RCT class # 13

Question 1

Lecture 13 is on what

Answer 1

additional trial designs: simple; N of 1; adaptive,
SMART
Platform trials

Question 2

what is a large simple trial

Answer 2

an RCT with a relatively large sample size, few variables and pheraps short follow up.

Question 3

Pros to large simple design

Answer 3

low cost, suitable if intervention is expected to have modest consistent benefits and is easily administered in a large recruitable population.

Question 4

Cons of large simple design

Answer 4

they are unsuitable if the interventions are complex.

• long term followup with adherence required
• subgroups analysis or supportive analysis are needed

Question 5

one period of an N-of-1 trial

one pair of an N of 1 trial

Answer 5

one period is the experimental trial then the second period of the pair is the placebo. This is a pair.

Question 6

pairs of treatment for an n of 1 trial

Answer 6

ie period one is experimental

and the other is alt period. the order of the pair is randomized.

Question 7

how does the clinician monitor the therapy in n of 1 trials.

Answer 7

drug diaries from the pts

Question 8

the condition of the n of .1 trial must be ___

Answer 8

chronic bc acute conditions will resolve too quickly.

Question 9

effects of a therapy (experimental or alt )must be short or long in 1 trial

Answer 9

short (or will last too long)

Question 10

to make a decision of efficacy, harm or lack of effect usually need how many treatment periods

Answer 10

3 periods.

Question 11

who is the control of an n of 1 trial

Answer 11

the patient is there own control. (they are the best control, basically a counter factual

Question 12

example he gave of n of 1

Answer 12

hiv med in a patient for whom SOC has not been effective.

Question 13

main advantage of N of 1 trial

Answer 13

avoids long term expense.

Question 14

How does n of 1 move a drig toward approval w FDA

Answer 14

it doesn’t.

Question 15

adaptive design def

Answer 15

adapt some aspect of design during the trial

Question 16

adoative design formal def

Answer 16

Adaptive Design for a clinical trial is a trial protocol that allows certain design features to change from an initial specification based on evolving trial information while maintaining statistical, scientific, and ethical integrity. (interm data assessment

Question 17

example of adaptive designs

Answer 17

stop for futility/benefit./efficacy

-change of a dose to reach

Question 18

example of adaptive designs

Answer 18

changing antidepression drugs based on adaptive designs

Question 19

key for adaptive designs

Answer 19

must be prespecified

Question 20

key best way to use adaptive designs

Answer 20

adjust sample size based on nuisance parameters. (ie not the observed treatment effect itself

Question 21

3 examples of nusciance parameters of adaptive designs

Answer 21

i. event rate lower than expected
ii. variability in a contious outcome is gr than expected
iii. worse adherence than expected.

Question 22

crossover design only done for __ dz

Answer 22

chronic (bc cant go away)

Question 23

withdrawal design is only valid if ____

Answer 23

nonrestrictive

Question 24

factorial designs problem

Answer 24

low power need large sample size.

Question 25

why is it usually inappropriate to have an adaptive design as a phase III (other than interim analysis etc) (2)

exceptions (2)

Answer 25

1. issues with type I errors control.
2. The question changes.

exceptions (2)

1. prospective
2. type I error controlled and question is clear

Question 26

adaptive designs must maintain these 3 forms of integrity

Answer 26

1. statistical 2. scientific. 3. ethical integrity

Question 27

statistical problem if adaptive designs

Answer 27

Statistically valid only if all adaptations which may occur are specified in advance, and control of overall type 1 error at 0.05 or less error is demonstrated.

Question 28

4 expamples of newer adaptive designs he gives

Answer 28

1. dose selection studies drop an inferior arm
2. adaptive randomization based on relative treatment group responsive
3. adapt of sample size based on interim effect size estimates not just nuciance parameters
   (such as
   sd)

Question 29

platform trials

Answer 29

test multiple treatments within the same trial (ie genetic studies that base treatments based on gene signature ie personalized medicine).

Question 30

problem with platform trials

Answer 30

1. control of type i error is unresolved still need phase III trial.

Question 31

**platform type trials are useful as at this level of trial

Answer 31

phase II

Question 32

SMART designs stands for

Answer 32

Sequential multiple assignment randomized trial design –> basically decision analysis type designs

Question 33

smart designs are a fancy type of __

Answer 33

adaptive design

Question 34

problem with SMART designs

Answer 34

increased chance of alpha error.

Question 35

again biggest problem with adaptive, SMART and platform designs

Answer 35

controlling the alpha error.

Question 36

Dr. JT likes adaptive designs for phase __

Answer 36

II.

Question 37

what is an enrichment design

Answer 37

only take patients with treatment effects or failures.

Question 38

based on FDA rules for a phase III trial a ___ trial design should be used

Answer 38

simple

Question 39

what is a program of successor trials

Answer 39

?