phase III Trial

Question 1

what are the 5 objectives of phase 3 trials?

Answer 1

1. (survival- primary) Does someone live longer than someone else?
2. (disease free survival- secondary) how long does patient live after you remove disease and give treatment? how long before disease comes back?
3. (progression free survival) - If there is disease and you’re trying to shrink it and keep it the same, how long before disease starts to grow again?
4. quality of life - what is the quality of life difference between the 2 arms?
5. (does disease respond to treatment? - rare)

Question 2

how do you set up and determine how many patients you need for clinical phase 3 study?

Answer 2

sample size determined by the following probabilities;
alpha - false positive (drug actually fails) (accepting H1 when H0 true)
beta - false negative (drug actually works) (accepting H0 when H1 true)
delta - significant difference you want to detect

Question 3

what is the holy grail for determining wether drug works or not and getting it licensed?

Answer 3

randomized
placebo- controlled
double blinded
multiinstitutional

Question 4

phase 3 studies in a nutshell

Answer 4

intent to treat patient
interim analysis
data monitoring committee not composed of study leaders calculate survival curves, alternative endpoints
positive outcomes required for FDA approval

Question 5

data management

Answer 5

protocol development
data collection
computing
quality control
accurate reporting

Question 6

calculating and reporting survival times

Answer 6

kaplan -meyer product limit where you count all patients who started

Question 7

kaplan meier survival curves

Answer 7

calculate cumulative chance of surviving until the next observation
multiplies probability of surviving at prior observation by probability of surviving at current observation among those surviving prior observation

Question 8

what hypothesis is tested?

Answer 8

we are trying to disprove the null hypothesis that both arm means are the same with given alpha, beta, and different delta

Question 9

what is a delta?

Answer 9

minimal clinically significant difference (not a statistically significant difference)

Question 10

a toxic rx vs standard no treatment would need a?

Answer 10

large benefit to be worthwhile with very significant pvalue<0.1

Question 11

new treatment vs existing rx requires?

Answer 11

smaller benefit

Question 12

sample size is driven by?

Answer 12

number of deaths expected

Question 13

if youre going to measure a disease that kills patients quickly, what do you need?

Answer 13

you’re going to need smaller population to sample in one year

Question 14

what are solutions to slow recruitment for trials?

Answer 14

• accept smaller number of patients than planned
• relax inclusion criteria
• extend time of recruitment or add centers for recruitment (best option)
• change design
• recycling patients who did not meet eligibility criteria the first time

Question 15

You calculate your delta, with a given alpha and given beta to give you the number of patients you need to tell the difference and give answer. any other analysis are?

Answer 15

wrong and cannot be used to predict an outcome

Question 16

the more tests you have the higher your?

Answer 16

type 1 false positives are

Question 17

the interim analysis you have

Answer 17

the higher the chances of false positives (drug not actually working)

Question 18

whats interim analysis?

Answer 18

an analysis of data conducted before data collection has been completed.