Study Endnote ID:

1st Author, year:

Level of Review

Title and Abstract

Full‐text

Elements

Inclusion

Exclusion

Study design

Randomized controlled trial (RCT)

Quasi‐RCT/controlled clinical trial

Observational design with comparison/control

Uncertain – obtain full‐text

Case series

Case reports

Population

Adult or child over the age of 4 weeks

Invasive mechanical ventilation

Admitted to a high intensity care setting such as an ICU, specialized weaning centre, or high dependency unit

Uncertain – obtain full‐text

Home, community, and long‐term care settings

Intervention

LVR alone

LVR with MAC

MAC alone

MI‐E alone

MI‐E with MAC

Uncertain – obtain full‐text

Comparison/controls

No cough augmentation

Uncertain – obtain full‐text

Outcome(s)

Weaning success

Reintubation

Duration of mechanical ventilation and weaning;

ICU and hospital length of stay

New tracheostomy insertion

Decannulation

Harms associated with cough augmentation

Decision

Reason for Exclusion

INCLUDE

EXCLUDE

UNSURE – further discussion needed

Design Comparison/Controls

Population Outcome(s)

Intervention

Comments

Decision based on:

Abstract only

Abstract and full‐text

Data Abstraction Form

Please record any missing information as unclear or not described, to make it clear that the information was not found in the study report(s), not that you forgot to extract it

Reviewer Initials

Review Date

Primary author

Year

Confirm study eligibility

Yes

No

If No, list reason for exclusion on screening tool

Study Design

Simple RCT

Quasi‐RCT

Non‐randomized controlled trial

Randomized cross‐over study

Prospective cohort study

Retrospective cohort study

Case‐control study

Other design (please describe)

Unit of allocation

Individual

Cluster

Setting

Participating site country(ies):

Single

Multi‐site

Academic hospital

Non‐teaching hospital

Not reported

Mixed ICU

MICU

SICU

Other

Participant inclusion criteria (please list):

Exclusion criteria (please list):

Population description (from which study participants are drawn):

General Notes:

PARTICIPANTS

INTERVENTION

CONTROL

Total N randomized

Total N randomized

Total N of population at start of study for non‐randomized

Total N of population at start of study for non‐randomized

Withdrawals

Withdrawals

Exclusions

Exclusions

Age, mean (SD)

Age, mean (SD)

Male n (%)

Male n (%)

Reasons for ICU admission or mechanical ventilation (list all)

Reasons for ICU admission or mechanical ventilation (list all)

Severity of illness measure used

Severity of illness measure used

Severity of illness score
mean (SD)

Severity of illness score
mean (SD)

Subgroups measured

Subgroups measured

INTERVENTION

Describe cough augmentation intervention (please describe verbatim including method and settings used, frequency and timing, who delivered the intervention)

Describe additional ventilation and weaning methods as well as description of other standard medical therapy and relevant co‐interventions outlined in the paper (verbatim)

CONTROL

Describe ventilation and weaning methods used for control group as well as description of other standard medical therapy and relevant co‐interventions outlined in the paper (verbatim)

OUTCOMES

PLEASE RECORD UNIT of MEASUREMENT for ALL OUTCOMES (days/hours)

INTERVENTION (n = )

CONTROL (n = )

Weaning Success (verbatim description of how defined)

n/N (%)

n/N (%)

Reintubation (verbatim description of how defined)

n/N (%)

n/N (%)

Duration of weaning (describe how defined i.e. when weaning starts and stops)

n/N (%) weaned

mean (SD)

median (IQR)

n/N (%) weaned

mean (SD)

median (IQR)

Duration of ventilation (describe how defined i.e. when ventilation starts and stops)

n/N (%)

mean (SD)

median (IQR)

n/N (%)

mean (SD)

median (IQR)

ICU length of stay

n/N (%)

mean (SD)

median (IQR)

n/N (%)

mean (SD)

median (IQR)

Hospital length of stay

n/N (%)

mean (SD)

median (IQR)

n/N (%)

mean (SD)

median (IQR)

Mortality n/N (%)

ICU

28/30 day

60 day

90 day

Hospital

Mortality n/N (%)

ICU

28/30 day

60 day

90 day

Hospital

New tracheostomy, n/N (%)

New tracheostomy, n/N (%)

Decannulation, n/N (%)

Decannulation, n/N (%)

Haemodynamic compromise, n/N (%)

Haemodynamic compromise, n/N (%)

Arrhythmias, n/N (%)

Arrhythmias, n/N (%)

Pneumothorax, n/N (%)

Pneumothorax, n/N (%)

Haemoptysis, n/N (%)

Haemoptysis, n/N (%)

Mucous plugging, n/N (%)

Mucous plugging, n/N (%)

CONCLUSIONS

Key Conclusions made by authors

PERSONAL COMMUNICATION

List any personal communication with authors & corresponding dates

RISK OF BIAS ASSESSMENT FOR RCTS and Quasi‐RCTS

Domain

Description (verbatim)

Judgement

Sequence generation

Was the allocation sequence adequately generated?

