Risk of bias for analysis 1.1 Health‐related quality of life (HRQoL): adjusted SGRQ total score (primary analysis).
| 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 | |
| Gallefoss 1999 | Low risk of bias | Comment: At inclusion they signed a written consent and were then randomised to an intervention group or a control group. | High risk of bias |
Effect of assignment:
Comment: No information reported about blinding, but it is almost impossible to blind these patients because of the nature of the intervention. Furthermore, no information was reported whether deviations arose from the intended intervention because of the trial context. Effect of adhering: "Forty‐six percent of those educated (12 of 26) received a standard treatment plan. Non‐standard treatment plans, incorporating the use of oral steroids as the first line of action in the yellow zone, were followed in some cases, for example, if the patient already used high dosages of inhaled steroids as maintenance therapy, or could report that a double or triple increase in inhaled steroids previously had shown marginal effect on the course of attacks/exacerbations. Among those 14 patients receiving non‐standard treatment plans, eight patients did not want to or were not able to use peak flow monitoring as a basis for change in medication. For those patients, symptom‐only based treatment plans were issued." Gallefoss 2002, p. 425. "In the intervention group, four patients failed to complete the educational program (social problems (n = 1), unannounced emigration (n = 1), failure to meet at educational group sessions for unknown reasons (n = 1) and serious myocardial infarction (n = 1))." Gallefoss 2002, p. 427. Comment: No information reported about adherence to the programme of the other patients (who completed the programme). |
High risk of bias | “In the intervention group, four patients failed to complete the educational programme (social problems (n = 1), unannounced emigration (n = 1), failure to meet at educational group sessions for unknown reasons (n = 1) and serious myocardial infarction (n = 1)). Another patient was withdrawn from the study during the follow‐up due to lymphoma (n = 1). This left us with 26 patients (81%) for a 1‐year follow‐up. The patients who were withdrawn from the intervention group did not, to our knowledge, have any serious deterioration in their obstructive lung disease, and none were hospitalised. In the control group four patients were withdrawn (lack of co‐operation (n = 2), diagnosis of rectal cancer (n = 1) and emigration (n = 1)). Two of the withdrawn control group patients were hospitalised for exacerbations of their COPD. This left us with 27 patients (84%) for the 1‐year follow‐up” Gallefoss 2002, p. 427. Comment: The number of dropouts was relatively low, and reasons for dropout were comparable over groups |
High risk of bias | "Prebronchodilator spirometry was performed before randomization and at 12 mo follow‐up by standard methods using a Jaeger MasterLab Body Box (Würzburg, Germany). The technical staff did not know whether the patients belonged to the control or intervention groups." Gallefoss 1999, p. 2003. Comment: No information reported regarding the assessors of the primary outcome. Number of prednisolone courses was retrospectively self‐reported at 12 months of follow‐up. |
Some concerns | "We defined a priori the patient as compliant when dispensed regular medication was greater than 75% of prescribed regular medication during the study period." Gallefoss 1999, p. 2002. | High risk of bias | Unpredictable direction of the outcome. |
| Bourbeau 2003 | Low risk of bias | “… central computergenerated list of random numbers. Randomization was stratified per center and in blocks of 6, and patients were assigned to the self‐management program (intervention group) or to usual care.” p. 586. “The blocking factor was not known by the investigators or their staff in each participating center." p. 586. “The use of respiratory medications was similar between study groups, except that oral steroids were used less commonly in the intervention group (7%) than in the usual care group (13%). None of the disease severity characteristics were otherwise different between the study groups.” p. 586. Comment: Random sequence allocation was adequately performed. |
High risk of bias |
Effect of assignment:
"Since a double‐blind design was impossible..." p. 586.
