***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Strong opioids are recommended for treating severe cancer pain in the advanced stages of the disease . Few data are available concerning the efficacy of buprenorphine in cancer pain . We compared transdermal buprenorphine 70 microg/h ( BUP TDS ) to placebo in an enriched design study . Opioid-tolerant patients with cancer pain requiring strong opioids in the dose range of 90 - 150 mg/d oral morphine equivalents entered a two-week run-in phase , during which they were converted to BUP TDS .  Patients who could be stabilized on BUP TDS were r and omized to BUP TDS or placebo patch for a two-week maintenance phase . Rescue medication ( buprenorphine sublingual tablets 0.2 mg ) was allowed as required . Response was defined as a mean pain intensity of < 5 ( 0 - 10 scale ) and a mean daily buprenorphine sublingual tablet intake of < or = 2 tablets during the maintenance phase . Of 289 patients who entered the run-in phase , 100 discontinued treatment due to lack of efficacy or adverse events ; 189 patients continued treatment in the maintenance phase ( 94 BUP TDS , 95 placebo ) , of whom 31 discontinued treatment ( 7 BUP TDS , 24 placebo ) . A significant difference in the number of treatment responders was observed : 70 BUP TDS ( 74.5 % , 65.7 - 83.3 ) vs. 47 placebo ( 50 % , 39.9 - 60.1 ) ( P=0.0003 ) . This result was supported by a lower daily pain intensity , lower intake of buprenorphine sublingual tablets and fewer dropouts in the BUP TDS group . The incidence of adverse events was slightly higher for BUP TDS . In conclusion , BUP TDS 70 microg/h is an efficacious and safe treatment for patients with severe cancer pain This large , open-label , r and omized , parallel-group , multicenter study compared two oral sustained-release opioids (SROs)--AVINZA ( A-MQD ) , morphine sulfate extended-release capsules given once a day , and OxyContin ( O-ER ) , oxycodone modified-release tablets given twice a day -- in SRO-naive subjects ages 30 to 70 with chronic , moderate to severe low back pain . Of the 392 subjects enrolled and r and omized , 266 ( 132 in the A-MQD group and 134 in the O-ER group ) completed the  opioid dose titration phase and entered an eight-week evaluation phase . During the evaluation phase , A-MQD achieved significantly better pain control than O-ER , as demonstrated by a greater decrease from baseline in pain scores obtained four times daily during weeks one , four , and eight ( p = 0.002 ) . The number of breakthrough-pain rescue medication doses adjusted for the number of patient days was significantly lower in the A-MQD group ( p < 0.0001 ) . Better pain control with A-MQD was achieved with a significantly lower daily opioid dose than with O-ER ( mean 69.9 mg and 91 mg morphine equivalents , respectively ; p = 0.0125 ) . Quality of sleep was significantly better with A-MQD for the entire evaluation phase ( p = 0.0026 ) . The incidence and severity of elicited opioid side effects were similar in the two groups . This trial demonstrated that once-daily A-MQD provides consistent around-the-clock pain relief in patients with low back pain . In patients who completed opioid dose titration , A-MQD was significantly better than O-ER for reducing pain and improving sleep , while requiring a lower daily opioid dose OBJECTIVE This study compared the efficacy and safety profile of buprenorphine transdermal delivery system ( BTDS ) and placebo in subjects with persistent noncancer-related pain who required opioid analgesics .  METHODS This was a multicenter , double-blind , parallel-group study in adult subjects ( age > /=18 years ) with at least a 2-month history of noncancer-related pain for which they received oral opioid combination agents .  