National Drug Safety Research Articles

Study protocol of the CREDO randomised controlled trial: evaluation of a structured return home consultation for patients suffering from metastaticcancer

IntroductionPatients suffering from cancer are often managed by multiple health professionals. General practitioners with specific skills in oncology could facilitate care coordination between hospital and general practice in the management...

Assessment of Safety Signals for Aztreonam in Different Age Groups: National and International Drug Safety Monitoring

Aztreonam is the only approved monocyclic β-lactam antibiotic for human use that is active against Gram-negative aerobes, primarily Pseudomonas аeruginosa. Aztreonam has been used for more than 35 years, and aztreonam lysine has been on the market for 15 years. Although the medicinal products show clinical and microbiological efficacy in severe infections and are significant for cystic fibrosis patients, little information is published on their safety. In the meantime, new data have accumulated.The aim of the study was to analyse the data on adverse reactions in patients of different age groups receiving aztreonam, collected in the safety monitoring databases VigiBase and Pharmacovigilance.Materials and methods: the data on adverse reactions associated with aztreonam, in any dosage form, from the individual case reports submitted to VigiBase (the database of the Uppsala Monitoring Centre) before 15.09.2021 and to Pharmacovigilance (the database for spontaneous reports in the Automated Information System of the Federal Service for Surveillance in Healthcare of the Russian Federation) before 05.10.2021.Results: the analysis of adverse reactions during the use of aztreonam for approved indications showed differences in frequency, types and severity of the adverse reactions amongst the age groups. The most common adverse reaction with aztreonam was cystic fibrosis referred to in 1828 reports (12.0%). It was recorded more often in patients aged 18–44 years (39.2%).Conclusions: the data obtained allowed the authors to identify a new safety signal for aztreonam, namely an increased risk of inefficacy or insufficient efficacy in cystic fibrosis considered an adverse reaction in the individual reports from the databases of spontaneous reports. Confirmation of the signal requires further monitoring.

A National Survey of Community Pharmacists' Viewpoints About Pharmacovigilance and Adverse Drug Reaction Reporting in Saudi Arabia.

This study assessed the knowledge, attitudes, and practices of community pharmacists regarding pharmacovigilance and adverse drug reaction (ADR) reporting system in Saudi Arabia. A cross-sectional survey of community pharmacists from different regions in Saudi Arabia was performed through convenience sampling between November 2020 and January 2021. The responses were received from 1,172 community pharmacists. Most respondents (86.7%) were familiar with the National Pharmacovigilance and Drug Safety Center, and 830 (70.8%) knew about the ADR reporting form. The majority (94%) of the respondents agreed with the importance of reporting ADRs for patient care and national health. Although 92.2% of the participants asked their patients about ADRs, 90.2% agreed that more training programs are required to be organized by the Saudi Food and Drug Authority for healthcare professionals on the ADR detection and reporting system. Analgesic agents were the most common drug category for which ADRs were reported (67.4%). The majority (92.1%) of ADRs reportedly occurred in patients with chronic diseases. The study concluded that most community pharmacists in Saudi Arabia are knowledgeable and have good attitudes and practices regarding pharmacovigilance and ADR reporting.

OP0138 RISK OF CANCER AFTER BIOLOGIC AND TARGETED SYNTHETIC DMARDS INITIATION IN PATIENTS WITH RHEUMATIC DISEASES AND A HISTORY OF PRIOR MALIGNANCY: DATA FROM THE BIOBADASER REGISTRY

