RANDOM
SEQUENCE GENERATION
Selection
bias (biased allocation to interventions) due to inadequate generation
of a randomised sequence. |
Criteria for a judgement of ‘Low risk’ of bias. |
The investigators describe a random component in the
sequence generation process such as:
Referring
to a random number table;
Using
a computer random number generator;
Coin
tossing;
Shuffling
cards or envelopes;
Throwing
dice;
Drawing
of lots;
Minimization*.
*Minimization may be implemented without a random
element, and this is considered to be equivalent to being random. |
Criteria for the judgement of ‘High risk’ of bias. |
The investigators describe a non-random component in
the sequence generation process. Usually, the description would involve
some systematic, non-random approach, for example:
Sequence
generated by odd or even date of birth;
Sequence
generated by some rule based on date (or day) of admission;
Sequence
generated by some rule based on hospital or clinic record number.
Other non-random approaches happen much less frequently
than the systematic approaches mentioned above and tend to be obvious.
They usually involve judgement or some method of non-random categorization
of participants, for example:
Allocation
by judgement of the clinician;
Allocation
by preference of the participant;
Allocation
based on the results of a laboratory test or a series of tests;
Allocation
by availability of the intervention.
|
Criteria for the judgement of ‘Unclear
risk’ of bias. |
Insufficient information about the sequence generation
process to permit judgement of ‘Low risk’ or ‘High risk’. |
ALLOCATION
CONCEALMENT
Selection bias (biased allocation to interventions)
due to inadequate concealment of allocations prior to assignment. |
Criteria for a judgement of ‘Low risk’ of bias. |
Participants and investigators enrolling participants
could not foresee assignment because one of the following, or an equivalent
method, was used to conceal allocation:
Central
allocation (including telephone, web-based and pharmacy-controlled randomization);
Sequentially
numbered drug containers of identical appearance;
Sequentially
numbered, opaque, sealed envelopes.
|
Criteria for the judgement of ‘High risk’ of bias. |
Participants or investigators enrolling participants
could possibly foresee assignments and thus introduce selection bias,
such as allocation based on:
Using
an open random allocation schedule (e.g. a list of random numbers);
Assignment
envelopes were used without appropriate safeguards (e.g. if envelopes
were unsealed or nonopaque or not sequentially numbered);
Alternation
or rotation;
Date
of birth;
Case
record number;
Any
other explicitly unconcealed procedure.
|
Criteria for the judgement of ‘Unclear
risk’ of bias. |
Insufficient information to permit judgement of ‘Low
risk’ or ‘High risk’. This is usually the case if the method of concealment
is not described or not described in sufficient detail to allow a definite
judgement – for example if the use of assignment envelopes is described,
but it remains unclear whether envelopes were sequentially numbered, opaque
and sealed. |
BLINDING
OF PARTICIPANTS AND PERSONNEL
Performance bias due to knowledge of the
allocated interventions by participants and personnel during the study. |
Criteria for a judgement of ‘Low risk’ of bias. |
Any one of the following:
No blinding or incomplete
blinding, but the review authors judge that the outcome is not likely
to be influenced by lack of blinding;
Blinding of participants
and key study personnel ensured, and unlikely that the blinding could
have been broken.
|
Criteria for the judgement of ‘High risk’ of bias. |
Any one of the following:
No blinding or incomplete
blinding, and the outcome is likely to be influenced by lack of blinding;
Blinding
of key study participants and personnel attempted, but likely that the
blinding could have been broken, and the outcome is likely to be influenced
by lack of blinding.
|
Criteria for the judgement of ‘Unclear
risk’ of bias. |
Any one of the following:
|
BLINDING
OF OUTCOME ASSESSMENT
Detection bias due to knowledge of the allocated
interventions by outcome assessors. |
Criteria for a judgement of ‘Low risk’ of bias. |
Any one of the following:
No blinding of outcome
assessment, but the review authors judge that the outcome measurement
is not likely to be influenced by lack of blinding;
Blinding of outcome assessment
ensured, and unlikely that the blinding could have been broken.
