Study Design Flashcards
double blind
both experimenter and subjects are blinded
crossover study
Each study participant receives all treatments that are being investigated but at different times
Order of treatments is randomized
Washout often included between treatments
partial crossover or incomplete block
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
Pros of Crossover Study Design
Each patient serves as their own control.
Reduces between-subject variability.
Allows for detection of smaller effect sizes with reduced sample sizes.
Effect Size
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.
Parallel Study
Two groups of treatments: A & B
One group receives only A, other group receives only B
Longitudinal Study
Repeated observations of the same variables over short or long periods of time.
Often observational but can be structured as longitudinal randomized experiments.
Large Effect Size
Can be seen by the naked eye, easily observed.
Small Effect Size
There is a real effect, i.e. something is really happening in the world - but which you can only see through careful study.
Confounders
Variable that influences both dependent and independent variables.
Why is the influence of confounders reduced in crossover studies?
Each patient is their own control.
Optimal crossover designs require ________ subjects.
fewer
Which patient population best aligns with crossover study design?
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.
What are two main issues with crossover studies?
- “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.
- “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.
A randomization method in which all subjects have the same chance to receive each treatment
Unrestricted Randomization
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)
Non - inferiority trial
-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
Single Blind study
The formal evaluation of the quantitative evidence from two or more trials bearing on the same question
Meta-analysis
a randomization method in which the likelihood of subsequent assignments changes based on previous ones
Dynamic randomization
Comparator (product)
An investigational or marketed product (i.e. active control) or placebo, used as reference in a clinical trial
Non-inferiority Trial
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)
A variable that provides an indirect measurement of effect in situations where direct measurement of clinical effect is not feasible or practical
surrogate variable
Therapeutic Confirmatory Study
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
Human Pharmacology Study
- Assess Tolerance
- Define/Describe Pharmacokinetics and pharmacodynamics
- explore drug Metabolism and drug intractions
- estimate Activity
TAMP
investigational product
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
Exploratory Trial
- 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
Audit Trial
Documentation that allows reconstruction of the course of events
Pharmacokinetics study
- 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
Stratified randomization trial
a randomization method in which subjects with shared characteristics are divided into strata; each stratum is then randomized seperatley
A trial with the primary objective of showing that the response to the investigational product is superior to a comparative agent (active or placebo)
Superiority Trial
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
Frequentist Methods
Block Randomization
a randomization method in which subjects are randomized in blocks, each containing a predefined combination of treatments
composite variable
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
Full analysis set
the set of subjects that is as close as possible to the ideal implied by the intention-to treat principle
Primary Variable
of greatest importance to the trial’s primary objective, and usually the one used in the sample size calculation.
Global Assessment Variables
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.
Double dummy
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)
Bayesian Approaches
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.
Factorial Design
two or more treatments are studied simultaneously through the use of varying combinations of treatment
biomedical studies not performed on human subjects
nonclincal studies
What is central randomization
a randomization method used in multicentre trials to obtain the desired overall distribution across treatment arms
CRO
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
Equivalence trial
A trial where the primary objective of showing the response to 2 or more treatment differs by an amount which is clinically important
content validity
Assesses whether a test/trial is representative of all aspects of the construct/ domain.