BackgroundPatients with a history of cancer are routinely excluded from randomized controlled trials. As consequence, data on the safety of biologic disease modifying antirheumatic drugs (bDMARDS) and targeted synthetic (ts) DMARDs are limited. Although real world data from various national registries have not provided evidence of increased cancer recurrence, additional data from real-world registries may help to confirm safety of non-TNFi bDMARDs and tsDMARDs regarding cancer recurrence to guide treatment decisions.ObjectivesTo compare the risk of incident malignancy with exposure to different bDMARDs and tsDMARDs in patients with rheumatic diseases and a prior malignancy.MethodsThe study population comprised patients with a prior malignancy from the BIOBADASER 3.0 up to 2021. BIOBADASER is a large national drug safety registry of patients with rheumatic diseases starting treatment with any bDMARD or tsDMARD and followed thereafter at the time an adverse event or a change in biological therapy occurs. Incident cancer was defined as any cancer (new primaries, local recurrence or metastases) during the exposure classified according to Meddra dictionary. Incidence rate ratios of cancer per 1000 patients-year (PY) and 95% CI were estimated. Rates of incident cancer in tsDMARDs and other bDMARDs versus anti-TNF treated patients were compared.ResultsA total of 9,129 patients treated with bDMARDs and tsDMARDs are included in BIOBADASER 3.0 at the time of the study. Of them, 352 with a prior history of malignancy at time of enrollment were selected for analysis (Figure 1). Overall, there were 32 incident malignancies (17 solid cancer, 14 non-melanoma skin cancer and 1 melanoma). The overall rate of incident malignancy was 27.1 (95% CI 18.6-38.3) events/1,000 PY, ranging between none events/1000 PY in the anti-IL17 group to 51.7 events/1000 PY in the anti-CTLA-4 group (Table 1). The overall rate of incident cancer did not differ significantly in patients exposed to JAKi [0.6 (95% CI 0.1-2.5)], anti-CD20 [0.3 (95% CI 0.1-1.4)], anti-IL6 [1.2 (95% CI 0.5-3.4)] or anti-CTLA-4 [1.3 (95% CI 0.5-3.6) versus anti-TNF therapy. The rate of different types of cancer (melanoma, non-melanoma skin cancer or solid tumors) did not differ between the different treatment groups when compared to anti-TNF therapy (Table 1).Table 1.Baseline characteristics and rate of incident cancer.Anti-TNF(n = 185)JAKi(n = 61)Anti-CD20(n= 61)Anti-IL6(n= 68)Anti-CTLA-4(n= 47)Anti-IL17(n= 39)Total(n=352)Female, n (%)129 (69.7)49 (80.3)43 (70.5)54 (79.4)34 (72.3)21 (53.9)247 (70.2)Age, mean (SD)64.4 (13.1)66.7 (13.1)67.8 (10.0)70.5 (11.6)71.8 (10.4)59.5 (14.6)65.3 (13.0)Start treatment age, mean (SD)60.0 (12.9)64.8 (12.8)65.7 (9.6)67.3 (11.3)62.8 (12.7)56.9 (14.5)61.6 (12.8)Disease duration, median (IQR)6.7 (3.0-13.1)12.3 (7.4-19.6)10.8 (6.3-19.4)8.5 (4.0-16.8)8.2 (4.1-16.6)8.4 (4.7-16.1)7.0 (2.9-15.5)Time of follow-up months, mean (SD)23.1 (25.3)15.9 (13.3)11.5 (2.5)16.8 (17.6)23.7 (22.6)18.4 (15.5)17.5 (18.2)Charlson comorbidity index4.9 (2.0)5.2 (2.2)5.1 (2.0)5.5 (2.1)6.1 (2.6)6.9 (2.6)5.2 (2.1)Prior malignancyNon-lymphoproliferative (solid or melanoma), n (%)174 (94.5)58 (95.1)54 (88.5)65 (95.6)46 (97.9)36 (92.3)331 (94.0)Lymphoproliferative, n (%)9 (4.9)3 (4.9)13 (21.3)4 (5.9)4 (8.5)5 (12.8)29 (8.2)Metastatic cancer, n (%)2 (1.1)2 (3.3)2 (3.3)1 (1.5)3 (6.4)0 (0.0)7 (2.0)Incident cancerNew cancer diagnosis, n (%)182255032Time of exposure, sum (years)470,191,6163104,996,863,81178,6Rate of incident cancer (per 1,000 PY)38.3 (24.1-60.8)21.8 (5.5-87.3)12.3 (3.1-49.1)47.7 (19.8-114.5)51.7 (21.5-124.1)0 (0-0)27.1 (18.6-38.3)Rate ratio of incident cancer (vs anti-TNF)-0.6 (0.1-2.5)0.3 (0.1-1.4)1.2 (0.5-3.4)1.3 (0.5-3.6)--Figure 1.Flowchart of patients included.ConclusionThe risk of incident cancer in patients with rheumatic diseases and a prior malignancy does not differ according to the type of bDMARD and tsDMARD exposure.Disclosure of InterestsNone declared

Community pharmacists’ challenges regarding adverse drug reaction reporting: a cross-sectional study