Comment: Participants and personnel were not blinded. ITT analysis was performed. Effect of adhering: "Since a double‐blind design was impossible..." p. 586. Comment: Participants and personnel were not blinded. Comment: There might be some imbalance in non‐protocol interventions such as exercise evaluation (not mandatory). However, no information available. |
Low risk of bias | ‐ | Low risk of bias | "...an independent evaluator unaware of the patient assignment was responsible for the evaluation process in each center. The evaluator was cautioned not to ask about the workbook modules and types of contact.” p. 586. Comment: Outcome assessment was blinded. |
Some concerns | Comment: No protocol or prespecified analysis plan available. | High risk of bias | Unpredictable direction of the outcome. |
| Coultas 2005 | Low risk of bias | “Patients were randomly assigned to one of three intervention groups (usual care (UC), nurse‐assisted medical management (MM), or nurse‐assisted collaborative management (CM)) using a computer‐generated random list.” p. 2018. “Although the distribution of most of the baseline characteristics of the three groups was similar (Tables 2 and 3), only the distribution of gender and the tangible domain of social support were significantly different among the intervention groups.” p. 2020. Comment: It is unclear how allocation concealment was guaranteed. Observed imbalances are probably compatible with chance. Random sequence generation was adequately performed. |
High risk of bias |
Effect of assignment:
“Of the 217 patients enrolled in the study, 151 (69.6%) completed the 6‐month intervention and follow‐up data collection.” p. 2020.
“The reasons for the failure to complete the study were patient was unavailable for follow‐up (26.7%) and death (3.7%) [Fig 1]. The frequency of patients being unavailable for follow‐up was equally distributed among the three intervention groups (Fig 1). Overall, the demographic characteristics of the patients who dropped out of the study were similar to those who completed the study (data not shown). However, patients who dropped out of the study had more severe airflow obstruction, higher levels of distress, and lower quality of life, as measured with the SGRQ, compared with the patients who had completed the study (data not shown).” p. 2020.
Comment: Not reported whether deviations arose because of the trial context. Only patients who completed the 6‐month intervention and follow‐up data collection were analysed (per‐protocol analyses). Effect of adhering: Comment: Patients and personnnel were probably aware of assignment to the intervention during the trial. |
High risk of bias | “The reasons for the failure to complete the study were patient was unavailable for follow‐up (26.7%) and death (3.7%).” p. 2020. “However, patients who dropped out of the study had more severe airflow obstruction, higher levels of distress, and lower quality of life, as measured with the SGRQ, compared with the patients who had completed the study (data not shown).” p. 2020. Comment: Only patients who completed the 6‐month intervention and follow‐up data collection were analysed. |
Low risk of bias | “To limit interviewer bias, each interviewer who obtained the baseline and 6‐month outcome data was blinded to the patient’s treatment group.” p. 2023. "Although self‐reported health‐care utilization may be subject to recall bias, it has been shown to be an acceptable method of measurement and may actually result in an underestimation of utilization with more frequent use.” p. 2023. |
Some concerns | Comment: No protocol available. Measures and analysis intentions were only reported in the method section of the paper. | High risk of bias | Unpredictable direction of the outcome. |
| Coultas 2005 | Low risk of bias | “Patients were randomly assigned to one of three intervention groups (usual care (UC), nurse‐assisted medical management (MM), or nurse‐assisted collaborative management (CM)) using a computer‐generated random list.” p. 2018. “Although the distribution of most of the baseline characteristics of the three groups was similar (Tables 2 and 3), only the distribution of gender and the tangible domain of social support were significantly different among the intervention groups.” p. 2020. Comment: It is unclear how allocation concealment was guaranteed. Observed imbalances are probably compatible with chance. Random sequence generation was adequately performed. |
High risk of bias |
Effect of assignment:
“Of the 217 patients enrolled in the study, 151 (69.6%) completed the 6‐month intervention and follow‐up data collection.” p. 2020.
