Budget Impact and Cost-Effectiveness of Intravenous Meloxicam to Treat Moderate-Severe Postoperative Pain.

INTRODUCTION: This study assesses the budget impact and cost-effectiveness of intravenous meloxicam (MIV) to treat moderate-severe acute postoperative pain in adults. METHODS: A two-part Markov cohort model captured the pharmacoeconomic impact of MIV versus non-opioid intravenous analgesics (acetaminophen, ibuprofen, ketorolac) among a hypothetical adult cohort undergoing selected inpatient procedures and experiencing moderate-severe acute postoperative pain: Part 1 (postoperative hour 0 to discharge, cycled hourly), health states were defined by pain level. Pain transition rates, adverse event probabilities, and concomitant opioid utilization were derived from a network meta-analysis. Part 2 (discharge to week 52, cycled weekly), health states were defined by the presence/absence of pain-related readmission and opioid use disorder as determined by literature-based inputs relating to pain control outcomes. Healthcare utilization and direct medical costs were derived from an administrative claims database analysis. Primary outcomes were the incremental cost per member per month (PMPM) and cost per quality-adjusted life year (QALY) gained. Scenario, univariate, and probabilistic sensitivity analyses were conducted. The model assumed a private payer perspective in the USA (no discounting, 2019 US$). RESULTS: Modeled outcomes indicated MIV was associated with lower accumulated postoperative pain, fewer adverse events, and less opioid utilization for most procedures and comparators, with longer-term outcomes also generally favoring MIV. The budget impact of MIV was - $0.028 PMPM. From a cost-effectiveness perspective, MIV had lower costs and better outcomes for all comparisons except against ketorolac in orthopedic procedures where the former was cost-effective but not cost saving ($95,925/QALY). Scenario and sensitivity analyses indicated that modeled outcomes were robust to alternative inputs and underlying input uncertainty. Differences in direct medical costs were driven by reduced costs attributable to length of stay and opioid-related adverse drug events. CONCLUSION: MIV was associated with modeled clinical and economic benefits compared to commonly used non-opioid intravenous analgesics.

Economic Impact of Preoperative Meloxicam IV Administration in Total Knee Arthroplasty: A Randomized Trial Sub-Study.

We evaluated the economic impact associated with preoperative meloxicam IV 30 mg vs placebo administration among adult total knee arthroplasty (TKA) recipients enrolled in Phase IIIB NCT03434275 trial. Data on total hospital costs and length of stay (LOS) obtained from the trial were compared between meloxicam IV 30 mg and placebo groups. Patients in the meloxicam IV 30 mg vs placebo group (n = 93 vs 88) incurred an adjusted $2,266 (95% CI: -$1,035, $5,116; p = 0.1689) lower total hospital costs and an adjusted 8.6% (95% confidence interval [CI]: -2.0%, 18.1%; p = 0.1082) shorter LOS. While statistically non-significant, based on 95% CIs, the results from this sub-study may suggest a favorable impact associated with meloxicam IV 30 mg on hospital costs and LOS.

Safety and Efficacy of Perioperative Intravenous Meloxicam for Moderate-to-Severe Pain Management in Total Knee Arthroplasty: A Randomized Clinical Trial.

OBJECTIVE: To evaluate the effect of perioperative meloxicam IV 30 mg on opioid consumption in primary total knee arthroplasty (TKA). DESIGN: Multicenter, randomized, double-blind, placebo-controlled trial. SUBJECTS: In total, 181 adults undergoing elective primary TKA. METHODS: Subjects received meloxicam 30 mg or placebo via an IV bolus every 24 hours, the first dose administered prior to surgery as part of a multimodal pain management protocol. The primary efficacy parameter was total opioid use from end of surgery through 24 hours. RESULTS: Meloxicam IV was associated with less opioid use versus placebo during the 24 hours after surgery (18.9 ± 1.32 vs 27.7 ± 1.37 mg IV morphine equivalent dose; P < 0.001) and was superior to placebo on secondary endpoints, including summed pain intensity (first dose to 24 hours postdosing, first dose to first assisted ambulation, and first dose to discharge) and opioid use (48-72 hrs., 0-48 hrs., 0-72 hrs., hour 0 to end of treatment, and the first 24 hours after discharge). Adverse events (AEs) were reported for 69.9% and 92.0% of the meloxicam IV and placebo groups, respectively; the most common AEs were nausea (40% vs. 59%), vomiting (16% vs 22%), hypotension (14% vs 15%), pruritus (15% vs 11%), and constipation (11% vs 13%). CONCLUSIONS: Perioperative meloxicam IV 30 mg as part of a multimodal analgesic regimen for elective primary TKA reduced opioid consumption in the 24-hour period after surgery versus placebo and was associated with a lower incidence of AEs typically associated with opioid use.

