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Study | Bias | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Randomisation process | Deviations from intended interventions | Missing outcome data | Measurement of the outcome | Selection of the reported results | Overall | |||||||
Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | |
FitzGerald 2004 |
Low risk of bias |
Patients were randomised to treatment groups at visit 2 according to a blocked computer generated randomisation list for each centre. As a randomisation list was generated for each centre, this sounds like it was centrally generated.
|
High risk of bias |
Methods state 'double blind' so assume this means participants.
|
Some concerns |
Number of participants lost to folLow risk up were larger than the number of events and only participants who started study inhaler were included in the analyses.
|
Low risk of bias |
Method of measuring the outcome was appropriate.
|
Some concerns |
No study protocol or trial registration record is available.
|
High risk of bias |
Used the tool algorithm. |
Garrett 1998 |
Low risk of bias |
Only information about the allocation is that the children were randomised by the hospital pharmacist and the investigators were blinded to this allocation.
|
High risk of bias |
Used a blinded inhaler delivered by the participant.
|
High risk of bias |
Only those with completed pairs of exacerbations were included in the final analysis - 10/28 excluded from the analyses as they only had an exacerbation in one arm.
|
Low risk of bias |
Method for measuring the outcome was appropriate, and unlikely to differ between groups.
|
Some concerns |
No trial registration, study protocol or SAP (even though article mentions a study protocol).
|
High risk of bias |
Used algoritm.
|
Harrison 2004 |
Low risk of bias |
An independent pharmacist randomly allocated individuals using computer generated random number tables.
|
Low risk of bias |
Study report does not explicitly state "double‐blind", but a placebo was used which implies that it was not open label, and text mentions "A range of active and placebo study inhalers was available to enable the type of inhaler and daily dose to be matched to patients’ regular inhaled corticosteroid, type of inhaler, and dose". Participants delivered the intervention themselves.
|
Low risk of bias |
Nearly all data available and number withdrawn much smaller than the number of events observed. 8.9 and 10.1% withdrew from the intervention and placebo groups respectively which is relatively Low risk and balanced, although the study does not report whether and how missing data were imputed.
|
Low risk of bias |
Method for measuring the outcome was appropriate. Participants were given a 10-day course of prednisolone (30 mg per day) to be taken if their asthma control deteriorated to the point that they would usually start oral corticosteroids, or if their peak fLow risk fell by 40% from the mean run-in value.
|
Some concerns |
No publicly available trial registration, study protocol or SAP (SAP is mentioned in the study report).
|
Low risk of bias |
Overall risk of bias assessed as Low risk as the only 'some concerns' was due to no trial registration or study protocol details, but this is an old trial when making these available was not standard. |
Jackson 2018 |
Some concerns |
Method of sequence generation and allocation concealment not described (in paper, supplementary materials of protocol). However, the report mentions stratification which implies the sequence was computer generated.
|
Low risk of bias |
Participants and their carers/parents were blinded.
|
Low risk of bias |
Number of participants lost to folLow risk up is similar to the number of events; however, most participants were included in the study for most of the duration [mean folLow risk-up among all 127 participants in each group was 42.5 weeks and 40.3 weeks, respectively (i.e. most of the full 48 week folLow risk-up)]. |
Low risk of bias |
Method of measuring the outcome was appropriate.
|
Low risk of bias |
Protocol dated February 2014 and trial enrolment began in August 2014.
|
Low risk of bias |
Insufficient reporting warrants an assessment of 'some concerns' for the randomisation process, but the overall reporting and conduct of the trial suggests that rigorous procedures were folLow risked to minimize bias. |
Martinez 2011 |
Low risk of bias |
The Data Coordinating Center generated the random allocation sequence via computer software.The DCC had no contact with participants.
|
Low risk of bias |
States double blind and placebo interventions were used.
|
Low risk of bias |
Withdrawals from the study were relatively Low risk and even between the two groups included in this review: 11.3% in the intervention group (double ICS) and 12.5% in the control group (stable ICS). However, in some groups the number of events was similar to the number of participants with missing data, therefore their outcomes could impact the estimated effect of intervention.
