ICH E8 General Considerations for Clinical Trials Flashcards
1. Considerations for development plan 2. Basic trial design 3. Stages of drug development
Phase 1 type of study
Human pharmacology
Phase 2 type of study
Therapeutic Exploratory
Phase 3 type of study
Therapeutic Confirmatory
Phase 4 type of study
Therapeutic Use
Post Marketing
Objective of Phase 1
Initial Safety
Assess Tolerance
Assess efficacy
Pharmacokinetics
Pharmacodynamics
drug interactions
Define PK/PD
-tolerability of dose ranges and nature of AEs expected
Objective of Phase 2
Explore use of safety and efficacy in targeted indication
-refine effective dose and regimen
-Provide basis for confirmatory study
-explore use of therapeutic efficacy
Objective of Phase 3
Demonstrate/ confirm efficacy in previous trials
Provide and adequate basis for Assessing the benefit/risk
establish safety profile in larger, more representative populations
basis for marketing approval
investigate subgroups / special populations
*Study endpoints selected for confirmatory studies should be clinically relevant
-confirm therapeutic benefit
Objective of Phase 4
further understand safety and efficacy
long term follow-up
increase study population
drug in real world setting
ID less common AEs
refine dosing
-go beyond drug prior demonstration
Single and multiple dose PK and or PD studies
(What drug Phase)
Phase 1
Drug interaction studies
(What Phase)
Phase 1
Trials in relatively short duration, well defined narrow patient populations using surrogate or pharmacologic endpoints or clinical measures
Phase 2
biomarker studies
Phase 2
Dose-response exploration studies
Phase 2
Well controlled studies to establish efficacy
Phase 3
What phase do parallel dose studies to establish efficacy in larger populations occur?
Phase 3
Clinical safety studies
Phase 3
Large simple randomized trials
Phase 4
Comparative studies (what Phase)
Phase 3
Pharmacoeconomic studies
Phase 4
What are the stages of drug development?
Phase 1 - Human Pharmacology
Phase 2 - Therapeutic exploratory
Phase 3 - Therapeutic confirmation
Phase 4 - Therapeutic Use/Post Marketing
What are the stages of drug development?
Phase 1: Human pharmacology
Phase 2: Therapeutic exploratory
Phase 3: Therapeutic confirmatory
Phase 4: Therapeutic use / Post Marketing
The ethical principles underlying clinical study management are stated in
a) Declaration of Helsinki
b) Belmont report
c) Nuremberg Code
d) CIOMS guidelines
The ethical principles underlying clinical study management are stated in
a) Declaration of Helsinki
The term non-clinical studies refers to
a) Studies in vitro cell culture models
b) Studies in organ culture
c) Studies in animal models
d) Pilot human studies
The term non-clinical studies refers to
c) Studies in animal models
Nonclinical studies
a) Should be performed in at least three species
b) Must include a disease animal model
c) Should be sufficient to indicate safety in human studies
d) Are not needed before some human studies
Nonclinical studies
c) Should be sufficient to indicate safety in human studies
Toxicology studies in animal models
a) Should be reviewed by qualified experts
b) Assessed for their implications of subject safety
c) a only
d) a and b
Toxicology studies in animal models
d) a and b
a) Should be reviewed by qualified experts
b) Assessed for their implications of subject safety
Clinical trial protocols should reflect
a) Reasonable costs for the clinical trial
b) Minimize sample sizes to reduce risks
c) Sound scientific design
d) The use of control groups whenever possible.
