Jarad NA, Wedzicha JA, Burge PS, et al. An observational study of inhaled corticosteroid withdrawal in stable chronic obstructive pulmonary disease. Respiratory Medicine 1999;93:161-66.
PubMed link: https://www.ncbi.nlm.nih.gov/pubmed/10464871
Full text article: https://www.sciencedirect.com/science/article/pii/S095461119990001X?via%3Dihub
| Methods | Study design: Prospective cohort study
Number of groups: Two groups |
| Participants | Number of participants: 272 enrolled
· Active deprescribing group: 160 enrolled · Control group: 112 enrolled Age: median 66 (41 to 75 years) Sex: 119 female, 42 male Participants with dementia: No Inclusion criteria: · Clinical history of COPD · Aged between 40 and 75 years · Evidence of significant airflow obstruction with an forced expiratory volume, greater than 0.8 but less than 70% of predicted values 30min after receiving 400mcg salbutamol from a metered dose inhaler via a spacer · Forced expiratory volume/forced volume capacity ratio was less than 75%, and none showed more than a 10% of predicted forced expiratory volume, improvement from baseline after the inhaled salbutamol · Clinically stable for at least 3 months before entry Exclusion criteria: · Concurrent life-threatening illnesses · Clinical features suggestive of bronchial asthma or a previous physician diagnosis of asthma were excluded · Regular oral prednisolone Country: England Setting: Community – six of the centers participating in the main study recruited from hospital out-patient departments and general practice |
| Interventions | Medicine: Inhaled corticosteroids – regular inhaled corticosteroids (median daily dose 800 mcg, range 50-2400) as either beclomethasone dipropionate or budesonide
Withdrawal schedule: Told to withdraw these at their own discretion during the next 7 days Comparator: Participants who had not previously used inhaled corticosteroids |
| Outcomes | Exacerbations |
| Dates | Dates: Not described
Follow-up duration: Two months |
| Funding sources | “GlaxoWellcome Research and Development…. Fluticasone propionate is manufactured by Allen and Hanburys, which is owned by GlaxoWellcome.”
Funding source not stated in the current paper, but declared in the paper of the main study: Burge, P. Sherwood, et al. “Randomized, double-blind, placebo-controlled study of fluticasone propionate in patients with moderate-to-severe chronic obstructive pulmonary disease: the ISOLDE trial.” BMJ 320.7245 (2000): 1297-1303.” |
| Notes | Abstract says that all had been clinically stable for at least 6 weeks before the study, the text says that those who had not been clinically stable for 3 months or longer were excluded.
This paper reported the run-in phase for the main study. |
Risk of bias table
| Bias | Authors’ judgment | Support for judgment |
| Random sequence generation (selection bias) | High risk | Not randomized |
| Allocation concealment (selection bias) | High risk | Open study |
| Blinding of participants and personnel (performance bias) | 5 out of 5 | Open study |
| Blinding of outcome assessment (detection bias) | 5 out of 5 | As above |
| Incomplete outcome data (attrition bias) | 1 out of 5 | It appears to be 100% follow-up data. |
| Selective reporting (reporting bias) | 5 out of 5 | It appears that they had a protocolthough it is not known if they had a pre-specified analysis plan. However, the stated objectives have been broadly reported on.
The predefined definition of an exacerbation of COPD was an episode of increased shortness of breath and/or sputum production requiring treatment with antibiotics and/or prednisolone”. This is a subjective assessment in an open study. |
| Confounding (non-randomized) | 4 out of 5 | The control group (people who had not taken a prior inhaled corticosteroid) is a different population than those who have taken an inhaled corticosteroid.
There are many confounders discussed in the paper. Most were not eliminated. |
| Other bias | High risk | Industry-sponsored. |
| Newcastle-Ottawa scale | ||
| Selection bias | Representativeness of the exposed cohort | The intervention group is somewhat representative of the average older adult with COPD,who were prescribed inhaled corticosteroids in the community. |
| Selection of the non-exposed cohort | The control cohort is drawn for a different population. | |
| Ascertainment of exposure | Ascertainment of exposure was by secure interview. | |
| Demonstration that outcome of interest was not present at start of study | It was demonstrated that outcome of interest was not present at the start of study. | |
| Comparability bias | Comparability of cohorts on the basis of the design or analysis | The study controls for inhaled corticosteroid withdrawal. |
| Outcome bias | Assessment of outcome | Outcome assessment was by self-report. |
| Was follow-up long enough for outcomes to occur | Follow-up duration may have been sufficient for outcomes of interest to occur. | |
| Adequacy of follow-up of cohorts | There was complete follow-up of participants, with all subjects accounted for. | |
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