|
Low risk of bias |
Method for measuring the outcome was appropriate
|
Some concerns |
Trial registered before participant enrolment began (https://clinicaltrials.gov/ct2/show/study/NCT00394329). However, registry record contains no prospective information about statistical analyses and no protocol or SAP available.
|
Low risk of bias |
Overall risk of bias assessed as Low risk as the only 'some concerns' was due to no study protocol or SAP available. However, it was registered and no other details from the trial for this outcome gives us reason to believe that there are some concerns regarding risk of bias. |
Oborne 2009 |
Low risk of bias |
An allocation sequence of random permuted blocks of 10 was generated using a random number table by an independent pharmacist and implemented by one of the study investigators once participants were enrolled into the trial. Mentions an investigator providing the randomization schedule and concealed allocation of masked inhalers.
|
Low risk of bias |
Double-blind, placebo inhaler was used.
|
Low risk of bias |
The number of events was less than the number of participants with missing. Thirty-eight drop-outs in active vs 39 dropouts in placebo vs 18 events in active vs 29 events in placebo. However, all participants contributed data for the intention-to-treat analysis up to the point at which they left the study. Only three were lost to folLow risk-up with no outcome data. |
Low risk of bias |
Method of measuring the outcome was appropriate.
|
Some concerns |
The trial was rgeistered (http://www.isrctn.com/ISRCTN46018181). It was registered after participant enrolment began but before recruitment was completed. The registry doesn't include anything about the anlyses and a protocol/SAP isn't available.
|
Low risk of bias |
Overall risk of bias assessed as Low risk as the only 'some concerns' was due to no study protocol or SAP available. However, it was registered before recruitment completed and no other details from the trial from this outcome gives us reason to believe that there are some concerns regarding risk of bias. |
Rice-McDonald 2005 |
Low risk of bias |
Method of sequence generation not described but "order and allocation of treatment by concealed randomisation"
|
High risk of bias |
A double-blind, double-dummy study with order and allocation of treatment by concealed randomisation. The participants administered the intervention.
|
High risk of bias |
Of the 35 people ranomised, 13 withdrew from the study (and unclear in what intervention or period they were in). Also, 11 participants had exacerbationsand went straight to oral corticosteroids (no study inhaler) as their symptoms were very bad (excluded from analysis and unsure which period and intervention each were in).
|
Low risk of bias |
Method for measuring the outcome was appropriate, and unlikely to differ between groups. Treatment failure well defined.
|
Some concerns |
No trial registry, protocol or SAP available.
|
High risk of bias |
Algorithm used.
|
Wainwright 2009 |
Low risk of bias |
"Stratified block randomisation by age (3-5, 6-10, 11-14), gender, centre". "Sequential study number allocated from a list according to blocking details". "...blocking details emailed to Dept of Epidemiology and Preventative Medicine, Monash Med School, Melbourne". "Study puffer number was allocated. Pre-numbered puffers were held at RCH Brisbane pharmacy"
|
Some concerns |
Placebo inhalers were used to presume this was to blind participants and personnel from the study medication, but no explicit definition of masking procedures
|
Low risk of bias |
Outcome data accounted for and a much High risker number of events than those who withdrew. 11 in the intervention group (8.7%) an 10 in the control group (8.1%) withdrew from the study - Low risk and balanced. Only those having an exacerbation could be included in the main analyses.
|
Low risk of bias |
The method of measuring the outcome was appropriate.
|
Some concerns |
Trial registered (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=630) but after participant enrollment was completed. No details about the analyses available. No published journal report.
|
Some concerns |
Overall risk of bias from tool algorithm. |
Study | Bias | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Randomisation process | Deviations from intended interventions | Missing outcome data | Measurement of the outcome | Selection of the reported results | Overall | |||||||
Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | |
FitzGerald 2004 |
Low risk of bias |
Patients were randomised to treatment groups at visit 2 according to a blocked computer generated randomisation list for each centre. As a randomisation list was generated for each centre, this sounds like it was centrally generated.
|
Low risk of bias |
Methods state 'double blind' so assume this means participants.
