arises about the safety of marketed drugs that may change decision making by healthcare providers and patients. Since their inception, over 250 Drug Safety Communications have been issued alerting consumers and prescribers in the USA about safet...
Source: Drug Safety - July 13, 2019 Category: Drugs & Pharmacology Source Type: research

Patient Registries: An Underused Resource for Medicines Evaluation
ConclusionsThese are the first explicit proposals, from a regulatory perspective, on operational methods for increasing the use of patient registries in medicines regulation. They apply to registry holders, patients, regulators, marketing authorisation holders/applicants and healthcare stakeholders broadly, and their implementation would greatly facilitate the use of these valuable data sources in regulatory decision-making. (Source: Drug Safety)
Source: Drug Safety - July 13, 2019 Category: Drugs & Pharmacology Source Type: research

Prevalence of Medication Errors Among Paediatric Inpatients: Systematic Review and Meta-Analysis
ConclusionsMedication errors are a frequent occurrence in paediatric inpatient settings, particularly in intensive care wards and emergency departments. Hospitals using electronic charts tended to have a lower rate of medication errors compared to those using paper charts. Future research employing controlled designs is needed to determine the true impact of electronic charts and other interventions on medication errors and associated harm among hospitalized children. (Source: Drug Safety)
Source: Drug Safety - July 9, 2019 Category: Drugs & Pharmacology Source Type: research

Evaluating Renal Stress Using Pharmacokinetic Urinary Biomarker Data in Critically Ill Patients Receiving Vancomycin and/or Piperacillin –Tazobactam: A Secondary Analysis of the Multicenter Sapphire Study
ConclusionAfter exposure to piperacillin –tazobactam and vancomycin in combination, there was a greater release of AKI biomarkers in patients who develop AKI than with piperacillin–tazobactam or vancomycin monotherapy and the combination is associated with possible increased long-term adverse outcomes. (Source: Drug Safety)
Source: Drug Safety - June 25, 2019 Category: Drugs & Pharmacology Source Type: research

Androgen Deprivation Therapy for Prostate Cancer and the Risk of Rheumatoid Arthritis: A Population-Based Cohort Study
ConclusionIn this population-based study, the use of ADT was not associated with an increased risk of RA in men with prostate cancer. (Source: Drug Safety)
Source: Drug Safety - June 25, 2019 Category: Drugs & Pharmacology Source Type: research

Effectiveness and Safety of Switching Originator and Biosimilar Epoetins in Patients with Chronic Kidney Disease in a Large-Scale Italian Cohort Study
ConclusionsIn this large-scale Italian observational multi-database study, switching versus non-switching as well as switching from biosimilar/originator ESA  α to any other epoetin in CKD patients is not associated with any effectiveness and safety outcomes. (Source: Drug Safety)
Source: Drug Safety - June 21, 2019 Category: Drugs & Pharmacology Source Type: research

Intravenous Infusion Administration: A Comparative Study of Practices and Errors Between the United States and England and Their Implications for Patient Safety
ConclusionInfusion administration is a complex adaptive system with multiple interacting agents (professionals, patients, software systems, etc.) that respond in rich ways to their environments; safety depends on complex, interrelated factors. (Source: Drug Safety)
Source: Drug Safety - June 13, 2019 Category: Drugs & Pharmacology Source Type: research

Pooling Different Safety Data Sources: Impact of Combining Solicited and Spontaneous Reports on Signal Detection In Pharmacovigilance
ConclusionsThis analysis of simulated data suggests that pooling AE data from solicited sources with spontaneous case data may impact the results of disproportionality analyses, masking true safety signals and identifying false positives. Therefore, increased volumes of safety data do not necessarily correlate with improved safety signal detection. (Source: Drug Safety)
Source: Drug Safety - June 12, 2019 Category: Drugs & Pharmacology Source Type: research

Randomized Placebo-Controlled Trial Evaluating the Ophthalmic Safety of Single-Dose Tafenoquine in Healthy Volunteers
ConclusionThere was no evidence of any pharmacodynamic effect of 300-mg single-dose tafenoquine on the retina or any short-term clinically relevant effects on ophthalmic safety. This clinical trial is registered with ClinicalTrials.gov (identifier: NCT02658435). (Source: Drug Safety)
Source: Drug Safety - June 11, 2019 Category: Drugs & Pharmacology Source Type: research

Comparative Effectiveness and Safety of Direct Oral Anticoagulants in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis of Observational Studies
ConclusionsAs head-to-head trials comparing different DOACs do not exist, available evidence derives exclusively from observational studies. These data suggest that while dabigatran, rivaroxaban, and apixaban have a similar effect on the risk of ischemic stroke, apixaban may be associated with a decreased risk of major bleeding compared with either dabigatran or rivaroxaban. (Source: Drug Safety)
Source: Drug Safety - June 7, 2019 Category: Drugs & Pharmacology Source Type: research

Prevalence, Safety and Long-Term Retention Rates of Biologics in Hong Kong from 2001 to 2015
ConclusionThis population-based study revealed an increasing prevalence of biologic prescribing. Results from the study described the long-term retention rates and incidence rates of serious infections of biologic treatments for all indications, and confirmed the safety of biologic treatments. Since this study provides an overview of all biologic utilization, further studies on cost effectiveness, safety and compliance of treatment in different patient groups are still warranted. (Source: Drug Safety)
Source: Drug Safety - June 5, 2019 Category: Drugs & Pharmacology Source Type: research

Antidepressants and the Risk of Hemorrhagic Stroke in the Elderly: a Nested Case –Control Study
ConclusionOur study shows that the use of medications inhibiting serotonin and/or noradrenaline reuptake increases the risk of HS in patients aged 65  years and older and that the risk varies across individual ADs. (Source: Drug Safety)
Source: Drug Safety - June 4, 2019 Category: Drugs & Pharmacology Source Type: research

Unintended Effects of Communicating About Drug Safety Issues: A Critical Review of the Literature
AbstractCommunications about the safety and effectiveness of human drugs can influence patients ’ and prescribers’ perceptions and behaviors, which in turn can affect the public’s health more broadly. We conducted a critical review of the literature on the unintended effects from communicating information to the public about safety issues with prescription and over-the-counter drugs. We searched PubMed for peer-reviewed studies published from 1990 to 2017 where study authors reported probable unintended effects of communicating drug safety. The types of communications included in these studies were news r...
Source: Drug Safety - May 31, 2019 Category: Drugs & Pharmacology Source Type: research