Preoperative intravenous meloxicam for moderate-to-severe pain in the immediate post-operative period: a Phase IIIb randomized clinical trial in 55 patients undergoing primary open or laparoscopic colorectal surgery with bowel resection and/or anastomosis.

Aim: Evaluate safety/efficacy of intravenous meloxicam in a colorectal enhanced recovery after surgery protocol. Methods: Adults undergoing primary open or laparoscopic colorectal surgery with bowel resection and/or anastomosis received meloxicam IV 30 mg (n = 27) or placebo (n = 28) once daily beginning 30 min before surgery. Results: Adverse events: meloxicam IV, 85%; placebo, 93%. Adverse events commonly associated with opioids: 41 versus 61% - including nausea (33 vs 50%), vomiting (19 vs 18%) and ileus (4 vs 18%). Wound healing satisfaction scores (physician-rated), clinical laboratory findings and vital signs were similar in both groups. No anastomotic leaks were reported. Opioid consumption, postoperative pain intensity, length of stay and times to first bowel sound, first flatus and first bowel movement were significantly lower with meloxicam IV versus placebo. Most subjects (>92%) were satisfied with postoperative pain medication. Conclusion: Meloxicam IV was generally well tolerated and associated with decreased opioid consumption, lower resource utilization and functional benefits. Clinical Trial Registration: NCT03323385 (ClinicalTrials.gov).

Efficacy of non-opioid analgesics to control postoperative pain: a network meta-analysis.

BACKGROUND: The aim of this network meta-analysis (NMA) was to evaluate the safety and efficacy of intravenous (IV) Meloxicam 30 mg (MIV), an investigational non-steroidal anti-inflammatory drug (NSAID), and certain other IV non-opioid analgesics for moderate-severe acute postoperative pain. METHODS: We searched PubMed and CENTRAL for Randomized Controlled Trials (RCT) (years 2000-2019, adult human subjects) of IV non-opioid analgesics (IV NSAIDs or IV Acetaminophen) used to treat acute pain after abdominal, hysterectomy, bunionectomy or orthopedic procedures. A Bayesian NMA was conducted in R to rank treatments based on the standardized mean differences in sum of pain intensity difference from baseline up to 24 h postoperatively (sum of pain intensity difference: SPID 24). The probability and the cumulative probability of rank for each treatment were calculated, and the surface under the cumulative ranking curve (SUCRA) was applied to distinguish treatments on the basis of their outcomes such that higher SUCRA values indicate better outcomes. The study protocol was prospectively registered with by PROSPERO (CRD42019117360). RESULTS: Out of 2313 screened studies, 27 studies with 36 comparative observations were included, producing a treatment network that included the four non-opioid IV pain medications of interest (MIV, ketorolac, acetaminophen, and ibuprofen). MIV was associated with the largest SPID 24 for all procedure categories and comparators. The SUCRA ranking table indicated that MIV had the highest probability for the most effective treatment for abdominal (89.5%), bunionectomy (100%), and hysterectomy (99.8%). MIV was associated with significantly less MME utilization versus all comparators for abdominal procedures, hysterectomy, and versus acetaminophen in orthopedic procedures. Elsewhere MME utilization outcomes for MIV were largely equivalent or nominally better than other comparators. Odds of ORADEs were significantly higher for all comparators vs MIV for orthopedic (gastrointestinal) and hysterectomy (respiratory). CONCLUSIONS: MIV 30 mg may provide better pain reduction with similar or better safety compared to other approved IV non-opioid analgesics. Caution is warranted in interpreting these results as all comparisons involving MIV were indirect.

