This review concluded that oxymorphone was superior to placebo for the treatment of chronic non-malignant pain and that it may be effective for pain control in cancer. The conclusions should be treated with some caution given a number of limitations in the review and that all the included trials conducted by the same pharmaceutical company.

To assess the effectiveness of controlled release oxymorphone for the relief of chronic pain.

The following databases were searched: MEDLINE (dates not provided), EMBASE (dates not provided) and the Cochrane Central Register of Controlled Trials (CENTRAL, 2007). Search terms were reported. Reference lists of retrieved articles and other relevant literature, such as pain or opioid reviews, were also scanned. Only full journal publications in English were included in the review.

To be eligible for the review, studies had to be trials of oxymorphone for the treatment of chronic pain and be of a medium or high quality study design. The review assessed changes in pain intensity scores.

Across the included trials, patients had chronic lower back pain, osteoarthritis or chronic cancer pain. The five trials of non-malignant pain compared oxymorphone to placebo or to both placebo and active drug. Two trials were of long-term duration (12 weeks) and four trials were of a short-term nature (two to four weeks). Doses of oxymorphone varied. Two trials used a study design whereby patients were enrolled and titrated to an optimal analgesic dose in an open-label period and only those responding were randomised to the double blind period of the trial.

Each study was assessed independently by two reviewers.

A published checklist was adapted for use in the review. Internal validity components were: allocation procedure; concealment of allocation; blinding of participants, caregivers and study personnel; blinding of outcome assessors; comparability at baseline; identical treatment apart from the intervention and accounting for all participants; and use of intention to treat (ITT) analysis. Lower quality trials were excluded (two non randomised studies and one single-dose trial). External validity was assessed in terms of relevance to clinical practice and was graded high, medium or low.

Each trial was assessed independently by two reviewers.

A specific form was designed and data were extracted for each trial by two reviewers independently. For each trial, treatment effect was expressed as a weighted mean difference. Standard errors were extracted or calculated as appropriate.

Trials were pooled using random-effects meta-analysis to compare oxymorphone and placebo in terms of pain intensity. Heterogeneity was assessed using the Χ² and I² statistics.

Six RCTs met the inclusion criteria for the review (n=1,489 participants randomised, of which 1,426 patients completed at least one pain assessment and were included in intention-to-treat analyses; 831 patients completed the trials). Three trials received a high quality score, and three trials a medium quality score. Sample size estimations were reported in five trials. Methods for randomisation and allocation concealment were reported in four trials. External validity was rated high in the one trial of malignant pain, medium in three trials and low in two trials.

Oxymorphone in chronic non-malignant pain (five RCTs; n=1,384 patients analysed): The analgesic effect of 20mg of oxymorphone did not differ from placebo (one trial). Pain intensity was significantly reduced for oxycodone compared to placebo groups for doses of: 40mg (-12.41, 95% CI -21.42 to -3.39; two RCTs) with considerable heterogeneity; doses of 80mg (-15.27, 95% CI -21.59 to -8.95; four trials) with considerable heterogeneity; and doses of 100mg (-12.20, 95% CI -20.90 to -3.50; one RCT). Most of the adverse events were those commonly observed with opioid treatment, with constipation occurring at the highest rate. The authors stated that the drop-out rates due to adverse events were high in trials of non-malignant pain (rates were above 30% in three trials).

Oxymorphone in malignant pain (one RCT; n=42 randomised patients): In this crossover trial, pain was well controlled and indistinguishable for oxymorphone and oxycodone. Adverse events were mild to moderate and related to the opioids.

Oxymorphone was superior to placebo for the treatment of chronic non-malignant pain. There was some limited evidence to suggest that it was effective for pain control in cancer.

This review had broad inclusion criteria for participants, intervention and study design. Outcome criteria did not appear to be pre-specified. Searching included electronic databases (but not all search dates were specified) and other methods. The exclusion of studies in languages other than English may have led to studies being missed; the exclusion of unpublished studies could have led to publication bias. Two authors were involved in study selection, data extraction and validity assessment, which helped to minimise bias in the review process.

Validity was assessed and low quality trials were excluded from the review. However, the impact of quality on the results was not fully explored. Meta-analysis may not have been appropriate given differences in the study designs.

These issues combined with the fact that the included trials were of variable quality, some trials had high drop-out rate and all included trials were conducted by the same pharmaceutical company (funded by Endo Pharmaceuticals, manufacturers of oxymorphone), imply that the conclusions of the review should be treated with some caution.

Practice: The authors did not state any implications for practice.

Research: The authors stated that studies on the clinical pharmacology of oxymorphone and studies of the impact of genetic factors on pharmacology are required in addition to drug interaction studies. Additional studies are needed to compare oxymorphone with morphine, especially in patients with cancer. Dose conversion ratios for other opioids or opioid formulations need to be established in head-to-head comparisons. Placebo controlled studies may be conducted in patients with cancer under certain conditions (unspecified).

Not stated

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.