به نام ايزد يکتا clinical trial design dr. khalili 1 the common types advantages and...
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به نام ايزد يکتا
Clinical Trial Design
Dr. Khalili
The common types Advantages and limitations Usual applications
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Clinical Trial (on patients)
vs.
Field Trial (on healthy people)
Community Trial (on communities)
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AfterBefore Intervention
In phase II clinical trials OR in serious diseases such as cancers
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Notice: the standard methods for sample size calculation and data analysis considering subject as analysis unit are not appropriate here.
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• Advantages:
Allows within-patients comparisons of treatments
Removes interpatient variabilityProvides the best unbiased estimates for
the differences between treatmentsDecreases number of patients needed
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• Limitations:• It is applicable where:
Objective measures for efficacy and safety are obtained Chronic and relatively stable disease Prophylactic drugs with relatively short half life Relatively short treatment periods Baseline and washout periods are feasible
• It increases the duration of the study• Its analysis is not straightforward:
The paired design The period and carry-over effects
• The effect of loss to follow-up
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• Sequence (Period) Effect: The order in which the therapies are given may
elicit psychological responses. Patients may react differently to the first
therapy given in a study as a result of the enthusiasm may diminish over
time.
• Carryover Effect: If a subject is changed from therapy A to therapy B and
observed under each therapy, the observations under therapy B will be
valid only if there is no residual carryover from therapy A. There must be
enough of a washout period to be sure none of therapy A or its effect
remains.
Two applications:1. Quantifying the interaction between the
two treatments2. Opportunistic situations
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A Full (a+1) * (b+1) Factorial Design for Combination Therapy of Two Components at a and b Dose Levels
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Designs with ethical considerations
• Adaptive Randomization
• Zelen design
• Variations of placebo-controlled trials:
• Add-on design
• Replacement design
• Randomized Withdrawal design
• Sequential analysis