Exploring pharmacological interventions in benign prostate hyperplasia: the role of cost-effectiveness analysis in daily practice and future directions.

INTRODUCTION: Benign Prostate Hyperplasia (BPH) significantly impacts men's health and quality of life, with its prevalence rising with age. This review critically examines the cost-effectiveness of pharmacological interventions for BPH to optimize patient outcomes and healthcare resource utilization. AREAS COVERED: This review explores the integration of cost-effectiveness analysis (CEA) into clinical practice, balancing clinical efficacy with economic efficiency in BPH management. We performed a critical literature search, including recent studies on the economic evaluation of BPH treatments, focusing on pharmacotherapies such as alpha-blockers and 5-alpha reductase inhibitors. Additionally, we discussed the concept of CEA and evaluated the role of medicinal reconciliation and the avoidance of polypharmacy in favor of optimal BPH treatment. EXPERT OPINION: Cost-effectiveness analysis is crucial for evaluating BPH treatments, with evidence suggesting a shift towards surgical interventions may offer greater long-term economic benefits. However, these models must be applied cautiously, considering clinical evidence and patient preferences to ensure equitable and patient-centric healthcare.

Comparing Clinical and Economic Outcomes Associated with Early Initiation of Combination Therapy of an Alpha Blocker and Dutasteride or Finasteride in Men with Benign Prostatic Hyperplasia in the United States.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in men that is characterized by lower urinary tract symptoms. Pharmacologic treatment with alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) is recommended to alleviate symptoms, prevent disease progression that can lead to complications, and reduce health care costs. OBJECTIVE: To compare clinical, economic, and health care resource utilization outcomes among BPH patients treated with early continuous combination AB and 5ARI therapy (dutasteride vs. finasteride) using administrative claims data from the United States. METHODS: A retrospective analysis of administrative claims data from 2003-2013 was conducted to compare outcomes between patients with claims for early combination therapy with dutasteride + AB and patients with claims for early finasteride + AB. The study population included males aged older than 50 years with at least 1 medical claim with a diagnosis of BPH and pharmacy dispensing for AB and 5ARI therapies. Outcomes included acute urinary retention (AUR), prostate-related surgery, clinical progression, medical and pharmacy costs, and health care resource utilization. Inverse probability of treatment (IPT) weighted Cox proportional hazards, linear, and Poisson regression models were used to assess the association between outcomes and early combination therapy as appropriate. RESULTS: A total of 2,778 patients were included in the early finasteride + AB treatment cohort, and 4,125 patients were included in the early dutasteride + AB cohort. Dutasteride users were younger than finasteride users (mean age: 64.8 vs. 67.5 years, P < 0.001) and had a greater mean number of urologist visits (10.7 vs. 7.9, P < 0.001) during baseline. After adjusting for confounding using IPT weighting, no statistically significant difference was observed between dutasteride and finasteride for AUR (hazard ratio [HR] = 0.845, 95% CI = 0.660-1.070, P = 0.1643), prostate-related surgery (HR = 0.806, 95% CI = 0.568-1.171, P = 0.2525), and clinical progression (HR = 0.834, 95% CI = 0.663-1.043, P = 0.1122). While dutasteride was associated with higher pharmacy costs per month (adjusted monthly cost difference = $79, 95% CI = $45-$105), total all-cause medical costs were not significantly different between the 2 cohorts (adjusted monthly cost difference = -$44, 95% CI = -$110-$22). CONCLUSIONS: Clinical and economic outcomes were similar between the early dutasteride + AB and early finasteride + AB cohorts, with no statistically significant differences detected. DISCLOSURES: Funding for this study was provided by GlaxoSmithKline (HO-14-15325 and AVO110072). Bell and Swensen are employees of GlaxoSmithKline. DerSarkissian, Xiao, Duh, and Lefebvre are employed by Analysis Group, a consulting company that received research grants from GlaxoSmithKline to conduct this study. Study concept and design were contributed by Bell, Swensen, Lefebvre, and Duh. Bell and Duh acquired the data. DerSarkissian and Xiao performed the statistical analysis and interpreted the data along with Lefebvre, Duh, and Bell. DerSarkissian and Bell drafted the manuscript. All authors contributed equally to critically revising the manuscript and providing final approval of the submitted manuscript.