The study employed a maintenance-of-analgesia , or r and omized-withdrawal , design . During a 7- to 21-day open-label run-in phase , all subjects received BTDS , titrated as needed . Subjects who achieved stable pain control and were able to tolerate BTDS in the run-in phase were r and omly assigned to continue BTDS at the dose achieved during the run-in phase or to receive placebo for up to 14 days . Acetaminophen 500-mg tablets were provided as escape ( rescue ) medication . Subjects completed the study on day 14 or when they met predefined criteria for ineffective treatment : requiring > 1 g of acetaminophen as escape medication on any day of the double-blind evaluation phase , requiring a change in study drug dose , having difficulty keeping the patch affixed , or discontinuing because of ineffective treatment without meeting any of the first 3 criteria . The primary efficacy variable was the proportion of subjects with ineffective treatment . Secondary efficacy variables were the time to ineffective treatment ; the proportion of subjects who reached ineffective treatment or discontinued for any reason other than ineffective treatment ; and the amount of escape medication used . Assessment of the safety profile was based on adverse events and changes in vital signs and physical and laboratory findings . RESULTS Five hundred eighty-eight subjects entered the open-label run-in phase , and 267 ( 129 BTDS , 138 placebo ) were subsequently r and omized to doubleblind treatment . Demographic characteristics were similar between the double-blind BTDS and placebo groups ( 61.2 % and 63.8 % female , respectively ; 99.2 % and 98.6 % white ; mean [ SD ] age , 56.2 [ 13.3 ] and 59.2 [ 11.5 ] years ) . In the primary efficacy analysis , the proportion of subjects with ineffective treatment was lower with BTDS than with placebo ( 51.2 % vs 65.0 % ; 95 % CI , 1.09 - 2.95 ) ; the odds of ineffective treatment were 1.79 times greater for placebo relative to BTDS ( P = 0.022 ) . In the secondary efficacy analyses , the median time from the first dose of double-blind study drug to ineffective treatment was significantly longer with BTDS than with placebo ( median , 10 vs 3 days ; P = 0.011 ) . The proportion of subjects who reached ineffective treatment or discontinued for reasons other than ineffective treatment was lower in the BTDS group compared with the placebo group ( 55.0 % vs 67.9 % ) ; the odds of ineffective treatment or discontinuation for a reason other than ineffective treatment was 1.76 times greater with placebo compared with BTDS ( P = 0.028 ) . The mean amount of escape medication used was significantly lower in the BTDS group than in the placebo group ( 1.7 vs 2.2 acetaminophen tablets per day ; P = 0.015 ) . The most common adverse events in the open-label run-in or double-blind phase occurring at a higher incidence with BTDS than with placebo were pruritus at the patch application site ( 9.3 % vs 5.1 % , respectively ) , headache ( 3.9 % vs 2.2 % ) , and somnolence ( 2.3 % vs 0.7 % ) . CONCLUSION In this population of adult subjects with persistent noncancer-related pain who required opioid therapy , BTDS use was associated with analgesic efficacy and was generally well tolerated . Results of this study were presented in part at the annual meeting of the American Pain Society , March 30-April 2 , 2005 , Boston , Massachusetts Abstract Objective : This multicenter , double-blind , placebo-controlled study using a r and omized withdrawal design evaluated the efficacy and safety of once-daily OROS hydromorphone ER in the treatment of opioid-tolerant patients with chronic moderate-to-severe low back pain ( LBP ) . Main outcome measures : The primary efficacy assessment was mean change in pain intensity based on patient diary Numeric Rating Scale ( NRS ) scores from baseline to final visit of the 12-week double-blind phase . Secondary endpoints included mean change from baseline to each visit in patient diary NRS scores ; and office NRS scores ; time to treatment failure ; Patient Global Assessment ; rescue medication use ; and Rol and Morris Disability Question naire total scores . Clinical Trial Registration : Trial registration : Clinical Trials.gov identifier : NCT00549042 . Results : For the primary outcome measure , hydromorphone ER  significantly reduced pain intensity compared to placebo ( p < 0.001 ) . Median diary NRS score change from baseline to endpoint was significantly lower for hydromorphone ER ( 0.2 units ) compared to placebo ( 1.2 units ) . A significantly higher proportion of hydromorphone ER ( 60.6 % ) vs. placebo ( 42.9 % ) patients had at least a 30 % reduction in diary NRS pain score from screening to endpoint ( p < 0.01 ) . Hydromorphone ER was well-tolerated , although 60 ( 13 % ) discontinued during the enrichment phase for adverse events and more active ( 9 , 6.7 % ) than