scholarly journals Cardiovascular Paediatric Medicines Development: Have Paediatric Investigation Plans Lost Heart?

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1176
Author(s):  
Bethany Faulkner ◽  
M. Begoña Delgado-Charro
Keyword(s):  
Cardiovascular Diseases ◽  
Health Technology ◽  
European Medicines Agency ◽  
Therapeutic Area ◽  
The European Union ◽  
Off Label Use ◽  
Off Label ◽  
Treat Heart Failure ◽  
Paediatric Medicines

This work aimed to establish whether paediatric needs in cardiovascular diseases have been met by paediatric investigation plans (PIPs) produced since the development of the European Union Paediatric Regulation in 2007. The European Medicines Agency repository was searched for patterns in the development of paediatric medicines in general. Next, positive PIPs related to cardiovascular diseases were scrutinized for outcomes and compared to specific paediatric cardiovascular needs. In total, 1866 PIPs were identified with 12% corresponding to decisions taken for cardiovascular medicines. However, despite this therapeutic area having the greatest number of overall PIPs, only 14% of established needs in paediatric cardiovascular diseases were addressed by PIPs with positive decisions. Further, 71.9% of PIPs with decisions in cardiovascular disease corresponded to full waivers, so the product would not be studied in paediatrics. Despite the progress found in overall numbers of PIPs published, cardiovascular products are still commonly used off-label in paediatrics. Particularly, there is a need to develop products to treat heart failure and hypertension, two areas with clear unmet clinical needs in paediatrics. A case study on valsartan showed that industry, regulators, health technology assessment bodies, and prescribers should work together to reduce off-label use of paediatric cardiovascular diseases (CVD).

scholarly journals Off-label prescription of medicines: what do we know about the legislation in EU member states?

2021 ◽  
Author(s):  
Renske Caminada ◽  
Max Polano ◽  
Anna M. G. Pasmooij ◽  
Violeta Stoyanova-Beninska
Keyword(s):  
Treatment Guidelines ◽  
European Medicines Agency ◽  
The European Union ◽  
Off Label Use ◽  
Drug Label ◽  
Member States ◽  
National Legislation ◽  
Off Label ◽  
Eu Member States ◽  
Label Use

Aim: Off-label prescription is not regulated on the European Union (EU) level and therefore not harmonised in the EU Member States (MS). Despite this, the use of medicines outside of the drug label occurs in clinical practice, and it can be included in treatment guidelines and/or reimbursed in some cases. It is, however, currently not clear to what extent off-label use can be included in regulatory discussions at a European level at the different committees at the European Medicines Agency. In this article, we provide an overview of the current legislation on MS level regarding off-label prescription in order to support EU regulatory discussions. Methods: Relevant national legislation regarding off-label prescription from MS was identified by distributing a questionnaire to EMACOLEX. Case law was excluded. The identified categorical elements and prerequisites in the national legislation were then categorised. Subsequently, a comparison was made to the five Good Off-Label Use Practice (GOLUP) principles. Results: Based on the obtained responses from 10 MS, we observed a large heterogeneity in the legislation of MS regarding off-label prescription. Five (out of 10) MS regulate off-label prescription explicitly and seven (out of 10) MS have prerequisites. One or more prerequisites per MS were reflected in the GOLUP principles as formulated in 2017. Conclusion: The main contribution of this work is to flag that off-label prescription actually needs to be well defined and understood before it can be appropriately taken into consideration in regulatory discussions. There is a heterogeneity in legislation regarding off-label prescription in the investigated MS, which may lead to different perspectives. A common understanding of the concept and more alignment in off-label prescription practices and their regulation at MS level may contribute to further regulatory discussions.

scholarly journals An analysis of characteristics of post-authorisation studies registered on the ENCePP EU PAS Register

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1447 ◽  
Author(s):  
Robert Carroll ◽  
Sreeram V. Ramagopalan ◽  
Javier Cid-Ruzafa ◽  
Dimitra Lambrelli ◽  
Laura McDonald
Keyword(s):  
Risk Assessment ◽  
Chart Review ◽  
Drug Utilisation ◽  
Data Capture ◽  
Primary Data ◽  
European Medicines Agency ◽  
Therapeutic Area ◽  
The European Union ◽  
Study Designs ◽  
The Eu

