Clinical Trial Designs Flashcards
List eight advantages of proper clinical trial design
- Allows investigators to satisfy ethical constraints.
- Permits efficient use of scarce resources.
- Isolates the treatment effect of interest from confounders.
- Controls precision
- Reduces selection bias and observer bias
- Minimizes and quantifies random error or uncertainty
- Simplifies and validates the analysis.
- Increases the external validity of the trial.
Clinical trial design should accomplish the following 6 things.
- Quantifying reduce errors due to chance
- Reduce or eliminate bias.
- yield clinically-relevant estimates of effects and precision.
- Be simple in design and analysis.
- Provide a high degree of credibility reproducibility and external validity.
- Influence future clinical practice.
Give two examples of uncontrolled observational study types
A case report and a case series.
A case report can only demonstrate that what?
A clinical event of interest is possible.
Can a k-series prove efficacy of a treatment? Why or why not?
A case series and case reports are susceptible to large selection biases.
Difference between database analysis and case series.
A database analysis may have a control group depending on the data source.
Two types of epidemiologic studies
Case control or cohort design, both comparative observational studies.
Give an example of an epidemiological study.
a trial that measures the risk of illness or death in an expose population compared to that risk in an identical unexposed population.
What’s a case-control study?
A retroactive analysis which identifies cases, subjects with the disease, and controls, subjects without the disease.
What bias is inherent to a case-control study and why?
Selection bias. The investigator selects cases and controls retrospectively.
What is a prospective cohort study?
Individuals are followed forward in time with subsequent evaluations to determine which individuals develop into cases.
Pro and con of prospective cohort design
prospective studies tend to have fewer design problems and less bias than retrospective studies but they are more expensive with respect to time and cost.
What type of trial contains all of the key components of a true experimental design?
A replicated and controlled clinical trial.
Experimental unit vs. Observational unit
Experimental unit receives the treatment directly. Observational unit has measurements taken on it.
Give an example when the experimental unit is different than the observational unit.
Treatment administered to mother rat (experimental unit) observational unit could be pups.
Factor definition
Variables that are controlled
One-way design vs. Two-way design. Give example of each.
One-way design is only one factor, treatment with a few levels.
Two-way factorial design tests various combinations of two factors. For example temperature and pressure, or various combinations of doses of two chemotherapeutic agents comprising the treatment arms.
Parallel vs. Crossover design
In a parallel design patients remain on the same treatment they are randomized to throughout the course of the trial.
Randomization removes what bias.
Selection
Selection bias occurs when?
A physician decides treatment assignment and systematically selects a certain type of patient for a particular treatment.
Blocking and stratification are used to control what?
Variation.
Stratification example
Assume younger patients are healthier. Therefore stratify into age groups. For example age 18 to 30, age 31 to 50 etc. Allow limited number of people into each group.
Additional benefit of stratification
Interim subgroup analysis.
Treatment masking is?
Blinding
Blinding ensures what?
Objectivity in person measuring outcome.
Example of when blinding is impossible
Surgical procedure.
Confounding definition
The effect of other relevant factors on the outcome that may be incorrectly attributed to the difference between study groups.
Internal validity refers to
Observed difference in outcome between study groups is real and not due to bias chance or confounding.
External validity refers to
How well study results can be generalized to a broader population.
What is a large simple trial?
the trial whose purpose it is to attempt to discover small advantages of a treatment that is expected to be used in a large population.
What is a pragmatic trial?
Pragmatic trials study treatment in practices outside academic medical centers. This can involve a broad range of clinical practices.
Not all trials aim to prove superiority of new treatment. Explain.
Some studies test equivalency and non-inferiority.
Explain what a TM trial is.
Treatment mechanism; ie pKs looking at bioavailability, or studying an operative procedure.
DF trial looks for what?
DF=dose finding. Looks for MTD.
Phase IV study
Expanded safety study. After FDA approval
Prevention trial is
Is done in healthy individuals to determine if there’s prevents a disease.
Diagnostic or screening trial.
Used to determine if agent can diagnose a disease.