Objective The effectiveness of the national drug safety monitoring program directly depends on the active participation of healthcare professionals in reporting suspected adverse drug reactions (ADRs). The aim of the study was to explore community pharmacists’ comprehension of pharmacovigilance, their perspectives toward reporting ADRs and investigate the current practice of ADR reporting among pharmacists in Serbia. Methods This descriptive cross-sectional study was performed on a sample of pharmacists in Serbia between November 2019 and March 2020 using a pre-tested questionnaire distributed online. Eligible participants were community pharmacists in Serbia who were willing to participate in the study during the data collection period. Non-parametric statistical tests were performed in the analysis of knowledge, perspectives and ADR reporting. The validity and reliability of the survey were measured by exploratory factor analysis. Results The median knowledge score was 6 out of 10 (interquartile range 5–7, range 2–10). No significant differences in the knowledge scores of pharmacists were found based on weekly working hours (U = 24,805, p = .374), working experience (χ 2 = 4.011, DF = 2, p = .135), being a member of a professional organization (U = 24,312, p = .209), or highest level of pharmacy qualification obtained (χ 2 = 3.233, DF = 3, p = .506). Only 28.8% of pharmacists reported ADR at least once a year, while the majority of them have never reported any ADRs. Conclusions Despite the community pharmacists’ positive attitude toward adverse drug reporting and their role in the process, they show limited knowledge regarding the issue and highly prevalent under-reporting of ADRs. Educational programs are necessary to increase ADRs reporting.

Features of intellectual property protection mechanisms on the example of orphan drugs circulation

Objective: to study features of intellectual property protection mechanisms on the example of drugs for the treatment of rare (orphan) diseases.Material and methods. Analysis of pharmaceutical market data was performed with the DSM Group analytical database. The approach proposed by the Russian Federal Industrial Property Service was used for creating patent landscape. The method supposes conducting a patent search and analysis of the documents found for date of filing, office (country) of filing, applicant, as well as analysis of the patent activity (dynamics) for the subject, in this case, for orphan drugs having a defined structure.Results. We proposed the complex conclusions to increase national drug safety. Intellectual property limitations for importing countries such as data exclusivity, do not allow to reproduce clinical trials, which leads to non-disclosure of medical data to all parties – medical society and patients, all other market participants, including local pharmaceutical producers. Current intellectual property restrictions conceal crucial data from medical and patient society and other market players and affect accuracy of diagnosis and treatment. Along with outstanding cost of new therapies it causes enormous budget burden for the healthcare system and prevents the introduction of objective criteria in the appointment and use of medicines. Prior to the approval and submission of the registration certificate by the regulatory authority, it is necessary to establish reasonable marginal prices, to form a sufficient set and volume of clinical guidelines and to determine in advance the sources of financing and mechanisms of integration into the national system of drug provision.Conclusion. The introduction of drugs for the treatment of rare diseases into circulation leads to a sharp increase in the burden on the budgets of the healthcare system at all levels. Current restrictions and obligations in the field of intellectual property rights protection, the degree of disclosure of medical data in the process of registration and admission to the market require significant changes to the traditional system of drug provision and the system of placing state orders, as well as the introduction of new regulatory mechanisms (for example, compulsory licensing or producing individual dosage forms in pharmacy organizations), contributing to the development of the local pharmaceutical industry and providing the national health system with the necessary volume of drugs with a sufficient level of quality and safety.

Prescription de psychotropes potentiellement inappropriés chez les sujets âgés en Occitanie Ouest

