SEQUENCE
GENERATION
Was the allocation sequence
adequately generated? [Short form: Adequate sequence generation?] |
Criteria for a judgement of ‘YES’ (i.e. 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 ‘NO’ (i.e. 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.
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Criteria for the judgement of ‘UNCLEAR’ (uncertain
risk of bias). |
Insufficient information about the sequence generation
process to permit judgement of ‘Yes’ or ‘No’. |
ALLOCATION
CONCEALMENT
Was allocation adequately
concealed? [Short form: Allocation concealment?] |
Criteria for a judgement of ‘YES’ (i.e. 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 ‘NO’ (i.e. 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’ (uncertain
risk of bias). |
Insufficient information to permit judgement of ‘Yes’
or ‘No’. 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, PERSONNEL AND OUTCOME ASSESSORS
Was knowledge of the
allocated interventions adequately prevented during the study? [Short
form: Blinding?] |
Criteria for a judgement of ‘YES’ (i.e. low risk of
bias). |
Any one of the following:
No blinding,
but the review authors judge that the outcome and the outcome measurement
are 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;
Either
participants or some key study personnel were not blinded, but outcome
assessment was blinded and the non-blinding of others unlikely to introduce
bias.
|
Criteria for the judgement of ‘NO’ (i.e. high risk
of bias). |
Any one of the following:
No blinding
or incomplete blinding, and the outcome or outcome measurement 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;
Either
participants or some key study personnel were not blinded, and the non-blinding
of others likely to introduce bias.
|
Criteria for the judgement of ‘UNCLEAR’ (uncertain
risk of bias). |
Any one of the following:
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INCOMPLETE
OUTCOME DATA
Were incomplete outcome
data adequately addressed? [Short form: Incomplete outcome data addressed?] |
Criteria for a judgement of ‘YES’ (i.e. 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 ‘NO’ (i.e. 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’ (uncertain
risk of bias). |
Any one of the following:
Insufficient
reporting of attrition/exclusions to permit judgement of ‘Yes’ or ‘No’
(e.g. number randomized not stated, no reasons for missing data provided);
The
study did not address this outcome.
|
SELECTIVE
OUTCOME REPORTING
Are reports of the study
free of suggestion of selective outcome reporting? [Short form: Free
of selective reporting?] |
Criteria for a judgement of ‘YES’ (i.e. 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 ‘NO’ (i.e. 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’ (uncertain
risk of bias). |
Insufficient information to permit judgement of ‘Yes’
or ‘No’. It is likely that the majority of studies will fall into this
category. |
OTHER
POTENTIAL THREATS TO VALIDITY
Was the study apparently
free of other problems that could put it at a risk of bias? [Short form:
Free of other bias?] |
Criteria for a judgement of ‘YES’ (i.e. low risk of
bias). |
The study appears to be free of other sources of bias. |
Criteria for the judgement of ‘NO’ (i.e. high risk
of bias). |
There is at least one important risk of bias. For example,
the study:
Had
a potential source of bias related to the specific study design used;
or
Stopped
early due to some data-dependent process (including a formal-stopping
rule); or
Had
extreme baseline imbalance; or
Has
been claimed to have been fraudulent; or
Had
some other problem.
|
Criteria for the judgement of ‘UNCLEAR’ (uncertain
risk of bias). |
There may be a risk of bias, but there is either:
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