Actual medical management of lower urinary tract symptoms related to benign prostatic hyperplasia: temporal trends of prescription and hospitalization rates over 5 years in a large population of Italian men.

PURPOSE: The purpose of the study is to estimate the trends in drug prescriptions and the hospitalization rates for lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) in real-life clinical practice, using information deriving from administrative databases of the Italian health care system. METHODS: Prescription data on approximately 1,500,000 men over 40 were examined, and prescribed boxes of alpha-blockers (ABs) and/or 5 alpha reductase inhibitors (5ARI) were calculated for 5 consecutive years, from 2004 to 2008. Annual use prevalence and incidence rates for each drug class and for the combination therapy (CT) were calculated according to age for the entire study period. Hospitalization rates for reasons related to LUTS/BPH were also evaluated for the same time period. RESULTS: The overall distribution of drugs for LUTS/BPH, in terms of number of boxes prescribed, increased by 43 %. This increase was accounted for by both classes of drugs although it was greater for 5ARI than for AB (+49 vs +41 %). The prevalence of CT showed a substantial increase to almost 25 % in patients aged ≥75. Hospitalization rate for BPH/LUTS-related reasons decreased during the study period (8 and 3 % per year for non-surgical and surgical reasons, respectively). CONCLUSIONS: The prevalence of the use of drugs prescribed for LUTS/BPH has steadily increased. An increase in terms of prescribed boxes was observed for both classes of drugs, even though the increase was greater for 5ARIs. The reduction in the hospitalization rates needs additional researches.

Medical expulsive therapy versus early endoscopic stone removal for acute renal colic: an instrumental variable analysis.

PURPOSE: The use of medical expulsive therapy to hasten stone passage potentially decreases expenditures around episodes of renal colic. However, these efficiency gains may be mitigated if patients treated with medical expulsive therapy have frequent health care encounters due to pain while waiting for the stones to pass. MATERIALS AND METHODS: Using claims data (2002 to 2006) we identified adult men with acute renal colic. We compared 6-week payments as well as frequency of hospitalization and emergency department revisits associated with an initial course of medical expulsive therapy with those for early endoscopic stone removal. To account for unmeasured confounding we performed an instrumental variable analysis, exploiting variation in recommended treatments based on the day of the week that a patient's first emergency department visit occurred. RESULTS: Overall 1,835 and 4,397 men underwent medical expulsive therapy or early endoscopic stone removal, respectively. Although minimal differences existed between men with respect to the day of the week of emergency department presentation, weekend encounters were strongly associated with receiving medical expulsive therapy (p <0.001). Two-stage least squares regression revealed 6-week payments to be tenfold lower for men on medical expulsive therapy who were candidates for either treatment (p <0.001). While there was no difference in frequency of hospitalization, these men were more likely to have a repeat emergency department visit compared to those who underwent endoscopic stone removal (68.8% vs 39.6%, respectively, p = 0.025). CONCLUSIONS: Findings on medical expulsive therapy are mixed, with lower 6-week payments but more frequent repeat emergency department visits. These data inform patients who are candidates for medical expulsive therapy or endoscopic stone removal when making decisions about their care.

OTC tamsulosin for benign prostatic hyperplasia.

Earlier this year, tamsulosin, an alpha blocker previously only available on prescription, became available for sale by pharmacists as a treatment for functional symptoms of benign prostatic hyperplasia (BPH) in men aged 45-75 years (Flomax Relief MR - Boehringer Ingelheim). A television advert for the over-the-counter (OTC) product claims that it is a "simple and effective" treatment that can relieve symptoms within 1 week, allowing the user to "take control of your annoying pee problems".¹ Here we review the evidence on tamsulosin and assess whether its availability as an OTC product confers worthwhile advantages.