Psychotropic drugs remain frequently prescribed in elderly people. Some of them are classified as «inappropriate» because they could increase the risk of adverse drug reactions. The aim of this study is to evaluate the prevalence of exposure to potentialy inappropriate psychotropic drugs (PIPs) in the elderly living in nursing home residents (EHPAD) in West Occitanie area. We carried out a retrospective study on the cohort of PAAPI program (Personne âgée et amélioration des prescriptions inappropriées) participating in PAAPI program set up in West Occitanie in 2016 including 3095 patients during 2 years. PIPs were identified by the list EU(7)PIM and completed with the guidelines mailed by the National Drug Safety Agency. We measured the prevalence of exposure to PIPs in this population. The majority of the residents (n=2301, 74.4%) were female of the average age was 87.1±8.1 years and. The prevalence of exposure to psychotropic drugs was about 77.5% with an average of 1.6 prescription lines per patient (±1,1). We found antidepressants (36.5% of PIP) with mainly paroxetine (37.3% of antidepressants PIP), followed by venlafaxine (32.8%), hypnotics and sedatives (26.6% of PIP) with zopiclone with inappropriate dose (59.4% of hypnotics PIP), anxiolytics (25.8% of PIP) with alprazolam (37.9% of anxiolytics PIP), followed by bromazepam (16%) and antipsychotics (11.2% of PIP) with cyamemazine (100% of inappropriate prescription) followed by aripiprazole and haloperidol (respectively 100% and 14.7% of inappropriate prescription). According to our data, third of elderly people in Nursing Homes were exposed to a PIP suggesting that guidelines about psychotropic drugs prescription are not well followed. Then, information campaign of healthcare professionnals could be useful to improve psychotropic drug prescription in the elderly population.

Patterns of adverse drug reactions (ADRs) in Saudi Arabia

BackgroundPharmacovigilance enhances post-market drug safety. However, analytical reports of a pattern of adverse drug reactions (ADRs) experienced by patients in Saudi Arabia are demanded. ObjectiveTo describe patterns of ADRs submitted to the Saudi Central National Pharmacovigilance and Drug Safety Center (NPC), Saudi Food and Drug Administration (SFDA), from its inception in 2015 until the end of 2017 to understand the pattern of ADR reporting in Saudi Arabia. MethodsIn this retrospective study, data from cases reported to the NPC were used to determine ADRs and identify the most common associated drug classes based on anatomical therapeutic chemical (ATC) classification system. ResultA total of 17,730 ADR cases were reported during study period. An annual increase in ADRs was clearly evident. Approximately 54% of the total ADRs reported were serious. Most commonly reported ATC drug classes were anti-infective agents for systemic use (22.27%), antineoplastic and immunomodulating agents (21.49%), alimentary tract and metabolism (15.48 %), cardiovascular system (11.11%) and nervous system (10.23%). Vancomycin (2.7%), ceftiraxone (1.8%), fingolimod (1.4%) and paracetamol (1.4%) were the most common drugs associated with serious ADRs. ConclusionThis study provide valuable insights in hypothesis generation for future studies on drug-event interactions and amplification studies. The NPC educational programs and awareness campaigns to promote systematic reporting of ADRs among healthcare professionals and general public should be continued.

Disproportionality analysis of reported drug adverse events to assess a potential safety signal for pentavalent vaccine in 2019 in El Salvador

Detection and surveillance of vaccine safety hazards is a public health staple. In the post-marketing phase, when vaccines are used in mass, it is crucial to monitor potential signals of adverse reactions that may have been missed in the pre-marketing phase. We analysed spontaneous reports of drug adverse events in El Salvador to assess a potential safety signal related to an increase in febrile seizures following the pentavalent (diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae Type B) vaccine in 2019.This was a retrospective observational study of adverse event notifications in the national electronic drug safety database from 2011 to 2019. We performed standard disproportionality analysis computing Proportional Reporting Risk (PRR), Reporting Odds Ratio (ROR), Relative Reporting Ratio (RRR), Chi-squared, and Information Component (IC), comparing the pairing of febrile seizures and pentavalent vaccine to all other drugs and adverse events recorded in 2019.The occurrence of febrile seizures following pentavalent vaccination exceeded the WHO expected rate of six cases × 100 000 doses administered from April 2019, with a maximum of 9.2 in September. IC was 4.3, ORR 421.9 (95% Confidence Interval, CI: 123.8–1437.7), PRR 223.5 (95 %CI: 70.2–710.9), RRR was 19.5. The first booster presented the highest rate (14.6 per 100,000 doses) of febrile seizures, more than double than expected. Rates for 2018 remained below expected. Reports of febrile seizures following pentavalent vaccine were also on the increase globally since 2014, with highest rates in 2018 and 2019.There was a disproportion of febrile seizures notifications following pentavalent in El Salvador in 2019, suggesting the existence of a safety signal. This may be due to the change in provider. Further studies should assess the causes of the increase and compute costs and benefits of this vaccination to determine if switching to a less reactogenic vaccine formulation is indicated.

