Benign Prostatic Hyperplasia (BPH) Screening Tool Case Finding Study in Subjects >=50 Years

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02757963
• Collaborator: (none)
• Enrollment: 1,679
• Locations: 45
• Arm: 1
• Actual Duration (Months): 9.6
• Patients Per Site: 37.3
• Patients Per Site Per Month: 3.9

Study Details

Study Description

Brief Summary

This non-randomized, interventional study will be conducted in a general practice setting to assess the utility of a benign prostatic enlargement (BPE)/benign prostatic obstruction (BPO) screening tool in conjunction with prostate specific antigen (PSA) in finding men confirmed to have BPH on full urologist assessment of diagnostic test results. The tool may help a General Practitioners (GP) to identify subjects who may have BPH for further tests and improve the speed of referrals to specialists when this is appropriate. The utility of the screening tool will be compared to the validated tool in wide clinical use, the International Prostate Symptom Score (IPSS). This study does not have any formal hypothesis in terms of the primary and secondary endpoint proportions. A BPE/BPO screening tool identifies lower urinary tract symptoms (LUTS) probably due to BPH in men not yet presenting with LUTS. The results of this screening tool will be used for further investigation. All subjects testing positive on the BPE/BPO screening tool (score >=3) tool or on the IPSS (score >=8) will be enrolled and offered a PSA test and urinalysis to establish a diagnosis of probable BPH (Part I-Visit 1). The GP may perform a digital rectal examination (DRE) which will be repeated by the urologist to confirm the diagnosis and to rule out an abnormality suggesting prostate cancer. The GP will make a diagnosis of probable BPH based upon screening results and lab tests which suggest that they are related to BPH and not other causes of such symptoms. The GP will phone the subject to report yes or no for probable BPH Part II (Visit 2). If the subject has probable BPH, the GP will schedule the subject for Visit 3 with an urologist. If the subject does not have probable BPH, then it will be considered that the subject has completed the study. Subjects that proceed to Part II (Visit 3) will be scheduled for a urology assessment performed by an urologist. This assessment includes a DRE and a brief physical exam and review of the PSA test, for a confirmatory diagnosis of BPH and estimation of risk of progression of BPH. Approximately 1,500 subjects presenting to a GP for reasons unrelated to this study will be screened for probable BPH to yield 500 subjects being referred to an urologist. The duration of the study will be 1 week (+/- 4 days) and up to 6 weeks to allow for GP and urologist visit scheduling.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Hyperplasia	Other: Benign prostatic enlargement (BPE)/Benign prostatic obstruction (BPO) screening tool; Other: International Prostate Symptom Score (IPSS) screening tool	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 1679 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Screening
• Official Title: Implementation of a Screening Tool for Subjects With Benign Prostatic Enlargement/Obstruction to Identify Men >=50 Years Presenting in General Practice With Other Co-morbidities Who Should be Assessed for BPH
• Actual Study Start Date: May 12, 2016
• Actual Primary Completion Date: Feb 27, 2017
• Actual Study Completion Date: Feb 27, 2017

Arms and Interventions

Arm

Intervention/Treatment

Other: BPE/BPO screening and IPSS screening tool Subjects presenting to a GP with a primary complaint other than LUTS will be screened for probable BPH using BPE/BPO screening tool and the IPSS screening tool. Subjects testing positive on the BPE/BPO screening tool or on the IPSS will be enrolled and offered a prostate specific antigen (PSA) test and urinalysis to establish a diagnosis of probable benign prostatic hyperplasia (BPH) (Part I - Visit 1). If the GP determines that the subject has probable BPH (IPSS >=8 and/or BPE/BPO questionnaire >=3 with a PSA >=2 ng per ml), the subject will proceed to Part II and will be scheduled for an urologist assessment and diagnostic tests to confirm or refute a BPH diagnosis and to assess risk of progression of BPH.