Medical expulsive therapy for ureteral calculi in the real world: targeted education increases use and improves patient outcome.

PURPOSE: In controlled trials medical expulsive therapy has improved outcomes in patients with ureteral stones but its real-world use and effectiveness outside a clinical trial have not been thoroughly examined. We studied the impact of targeted education of emergency department physicians about medical expulsive therapy and analyzed its impact on patient outcomes and cost. MATERIALS AND METHODS: In 2006 emergency department physicians at our institution were formally educated about medical expulsive therapy. Retrospective emergency department data were collected on patients with ureteral stones from 2003 and 2005 (before educational intervention), and 2007 (after intervention). Cost and 90-day post-emergency department event data were gathered from a health maintenance organization owned and operated by our medical center. Medical expulsive therapy prescribing trends, adverse outcome (repeat emergency department visit, hospital admission or surgery) and total cost related to ureteral calculus diagnosis were analyzed. RESULTS: Of 166 health maintenance organization patients with ureteral calculi who met all study requirements 97 (58.4%) were prescribed medical expulsive therapy and 53 (31.9%) filled the medical expulsive therapy prescription, while 113 did not. Analysis revealed a 2-fold increase in medical expulsive therapy prescribing and a 4-fold increase in prescribing alpha-blockers in each time increment. Bivariate analysis showed that the frequency of adverse outcomes was lower in the medical expulsive therapy group (37.7% vs 53.1%) and medical expulsive therapy was associated with a lower mean total cost per patient ($1,805 vs $2,372). CONCLUSIONS: Targeted educational intervention can increase the use of preferred medical expulsive therapy (alpha-blockers) in the emergency department. Medical expulsive therapy decreases the incidence of adverse events by 29% and decreases the total cost associated with ureteral stones by 24%.

[Economic evaluation of medical treatment of benign prostatic hyperplasia (BPH) in the specialised care setting in Spain. Application to the cost-effectiveness of two drugs frequently used in its treatment]. / Evaluación económica del tratamiento médico de la hiperplasia benigna de próstata (HBP) en España en atención especializada. Aplicación al coste- efectividad de dos fármacos habitualmente utilizados en su tratamiento.

OBJECTIVES: To develop a pharmacoeconomic study in order to know the average cost of BPH diagnosis and follow-up in Spain in the Urology Department setting from the perspective of the public health system, considering two frequently used drugs in the Spanish Healthcare environment, an alpha-blocker (tamsulosin) and the lipido-sterolic extract of Serenoa repens (Permixon). MATERIAL AND METHODS: Direct healthcare costs of BPH diagnosis and treatment were determined for each clinical stage according to the International Prostate Symptom Score (IPSS): mild, moderate and severe. Data on the usage and unit costs of healthcare resources were obtained from a semi-structured interview with clinical experts. The clinical efficacy of the medical treatments was obtained from the PERMAL clinical study, where therapeutic equivalence between the two studied drugs was observed. RESULTS: For patients treated in the Urology Department setting, the average annual cost of diagnostic tests and medical visits related to mild, moderate or severe BPH symptoms were, respectively, Euro 124, Euro 207, and Euro 286. The average annual cost of the drugs, including adverse effects treatment, was Euro 211 for Permixon and Euro 346 for tamsulosin. DISCUSSION: Costs of medical care of BPH increases with symptom intensity. Pharmacological treatment makes up a significant part of the disease's cost. According to the model used, treatment with Permixon is considerably more cost-effective than with tamsulosin, offering average yearly savings of Euro 135 per patient.

Cost-effectiveness of medical expulsive therapy using alpha-blockers for the treatment of distal ureteral stones.

