Complying with the European Clinical Trials directive while surviving the administrative pressure - an alternative approach to toxicity registration in a cancer trial.
The European Clinical Trials Directive of 2004 has increased the amount of paper work and reduced the number of initiated clinical trials. Particularly multinational trials have been delayed. To meet this challenge we developed a novel, simplified, fast and easy strategy for on-line toxicity registration for patients treated according to the Nordic/Baltic acute lymphoblastic leukaemia protocol, NOPHO ALL 2008, for children and young adults, including three randomisations. We used a risk-assessment based approach, avoiding reporting of expected adverse events and instead concentrating on 20 well-known serious, but rarer events with focus on changes in therapy introduced in the treatment protocol. This toxicity registration strategy was approved by the relevant regulatory authorities in all seven countries involved, as compliant within the EU directive of 2004. The centre compliance to registration was excellent with 98.9% of all patients being registered within 5weeks from the requested quarterly registration. Currently, four toxicities (thrombosis, fungal infections, pancreatitis and allergic reactions) have been chosen for further detailed exploration due to the cumulative fraction of patients with positive registrations exceeding 5%. This toxicity registration offers real-time toxicity profiles of the total study cohort and provides early warnings of specific toxicities that require further investigation.
Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. Electronic address: thomas.leth.frandsen@regionh.dk.
Thomas Leth
TL
Frandsen
Department of Paediatrics, University Hospitals, Astrid Lindgrens Barnsjukhus, Stockholm, Sweden.
Mats
M
Heyman
Institution of Clinical Sciences, Department of Paediatrics, Queen Silvias Childrens Hospital, Gothenburg, Sweden.
Jonas
J
Abrahamsson
Department of Paediatrics, University of Tampere, Finland.
Kim
K
Vettenranta
Department of Paediatrics, University Hospital of Trondheim, Norway.
Ann
A
Åsberg
Centre for Paediatric Oncology and Haematology, University Children's Hospital, Vilnius, Lithuania.
Goda
G
Vaitkeviciene
Tallinn Children's Hospital, Tallinn, Estonia.
Kaie
K
Pruunsild
Department of Haematology, Copenhagen University Hospital, Herlev, Denmark.
Nina
N
Toft
Department of Haematology, Copenhagen University Hospital, Herlev, Denmark.
Henrik
H
Birgens
Department of Hematology, Uppsala University Hospital, Uppsala, Sweden.
Helena
H
Hallböök
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Petter
P
Quist-Paulsen
Department of Intensive Chemotherapy and Bone Marrow Transplantation, Vilnius University Hospital, Vilnius, Lithuania.
Laimonas
L
Griškevičius
Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Louise
L
Helt
Copenhagen University, GCP Unit, University Hospital of Copenhagen, Bispebjerg, Copenhagen N, Denmark.
Birgitte Vilsbøll
BV
Hansen
Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; Institute of Gynaecology, Obstetrics and Paediatrics, Faculty of Medicine, University of Copenhagen, Denmark. Electronic address: kjeld.schmiegelow@regionh.dk.
Kjeld
K
Schmiegelow
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards*; D005062:European Union; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology; D007223:Infant; D009181:Mycoses / Q000209:etiology; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000592:standards*; D010195:Pancreatitis / Q000209:etiology; D017410:Practice Guidelines as Topic / Q000592:standards*; D058028:Research Report / Q000592:standards; D018570:Risk Assessment / Q000379:methods / Q000592:standards*; D012307:Risk Factors; D013927:Thrombosis / Q000209:etiology
Acute lymphoblastic leukaemia; Chemotherapy; Children; Clinical trial; Registration; Toxicity