Les méningiomes : mise au point sur les connaissances actuelles

Meningiomas are the most frequent among intracranial tumors, and represent more than 30% of primitive central nervous system neoplasms. Arising from the meninges, they are generally benign lesions and can be treated by either radio-clinical follow-up or surgical resection with excellent outcome. However, more than 20% of meningiomas harbor atypical or malignant features and represent challenges for both prognostic evaluation and therapeutic strategy. The discovery of the genetic and epigenetic landscapes of meningiomas enabled the identification of new prognostic markers and potential therapeutic targets for refractory meningiomas. This review summarizes current epidemiology, histological and molecular characteristics, diagnosis and treatments for meningiomas, and highlights the close relationship between the development of meningiomas and hormonal intake, as illustrated by recent recommendations of the “Agence Nationale de Securité du Medicament”, the French national drug safety agency.

An assimilation of risk factors, mechanisms,and plausible measures to intercept druginduced pulmonary diseases

The havoc created by a plethora of drug-induced diseases in the field of medical practice is devastating. A drug being introduced for its appropriate indication simultaneously evokes the risks of unwanted adverse effects of these medications in the patients. Researchers, clinicians, pharmacists, and various national and international drug safety centres are constantly involved in the quest to identify, investigate, mitigate and document the adverse effects caused by the countless number of drugs introduced to treat a multitude of human diseases. This article is intended to summarize the different types, mechanisms, risk factors, and basic measures to manage various drug-induced pulmonary disorders and their manifestations.

Drug Safety Governance: Framework and Development Path

Objective: The necessity of shifting from management to governance of drug safety has gained a wide consensus in both academic and practical circles, but how to act and develop has not been adequately discussed and become a key issue that needs to be addressed nowadays. This article combines the theoretical essence of governance to establish an analytical framework of “initial conditions-joint action-governance effectiveness” based on governance theory to analyze and explain the connotation and mechanism of cross-sector cooperative governance of drug safety. Methods: The essence of governance lies in the creation of joint action capabilities through cross-sector cooperation, as well as the construction of a national drug safety governance action framework of “3 stages + 1 incubation period”. This article analyzes the connotation of each stage and possible problems or obstacles. Results: Three deep-seated challenges stem from the lack of information sharing, resource action sharing, and power sharing. Conclusion: In order to improve the modernization construction of China’s drug safety governance system and capacity, it is recommended to continuously improve Chinese drug safety governance in terms of governance norms, communication mechanisms, capacity development, and cross-sector coordination based on a holistic perspective.

Stakeholders’ perspectives on a patient-reported outcome measure-based drug safety monitoring system for immune-mediated inflammatory diseases

ABSTRACT Background Biologics are used as effective therapeutics to treat a variety of diseases. Even though biologics are widely used, knowledge on the post-marketing experience of patients is limited. Therefore, a framework was established for a patient-reported outcome measure (PROM)-based drug safety monitoring system for ADRs attributed to biologics, known as the ‘Dutch Biologic Monitor’. Objective Generation of a multi-stakeholder perspective on the preferred setup, potential and added value of a PROM-based national drug safety monitoring system. Methods Nineteen stakeholders were interviewed following a structured interview guide. Transcribed data were coded and analyzed to count frequencies and to generate recurring themes. Results Stakeholders (84.2%) support the establishment of a national drug safety monitoring system, but the feasibility depends on the implementation process. The need for integration and assessment of PROMs on ADRs in clinical practice and the preference to monitor small molecules and new drugs were emphasized. Preferably, all pharmacological options per indication should be monitored. Conclusions Stakeholders recommend to establish a PROM-based national drug safety monitoring system focused on ADRs attributed to biologics, small molecules, and new drugs. Moreover, PROMs on ADRs ideally need to become integrated in clinical practice to provide health-care providers more insight in patients’ perspectives.

