Does the EU's Paediatric Regulation work for new medicines for children in Denmark, Finland, Norway and Sweden? : A cross-sectional study

Objective The aim of this study was to assess the marketing status of the new paediatric medicinal products listed in the 10-year report as initially authorised between 2007 and 2016, reflecting the product availability in four Nordic countries. Design This is a cross-sectional study. Setting Analysis of the national medicine agency's databases in Denmark, Finland, Norway and Sweden. Data source New medicinal products with paediatric indications and new paediatric formulations listed in the Annex of European Medicines Agency's EU Paediatric Regulation 10-year report. Data analysis The products were classified according to national marketing status between January 2019 and March 2019, whether a product was authorised and whether the product was marketed. Main outcome measures The percentages of the new medicinal products with paediatric indications and new paediatric formulations having a valid marketing authorisation and being marketed, both in terms of the sums of all countries and separately for each country. Results Across the four countries, 21%-32% (16/76-24/76) of the new medicinal products were not marketed. Of the new formulations relevant to children, 29%-50% (16/56-28/56) were not marketed, and a significant proportion of these products had never been marketed. Conclusions This study reflects the reality of the implementation of the Paediatric Regulation. The results show that several new paediatric medicines and new formulations are not marketed. This affects the product availability. Similar data from other countries are needed to evaluate the overall European status to find remedies to current situation and increase the availability of the medicines for children. ©Peer reviewe

Paediatric intensive care in Sweden. : I Mechanical ventilation and central haemodynamics. II Outcome of paediatric intensive care with special reference to respiratory failure

The ABC of acute care is to maintain Airway, Breathing and Circulation or oxygen delivery, which depends on the product of cardiac output (CO) and oxygenation. Thus knowledge of how different modes of mechanical ventilation affect central haemodynamics is essential. Paper I: Improved triggering function made pressure support ventilation (PSV) possible for neonates and infants. We evaluated the effect on cardiac output of this mode in comparison with conventional pressure control ventilation in infants (n=9). We found a significant improvement in cardiac output by 16% during PSV. This finding may be of importance for critically ill infants. Paper II: In Paper I we did not find any significant change in heart rate, thus the increase in CO was caused by an increase in stroke volume (SV). The ability of the neonatal heart to change stroke volume has been debated. In a study of anaesthetized infants on mechanical ventilation (n=6), the PEEP-level was changed and CO measured. Data on CO, SV and heartrate were analysed together with data from Paper I. There was an almost linear significant change in CO, from +16% to -13% without changes in heart rate. Thus we found that when mean airway pressure is altered the changes in CO is an effect of changes in SV. Paper III: High frequency oscillatory ventilation (HFOV) is a new method of mechanical ventilation with tidal volumes Few studies have been carried out on the incidence and outcome of paediatric intensive care or more specifically on respiratory failure. There are also differences regarding population, mortality and health between different regions. Thus international studies may not apply to Scandinavia. To investigate the circumstances in Sweden the following studies were performed: Paper IV: An ambidirectional multicentre population based collection of data on all admissions to ICU of children aged 6 months (in PICU 1 month) to 16 years of age during 36 months 1998-2001. Only a minority of children needing intensive care in Swedenreceived that in a designated paediatric ICU (PICU). Mortality was similar in PICU and adult ICUs. There is a continued increased mortality for at least five years after admission to an ICU. Studies are needed to evaluate if centralization of paediatric intensive care in Sweden would be beneficial to the paediatric population. Paper V: The subgroup with respiratory failure in PICU, were further studied; 20% of admissions were ventilated >24 hours. NO, HFOV and ECMO was used in 15% of these cases indicating a severe respiratory disease. This group had an initial increased mortality but one year after discharge from ICU the mortality was not increased. Results from one PICU, show that ARDS is relatively uncommon but accounts for close to 1/3 of the total ICU mortality in this PICU. This suggests that ARDS may be a significant health issue in children in Sweden

Sömnstörningar hos barn : kunskapsdokument

Ett möte med experter på barns sömnproblem genomfördes i februari 2014 varvid detta kunskapsdokument togs fram. Kunskapssammanställningen och rekommendationerna har tagits fram gemensamt av experterna och bygger på konsensus bland deltagarna. Läkemedelsverkets ansvar var att facilitera mötet samt att tillsammans med experterna sammanställa kunskapsdokumentet. Som stöd för kunskapsdokumentet finns bakgrundsdokument som respektive författare ansvarar för. I bakgrundsdokumenten finns, förutom detaljerad information om varje ämnesområde, även referenser. Socialstyrelsen medverkade vid expertmötet, liksom i framtagandet av kunskapsdokumentet. Inför mötet har SBU (2013) identifierat kunskapsluckor inom området, vilka publicerats i SBU:s databas över vetenskapliga kunskapsluckor, se www.sbu.se. En vetenskaplig kunskapslucka innebär att systematiska litteraturöversikter saknas eller att de visar på osäker effekt. Man fann att detta gäller "Melatonin till barn som har flera funktionsnedsättningar och sömnproblem", "Melatonin som behandling av sömnproblem hos barn med adhd" och " Melatonin för i övrigt friska barn med sömnproblem". SBU konstaterade tidigare (2010) att "Effekten av alimemazin vid behandling av sömnbesvär" också är envetenskaplig  kunskapslucka

New strategies for the conduct of clinical trials in paediatric Pulmonary Arterial Hypertension (PAH): Outcome of a multi-stakeholder meeting with patients, academia, industry and regulators held at EMA on Monday 12th June 2017

Aims: Drug development for paediatric pulmonary arterial hypertension (PAH) ispressingly needed. Experts from the US Food and Drug Administration, EuropeanMedicines Agency, Health Canada, key opinion leaders, academia, patients, and industry representatives held a workshop on 12th June 2017 dedicated to addressing challenges and unmet needs. This report summarises the approaches proposed during the meeting to address key issues in extrapolation, trial design, and study endpoints in pediatric drug development.Methods and Results: A pre-workshop stakeholder survey was conducted and showed that most respondents believe the pathophysiology of heritable PAH and some forms of idiopathic PAH is thought to be sufficiently similar in adult and paediatric patients, although the clinical manifestations may differ. In this situation, placebo-controlled trials might not be required to confirm clinical benefit in paediatrics. The study endpoints used to support drug approvals in adults were reviewed to determine if these existing study endpoints can be applied in paediatric PAH efficacy trials. It showed that non-invasive study endpoints, such as the time to clinical worsening, WHO functionalclass, and 6-Minute-Walk-Test could be applicable in paediatric PAH trials, although each presents some limitations in paediatrics.Conclusion: Extrapolation of efficacy from informative adult studies may be appropriate in some forms of PAH. Initial dose-finding studies and exposure-response modelling are warranted in paediatric PAH, followed by an efficacy and safety study to explore the response to treatment and exposure-response relationship. A novel, non-invasive, developmentally-appropriate, and reliable study endpoint needs to be developed