|
High risk of bias |
Statistical analysis used the "all patients treated" (APT) approach but most did not meet the threshold to start the study inhaler and so were not included in the analysis. In the full population, Of the 148 randomised to the control group, 115 completed the study (22% dropout), and 117/142 in the intervention group completed the study (17.6% dropout) which is High risker than the % who experienced an event in each group.
|
Low risk of bias |
Method of measuring the outcome was appropriate.
|
Some concerns |
No study protocol or trial registration record is available.
|
High risk of bias |
Used the tool algorithm. |
Garrett 1998 |
Low risk of bias |
Only information about the allocation is that the children were randomised by the hospital pharmacist and the investigators were blinded to this allocation.
|
Some concerns |
Used a blinded inhaler delivered by the participant.
|
High risk of bias |
Only participants who had two matching pairs of exacerbations were analysed, which was 18 out of 28 enrolled. Those who had 1 or 3+ exacerbations during the study were not included.
|
Low risk of bias |
Method for measuring the outcome was appropriate, and unlikely to differ between groups.
|
Some concerns |
No trial registration, study protocol or SAP (even though article mentions a study protocol).
|
High risk of bias |
Used alogorithm.
|
Harrison 2004 |
Low risk of bias |
An independent pharmacist randomly allocated individuals using computer generated random number tables.
|
High risk of bias |
Study report does not explicitly state "double‐blind", but a placebo was used which implies that it was not open label, and text mentions "A range of active and placebo study inhalers was available to enable the type of inhaler and daily dose to be matched to patients’ regular inhaled corticosteroid, type of inhaler, and dose". Participants delivered the intervention themselves.
|
Low risk of bias |
8.9 and 10.1% withdrew from the total intervention and placebo groups respectively which is relatively Low risk and balanced, although the study does not report whether and how missing data were imputed.
|
Low risk of bias |
Method for measuring the outcome was appropriate. Participants were given a 10-day course of prednisolone (30 mg per day) to be taken if their asthma control deteriorated to the point that they would usually start oral corticosteroids, or if their peak fLow risk fell by 40% from the mean run-in value.
|
Some concerns |
No publicly available trial registration, study protocol or SAP (SAP is mentioned in the study report).
|
High risk of bias |
Overall risk of bias assessed as Low risk as the only 'some concerns' was due to no trial registration or study protocol details, but this is an old trial when making these available was not standard. |
Martinez 2011 |
Low risk of bias |
The Data Coordinating Center generated the random allocation sequence via computer software.The DCC had no contact with participants.
|
Low risk of bias |
States double blind and placebo interventions were used.
|
Low risk of bias |
The same raw data were used in the ITT and per protocol anlayses for this review because the study's design implies all participants would have used their study inhaler. Withdrawals from the study were relatively Low risk and even between the two groups included in this review: 11.3% in the intervention group (double ICS) and 12.5% in the control group (stable ICS). However, in some groups the number of events was similar to the number of participants with missing data, therefore their outcomes could impact the estimated effect of intervention.
|
Low risk of bias |
Method for measuring the outcome was appropriate
|
Some concerns |
Trial registered before participant enrolment began (https://clinicaltrials.gov/ct2/show/study/NCT00394329). However, registry record contains no prospective information about statistical analyses and no protocol or SAP available.
|
Low risk of bias |
Overall risk of bias assessed as Low risk as the only 'some concerns' was due to no study protocol or SAP available. However, it was registered and no other details from the trial for this outcome gives us reason to believe that there are some concerns regarding risk of bias. |
Oborne 2009 |
Low risk of bias |
An allocation sequence of random permuted blocks of 10 was generated using a random number table by an independent pharmacist and implemented by one of the study investigators once participants were enrolled into the trial. Mentions an investigator providing the randomization schedule and concealed allocation of masked inhalers.
|
High risk of bias |
Placebo inhaler was used.
|
High risk of bias |
The per protocol analysis based on only participants who started their study inhaler represents a relatively small, non-randomized proportion of the full cohort, and there was an imbalance in the number of people in each group who did so.
