ICH E11 - Clinical Investigation of Medicinal Products in the Paediatric Population Flashcards
What is the most important factor in the early initiation of pediatric studies?
The presence of a serious or life-threatening disease for which the medicinal product represents a potentially important advance in therapy.
The Paediatric development program should not ______ adult studies and availability of medicinal products for adult
delay
It should not be noted that the most relevant safety data for paediatrics studies ordinarily come from______exposure
adult
There is a need for paediatric formulations that permit accurate dosing and enhance patient compliance such as ________
- flavors
- colours
- liquids
- suspensions
- chewable tablets, etc.
Since development of paediatric formulations can be difficult and time consuming, it is important to consider the development of these formulations _______.
early in product development
For products exclusively used in paediatric populations, the entire development will be conducted in the paediatric population except for initial _____data (usually obtained from adults)
safety and tolerability
The presence of a ________for which the product represents a potentially important advance in therapy suggests the need for relatively urgent and early initiation of paediatric studies.
serious or life threatening disease
A pharmacokinetic/pharmacodynamic approach combined with safety and other relevant studies could avoid the need for _____..
clinical efficacy studies
When would clinical efficacy studies be needed in a paediatric population?
when novel implications are being sought for medicinal product in paeds or when novel implications of therapy are likely to be different between adults and paeds.
Pharmacokinetic studies should be done to support what type of development?
formulation
Why do we need to determine different pharmacokinetic parameters in different age groups?
to determine dosing recommendations
Measurement of _______such as pain requires different assessment instruments for patients of different ages.
subjective symptoms
Normally the paediatric database is limited at time of approval. Therefore, ___________ is particularly important
post marketing surveillance
Any classification of the paediatric population into age categories is somewhat _______
arbitrary
What are the possible/ examples of age categorizations given in E11?
- Preterm newborns
- newborns 0-27 days
- infant and toddlers (28 days to 23 months)
- children (2-11 years old)
- adolescents (12-16/ depending puberty and region
Study design issues to be considered with neonates include
1 - weight and age
2 - small blood volumes
3 - small number of patients given at the centre
4- difficulties assessing outcomes
By 1 or 2 years of age, _______of many drugs on a mg/kg basis may exceed adult values.
clearance
Factors useful in measuring the effects of medicinal product on children include?
- weight gain
- school attendance/ performance
- skeletal growth
As a rule, a pediatric subject is legally unable to provide informed consent. Where appropriate, participants should assent to enroll in a study. Age of assent is determined by?
The REB or to be consistent with local legal requirements.
Participants of appropriate intellectual maturity should personally sign and date either a separately designed, ______.
written assent form or the written informed consent.
Emancipated or mature minors (defined by local laws) may be capable of_____.
Giving autonomous consent
Mechanisms should be in place to ensure that a study can be rapidly terminated should _______ be noted.
an unexpected hazard
A fundamental principal in paediatric drug development requires that children should not be enrolled in a clinical study unless necessary to achieve ______.
an important pediatric public health need
When obtaining child assent, relevant elements of informed consent should be provided that are _______.
Appropriate to the child’s capability to understand.
It may be necessary to reasss the assent of a child in recognition of their __________and competency
advancing age and maturity
During clinical studies there is a requirement for obtaining adequate informed consent for continued participation from paediatric participants once a child reaches _______.
the age of legal consent
_____regulations related to confidentiality and privacy of paediatric participants must be followed.
local
A _______, not common regional requirements, is at the cornerstone of efficient paediatric drug development and timely delivery of safe and effective medicines for children.
common scientific approach
The neonatal period and preterm newborn infants is defined as __________.
the day of birth through the expected date of delivery plus 27 days.
Sometimes, there are difficulties with generating data across paediatric population due to..
a variety of ethical considerations and feasibility issues.
What is paediatric extrapolation
An approach to providing evidence in support of a drug/ treatment in paediatric population when it can be assumed that the course of the disease and expected response to a drug would be sufficiently similar in the paediatric and reference population.
When a drug is studied in a paediatric population, one should consider all factors which may result in different drug responses, such as ________factors that could impact on the extrapolation of data from one population to the other.
intrinsic and extrinsic
What are intrinsic factors?
factors that act within the individual e.g. development, attention
What are extrinsic factors?
factors that influence from outside eg. geographical
____ can help quantify available information and assist in defining the design of pediatric clinical studies and/or the dosing strategy.
Modelling and simulation
Well conducted M&S can inform on the pharmacokinetics, pharmacodynamics, ______ and safety of a drug.
efficacy
Three key practical factors to consider in pediatric clinical trials are ____________.
(1) feasibility, (2) outcome assessments, and (3) long-term clinical aspects, including safety
Pediatric drug development faces unique feasibility issues, including __________. (3 things)
(1) small number of eligible children for clinical research, (2) limited pediatric specific resources at research centers, and(3) the scarcity of dedicated pediatric trial networks
Strategies that foster _________ can facilitate participation, recruitment, and acceptability of a clinical study.
input from children, their caregivers, and the advocacy communities
A range of quantitative approaches to characterize the interactions between a drug and an organ system which could predict quantitative outcomes of the drug and/or system’s behavior in future experiments.
Modelling and simulation