“The reasons for the failure to complete the study were patient was unavailable for follow‐up (26.7%) and death (3.7%) [Fig 1]. The frequency of patients being unavailable for follow‐up was equally distributed among the three intervention groups (Fig 1). Overall, the demographic characteristics of the patients who dropped out of the study were similar to those who completed the study (data not shown). However, patients who dropped out of the study had more severe airflow obstruction, higher levels of distress, and lower quality of life, as measured with the SGRQ, compared with the patients who had completed the study (data not shown).” p. 2020.
Comment: Not reported whether deviations arose because of the trial context. Only patients who completed the 6‐month intervention and follow‐up data collection were analysed (per‐protocol analyses). Effect of adhering: Comment: Patients and personnnel were probably aware of assignment to the intervention during the trial. |
High risk of bias | “The reasons for the failure to complete the study were patient was unavailable for follow‐up (26.7%) and death (3.7%).” p. 2020. “However, patients who dropped out of the study had more severe airflow obstruction, higher levels of distress, and lower quality of life, as measured with the SGRQ, compared with the patients who had completed the study (data not shown).” p. 2020. Comment: Only patients who completed the 6‐month intervention and follow‐up data collection were analysed. |
Low risk of bias | “To limit interviewer bias, each interviewer who obtained the baseline and 6‐month outcome data was blinded to the patient’s treatment group.” p. 2023. "Although self‐reported health‐care utilization may be subject to recall bias, it has been shown to be an acceptable method of measurement and may actually result in an underestimation of utilization with more frequent use.” p. 2023. |
Some concerns | Comment: No protocol available. Measures and analysis intentions were only reported in the method section of the paper. | High risk of bias | Unpredictable direction of the outcome. |
| Rice 2010 | Some concerns | "We assigned subjects in equal proportions to each of the two treatment arms by permuted‐block randomisation." Appendix 1, p. 3. "The baseline characteristics of the two treatment groups were generally well matched, with differences in age, lung function, and ED visits (not significant)." p. 891. Comment: Information on the method of allocation concealment was not reported. |
High risk of bias |
Effect of assignment:
"We performed a randomized, adjudicator‐blinded, controlled, 1‐year trial." p. 890.
"The status of all 743 patients was determined after 1 year. Electronic medical records were available for all hospitalizations and ED visits that occurred within the VA medical system. The success rate for obtaining discharge summaries and ED records for self‐reported events that occurred outside the VA was 99% in the usual care group and 98% in the disease management group." p. 891. Effect of adhering: Comment: 336 out of 372 (90.3%) patients completed disease management 323 out of 371 (87%) completed usual care. |
Low risk of bias | "55% of patients in the usual care group and 60% of patients in the disease management group returned a completed the Saint George’s Respiratory Questionnaire in response to a single mailing at the end of the study. low response rates on SGRQ leading to a high risk of bias. However, data on healthcare utilisation seem complete with no risk of bias." p. 892. | Low risk of bias | "Blinded pulmonologists independently reviewed all discharge summaries and ED reports and assigned a primary cause for each." p. 891. | High risk of bias | Comment: Primary outcome in the paper is reported as a combined outcome measure, whereas it was planned to analyse the two outcomes separately. | High risk of bias | Unpredictable direction of the outcome. |
| Bucknall 2012 | Low risk of bias | “We used a minimisation technique to stratify randomisation of participants by demographic factors (deprivation category of area of residence,11 age and sex, FEV1 per cent predicted at the time of randomisation, smoking status, participation in pulmonary rehabilitation within two years, and number of previous admissions) to control for key aspects of disease severity and predictors of readmission. We constructed a computer generated sequence by using the method of randomised permuted blocks of length four, with two allocations being made at random and two by minimisation. Treatment group allocations were obtained by telephone, after baseline assessments had been made.” p 2. Comment: Random sequence allocation was adequately performed. |