Other: Benign prostatic enlargement (BPE)/Benign prostatic obstruction (BPO) screening tool; The BPE/BPO screening tool has been developed using the currently recommended Food and Drug Administration (FDA) 2009 guidelines for developing patient-completed questionnaires such as Patient Reported Outcomes. The tool to be used in this study in the General Practice setting has undergone validation in a urology setting to demonstrate the validity of the tool in populations with and without a definite diagnosis of BPH. Subjects who have a positive score on the BPE/BPO screening tool (total score >=3) and meet all other eligibility requirements will be enrolled in Part I of the study.; Other: International Prostate Symptom Score (IPSS) screening tool; The International Prostate Symptom Score (IPSS) score is a validated tool to assess the severity of LUTS symptoms, and has similarly been used for assessing symptomatic efficacy of treatments for BPH. Subjects who have a positive score on the IPSS tool (score >=8) and meet all other eligibility requirements will be enrolled in Part I of the study.

Outcome Measures

Primary Outcome Measures

1. Number of Men With Confirmed Diagnosis of BPH [Up to 6 weeks]

   Confirmed diagnosis of BPH was based on full urologist diagnostic testing with a positive result on the BPE/BPO screening tool (score >=3) and serum PSA >=2 ng/mL. The BPE/BPO questionnaire consists of three questions each with a score ranging from 0= never experienced to 5= almost always experienced. Participants with probable BPH underwent full urologist diagnostic testing, which included review of medical history, symptoms and previous tests, brief physical examination, Digital rectal examination (DRE). Proportion of participants was calculated by dividing number of participants with a positive result on the BPE/BPO screening tool (Score >= 3) and a diagnosis of BPH by the urologist (Numerator) by number of participants with a positive result on the BPE/BPO screening tool (Score >= 3) and a BPH assessment by the urologist (Denominator). 95% confidence interval on the proportion was calculated by using the exact (Clopper-Pearson) method.

Secondary Outcome Measures

1. Number of Men That Are Confirmed to Have BPH Based on Full Urologist Assessment of Diagnostic Test Results Among Men With a Positive Result on the IPSS, BPE/BPO and IPSS, and BPE/BPO or IPSS Screening Tools and Serum PSA >=2 ng/mL [Up to 6 weeks]

   Confirmed diagnosis of BPH was based on full urologist diagnostic testing with a positive result on the IPSS, BPE/BPO and IPSS, BPE/BPO or IPSS screening tools and serum PSA >=2 ng/mL. The BPE/BPO questionnaire consists of three questions each with a score ranging from 0= never experienced to 5= almost always experienced. IPSS tool is used to assess the severity of LUTS symptoms with a score ranging from 0= never experienced to 5= almost always experienced. Participants with probable BPH underwent full urologist diagnostic testing, which included review of medical history, symptoms and previous tests, brief physical examination, DRE. Proportion of participants was calculated by dividing number of participants with a positive result on the screening tool and a diagnosis of BPH by the urologist (Numerator) by number of participants with a positive result on the screening tool and a BPH assessment by the urologist(Denominator).

2. Number of Men That Are Confirmed to be at Risk for BPH Progression Based Upon Full Urologist Assessment Among Men With a Positive Result on the BPE/BPO, IPSS, BPE/BPO and IPSS, and BPE/BPO or IPSS Screening Tools and Serum PSA >=2 ng/mL [Up to 6 weeks]

   Confirmed risk for BPH was based on full urologist diagnostic testing with a positive result on the BPE/BPO and/or IPSS screening tool and probable GP BPH diagnosis. The BPE/BPO questionnaire consists of 3 questions each with a score from 0= never experienced to 5= almost always experienced. IPSS tool is used to assess the severity of LUTS symptoms with a score from 0= never experienced to 5= almost always experienced. Participants with probable BPH underwent full urologist diagnostic testing, which included review of medical history, symptoms and previous tests, physical examination, DRE. Participants with PSA >=2.0 ng/mL and other tests were considered as at risk for BPH. Proportion of participants was calculated by dividing number of participants with a positive result on the screening tool and diagnosis of BPH progression risk (Numerator) by number of participants with a positive result on the screening tool and a BPH progression risk assessment by the urologist (Denominator).