|
Low risk of bias |
Method of measuring the outcome was appropriate.
|
Some concerns |
The trial was rgeistered (http://www.isrctn.com/ISRCTN46018181). It was registered after participant enrolment began but before recruitment was completed. The registry doesn't include anything about the anlyses and a protocol/SAP isn't available.
|
High risk of bias |
Used algorithm. |
Rice-McDonald 2005 |
Low risk of bias |
Method of sequence generation not described but "order and allocation of treatment by concealed randomisation"
|
Low risk of bias |
A double-blind, double-dummy study with order and allocation of treatment by concealed randomisation. The participants administered the intervention.
|
High risk of bias |
Of 35 randomized participants, 13 subsequently withdrew prior to any asthma exacerbations.
|
Low risk of bias |
Method for measuring the outcome was appropriate, and unlikely to differ between groups. Treatment failure well defined.
|
Some concerns |
No trial registry, protocol or SAP available.
|
High risk of bias |
Used algorithm.
|
Wainwright 2009 |
Low risk of bias |
"Stratified block randomisation by age (3-5, 6-10, 11-14), gender, centre". "Sequential study number allocated from a list according to blocking details". "...blocking details emailed to Dept of Epidemiology and Preventative Medicine, Monash Med School, Melbourne". "Study puffer number was allocated. Pre-numbered puffers were held at RCH Brisbane pharmacy"
|
High risk of bias |
Placebo inhalers were used to presume this was to blind participants and personnel from the study medication, but no explicit definition of masking procedures
|
Low risk of bias |
Have assumed that all participants who used oral steroid rescue had an exacerbation. Outcome data accounted for and a much High risker number of events than those who withdrew.
|
Low risk of bias |
The method of measuring the outcome was appropriate.
|
Some concerns |
Trial registered (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=630) but after participant enrollment was completed. No details about the analyses available. No published journal report.
|
High risk of bias |
Used algorithm |
Study | Bias | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Randomisation process | Deviations from intended interventions | Missing outcome data | Measurement of the outcome | Selection of the reported results | Overall | |||||||
Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | |
Subgroup 1.3.1 Serious | ||||||||||||
Martinez 2011 |
Low risk of bias |
The Data Coordinating Center generated the random allocation sequence via computer software.The DCC had no contact with participants.
|
Low risk of bias |
States double blind and placebo interventions were used.
|
Low risk of bias |
Withdrawals from the study were relatively Low risk and even between the two groups included in this review: 11.3% in the intervention group (double ICS) and 12.5% in the control group (stable ICS). Raw numbers are available for the review's analyses. However, in some groups the number of events was similar to the number of participants with missing data, therefore their outcomes could impact the estimated effect of intervention.
|
Some concerns |
Study report mentions a data and safety monitoring board which implies adverse event measuring procedures were folLow risked.
|
Some concerns |
Trial registered before participant enrolment began (https://clinicaltrials.gov/ct2/show/study/NCT00394329). However, registry record contains no prospective information about analyses and no SAP or protocol available.
|
Some concerns |
Used tool algorithm to generate overall risk of bias. |
Wainwright 2009 |
Low risk of bias |
"Stratified block randomisation by age (3-5, 6-10, 11-14), gender, centre". "Sequential study number allocated from a list according to blocking details". "...blocking details emailed to Dept of Epidemiology and Preventative Medicine, Monash Med School, Melbourne". "Study puffer number was allocated. Pre-numbered puffers were held at RCH Brisbane pharmacy"
|
High risk of bias |
Placebo inhalers were used to presume this was to blind participants and personnel from the study medication, but no explicit definition of masking procedures
|
High risk of bias |
Number of events similar to the number that withdrew, and no reasons for withdrawal specified.
|
Low risk of bias |
No information about the method of measuring the outcome.
|
Some concerns |
Trial registered (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=630) but after participant enrollment was completed. No details about the analyses available. No published journal report.
|
High risk of bias |
Used algorithm |
Subgroup 1.3.2 Non-serious | ||||||||||||
Foresi 2000 |
Low risk of bias |
Described as randomized but no details to assess sequence generation or allocation concealment.
