Perrin 2010.
| Methods | Randomized controlled trial | |
| Participants | The study location was Medical Research Institute of New Zealand and the P3 Research Clinical Trials Unit at Bowen Hospital, Wellington, New Zealand 57 participants were randomized to the intervention group and 54 participants were randomized to the control group The inclusion criteria were adults in the Wellington region age 16 to 65 years with a diagnosis of asthma, recruited from existing research volunteer databases, newspaper advertisements, and letters via family doctors with a diagnosis of asthma and to be currently taking ICS at a stable dose with or without a separate LABA inhaler The exclusion criteria were a diagnosis of chronic obstructive pulmonary disease, current use of a combination ICS/LABA inhaler, women who were pregnant or lactating, a history of other clinically significant disease, or a significant exacerbation of asthma in the previous month requiring a clinic or hospital attendance |
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| Interventions | Intervention: COMBINATION METERED DOSE INHALER (MDI)
Subjects received the intervention treatment regimen for a duration of 24 weeks that involved 125 mg FP and 25 mg salmeterol in a combination Smartinhaler, 2 actuations twice daily. Participants were seen in the clinic on 5 occasions. At the first visit, subjects were randomized and issued the appropriate Smartinhalers, and inhaler technique was checked. Subjects were instructed to take 2 actuations of the study medications twice daily, resulting in a daily dose of 500 mg FP and 100 mg salmeterol with both regimens. Subjects were advised that the study was designed to compare the efficacy of the 2 regimens but were not informed that adherence would be monitored. They were told that the MDI casing looked different because it was possible to program it with a reminder alarm, but that this function would not be used in this study Control: SEPARATE METERED DOSE INHALER (MDI) Subjects received a treatment regimens for a duration of 24 weeks of 125 mg FP and 25 mg salmeterol in separate Smartinhalers, 2 actuations twice daily. Participants were seen in the clinic on 5 occasions. At the first visit, subjects were randomized and issued the appropriate Smartinhalers, and inhaler technique was checked. Subjects were instructed to take 2 actuations of the study medications twice daily, resulting in a daily dose of 500 mg FP and 100 mg salmeterol with both regimens. Subjects were advised that the study was designed to compare the efficacy of the 2 regimens but were not informed that adherence would be monitored |
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| Outcomes | The measures of adherence were 1) the number of doses taken as a percentage of those prescribed during the final (4th) 6‐week period of the study; 2) adherence in the first, second, and third 6‐week periods of the study; 3) number of adherent days in which the prescribed 2 doses were taken twice daily in each 6‐week period of the study; 4) and the proportion of patients who took > 50%, > 80%, and > 90% of doses in each of the 6‐week periods of the study. At 4 clinic visits after randomization, adherence data were uploaded from the Smartinhaler to a computer The patient outcomes were results from the Asthma Control Questionnaire and FEV1 |
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| Notes | ― | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Random code computer was used. "Randomization was by computer‐generated random code supplied by a statistician. The sequence was imbedded in a Microsoft Access Database (Microsoft Corp, Redmond, Wash) by a third party and concealed from the researchers until the time the subject was enrolled and entered into the database." (pg 507) |
| Allocation concealment (selection bias) | Low risk | The allocation code was code was concealed. "Randomization was by computer‐generated random code supplied by a statistician. The sequence was imbedded in a Microsoft Access Database (Microsoft Corp, Redmond, Wash) by a third party and concealed from the researchers until the time the subject was enrolled and entered into the database." (pg 507) |
| Selective reporting (reporting bias) | Unclear risk | No protocol available; although it appears that everything was reported it is difficult to determine this without a protocol |
| Other bias | Unclear risk | Other possible sources of bias are: 1. Drug sponsored study (GlaxoSmithKline) (pg 505). 2. Subjects were informed that the purpose of the study was to compare single with combination inhaler therapy (pg 508). 3 Because subjects were recruited from an existing volunteer trial participant list, some may have become aware that the inhaler device was monitoring their drug use (pg 509). 4. Having been enrolled in a previous study, some may have been more compliant (pg 509). 5. The authors state the study may have been underpowered to detect small but clinically important differences in compliance (pg 509) |
| Blinding of outcome assessment (detection bias) Adherence measure | Unclear risk | (PRIMARY) METERED DOSE INHALER ‐ Blinding of staff collecting the data not mentioned (the inhalers had different colors and the control group would have 2 inhalers rather than 1 for the intervention group). The data from the Smartinhalers were uploaded to a computer. Data were somewhat manipulated because doses were excluded that had 10 or more actuations within a 3‐hour period |
| Blinding of outcome assessment (detection bias) Patient outcome | Unclear risk | (PRIMARY) ASTHMA CONTROL QUESTIONNAIRE ‐ Subjective questionnaire, no mention of blinding, unclear if this might influence outcome |
| Blinding of participants (performance bias) Adherence measure | Unclear risk | (PRIMARY) METERED DOSE INHALER ‐ Patients were not told their dose taking was being monitored but because they were in a previous study, some may have guessed that the unique inhaler was a monitor |
| Blinding of participants (performance bias) Patient outcome | High risk | (PRIMARY) ASTHMA CONTROL QUESTIONNAIRE ‐ Subjective questionnaire, no mention of blinding, unclear if this might influence outcome |
| Blinding of personnel (performance bias) Adherence measure | Unclear risk | (PRIMARY) METERED DOSE INHALER ‐ No information on blinding given. There is insufficient information to permit judgment of 'Low risk' or 'High risk' |
| Blinding of personnel (performance bias) Patient outcome | Unclear risk | (PRIMARY) ASTHMA CONTROL QUESTIONNAIRE ‐ Subjective questionnaire, no mention of blinding, unclear if this might influence outcome |
| Incomplete outcome data (attrition bias) Adherence measure | Unclear risk | (PRIMARY) METERED DOSE INHALER ‐ Attrition reported but there were almost 10% fewer subjects in the control group at study's end but reasons for dropouts were similar in intervention and control; however, the authors state that the study was likely underpowered. Bias unclear |
| Incomplete outcome data (attrition bias) Patient outcome | Unclear risk | (PRIMARY) ASTHMA CONTROL QUESTIONNAIRE ‐ Attrition reported but there were almost 10% fewer subjects in the control group at study's end. Reasons for dropouts were similar in intervention and control groups; however, the authors state that the study was likely underpowered. Bias unclear |