Risk of hospitalization for common neonatal morbidities in preterm and term infants: assessing the impact of one or more major congenital anomalies.

OBJECTIVE: To analyze the impact of ≥1 major congenital anomaly (CA) on risk and hospitalization for common neonatal morbidities. STUDY DESIGN: Retrospective infant cohort: 241,033 preterm and 3,446,156 term singletons in the US Premier Healthcare database (2006-2013) with up to 1-year follow-up. Discharge records were searched for ≥1 CA and neonatal morbidities. RESULTS: Five morbidities demonstrated strong increasing rates as GA decreased. RRs in preterm infants with CAs relative to those without CAs were: RDS (2.17, 95% CI 2.14-2.21), sepsis (2.42, 95% CI 2.37-2.46), apnea (2.04, 95% CI 2.01-2.07), infectious diseases (2.37, 95% CI 2.34-2.41), and hyperbilirubinemia (1.25, 95% CI 1.24-1.26). Median length of NICU stay (days) was consistently longer in infants with ≥1 CA relative to infants without CA during each GA period. CONCLUSIONS: Preterm infants with ≥1 major CA have increased risk of hospitalization for common morbidities, implying compromised neonatal health regardless of CA type.

Incremental Cost of Prematurity by Week of Gestational Age.

Objective This study was aimed to compare health care costs and utilization at birth through 1 year, between preterm and term infants, by week of gestation. Methods A cross-sectional study of infants born at ≥ 23 weeks of gestational age (GA) at Kaiser Permanente Northern California facilities between 2000 and 2011, using outcomes data from an internal neonatal registry and cost estimates from an internal cost management database. Adjusted models yielded estimates for cost differences for each GA group. Results Infants born at 25 to 37 weeks incur significantly higher birth hospitalization costs and experience significantly more health care utilization during the initial year of life, increasing progressively for each decreasing week of gestation, when compared with term infants. Among all very preterm infants (≤ 32 weeks), each 1-week decrease in GA is associated with incrementally higher rates of mortality and major morbidities. Conclusion We provide estimates of potential cost savings that could be attributable to interventions that delay or prevent preterm delivery. Cost differences were most extreme at the lower range of gestation (≤ 30 weeks); however, infants born moderately preterm (31-36 weeks) also contribute substantially to the burden, as they represent a higher proportion of total births.

Increased risk of morbidities and health-care utilisation in children born following preterm labour compared with full-term labour: A population-based study.

AIM: Recent evidence is emerging indicating long-term effects in infants born after an episode of preterm labour (PTL), even if birth is at term. This population-based study compared long-term rates of outcomes and health-care utilisation (HCU) in children born following spontaneous preterm labour, irrespective of gestational age at delivery or of an uncomplicated pregnancy (SPTLu), with children born following full-term labour (FTL), overall stratified by comorbidity status and assessed using a composite morbidity measure (CM). METHODS: Retrospective data on mother-neonate pairs were collected from a patient-linked dataset from the Netherlands Perinatal Registry and the PHARMO Database Network. Children born between 2000 and 2010 were followed until 2012. RESULTS: Of pregnancies in 134 006 mother-neonate pairs, 122 894 (92%) pregnancies resulted in FTL, and 11 112 (8%) resulted in PTL. Of the PTL pregnancies, 6599 (59%) were SPTLu. Mean follow-up after birth was 6.6-6.7 years. Children from SPTLu pregnancies were at increased risk of neurodevelopmental and respiratory conditions compared with those from FTL pregnancies. In children from SPTLu pregnancies, the presence of the CM was associated with an increased risk of respiratory conditions and failure to thrive. Post-natal hospitalisations (incidence rate (IR) per 100 patient-years: 18.1 vs. 11.7) and specialist referrals (IR per 1000 patient-years: 290.6 vs. 184.5) occurred significantly more frequently in children from SPTLu versus FTL pregnancies. CONCLUSION: The increased risk of morbidities and HCU in children born following SPTLu pregnancy in this population-based setting reinforces the need for safe interventions that can effectively halt labour and lead to an improvement in childhood outcomes.