|
Criteria for the judgement of ‘High risk’ of bias. |
Any one of the following:
No blinding of outcome
assessment, and the outcome measurement is likely to be influenced by
lack of blinding;
Blinding of outcome assessment,
but likely that the blinding could have been broken, and the outcome measurement
is likely to be influenced by lack of blinding.
|
Criteria for the judgement of ‘Unclear
risk’ of bias. |
Any one of the following:
|
INCOMPLETE
OUTCOME DATA
Attrition bias due to amount, nature or handling
of incomplete outcome data. |
Criteria for a judgement of ‘Low risk’ of bias. |
Any one of the following:
No missing
outcome data;
Reasons
for missing outcome data unlikely to be related to true outcome (for survival
data, censoring unlikely to be introducing bias);
Missing
outcome data balanced in numbers across intervention groups, with similar
reasons for missing data across groups;
For
dichotomous outcome data, the proportion of missing outcomes compared
with observed event risk not enough to have a clinically relevant impact
on the intervention effect estimate;
For
continuous outcome data, plausible effect size (difference in means or
standardized difference in means) among missing outcomes not enough to
have a clinically relevant impact on observed effect size;
Missing
data have been imputed using appropriate methods.
|
Criteria for the judgement of ‘High risk’ of bias. |
Any one of the following:
Reason
for missing outcome data likely to be related to true outcome, with either
imbalance in numbers or reasons for missing data across intervention groups;
For
dichotomous outcome data, the proportion of missing outcomes compared
with observed event risk enough to induce clinically relevant bias in
intervention effect estimate;
For
continuous outcome data, plausible effect size (difference in means or
standardized difference in means) among missing outcomes enough to induce
clinically relevant bias in observed effect size;
‘As-treated’
analysis done with substantial departure of the intervention received
from that assigned at randomization;
Potentially
inappropriate application of simple imputation.
|
Criteria for the judgement of ‘Unclear
risk’ of bias. |
Any one of the following:
Insufficient
reporting of attrition/exclusions to permit judgement of ‘Low risk’ or
‘High risk’ (e.g. number randomized not stated, no reasons for missing
data provided);
The
study did not address this outcome.
|
SELECTIVE
REPORTING
Reporting bias due to selective outcome reporting. |
Criteria for a judgement of ‘Low risk’ of bias. |
Any of the following:
The
study protocol is available and all of the study’s pre-specified (primary
and secondary) outcomes that are of interest in the review have been reported
in the pre-specified way;
The
study protocol is not available but it is clear that the published reports
include all expected outcomes, including those that were pre-specified
(convincing text of this nature may be uncommon).
|
Criteria for the judgement of ‘High risk’ of bias. |
Any one of the following:
Not
all of the study’s pre-specified primary outcomes have been reported;
One
or more primary outcomes is reported using measurements, analysis methods
or subsets of the data (e.g. subscales) that were not pre-specified;
One
or more reported primary outcomes were not pre-specified (unless clear
justification for their reporting is provided, such as an unexpected adverse
effect);
One
or more outcomes of interest in the review are reported incompletely so
that they cannot be entered in a meta-analysis;
The
study report fails to include results for a key outcome that would be
expected to have been reported for such a study.
|
Criteria for the judgement of ‘Unclear
risk’ of bias. |
Insufficient information to permit judgement of ‘Low
risk’ or ‘High risk’. It is likely that the majority of studies will fall
into this category. |
OTHER
BIAS
Bias due to problems not covered elsewhere
in the table. |
Criteria for a judgement of ‘Low risk’ of bias. |
The study appears to be free of other sources of bias. |
Criteria for the judgement of ‘High risk’ of bias. |
There is at least one important risk of bias. For example,
the study:
|
Criteria for the judgement of ‘Unclear
risk’ of bias. |
There may be a risk of bias, but there is either:
|