High risk of bias |
Effect of assignment:
Comment: No blinding of patients and personnel. Data for the primary outcome (time to first acute COPD hospital admission or death) were available for all patients and analysed with a Cox proportional hazards model adjusting for the stratification variables. Effect of adhering: Comment: No blinding of patients and personnel. Seventy‐five (42%) of 180 intervention group participants who completed 12 months of follow‐up were judged to have become successful self managers. |
High risk of bias | Comment: For secondary outcome measures (e.g. SGRQ, HADS, CSES) not all data were available for all patients randomised (Table 2). | Low risk of bias | ‐ | Some concerns | ‐ | High risk of bias | Unpredictable direction of the outcome. |
| Fan 2012 | Low risk of bias | “Randomization lists were generated on the basis of random, permuted blocks of variable size to ensure approximate balance over time.” p. 674. “The CSP Coordinating Center in Boston, Massachusetts, randomly assigned eligible patients in equal numbers to 2 groups, stratifying patients per site to allow for possible regional differences in patient characteristics and clinical practice patterns.” p. 674. Comment: Random sequence generation was adequately performed. The allocation was adequately concealed. Authors didn’t report whether there were any significant differences. Most characteristics are equally balanced, but there is a bit larger difference in the following characteristics (>5%):
|
High risk of bias |
Effect of assignment:
“The 2 groups differed on the basis of a complex behavioral intervention that made blinding impossible.” p. 674.
Comment: No blinding of participants and personnel.
"For the primary intention‐to‐treat analysis, the null hypothesis was that the COPD hospitalization hazard rate for intervention did not differ from that for standardized care."p. 675.
"Also, with respect to time to first COPD hospitalization, we conducted a futility analysis to assess what might have resulted if the trial had continued." p. 676.
"When the study was stopped, the 1‐year cumulative incidence of COPD‐related hospitalization was 27% in the intervention group and 24% in the usual care group (hazard ratio, 1.13 [95% CI, 0.70 to 1.80]; P 0.62)." p. 677. Effect of adhering: "During the entire follow‐up period extending to September 2009, a total of 8 patients in the intervention group and 10 in the usual care group either did not attend scheduled study visits or formally withdrew from the study. Among patients in the intervention group, 87% completed all 4 individual educational visits and 57% completed the group visit. A review of the recorded sessions found that case managers covered 77% to 89% of the educational items in each session. The ranges of average scores across sites that provided audio recordings for each session were 18.3 to 31 for session 1 (13 sites), 12 to 19 for session 2 (12 sites), 12.7 to 23 for session 3 (10 sites), and 6 to 18 for session 4 (10 sites)." p. 677. |
High risk of bias | “This multisite, randomized, controlled trial of an educational and acute care management program was stopped early when a safety monitoring board noted more deaths in the intervention group.” p. 674 Comment: There is incomplete outcome data due to early termination of the study. |
Low risk of bias | “Telephone‐based ascertainment of study outcomes (COPD hospitalizations and exacerbations) was performed by centralized research staff blinded to assignment. All outcomes were collected by centralized staff blinded to study group, and all hospitalizations were adjudicated by a committee that was also blinded to study group.” p. 674. Comment: Research staff blinded to study group contacted patients every 2 months to determine whether they developed symptoms of a COPD exacerbation, along with details of treatment and health care use. Deaths were ascertained by staff at the study sites, by review of VA electronic medical and administrative records and by a search of the Social Security Death Index. Extensive multivariate analyses failed to identify any factors alone or combined that could plausibly explain the difference in mortality. Two of the authors who were blinded to study group reviewed all available medical information and did not find anything in the deaths that would not be expected in frail patients with COPD. |
