Article type
Year
Abstract
Background: opioids are often prescribed for chronic non-cancer pain (CNCP). Thus far, systematic reviews have pooled different opioids assuming a common effect; however, the comparative effectiveness of individual opioids, and of long-acting (LA) versus short-acting (SA) opioids, on pain relief is uncertain.
Objectives: we conducted a network meta-analysis (NMA) to inform these issues.
Methods: we searched Embase, MEDLINE, CINAHL, AMED, PsycINFO and the Cochrane Central Registry of Controlled Trials (CENTRAL), from inception to March 2019, to identify trials that randomized CNCP patients to an oral or transdermal opioid versus placebo, or other opioids, and followed participants for four weeks or longer. We performed a frequentist NMA exploring effects on a 10 cm visual analogue scale for pain (1 cm is the minimally important difference) and assessed the quality of evidence using the GRADE approach (dichotomized as 'moderate-to-high' or 'low-to-very-low' quality of evidence). To optimize interpretation of NMA results, we used an innovative approach described in detail in another abstract submission; we categorized opioids first based on their effectiveness versus placebo and then versus other competing interventions, and finally according to GRADE quality of evidence ratings.
Results: we included 76 studies with 21,752 participants that evaluated 15 individual opioids, of which four were SA and 11 were LA. The surface under the cumulative ranking curve (SUCRA) method suggested codeine extended-release (ER; 94.2%) and oxymorphone-ER (88.1%) as the best opioids for pain relief. The quality of evidence for both these drugs relative to placebo was, however, low (Table 1). All comparisons supported by moderate-to-high-quality evidence demonstrated that opioids were more effective than placebo, but that none were superior to others. Low-to-very-low-quality evidence suggested that tramadol normal-release (NR), morphine-mixed (both NR and ER), oxycodone-NR and hydromorphone-ER, may be inferior to the most effective interventions (codeine-ER and oxymorphone-ER), but superior to placebo and tapentadol NR (which was not more effective than placebo). Low-quality evidence suggested a statistically significant, but clinically unimportant, advantage of SA versus LA opioids for pain relief (weighted mean difference 0.18 cm, 95% confidence interval 0.06 to 0.29).
Conclusions: our findings suggest that apparent differences in effectiveness between opioids, when ranked according to SUCRA, result from the failure to consider the quality of evidence. The new approach to interpreting results from an NMA that we used highlights its advantages relative to relying solely or largely on SUCRA values.
Patient or healthcare consumer involvement: clinicians using NMAs need to interpret results in the light of quality of evidence to prevent misleading inferences and ensure that patients are offered optimal treatment choices.
Objectives: we conducted a network meta-analysis (NMA) to inform these issues.
Methods: we searched Embase, MEDLINE, CINAHL, AMED, PsycINFO and the Cochrane Central Registry of Controlled Trials (CENTRAL), from inception to March 2019, to identify trials that randomized CNCP patients to an oral or transdermal opioid versus placebo, or other opioids, and followed participants for four weeks or longer. We performed a frequentist NMA exploring effects on a 10 cm visual analogue scale for pain (1 cm is the minimally important difference) and assessed the quality of evidence using the GRADE approach (dichotomized as 'moderate-to-high' or 'low-to-very-low' quality of evidence). To optimize interpretation of NMA results, we used an innovative approach described in detail in another abstract submission; we categorized opioids first based on their effectiveness versus placebo and then versus other competing interventions, and finally according to GRADE quality of evidence ratings.
Results: we included 76 studies with 21,752 participants that evaluated 15 individual opioids, of which four were SA and 11 were LA. The surface under the cumulative ranking curve (SUCRA) method suggested codeine extended-release (ER; 94.2%) and oxymorphone-ER (88.1%) as the best opioids for pain relief. The quality of evidence for both these drugs relative to placebo was, however, low (Table 1). All comparisons supported by moderate-to-high-quality evidence demonstrated that opioids were more effective than placebo, but that none were superior to others. Low-to-very-low-quality evidence suggested that tramadol normal-release (NR), morphine-mixed (both NR and ER), oxycodone-NR and hydromorphone-ER, may be inferior to the most effective interventions (codeine-ER and oxymorphone-ER), but superior to placebo and tapentadol NR (which was not more effective than placebo). Low-quality evidence suggested a statistically significant, but clinically unimportant, advantage of SA versus LA opioids for pain relief (weighted mean difference 0.18 cm, 95% confidence interval 0.06 to 0.29).
Conclusions: our findings suggest that apparent differences in effectiveness between opioids, when ranked according to SUCRA, result from the failure to consider the quality of evidence. The new approach to interpreting results from an NMA that we used highlights its advantages relative to relying solely or largely on SUCRA values.
Patient or healthcare consumer involvement: clinicians using NMAs need to interpret results in the light of quality of evidence to prevent misleading inferences and ensure that patients are offered optimal treatment choices.
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