iPads as effective as sedatives in reducing anxiety before surgery, paediatric trial shows

2016 ◽  
Keyword(s):  
Paediatric Trial

scholarly journals Ethical Issues and Barriers for Multi-National Paediatric Clinical Trials: The Challenging Experience of the DEEP Project

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4820-4820
Author(s):  
Viviana Giannuzzi ◽  
Mariagrazia Felisi ◽  
Hugo Devlieger ◽  
Aurelio Maggio ◽  
George Papanikolaou ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Ethical Issues ◽  
Descriptive Analysis ◽  
National Level ◽  
Comparative Trial ◽  
Phase Iii ◽  
Eu Countries ◽  
Paediatric Trial ◽  
Significant Difference ◽  
The Eu

Introduction: The procedures and requirements for the clinical trial application (CTA) to Ethics Committees (ECs) and/or Competent Authorities (CAs) are not fully harmonised, and this is even more evident when non-EU countries are involved. This lack of harmonisation makes more difficult the approach in the case of 'small populations', such as children and patients affected by rare diseases. A phase III efficacy-safety comparative trial (DEEP-2) involving paediatric patients affected by transfusion dependent haemoglobinopathies from seven European and non-European countries (Albania, Cyprus, Greece, Italy, United Kingdom, Egypt, Tunisia) was carried out in the context of a FP7 project (HEALTH-F4-2010-G.A. n. 261483) and included in an agreed Paediatric Investigation Plan. Aims: The aims of this paper are to describe in a complex multi-national/multi-ethnic framework the different provisions and procedures to authorise a paediatric trial in EU/non-EU countries and to evaluate the possible impact of the following key indicators on the timing of ECs approval and CAs authorisation: complexity of the national/local provisions and procedures to authorise a paediatric trial, including the number of ECs and CAs to be addressed; number and type of additional local/national documentation; number of queries from CAs and ECs; geographic setting (EU and non-EU). Methods: The following information was collected from official websites and through a survey addressed to Principal Investigators: The regulatory and legal frameworks in force at the time of the submission of DEEP-2 in each involved country;The procedures required at local/national level (i.e. number of ECs and CAs to be addressed, parallel or subsequent submission to the CA and the EC, preparation of the CTA form and documents required from CAs and ECs);The timing of ECs approval and CAs authorisation, including number and types of queries, were collected from DEEP-2 Trial Master File. Descriptive analysis, Wilcoxon Rank-Sum test and General Linear Model (GLM) analysis were used to describe results and to analyse significance of the considered indicators. Results: In the EU countries, relevant legislative acts apply and include GCP and specific procedures for paediatric trials, in non-EU countries GCP guidelines apply but have not been implemented in the national laws regulating clinical trials. Moreover, within the 4 EU Member States a different approach was in place, even if under the same rules (i.e. Directive 2001/20/EC as implemented in the national law) with distinctive documents required for the CTA in almost all the EU countries compared with the EC provisions. The CTAs were performed in the period June 2012 - September 2015 in 23 trial sites. The EC approvals and CA authorisations were issued between January 2013 - September 2015. In the EU countries, the authorisation process was completed within 7,3 to 33,8 months (median = 15 months), while in non-EU countries, the authorisation process was completed by 7 months (median = 4 months) (figure 1). In particular, the comparison of the CA time authorisation shows a significant difference between EU and non-EU clusters (p = 0.001); however, if the statistical model is adjusted for the number of EC requests as covariate, the difference is not significant. Thus, it seems that the main factor influencing the time for EC approval is the number of requests for changes/clarifications (mainly on informed consent/assent, study protocol, insurance) (figure 2). Conclusion: Delays in completion of the authorisation phase in many countries seems to be a relevant issue and the timeframes for the authorisation in EU countries are not compliant with the European requirements (60 days for single opinion release and 30 days for its acceptance, as stated in Directive 2001/20/EC). The main reasons for delay is the complexity of the procedures and the requests from the ECs/CAs. In non-EU countries, procedures are different and faster with less requests from ECs and CAs. The upcoming application of a stronger set of rules, CT-Regulation (EU) 536/2014, is expected to harmonise practices in Europe and possibly outside Europe. The final aim of this change should be to assure a good balance between a timely approval and a high-level of children protection. Disclosures Reggiardo: CVBF: Consultancy. Tricta:ApoPharma: Employment.

scholarly journals Ethical and Procedural Issues For Applying Researcher-Driven Multi-National Paediatric Clinical Trials in and Outside The European Union: The Challenging Experience of The DEEP Project

2021 ◽  
Author(s):  
Viviana Giannuzzi ◽  
Mariagrazia Felisi ◽  
Donato Bonifazi ◽  
Hugo Devlieger ◽  
George Papanikolaou ◽  
...  
Keyword(s):  
European Union ◽  
Ethics Committees ◽  
Paediatric Population ◽  
European Countries ◽  
The European Union ◽  
Clinical Trial Application ◽  
Paediatric Trial ◽  
General Linear Model Analysis ◽  
Wilcoxon Rank Sum Test ◽  
The Impact

