Identifying best practices for obtaining ethical consent and for data and sample collection in pediatric rheumatic diseases – the role of the EU-wide ethics process in real-life

Rare pediatric diseases have incidences as low as 1/million, but the entire sum of all various those rare diseases still affects thousands, if not millions of young patients across Europe. Scientists in every country have made substantial contributions to improve treatment strate-gies with the goal of developing early-onset therapies preventing irreversible organ damage and improving long-term prognosis. International collaboration can foster progress, but still many scientists struggle with the immense variety of ethical requirements, the regulations for data and sample sharing and biobanking structures. A unified, standardized framework applicable for all member states of the European Union is still missing. In order to design recommendations for this urgently needed standardization of the research process, we performed a systematic literature review and several real-life studies with the aim of identifying the best practices of and barriers to transnational pediatric research. An ethics proposal was designed to evaluate the real-life work of research ethics boards across Europe. A study on the investigator perspective was sent to multiple research partners to evaluate their level of experience and ideas to improve the current ways of conducting pediatric re-search. A study on the REB perspective was performed with REBs across Germany to ex-amine their structural and procedural differences. With these practical approaches, accom-panied by a comprehensive literature review, barriers for pediatric research have been iden-tified. Recommendations to overcome these barriers have been drafted, revised, and final-ized with the help of research ethics board members and European experts for ethical and legal aspects of pediatric research. The results of the ethics proposal showed the greatest possible variety. Some research eth-ics boards have denied the proposal while others have approved it. The study on the inves- 136 tigator perspective has shown a great need for more support of pediatricians involved in research projects. The study on the REB perspective supported the wide variety of findings of the ethics proposal with personnel composition and organizational characteristics differ-ing greatly. These findings have been analysed and led to a total of 21 recommendations. The issues that were addressed include 1) general principles, 2) ethics, 3) pediatric princi-ples, 4) consent to pediatric research, 5) pediatric data and biobanks, 6) sharing of data and samples and 7) commercialization and third parties. The process of the evidence synthesis and the resulting recommendations were published in our study: “Recommendations for collaborative paediatric research including biobanking in Europe: a Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative.” 25 These recommendations for collaborative pediatric research on a European scale including data- and sample-biobanking and sharing across borders are the first of their kind and show the urgent need for a unified European legislative framework and evidence-based guidance for its implementation. Children with rheumatic conditions and the many others suffering from rare diseases should no longer be left behind when life-changing research discoveries can be made

Recommendations for collaborative paediatric research including biobanking in Europe: a Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative

Innovative research in childhood rheumatic diseases mandates international collaborations. However, researchers struggle with significant regulatory heterogeneity; an enabling European Union (EU)-wide framework is missing. The aims of the study were to systematically review the evidence for best practice and to establish recommendations for collaborative research. The Paediatric Rheumatology European Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) project enabled a scoping review and expert discussion, which then informed the systematic literature review. Published evidence was synthesised; recommendations were drafted. An iterative review process and consultations with Ethics Committees and European experts for ethical and legal aspects of paediatric research refined the recommendations. SHARE experts and patient representatives vetted the proposed recommendations at a consensus meeting using Nominal Group Technique. Agreement of 80% was mandatory for inclusion. The systematic literature review returned 1319 records. A total of 223 full-text publications plus 22 international normative documents were reviewed; 85 publications and 16 normative documents were included. A total of 21 recommendations were established including general principles (1-3), ethics (4-7), paediatric principles (8 and 9), consent to paediatric research (10-14), paediatric databank and biobank (15 and 16), sharing of data and samples (17-19), and commercialisation and third parties (20 and 21). The refined recommendations resulted in an agreement of >80% for all recommendations. The SHARE initiative established the first recommendations for Paediatric Rheumatology collaborative research across borders in Europe. These provide strong support for an urgently needed European framework and evidence-based guidance for its implementation. Such changes will promote research in children with rheumatic diseases

Germline mutation within COL2A1 associated with lethal chondrodysplasia in a polled Holstein family

Abstract Background The bulldog calf syndrome is a lethal form of the inherited congenital chondrodysplasias. Among the progeny of the polled Holstein bull Energy P cases of lethal chondrodysplasia were observed. Pedigrees of the cases and the frequency of 3/8 cases among the offspring of Energy P at our teaching and experimental farm Ruthe (LuFG Ruthe) supported the assumption of a germline mutation with a mosaic of normal and defective sperm. Results All three malformed calves were examined using necropsy, histopathology and computed tomography scanning. The phenotypic appearance of the affected calves was highly similar; they presented with severe disproportionate dwarfism and reduced body weight. The syndrome was characterized by brachygnathia superior, bilateral palatoschisis, shortening and compression of the body due to malformed vertebrae, in their size reduced and malformed ribs and reduced length of the long bones of the limbs. The bones had small irregular diaphyses and enlarged epiphyses. Whole genome sequencing of one bulldog calf, sperm of its sire Energy P and a normal progeny of Energy P identified a deleterious missense mutation (g.32476082G > A, c.2986G > A, ss2019324576) within COL2A1 on bovine chromosome (BTA) 5. Sanger sequencing confirmed the ss2019324576 variant in the affected calves and sperm of Energy P. This mutation is located within the collagen triple helix repeat and causes an exchange of glycine to serine (p.996G > S) in COL2A1. This private single nucleotide variant (SNV) was present as a gonadal mosaic in sperm of the bull. All affected calves were in a heterozygous state whereas normal half-siblings and all dams of the progeny from Energy P were missing this SNV. Validation in polled Holstein bulls and normal Holstein calves randomly sampled from several herds and from the LuFG Ruthe confirmed this SNV as private. Conclusions The identified spontaneous missense mutation within COL2A1 is most likely the cause of lethal chondrodysplasia in the progeny of Energy P through a dominant negative effect. This example suggests that it would be beneficial to conduct whole genome sequencing of sperm from bulls widely used in artificial insemination in order to detect germline mosaicism

Vie médico-chirurgicale d'un médecin retenu pendant deux ans en captivité allemande

Contient une table des matièresAvec mode text

Recommendations for collaborative paediatric research including biobanking in Europe: a Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative

Innovative research in childhood rheumatic diseases mandates international collaborations. However, researchers struggle with significant regulatory heterogeneity; an enabling European Union (EU)-wide framework is missing. The aims of the study were to systematically review the evidence for best practice and to establish recommendations for collaborative research. The Paediatric Rheumatology European Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) project enabled a scoping review and expert discussion, which then informed the systematic literature review. Published evidence was synthesised; recommendations were drafted. An iterative review process and consultations with Ethics Committees and European experts for ethical and legal aspects of paediatric research refined the recommendations. SHARE experts and patient representatives vetted the proposed recommendations at a consensus meeting using Nominal Group Technique. Agreement of 80% was mandatory for inclusion. The systematic literature review returned 1319 records. A total of 223 full-text publications plus 22 international normative documents were reviewed; 85 publications and 16 normative documents were included. A total of 21 recommendations were established including general principles (1-3), ethics (4-7), paediatric principles (8 and 9), consent to paediatric research (10-14), paediatric databank and biobank (15 and 16), sharing of data and samples (17-19), and commercialisation and third parties (20 and 21). The refined recommendations resulted in an agreement of >80% for all recommendations. The SHARE initiative established the first recommendations for Paediatric Rheumatology collaborative research across borders in Europe. These provide strong support for an urgently needed European framework and evidence-based guidance for its implementation. Such changes will promote research in children with rheumatic diseases.status: publishe

Proceedings Of The 23Rd Paediatric Rheumatology European Society Congress: Part Two

PubMe