|
High risk of bias |
Not described fully but described as double-blind - placebo used to blind intervention in the event of an exacerbation.
|
High risk of bias |
Per-protocol analysis was performed on 175 out of 213 randomized patients (191 who completed minus 38 with protocol violations), and adverse events were only reported for those who had an exacerbation (minority of population). Those included in the analysis were those who had an exacerbation, for which rates differed across groups and relate to asthma severity and effectiveness of the intervention. Withdrawal rates fromthe study also likely to be related to participants’ health status, as these include adverse events and other reasons. |
Low risk of bias |
No information about how adverse events were measured or managed. However, all participants visited the clinic once a month to discuss progress, symtpoms and adherence, and all kept daily symptom/management diaries.
|
High risk of bias |
No trial registration, study protocol or SAP.
|
High risk of bias |
Used algorithm. |
Oborne 2009 |
Low risk of bias |
An allocation sequence of random permuted blocks of 10 was generated using a random number table by an independent pharmacist and implemented by one of the study investigators once participants were enrolled into the trial. Mentions an investigator providing the randomization schedule and concealed allocation of masked inhalers.
|
Some concerns |
"double-blind, placebo-controlled trial" "Drug groups were labelled as A, B, C, and D to mask statisticians to treatment group during the first complete run-through of data analyses." "Active and placebo inhalers were…identical apart from the presence or absence of inhaled corticosteroid, to achieve allocation concealment and blinding of investigators and pariticipants".
|
High risk of bias |
Only 94 out of 403 participants (23%) started the study inhaler, so most of the population were not included in the analysis of adverse events
|
High risk of bias |
No information about how adverse events were measures or monitored. The participant's management plan only requested the daily diary of symptoms was completed if they felt their asmtha was deterioating. As there were more exacerbations in the active group we can assume more patients deteriotaed. Therefore, more participants in the active group would have been capturing other non-series adverse events in their diaries (and possibly why the active group had 9 events and the placebo 3). |
High risk of bias |
The trial was rgeistered (http://www.isrctn.com/ISRCTN46018181). It was registered after participant enrolment began but before recruitment was completed. The registry doesn't include anything about the anlyses and a protocol/SAP isn't available.
|
High risk of bias |
Used tool algorithm. |
Study | Bias | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Randomisation process | Deviations from intended interventions | Missing outcome data | Measurement of the outcome | Selection of the reported results | Overall | |||||||
Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | |
FitzGerald 2004 |
Low risk of bias |
Patients were randomised to treatment groups at visit 2 according to a blocked computer generated randomisation list for each centre. As a randomisation list was generated for each centre, this sounds like it was centrally generated.
|
High risk of bias |
Methods state 'double blind' so assume this means participants. The participants themselves delivered the interventin.
|
Some concerns |
Number of participants lost to folLow risk up were larger than the number of events.
|
Low risk of bias |
Method of measuring the outcome was appropriate and the same between groups.
|
Some concerns |
No study protocol or trial registration record is available.
|
High risk of bias |
Used algorithm. |
Harrison 2004 |
Low risk of bias |
An independent pharmacist randomly allocated individuals using computer generated random number tables.
|
Low risk of bias |
Study report does not explicitly state "double‐blind", but a placebo was used which implies that it was not open label, and text mentions "A range of active and placebo study inhalers was available to enable the type of inhaler and daily dose to be matched to patients’ regular inhaled corticosteroid, type of inhaler, and dose". Participants delivered the intervention themselves.
|
Low risk of bias |
Nearly all data available though number withdrawn similar to the number of events (31 in intervention, 28 in placebo). 8.9 and 10.1% withdrew from the intervention and placebo groups respectively which is relatively Low risk and balanced, although the study does not report whether and how missing data were imputed.
|
Low risk of bias |
Method for measuring the outcome was appropriate.
|
Some concerns |
No trial registration, study protocol or SAP.
