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Flashcards in Clinical Trials Deck (27):

Whats the ABC's of clinical trial design?

A = Assignment
B = Blinding
C = Comparison
s = Sequence


What are the two types of assignment?

- First come first served

- Randomized (inc; balanced, stratified)


What does the first come first served method involve?

- Range of possibilites that will induce bias
- Main source of bias is the lack of blinding I.e everyone knows whos getting treatment vs placebo etc


What is the randomized assignment method?

Subjects are randomized into control and subject groups

- Can be done evenly (balanced)
- Or stratified based on age, gender etc


What is blinding used for?

To reduce bias


What are the types of blinding?

- Open
- Single Blind (subjects dont know)
- Double blind
-Double dummy (two physically different treatments i.e inhaler vs tablet)
- Triple blind (randomized sequence is lost or misinterpreted) - nobody ever knows what treatment was given


What are the types of comparison?

- Active
- Placebo
- Standard treatment


What is is active comparison?

- Dose controlled
- Concentration controlled
- Biomarker controlled i.e cholesterol level

Comparing the treatments based on their differences. To learn about the relationship between intensity of treatment and outcome


What is standard treatment comparison?

- All subjects recieve the treatment and then some get an add-on (testing drug)

(non-inferiority) refers to trial that shows that the new treatment is no worse than the standard.


What is sequence?

The sequence of treatments can influenced what is learned from a trial and the kind of bias that can araise


What are the types of sequence?

- Parallel
- Crossover
- Titration


What is parallel sequence?

Different treatments given to different groups at the same time


Whats the upside and downside to parallel sequence?

Answers the does the drug work question but cant answer learning questions such as shape of the dose response curve


What is crossover sequence?

Two or more treatments in each subject

Allows formation of dose-reponse curve and may be more statistically valuable


Whats wrong with the crossover design?

There may be carryover affect i.e during the time of off medication


What is the titration design?

Fixed sequential doses (Forced)

Change in dose till therapeutic response level is achieved (flexible)


What is analysis?

Two questions

Does it work? (confirming Qs) i.e does it lower BP

How well does it work? (learning Qs) - scales i.e what does is needed to produce this response..


What are some methods for determining does it work?

Simple comparison i.e drug vs placebo

- t-test (two groups)
- Anova (several)
- log rank test (survival)


What factors are considered in the size of the response?


How much Q's - i.e how much drug to produce this response


What are the methods behind how well does it work questions?

PK and PD methods


Why are PK, PD and PKPD models for how well does it work questions, better than hypothesis testing?

They account for:

Execution differences i.e
- Adherence (stop taking meds)
- Drop out

Co-variates (inter-individual differences)
- Renal function, size, gender


What is a power analysis?

A power analysis is used to determine the likelihood that a clinical trial will detect a drug effect if the drug effect really exists


Why would we use a power analysis?

We would use a power analysis because of human variability that means the testing does not show the true effect of the drug because its effect is lost to "noise"

It generates a % likelihood that the null hypothesis will be rejected (good) based on criteria


What questions are asked in a power analysis?

- What is the size of the effect
- What is the variability in the response
- What is the desired p value

- What is the desired power i.e 0.8 (good)


What are the two analysis perspectives for analyzing clinical trials?

- Intention to treat
- As treated


What does the intention to treat perspective encompass?

- Only takes into account treatment assessment
- Doesnt take into account if the subject took the treatment or not "use effectiveness"
- Good for pharmacoeconomics


What does the as treated perspective encompass?

- Whether or not the subject took the meds (Method effectiveness)
- Development of scientific perspective