Low

High

Unclear

Allocation concealment

Was allocation adequately concealed?

Low

High

Unclear

Blinding (participants/personnel)

Was knowledge of the allocated intervention adequately prevented during the study?

Low

High

Unclear

Blinding (outcome assessment)

Was knowledge of the allocated intervention adequately prevented during the study?

Low

High

Unclear

Incomplete outcome data

Were incomplete outcome data adequately addressed?

State whether attrition and exclusions were reported, the numbers in each intervention group (compared with total randomized participants), reasons

Low

High

Unclear

Selective outcome reporting

Are reports of the study free of suggestion of selective outcome reporting?

Low

High

Unclear

Other sources of bias

Role of , possible conflicts of interest for study authors

Low

High

Unclear

SIGN: Checklist: Cohort studies

Section 1: INTERNAL VALIDITY

In a well conducted cohort study:

Does this study do it?

1.1

The study addresses an appropriate and clearly focused question¹

Yes

No

Unclear

SELECTION OF STUDIES

1.2

The two groups being studied are selected from source populations that are comparable in all respects other than the factor under investigation²

Yes

No

Unclear

Does not apply

1.3

The study indicates how many of the people asked to take part did so, in each of the groups being studied³

Yes

No

Unclear

Does not apply

1.4

The likelihood that some eligible subjects might have the outcome at the time of enrolment is assessed and taken into account in the analysis⁴

Yes

No

Unclear

Does not apply

1.5

What percentage of individuals or clusters recruited into each arm of the study dropped out before the study was completed⁵

1.6

Comparison is made between full participants and those lost to follow‐up, by exposure status⁶

Yes

No

Unclear

Does not apply

ASSESSMENT

1.7

The outcomes are clearly defined⁷

Yes

No

Unclear

1.8

The assessment of outcome is made blind to exposure status. If the study is retrospective this may not be applicable⁸

Yes

No

Unclear

Does not apply

1.9

Where blinding was not possible, there is some recognition that knowledge of exposure status could have influenced the assessment of outcome⁹

Yes

No

Unclear

1.10

The method of assessment of exposure is reliable¹⁰

Yes

No

Unclear

1.11

Evidence from other sources is used to demonstrate that the method of outcome assessment is valid and reliable¹¹

Yes

No

Unclear

Does not apply

1.12

Exposure level or prognostic factor is assessed more than once¹²

Yes

No

Unclear

Does not apply

CONFOUNDING

1.13

The main potential confounders are identified and taken into account in the design and analysis¹³

Yes

No

Unclear

STATISTICAL ANALYSIS

1.14

Have confidence intervals been provided?¹⁴

Yes

No

Section 2: OVERALL ASSESSMENT OF THE STUDY

2.1

How well did the study minimize the risk of bias or confounding?¹⁵

High quality (++)

Acceptable (+)

Unacceptable – reject 0

2.2

Taking into account clinical considerations, your evaluation of the methodology used, and the statistical power of the study, do you think there is clear evidence of an association between exposure and outcome?

Yes

No

Unclear

2.3

Are the results of this study directly applicable to the patient group targeted in this guideline?

Yes

No

2.4

Notes. Summarize the authors’ conclusions. Add any comments on your own assessment of the study, and the extent to which it answers your question and mention any areas of uncertainty raised above

SIGN: Case‐control studies

Section 1: INTERNAL VALIDITY

In a well conducted case‐control study:

Does this study do it?

1.1

The study addresses an appropriate and clearly focused question¹

Yes

No

Unclear

SELECTION OF SUBJECTS

1.2

The cases and controls are taken from comparable populations²

Yes

No

Unclear

1.3

The same exclusion criteria are used for both cases and controls³

Yes

No

Unclear

1.4

What percentage of each group (cases and controls) participated in the study?⁴

Cases:

Controls:

1.5

Comparison is made between participants and non‐participants to establish their similarities or differences⁵

Yes

No

Unclear

1.6

Cases are clearly defined and differentiated from controls⁶

Yes

No

Unclear

1.7

It is clearly established that controls are non‐cases⁷

Yes

No

Unclear

ASSESSMENT

1.8

Measures will have been taken to prevent knowledge of primary exposure influencing case ascertainment⁸

