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Clinical Trial Design

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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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Be relax forfew minutes

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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.

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To resolve the problom:

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

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And more complex DESIGNS …