Some concerns | Comment: The primary and secondary outcomes were reported, only healthcare costs as (secondary objective) were not reported. | High risk of bias | Predicted directon: Favours comparator, because more deaths in the intervention group were observed. There is still a chance that this was because of chance. |
| Walters 2013 | High risk of bias |
Randomisation process:
"After recruitment, practices were randomised using a code generated by investigators from a random numbers table stratified in blocks of four by Rural, Remote and Metropolitan Areas (RRMA) classifications in Tasmania. Allocation occurred independently using sequentially numbered, opaque and sealed envelopes." p. 2. Timing of identification or recruitment of participants: GPs identified patients with COPD aged over 45 years seen within the previous 12 months through database searches, based on a diagnostic code for COPD or prescription of tiotropium. Comment: Most variables are equally distributed, but more smokers (not statistically significant, p=0.102) and more previous admissions in the intervention group (statistically significant, p=0.028), so potentially more room for improvement. Although, this small number of differences identified as ‘statistically significant’ at the conventional 0.05 threshold should usually be considered to be compatible with chance. |
High risk of bias |
Effect of assignment:
‐ Effect of adhering: "The limitations of the study were the high rate of misclassification of COPD in general practices, which impacted on enrolment, and higher than expected withdrawal rates, especially in the HM group, which reduced the intended statistical power." p. 6. Comment: Nine patients discontinued and 8 patients withdrew in the intervention group. |
Low risk of bias | Comment: Figure 1: 9 intervention patients discontinued, but they attended follow‐up. In Table 2, no patient numbers are mentioned. | Low risk of bias | Comment: Blinding of participants or research officers was not possible given the nature of the study. | Low risk of bias | Comment: Data that produced this result analysed in accordance with a pre‐specified analysis plan. | High risk of bias | Unpredictable direction of the outcome. |
| Hernández 2015 | Low risk of bias | "A computer‐generated list of random numbers with no restrictions and administered by personnel who were not involved in the study ensured blinded randomisation." p. 2. "(…) and administered by personnel who were not involved in the study." p. 2. Comment: Random sequence generation was adequately performed. No blinding of participants or personnel. The patients of the two groups showed similar characteristics, except that influenza and pneumococcal vaccination were more prevalent in the IC group (P<0.01). |
High risk of bias |
Effect of assignment:
Comment: It was not possible to blind the treatment for patients and people delivering the treatment. Intention‐to‐treat analysis performed. Effect of adhering: "As a sensitivity analysis, we repeated all analyses after excluding patients who had a previous contact with any IC programme (n = 15)." p. 2. "25 patients (22%) died and 16 (14%) were lost during the 1‐year follow‐up, and the remaining 114 patients (IC, n = 59 and UC, n = 55) completed the 12‐month assessment visit. Patients lost to follow‐up exhibited a higher affectation of activities of daily living and health‐related quality of life at baseline than those who were followed up, without differences in other sociodemographic, clinical, functional and medical care‐related variables." p. 3. Comment: It is not mentioned in which way these patients were distributed over the two groups, nor are the results of the sensitivity analysis reported. Although the approach was not adequately adopted at the community level and thus the intervention was not continued after the 1 year of follow‐up, this was not a failure of implementing the intervention, since the intervention stopped at 1 year according to the protocol. |
High risk of bias | Comment: Refusal of n=5 in the intervention group. Lost to follow‐up 12 in intervention group and 29 in usual care group. So in total 22% died and 14% were lost to follow‐up. Patients lost to follow‐up exhibited a higher affectation of activities of daily living and health‐related quality of life at baseline than those who were followed up, (no differences in other sociodemographic, clinical, functional and medical care‐related variables) this could have biased the results between the intervention group and usual care group. | Low risk of bias | "A blind evaluation of the study group carried out before randomisation and after the 12‐month follow‐up consisted of a patient interview and analysis of medical records, self‐administered questionnaires and lung function testing." p. 2. | Some concerns | "Although the study was officially registered as part of the EU Grant (CIP‐ICT‐PSP‐2007.225025), the RCT was not included in the clinicaltrials.gov registry because at that time it was not compulsory." p. 5. Comment: No protocol available. |