3. Number of Men That Are Diagnosed With Probable BPH as Assessed by the GP Among Men With a Positive Result on the BPE/BPO, IPSS, BPE/BPO and IPSS, and BPE/BPO or IPSS Screening Tools [Up to 6 weeks]

   Diagnosis of probable BPH was based on GP assessment among men with a positive result on the BPE/BPO and/or IPSS screening tool. The BPE/BPO questionnaire consists of 3 questions each with a score from 0= never experienced to 5= almost always experienced. IPSS tool is used to assess the severity of LUTS symptoms with a score from 0= never experienced to 5= almost always experienced. Probable BPH is the presumptive diagnosis of urinary tract obstruction from an enlarged prostate based on clinical symptoms and findings where urinary symptoms are not apparently related to any other cause. Participants underwent GP assessment and lab result review by GP. Participants with PSA >=2 ng/mL were assessed for probable BPH. Proportion of participants was calculated by dividing number of participants with a positive result on the screening tool and diagnosis of probable BPH (Numerator) by number of participants with a positive result on the screening tool and a BPH assessment by GP (Denominator).

4. Summary of Agreement Between BPE/BPO and IPSS Screening Tools [Day 1]

   Agreement between the IPSS and BPE/BPO tools had to utilize the screened population, as the evaluable population did not include any participants with IPSS <8 and BPE/BPO<3. All screened participants with IPSS and BPE/BPO results were utilized (2327 of the 2343 participants had IPSS and BPE/PO results). There were 16 participants (2343 minus 2327) in the screened population without IPSS and BPE/BPO results, and hence were not included in the calculation of the Kappa statistic. Kappa statistic values of <0 were characterized as no agreement, 0 to 0.20 as slight, 0.21 to 0.40 as fair, 0.41 to 0.60 as moderate, 0.61 to 0.80 as substantial, and 0.81 to 1.00 as almost perfect agreement. The 95% confidence interval for the Kappa statistic is based on the asymptotic standard error.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Greater than or equal to (>=) 50 years of age at the time of signing the informed consent form.

• Male.

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and protocol.

• Present in a General Practice setting for a reason unrelated to this study.

• Positive IPSS score >=8 and/or positive BPE/BPO screening tool score >=3.

Exclusion Criteria:

• History of BPH for which they have received test procedures, medical intervention and/or medicine.

• History of prostate-related LUTS for which they have received test procedures, medical intervention and/or medicine.

• History of prostatic surgery (including transurethral resection of the prostate (TURP), balloon dilatation, thermotherapy, and/or stent replacement) or other invasive or minimally invasive procedures to treat BPH.

• Has other conditions that may cause urinary symptoms (e.g., neurogenic bladder, bladder neck contracture, urethral stricture, bladder malignancy, acute or chronic prostatitis, or acute or chronic urinary tract infections, etc.).

• History or evidence of prostate cancer (e.g., positive biopsy or ultrasound, suspicious DRE and/or rising PSA).

• Current or prior use of the following: 5alpha-reductase inhibitors (finasteride or dutasteride); anti-cholinergics (e.g. oxybutynin, propantheline, tolterodine, solifenacin, darifenacin, mirabegron) alpha-adrenoreceptor blockers (i.e., indoramin, prazosin, terazosin, tamsulosin, alfuzosin, doxazosin and silodosin), herbal products for urinary symptoms; Use of any investigational study drug within 30 days or 5 half-lives of the drug in question, (whichever is longer), preceding the first study visit.

• Use within previous 30 days at Visit 1 of: phosphodiesterase type 5 inhibitor (PDE-5) inhibitors for erectile dysfunction; anabolic steroids

