Study Design

Question 1

double blind

Answer 1

both experimenter and subjects are blinded

Question 2

crossover study

Answer 2

Each study participant receives all treatments that are being investigated but at different times

Order of treatments is randomized

Washout often included between treatments

Question 3

partial crossover or incomplete block

Answer 3

In some crossover designs, particularly ones with more than 2 treatments, patients may not receive all treatments under investigation, but would receive more than 1

Question 4

Pros of Crossover Study Design

Answer 4

Each patient serves as their own control.

Reduces between-subject variability.

Allows for detection of smaller effect sizes with reduced sample sizes.

Question 5

Effect Size

Answer 5

Quantitative measure of the magnitude of a phenomenon (eg. the correlation between 2 variables)

Small effect size is one in which there is a real effect, i.e. something is really happening in the world - but which you can only see through careful study.

Question 6

Parallel Study

Answer 6

Two groups of treatments: A & B

One group receives only A, other group receives only B

Question 7

Longitudinal Study

Answer 7

Repeated observations of the same variables over short or long periods of time.

Often observational but can be structured as longitudinal randomized experiments.

Question 8

Large Effect Size

Answer 8

Can be seen by the naked eye, easily observed.

Question 9

Small Effect Size

Answer 9

There is a real effect, i.e. something is really happening in the world - but which you can only see through careful study.

Question 10

Confounders

Answer 10

Variable that influences both dependent and independent variables.

Question 11

Why is the influence of confounders reduced in crossover studies?

Answer 11

Each patient is their own control.

Question 12

Optimal crossover designs require ________ subjects.

Answer 12

fewer

Question 13

Which patient population best aligns with crossover study design?

Answer 13

Crossover studies are often done to improve symptoms of patients with chronic conditions.

May be infeasible or unethical for curative treatments or rapidly changing conditions.

Question 14

What are two main issues with crossover studies?

Answer 14

1. “Order” Effects. Order of treatment may effect outcome, eg. drug with many adverse effects given first, making patients taking a 2nd, less harmful medication, more sensitive to any adverse effects.
2. “Carry-over”. Carry-over between treatments which confounds estimates of treatment effects. In practice “carry-over” effects can be avoided with a sufficiently long “wash-out” period between treatments. However, planning for sufficently long wash-out periods requires expert knowledge of the dynamics of the treatment, which is often unknown.

Question 15

A randomization method in which all subjects have the same chance to receive each treatment

Answer 15

Unrestricted Randomization

Question 16

A trial with the primary objective of showing that the response to the investigational product is not clinically inferior to a comparative agent (active or placebo)

Answer 16

Non - inferiority trial

Question 17

-Trial where the treatment assignment is not known by the study participant - The investigator and staff are aware of the treatment but the subject is not, or vice-versa

Answer 17

Single Blind study

Question 18

The formal evaluation of the quantitative evidence from two or more trials bearing on the same question

Answer 18

Meta-analysis

Question 19

a randomization method in which the likelihood of subsequent assignments changes based on previous ones

Answer 19

Dynamic randomization

Question 20

Comparator (product)

Answer 20

An investigational or marketed product (i.e. active control) or placebo, used as reference in a clinical trial

Question 21

Non-inferiority Trial

Answer 21

A trial with the primary objective of showing that the response to the investigational product is not clinically inferior to a comparative agent (active or placebo)

Question 22

A variable that provides an indirect measurement of effect in situations where direct measurement of clinical effect is not feasible or practical

Answer 22

surrogate variable

Question 23

Therapeutic Confirmatory Study

Answer 23

Phase III

-demonstrate/confirm efficacy (the ability to produce a desired or intended result).
-establish safety profile
-provide an adequate basis for assessing the benefit/risk
relationship to support licensing
-establish dose-response relationship

Question 24

Human Pharmacology Study

Answer 24

• Assess Tolerance
• Define/Describe Pharmacokinetics and pharmacodynamics
• explore drug Metabolism and drug intractions
• estimate Activity

TAMP

Question 25

investigational product

Answer 25

a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use

Question 26

Exploratory Trial

Answer 26

• Performed earlier in Phase I
• Prior to dose esclation, safety and tolerability trials.
• Usually small number of patients or healthy subjects and expose them to a low dose of IP.
• objectives may not always lead to simple tests of pre-defined hypothesis

Question 27

Audit Trial

Answer 27

Documentation that allows reconstruction of the course of events

Question 28

Pharmacokinetics study

Answer 28

• PK
• The study of how the body affects a drug after administration.
• Studies: (CAD)
• Clearance of the drug
• Possible Accumulation of parent drug or metabolites
• Potential Drug-drug interactions

Question 29

Stratified randomization trial

Answer 29

a randomization method in which subjects with shared characteristics are divided into strata; each stratum is then randomized seperatley

Question 30

A trial with the primary objective of showing that the response to the investigational product is superior to a comparative agent (active or placebo)

Answer 30

Superiority Trial

Question 31

statistical methods, such as significance tests and confidence intervals, which can be interpreted in terms of the frequency of certain outcomes occurring in hypothetical repeated realizations of the same experimental situation

Answer 31

Frequentist Methods

Question 32

Block Randomization

Answer 32

a randomization method in which subjects are randomized in blocks, each containing a predefined combination of treatments

Question 33

composite variable

Answer 33

when a single primary variable can’t be selected from multiple measurements associated with primary variable. A useful strategy is to combine the multiple measurements into a single variable

Question 34

Full analysis set

Answer 34

the set of subjects that is as close as possible to the ideal implied by the intention-to treat principle

Question 35

Primary Variable

Answer 35

of greatest importance to the trial’s primary objective, and usually the one used in the sample size calculation.

Question 36

Global Assessment Variables

Answer 36

A single variable, usually in the form of a scale of ordered categorical ratings, which integrates objective variables and the investigator’s overall impression about the state or change in state of a subject as result of the tria’s intervention or therapy.

Question 37

Double dummy

Answer 37

Double dummy is a technique for retaining the blind when administering supplies in a clinical trial, when the two treatments cannot be made identical. Supplies are prepared for Treatment A (active and indistinguishable placebo) and for Treatment B (active and indistinguishable placebo). Subjects then take 2 sets of treatment: either A (active) and B (placebo) or A (placebo) and B (active)

Question 38

Bayesian Approaches

Answer 38

Approaches to data analysis that provide a posterior probablity distribution for some parameter, derived from observed data and a prior probability distribution for the parameter. it provides people the tools to update their beliefs based on new evidence/ data.

Question 39

Factorial Design

Answer 39

two or more treatments are studied simultaneously through the use of varying combinations of treatment

Question 40

biomedical studies not performed on human subjects

Answer 40

nonclincal studies

Question 41

What is central randomization

Answer 41

a randomization method used in multicentre trials to obtain the desired overall distribution across treatment arms

Question 42

CRO

Answer 42

Contract Research Organization

• a person or organization contracted out by the sponsor to perform one or more of the sponsor’s trial related duties and functions

Question 43

Equivalence trial

Answer 43

A trial where the primary objective of showing the response to 2 or more treatment differs by an amount which is clinically important

Question 44

content validity

Answer 44

Assesses whether a test/trial is representative of all aspects of the construct/ domain.