High risk of bias | Direction: favours experimental. Comment: More patients were lost to follow‐up in the usual care group and patients lost to follow‐up exhibited a higher affectation of activities of daily living and health‐related quality of life at baseline than those who were followed up. |
| Jonsdottir 2015 | Low risk of bias | "After accepting the invitation, prior to entering the research centre, the research nurses randomized the patients to experimental and control groups in accordance with CONSORT requirements using a computer‐generated list of random numbers." p. 2638. | High risk of bias |
Effect of assignment:
Comment: Not possible to blind the treatment for patients and people delivering the treatment. Intention‐to‐treat analysis was not carried out as stated in the article, but in table 3 all patients that completed the follow‐up seem to be included. Effect of adhering: "To minimize treatment bias the data were concealed from the nurses providing the treatment and the treatment notes were concealed from the nurses conducting data collection." p. 2640. "Both groups followed standardized protocols and had regular meetings to maintain consistency. Few family members participated. This actually changed the nature of the study from being a family‐centered intervention as planned, into becoming focused on patients, with family involvement when possible." p. 2640. "Attendance at treatment sessions in the experimental group was more than 80% in the patient/family conversations (43/48 attended three or four out of the four possible meetings) and the group meeting (40/48). Half of the patients in the experimental group smoked (24/48). Of those, 58% (14/24) participated in the smoking cessation treatment." p. 2641. |
High risk of bias | "Three patients died in the experimental group... The dropout rate was 20% (n = 12) in the experimental group and 12% (n = 7) in the control group. Also additional missing data on outcome variables as displayed in table 3. The dropout rate for family members was 31% (n = 5) and 50% (n = 7) in the experimental and control groups respectively." p. 2640. Comment: No info on dropout reasons or characteristics of dropouts. |
Low risk of bias | "To minimize treatment bias the data were concealed from the nurses providing the treatment and the treatment notes were concealed from the nurses conducting data collection." p. 2640. | High risk of bias | No information, not registered in a trial register. | High risk of bias | Unpredictable direction of the outcome. |
| Titova 2015 | High risk of bias |
Randomisation process:
“They were randomly allocated to either integrated care (IC) or usual care (UC) based on their address of permanent residence. In order to create two pairs of districts with approximately equal numbers of citizens, a pair‐wise matching of districts was carried out. It was decided by lottery that participants from District Pair 1 were assigned to the UC group, and participants from District Pair 2 were assigned to the IC group.” Titova 2015, p. 2.
“There were no significant differences in baseline characteristics between the IC and the UC groups, but when comparing those who died during follow‐up with those who were still alive after two years, those who died had a significantly higher PaCO2 and lower BMI at baseline (Table 1). Those who died during follow‐up also had significantly more HA and HD during the year prior to study start.” Titova 2015, p. 4.
Comment: No information provided about the allocation concealment. Timing of identification or recruitment of participants: "They were randomly allocated to either IC or UC group based on their address of permanent residence. Patient data were registered at discharge and 6, 12, and 24 months after discharge from the TUH." Titova 2017, p 3. Comment: If allocation was known before study inclusion, suitable patients could be selected for the intervention. |
High risk of bias |
Effect of assignment:
“The study was a prospective, open, single‐centre intervention study.” Titova 2015, p. 2.
"The principal comparisons of changes were performed on an intention‐to treat basis." Titova 2017, p. 4.