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Aigrefeuille Sur Maine		France	44140
2	GSK Investigational Site	Grenay		France	62160
3	GSK Investigational Site	Haute Goulaine		France	44115
4	GSK Investigational Site	La Montagne		France	44620
5	GSK Investigational Site	Nantes cedex 2		France	44277
6	GSK Investigational Site	Rosiers-d'Egletons		France	19300
7	GSK Investigational Site	Rouen		France	76000
8	GSK Investigational Site	Thouars		France	79100
9	GSK Investigational Site	Weinheim	Baden-Wuerttemberg	Germany	69469
10	GSK Investigational Site	Muenchen	Bayern	Germany	80339
11	GSK Investigational Site	Floersheim	Hessen	Germany	65439
12	GSK Investigational Site	Buchholz	Niedersachsen	Germany	21244
13	GSK Investigational Site	Dippoldiswalde	Sachsen	Germany	01744
14	GSK Investigational Site	Freital	Sachsen	Germany	01705
15	GSK Investigational Site	Leipzig	Sachsen	Germany	04329
16	GSK Investigational Site	Berlin		Germany	10117
17	GSK Investigational Site	Magdeburg		Germany	39120
18	GSK Investigational Site	Aradeo	Puglia	Italy	73040
19	GSK Investigational Site	Cutrofiano (LE)	Puglia	Italy	73020
20	GSK Investigational Site	Galatina (LE)	Puglia	Italy	73013
21	GSK Investigational Site	Ruffano (LE)	Puglia	Italy	73049
22	GSK Investigational Site	Civitella Paganico (GR)	Toscana	Italy	58045
23	GSK Investigational Site	Grosseto	Toscana	Italy	58100
24	GSK Investigational Site	Arkhangelsk		Russian Federation	163020
25	GSK Investigational Site	Ivanovo		Russian Federation	153005
26	GSK Investigational Site	Izhevsk		Russian Federation	426063
27	GSK Investigational Site	Moscow		Russian Federation	123098
28	GSK Investigational Site	Naro-Fominsk		Russian Federation	143300
29	GSK Investigational Site	Novosibirsk		Russian Federation	630099
30	GSK Investigational Site	Odintsovo		Russian Federation	143005
31	GSK Investigational Site	Saint Petersburg		Russian Federation	195067
32	GSK Investigational Site	Saint Petesburg		Russian Federation	195030
33	GSK Investigational Site	Saint-Petersburg		Russian Federation	195271
34	GSK Investigational Site	Saint-Petersburg		Russian Federation	198328
35	GSK Investigational Site	Smolensk		Russian Federation	214031
36	GSK Investigational Site	St'Petersburg		Russian Federation	197706
37	GSK Investigational Site	Tomsk		Russian Federation	634 050
38	GSK Investigational Site	Ulyanovsk		Russian Federation	432063
39	GSK Investigational Site	Yaroslavl		Russian Federation	150000
40	GSK Investigational Site	Bormujo (Sevilla)		Spain	41930
41	GSK Investigational Site	Cadiz		Spain	11009
42	GSK Investigational Site	Granada		Spain	18014
43	GSK Investigational Site	Sevilla		Spain	41014
44	GSK Investigational Site	Valencia		Spain	46010
45	GSK Investigational Site	Valencia		Spain	46026

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Jan 18, 2016
• Statistical Analysis Plan - Apr 20, 2017

More Information

Publications

• Tubaro A, Niero M, Adalig B, Lulic Z, Plastino J, Kimbrough C, Manyak MJ. Evaluation of a 3-item screening tool to identify men with benign prostatic enlargement/obstruction in a primary care cohort. Minerva Urol Nephrol. 2022 Feb;74(1):85-92. doi: 10.23736/S2724-6051.20.03834-5. Epub 2020 Sep 29.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02757963
• Other Study ID Numbers: 116114
• First Posted: May 2, 2016
• Last Update Posted: Jan 5, 2021
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Screening tool; International Prostate Symptom Score; Lower urinary tract symptoms; BPO; BPE; Benign prostatic enlargement; Benign prostatic obstruction; LUTS; Benign prostatic hyperplasia; IPSS; BPH
• Additional relevant MeSH terms: Prostatic Hyperplasia; Hyperplasia

Study Results

Participant Flow

Recruitment Details	A total of 1658 male participants, >=50 years of age, with reasons not related to lower urinary tract symptoms (LUTS) were included in evaluable Population. The study was conducted at 47 centers in 5 countries; 8 centers in France, 9 centers in Germany, 6 centers in Italy, 18 centers in Russia and 6 centers in Spain.
Pre-assignment Detail	A total of 2343 male participants were screened for probable Benign prostatic hyperplasia (BPH). Of these, 1679 participants were enrolled, 1658 participants were included in the evaluable population. 21 participants progressed in the study but were found to have not met eligibility criteria. Overall, 561 participants completed all 3 visits.