Background: The objective of this study was to investigate the study design characteristics of Post-Authorisation Studies (PAS) requested by the European Medicines Agency which were recorded on the European Union (EU) PAS Register held by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). Methods: We undertook a cross-sectional descriptive analysis of all studies registered on the EU PAS Register as of 18th October 2016. Results: We identified a total of 314 studies on the EU PAS Register, including 81 (26%) finalised, 160 (51%) ongoing and 73 (23%) planned. Of those studies identified, 205 (65%) included risk assessment in their scope, 133 (42%) included drug utilisation and 94 (30%) included effectiveness evaluation. Just over half of the studies (175; 56%) used primary data capture, 135 (43%) used secondary data and 4 (1%) used a hybrid design combining both approaches. Risk assessment and effectiveness studies were more likely to use primary data capture (60% and 85% respectively as compared to 39% and 14% respectively for secondary). The converse was true for drug utilisation studies where 59% were secondary vs. 39% for primary. For type 2 diabetes mellitus, database studies were more commonly used (80% vs 3% chart review, 3% hybrid and 13% primary data capture study designs) whereas for studies in oncology, primary data capture were more likely to be used (85% vs 4% chart review, and 11% database study designs). Conclusions: Results of this analysis show that study objectives and therapeutic area influence PAS design in terms of type of data capture used.

scholarly journals Off-label innovation: characterization through a case study of rhBMP-2 for spinal fusion

2016 ◽  
Vol 25 (3) ◽  
pp. 406-414 ◽  
Author(s):  
Zane Schnurman ◽  
Michael L. Smith ◽  
Douglas Kondziolka
Keyword(s):  
Interbody Fusion ◽  
Bone Morphogenetic Protein 2 ◽  
Lumbar Interbody Fusion ◽  
Off Label Use ◽  
Off Label ◽  
Publication Patterns ◽  
Publication Data ◽  
Number Of Patients ◽  
Label Use

OBJECTIVE Off-label therapies are widely used in clinical practice by spinal surgeons. Some patients and practitioners have advocated for increased regulation of their use, and payers have increasingly questioned reimbursment for off-label therapies. In this study, the authors applied a model that quantifies publication data to analyze the developmental process from initial on-label use to off-label innovation, using as an example recombinant human bone morphogenetic protein 2 (rhBMP-2) because of its wide off-label use. METHODS As a case study of off-label innovation, the developmental patterns of rhBMP-2 from FDA-approved use for anterior lumbar interbody fusion to several of its off-label uses, including posterolateral lumbar fusion, anterior cervical discectomy and fusion, and posterior lumbar interbody fusion/transforaminal lumbar interbody fusion, were evaluated using the “progressive scholarly acceptance” (PSA) model. In this model, PSA is used as an end point indicating acceptance of a therapy or procedure by the relevant scientific community and is reached when the total number of peer-reviewed studies devoted to refinement or improvement of a therapy surpasses the total number assessing initial efficacy. Report characteristics, including the number of patients studied and study design, were assessed in addition to the time to and pattern of community acceptance, and results compared with previous developmental study findings. Disclosures and reported conflicts of interest for all articles were reviewed, and these data were also used in the analysis. RESULTS Publication data indicated that the acceptance of rhBMP-2 off-label therapies occurred more rapidly and with less evidence than previously studied on-label therapies. Additionally, the community appeared to respond more robustly (by rapidly changing publication patterns) to reports of adverse events than to new questions of efficacy. CONCLUSIONS The development of off-label therapies, including the influence of investigative methods, regulation, and changing perspectives, can be characterized on the basis of publication patterns. The approach and findings in this report could inform future off-label development of therapies and procedures as well as attempts to regulate off-label use.

scholarly journals Analysis of primary outpatient data for off-label use of medicines in neurology

Pharmacia ◽  
2019 ◽  
Vol 66 (4) ◽  
pp. 165-170
Author(s):  
Maria Drenska ◽  
Savina Elitova ◽  
Velina Grigorova ◽  
Emilia Naseva ◽  
Ilko Getov
Keyword(s):  
Product Information ◽  
National Level ◽  
The European Union ◽  
Off Label Use ◽  
Off Label ◽  
Medical Needs ◽  
Wide Range ◽  
Adults And Children ◽  
The One ◽  
Label Use

