Good Pharmacovigilance Practice in Paediatrics: An Overview of the Updated European Medicines Agency Guidelines

Sultana, Janet; Zaccaria, Cosimo; Lisa, Roberto de; Rossi, Francesco; Capuano, Annalisa; Ferrajolo, Carmen

doi:10.1007/s40272-019-00350-w

Cited by 10 publications

(7 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is due to a different and immature pharmacokinetic and pharmacodynamics profile (i.e. different volumes of distribution and activities of drugmetabolizing enzymes/transporters), uncertainties on the longterm drug risk-benefit profile, and frequent off-label use of drugs (Lerose et al, 2012;Shebley et al, 2019;Sultana et al, 2019). Indeed, medicines authorized for the use in pediatric age are still very few, due to major barriers existing in testing and licensing medications for children such as small market size and fewer chronic illnesses and the resulting difficulty in enrolling a sufficient number of pediatric patients (Milne and Bruss, 2008).…”

Section: Introductionmentioning

confidence: 99%

Safety of Anticancer Agents Used in Children: A Focus on Their Off-Label Use Through Data From the Spontaneous Reporting System

et al. 2020

View full text Add to dashboard Cite

Background: Among factors influencing the higher risk of developing unknown or rare adverse drug reactions (ADRs) among children and adolescents, there is the frequent offlabel use of drugs that seems to be very common in pediatric oncological patients. Our study aim to collect and evaluate data on the safety profile of antineoplastic drugs and their off-label use in the pediatrics population using real life data. Methods:We retrieved Individual Case Safety Reports (ICSRs) with an anticancer agent as suspected drug among those reported through the Campania spontaneous reporting system from 1 January 2013 to 30 September 2019. We classified ICSRs into four offlabel categories: "age," "route of administration," "weight," and "therapeutic indication." We defined an ICSR as an off-label case if it met at least one of the aforementioned categories for at least one of the reported suspected antineoplastic drugs.Results: A total of 18 ICSRs (7.6%) out of 236 were classified as off-label cases. The median age of patients was 13 years (interquartile range, IQR: 6-16), with 94.4% of cases occurring in male patients. In the classification of the off-label category, 16 ICSRs were categorized according to the "therapeutic indication" and two for the "age." No case was categorized for the off-label categories "route of administration" and "weight." The two offlabel cases categorized as "age" were both related to the use of brentuximab vedotin for Hodgkin's lymphoma in patients aged 16 years. Twenty-nine ADRs (1.6 suspected adverse drug reactions per ICSR) were identified among off-label cases. Among ADRs, those reported more than one were diarrhea (N = 3), neutropenia (N = 3), nausea (N = 2), pyrexia (N = 2), and vomit (N = 2). Conclusions: Our findings showed a low number of ICSRs classified as off-label. The majority of off-label ICSRs were categorized for the "therapeutic indication." This low number of off-label ICSRs might be largely due to the underreporting phenomenon, which

show abstract

Section: Introductionmentioning

confidence: 99%

Safety of Anticancer Agents Used in Children: A Focus on Their Off-Label Use Through Data From the Spontaneous Reporting System

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The Paediatric Regulation (EC) (No. 1901/2006) was conceived and adopted by the EMA to address the challenges of differing pharmacokinetic and pharmacodynamic profiles compared to adults, uncertainty about the longterm drug risk-benefit profile and the additional risks due to off-label medicine use, to identify research priorities and increase the volume and quality of paediatric research [12].…”

Section: European Unionmentioning

confidence: 99%

“…A wide variety of different physiologies are found in the paediatric population, representing the extremely varied duration from the fatal and embryonic stages, through birth and infancy, through puberty and adolescence. This makes children very susceptible to ADRs [ 1].…”

Section: Introductionmentioning

confidence: 99%

Global Perspective of Paediatric Pharmacovigilance and its Importance: Where Have We Reached?

