clinical trial design

1

به نام ايزد يکتا

Clinical Trial Design

Dr. Khalili

The common types Advantages and limitations Usual applications

Dr. Khalili 2

Clinical Trial (on patients)vs.

Field Trial (on healthy people)

Community Trial (on communities)

Dr. Khalili 3

Dr. Khalili 4

AfterBefore Intervention

In phase II clinical trials OR in serious diseases such as cancers

Dr. Khalili 5

Dr. Khalili 6

Dr. Khalili 7

Dr. Khalili 8

Dr. Khalili 9

Dr. Khalili 10

Dr. Khalili 11

Dr. Khalili 12

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

Dr. Khalili 13

Be relax forfew minutes

Dr. Khalili 14

Dr. Khalili 15

• Advantages:

Allows within-patients comparisons of treatments

Removes interpatient variabilityProvides the best unbiased estimates for

the differences between treatmentsDecreases number of patients needed

Dr. Khalili 16

• 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

Dr. Khalili 17

• 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.

Dr. Khalili 18

Dr. Khalili 19

To resolve the problom:

Two applications:1. Quantifying the interaction between the

two treatments2. Opportunistic situations

Dr. Khalili 21

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

Dr. Khalili 22

Designs with ethical considerations

• Adaptive Randomization

• Zelen design

• Variations of placebo-controlled trials:

• Add-on design

• Replacement design

• Randomized Withdrawal design

• Sequential analysis

Dr. Khalili 23

And more complex DESIGNS …