Statistical Principles in Clinical Trials

Question 1

The primary concern in a confirmatory trial is
A.) Efficacy
B.) Safety
C.) Pharmacodynamics
D.) Pharmacokinetics

Answer 1

A.) Efficacy

Question 2

Statistical principles are relevant to
A.) Phase I trials
B.) Phase II trials
C.) Phase III trials
D.) All of the above

Answer 2

D.) All of the above

Question 3

Bias is defined as
A.) Error in miscalculation of the final drug effect
B.) Trend to extrapolation in missing values
C.) Deviation in the estimation of a treatment effect from its true value
D.) Failure to use a complete data set for analysis

Answer 3

C.) Deviation in the estimation of a treatment effect from its true value

Question 4

Factors associated with bias can include
A.) Study design
B.) Study conduct
C.) Data analysis and interpretation
D.) All of the above

Answer 4

D.) All of the above

Question 5

Robustness refers to all of the following except
A.) Sensitivity of the conclusions to various limitations of data
B.) Sensitivity to the conclusions data to various limitations of assumptions
C.) Lack of an effect of study conclusions to alternative analytic approaches
D.) The health status of the subject in the clinical trial

Answer 5

D.) The health status of the subject in the clinical trial

Question 6

A development plan purpose is to
A.) Find a dose range that is simultaneously safe and effective
B.) Prove that the risk benefit relationship is acceptable
C.) Identify the subjects who would most benefit and indications for the use
C.) All of the above

Answer 6

C.) All of the above

Question 7

In a confirmatory trial the following apply
A.) Phase I results are verified in phase II trials
B.) Test the key hypothesis, effect size and clinical significance
C.) Conduct the trial in a large sample of subjects
D.) The design is that described for the use of an approved drug

Answer 7

B.) Test the key hypothesis, effect size and clinical significance

Question 8

Exploratory trials (Select all that apply)
A.) Explore a wide range of hypotheses
B.) Provide formal proof of efficacy
C.) Need flexible designs
D.) Are designed to explore new uses for an approved drug

Answer 8

A.) Explore a wide range of hypotheses
C.) Need flexible designs

Question 9

The population of a clinical trial reflects all of the following except:
A.) My be narrow in early trials to maximize effects
B.) Tend to mirror the target disease population in later trials
C.) Is always significantly large in Phase I trials to ensure reliable toxicology results
D.) Must balance eligibility criteria and treatment effect

Answer 9

C.) Is always significantly large in Phase I trials to ensure reliable toxicology results

Question 10

The primary variable reflects all of the following except
A.) Must provide convincing evidence of the primary objective
B.) Is usually the efficacy variable
C.) Must provide significant support for secondary variables
D.) May be restricted in some trials only to safety and tolerability

Answer 10

C.) Must provide significant support for secondary variables

Question 11

Secondary variables must
A.) Be supportive measurements related to the primary objectives
B.) Need to have their role and importance defined carefully in a clinical trial
C.) Should be limited answering a limited number of questions in the trial
D.) All of the above

Answer 11

D.) All of the above

Question 12

Global assessment variables reflect all of the following except
A.) They are developed to measure the overall usefulness of treatment
B.) Require that a scale be developed and detailed in the protocol
C.) Should define how to assign subjects to a unique category on a scale
D.) Are never used as a primary variable in most clinical trials

Answer 12

D.) Are never used as a primary variable in most clinical trials

Question 13

Which of the following statements regarding surrogate variables is false?
A.) They are used when direct observation of clinical efficacy is not practical
B.) May show an effect in the absence of a clinical outcome
C.) May not yield a quantitative measure of clinical benefit
D.) Often allow for an assessment of benefits relative to adverse effects

Answer 13

D.) Often allow for an assessment of benefits relative to adverse effects

Question 14

For a surrogate variable to be reliable, they should
A.) Have a plausible relationship to clinical outcome
B.) Be supported by epidemiologic evidence
C.) Reflect a treatment effect that corresponds to clinical outcome
D.) All of the above

Answer 14

D.) All of the above

Question 15

A double blind trial is one in which the following are unaware of the treatment received
A.) Sponsor
B.) Investigator
C.) Subject
D.) All of the above

Answer 15

D.) All of the above

Question 16

In a double blind trial the person who should be unaware of the treatment should not be involved in assessing
A.) Eligibility
B.) Endpoints
C.) Compliance
D.) All of the above

Answer 16

D.) All of the above

Question 17

In a single blind trial the person who is unaware of the treatment
A.) Subject
B.) Investigator
C.) Monitor
D.) Clinical coordinator