OBJECTIVE: Medical expulsive therapy (MET) has recently emerged as an efficacious and safe option for the initial management of ureteral stones. The objective of this study was to assess the cost-effectiveness of MET compared with conservative therapy for the treatment of ureteral stones using international cost data from the United States and four European countries. MATERIAL AND METHODS: A decision analysis model was built with the use of TreeAge Pro 2004 software with linear success rate assumptions. The likelihood of spontaneous passage of ureteral stones according to their size and location was estimated with the use of data derived from a published meta-analysis. The estimated cost of ureteroscopy (URS) in the United States ($4973) was based on the mean cost of 121 consecutive cases performed at a large metropolitan hospital. URS costs for other countries were obtained from a published international survey. The cost of tamsulosin ($2.08 per day), currently the most commonly used medical expulsive agent, was estimated as a mean of the costs obtained from two national pharmacy chains. MET and conservative therapies were compared with the use of one-way and two-way sensitivity analyses. RESULTS: In the United States, MET using tamsulosin resulted in a $1132 cost advantage over observation. MET maintained its cost advantage even in countries where the cost of URS is much lower than in the United States. Two-way sensitivity analysis showed that MET remained cost-effective even with very low rates of spontaneous passage, minimal benefit of MET, or low cost of URS. CONCLUSION: MET is a cost-effective strategy for the management of distal ureteral stones--even those with a low rate of spontaneous passage--providing another incentive for initial "facilitated observation" before embarking on surgical intervention.

The long-term outcome of medical therapy for BPH.

OBJECTIVES: The lack of cure with medical therapy implies life-long treatment emphasising the need for a thorough understanding of the long-term outcome. We review the natural history, markers for progression, placebo effect, efficacy, pharmacoeconomic aspects, and preventive measures. METHODS: Literature review with particular reference to long-term controlled studies using plant extracts, alpha1-blockers, 5alpha-reductase inhibitors (5-ARIs), and combination therapy. RESULTS: There is a long-lasting (>or=12 mo) placebo response of symptoms (20% decrease) and maximum flow rate (10% rise). The five long-term controlled trials of plant extracts are inconclusive and therefore their role in contemporary medical management is still controversial. The alpha1-blockers provide fast amelioration of symptoms yet have no relevant impact on the risk of acute urinary retention or surgery. Combination therapy should be reserved for moderately or severely symptomatic patients with a high risk of progression; in the majority of patients the alpha1-blocker can be safely stopped after 6-12 mo. The preventive use of 5-ARIs in men with no or mild symptoms at risk of progression is scientifically sound yet not generally accepted mainly for economic reasons. CONCLUSIONS: A sharp contrast exists between the duration of the longest controlled trial (4.5 yr) and the situation in real life with treatment periods up to one or two decades of life. Real-life and registry data will be the only source of this important information in the future.

Durability and cost-effectiveness of transurethral needle ablation of the prostate as an alternative to transurethral resection of the prostate when alpha-adrenergic antagonist therapy fails.

