ADR Adverse drug reaction
All untoward and unintended response to an
investigational medicinal product (pre-marketing) or
medicinal product (post-marketing) related to any
dose administered
Causal relationship
Report:
- 7 days: fatal or life-threatening
- 15 days: Serious ADR report
ADR Adverse drug reaction
Pre-marketing: all untoward and unintended
responses to an investigational MP related to any dose
administered
Post-marketing: a response to a MP who is noxious
and unintended
Unexpected ADR: adverse reaction in the nature,
severity, specificity or outcome of which is not
consistent with the terms or description used in the
local/regional product labelling (PI, SPC)
AE Adverse event
Any untoward medical occurrence in a patient or
clinical trial subject administered a pharmaceutical
product and which does not necessarily have to have
a causal relationship with the treatment
Classification:
- Seriousness/significant
- Expectedness: what might be anticipated from the
pharmacological properties of the MP
- Causal relationship: done by both investigator and
sponsor, per event, blinded manner
ALCOA Data should meet fundamental elements of quality, data
should follow ALCOA
Attributable (toekenbaar)
Legible (duidelijk)
Contemporaneous (gelijktijdig;tijdelijk)
Original
Accurate (nauwkeurig)
ANDA Abbreviated new drug application
Generic
US Legal framework
ASPR Anonymised single patient report
UK only
ASR Annual safety report
Assent form An assent form is a document used in clinical research to
obtain agreement from minors (typically children and
adolescents) who are not legally able to provide full
informed consent on their own. It is designed to ensure that
the child understands the study to the extent possible and
agrees to participate. Assent forms are used in conjunction
with parental or guardian consent forms, as the legal
responsibility for the child's participation still rests with the
parents or guardians.
Used to obtain agreement from minors to participate
in a study alongside parental/guardian consent
, Key components: age-appropriate language, study
explanation, procedures, voluntary participation, risk
and benefits, confidentiality, questions & support
Audit Systematic & independent examination of trial related
activities and documents to determine whether the
evaluated trial related activities were conducted, and the
data were recorded, analysed and accurately reported
according to the protocol, sponsors SOP, GCP, and the
applicable regulatory requirements.
Overviewed by the quality departments
Sponsor appoint individuals (independent) to conduct
audits
QA auditors are independent of the operational team
Auditors are qualified by training and experiences
Objective is to verify that:
- Regulatory requirements are respected
- Data is reliable & accurate
- Procedure & protocol is understood & correctly
applied
Different types of audits
Audit report
CAPA management: follow up of the CAPA plan
Audit trail Documentation that allows reconstruction of the course of
events.
Eg ICF with a date & signed
Data entry in database
Belgium CTL Belgium clinical trial legislation
Law: directly binding within Belgium
Royal decree: binding implementation/clarification of
the law
Circular letter: Belgian consensus on interpretative
issues
BLA Biologic license application
US legal framework
Blinding Blinding is used to decrease the biases that occur in a
clinical trial when patients are evaluated during a trial, to
avoid placebo effect that occurs often in open-label trials.
Prevent identification of the treatment until all opportunities
of bias have been passed
Allows strongest interpretation of data if conditions
described in double blind trials are met
Types:
- Open label: everybody knows the treatment given
to the subject
- Single blind: a type of masking in which one party
involved with the clinical trial, either the
investigator or the subject, does not know which
participants has been assigned the IMP
- Double blind: both, subject and investigator are
blind to treatment assigned of the patients are
blind to treatment assignment of the patient
- Triple blind: also the clinical project team of the
, sponsor is blinded, best guarantee for unbiased
results
2-physician method to preserve the blind
Breaking the blind: only in case of emergency,
procedure will be specified in the protocol
CAPA Corrective and preventive action
consists of improvements to an organization's
processes taken to eliminate causes of non-
conformities or other undesirable situations
Causality Causality of AES
assessment Done by investigator and sponsor independently
Per event
Blind manner
Centralised CT Conducted entirely at clinical sites, ensuring controlled and
supervised conditions for all trial activities.
CFR Code of federal regulation
US legal framework
CIOMS Council for international organisations of medical sciences
European format for ADR report for authorities
Clinical Why? A regulatory will grant official permission to use the MP
research in a general population, only if there is evidence about
safety & efficacy
When?
- Pre-registration: to investigate a new treatment, a
new indication, a new population
- Post-registration: compare with competitors,
evaluate the therapeutic value, observe safety in a
large population
Steps clinical research
- Discovery: 2 -10y
- Preclinical: 4y
- Phase 0: human microdosing trial
Look if the drug or agents behaves in human
subjects as expected from preclinical studies
Administration of single therapeutic doses of
the study drug in a small number of subjects
To gather preliminary data on the agents PK
No safety of efficacy
Goals: to generate data to inform subsequent
development, enhance efficiency, increase
chance of success of subsequent development
- Phase I: human pharmacology trial (20-100)
First administration in man, biological effect
and safety evaluation
Healthy volunteers
Safety, tolerance, PK, PD, duration & dose of
activity
Ia: single ascending dose => Participants are
given a single dose of the investigational drug.