Introduction: The off-label use of medicines is a common practice that covers a wide range of therapeutic areas in both, adults and children. So far, the extent of off-label use among neurology patients in Bulgaria has not been studied. The aim of this study is to provide data on the off-label use in neurology patients in Bulgaria and to contribute to planning actions by the European Commission and EMA to provide a harmonized guideline and to regulate the off-label use of medicines within the European Union. Materials and methods: The data on prescriptions of 360 neurology outpatients, treated in a 1 – year period, were recorded and provided for analyses. The Summaries of Product Characteristics, were used as reference documents for assessment of prescriptions. Results: The results from this study show that most neurology patients (63%) were exposed to off-label use. Most of the medicines prescribed off-label (90%), were used for a therapeutic indication, other than the one listed in the authorized product information. Meloxicam is found to be the most commonly prescribed off-label medicine. Other medicines, like trasadone, pentoxyfylline and fupentixol / melitracen were prescribed less frequently, but deserve special attention, as they were found to be used off-label to a very large extent, some of them in 100% of prescriptions. Half of the top 10 medications, most commonly used off-label in neurology, were found to be non-steroidal anti-inflammatory drugs. Conclusion: The results reveal a big gap between the authorized medicines and the real medical needs. Further studies based on a larger number of medical centers are needed to establish more accurate data on off-label prescribing in neurology patients on a national level.

scholarly journals Off-label Use of Drugs in Childhood Asthma

2015 ◽  
Vol 01 (01) ◽  
pp. 16 ◽  
Author(s):  
António J Cabral ◽  
Mário Morais-Almeida ◽  
◽  
◽  
◽  
...  
Keyword(s):  
Childhood Asthma ◽  
Symptom Control ◽  
European Medicines Agency ◽  
Off Label Use ◽  
Drug Reactions ◽  
Off Label ◽  
Increased Risk ◽  
Common Illnesses ◽  
A Minor ◽  
Medicines For Children

Asthma is among the most common illnesses in childhood and may require off-label drug use for adequate symptom control. Several studies have assessed that this use is common mainly due to a lack of clinical research. The leading concerns are the increased risk of adverse drug reactions and prescription errors. However, off-label prescriptions are not necessarily incorrect. The European Medicines Agency released the Paediatric Regulation to promote research in the medicines for children; yet, recent data suggest only a minor impact.

scholarly journals Research on Approaches for Regulation of the “Off-label” use of Medicinal Products in the European Union

2017 ◽  
Vol 44 (1) ◽  
pp. 17-21 ◽  
Author(s):  
M. Drenska ◽  
I. Getov
Keyword(s):  
European Union ◽  
European Countries ◽  
Time Range ◽  
The European Union ◽  
Off Label Use ◽  
Medicinal Products ◽  
Weak Point ◽  
Off Label ◽  
Regulatory Information ◽  
Label Use

Abstract Despite the increasingly strict legislation on medicinal products, the „off-label use“ or „use of medicinal product outside the approved summary of product characteristics (SmPC)“ is a weak point of today’s drug regulation and raises many questions about the risk, ethics, and legality of this type of practice. In recent years, through guidance and legal changes in some countries were defined the conditions and responsibilities, but in the most European countries still lack rules for off-label prescribing. The purpose of this study was to identify and analyse different approaches to regulation, adopted by some member states as well as to summarize the efforts in demand of common harmonized approach to solve this problem within the European Union. In the study, we used the available regulatory information in different electronic resources associated with the off-label drug use in selected European countries without limited time range. The results show that decisions taken to regulate the issue have significant differences and specific approach, while none of them is enough satisfactory and comprehensive. In conclusion, it can be claimed that the existing regulatory rules in various countries require significant improvement and update.

scholarly journals Off-Label Medicines Use: Complex Problem of Modern Clinical Practice

2020 ◽  
Vol 16 (2) ◽  
pp. 324-334
Author(s):  
S. R. Gilyarevskiy
Keyword(s):  
Randomized Clinical Trials ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Complex Problem ◽  
The European Union ◽  
Off Label Use ◽  
Off Label ◽  
Medicines Use ◽  
The Usa ◽  
History Of

World experience in off-label medicines use is presented in the article. Data on the history of changes in tactics and approaches to solve the problem of medicines off-label use in the USA and some European countries, as well as in the European Union as a whole, are presented. The reasons, why doctors should use medicines off-label, are discussed. The expert opinion on the conditions ensuring the maximum safety in off-label medicines use is presented. In particular, the validity of obtaining patient informed consent is discussed. The article does not apply to the Russian regulation regarding “off-label” therapy but describes the foreign practice related to off-label medicines use. In addition, the results of some recently completed randomized clinical trials evaluating the effects of direct oral anticoagulants are presented in order to demonstrate the need to clarify the effectiveness and safety of medicines used in certain clinical situations. The results of such studies clarify the indications for the drug use, which are subsequently entered into the summary of product characteristics.