The medical uses of manosonic nebulizers (AMSA®) in 2018

AimsThe purpose of repeated application of manosonic nebulizers (AMSA®) is to ensure active Eustachian tube rehabilitation and optimal middle-ear drug diffusion. In response to recent changes in marketing authorizations issued by the French National Drug Safety Agency (ANSM), the present study investigated how AMSA® is used in the Auvergne-Rhône-Alpes Region of France. Material and methodsA prospective non-interventional regional 1-year survey was conducted in 701 general practitioners and community and hospital ENT physicians in the Auvergne-Rhône-Alpes Region, using a questionnaire sent by mail with a reminder at 2 months. Percentage responses were compared on Chi2 test with alpha risk of 5%. Non-respondents were excluded. EndpointsThe main endpoints were rate of AMSA® prescription, and prescription modalities in a specific geographical territory (Auvergne-Rhône-Alpes Region) in 2018. Results93% of the 114 respondents prescribed AMSA®, with 4,000 prescriptions in 1 year. 66.7% prescribed this treatment to avoid recourse to myringotomy. Mean treatment duration was 2 weeks (50.9% of respondents). The most frequent nebulized substance was saline serum (68.4% of respondents), sometimes associated to corticosteroids or mucolytics. ConclusionThe majority of physicians in the Auvergne-Rhône-Alpes Region, and notably the ENT physicians, were AMSA® prescribers for the treatment of Eustachian tube dysfunction and its consequences. However, the duration and modalities of use of AMSA® were very heterogeneous, and further studies are needed to standardize prescription.

The Adverse Effects Reporting of Antibiotic Induced Diarrhea

Introduction: In Saudi Food and Drug Authority, there is a center called National Pharmacovigilance and Drug Safety Center responsible for adverse events reporting. This study aims to demonstrate the antibiotic induced diarrhea reporting by National Pharmacovigilance and Drug Safety Center in Saudi Arabia.
 Methodology: This is a retrospective study about the reporting of diarrhea adverse effects caused by antibiotics. The data were collected from the adverse effects reports that were submitted to Saudi Food and Drug Authority in 2017 and 2018.
 Results: Gastrointestinal adverse effects reports were mainly for penicillin antibiotics. The major gastrointestinal adverse effect of penicillin was diarrhea (100 reports out of 147 reports for penicillin include diarrhea). Most of the diarrhea reports were caused by Amoxicillin/Clavulanate followed by Amoxicillin.
 Conclusion: One of the major adverse effects for antibiotics is diarrhea that is mainly occurred by penicillin antibiotics. The majority of cases of antibiotics-associated diarrhea are not serious, but still affect the patients’ quality of life. Therefore, it is important to increase the awareness regarding medications adverse effects and their reporting.

Intravenous versus subcutaneous route pharmacokinetics of paracetamol (acetaminophen) in palliative care patients: study protocol for a randomized trial (ParaSCIVPallia)

BackgroundAmong palliative care (PC) patients who are administered paracetamol, the subcutaneous (SC) route is often an alternative to the intravenous (IV) route. Yet pharmacological and clinical data on whether these are equivalent pharmacokinetically are lacking. Many French palliative teams are now empirically using paracetamol by the SC route, but there are no data to support this practice. This trial aims to compare the pharmacokinetic (PK) parameters of paracetomol between the IV and SC routes in PC patients.Methods/designThis is a randomized, open, crossover study in two PC centers. The primary endpoints are AUC0-t, AUC0-∞, Cmax, Vd, and t1/2. All adverse events will be reported for a safety analysis. Twenty adult PC patients with an IV device having spontaneous pain not related to care, with a numeric pain rate scale > 3/10, or having a systematic prescription of paracetamol as the usual treatment will be included. All patients also have to meet all eligibility criteria.ConclusionThis is the first study comparing PK parameters for IV paracetamol versus SC paracetamol in PC patients.Trial registrationClinicalTrials.gov, NCT03944044. Registered on 4 June 2019.Committee for the protection of persons (CPP) 18.09.05.58206 approval 4 October 2018.National Drug Safety Agency (ANSM; Agence Nationale de Sécurité Médicament) MEDAECNAT-2018-09-00009 approval 29 November 2018.

Regulatory aspects of prospective and retrospective clinical research in France in 2018

In France, the so-called “Jardé law” (named for its proposer) on human research, implemented since 2016, defines the regulatory and legal framework for “prospective” studies, formerly known as “biomedical research” or “common care”. Three categories are distinguished: type 1 is at-risk drug or non-drug interventional research, type 2 is low-risk, low-burden interventional research, and type 3 is non-interventional research. The decrees of April 12, 2018 precisely define a list of research categories for types 2 and 3, thereby clarifying the regulatory procedures. The Sponsor registers the trial on the database of the National Drug Safety Agency (ANSM), or the European EudraCT database for drug studies, to obtain an identification number. Regulatory procedures are undertaken with the IRB and ANSM and then the Data Protection Commission (CNIL). Retrospective research on previously collected data (other than genetic) does not come under the Jardé law, and is governed by the 1978 data protection law, updated by the application decree of December 2016 and the law No. 2018-493 of June 20, 2018 on protection of personal data. This article presents a clarification of the key methodologic and regulatory steps.

