Clinical Progression and Costs in Benign Prostatic Hyperplasia Patients Treated With Early Versus Delayed Combination Therapy

In patients with benign prostatic hyperplasia (BPH), combination therapy with an alpha-blocker (AB) and a 5 alpha-reductase inhibitor (5ARI) has been shown to reduce the progression of acute urinary retention (AUR) and the incidence of prostate surgery, and also provides symptom relief.

The objective of this study is to compare the likelihood of clinical progression (defined as AUR and/or prostate-related surgery) and costs in BPH patients who were treated with delayed combination therapy to BPH patients who were treated with early combination therapy using data from a United States (US) healthcare claims database. The hypothesis of this study is that patients who are prescribed combination therapy early in their BPH treatment will experience better clinical outcomes and lower healthcare costs compared with patients treated with delayed combination therapy. The null hypothesis is that no difference will be observed in outcomes or direct medical costs for patients treated with early combination therapy and patients treated with delayed combination therapy.

The US healthcare claims database includes data from patients with Medicare Advantage as well as private health plan coverage including the Impact health plan. About 14 million people were covered by this set of health plans in 2007 and were geographically diverse across the US. Data from 2000 through 2009 were utilized.

The study is a retrospective cohort analysis.

Study Overview

• Status: Completed
• Conditions: Benign Prostatic Hyperplasia
• Intervention / Treatment: Drug: Early combination therapy; Drug: Delayed combination therapy

• Study Type: Observational
• Enrollment (Actual): 13551

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Insured male patients, aged 50 and older, with a diagnosis of benign prostatic hyperplasia (BPH) as identified by International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9) codes for BPH (ICD-9 = 222.2x or 600.xx)

Description

Inclusion Criteria:

• Male
• Age 50 or older at the index date (the date of the first filled prescription for an AB or 5ARI during the enrollment period)
• At least one claim with an ICD-9 diagnosis code for BPH (222.2 or 600.xx) in any position and at least one pharmacy claim for an AB (alfuzosin, doxazosin, tamsulosin, or terazosin) or at least one fill for a 5ARI (dutasteride or finasteride) (with or without a diagnosis for BPH)
• Continuous enrollment with medical and pharmacy benefits for 6 months prior to the index date (i.e., baseline period) and 12 months after the index date (follow-up period)

Exclusion Criteria:

• At least one pharmacy claim for an AB (alfuzosin, doxazosin, tamsulosin, or terazosin) any time during the pre-index period prior to the index date
• At least one fill for a 5ARI (dutasteride or finasteride) any time during the pre-index period prior to the index date
• A diagnosis code for prostate cancer (ICD-9 = 185, 198.82, 233.4, 236.5, 239.5, V10.46) or bladder cancer (ICD-9 =188, 198.1, 223.3, 233.7, 239.4, V10.51) in any position during the pre-index or follow-up period
• A pharmacy claim for finasteride 1 mg tablets (i.e., treatment of male-pattern baldness) during the pre-index or follow-up period
• Prostate surgery anytime during the pre-index period or 5 months after the index date

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients with Benign Prostatic Hyperplasia (BPH); Insured male patients age 50 or older with BPH but no evidence of acute urinary retention (AUR) or prostate surgery at the index date

Drug: Early combination therapy; If index drug was an alpha-blocker (AB) (alfuzosin, doxazosin, tamsulosin, or terazosin), a pharmacy claims for a 5-alpha reductase inhibitor (5ARI) (dutasteride, finasteride) on or within 30 days after the index date or if index drug was 5ARI, fill for an AB on or within 30 days after the index date; Other Names: Inc; Avodart® is a registered trademark of GlaxoSmithKline; Proscar® is a registered trademark of Merck; Hytrin® is a registered trademark of Abbott Laboratories; Flomax® is a registered trademark of Astellas Pharma; Cardura® is a registered trademark of Pfizer Inc; Uroxatral® is a registered trademark of Sanofi-Aventis; Rapaflo® is a registered trademark of Watson Pharmaceuticals; Drug: Delayed combination therapy; If index drug was an AB (alfuzosin, doxazosin, tamsulosin, or terazosin), a pharmacy claim for a 5ARI (dutasteride, finasteride) more than 30 days but less than or equal to 180 days of the index date; Other Names: Inc; Avodart® is a registered trademark of GlaxoSmithKline; Proscar® is a registered trademark of Merck; Hytrin® is a registered trademark of Abbott Laboratories; Flomax® is a registered trademark of Astellas Pharma; Cardura® is a registered trademark of Pfizer Inc; Uroxatral® is a registered trademark of Sanofi-Aventis; Rapaflo® is a registered trademark of Watson Pharmaceuticals

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with a code that indicates clinical progression	The number of participants who experience clinical progresion (BPH-surgery or AUR) based on treatment or diagnosis codes and compared between participant records of BPH patients treated with early combination therapy compared with delayed combination therapy	Data collected over a 9-year time period from 2000 to 2009.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean BPH-related medical costs	The mean cost of medical treatment related to BPH in US dollars for records of patients who were treated with early combination therapy and those treated with delayed combination therapy	Data collected over a 9-year time period from 2000 to 2009

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (ACTUAL): March 1, 2011
• Study Completion (ACTUAL): March 1, 2011

Study Registration Dates

• First Submitted: September 15, 2011
• First Submitted That Met QC Criteria: September 15, 2011
• First Posted (ESTIMATE): September 19, 2011

Study Record Updates

• Last Update Posted (ACTUAL): May 16, 2017
• Last Update Submitted That Met QC Criteria: May 15, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: surgery; benign prostatic hyperplasia; enlarged prostate; 5-alpha-reductase inhibitor; acute urinary retention
• Additional Relevant MeSH Terms: Pathologic Processes; Prostatic Diseases; Prostatic Hyperplasia; Hyperplasia; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Urological Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Steroid Synthesis Inhibitors; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; 5-alpha Reductase Inhibitors; Tamsulosin; Alfuzosin; Dutasteride; Doxazosin; Silodosin; Finasteride; Terazosin
• Other Study ID Numbers: 113908