PURPOSE: We analyzed the adverse event profile, long-term efficacy and cost-effectiveness of transurethral needle ablation of the prostate for lower urinary tract symptoms associated with benign prostatic hyperplasia as an alternative to transurethral resection of the prostate in men with symptoms uncontrolled by medical therapy. MATERIALS AND METHODS: A total of 71 men on a waiting list for transurethral resection of the prostate after failed medical therapy underwent transurethral needle ablation of the prostate. Symptom scores, uroflowmetry and residual urine were measured before and up to 10 years following treatment. Transrectal ultrasound and pressure flow studies were performed before, and 3 and 12 months following treatment, respectively. Treatment failure was defined as lower urinary tract symptoms progression requiring further therapy or associated with deteriorating quality of life assessment. RESULTS: Apart from transient postoperative urinary retention, no significant treatment emergent adverse events due to transurethral needle ablation of the prostate were observed. Treatment failure occurred in 58 men (83%) at a median of 20 months. A total of 36 men (51%) underwent invasive treatment (transurethral resection of the prostate 33, bladder neck incision 2, microwave thermal ablation 1), 2 men (3%) were deemed unfit for anesthesia and now practice clean intermittent self-catheterization, 14 men (20%) reported improvement following resumption of treatment with an alpha-adrenergic antagonist after transurethral needle ablation of the prostate and 6 men (9%) have experienced deterioration in lower urinary tract symptoms with reduction in quality of life assessment (International Prostate Symptom Score 3 or greater) but have declined further intervention. There were 12 men (17%) who remained symptom-free up to 10 years after transurethral needle ablation of the prostate. The estimated additional cost of treatment for lower urinary tract symptoms per man treated with transurethral needle ablation of the prostate during the 10-year followup was $1,377. CONCLUSIONS: Despite documented safety and lack of morbidity, the high re-treatment rate associated with transurethral needle ablation of the prostate renders it relatively expensive when viewed as a long-term alternative to transurethral resection of the prostate for the management of lower urinary tract symptoms associated with benign prostatic hyperplasia in men in whom medical therapy failed. Of men failing alpha-blockade therapy 20% will benefit from a combination of transurethral needle ablation of the prostate and alpha-blockade.

Medical therapy versus surgery and minimally invasive surgical therapies for lower urinary tract symptoms and benign prostatic hyperplasia: what makes better economic sense?

From a clinical standpoint, the emergence of selective pharmacologic therapies and minimally invasive procedural treatments has changed clinical management paradigms for benign prostatic hyperplasia (BPH). Choosing from among the available treatment options can be complex for both patient and physician as factors including clinical outcomes, cost, and reimbursement are weighed and evaluated. Pharmacologic therapies produce modest improvements in objective outcomes measures and subject patients to long-term costs and risks including disease progression and the potential need for subsequent procedural treatment. Procedural interventions for obstructive BPH have changed dramatically in the past several decades as minimally invasive therapies have been developed to produce substantial improvement in outcomes measures and limit the potential morbidity associated with traditional surgical therapies. This paper reviews the current literature to provide a framework for understanding the relationship between clinical outcomes and costs with respect to commonly used medical and procedural therapies for the management of symptomatic BPH and associated lower urinary tract symptoms. The objective is to provide the clinician with an assessment of peer-reviewed evidence-based data to facilitate informed decision making on patient treatment for obstructive BPH.

BPH: costs and treatment outcomes.

The current treatments for benign prostatic hyperplasia (BPH) include pharmacotherapy with alpha1-selective adrenergic receptor (a1-AR) antagonists, 5-alpha-reductase inhibitors (5-aRIs), and a range of invasive and minimally invasive interventions, each of which is effective in the amelioration of lower urinary tract symptoms (LUTS) and the prevention of symptom progression and BPH-related complications. Pharmacotherapy is considered the mainstay of treatment for LUTS caused by BPH. The available a1-AR antagonists have comparable efficacy for the relief of LUTS and to enhance patients' quality of life. The use of nonsubtype-selective drugs in this class may precipitate vasodilatory adverse events such as dizziness, somnolence, and orthostatic hypotension. Based on current studies, a1-AR antagonists are more cost effective (particularly the subtype-selective a1-AR antagonist, tamsulosin) than the 5-aRIs (eg, finasteride) and comparable in cost to transurethral resection of the prostate and minimally invasive therapies. There are few cost-effectiveness studies comparing the various pharmacologic interventions for BPH. Only 1 cost-analysis model has addressed the impact of adverse events on the cost effectiveness of pharmacotherapy for BPH. The publication of additional analyses would contribute to the appropriate selection of therapy in patients with BPH.

An evaluation of the economic costs and patient-related consequences of treatments for benign prostatic hyperplasia.