Antipsychotic Prescribing to Patients Diagnosed with Dementia Without a Diagnosis of Psychosis in the Context of National Guidance and Drug Safety Warnings: Longitudinal Study in UK General Practice.

IntroductionPolicy interventions to address inappropriate prescribing of antipsychotic drugs to older people diagnosed with dementia are commonplace. In the UK, warnings were issued by the Medicines Healthcare products Regulatory Agency in 2004, 2009 and 2012 and the National Institute for Health and Care Excellence guidance was published in 2006. It is important to evaluate the impact of such interventions.MethodsWe analysed routinely collected primary-care data from 111,346 patients attending one of 689 general practices contributing to the Clinical Practice Research Datalink to describe the temporal changes in the prescribing of antipsychotic drugs to patients aged 65 years or over diagnosed with dementia without a concomitant psychosis diagnosis from 2001 to 2014 using an interrupted time series and a before-and-after design. Logistic regression methods were used to quantify the impact of patient and practice level variables on prescribing prevalence.ResultsPrescribing of first-generation antipsychotic drugs reduced from 8.9% in 2001 to 1.4% in 2014 (prevalence ratio 2014/2001 adjusted for age, sex and clustering within practices (0.14, 95% confidence interval 0.12–0.16), whereas there was little change for second-generation antipsychotic drugs (1.01, confidence interval 0.94–1.17). Between 2004 and 2012, several policy interventions coincided with a pattern of ups and downs, whereas the 2006 National Institute for Health and Care Excellence guidance was followed by a gradual longer term reduction. Since 2013, the decreasing trend in second-generation antipsychotic drug prescribing has plateaued largely driven by the increasing prescribing of risperidone.ConclusionsIncreased surveillance and evaluation of drug safety warnings and guidance are needed to improve the impact of future interventions.Electronic supplementary materialThe online version of this article (doi:10.1007/s40264-017-0538-x) contains supplementary material, which is available to authorized users.

Factors associated with underreporting of adverse drug reactions by nurses: A narrative literature review

Spontaneous reporting of adverse drug reactions (ADRs) by health-care professionals is the basic method for the identification and prevention new and serious ADRs of marketed drugs. The contribution of nurses in this task can improve patient safety and reduce the extra financial burden associated with it. Although a total of 11% of ADRs in National Pharmacovigilance and Drug Safety Center were reported by nurses. The objectives of this review were to identify the possible factors that lead to underreporting of ADRs by nurses and define strategies that increase the reporting. This review has revealed various factors that influence the underreporting of ADRs and strategies to encourage reporting by nurses. Most of the identified factors are potentially modifiable. To overcome the underreporting of ADRs by nurses' main interventions should be based on education, motivation, and determination.

Syndrome de Lyell à l’acide fusidique oral d’évolution fatale

Herein, we report the first case of toxic epidermal necrosis due to oral fusidic acid having a fatal outcome. An 82-year-old woman was referred to our dermatology department for generalized bullous skin eruption. Clinical examination showed fever, oral and ocular ulcerations, and epidermal detachment involving more than 70 % of her body surface area together with a positive Nikolsky sign. Lyell's syndrome was diagnosed. Cutaneous histology showed total epidermal necrosis and a normal dermis. Oral fusidic acid had been prescribed 12 days earlier for a chronic sacral pressure sore. No other treatment had been introduced during the previous two months. The outcome was fatal within 24 hours. Fusidic acid is commonly used topically by dermatologists for limited staphylococcal skin infections. Oral treatment is rare and is recommended only for skin, bone or joint infections. This is the first reported case of toxic epidermal necrolysis due to oral fusidic acid. The French national drug safety monitoring register contains only one case in which fusidic acid was a possible culprit. Fusidic acid must be considered a potential source of serious cutaneous adverse reactions, particularly toxic epidermal necrolysis.