title: Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events? The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Efficacy and Safety of Dutasteride in Chinese Adults with Symptomatic Benign Prostatic Hyperplasia Efficacy and Safety of Dutasteride in Chinese Adults with Symptomatic Benign Prostatic Hyperplasia : A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study with an Open-Label Extension. Natural history of prostatism: risk factors for acute urinary retention. Comparison of α-Blocker Monotherapy and α-Blocker plus 5α-Reductase Inhibitor Combination Therapy Based on Prostate Volume for Treatment of Benign Prostatic Hyperplasia Efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia. The effects of dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the CombAT study. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia.
abstract: CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P<.001 ; chi2 test ) . Logistic regression analyses indicated that funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data BACKGROUND Combination therapy with dutasteride and tamsulosin provides significantly greater benefit than either monotherapy for various patient-reported outcomes in men with moderate-to-severe lower urinary tract symptoms ( LUTS ) due to benign prostatic hyperplasia ( BPH ) and prostatic enlargement . OBJECTIVE To investigate whether combination therapy is more effective than either monotherapy in reducing the relative risk for acute urinary retention ( AUR ) , BPH-related surgery , and BPH clinical progression over 4 yr in men at increased risk of progression . DESIGN , SETTING , AND PARTICIPANTS The Combination of Avodart and Tamsulosin ( CombAT ) study was a 4-yr , multicenter , r and omised , double-blind , parallel-group study in 4844 men > or = 50 yr of age with a clinical diagnosis of BPH , International Prostate Symptom Score > or = 12 , prostate volume > or = 30 cm(3 ) , prostate-specific antigen 1.5 - 10 ng/ml , and maximum urinary flow rate ( Q(max ) ) > 5 and < or = 15 ml/s with minimum voided volume > or = 125 ml . INTERVENTION Oral daily tamsulosin , 0.4 mg ; dutasteride , 0.5 mg ; or a combination of both . MEASUREMENTS The 4-yr primary end point was time to first AUR or BPH-related surgery . Secondary end points included BPH clinical progression , symptoms , Q(max ) , prostate volume , safety , and tolerability . RESULTS AND LIMITATIONS Combination therapy was significantly superior to tamsulosin monotherapy but not dutasteride monotherapy at reducing the relative risk of AUR or BPH-related surgery . Combination therapy was also significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression . Combination therapy provided significantly greater symptom benefit than either monotherapy at 4 yr . Safety and tolerability of combination therapy was consistent with previous experience with dutasteride and tamsulosin monotherapies , with the exception of an imbalance in the composite term of cardiac failure among the three study arms . The lack of placebo control is a study limitation . CONCLUSIONS The 4-yr CombAT data provide support for the long-term use of dutasteride and tamsulosin combination therapy in men with moderate-to-severe LUTS due to BPH and prostatic enlargement . CLINICAL TRIALS.GOV IDENTIFIER : NCT00090103 ( http://www . clinical trials.gov/ct2/show/NCT00090103 ) Abstract Background : Dutasteride is a dual inhibitor of type I and type II 5α-reductases and provides nearly complete suppression of dihydrotestosterone , which plays a key role in the aetiology and development of benign prostatic hyperplasia ( BPH ) . Most knowledge about the efficacy and safety of dutasteride in BPH derives from three pivotal phase III studies conducted primarily in Caucasian population s. Objective : This study aim ed to evaluate the efficacy and safety of dutasteride in Chinese adults with symptomatic BPH . Methods : This was a r and omized , double-blind , parallel-group , placebo-controlled study conducted over 6 months , followed by an open-label extension of 12 months . A total of 253 BPH subjects with a total prostate volume ( TPV ) of ≥30 cm3 , a maximal urinary flow rate ( Qmax ) between 5 and 15 mL/s , and an American Urology Association Symptom Index ( AUA-SI ) score of ≥12 units were r and omized to dutasteride 0.5 mg/day orally or matching placebo treatment