Experience of Symptoms and Disease Impact in Patients with Adenomyosis.

BACKGROUND: Adenomyosis is a poorly understood, benign disease of the uterus. OBJECTIVE: In this study, patient interviews were conducted to characterize the symptoms and impact of adenomyosis. METHODS: This was a cross-sectional study in which women with adenomyosis were recruited from five US clinics and a health-related social network forum. Participants (aged 18-55 years) were pre-menopausal with a history of regular menstrual cycles. Participants were interviewed about their experiences with adenomyosis, symptoms and impacts on day-to-day activities (concept elicitation), and subsequently about the occurrence, relative severity, and impact of symptoms (card-sorting exercise). RESULTS: In total, 31 women were interviewed. Mean duration since onset of first adenomyosis symptom was 5.7 years; 41.9% reported severe/very severe adenomyosis. Over 50 symptoms and 30 impacts of adenomyosis were reported in the concept elicitation; 87% of symptoms were reported after 7 interviews and 78% of impacts after 5 interviews, indicating a condition with a significant symptom burden and a consistent presentation. The most common symptoms were heavy menstrual bleeding (87%), cramps (84%), and blood clots during menstrual bleeding (84%). The most common impacts were burdensome self-care hygiene (71%), and fatigue/low energy (71%). In the card-sorting exercise, the most commonly endorsed symptoms were pain during menstruation/menstrual cramps and heavy menstrual bleeding (both frequently rated as severe). The symptom with the highest impact was heavy menstrual bleeding. CONCLUSION: Initiatives to understand women's experiences with adenomyosis may improve management of the condition. This study provides a first step in understanding their experience and new information on the symptom profile of adenomyosis.

Outcomes of Admissions for Preterm Labor.

Objective This study aims to quantitate the incidence of preterm labor (PTL) admissions and determine the frequency and predictors of preterm delivery (PTD) during these admissions. Study Design Retrospective cohort of singleton pregnancies within Kaiser Permanente Northern California, 2001 to 2011. PTL admissions were defined as inpatient encounters > 24 hours with an International Classification of Diseases, 9th Revision code for PTL. Results Total study population was 365,897 with PTL admission rate 11%. PTD occurred in 85% of pregnancies with PTL admission. Delivery occurred within 48 hours of admission in 96% ≥34 weeks, 67% 31 to 33 weeks, and 51.9% <31 weeks. Predictors of delivery during PTL admission included gestational age 34 to 36 weeks (adjusted odds ratio [aOR], 6.90), chorioamnionitis (aOR, 105.58), and preterm rupture of membranes (aOR 19.29). Conclusion We demonstrate a high rate of PTD per PTL admission in a highly integrated health care system. More work is needed to determine optimal practices for hospitalization and treatment of women diagnosed with PTL.

Incremental Hospital Costs Associated With Comorbidities of Prematurity.

PURPOSE: Preterm birth (PTB), defined as birth at a gestational age (GA) of less than 37 weeks, is associated with increased hospital costs. Lower GA at birth is negatively correlated with the presence of neonatal comorbidities, further increasing costs. This study evaluated incremental costs associated with comorbidities of PTB following spontaneous labor at 24-36 weeks. DESIGN: Birth records from January 2001 to December 2010 at the Medical University of South Carolina were screened to identify infants born at GA 23-37 weeks after uncomplicated singleton pregnancies and surviving to discharge. METHODOLOGY: Comorbidities of interest and incremental costs were analyzed with a partial least squares (PLS) regression model adjusted for comorbidities and GA. Incremental comorbidity-associated costs, as well as total costs, were estimated for infants of GA 24-36 weeks. RESULTS: A total of 4,292 delivery visit records were analyzed. Use of the PLS regression model eliminated issues of multicollinearity and allowed derivation of stable cost estimates. Incremental costs of comorbidities at a mean GA of 34 weeks ranged from $4,529 to $23,121, and exceeded $9,000 in 6 cases. Incremental costs rangedfrom a high of $41,161 for a GA 24-week infant with a comorbidity of retinopathy of prematurity requiring surgery (ROP4) to $3,683 for a GA 36-week infant with a comorbidity of convulsions. Incremental comorbidity costs are additive, so the costs for infants with multiple comorbidities could easily exceed the high of $41,161 seen with ROP4. CONCLUSIONS: The PLS regression model allowed derivation of stable cost estimates from multivariate and highly collinear data and can be used in future cost analyses. Using this data set, predicted costs of all comorbidities, as well as total costs, negatively correlated with GA at birth.