Answer 17

A.) Subject

Question 18

In an open label trial the persons who should be aware that the treatment is being administered are
A.) Subject and investigator
B.) Pharmacist and investigator
C.) Sponsor and investigator
D.)Monitor and investigator

Answer 18

A.) Subject and investigator

Question 19

Breaking the blind for a single subject
A.) Implies breaking the blind for the study group
B.) May be done at the discretion of the monitor
C.) Should be implemented when deemed essential for subject’s care
D.) Always involves a serious adverse event

Answer 19

C.) Should be implemented when deemed essential for subject’s care

Question 20

In a parallel group design the subjects
A.) Randomized to two arms each with a different treatment
B.) Are evaluated before and after drug administration
C.) Are randomized to a sequence of two treatments
D.) Are evaluated simultaneously for varying combinations of treatments

Answer 20

A.) Randomized to two arms each with a different treatment

Question 21

In a crossover design the subjects
A.) Randomized to two arms each with different treatment
B.) Are evaluated before and after drug administration
C.) Are randomized to a sequence of two treatments
D.) Are evaluated simultaneously for varying combinations

Answer 21

C.) Are randomized to a sequence of two treatments

Question 22

In a pre-post design the subjects
A.) Randomized to two arms each with different treatment
B.) Are evaluated before and after drug administration
C.) Are randomized to a sequence of two treatments
D.) Are evaluated simultaneously for varying combinations

Answer 22

B.) Are evaluated before and after drug administration

Question 23

In a factorial design the subjects
A.) Randomized to two arms each with different treatment
B.) Are evaluated before and after drug administration
C.) Are randomized to a sequence of two treatments
D.) Are evaluated simultaneously for varying combinations

Answer 23

D.) Are evaluated simultaneously for varying combinations

Question 24

The most commonly used study design in clinical trials is:
A.) Parallel design
B.) Crossover design
C.) Pre-post design
D.) Factorial design

Answer 24

D.) Factorial design

Question 25

For a successful crossover design:
A.) Carryover form a previous treatment should be minimized
B.) The disease should be chronic and stable
C.) Drug effects should develop fully within the treatment period
D.) All of the above

Answer 25

D.) All of the above

Question 26

Multi center trials have the following features except
A.) They are more efficient as they accrue sufficient subjects
B.) May facilitate generalization of findings
C.) May present the only method for accruing subjects in rare diseases
D.) Are easily administered for uniform implementation of the protocol

Answer 26

D.) Are easily administered for uniform implementation of the protocol

Question 27

Drug efficacy is best established by
A.) Demonstrating superiority to placebo in a placebo control trial
B.) Demonstrating superiority in an active control trial
C.) Demonstrating a dose response relationship
D.) All of the above

Answer 27

D.) All of the above

Question 28

A placebo controlled trial would be considered unethical if
A.) The drug has been shown to be efficacious in a superiority trial
B.) The drug has been shown equivalent to active control in a non-inferiority trial
C.) Drug has shown serious side effects in preclinical studies
D.) All of the above

Answer 28

A.) The drug has been shown to be efficacious in a superiority trial

Question 29

An equivalence or non-inferiority trial is one which
A.) Efficacy of a test drug is no worse than an active comparator
B.) Multiple doses of a test drug are compared to multiple doses of as standard drug
C.) A only
D.) A and B

Answer 29

D.) A and B

Question 30

An active control is best represented by
A.) Any drug that has shown activity against the disease
B.) A drug that has been shown to be non-inferior in an equivalence trial
C.) A drug that has shown efficacy in a superiority trial
D.) All of the above

Answer 30

C.) A drug that has shown efficacy in a superiority trial

Question 31

In assessing sample size the items that need to be specified include all except
A.) The primary variable and test statistic
B.) The null and alternative hypothesis
C.) The projected cost of the trial for the designated sample size
D.) Type I and Type II errors

Answer 31

C.) The projected cost of the trial for the designated sample size

Question 32

The probability of erroneously rejecting the null hypothesis is described as
A.) Type I error
B.) Type II error
C.) Type III error
D.) Risk assessment

Answer 32

A.) Type I error

Question 33

The probability of erroneously failing to reject the null hypothesis is described as
A.) Type I error
B.) Type II error
C.) Type III error
D.) Risk assessment

Answer 33

B.) Type II error

Question 34

Data collection in a clinical trial usually employs
A.) Paper case record forms
B.) Remote site monitoring
C.) Medical computer systems and electronic transfer
D.) All of the above

Answer 34

D.) All of the above

Question 35

The type of monitoring in a confirmatory clinical trial may include
A.) Oversight of the quality of the clinical trial
B.) Breaking the blind for treatment comparison and interim analysis
C.) A only
D.) A and B