in a 1 : 1 ratio . After 6 months , eligible subjects who volunteered to enter the open-label extension received dutasteride 0.5 mg/day orally . Changes in TPV , Qmax and AUA-SI as well as drug safety were evaluated . Results : Dutasteride significantly reduced mean TPV compared with placebo at 3 and 6 months ( both p<0.05 ) . At 6 months , mean TPV decreased by 17.14 % versus 3.71 % in the dutasteride and placebo groups , respectively . Numerically higher improvements in Qmax and AUA-SI were observed in the dutasteride group at 3 and 6 months , but there was no statistically significant difference between treatment groups . However , ad hoc analysis indicated that , at 6 months , significantly higher proportions of subjects in the dutasteride group experienced a Qmax improvement of ≥3 mL/s , or an AUA-SI improvement of ≥1 unit , compared with the placebo group ( both p<0.05 ) . According to these criteria , the Qmax responder rates were 33.63 % and 19.83 % in the dutasteride- and placebo-treated groups , respectively , and the AUA-SI responder rates were 87.61 % and 76.92 % , respectively . During the open-label extension , continuous improvements in TPV , Qmax and AUA-SI were noted in both groups . Dutasteride was well tolerated with a low incidence of treatment-related adverse events over 18 months . Conclusion : Dutasteride was effective compared with placebo in the treatment of symptomatic BPH among Chinese patients . The efficacy data from trials involving subjects of different ethnic origins showed some similarities . Dutasteride was generally well tolerated during the study period BACKGROUND Dutasteride is a dual inhibitor of type I and type II 5α-reductases and provides nearly complete suppression of dihydrotestosterone , which plays a key role in the aetiology and development of benign prostatic hyperplasia ( BPH ) . Most knowledge about the efficacy and safety of dutasteride in BPH derives from three pivotal phase III studies conducted primarily in Caucasian population s. OBJECTIVE This study aim ed to evaluate the efficacy and safety of dutasteride in Chinese adults with symptomatic BPH . METHODS This was a r and omized , double-blind , parallel-group , placebo-controlled study conducted over 6 months , followed by an open-label extension of 12 months . A total of 253 BPH subjects with a total prostate volume ( TPV ) of ≥30 cm3 , a maximal urinary flow rate ( Qmax ) between 5 and 15 mL/s , and an American Urology Association Symptom Index ( AUA-SI ) score of ≥12 units were r and omized to dutasteride 0.5 mg/day orally or matching placebo treatment in a 1 : 1 ratio . After 6 months , eligible subjects who volunteered to enter the open-label extension received dutasteride 0.5 mg/day orally . Changes in TPV , Qmax and AUA-SI as well as drug safety were evaluated . RESULTS Dutasteride significantly reduced mean TPV compared with placebo at 3 and 6 months ( both p<0.05 ) . At 6 months , mean TPV decreased by 17.14 % versus 3.71 % in the dutasteride and placebo groups , respectively . Numerically higher improvements in Qmax and AUA-SI were observed in the dutasteride group at 3 and 6 months , but there was no statistically significant difference between treatment groups . However , ad hoc analysis indicated that , at 6 months , significantly higher proportions of subjects in the dutasteride group experienced a Qmax improvement of ≥3 mL/s , or an AUA-SI improvement of ≥1 unit , compared with the placebo group ( both p<0.05 ) . According to these criteria , the Qmax responder rates were 33.63 % and 19.83 % in the dutasteride- and placebo-treated groups , respectively , and the AUA-SI responder rates were 87.61 % and 76.92 % , respectively . During the open-label extension , continuous improvements in TPV , Qmax and AUA-SI were noted in both groups . Dutasteride was well tolerated with a low incidence of treatment-related adverse events over 18 months . CONCLUSION Dutasteride was effective compared with placebo in the treatment of symptomatic BPH among Chinese patients . The efficacy data from trials involving subjects of different ethnic origins showed some similarities . Dutasteride was generally well tolerated during the study period PURPOSE We determined the occurrence of and risk factors for acute urinary retention in the community setting . MATERIAL S AND METHODS A cohort of 2,115 men 40 to 79 