Burden of Illness in Prostate Cancer Patients with a Low-to-Moderate Risk of Progression: A One-Year, Pan-European Observational Study.

Objective. To assess the impact of low-to-moderate risk prostate cancer on patients' quality of life (QoL) at diagnosis and within the first year of treatment. Subjects and Methods. Men (n = 672) aged 50-75 years with prostate cancer (Gleason score ≤7, PSA ≤20 ng/mL and clinical staging T1c-T2b) were enrolled in five European countries. Patients completed five questionnaires, including EORTC Quality of Life Questionnaire-Prostate Cancer 25 (QLQ-PR25) and EORTC Quality of Life Questionnaire-Cancer 30 (QLQ-C30). Questionnaires were completed at baseline, at 3 months and 12 months after starting treatment. The primary endpoint was the change in QLQ-PR25 urinary symptoms subscale score from baseline to the assessment at 3 months. Results. Mean (SD) age was 65.0 (5.7) years and 400 (66%) men had Gleason score ≤6 prostate cancer. The most frequently used initial treatment was radical prostatectomy (71% of patients). QLQ-PR25 urinary symptoms subscale score was significantly increased at 3 months (P < 0.001), indicating that urinary symptoms worsened after treatment. The score was lower at 12 months than at 3 months, but it was still significantly higher than at baseline (P < 0.001). Hormonal treatment-related symptoms, sexual functioning, and sexual activity scores significantly worsened at 3 and 12 months (all P < 0.001). For the QLQ-C30 questionnaire, global health status/QoL score significantly decreased at month 3 but was not different from baseline by month 12. Scales for physical, role, and social functioning, and fatigue, showed significant deterioration at 3 and 12 months. Conclusions. Low-to-moderate risk prostate cancer may have a substantial effect on patients' QoL within one year following treatment.

Safety and efficacy of epelsiban in the treatment of men with premature ejaculation: a randomized, double-blind, placebo-controlled, fixed-dose study.

AIM: To assess the efficacy and safety of the selective oxytocin receptor antagonist epelsiban in the treatment of premature ejaculation (PE). METHODS: Double-blind, randomized, parallel-group, placebo-controlled, stopwatch-monitored, phase 2, multicenter study (GSK557296; NCT01021553) conducted in men (N=77) 18-55 years of age, with PE defined as per International Society for Sexual Medicine consensus definition. Patients provided informed consent prior to a 4-week un-medicated run-in to determine baseline intravaginal ejaculatory latency times (IELT) recorded in an electronic diary. Patients needed to make a minimum of four intercourse attempts and have a mean IELT<65 seconds to be considered for randomization. Men with moderate-to-severe erectile dysfunction were excluded from the study. Eligible patients were randomized to placebo, epelsiban 50 mg, or 150 mg, taken 1 hour before sexual activity. Active treatment IELT times were recorded in an electronic diary, along with subjective measures of intercourse satisfaction, over an 8-week treatment period. The Modified Index of Premature Ejaculation and International Index of Erectile Function were completed at study visits. MAIN OUTCOME MEASURES: Stopwatch timed IELT recordings and a modified version of the patient-reported outcome questionnaire the IPE were used in this study to determine the effect of epelsiban when taken orally prior to intercourse in subjects diagnosed with PE. RESULTS: The baseline (mean) IELT for patients pretreatment was (0.52, 0.63, and 0.59 minutes) for placebo, epelsiban 50 mg and 150 mg, respectively. On-treatment, average geometric least squares means of the median IELT values (mean) were slightly higher in the 50 mg and 150 mg groups (0.72 and 0.69 minutes), respectively, vs. the placebo group (0.62 minutes). Headache was the most common adverse event, and rates were similar across all groups. CONCLUSIONS: Epelsiban 50 mg and 150 mg were well tolerated, but did not result in a clinically or statistically significant change in IELT in men with PE, compared with placebo.

