1. به نام ايزد يکتا Clinical Trial Design Dr. Khalili 1  The common types  Advantages and limitations  Usual applications

2. Dr. Khalili2  Clinical Trial (on patients) vs.  Field Trial (on healthy people)  Community Trial (on communities)

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4. 4 After Before Intervention In phase II clinical trials OR in serious diseases such as cancers

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12. Dr. Khalili12 Notice: the standard methods for sample size calculation and data analysis considering subject as analysis unit are not appropriate here.

13. Dr. Khalili13 Be relax for few minutes

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15. Dr. Khalili15 Advantages:  Allows within-patients comparisons of treatments  Removes interpatient variability  Provides the best unbiased estimates for the differences between treatments  Decreases number of patients needed

16. Dr. Khalili16 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

17. Dr. Khalili17 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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19. Dr. Khalili19 To resolve the problom:

20. Two applications: 1.Quantifying the interaction between the two treatments 2.Opportunistic situations

21. Dr. Khalili21 A Full (a+1) * (b+1) Factorial Design for Combination Therapy of Two Components at a and b Dose Levels

22. Dr. Khalili22 Designs with ethical considerations Adaptive Randomization Zelen design Variations of placebo-controlled trials: Add-on design Replacement design Randomized Withdrawal design Sequential analysis

23. Dr. Khalili23 And more complex DESIGNS …