Paedeatric trials Flashcards
What percentage of childhood cancers occur before the age of 5?
46%
Why is treatment in paediatric oncology so successful?
Few genetic events have occurred
Pro-apoptotic pathways intact
Children tolerate intensive chemo as they have no co-morbidities
Supportive care has improved
What is considered as the best standard of care for most newly diagnosed childhood cancers
Entry into a phase III clinical trial. Have as much as 80-90% recruitment (especially in leukaemia)
What are special considerations for treating children?
Doses must be adapted for age, weight and organ maturity depending on the child’s age.
May be possible that some organs are sensitive to late effects of chemo e.g cardiotoxicity.
What are some of the late effects imparted on cured childhood cancers?
Deafness and language development - platinum toxicity
Growth hormone deficiency - radiotherapy in brain tumours
delayed cosmetic deformity in growing child with radiotherapy
risk of second malignancies, especially with multimodality therapy.
Future fertility
What ethical problems are encountered in childhood cancer trials
Unlikely to be able to give direct consent (competency)
Are multiple biopsies for research into pharmacodynamics acceptable in child populations?
What are the recruitment problems associated with child cancers?
Because cancers in children tend to be rare; to recruit enough patients to produce a study with adequate power, trials tend to be conducted over multiple countries and a large amount of centres. This increases cost and requires a huge amount of organisation.
What is a problem associated with drug delivery in children compared to adults?
Drugs designed for adults tend to be oral pills. These aren’t appropriate for children so drugs have to be made into oral suspensions. This is very expensive for the drug company to produce.
What effect might the timing of a parent giving consent have on their decision?
clinicians expressed concern about information overload and about the fact that the consent discussion often occurs while the parents are still in a state of shock about the diagnosis.
What has failed if a parent is incapable of distinguishing research from their childs medical treatment? (often seen)
Failed at the process of informing - the importance of clearly explaining that the treatment is optional.
What is assent
The expression of approval or agreement. It is a less active form of agreement when compared to consent. It is used to engage children in the process of consent. Hard to judge wat qualifies so overall consent left to the parent.
Why are phase I studies in children so important?
Because pharmacokinetics and toxic effects of drugs differ in children and adults. Phase I trials are important to determine adverse events that would otherwise be unpredictable. Also, some cancers are unique to the child population, phase I studies are therefore required for research to develop novel treatments for unique paediatric diseases.
What are the main ethical issues with phase I trials in children?
Because they are dose escalation, there is a likelihood that some children will not receive any benefit from the drug if given at a low dose, whilst others will receive a high dose that is toxic. Does the trial offer sufficient benefit to justify the risks?
What is clinical equipoise?
clinical equipoise means that there is genuine uncertainty in the expert medical community over whether a treatment will be beneficial. This applies also for off-label treatments performed before or during their required clinical trials.