Quantifying the contribution of symptom improvement to satisfaction of men with moderate to severe benign prostatic hyperplasia: 4-year data from the CombAT trial.

PURPOSE: We quantified the magnitude of symptom improvement required to achieve different levels of patient reported satisfaction, as assessed by the Patient Perception of Study Medication questionnaire. MATERIALS AND METHODS: This multicenter, international, double-blind, randomized study included men 50 years old or older with International Prostate Symptom Score 12 or greater, prostate volume 30 cc or greater, total prostate specific antigen 1.5 to 10.0 ng/ml, maximum urinary flow greater than 5 and less than or equal to 15 ml per second and minimum voided volume 125 ml or greater. Patients were randomized to dutasteride (0.5 mg) and/or tamsulosin (0.4 mg) but results are reported without respect to treatment. International Prostate Symptom Score and Patient Perception of Study Medication responses were assessed at baseline and at 3-month intervals for 48 months. Using pooled data Patient Perception of Study Medication responses were correlated with changes in International Prostate Symptom Score from baseline for 2 Patient Perception of Study Medication measures, including 1) total score and 2) overall satisfaction on question 11, "Overall how satisfied are you with the study medication and its effect on your urinary problems?" RESULTS: Patient Perception of Study Medication total score and question 11 correlated significantly with the mean change in International Prostate Symptom Score from baseline (p <0.0001). A response of very satisfied to question 11 was associated with an International Prostate Symptom Score improvement of -9.4 points while a response of very dissatisfied was associated with 1.3-point worsening. There was only moderate correlation between Patient Perception of Study Medication question 11 and changes in symptoms (r = 0.38). Thus, factors other than lower urinary tract symptoms also contribute to satisfaction and they could not be formally analyzed in this report. CONCLUSIONS: We noted correlations between patient satisfaction and the magnitude of the International Prostate Symptom Score change from baseline, which allowed us to determine treatment outcomes in terms of true clinical instead of only statistical significance.

Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial.

BACKGROUND: We aimed to investigate the safety and efficacy of dutasteride, a 5α-reductase inhibitor, on prostate cancer progression in men with low-risk disease who chose to be followed up with active surveillance. METHODS: In our 3 year, randomised, double-blind, placebo-controlled study, undertaken at 65 academic medical centres or outpatient clinics in North America, we enrolled men aged 48-82 years who had low-volume, Gleason score 5-6 prostate cancer and had chosen to be followed up with active surveillance. We randomly allocated participants in a one-to-one ratio, stratified by site and in block sizes of four, to receive once-daily dutasteride 0·5 mg or matching placebo. Participants were followed up for 3 years, with 12-core prostate biopsy samples obtained after 18 months and 3 years. The primary endpoint was time to prostate cancer progression, defined as the number of days between the start of study treatment and the earlier of either pathological progression (in patients with ≥1 biopsy assessment after baseline) or therapeutic progression (start of medical therapy). This trial is registered with ClinicalTrials.gov, number NCT00363311. FINDINGS: Between Aug 10, 2006, and March 26, 2007, we randomly allocated 302 participants, of whom 289 (96%) had at least one biopsy procedure after baseline and were included in the primary analysis. By 3 years, 54 (38%) of 144 men in the dutasteride group and 70 (48%) of 145 controls had prostate cancer progression (pathological or therapeutic; hazard ratio 0·62, 95% CI 0·43-0·89; p=0·009). Incidence of adverse events was much the same between treatment groups. 35 (24%) men in the dutasteride group and 23 (15%) controls had sexual adverse events or breast enlargement or tenderness. Eight (5%) men in the dutasteride group and seven (5%) controls had cardiovascular adverse events, but there were no prostate cancer-related deaths or instances of metastatic disease. INTERPRETATION: Dutasteride could provide a beneficial adjunct to active surveillance for men with low-risk prostate cancer. FUNDING: GlaxoSmithKline.