placebo ( 4 , 3.0 % ) patients discontinued treatment for adverse events during the r and omized phase . Conclusions : These results provide evidence for the efficacy and safety of hydromorphone ER in opioid-tolerant patients with chronic moderate-to-severe LBP . Potential limitations include the shortened dose-conversion/titration phase , limiting the daily allowable dose of hydromorphone ER to 64 mg , and the allowance of limited rescue medication throughout the entire double-blind phase . Other trial design elements such as the use of an enrichment phase and the inclusion of only opioid tolerant patients may limit the generalizabilty of these results OBJECTIVE This study compared the efficacy and tolerability of a once-daily controlled-release formulation of hydromorphone ( OROS ) hydromorphone , Janssen-Cilag , Beerse , Belgium ) and twice-daily extended-release ( ER ) oxycodone in patients with chronic , moderate to severe osteoarthritis ( OA ) pain .  OROS hydromorphone is currently available only in Europe . METHODS Adults who met American College of Rheumatology clinical criteria for OA of the knee or hip with moderate to severe mean daily pain intensity despite chronic use of stable doses of NSAIDs or other nonsteroidal , nonopioid therapies were eligible for participation in this r and omized , open-label study . The study consisted of a 14-day dose-titration and stabilization phase and a 28-day maintenance phase . OROS hydromorphone and ER oxycodone were initiated at dosages of 8 mg QD and 10 mg BID , respectively . Patients maintained diaries in which they rated their pain ( from 0 = none to 3 = severe ) and pain relief ( from 0 = no relief to 4 = complete relief ) . Other assessment s completed every 14 days included patient and investigator global evaluations of treatment effectiveness ( scale from 1 = poor to 5 = excellent ) , the Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index , and the Medical Outcomes Study ( MOS ) Sleep Scale . Adverse events ( whether observed by study personnel , identified in response to question ing , or spontaneously reported ) and vital signs were monitored throughout the study . The primary efficacy measures were the mean pain relief score at end point and the time from initiation of treatment to the third day of moderate to complete pain relief , as reported in the patient diary . Noninferiority analyses were conducted on all primary and secondary efficacy variables . RESULTS One hundred thirty-eight patients ( 71 OROS hydromorphone , 67 ER oxycodone ) received treatment ( safety population ) , and 83 ( 60.1 % ) completed the study . Data from 124 patients were included in the efficacy analyses ; the majority of these patients were white ( 85.5 % ) and female ( 69.4 % ) , with a mean age of 63.6 years . The most commonly affected joint was the knee ( 79.8 % ) . At end point , the OROS hydromorphone group had a mean pain relief score of 2.3 ( median , 2.0 ) and the ER oxycodone group had a mean pain relief score of 2.3 ( median , 2.3 ) ( 95 % CI , -0.30 to infinity ) . The mean time to the third day of moderate to complete pain relief was 6.2 days ( median , 4.0 ) in the OROS hydromorphone group and 5.5 days ( median , 5.0 ) in the ER oxycodone group ( 95 % CI , -0.31 to infinity ) . Mean pain intensity decreased from baseline to end point by 0.6 point in the OROS hydromorphone group and by 0.4 point in the ER oxycodone group . Mean scores on the patient global evaluation improved by a respective 1.2 and 1.0 points ( median , 1 in both groups ) . Approximately two thirds of patients in each group ( 67.2 % and 66.7 % ) rated the overall effectiveness of treatment as good to excellent at end point . There were no statistically significant differences between groups in total WOMAC scores at end point , and similar improvements from baseline in the WOMAC physical function , stiffness , and pain scales were observed in both groups . Whereas MOS sleep outcomes scores improved from baseline in both groups , ORO 
    Output:
    
The network meta- analysis showed no statistically significant difference in change of pain intensity between morphine and oxycodone , methadone and oxymorphone .
No clear superiority in efficacy and tolerability of morphine over other opioids was found in pair-wise and network analyses .