Comment: No blinding of participants and personnel. Effect of adhering: ‐ |
High risk of bias | “172 patients were randomly allocated to the IC group (n = 91) or the UC group (n = 81), respectively. After two years of follow‐up, a total of 100 patients (58% of the included patients), 51 patients in the IC group and 49 patients in the UC group, were available for evaluation (Figure 1).” Titova 2017, p. 5. "Those who died had a significantly higher PaCO2 and lower BMI at baseline (Table 1). Those who died during follow‐up also had significantly more HA and HD during the year prior to study start." Titova 2015, p. 4. Comment: No mortality reported; however, Figure 1 shows higher mortality for the IC group, n=35 (38.4%), compared to the UC group, n=21 (25.9%). |
High risk of bias | “Information concerning the number and duration of the COPD exacerbations, as well as the time from onset of symptoms until the start of self‐initiated treatment is insufficient due to many incomplete registrations in “My COPD book.” Titova 2015, p. 9. "“Data concerning HA (hospital admissions) and HD (hospital days) were collected from the hospital registry database’s medical charts.” Titova 2015, p. 3. Comment: Unclear who was the outcome assessor. |
Some concerns | Trial register reported number of hospitalisations as the primary outcome. Secondary outcomes were quality of life, lung function, use of medication, cost‐effectiveness. However, the article reported not all secondary outcomes (e.g. cost‐effectiveness). | High risk of bias | Unpredictable direction of the outcome. |
| Jolly 2018 | High risk of bias | "When a patient is identified as eligible for the study, and has given written, informed consent to take part, the researcher randomises the patient using a web‐based programme hosted by the Primary Care Clinical Trials Unit (PC‐CTU), University of Birmingham. Centre specific randomisation lists were produced by a statistician at the trials unit. Participants are individually randomised, stratified by centre. The four recruitment centres are Birmingham and West‐Midlands South; Greater Manchester; North West Midlands and Oxfordshire/Gloucestershire. Only the PC‐CTU have access to the allocation sequence." Sidhu 2015 (protocol paper), p. 4. "The study groups were generally well balanced in terms of patient characteristics, although there was a higher proportion of current smokers in the telephone health coaching group. The usual care group reported a higher level of self reported moderate and vigorous physical activity, but this was not reflected in the accelerometry data at baseline." Jolly 2018 (results paper), p. 5. |
High risk of bias |
Effect of assignment:
Comment: Patients were informed of their allocation at the end of the recruitment appointment; they were not masked to treatment allocation. All data were analysed by intention to treat. Effect of adhering: "We achieved good fidelity of delivery of the intervention, with 75% of intervention participants receiving all four calls and only four patients receiving none." p. 11. "The dose and coverage of intervention delivery were high: 86.4% (999/1156) of the scheduled calls were delivered and 75.4% (218/289) of participants received all four calls." No information regarding pulmonary rehabilitation, oxygen use. |
High risk of bias | "There was imbalance in the follow‐up rates between telephone health coaching (82.7%; 37 withdrawals) and usual care (96.2%; 7 withdrawals)." p. 4. "Participants who did not provide data at 12 months were more likely to be in GOLD stage 3, to be smokers, had lower levels of self‐reported physical activity, and to live alone than responders. " p. 5. Comment: For health‐related quality of life, data were available for 75% of intervention patients (217 of 289), although some sensitivity analyses were performed. |
Some concerns | "Patients were informed of their allocation at the end of the recruitment appointment; they were not masked to treatment allocation. Data were entered into the study database by researchers at the University of Birmingham who were masked to the treatment allocation." p. 3. Comment: No information about outcome assessors. |
Low risk of bias | ‐ | High risk of bias | Unpredictable direction of the outcome. |
| Kessler 2018 | Low risk of bias | "Patients were allocated to groups in a 1:1 fashion according to a pre‐specified randomisation list generated before the study by a partial‐minimisation computer algorithm under supervision of the study sponsor. Patients were assigned a randomisation number by study staff at each centre in sequential numerical order through a telephone‐based interactive voice response system. Randomisation was stratified by smoking status (current or former), need for respiratory assistance (none, or on LTOT and/or HMV), and centre." p. 3. | High risk of bias |
Effect of assignment:
"For practical reasons, the study was open; neither the patients nor the investigators were blinded to the COPD management strategy." p. 3.
"The primary analysis of the primary outcome was performed in the intention‐to‐treat (ITT) population (all patients who entered the follow‐up period). The number of hospitalisation days fitting the established criteria was normalised on a yearly basis for each patient and compared between both groups using the non‐parametric Wilcoxon rank‐sum test." p. 4.