Narmada

Gowrav

Akki

et al. 2021

JPRI

View full text Add to dashboard Cite

Pharmacovigilance is a tool proposed during the post-marketing process of the pharmaceutical product lifecycle to monitor drug safety in everyday life and to identify adverse drug reactions. The identification of adverse reactions, however, is a significant cause of concern and a challenge to pharmacovigilance structures. Regulators use three basic principles in determining the risk-benefit balance to decide whether to approve a drug or a biological product and to maintain it on the market: safety, quality and effectiveness. In particular, paediatric patients, especially new-borns and infants, are at risk of drug-related adverse reactions. Drugs are also prescribed in an unlicensed and/or off-label manner to new-borns, infants and teenagers, leading paediatric patients to a higher risk of experiencing adverse drug reactions (ADRs). ADRs in children < 2 years of age are often reported and can often be alarming. The practise of paediatric pharmacovigilance needs to be strengthened by stimulating spontaneous paediatric reporting and successful post-marketing surveillance. The current study highlights the importance of paediatric pharmacovigilance and the role of different stakeholders like healthcare providers, regulators, and consumers in increasing the ADR reporting rate. Also, it discusses the pharmacovigilance tools and various initiatives that are taken by various regulatory authorities like the United States, the United Kingdom, Japan, and India.

show abstract

“…The role of RWE is of importance in settings where it may be difficult to identify a sufficiently large population to perform robust analyses. A notable example of this is pediatric drug safety (30), where EMA Good Pharmacovigilance Practice (GVP) specifically mentioned the role of RWE especially in detecting serious and rare ADRs that cannot be captured in RCTs (31). There are several other specialized fields where the strengths of RWE could be useful, such as in the cases of orphan drugs and combinations or sequences of therapies, or in the case of new therapeutic indications of already marketed drugs.…”

Section: Rwe In the Post-marketing Regulatory Settingmentioning

confidence: 99%

What can real world evidence contribute to regulatory science in pre and post marketing setting?

Martini¹,

Sultana²,

Addis³

et al. 2020

Pharm Adv

View full text Add to dashboard Cite

Historically, information on drug safety and efficacy were derived from randomized clinical trials (RCT), although RCTs have several limitations. The need to generate evidence in a real-world setting has led to a massive growth in the field of observational research using real world data (RWD). Real word evidence (RWE) is already filling the gaps of pre-marketing clinical evidence through evidence generated in the post-marketing phase, becoming increasingly recognized as an essential element to inform healthcare decisions, both at the regulatory and clinical and organizational level. In the past decade, the role of RWE in regulatory setting has evolved significantly, consequently, several regulatory agencies such as Food and Drug (FDA) and the European Medicines Agency (EMA), have set up specific task forces to better define how RWD can be leveraged for regulatory purposes. RWE is currently recognized as a relevant source of information for conducting studies aimed at identifying and characterizing the risk of medicines in the post-marketing phase but, there is still a great debate on how to exploit this information in the pre-authorization phase. The role of RWE is of importance in settings where it may be difficult to identify a sufficiently large population to perform robust analyses, such as in pediatric drug safety or rare diseases, as well as in chronic diseases. The usefulness of RWE in both the pre-and post-marketing setting would justify the creation of national centers of excellence which can store and analyze RWD in a timely and appropriate manner. However, the creation of such centres of excellence must be accompanied by a greater of receptiveness of Health Technology Assessment and regulatory agencies. However, RWE also has its limitations. For example, RWD is usually generated for purposes other than research, as a result of which the quality and completeness of RWD is not always appropriate to address some research questions and there are limitations related to data accessibility.

show abstract

Good Pharmacovigilance Practice in Paediatrics: An Overview of the Updated European Medicines Agency Guidelines

Cited by 10 publications

References 7 publications

Safety of Anticancer Agents Used in Children: A Focus on Their Off-Label Use Through Data From the Spontaneous Reporting System

Safety of Anticancer Agents Used in Children: A Focus on Their Off-Label Use Through Data From the Spontaneous Reporting System

Global Perspective of Paediatric Pharmacovigilance and its Importance: Where Have We Reached?

What can real world evidence contribute to regulatory science in pre and post marketing setting?

Contact Info

Product

Resources

About