ICH E8 General Considerations for Clinical Trials

Question 1

Phase 1 type of study

Answer 1

Human pharmacology

Question 2

Phase 2 type of study

Answer 2

Therapeutic Exploratory

Question 3

Phase 3 type of study

Answer 3

Therapeutic Confirmatory

Question 4

Phase 4 type of study

Answer 4

Therapeutic Use
Post Marketing

Question 5

Objective of Phase 1

Answer 5

Initial Safety
Assess Tolerance
Assess efficacy
Pharmacokinetics
Pharmacodynamics
drug interactions
Define PK/PD
-tolerability of dose ranges and nature of AEs expected

Question 6

Objective of Phase 2

Answer 6

Explore use of safety and efficacy in targeted indication
-refine effective dose and regimen
-Provide basis for confirmatory study
-explore use of therapeutic efficacy

Question 7

Objective of Phase 3

Answer 7

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

Question 8

Objective of Phase 4

Answer 8

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

Question 9

Single and multiple dose PK and or PD studies
(What drug Phase)

Answer 9

Phase 1

Question 10

Drug interaction studies
(What Phase)

Answer 10

Phase 1

Question 11

Trials in relatively short duration, well defined narrow patient populations using surrogate or pharmacologic endpoints or clinical measures

Answer 11

Phase 2

Question 12

biomarker studies

Answer 12

Phase 2

Question 13

Dose-response exploration studies

Answer 13

Phase 2

Question 14

Well controlled studies to establish efficacy

Answer 14

Phase 3

Question 15

What phase do parallel dose studies to establish efficacy in larger populations occur?

Answer 15

Phase 3

Question 16

Clinical safety studies

Answer 16

Phase 3

Question 17

Large simple randomized trials

Answer 17

Phase 4

Question 18

Comparative studies (what Phase)

Answer 18

Phase 3

Question 19

Pharmacoeconomic studies

Answer 19

Phase 4

Question 20

What are the stages of drug development?

Answer 20

Phase 1 - Human Pharmacology
Phase 2 - Therapeutic exploratory
Phase 3 - Therapeutic confirmation
Phase 4 - Therapeutic Use/Post Marketing

Question 21

What are the stages of drug development?

Answer 21

Phase 1: Human pharmacology

Phase 2: Therapeutic exploratory

Phase 3: Therapeutic confirmatory

Phase 4: Therapeutic use / Post Marketing

Question 22

The ethical principles underlying clinical study management are stated in
a) Declaration of Helsinki
b) Belmont report
c) Nuremberg Code
d) CIOMS guidelines

Answer 22

The ethical principles underlying clinical study management are stated in
a) Declaration of Helsinki

Question 23

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

Answer 23

The term non-clinical studies refers to
c) Studies in animal models

Question 24

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

Answer 24

Nonclinical studies
c) Should be sufficient to indicate safety in human studies

Question 25

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

Answer 25

Toxicology studies in animal models d) a and b a) Should be reviewed by qualified experts b) Assessed for their implications of subject safety

Question 26

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.

Answer 26

Clinical trial protocols should reflect c) Sound scientific design

Question 27

The responsibility for the protection of clinical trial subjects rests with a) IRB/IEC b) Investigator c) Sponsor d) All of the above

Answer 27

The responsibility for the protection of clinical trial subjects rests with d) all of the above a) IRB/IEC b) Investigator c) Sponsor

Question 28

ICH defined Human pharmacology trial are a) Phase I b) Phase I| c) Phase III d) Phase IV

Answer 28

ICH defined Human pharmacology trial are a) Phase I

Question 29

ICH defined Therapeutic Exploratory studies are likely to be a) Phase I b) Phase II c) Phase III d) Phase IV

Answer 29

ICH defined Therapeutic Exploratory studies are likely to be b) Phase II

Question 30

ICH defined Therapeutic Confirmatory studies are likely to be a) Phase I b) Phase II c) Phase IIII d) Phase IV

Answer 30

ICH defined Therapeutic Confirmatory studies are likely to be c) Phase IIII

Question 31

ICH defined Therapeutic Use studies are likely to be a) Phase I b) Phase II c) Phase IIII d) Phase IV

Answer 31

ICH defined Therapeutic Use studies are likely to be d) Phase IV

Question 32

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

Answer 32

Studies which examine dose tolerance, PK and PD aspects of a drug are likely to be a) Human Pharmacology

Question 33

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

Answer 33

Characterization of drug's absorption, metabolism and excretion d) Continue throughout the development plan

Question 34

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

Answer 34

Studies which provide the most information for confirmatory study design are part of d) b only b) Phase II studies

Question 35

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

Answer 35

Trials of short duration in narrow patient populations using pharmacological endpoints or clinical measures are likely to be b) Phase II

Question 36

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

Answer 36

Studies which provide the most information for risk benefit relationship of a drug are likely to be c) Phase III

Question 37

Studies on which marketing approval hinges are likely to be a) Phase I b) Phase II c) Phase III d) Phase IV

Answer 37

Studies on which marketing approval hinges are likely to be c) Phase III

Question 38

Epidemiologic and pharmacoeconomic studies are likely to be a) Phase I b) Phase II c) Phase III d) Phase IV

Answer 38

Epidemiologic and pharmacoeconomic studies are likely to be d) Phase IV

Question 39

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

Answer 39

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

Question 40

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

Answer 40

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

Question 41

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

Answer 41

Pharmacokinetic studies include all except d) Comparative bioavailability studies

Question 42

Formulations of the drug should be characterized on a) Maximum tolerated dose b) Bioavailability c) Half -life d) Drug clearance

Answer 42

Formulations of the drug should be characterized on b) Bioavailability

Question 43

Special populations are:

Answer 43

populations that require additional investigation during drug development because they have unique risk/benefit considerations examples: pregnant and lactating women, children, geriatric populations

Question 44

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

Answer 44

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

Question 45

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

Answer 45

Study design considerations should include all of the following except a) Cost assessment of proposed clinical trial

Question 46

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

Answer 46

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

Question 47

The major purpose of a control group is

Answer 47

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

Question 48

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

Answer 48

Statistical assessment of sample size should include assessments of all of the following except a) Clinical trial logistics and cost controls

Question 49

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

Answer 49

Primary endpoints should have all of the following features except b) Exclude safety considerations

Question 50

The response variable is: Study endpoints are response variables chosen to ________ The primary endpoint should be capable of _____________

Answer 50

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

Question 51

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

Answer 51

Measurements of subjective and objective endpoints should be all of the following except d) Qualitative

Question 52

Methods to minimize bias include a) Randomization b) Blinding c) Compliance measures d) All of the above

Answer 52

Methods to minimize bias include d) All of the above a) Randomization b) Blinding c) Compliance measures

Question 53

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

Answer 53

The protocol should include all of the following except a) A section for assessment of conflict of interest

Question 54

Phase IV protocols generally follow a) Phase I protocols b) Phase Il protocols c) Phase Ill protocols d) Approved use by the regulatory agency

Answer 54

Phase IV protocols generally follow d) Approved use by the regulatory agency

Question 55

Response variables are closely related to a) Study endpoints b) Primary objectives c) Secondary Objectives d) Statistical Plan

Answer 55

Response variables are closely related to a) Study endpoints

Question 56

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

Answer 56

Phase 1 studies of a cancer drug are done in b) Subjects with cancer

Question 57

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

Answer 57

Methods to be used in assessing patient drug use and compliance are best d) Included in the study protocol

Question 58

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

Answer 58

Planning of clinical trials with children b) Should be planned with children in mind from the very outset