|
Low risk of bias |
Overall risk of bias assessed as Low risk as the only 'some concerns' was due to no study protocol or SAP available. However, it was registered and no other details from the trial for this outcome gives us reason to believe that there are some concerns regarding risk of bias. |
Wainwright 2009 |
Low risk of bias |
"Stratified block randomisation by age (3-5, 6-10, 11-14), gender, centre". "Sequential study number allocated from a list according to blocking details". "...blocking details emailed to Dept of Epidemiology and Preventative Medicine, Monash Med School, Melbourne". "Study puffer number was allocated. Pre-numbered puffers were held at RCH Brisbane pharmacy"
|
Some concerns |
Placebo inhalers were used to presume this was to blind participants and personnel from the study medication, but no explicit definition of masking procedures
|
Low risk of bias |
Outcome data accounted for and a much High risker number of events than those who withdrew. 11 in the intervention group (8.7%) an 10 in the control group (8.1%) withdrew from the study - Low risk and balanced.
|
Low risk of bias |
The method of measuring the outcome was appropriate.
|
Some concerns |
Trial registered (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=630) but after participant enrollment was completed. No details about the analyses available. No published journal report.
|
Some concerns |
Used algorithm |
Study | Bias | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Randomisation process | Deviations from intended interventions | Missing outcome data | Measurement of the outcome | Selection of the reported results | Overall | |||||||
Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | |
Garrett 1998 |
Low risk of bias |
Only information about the allocation is that the children were randomised by the hospital pharmacist and the investigators were blinded to this allocation.
|
High risk of bias |
Used a blinded inhaler delivered by the participant.
|
High risk of bias |
Only those with completed pairs of exacerbations were included in the final analysis - 10/28 excluded from the analyses as they only had an exacerbation in one arm. No mention of any children dropping out of the trial.
|
Low risk of bias |
The method for measuring the outcome as appropriate.
|
Some concerns |
No trial registration, study protocol or SAP (even though article mentions a study protocol).
|
High risk of bias |
Used algorithm.
|
Jackson 2018 |
Some concerns |
Method of sequence generation and allocation concealment not described (in paper, supplementary materials of protocol). However, the report mentions stratification which implies the sequence was computer generated.
|
Low risk of bias |
Participants and their carers/parents were blinded.
|
Low risk of bias |
Number of participants lost to folLow risk up is similar to the number of events; however, most participants were included in the study for most of the duration [mean folLow risk-up among all 127 participants in each group was 42.5 weeks and 40.3 weeks, respectively (i.e. most of the full 48 week folLow risk-up)]. |
Low risk of bias |
Method of measuring the outcome was appropriate.
|
Low risk of bias |
Protocol dated February 2014 and trial enrolment began in August 2014.
|
Low risk of bias |
Insufficient reporting warrants an assessment of 'some concerns' for the randomisation process, but the overall reporting and conduct of the trial suggests that rigorous procedures were folLow risked to minimize bias. |
Martinez 2011 |
Low risk of bias |
The Data Coordinating Center generated the random allocation sequence via computer software.The DCC had no contact with participants.
|
Low risk of bias |
States double blind and placebo interventions were used.
|
Low risk of bias |
Withdrawals from the study were relatively Low risk and even between the two groups included in this review: 11.3% in the intervention group (double ICS) and 12.5% in the control group (stable ICS). Raw numbers are available for the review's analyses. However, for this outcome there were 0 events reported so missing participant data could impact the estimated effect of intervention.
|
Low risk of bias |
Method for measuring the outcome was appropriate and would not have differed between groups.
|
Some concerns |
Trial registered before participant enrolment began (https://clinicaltrials.gov/ct2/show/study/NCT00394329). Registry record contains no prospective information about analyses and no SAP or protocol available. However, there was no analyses for SAEs.
|
Low risk of bias |
Overall risk of bias assessed as Low risk as the only 'some concerns' was due to no study protocol or SAP available. However, it was registered and no other details from the trial for this outcome gives us reason to believe that there are some concerns regarding risk of bias. |
Wainwright 2009 |
Low risk of bias |
"Stratified block randomisation by age (3-5, 6-10, 11-14), gender, centre". "Sequential study number allocated from a list according to blocking details". "...blocking details emailed to Dept of Epidemiology and Preventative Medicine, Monash Med School, Melbourne". "Study puffer number was allocated. Pre-numbered puffers were held at RCH Brisbane pharmacy"
|
Some concerns |
Placebo inhalers were used to presume this was to blind participants and personnel from the study medication, but no explicit definition of masking procedures
|
High risk of bias |
Outcome data accounted for but a much Low risker number of events than those who withdrew.