scholarly journals Open-Source Technology for Real-Time Continuous Glucose Monitoring in the Neonatal Intensive Care Unit: Case Study in a Neonate With Transient Congenital Hyperinsulinism

10.2196/21770 ◽  
2020 ◽  
Vol 22 (12) ◽  
pp. e21770
Author(s):  
Katarina Braune ◽  
Mandy Wäldchen ◽  
Klemens Raile ◽  
Sigrid Hahn ◽  
Tebbe Ubben ◽  
...  
Keyword(s):  
Open Source ◽  
Real Time ◽  
Continuous Glucose Monitoring ◽  
Newborn Infants ◽  
Glucose Monitoring ◽  
Congenital Hyperinsulinism ◽  
Off Label Use ◽  
Off Label ◽  
Label Use

Background Use of real-time continuous glucose monitoring (rtCGM) systems has been shown to be a low-pain, safe, and effective method of preventing hypoglycemia and hyperglycemia in people with diabetes of various age groups. Evidence on rtCGM use in infants and in patients with conditions other than diabetes remains limited. Objective This case study describes the off-label use of rtCGM and the use of an open-source app for glucose monitoring in a newborn with prolonged hypoglycemia secondary to transient congenital hyperinsulinism during the perinatal period. Methods The Dexcom G6 rtCGM system (Dexcom, Inc) was introduced at 39 hours of age. Capillary blood glucose checks were performed regularly. In order to benefit from customizable alert settings and detect hypoglycemic episodes, the open-source rtCGM app xDrip+ was introduced at 9 days of age. Results Time in range (45-180 mg/dL) for interstitial glucose remained consistently above 90%, whereas time in hypoglycemia (<45 mg/dL) decreased. Mean glucose was maintained above 70 mg/dL at 72 hours of life and thereafter. Daily sensor glucose profiles showed cyclic fluctuations that were less pronounced over time. Conclusions While off-label use of medication is both common practice and a necessity in newborn infants, there are few examples of off-label uses of medical devices, rtCGM being a notable exception. Real-time information allowed us to better understand glycemic patterns and to improve the quality of glycemic control accordingly. Severe hypoglycemia was prevented, and measurement of serum levels of insulin and further lab diagnostics were performed much faster, while the patient’s individual burden caused by invasive procedures was reduced. Greater customizability of threshold and alert settings would be beneficial for user groups with glycemic instability other than people with diabetes, and for hospitalized newborn infants in particular. Further research in the field of personal and off-label rtCGM use, efficacy studies evaluating the accuracy of low glucose readings, and studies on the differences between algorithms in translating raw sensor data, as well as customization of commercially available rtCGM systems, is needed.

scholarly journals An analysis of characteristics of post-authorisation studies registered on the ENCePP EU PAS Register

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1447 ◽  
Author(s):  
Robert Carroll ◽  
Sreeram V. Ramagopalan ◽  
Javier Cid-Ruzafa ◽  
Dimitra Lambrelli ◽  
Laura McDonald
Keyword(s):  
Risk Assessment ◽  
Chart Review ◽  
Drug Utilisation ◽  
Data Capture ◽  
Primary Data ◽  
European Medicines Agency ◽  
Therapeutic Area ◽  
The European Union ◽  
Study Designs ◽  
The Eu

Background: The objective of this study was to investigate the study design characteristics of Post-Authorisation Studies (PAS) requested by the European Medicines Agency which were recorded on the European Union (EU) PAS Register held by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). Methods: We undertook a cross-sectional descriptive analysis of all studies registered on the EU PAS Register as of 18th October 2016. Results: We identified a total of 314 studies on the EU PAS Register, including 81 (26%) finalised, 160 (51%) ongoing and 73 (23%) planned. Of those studies identified, 205 (65%) included risk assessment in their scope, 133 (42%) included drug utilisation and 94 (30%) included effectiveness evaluation. Just over half of the studies (175; 56%) used primary data capture, 135 (43%) used secondary data and 4 (1%) used a hybrid design combining both approaches. Risk assessment and effectiveness studies were more likely to use primary data capture (60% and 85% respectively as compared to 39% and 14% respectively for secondary). The converse was true for drug utilisation studies where 59% were secondary vs. 39% for primary. For type 2 diabetes mellitus, database studies were more commonly used (80% vs 3% chart review, 3% hybrid and 13% primary data capture study designs) whereas for studies in oncology, primary data capture were more likely to be used (85% vs 4% chart review, and 11% database study designs). Conclusions: Results of this analysis show that PAS design varies according to study objectives and therapeutic area.

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