Clinical trial protocols should reflect
c) Sound scientific design
The responsibility for the protection of clinical trial subjects rests with
a) IRB/IEC
b) Investigator
c) Sponsor
d) All of the above
The responsibility for the protection of clinical trial subjects rests with
d) all of the above
a) IRB/IEC
b) Investigator
c) Sponsor
ICH defined Human pharmacology trial are
a) Phase I
b) Phase I|
c) Phase III
d) Phase IV
ICH defined Human pharmacology trial are
a) Phase I
ICH defined Therapeutic Exploratory studies are likely to be
a) Phase I
b) Phase II
c) Phase III
d) Phase IV
ICH defined Therapeutic Exploratory studies are likely to be
b) Phase II
ICH defined Therapeutic Confirmatory studies are likely to be
a) Phase I
b) Phase II
c) Phase IIII
d) Phase IV
ICH defined Therapeutic Confirmatory studies are likely to be
c) Phase IIII
ICH defined Therapeutic Use studies are likely to be
a) Phase I
b) Phase II
c) Phase IIII
d) Phase IV
ICH defined Therapeutic Use studies are likely to be
d) Phase IV
Studies which examine dose tolerance, PK and PD aspects of a drug are likely to be
a) Human Pharmacology
b) Therapeutic Exploratory
c) Therapeutic Confirmatory
d) Therapeutic use
Studies which examine dose tolerance, PK and PD aspects of a drug are likely to be
a) Human Pharmacology
Characterization of drug’s absorption, metabolism and excretion
a) Are confined to Phase I studies
b) Can be conducted in Phase II studies if Phase I studies are inconclusive
c) Are never studied in Phase Ill studies
d) Continue throughout the development plan
Characterization of drug’s absorption, metabolism and excretion
d) Continue throughout the development plan
Studies which provide the most information for confirmatory study design are part of
a) Phase I studies
b) Phase II studies
c) a only
d) b only
Studies which provide the most information for confirmatory study design are part of
d) b only
b) Phase II studies
Trials of short duration in narrow patient populations using pharmacological endpoints or clinical measures are likely to be
a) Phase I
b) Phase II
c) Phase III
d) Phase IV
Trials of short duration in narrow patient populations using pharmacological endpoints or clinical measures are likely to be
b) Phase II
Studies which provide the most information for risk benefit relationship of a drug are likely to be
a) Phase I
b) Phase II
c) Phase III
d) Phase IV
Studies which provide the most information for risk benefit relationship of a drug are likely to be
c) Phase III
Studies on which marketing approval hinges are likely to be
a) Phase I
b) Phase II
c) Phase III
d) Phase IV
Studies on which marketing approval hinges are likely to be
c) Phase III
Epidemiologic and pharmacoeconomic studies are likely to be
a) Phase I
b) Phase II
c) Phase III
d) Phase IV
Epidemiologic and pharmacoeconomic studies are likely to be
d) Phase IV
Considerations for determining the nature and timing of non-clinical studies include
a) Duration and total exposure prosed in individual patients
b) Long half life
c) Route of administration
d) All of the above
Considerations for determining the nature and timing of non-clinical studies include
d) all of the above
a) Duration and total exposure prosed in individual patients
b) Long half life
c) Route of administration
For first in human studies the administered dose should be determined by
a) Pharmacokinetics
b) Drug pharmacology
c) Toxicological evaluations
d) All of the above
For first in human studies the administered dose should be determined by
d) all of the above
a) Pharmacokinetics
b) Drug pharmacology
c) Toxicological evaluations
Pharmacokinetic studies include all except
a) Dose response studies
b) Absorption, distribution and metabolism studies
c) Studies of the route of administration
d) Comparative bioavailability studies
Pharmacokinetic studies include all except
d) Comparative bioavailability studies
Formulations of the drug should be characterized on
a) Maximum tolerated dose
b) Bioavailability
c) Half -life
d) Drug clearance
Formulations of the drug should be characterized on
b) Bioavailability
Special populations are:
populations that require additional investigation during drug development because they have unique risk/benefit considerations
examples: pregnant and lactating women, children, geriatric populations
Study objectives in clinical trial design may include
a) Safety and efficacy characterization
b) Pharmacokinetic and pharmacological studies
c) Physiological and biochemical studies
d) All of the above
Study objectives in clinical trial design may include
d) all of the above
a) Safety and efficacy characterization
b) Pharmacokinetic and pharmacological studies