Yes

No

Unclear

Does not apply

1.9

Exposure status is measured in a standard, valid and reliable way⁹

Yes

No

Unclear

CONFOUNDING

1.10

The main potential confounders are identified and taken into account in the design and analysis¹⁰

Yes

No

Unclear

STATISTICAL ANALYSIS

1.11

Confidence intervals are provided¹¹

Yes

No

Section 2: OVERALL ASSESSMENT OF THE STUDY

2.1

How well did the study minimize the risk of bias or confounding?¹²

High quality (++)

Acceptable (+)

Unacceptable– reject 0

2.2

Taking into account clinical considerations, your evaluation of the methodology used, and the statistical power of the study, do you think there is clear evidence of an association between exposure and outcome?

Yes

No

Unclear

2.3

Are the results of this study directly applicable to the patient group targeted by this guideline?

Yes

No

2.4

Notes. Summarize the authors’ conclusions. Add any comments on your own assessment of the study, and the extent to which it answers your question and mention any areas of uncertainty raised above

¹ Unless a clear and well defined question is specified in the report of the review, it will be difficult to assess how well it has met its objectives or how relevant it is to the question you are trying to answer on the basis of the conclusions.

² Study participants may be selected from the target population (all individuals to which the results of the study could be applied), the source population (a defined subset of the target population from which participants are selected), or from a pool of eligible subjects (a clearly defined and counted group selected from the source population. If the study does not include clear definitions of the source population it should be rejected.

³ All selection and exclusion criteria should be applied equally to cases and controls. Failure to do so may introduce a significant degree of bias into the results of the study.

⁴ Differences between the eligible population and the participants are important, as they may influence the validity of the study. A participation rate can be calculated by dividing the number of study participants by the number of eligible subjects. It is more useful if calculated separately for cases and controls. If the participation rate is low, or there is a large difference between the two groups, the study results may well be invalid due to differences between participants and non‐participants. In these circumstances, the study should be downgraded, and rejected if the differences are very large.

⁵ Even if participation rates are comparable and acceptable, it is still possible that the participants selected to act as cases or controls may differ from other members of the source population in some significant way. A well conducted case‐control study will look at samples of the non‐participants among the source population to ensure that the participants are a truly representative sample.

⁶ The method of selection of cases is of critical importance to the validity of the study. Investigators have to be certain that cases are truly cases, but must balance this with the need to ensure that the cases admitted into the study are representative of the eligible population. The issues involved in case selection are complex, and should ideally be evaluated by someone with a good understanding of the design of case‐control studies. If the study does not comment on how cases were selected, it is probably safest to reject it as a source of evidence.

⁷ Just as it is important to be sure that cases are true cases, it is important to be sure that controls do not have the outcome under investigation. Control subjects should be chosen so that information on exposure status can be obtained or assessed in a similar way to that used for the selection of cases. If the methods of control selection are not described, the study should be rejected. If different methods of selection are used for cases and controls the study should be evaluated by someone with a good understanding of the design of case‐control studies.

⁸ If there is a possibility that case ascertainment can be influenced by knowledge of exposure status, assessment of any association is likely to be biased. A well conducted study should take this into account in the design of the study.

⁹ The primary outcome measures used should be clearly stated in the study. If the outcome measures are not stated, or the study bases its main conclusions on secondary outcomes, the study should be rejected. Where outcome measures require any degree of subjectivity, some evidence should be provided that the measures used are reliable and have been validated prior to their use in the study.

¹⁰ Confounding is the distortion of a link between exposure and outcome by another factor that is associated with both exposure and outcome. The possible presence of confounding factors is one of the principal reasons why observational studies are not more highly rated as a source of evidence. The study should indicate which potential confounders have been considered, and how they have been allowed for in the analysis. Clinical judgement should be applied to consider whether all likely confounders have been considered. If the measures used to address confounding are considered inadequate, the study should be downgraded or rejected. A study that does not address the possibility of confounding should be rejected.

¹¹ Confidence limits are the preferred method for indicating the precision of statistical results, and can be used to differentiate between an inconclusive study and a study that shows no effect. Studies that report a single value with no assessment of precision should be treated with extreme caution.

¹² Rate the overall methodological quality of the study, using the following as a guide: High quality (++): Majority of criteria met. Little or no risk of bias. Results unlikely to be changed by further research. Acceptable (+): Most criteria met. Some flaws in the study with an associated risk of bias, Conclusions may change in the light of further studies. Low quality (0): Either most criteria not met, or significant flaws relating to key aspects of study design. Conclusions likely to change in the light of further studies.