OBJECTIVE: To compare the costs and effectiveness of treatments for benign prostatic hyperplasia (BPH), including watchful waiting, pharmaceuticals (alpha-blockers, 5-alpha-reductase inhibitors, combined therapy), transurethral microwave thermotherapy (TUMT), and transurethral resection of the prostate (TURP). PATIENTS AND METHODS: This study used a Markov model over a 20-year period and the societal perspective to evaluate the costs of treatment alternatives for BPH. Markov states include urinary symptom improvement, symptom improvement with adverse effects, or no urinary symptom improvement. For the analysis, patients could remain on their initial treatment, change to a different treatment, have treatment failure that required TURP, or die (all-cause mortality). We used published data for outcomes, including systematic reviews when possible. Costs were estimated using a managed-care claims database and Medicare fee schedules. Costs and effectiveness outcomes were discounted at 3%/year where appropriate. Men (aged > or = 45 years) with moderate-to-severe lower urinary tract symptoms and uncomplicated BPH were included in the analysis, and results were stratified by age. Outcomes include costs, disease progression, surgery, hospitalization, and catheterization time. RESULTS: What is the 'best' treatment depends on the value that an individual and society place on costs and consequences. alpha-Blockers are less expensive than the alternatives, and are effective at relieving patient-reported symptoms. Unfortunately, they have little effect on clinical outcomes and have the highest BPH progression rate. Other treatments have lower disease progression and better clinical outcomes, but are more expensive and entail more invasive treatments, and/or more uncertainty. CONCLUSIONS: Treatment decisions are made using a variety of information, including the cost and consequences of treatment. The best treatment depends on the patient's preference and the outcome considered most important. alpha-Blockers are very effective at treating urinary symptoms but do not improve clinical outcomes, including disease progression, relative to other treatments. TURP remains the 'gold standard' for surgical procedures. The desire to avoid TURP or the 2 weeks of catheterization associated with TUMT might affect a patient's treatment decision when symptoms are severe. Therefore, more information about patient preferences and risk aversion is needed to inform treatment decision-making for BPH.

Erectile dysfunction in spinal cord injury: a cost-utility analysis.

BACKGROUND: There is a high incidence of erectile dysfunction after spinal cord injury. This can have a profound effect on quality of life. Treatment options for erectile dysfunction include sildenafil, intracavernous injections of papaverine/alprostadil (Caverject), alprostadil/papaverine/phentolamine ("Triple Mix"), transurethral suppository (MUSE), surgically implanted prosthetic device and vacuum erection devices. However, physical impairments and accessibility may preclude patient self-utilization of non-oral treatments. METHODS: The costs and utilities of oral and non-oral erectile dysfunction treatments in a spinal cord injury population were examined in a cost-utility analysis conducted from a government payer perspective. Subjects with spinal cord injury (n=59) reported health preferences using the standard gamble technique. RESULTS: There was a higher health preference for oral therapy. The cost-effectiveness results indicated that sildenafil was the dominant economic strategy when compared with surgically implanted prosthetic devices, MUSE(R) and Caverject. The incremental cost-utility ratios comparing sildenafil with triple mix and vacuum erection devices favoured sildenafil, with ratios less than CAN$20,000 per quality adjusted life year gained. CONCLUSION: Based on this study, we conclude that sildenafil is a cost-effective treatment for erectile dysfunction in the spinal cord injury population.

[Tamsulosin in the treatment of patients with ureteroliths of the lower third of the ureter clinical and pharmacoeconomic grounds].

Alpha1-adrenoblocker tamsulosin reduces muscle spasm in the ureteric wall, decreases peristalsis below and raises pressure above the stone thus facilitating stone passage. Patients on tamsulosin had spontaneous stone passage in 73.8% cases while only 22.4% patients on routine therapy became stone free. Tamsulosin also shortens hospital stay. Use of tamsulosin 0.4 mg daily in patients with distal ureteric stones is pathogenetically validated, is highly clinically and cost effective.