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Chronic obstructive pulmonary disease — SCE Respiratory MCQ

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HardStatisticsChronic obstructive pulmonary diseaseSCE Respiratory

A regional respiratory medicines committee reviews a placebo-controlled randomised trial of 12 months of prophylactic azithromycin in 1,200 people with COPD who continued to have at least 4 sputum-producing exacerbations annually despite optimised inhaled and non-pharmacological management. Participants with bronchiectasis, prolonged QT interval or positive mycobacterial cultures were excluded. Forty-six per cent were current smokers. The primary outcome was the annualised exacerbation rate. In the overall population, the rate ratio with azithromycin was 0.82 (95% confidence interval [CI] 0.70–0.96). Twelve baseline subgroup analyses were reported without adjustment for multiplicity. Smoking status was not a prespecified subgroup. The rate ratio was 0.68 (95% CI 0.52–0.89) in current smokers and 0.91 (95% CI 0.75–1.10) in former or never-smokers. The treatment-by-smoking interaction ratio was 0.75 (95% CI 0.53–1.06; P for interaction=0.11). Antimicrobial resistance was assessed at 12 months, but longer-term outcomes were not collected. The committee is asked whether these results justify immediately changing local eligibility for prophylactic azithromycin. Which is the most appropriate recommendation?

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Correct answer: A — Retain current eligibility pending guideline review, because the post hoc subgroup evidence is insufficient

NICE currently recommends considering prophylactic azithromycin for selected people with COPD who do not smoke, remain exacerbation-prone despite optimised management and undergo specified safety and microbiological assessment. A local committee should not immediately extend eligibility beyond that recommendation on the basis of this analysis. The overall trial result supports an average reduction in exacerbations, but it does not establish a smoking-specific treatment effect. Smoking status was one of 12 unadjusted, non-prespecified subgroup analyses, increasing the risk of a chance finding. Moreover, significance within current smokers but not within non-smokers is not evidence that treatment effects differ. That requires direct assessment of interaction; here, the interaction CI includes no interaction and P=0.11. Conversely, failure to demonstrate interaction does not prove identical effects or justify automatically applying the result to a population excluded by current guidance. The absence of outcomes beyond 12 months also leaves the longer-term benefit–resistance balance unresolved. A overinterprets a within-subgroup confidence interval. B and D commit the same error by comparing subgroup-specific significance rather than effects directly. C treats a non-significant interaction as proof of homogeneity and disregards current UK eligibility criteria. The findings could prompt formal guideline reassessment or a confirmatory study, but they are insufficient for immediate local expansion.

Reference: Chronic obstructive pulmonary disease in over 16s: diagnosis and management — Recommendations (Published 5 December 2018; updated 26 July 2019) — https://www.nice.org.uk/guidance/ng115/chapter/Recommendations CONSORT 2025 explanation and elaboration: updated guideline for reporting randomised trials (14 April 2025) — https://www.bmj.com/content/389/bmj-2024-081124