c) Physiological and biochemical studies
Study design considerations should include all of the following except
a) Cost assessment of proposed clinical trial
b) Primary and secondary endpoints and associated analyses
c) Methods to monitor adverse events
d) Use of appropriate comparators and adequate sample size
Study design considerations should include all of the following except
a) Cost assessment of proposed clinical trial
Which of the following statements is true
a) Trial subjects should not enroll in more than one trial at any given time
b) Women of childbearing potential should use highly effective contraception measures
c) Male subjects should be made aware of hazard of drug exposure to their sexual partners or progeny
d) All of the above
Which of the following statements is true
d) all of the above
a) Trial subjects should not enroll in more than one trial at any given time
b) Women of childbearing potential should use highly effective contraception measures
c) Male subjects should be made aware of hazard of drug exposure to their sexual partners or progeny
The major purpose of a control group is
to separate the effect of the treatment(s) from the effects of
other factors such as natural course of the disease, other medical care received, or observer or patient expectations
Statistical assessment of sample size should include assessments of all of the following except
a) Clinical trial logistics and cost controls
b) Treatment effect and data variability
c) Probability of error
d) Information in population subsets or secondary endpoints
Statistical assessment of sample size should include assessments of all of the following except
a) Clinical trial logistics and cost controls
Primary endpoints should have all of the following features except
a) Reflect clinically relevant effects
b) Exclude safety considerations
c) Be based on the principal objective
d) Be clearly distinguishable from secondary endpoints
Primary endpoints should have all of the following features except
b) Exclude safety considerations
The response variable is:
Study endpoints are response variables chosen to ________
The primary endpoint should be capable of _____________
an attribute of interest that may be affected by the drug (example pharmacokinetics, pharmacodynamics, efficacy, or safety of the drug, or to the use of the drug)
are the response variables that are chosen to assess drug effects
providing clinically relevant and convincing evidence related
to the primary objective of the study
Measurements of subjective and objective endpoints should be all of the following except
a) Accurate and precise
b) Reproducible and reliable
c) Responsive
d) Qualitative
Measurements of subjective and objective endpoints should be all of the following except
d) Qualitative
Methods to minimize bias include
a) Randomization
b) Blinding
c) Compliance measures
d) All of the above
Methods to minimize bias include
d) All of the above
a) Randomization
b) Blinding
c) Compliance measures
The protocol should include all of the following except
a) A section for assessment of conflict of interest
b) Analysis plan appropriate to objectives and design
c) Statistical methods
d) Plans for interim analysis
The protocol should include all of the following except
a) A section for assessment of conflict of interest
Phase IV protocols generally follow
a) Phase I protocols
b) Phase Il protocols
c) Phase Ill protocols
d) Approved use by the regulatory agency
Phase IV protocols generally follow
d) Approved use by the regulatory agency
Response variables are closely related to
a) Study endpoints
b) Primary objectives
c) Secondary Objectives
d) Statistical Plan
Response variables are closely related to
a) Study endpoints
Phase 1 studies of a cancer drug are done in
a) Healthy volunteers
b) Subjects with cancer
c) Subjects with cancer who have failed conventional therapy
d) Subjects with cancer with more than a year’s anticipated survival
Phase 1 studies of a cancer drug are done in
b) Subjects with cancer
Methods to be used in assessing patient drug use and compliance are best
a) Discussed verbally with the subject
b) Need not be mentioned in the informed consent
c) Need not be discussed with subjects
d) Included in the study protocol
Methods to be used in assessing patient drug use and compliance are best
d) Included in the study protocol
Planning of clinical trials with children
a) Should await the results of a trials in adults
b) Should be planned with children in mind from the very outset
c) Should exclude children ages
d) Should be planned predominantly in adolescents
Planning of clinical trials with children
b) Should be planned with children in mind from the very outset