years old was r and omly selected from an enumeration of the Olmsted County , Minnesota population ( 55 % response rate ) . Participants completed a previously vali date d baseline question naire that assessed symptom severity , and voided into a portable urometer to measure peak urinary flow rates . A 25 % r and om sub sample underwent transrectal sonographic imaging of the prostate to determine prostate volume . Followup was performed through a retrospective review of community medical records to determine the occurrence of acute urinary retention in the subsequent 4 years . RESULTS During the 8,344 person-years of followup 57 men had a first episode of acute urinary retention ( incidence 6.8/1,000 person-years , 95 % confidence interval [ CI ] 5.2 , 8.9 ) . Among men with no to mild symptoms ( American Urological Association symptom index score 7 or less ) the incidence of acute urinary retention increased from 2.6/1,000 person-years among men 40 to 49 years old to 9.3/1,000 person-years among men 70 to 79 years old . By contrast , rates increased from 3.0/1,000 person-years for men 40 to 49 years old to 34.7/1,000 person-years among men 70 to 79 years old among men with moderate to severe symptoms ( American Urological Association symptom index score greater than 7 ) . Men with depressed peak urinary flow rate ( less than 12 ml . per second ) were at 4 times the risk of acute urinary retention compared with men with urinary flow rates greater than 12 ml . per second ( 95 % CI 2.3 , 6.6 ) . Men with an enlarged prostate ( greater than 30 ml . ) experienced a 3-fold increase in risk ( 95 % CI 1.0 , 9.0 , p = 0.04 ) . CONCLUSIONS Lower urinary tract symptoms , depressed peak urinary flow rates , enlarged prostates and older age are associated with an increased risk of acute urinary retention in community dwelling men . These findings may help to identify men at increased risk of acute urinary retention in whom closer evaluation may be warranted OBJECTIVE : This study compared α-blocker monotherapy with combination therapy involving an α-blocker and a 5-α reductase inhibitor for benign prostatic hyperplasia ( BPH ) , according to baseline prostate volume . METHODS : Korean men diagnosed with BPH were r and omized to 12 months ' treatment with 0.2 mg tamsulosin or 0.2 mg tamsulosin plus 0.5 mg dutasteride . Prostate specific antigen ( PSA ) , prostate volume , transition zone volume ( TZV ) , International Prostate Symptom Score ( IPSS ) , maximal urinary flow rate ( Q max ) , postvoid residual urine volume and sexual function were assessed at baseline and after 12 months ' treatment . Variables were analysed based on baseline prostate volumes of ≤ 35 ml or > 35 ml . RESULTS : In total , 216 men with BPH were included . Combination therapy result ed in significant improvements in prostate volume , TZV , PSA , IPSS and Q max , which were most pronounced in men with a prostate volume > 35 ml . CONCLUSIONS : Tamsulosin monotherapy was sufficient treatment for BPH in Korean men with a prostate volume ≤ 35 ml . Combination tamsulosin and dutasteride therapy provided greater benefits than tamsulosin monotherapy in men with BPH whose prostate volume was > 35 ml OBJECTIVES To assess the efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia ( BPH ) . METHODS This was a r and omized , double-blind , placebo-controlled , parallel-group study . A total of 378 subjects with clinical BPH having an International Prostate Symptom Score ( IPSS ) of 8 points or greater , a prostate volume of 30 mL or greater , and a maximal urinary flow rate ( Qmax ) of 15 mL/s or less were r and omized to receive placebo or dutasteride once daily for 52 weeks . Subjects were stratified according to tamsulosin use at baseline . The numbers of subjects with and without tamsulosin  use were 242 and 136 , respectively . IPSS , Qmax , prostate volume and drug safety were evaluated . RESULTS Continued improvement in IPSS was noted in the dutasteride group , and dutasteride significantly decreased IPSS compared with placebo . At week 52 , dutasteride significantly improved Qmax and prostate volume compared with placebo . Drug-related sexual function events in the dutasteride group were infrequent and generally were not treatment limiting . CONCLUSIONS Dutasteride improves urinary symptoms and flow rate and reduces prostate volume . In Japanese