Cost-effectiveness of combination therapy for treatment of benign prostatic hyperplasia: a model based on the findings of the Combination of Avodart and Tamsulosin trial.

OBJECTIVE: • To evaluate the cost-effectiveness of combination therapy for benign prostatic hyperplasia (BPH) compared with alpha-blocker (AB), 5-alpha reductase inhibitor (5ARI) monotherapy or watchful waiting (WW) in male patients enrolled in the Combination of Avodart and Tamsulosin (CombAT) trial using a Norwegian economic model. PATIENTS AND METHODS: • A decision analytic model was constructed to evaluate the BPH treatment regimens using point estimate base-case analyses, one-way sensitivity testing and probabilistic sensitivity analyses. • Symptom severity and acute urinary retention/transurethral resection of the prostate (AUR/TURP) event data came from the 4-year evaluation of the CombAT trial with additional data from the Medical Therapy of Prostatic Symptoms (MTOPS) trial. The model makes use of Norwegian practice pattern data and unit cost and utility estimates were taken from the published literature. • The model calculates treatment costs and utility outcomes at two time horizons: 4 years and lifetime. Incremental cost-effectiveness ratios (ICERs) were calculated using WW as the basis of comparison. Costs and health state utilities were discounted after the first year. RESULTS: • At 4 years, ICER results for combination therapy are higher than AB monotherapy as a result of the higher drug cost, but the overall cost and quality-adjusted life-year (QALY) differences are small. • At the lifetime evaluation, the ICER results decrease from those at the 4-year horizon, although AB monotherapy remains less expensive than combination therapy. However, the incremental QALYs gained for combination therapy are twice those of AB monotherapy. CONCLUSIONS: • The model is sensitive to variability in estimates of health state utility assigned on the basis of symptom severity, indicating that both monotherapy and combination therapy have an advantage in maintaining patients in less severe symptom states. • Overall, combination therapy for BPH is expected to provide the greatest net monetary benefit at willingness-to-pay thresholds at or above ≈€6000 (£5400).

Lifetime economic burden of prostate cancer.

BACKGROUND: Prostate cancer (PCa) is the most common cancer affecting men in the United States. The initial treatment and subsequent monitoring of PCa patients places a large burden on U.S. health care systems. The objectives of this study were to estimate the total and disease-related per-patient lifetime costs using a phase-based model of cancer care for PCa patients enrolled in Medicare. METHODS: A model was developed to estimate life-time costs for patients diagnosed with PCa. Patients ≥ 65 years old and diagnosed with PCa between calendar years 1991-2002 were selected from the SEER database. Using SEER, we estimated survival times for PCa patients from diagnosis until death. The period of time patients contributed to treatment phases was determined using an algorithm designed to model the natural history of PCa. Costs were obtained from the US SEER-Medicare database and estimated during specific phases of care. Cost estimates were then combined with survival data to yield total and PCa-related life-time costs. RESULTS: Overall, the model estimated life-time costs of $110,520 (95% CI 110,324-110,739) per patient. PCa-related costs made up approximately 31% of total costs ($34,432). CONCLUSIONS: Prostate cancer places a significant burden on U.S. health-care systems with average life-time PCa-related costs in excess of $30,000.

The economic burden of prostate cancer.

In the present review we discuss expenditure on prostate cancer diagnosis, treatment and follow-up and evaluate the cost of prostate cancer and its management in different countries. Prostate cancer costs were identified from published data and internet sources. To provide up-to-date comparisons, costs were inflated to 2010 levels and the most recent exchange rates were applied. A high proportion of the costs are incurred in the first year after diagnosis; in 2006, this amounted to 106.7-179.0 million euros (€) in the European countries where these data were available (UK, Germany, France, Italy, Spain and the Netherlands). In the USA, the total estimated expenditure on prostate cancer was 9.862 billion US dollars ($) in 2006. The mean annual costs per patient in the USA were $10,612 in the initial phase after diagnosis, $2134 for continuing care and $33,691 in the last year of life. In Canada, hospital and drug expenditure on prostate cancer totalled C$103.1 million in 1998. In Australia, annual costs for prostate cancer care in 1993-1994 were 101.1 million Australian dollars. Variations in costs between countries were attributed to differences in incidence and management practices. Per patient costs depend on cancer stage at diagnosis, survival and choice of treatment. Despite declining mortality rates, costs are expected to rise owing to increased diagnosis, diagnosis at an earlier stage and increased survival. Unless new strategies are devised to increase the efficiency of healthcare provision, the economic burden of prostate cancer will continue to rise.