"The open design of the study, though necessary owing to the extensive differences between the two disease management programmes, may have led to some bias because doctors could have had a tendency to discharge patients in the disease management arm earlier than those in the usual management arm." p. 12. Effect of adhering: Comment: 15 patients (<10%) received <25% self‐management training. |
Low risk of bias | "…leaving 157 (91%) and 162 (94%) patients in the ITT population, 137 (80%) and 128 (74%) of whom completed at least 12 months of follow‐up." p. 5. | Low risk of bias | "Because hospitalisation decisions might have been subject to local practices, social considerations, bed availability, and so on, all hospitalisations were reviewed by an independent, three‐member end‐point validation committee (EVC) to assess the reason and appropriateness of each hospitalisation, determine whether the hospitalisation fulfilled the protocol definition, and determine the extent to which it was to be considered in the efficacy assessments (fully, partially, not at all)." p. 3. | Low risk of bias | "During the study, the protocol was amended to accelerate recruitment and allow study completion (supplementary material)." p. 3. Comment: Inclusion criteria were expanded from COPD patients receiving LTOT to patients with severe COPD, with or without LTOT; the minimum number of patients was reduced from 520 to 306 by retaining the initial assumptions for sample size and removing a multiple comparisons adjustment; the follow‐up period was reduced from 2 years to 1 year; and the contact frequency between DM patients and CMs was increased to improve patient training (either group or phone session, once per month). Prior to these changes, 72 patients on LTOT were enrolled in the study. | High risk of bias | Unpredictable direction of the outcome. |
| Wang 2019 | Low risk of bias | "The allocation sequence was generated and released to the interventionist on a case‐by‐case basis by an independent department that specialised in supplying randomly generated sequences for research. The randomisation sequence was recorded." p. 151. "Participants were randomly assigned to groups after consent was obtained and baseline data were collected." p. 151. "There were no significant differences in demographic and clinical data between the two groups at baseline (Table 1)." p. 151. |
High risk of bias |
Effect of assignment:
Comment: It is not possible to blind the treatment for patients and people delivering the treatment. Intention‐to‐treat analysis was used. Effect of adhering: "154 participants were enrolled, among whom, 143 completed the 12‐month study program. The attrition rate was 7.14%." p. 151. "...adherence to the self‐management intervention was reported by the participants but not monitored by the nurses." p. 155. Comment: No info on reasons of adherence by patients reported in the current publication. |
Low risk of bias | Comment: Relatively low attrition rate. | Low risk of bias | "To minimize researcher bias, the interventionists who provided care were blinded to the participants’ baseline and allocation sequence. The statistician was blinded to the participants’ results during the trial." p. 151. Comment: Not possible to blind the treatment for patients and people delivering the treatment. |
Some concerns | Comment: No pre‐specified analysis plan published which can be checked. However they mention: The statistician was blinded to the participants’ results during the trial. | High risk of bias | Unpredictable direction of the outcome. |
| Liang 2019 | High risk of bias | "Group or solo GP clinics with ≥1000 patients on their databases were approached directly or with assistance from primary care organisations. After obtaining signed agreement, clinics were block randomised (block sizes of four and six) to usual care or intervention arms using an externally managed web‐based randomisation programme. Clinics were notified of their allocation." p. 3. | High risk of bias |
Effect of assignment:
‐ Effect of adhering: "67 participants (43%) did not receive any part of the intervention." p. 7. "A key limitation is the low uptake of the intervention components." p. 10. |
High risk of bias | Comment: Data were not available for all patients randomised. | Low risk of bias | "The effective analysis was according to an intention‐to‐treat principle." p. 4. | Low risk of bias | Results were analysed according to the published design paper. | High risk of bias | Predicted direction: Favours comparator, because general practices could exclude patients from selection to participate in the intervention due to the cluster randomisation approach. Adherence to the intervention was low. |