men with BPH , it is effective and generally well tolerated during the one-year treatment period PURPOSE We investigated whether combination therapy with dutasteride and tamsulosin is more effective than either monotherapy alone for improving symptoms and long-term outcomes in men with moderate to severe lower urinary tract symptoms and prostatic enlargement ( 30 cc or greater ) . We report preplanned 2-year analyses . MATERIAL S AND METHODS The CombAT study is an ongoing , multicenter , r and omized , double-blind , parallel group study . Men 50 years or older with a clinical diagnosis of benign prostatic hyperplasia , International Prostate Symptom Score 12 points or greater , prostate volume 30 cc or greater , total serum prostate specific antigen 1.5 ng/ml or greater to 10 ng/ml or less and peak urinary flow greater than 5 to 15 ml per second or less with a minimum voided volume of 125 ml or greater were r and omized to 0.5 mg dutasteride , 0.4 mg tamsulosin or the combination once daily for 4 years . Symptoms were assessed every 3 months and peak urinary flow was assessed every 6 months . The primary end point at 2 years was the change in International Prostate Symptom Score from baseline . RESULTS Combination therapy result ed in significantly greater improvements in symptoms vs dutasteride from month 3 and tamsulosin from month 9 , and in benign prostatic hyperplasia related health status from months 3 and 12 , respectively . There was a significantly greater improvement from baseline in peak urinary flow for combination therapy vs dutasteride and tamsulosin monotherapies from month 6 . There was a significant increase in drug related adverse events with combination therapy vs monotherapies , although most did not result in the cessation of therapy . CONCLUSIONS In men with moderate to severe lower urinary tract symptoms and prostate enlargement ( 30 cc or greater ) combination therapy provides a significantly greater degree of benefit than tamsulosin or dutasteride monotherapy OBJECTIVES To study the efficacy and safety of dutasteride , a dual inhibitor of the 5-alpha-reductase isoenzymes types I and II . METHODS A total of 4325 men ( 2951 completed ) with clinical benign prostatic hyperplasia , moderate to severe symptoms ( American Urological Association-Symptom Index score of 12 points or greater ) , a peak flow rate of 15 mL/s or less , a prostate volume of 30 cm3 or greater ( as measured by transrectal ultrasonography ) , and a serum prostate-specific antigen level of 1.5 to 10.0 ng/mL ( inclusive ) were enrolled into three identical clinical trials and r and omized to 0.5 mg dutasteride daily or placebo . After a 1-month , single-blind , placebo lead-in , patients were followed up for 24 months in a double-blind trial with multiple interval assessment s. RESULTS At 24 months , serum dihydrotestosterone was reduced from baseline by a mean of 90.2 % ( median -93.7 % ; P < 0.001 ) , and the total prostate and transition zone volumes were reduced by a mean of 25.7 % and 20.4 % , respectively ( P < 0.001 ) . The symptom score was improved by as early as 3 months , with pooled significance from 6 months onward ( P < 0.001 ) and a reduction of 4.5 points ( 21.4 % ) at 24 months ( P < 0.001 ) . The maximal flow rate improved significantly from 1 month ( P < 0.01 ) , with an increase of 2.2 mL/s reported at 24 months ( P < 0.001 ) . Hence , the risk reduction of acute urinary retention was 57 % and the risk reduction of benign prostatic hyperplasia-related surgical intervention was 48 % compared with placebo . The drug was well tolerated . CONCLUSIONS Dutasteride is a potent inhibitor of dihydrotestosterone production that is safe and effective in terms of the reduction of prostate volume and symptoms , flow rate improvement , and the reduction of the risk of acute urinary retention and surgery during a 24-month study period
target: When comparing dutasteride with finasteride , no significant differences in symptom improvement or the rate of adverse events were observed .
  Conclusions Dutasteride can be used to improve urinary symptoms ( IPSS and Qmax ) and reduce TPV but with awareness of its potential adverse events .
background: Purpose To determine the efficacy and safety of dutasteride , alone or in combination , versus a placebo or control , used for the treatment of benign prostatic hyperplasia .