All untoward and unintended response to an
investigational medicinal product (pre-marketing) or
medicinal product (post-marketing) related to any
dose administered
Causal relationship
Report:
- 7 days: fatal or life-threatening
- 15 days: Serious ADR report
ADR Adverse drug reaction
Pre-marketing: all untoward and unintended
responses to an investigational MP related to any dose
administered
Post-marketing: a response to a MP who is noxious
and unintended
Unexpected ADR: adverse reaction in the nature,
severity, specificity or outcome of which is not
consistent with the terms or description used in the
local/regional product labelling (PI, SPC)
AE Adverse event
Any untoward medical occurrence in a patient or
clinical trial subject administered a pharmaceutical
product and which does not necessarily have to have
a causal relationship with the treatment
Classification:
- Seriousness/significant
- Expectedness: what might be anticipated from the
pharmacological properties of the MP
- Causal relationship: done by both investigator and
sponsor, per event, blinded manner
ALCOA Data should meet fundamental elements of quality, data
should follow ALCOA
Attributable (toekenbaar)
Legible (duidelijk)
Contemporaneous (gelijktijdig;tijdelijk)
Original
Accurate (nauwkeurig)
ANDA Abbreviated new drug application
Generic
US Legal framework
ASPR Anonymised single patient report
UK only
ASR Annual safety report
Assent form An assent form is a document used in clinical research to
obtain agreement from minors (typically children and
adolescents) who are not legally able to provide full
informed consent on their own. It is designed to ensure that
the child understands the study to the extent possible and
agrees to participate. Assent forms are used in conjunction
with parental or guardian consent forms, as the legal
responsibility for the child's participation still rests with the
parents or guardians.
Used to obtain agreement from minors to participate
in a study alongside parental/guardian consent
, Key components: age-appropriate language, study
explanation, procedures, voluntary participation, risk
and benefits, confidentiality, questions & support
Audit Systematic & independent examination of trial related
activities and documents to determine whether the
evaluated trial related activities were conducted, and the
data were recorded, analysed and accurately reported
according to the protocol, sponsors SOP, GCP, and the
applicable regulatory requirements.
Overviewed by the quality departments
Sponsor appoint individuals (independent) to conduct
audits
QA auditors are independent of the operational team
Auditors are qualified by training and experiences
Objective is to verify that:
- Regulatory requirements are respected
- Data is reliable & accurate
- Procedure & protocol is understood & correctly
applied
Different types of audits
Audit report
CAPA management: follow up of the CAPA plan
Audit trail Documentation that allows reconstruction of the course of
events.
Eg ICF with a date & signed
Data entry in database
Belgium CTL Belgium clinical trial legislation
Law: directly binding within Belgium
Royal decree: binding implementation/clarification of
the law
Circular letter: Belgian consensus on interpretative
issues
BLA Biologic license application
US legal framework
Blinding Blinding is used to decrease the biases that occur in a
clinical trial when patients are evaluated during a trial, to
avoid placebo effect that occurs often in open-label trials.
Prevent identification of the treatment until all opportunities
of bias have been passed
Allows strongest interpretation of data if conditions
described in double blind trials are met
Types:
- Open label: everybody knows the treatment given
to the subject
- Single blind: a type of masking in which one party
involved with the clinical trial, either the
investigator or the subject, does not know which
participants has been assigned the IMP
- Double blind: both, subject and investigator are
blind to treatment assigned of the patients are
blind to treatment assignment of the patient
- Triple blind: also the clinical project team of the
, sponsor is blinded, best guarantee for unbiased
results
2-physician method to preserve the blind
Breaking the blind: only in case of emergency,
procedure will be specified in the protocol
CAPA Corrective and preventive action
consists of improvements to an organization's
processes taken to eliminate causes of non-
conformities or other undesirable situations
Causality Causality of AES
assessment Done by investigator and sponsor independently
Per event
Blind manner
Centralised CT Conducted entirely at clinical sites, ensuring controlled and
supervised conditions for all trial activities.
CFR Code of federal regulation
US legal framework
CIOMS Council for international organisations of medical sciences
European format for ADR report for authorities
Clinical Why? A regulatory will grant official permission to use the MP
research in a general population, only if there is evidence about
safety & efficacy
When?
- Pre-registration: to investigate a new treatment, a
new indication, a new population
- Post-registration: compare with competitors,
evaluate the therapeutic value, observe safety in a
large population
Steps clinical research
- Discovery: 2 -10y
- Preclinical: 4y
- Phase 0: human microdosing trial
Look if the drug or agents behaves in human
subjects as expected from preclinical studies
Administration of single therapeutic doses of
the study drug in a small number of subjects
To gather preliminary data on the agents PK
No safety of efficacy
Goals: to generate data to inform subsequent
development, enhance efficiency, increase
chance of success of subsequent development
- Phase I: human pharmacology trial (20-100)
First administration in man, biological effect
and safety evaluation
Healthy volunteers
Safety, tolerance, PK, PD, duration & dose of
activity
Ia: single ascending dose => Participants are
given a single dose of the investigational drug.
