outcomes

Question 1

what should the primary outcoem be?

Answer 1

whatever marks the greatest theraputic importance to the studies research hypothesis

Question 2

what problems do we see in clinical trials regarding the outcome measures they use?

Answer 2

• studies measuring the effectivness of intterventions for the same condition use different outcome measures
• DEFINITION of outcome measure

different definitions exist for the same outcome measure. E.g., “singleton live birth” some definitions include and others exclude still births in it. LOOK UP THE DIFFERENT DEFINITIONS FOR OUTCOME MEASURES. inconsistent definitions big problem.

• measure used
  different methods might be used to measure the outcome measure which migh lead to diferent results
• reporting

bias reporting of outcome measure

Question 3

examples of different poutcome measures used

Answer 3

clinical measurment: blood test, urine test

clinician assessed outcomes: clinical global impression fo change, cause-specific mortality

• patient reported outcomes

Question 4

what do different definition of the outcmome measure impact?

Answer 4

sample size

meta analyses

policy

Question 5

how do different outcome measures affect the sample size?

Answer 5

because part of the sample size calculation requires the estimated effect size.

inconsistent definitions of the outcome measure increases the variability in the estimated effect size and variability of outcome

makes it hard to calculate the required sample size

can lead to both underpowered studies (not enough power to detect effect) or overpowered (unecessarily large or costly)

Question 6

how do inconsistent definitions of the outcome measure affect meta analyses

Answer 6

can lead to hetrogeneuity in the included analyses. harder to estimate the overall effect size of the intervention

impacts the implication

Question 7

what are patient reported outcome measures?

Answer 7

self report measure by n about the status of their health condition

different PROMS for a specific condition e.g., anxiety has lots

Question 8

what are the psychometric properties of different scales

Answer 8

reliability

validity

resposivness - doesthe scale detect changes over time that matter to N?

Question 9

ideally what do we want when picking an outcome measure?

Answer 9

use the same outcome as other studies addressing hte same research question

even when using hte same outcome, use the same measurment e.g., specific PROM

Question 10

different ways to measure medication adherence

objective vs subjective

Answer 10

objective - pill count, biochemical measurees

sbjective - self report

Question 11

problem when different types of outcome measures or different measures of the same outcome measure is used. What can we do to solve this?

Answer 11

use core outcome sets (COS)

these are a collection of outcome measures that are considered to be the minimum set of outcomes that should be reported for certain condition

these are chosen by patients, cllinicianc and researchers. ook through all outcoem measures then decide on the core outcome set.

Question 12

what is a CRF

Answer 12

case report form

used to collect thedata and information collected over the course of the trial

Question 13

why do we need to check the CRF to ensure statistical function is met?

Answer 13

make sure data collected will address the research question

make sure the outcomes specified in the protocol are collected

data is formatted in way that ensues analyses can be performed

validated PROMS are not altered and have no errors

Question 14

what are different outcome categories?

Answer 14

objective vs subjective

surrogate vs substantive

primary vs secondaty

composite primary outcome

Question 15

surrogate vs substantive outcome

Answer 15

substantive - what we want to know e.g., cardiovascular disease

surrogate - what we actually measure e.g., blood pressure

Question 16

what must the surrogate measure do?

Answer 16

capture the effect of the intervention on the clinical outcome

Question 17

why use a surrogate outcome?

Answer 17

reduces duration and size of trial - thus cheaper

less invasive

Question 18

primary vs secondary outcomes

Answer 18

primary outcom - the varaiable capturing the most clinically relvant and convincing evidence related to the primary trial objective

secondary - measures that support the primary objective of measures related to econdary objective

Question 19

what things do we need to know about the primary outcome for the sample size calculation?

Answer 19

1. how it will be measured
2. how often it will be measured
3. is it measured at baseline
4. do we know its distribution and variability

Question 20

what is the problem with having more than 1 primary outcome measure

Answer 20

issues of multiple testing

increases type 1 error

need to consider correlation between outcomes - result of one outcome might influence the result of another. if the outcomes are correlated it makes it harder to interpret the results.

Question 21

why is it a problem if two outcomes are correlated

Answer 21

• impairs interpretation of the study
• reduces the power in the study - might not be able to detect treatment effect even if it exists

Question 22

composite primary outcome

Answer 22

combinig omre than two variables into a single outcome

must be pre-defined

Question 23

why use a composite outcome measure

Answer 23

• increases numbe rof events detected reducing the required sample size
• avoids issue of picking an outcome measure when 2 areequally important
• avoids issues of multiplicity

Question 24

problems of composite outcoem measures

Answer 24

• difficultl to interpret
• sometime s only vertain variables within are significant - attributes innaprioriate treatment effect across all
• if some are not as strong as others can dilute treatment effect

Question 25

what do we need in an outcome measure for the trial protocol

Answer 25

• specific measurment used e.g., systolic blood pressure
• analysis metric - time-to-event? change from baseline
• method of aggregation e.g., proportion, mean
• time point for each outcome
• explain clinical relevance - how it relates to the study objectivesand how it evaluates the effecivness of an intervention
• explain how it measures the potential adverse effects in an intervention

Question 26

problems with dichotomising a continuous outcome variable?

Answer 26

loss of information - reduces power

n close to either side of the cut off judged as different rather than simmilar (which they are)

do not use the sample median as the cut off

Question 27

what are estimands?

Answer 27

a target of estimation for the treatment efefct.

Question 28

what are the four attributes of estimands?

Answer 28

• the population (n with high blood pressure)
• outcome - BP at 12 weeks
• specify how to accound for intercurrent events
• population summary of outcome (what we are comparing between groups e.g., change in BP between groups)

Question 29

what are intercurrent events?

Answer 29

events that occur during th ecourse of the trial that can affect the outcome measure

Question 30

how can we properly account for intercurrent events?

Answer 30

estimand in the trial design should specify how events that occur during the trial affecting outcomes will be addressed

e.g., rescue medication (given if treatment is not effective or leads to advrese events) might improve the outcome measure inflating the treatment effect. account for the effect e.g., include the use of rescue medication as a covariate