Table.

GRADE Evaluation of interventions for Constipation: opioid antagonists in people prescribed opioids.

Important outcomes	Frequency of bowel movements
Studies (Participants)	Outcome	Comparison	Type of evidence	Quality	Consistency	Directness	Effect size	GRADE	Comment
What are the effects of opioid antagonists for constipation in people prescribed opioids?
4 (1693)	Frequency of bowel movements	Alvimopan versus placebo or no treatment	4	–1	0	–1	0	Low	Quality point deducted for weak methods (1 of 4 RCTs at low risk of bias, diverse response criteria in analysis); directness point deducted for unclear generalisability (all based in secondary/tertiary care, all in chronic non-malignant pain)
6 (1610)	Frequency of bowel movements	Methylnaltrexone versus placebo/no treatment	4	–1	–1	0	0	Low	Quality point deducted for weak methods (3 of 6 RCTs at low risk of bias, diverse response criteria in analysis); consistency point deducted for significant heterogeneity
5 (955)	Frequency of bowel movements	Naloxone versus placebo/no treatment	4	–2	0	0	0	Low	Quality points deducted for weak methods (2 of 4 RCTs at low risk of bias, diverse response criteria in analysis, no ITT analysis in 1 RCT) and incomplete reporting of results

We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.