Answer 35

D.) A and B

Question 36

Oversight of the quality of a trial involves review of all of the following except
A.) Protocol adherence
B.) Conflict of interest
C.) Patient accrual and retention
D.) Review of design assumptions

Answer 36

B.) Conflict of interest

Question 37

Inclusion and exclusion criteria
A.) Can be set to maximize enrollment
B.) Are independent of preclinical studies
C.) Should remain constant during a clinical trial
D.) May change as needed during a clinical trial

Answer 37

C.) Should remain constant during a clinical trial

Question 38

The ideal data analysis set is one in which
A.) Procedures are followed perfectly
B.) Data records are complete
C.) There is no loss to patient follow up
D.) All of the above

Answer 38

D.) All of the above

Question 39

Irregularities in the data analysis set may arise from
A.) Protocol violations
B.) Patient withdrawals
C.) Missing values
D.) All of the above

Answer 39

D.) All of the above

Question 40

The intention to treat analysis set includes
A.) All treated subjects
B.) Only subjects with complete drug treatments
C.) Subjects who have undergone the minimum number of acceptable trial visits
D.) All randomized subjects

Answer 40

D.) All randomized subjects

Question 41

The per protocol analysis data set includes
A.) All randomized subjects
B.) All subjects who have not undergone SAEs
C.) Evaluable subjects compliant with the protocol
D.) Subjects with no missed visits as specified in the schedule of assessments

Answer 41

C.) Evaluable subjects compliant with the protocol

Question 42

Criteria used for inclusion of data in the per protocol data set include
A.) Completion of minimal exposure to treatment
B.) Available measure of the primary variables
C.) Absence of protocol violations and eligibility criteria
D.) All of the above

Answer 42

D.) All of the above

Question 43

In confirmatory trials, it is usual to analyze
A.) Full analysis set only
B.) Per protocol set only
C.) Full analysis and per protocol sets
D.) Null hypothesis analysis set

Answer 43

C.) Full analysis and per protocol sets

Question 44

Missing values in a data set
A.) Are generally discounted in data analysis
B.) Are eliminated by extrapolation
C.) Contribute to bias
D.) Have no effect on hypothesis testing

Answer 44

C.) Contribute to bias

Question 45

Covariates in a statistical analysis may include
A.) Variation in populations between centers in a multi-center trial
B.) Variations in age subgroups
C.) Variations by gender
D.) All of the above

Answer 45

D.) All of the above

Question 46

Pre analysis review should include considerations of
A.) Exclusion of subjects from the data set
B.) Transformation of the variables
C.) Impact an statistical treatment of outliers
D.) All of the above

Answer 46

D.) All of the above

Question 47

Safety and tolerability of the drug are best assessed in
A.) Phase I trials
B.) Phase II trials
C.) Continuously during drug development
D.) Phase III trials

Answer 47

C.) Continuously during drug development

Question 48

Blind review occurs
A.) At various stages of a clinical trial
B.) After study close out visit for all sites has been completed
C.) At pre-specified intervals
D.) Between trial completion and breaking of the blind

Answer 48

D.) Between trial completion and breaking of the blind

Question 49

The term double dummy refers to
A.) Double blinded trial
B.) Placebo controlled trial
C.) Technique to retain the blind when administering supplies to non-identical groups
D.) All of the above

Answer 49

C.) Technique to retain the blind when administering supplies to non-identical groups

Question 50

The DSMB monitors
A.) The safety data
B.) Patient accrual
C.) Data accuracy
D.) Missing data

Answer 50

A.) The safety data

Question 51

The DSMB can recommend
A.) Continuation, modification or termination of a sponsor’s trial
B.) The continued enrollment of patients in light of safety events
C.) The submission of serious adverse safety events for regulatory review
D.) The submission of serious adverse safety events to the IRB

Answer 51

A.) Continuation, modification or termination of a sponsor’s trial

Question 52

Methods to avoid the bias in clinical trial generally involve
A.) Single blind only
B.) Double blind only
C.) Single or double blind
D.) Open label

Answer 52

C.) Single or double blind

Question 53

A trial designed on the basis of some evidence benefits is leily to be
A.) Exploratory trial
B.) Confirmatory trial
C.) Phase IV trial
D.) Open label trial

Answer 53

B.) Confirmatory trial

Question 54

Multicenter trials can be implemented for
A.) Open label trials
B.) Exploratory trials
C.) Confirmatory trials
D.) Any stage of clinical drug development

Answer 54

D.) Any stage of clinical drug development