Proactively managing the risk of marketed drugs: experience with the EMA Pharmacovigilance Risk Assessment Committee

Arlett, Peter; Portier, Geraldine; Lisa, Roberto de; Blake, Kevin; Wathion, Noël; Dogné, Jean‐Michel; Spooner, Almath; Raine, June; Rasi, Guido

doi:10.1038/nrd3713-c1

Cited by 44 publications

(34 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The monitoring of the safety of medicines has been enhanced as a result of the new European pharmacovigilance legislation, which serves to proactively manage the risk of marketed drugs in a sustainable life‐cycle benefit‐risk management approach . Within this legislation, the PRAC is responsible both for implementing RMM and for overseeing their effectiveness . With this in mind, a key objective of the present study was to proactively assess the impact of the introduced measures on codeine prescribing for pain in “real‐world” clinical practice.…”

Section: Introductionmentioning

confidence: 99%

A European multicentre drug utilisation study of the impact of regulatory measures on prescribing of codeine for pain in children

Hedenmalm¹,

Blake²,

Donegan³

et al. 2019

Pharmacoepidemiology and Drug

Self Cite

View full text Add to dashboard Cite

Purpose In June 2013, following recommendations from the World Health Organization (WHO) and Food and Drug Administration (FDA), the European Medicines Agency agreed updates to the codeine product information regarding use for pain in children younger than 12 years and children undergoing tonsillectomy or adenoidectomy (TA) for obstructive sleep apnoea. This study was conducted to (a) assess effectiveness of these measures on codeine prescribing in the “real‐world” setting and (b) test feasibility of a study using a common protocol by regulators with access to databases. Methods The study was performed using BIFAP (Spain), CPRD (UK), and IMS® Disease Analyzer (France and Germany) databases. Prescribers included general practitioners (GPs) (France and UK), GPs and paediatricians together (Spain), and GPs, paediatricians, and ear, nose, and throat (ENT) specialists separately (Germany). Between January 2010 and June 2015, prevalence of codeine prescribing was obtained every 6 months, and a time series analysis (joinpoint) was performed. Codeine prescribing within ±30 days of TA was also identified. Furthermore, doses, durations, and prior prescribing of other analgesics were investigated. Results Over the 5‐year period, codeine prescribing decreased in children younger than 12 years (by 84% in France and Spain, 44% in GP practices in Germany, and 33% in the United Kingdom). The temporal pattern was compatible with the regulatory intervention in France and the United Kingdom, whereas a decrease throughout the study period was seen in Germany and Spain. Decreased prescribing associated with TA was suggested in ENT practices in Germany. Conclusions Codeine prescribing for children decreased in line with introduced regulatory measures. Multidatabase studies assessing impact of measures by EU regulators are feasible.

show abstract

Section: Introductionmentioning

confidence: 99%

A European multicentre drug utilisation study of the impact of regulatory measures on prescribing of codeine for pain in children

Hedenmalm¹,

Blake²,

Donegan³

et al. 2019

Pharmacoepidemiology and Drug

Self Cite

View full text Add to dashboard Cite

show abstract

“…This reflects the EU Pharmacovigilance legislation introduced in 2012. The legislation and the establishment of the Pharmacovigilance Risk Assessment Committee focus on all aspects of the risk management of drugs for human use, including the assessment of the risk of adverse reactions, while taking the therapeutic effect of the medicine into account. With regard to pregnancy data, in 2002 the FDA issued an amendment describing the requirement for the collection of pregnancy data through registries .…”

Section: Discussionmentioning

confidence: 62%

Registries supporting new drug applications

Jonker

Berg

Kwa

et al. 2017

Pharmacoepidemiology and Drug

View full text Add to dashboard Cite

PurposeKnowledge of the benefits and risks of new drugs is incomplete at the time of marketing approval. Registries offer the possibility for additional, post‐approval, data collection. For all new drugs, which were approved in the European Union between 2007 and 2010, we reviewed the frequency, the type, and the reason for requiring a registry.MethodsThe European Public Assessment Reports, published on the website of the European Medicine Agency, were reviewed for drugs approved by the Committee for Medicinal Products for Human Use. We searched for key characteristics of these drugs, including therapeutic area (ATC1 level), level of innovation (the score is an algorithm based on availability of treatment and therapeutic effect), and procedural characteristics. In addition, we identified if these registries were defined by disease (disease registry) or exposure to a single drug (drug registry).ResultsOut of 116 new drugs approved in the predefined period, for 43 (37%), 1 to 6 registry studies were identified, with a total of 73 registries. Of these 46 were disease registries and 27 (single) drug registries. For 9 drugs, the registry was a specific obligation imposed by the regulators. The level of innovation and the orphan status of the drugs were determinants positively predicting post‐approval registries (OR 10.3 [95% CI 1.0‐103.9] and OR 2.8 [95% CI 1.0‐7.5], respectively).ConclusionsThe majority of registries required by regulators are existing disease registries. Registries are an important and frequently used tool for post‐approval data collection for orphan and innovative drugs.

show abstract

“…) yet CD40 induced low‐level production. Both IL‐22 and IL‐21 have pro‐inflammatory properties, but the pleiotropic effects of IL‐21 include predominantly regulatory properties . CD40 and CD28 co‐stimulation independently were equivalent at inducing IL‐2 (Fig.…”

Section: Resultsmentioning

confidence: 99%

CD40‐mediated signalling influences trafficking, T‐cell receptor expression, and T‐cell pathogenesis, in the NOD model of type 1 diabetes

et al. 2017

View full text Add to dashboard Cite

CD40 plays a critical role in the pathogenesis of type 1 diabetes (T1D). The mechanism of action, however, is undetermined, probably because CD40 expression has been grossly underestimated. CD40 is expressed on numerous cell types that now include T cells and pancreatic β cells. CD40 CD4 cells [T helper type 40 (TH40)] prove highly pathogenic in NOD mice and in translational human T1D studies. We generated BDC2.5.CD40 and re-derived NOD.CD154 mice to better understand the CD40 mechanism of action. Fully functional CD40 expression is required not only for T1D development but also for insulitis. In NOD mice, TH40 cell expansion in pancreatic lymph nodes occurs before insulitis and demonstrates an activated phenotype compared with conventional CD4 cells, apparently regardless of antigen specificity. TH40 T-cell receptor (TCR) usage demonstrates increases in several Vα and Vβ species, particularly Vα3.2 that arise early and are sustained throughout disease development. TH40 cells isolated from diabetic pancreas demonstrate a relatively broad TCR repertoire rather than restricted clonal expansions. The expansion of the Vα/Vβ species associated with diabetes depends upon CD40 signalling; NOD.CD154 mice do not expand the same TCR species. Finally, CD40-mediated signals significantly increase pro-inflammatory Th1- and Th17-associated cytokines whereas CD28 co-stimulus alternatively promotes regulatory cytokines.

show abstract

Proactively managing the risk of marketed drugs: experience with the EMA Pharmacovigilance Risk Assessment Committee

Cited by 44 publications

References 6 publications

A European multicentre drug utilisation study of the impact of regulatory measures on prescribing of codeine for pain in children

A European multicentre drug utilisation study of the impact of regulatory measures on prescribing of codeine for pain in children

Registries supporting new drug applications

CD40‐mediated signalling influences trafficking, T‐cell receptor expression, and T‐cell pathogenesis, in the NOD model of type 1 diabetes

Contact Info

Product

Resources

About