Randomisation, Blinding And Protocol Deviations

Question 1

Define allocation concealment

Answer 1

Not revealing to the participants what group they have been allocated to

Question 2

CONSORT

Answer 2

Consolidated, standards of reporting trials

Question 3

CONSORT guidelines flow diagram ensures?

Answer 3

All potential ppts are accounted for
Everyone recruited is accounted for
Numbers a located to each ‘arm’
Number of drop out (and why)
Number of computers

Question 4

CONSORT allows?

Answer 4

US to see any obvious differences in number of participants between arms (eg groups) especially group allocation and drops outs

Question 5

Steps in CONSORT

Answer 5

Enrolment
Allocation
Follow up
Analysis

Question 6

Criteria for selection

Answer 6

Need people who have disease
Select population by choosing people who don’t have certain conditions
Often exclude: Old, children, pregnant and who don’t consent

Question 7

Advantages by simple randomisation

Answer 7

Can’t predict in advance who gets control and treatment
Control group roughly resembles treatment group
Not just characteristics you know about but also characteristics you don’t know about

Question 8

Disadvantages by simple randomisation

Answer 8

Can’t guarantee same number of participants in each group, especially if small study
Some factors that predict outcome of study may not be evenly distributed between the groups

Question 9

Advantages simple randomisation / block /stratified

Answer 9

Simple- reduces selection bias
Block - reduces selection bias and prevents unequal treatment group sizes
Stratified - reduces selection bias and prevents imbalance in prognostic characteristics

Question 10

Disadvantages simple randomisation / block /stratified

Answer 10

Simple- groups can be unequal unless trial very large
Block - imbalance in prognostic characteristics car still occur
Stratified - more elaborate and need to be certain about what characteristics are predictive

Question 11

Different types of blinding

Answer 11

Allocation concealment
Single blinding
Double blinding
Triple blinding

Question 12

Allocation concealment

Answer 12

Allocation of each participant not revealed until irrevocably entered trial (minimises selection bias)

Question 13

Single blinding

Answer 13

Usually participant kept unaware of assignment

Question 14

Double blinding

Answer 14

Keeping both participant and those involved in their management unaware of assignment

Question 15

Triple blinding

Answer 15

Keeping participant and those in involved in their management and performing blind data analysis

Question 16

How to do binding

Answer 16

Conceal allocation
Mask name of treatment
Think about appearance, taste, smell, colour and mode of delivery
If you have intervention + standard treatment, then may want to consider placebo + standard treatment

Question 17

Advantage of blinding for assessors

Answer 17

Minimises differential assessment of outcomes ( ascertainment/ information/ observer/ detection bias)

Question 18

Advantage of blinding: participants

Answer 18

Less likely to have biased psychological /physical response to intervention, especially it subjective measure e.g pair score
More likely to comply with treatment
Less likely to seek additional interventions
Less likely to leave trial early

Question 19

Advantage of blinding: investigators

Answer 19

Less likely to share inclinations
Less likely to seek additional interventions
Less likely to leave trial early

Question 20

Disadvantages of blinding

Answer 20

Less important for objective criteria (e.g death)

Question 21

Classes for protocol deviations

Answer 21

Major
Moderate
Minor

Question 22

Major protocol deviations

Answer 22

Failure to obtain informed consent
Failure to report serious adverse events
Failure to perform procedure that affects safety
Dosing error

Question 23

Moderate protocol deviations

Answer 23

Use of outdated/expired/unapproved consent form
Enrolment of ineligible participant (e.g outside age range)
Study visit outside of required timeframe

Question 24

Minor protocol deviations

Answer 24

Loss of original signed consent form or inappropriate documentation of informed consent
Failure to give participant copy
Over-enrolment
Pk sample obtained close to, but not as, assigned time

Question 25

Intention to treat analysis

Answer 25

All study participants taken into account in analysis, whether completed study or not

Question 26

Intention to treat analysis is analysed according to ?

Answer 26

Group to which they were allocated

Question 27

Intention to treat analysis keeps advantages of?

Answer 27

Randomisation (known and unknown features remain evenly distributed) and results more generalisable

Question 28

Intention to treat analysis: conservative approach

Answer 28

Underestimates benefits of interventions, avoids overestimation of treatment effects

Question 29

Per protocol analysis

Answer 29

Only takes account of participants who always adhered to study protocol I.e. always received intervention and completed follow up
All participants with protocol deviations excluded

Question 30

Per protocol analysis disadvantage

Answer 30

Can overestimate treatment effects ( people who stop treatment due to no benefit not included)

Question 31

Other types of per protocol analysis

Answer 31

As-treated analysis
Completers-only analysis

Question 32

As treated-analysis

Answer 32

Participants evaluated as ultimately treated regardless of assignment
Based on actual treatment received (some people may crossover between treatment groups)

Question 33

What per protocol analysis is useful to analyse side effects

Answer 33

As treated analysis

Question 34

Competers-only analysis

Answer 34

Only those who complete study included

Question 35

Which Per protocol analysis is used to manage participants with missing data?

Answer 35

Computers- only analysis