Abstract Background. We describe our experience from a multi-national application of a European Union-funded research-driven paediatric trial (DEEP-2, EudraCT 2012-000353-31; NCT01825512).This paper aims to evaluate the impact of the local and national rules on the trial authorisation process in European and non-European countries. National/local provisions and procedures, number of Ethics Committees and Competent Authorities to be addressed, documentation required, special provisions for the paediatric population, timelines for completing the authorisation process and queries received were collected; compliance with the European provisions were evaluated.Descriptive analysis, Wilcoxon Rank-Sum test and General Linear Model analysis were used to determine factors potentially influencing the timelines. The Cluster Analysis procedure was used to identify homogenous groups of cases.Result. The authorisation process was completed in 7,7 to 53,8 months in European countries and in 17,1 to 27,1 months in non-European countries. The main factors influencing these timelines resulted the requests for changes/clarifications in European countries and the different national legislations in non-European countries.Conclusion. This work confirms that the procedures and requirements for the clinical trial application of a paediatric trial are different. In the European Union, the timeframes for submission were generally harmonised but longer. In non-EU countries, delays were caused by national dispositions but the entire authorisation process resulted faster with less requests from ECs/CAs. The upcoming application of Regulation (EU) 536/2014 is expected to harmonise practices in Europe and possibly outside. Networks on paediatric research acting at international level will be crucial in this effort.

Barriers To Clinical Trial Enrolment For Teenagers and Young Adults With Acute Lymphoblastic Leukaemia: The Impact of Age Eligibility Criteria

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1401-1401
Author(s):  
Lorna Anne Fern ◽  
Clare Rowntree ◽  
Rachael E Hough ◽  
Ajay J Vora ◽  
Adele Fielding ◽  
...  
Keyword(s):  
Young Adults ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Eligibility Criteria ◽  
Incidence Data ◽  
Paediatric Trial ◽  
Time Period ◽  
Teenagers And Young Adults ◽  
The Uk ◽  
The Impact

Abstract Background Overall survival (OS) for teenagers and young adults (TYA) aged 15-24 years (yrs) with acute lymphoblastic leukaemia (ALL) is inferior to OS for children. In the UK, five-year OS for children up to 14 years with ALL is 89%, falling to 69% for 15-19 yr olds and 52% for 20-24 yr olds (O'Hara et al, National Cancer Intelligence Network, 2013). Both disease biology and choice of protocol are likely to be important in explaining these differences. However, lower rates of inclusion into clinical trials with increasing age may also be a significant factor. In the UK 3 national paediatric and adult ALL trials were open to recruitment between 1997-2006 (table 1). In 2006 the upper age eligibility criteria for UKALL2003 was increased from 18 to 24 yrs and the lower age limit of UKALL XII was correspondingly increased to reflect emerging evidence that TYA have improved outcomes when treated on paediatric protocols. Aims 1. To examine trial accrual rates (AR) by age over a ten year period (1997-2006) to three UK national ALL trials. 2. To determine the influence of amending the age eligibility criteria for UKALL2003 on TYA accrual Methods ALL incidence figures for patients aged 1-39 yrs during the study period of 1997-2006 were obtained from a national cancer registry. Incidence data was classified according to the morphology-based coding specifically for TYA (Birch et al, BJC, 2002). Accrual rates (AR) were expressed as the ratio of patients entered onto trials during the same time period compared to incidence cases. Descriptive statistics were applied for an observational dataset where sample size or incidence cases cannot be controlled (Fern et al. BJC, 2008). We obtained a further incidence data set for cases diagnosed in 2007 and 2008 to examine the impact of age eligibility amendments in 2006 and 2008 to UKALL2003. Results ALL was diagnosed in 4,579 patients aged 1-39 yrs between 1997-2006, 2,767 were under 10 yrs. The figure shows the proportion of newly diagnosed ALL patients entering trials 1997-2006. Red arrows show age eligibility criteria of the trials. 65% of all patients were enrolled onto one of the 3 trials. AR were highest for under 10's (71.5%), declining to 55.2% for 15-16 yr olds, 43.4% for 17-18 yr olds and 40% for those aged 21-24 yrs. The amendments to age inclusion criteria for UKALL2003 and UKALL XII improved AR for 17-18 yr olds to a level equivalent to AR for 15-16 yr olds. AR for 19-20 yr olds also improved to 62.5%. However, recruitment of 21-24 year olds did not change. During 1997-2006 three quarters of 17-18 yr olds recruited to trials were enrolled onto UKALLXII. After protocol amendments, three quarters of 17-18 yrs were recruited to the paediatric trial. Conclusions We have shown a decline in trial accrual with increasing age for teenagers and young adults with ALL despite the availability of national trials spanning the age range being available during the time period studied. Due to close cooperation between adult and paediatric trial management groups, major changes were made to age eligibility criteria for both paediatric and adult trials, following increasing evidence that TYA have better outcomes when treated on paediatric protocols. We have shown an increased accrual of older teenagers to ALL trials in the UK following these changes. No improvements were observed for 21-24 year olds. However, this age group were only eligible for UKALL 2003 during the last year of our analysis. This approach to trial eligibility design may serve as a model for future trials, both in ALL and other cancers. Disclosures: No relevant conflicts of interest to declare.

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