TABLE 3

GRADE (grading of recommendations assessment, development and evaluation) evidence profile: impact of xanthines on change from baseline in forced expiratory volume in 1 s (FEV₁) and risk of adverse events in chronic obstructive pulmonary disease (COPD) patients

	Quality assessment: impact of xanthines in COPD					Quality
	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Quality
Change from baseline in FEV₁
Should doxofylline versus theophylline be used in COPD patients?	Serious^#	Not serious	Not serious	Serious^¶	Dose response gradient	⊕⊕⊕○ Moderate
Should doxofylline versus aminophylline be used in COPD patients?	Serious^#	Not serious	Not serious	Serious^¶	Dose response gradient	⊕⊕⊕○ Moderate
Should doxofylline versus bamiphylline be used in COPD patients?	Very serious^#	Not serious	Not serious	Not serious	None	⊕⊕○○ Low
Should theophylline versus aminophylline be used in COPD patients?	Very serious^#	Not serious	Serious⁺	Serious^¶	Publication bias strongly suspected^§	⊕○○○ Very low
Should theophylline versus bamiphylline be used in COPD patients?	Very serious^#	Not serious	Very serious^ƒ	Not serious	Very strong association, publication bias strongly suspected^##	⊕○○○ Very low
Should aminophylline versus bamiphylline be used in COPD patients?	Very serious^#	Not serious	Very serious^ƒ	Not serious	Very strong association, publication bias strongly suspected^##	⊕○○○ Very low
Risk of adverse events
Should doxofylline versus theophylline be used in COPD patients?	Serious^#	Not serious	Not serious	Not serious	Strong association, dose response gradient	⊕⊕⊕⊕ High
Should doxofylline versus aminophylline be used in COPD patients?	Serious^#	Not serious	Not serious	Not serious	Very strong association, dose response gradient	⊕⊕⊕⊕ High
Should doxofylline versus bamiphylline be used in COPD patients?	Very serious^#	Not serious	Serious⁺	Serious^¶	Publication bias strongly suspected^§	⊕○○○ Very low
Should theophylline versus aminophylline be used in COPD patients?	Very serious^#	Not serious	Serious⁺	Serious ^¶	Publication bias strongly suspected^§	⊕○○○ Very low
Should theophylline versus bamiphylline be used in COPD patients?	Very serious^#	Not serious	Very serious^ƒ	Serious^¶	Publication bias strongly suspected^##	⊕○○○ Very low
Should aminophylline versus bamiphylline be used in COPD patients?	Very serious^#	Not serious	Very serious^ƒ	Serious^¶	Publication bias strongly suspected^##	⊕○○○ Very Low

GRADE working group grades of evidence: high quality (we are very confident that the true effect lies close to that of the estimate of the effect); moderate quality (we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different); low quality (our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect); very low quality (we have very little confidence in the effect estimate, the true effect is likely to be substantially different from the estimate of effect). ^#: confirmed by Jadad score values; ^¶: credible intervals cross the threshold between recommending and not recommending treatment; ⁺: drugs tested head-to-head in a small population; ^§: data from direct comparison of small studies; ^ƒ: drugs not tested head-to-head; ^##: data from indirect comparison of small studies.