|
Low risk of bias |
The method of measuring the outcome was appropriate. Clear instructions for what to do in the event of worsening symptoms and called weekly by study nurse - all events likely to have been recorded.
|
Some concerns |
Trial registered (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=630) but after participant enrollment was completed. No details about the analyses available. No published journal report.
|
High risk of bias |
Used algorithm |
Study | Bias | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Randomisation process | Deviations from intended interventions | Missing outcome data | Measurement of the outcome | Selection of the reported results | Overall | |||||||
Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | |
Harrison 2004 |
Low risk of bias |
An independent pharmacist randomly allocated individuals using computer generated random number tables.
|
Low risk of bias |
Study report does not explicitly state "double‐blind", but a placebo was used which implies that it was not open label, and text mentions "A range of active and placebo study inhalers was available to enable the type of inhaler and daily dose to be matched to patients’ regular inhaled corticosteroid, type of inhaler, and dose". Participants delivered the intervention themselves.
|
Low risk of bias |
8.9 and 10.1% withdrew from the intervention and placebo groups respectively which is relatively Low risk and balanced. However, the study does not report whether and how missing data were imputed and the outcome can only be measured in those who had an exacerbation which was a subset of the randomised population.
|
Low risk of bias |
Method for measuring the outcome was appropriate.
|
Some concerns |
No publicly available trial registration, study protocol or SAP (SAP is mentioned in the study report).
|
Low risk of bias |
Used tool algorithm for overall risk of bias. |
Study | Bias | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Randomisation process | Deviations from intended interventions | Missing outcome data | Measurement of the outcome | Selection of the reported results | Overall | |||||||
Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | |
Harrison 2004 |
Low risk of bias |
An independent pharmacist randomly allocated individuals using computer generated random number tables.
|
Low risk of bias |
Study report does not explicitly state "double‐blind", but a placebo was used which implies that it was not open label, and text mentions "A range of active and placebo study inhalers was available to enable the type of inhaler and daily dose to be matched to patients’ regular inhaled corticosteroid, type of inhaler, and dose". Participants delivered the intervention themselves.
|
Low risk of bias |
8.9 and 10.1% withdrew from the intervention and placebo groups respectively which is relatively Low risk and balanced. However, the study does not report whether and how missing data were imputed and the outcome can only be measured in those who had an exacerbation which was a subset of the randomised population.
|
Low risk of bias |
Method for measuring the outcome was appropriate.
|
Some concerns |
No publicly available trial registration, study protocol or SAP (SAP is mentioned in the study report).
|
Low risk of bias |
Used tool algorithm for overall risk of bias. |
Study | Bias | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Randomisation process | Deviations from intended interventions | Missing outcome data | Measurement of the outcome | Selection of the reported results | Overall | |||||||
Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | |
Harrison 2004 |
Low risk of bias |
An independent pharmacist randomly allocated individuals using computer generated random number tables.
|
Low risk of bias |
Study report does not explicitly state "double‐blind", but a placebo was used which implies that it was not open label, and text mentions "A range of active and placebo study inhalers was available to enable the type of inhaler and daily dose to be matched to patients’ regular inhaled corticosteroid, type of inhaler, and dose". Participants delivered the intervention themselves.
|
Low risk of bias |
8.9 and 10.1% withdrew from the intervention and placebo groups respectively which is relatively Low risk and balanced. However, the study does not report whether and how missing data were imputed and the outcome can only be measured in those who had an exacerbation which was a subset of the randomised population. |
Low risk of bias |
Method for measuring the outcome was appropriate.
|
Some concerns |
No publicly available trial registration, study protocol or SAP (SAP is mentioned in the study report).
|
Low risk of bias |
Used tool algorithm for overall risk of bias. |