Cost effectiveness of chemoprevention for prostate cancer with dutasteride in a high-risk population based on results from the REDUCE clinical trial.

BACKGROUND: The REDUCE trial examined whether chemoprevention with the dual 5-alpha reductase inhibitor, dutasteride, reduced risk of prostate cancer (PCa) detection on biopsy. OBJECTIVE: We examined the cost effectiveness of dutasteride compared with placebo in preventing PCa in men at increased risk as seen in REDUCE, from a US payer perspective. METHODS: A Markov model was developed to compare costs and outcomes of chemoprevention with dutasteride 0.5 mg/day or placebo with usual care in men aged 50-75 years, with serum prostate-specific antigen (PSA) of 2.5-10 ng/mL (men aged <60 years) or 3.0-10 ng/mL (men aged ≥60 years), and with a single negative prostate biopsy in the prior 6 months. The model simulated the REDUCE cohort annually through different health states over 4-, 10-year and lifetime time horizons. Risks of PCa for men receiving placebo and dutasteride were obtained from REDUCE. Rates of acute urinary retention events and benign prostate hyperplasia-related surgeries also came from REDUCE. Costs and utilities were obtained from published literature. All costs are reported in $US, year 2009 values. RESULTS: The model indicated that, over 10 years, dutasteride patients would experience fewer PCas (251 vs 312 per 1000 patients) at increased cost ($US15 341 vs $US12 316) than placebo patients. Although life-years were not substantially affected, the model calculated an increase in QALYs of 0.14 for dutasteride patients. Chemoprevention with dutasteride appeared to be cost effective, with an incremental cost per QALY of $US21 781 and cost per PCa avoided of $US50 254. The 4-year and lifetime incremental costs per QALY were $US18 409 and $US22 498, respectively. CONCLUSIONS: Despite increased cost due to taking a drug for prevention, dutasteride 0.5 mg/day may be cost effective in men at increased risk for PCa.

Dutasteride improves outcomes of benign prostatic hyperplasia when evaluated for prostate cancer risk reduction: secondary analysis of the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial.

OBJECTIVE: To investigate the effect of dutasteride versus placebo on the symptoms and associated complications of male lower urinary tract symptoms and benign prostatic hyperplasia (BPH) across a range of prostate volumes and BPH symptoms in men evaluated for prostate cancer risk reduction in the 4-year REduction by DUtasteride of prostate Cancer Events (REDUCE) trial. METHODS: REDUCE was a multicenter, randomized, double-blind, placebo-controlled study of prostate cancer risk reduction with daily dutasteride 0.5 mg or placebo. Eligible men were aged 50-75 years, with a prostate-specific antigen level of 2.5-10 ng/mL and a prostate volume of ≤80 cm3. The prespecified and post hoc analyses were performed on the incidence of acute urinary retention, BPH-related surgery, and urinary tract infections, as well as on changes in prostate volume, International Prostate Symptom Score, BPH Impact Index, and maximal urinary flow rate (Qmax). RESULTS: A total of 8122 men were included in the efficacy population. During the 4-year study, the International Prostate Symptom Score increased in placebo-treated patients, while dutasteride-treated patients had a stabilized or decreased International Prostate Symptom Score and improved BPH Impact Index and quality of life due to urinary symptom scores across all prostate volume quintiles (including prostate glands smaller than those studied in previous dutasteride trials). 48 months, the incidence of acute urinary retention or BPH-related surgery was significantly less in the dutasteride group (2.5%) than in the placebo group (9%) overall (P<.001) and in each baseline prostate volume quintile (P<.01). CONCLUSION: During the 4-year study, dutasteride was associated with a decreased risk of BPH progression in men with mild-to-moderate symptoms and normal or enlarged prostates.