Arm/Group Title	IPSS >=8 or BPE/BPO >=3
Arm/Group Description	Participants were screened using the Benign prostatic enlargement (BPE)/ benign prostatic obstruction (BPO) and International Prostate Symptom Score (IPSS) screening tools. Participants with positive responses (i.e. met entry criteria, including positive IPSS score >= 8 and/or BPE/BPO score >= 3) were enrolled and proceeded to Part I (GP Assessment). Participants with probable BPH [PSA>= 2 Nano gram per milliliter (ng/mL)] proceeded to Part II and were scheduled for a urologist assessment which was to confirm or refute a diagnosis of BPH and to estimate whether the participant is at risk of progression of BPH.
Period Title: Overall Study
STARTED	1658
COMPLETED	561
NOT COMPLETED	1097

Baseline Characteristics

Arm/Group Title	IPSS >=8 or BPE/BPO >=3
Arm/Group Description	Participants were screened using the BPE/BPO and IPSS screening tools. Participants with positive responses (i.e. met entry criteria, including positive IPSS score >=8 and/or BPE/BPO score >=3) were enrolled and proceeded to Part I (GP Assessment). Participants with probable BPH (PSA>=2 ng/mL) proceeded to Part II and were scheduled for a urologist assessment which was to confirm or refute a diagnosis of BPH and to estimate whether the participant is at risk of progression of BPH.
Overall Participants	1658
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.8 (8.26)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	1658 100%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage	2 0.1%
Asian - Central/South Asian Heritage	2 0.1%
White - Arabic/ North African Heritage	2 0.1%
White - White/ Caucasian/European Heritage	1550 93.5%
White - Mixed Race	1 0.1%
Mixed Race	2 0.1%

Outcome Measures

1. Primary Outcome

Title	Number of Men With Confirmed Diagnosis of BPH
Description	Confirmed diagnosis of BPH was based on full urologist diagnostic testing with a positive result on the BPE/BPO screening tool (score >=3) and serum PSA >=2 ng/mL. The BPE/BPO questionnaire consists of three questions each with a score ranging from 0= never experienced to 5= almost always experienced. Participants with probable BPH underwent full urologist diagnostic testing, which included review of medical history, symptoms and previous tests, brief physical examination, Digital rectal examination (DRE). Proportion of participants was calculated by dividing number of participants with a positive result on the BPE/BPO screening tool (Score >= 3) and a diagnosis of BPH by the urologist (Numerator) by number of participants with a positive result on the BPE/BPO screening tool (Score >= 3) and a BPH assessment by the urologist (Denominator). 95% confidence interval on the proportion was calculated by using the exact (Clopper-Pearson) method.
Time Frame	Up to 6 weeks

Outcome Measure Data

Analysis Population Description

All Evaluable Subject Population comprised of all participants who meet the entry criteria, including a positive IPSS screening result (score >=8) and/or a positive BPE/BPO screening result (score >=3).

Arm/Group Title	BPE/BPO >=3
Arm/Group Description	Participants were screened using the BPE/ BPO screening tools. Participants with a positive response to this tool (i.e. Participants met entry criteria, including a positive BPE/BPO score >= 3) were enrolled and proceeded to Part I (GP Assessment) of the study. Participants with probable BPH (PSA>= 2 ng/mL) proceeded to Part II and were scheduled for the urologist assessment to confirm diagnosis of BPH and to estimate whether the participant was at risk of progression of BPH
Measure Participants	1249
Numerator	386 23.3%
Denominator	437 26.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BPE/BPO >=3
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	0.883
	Confidence Interval	(2-Sided) 95%; 0.849 to 0.912
	Parameter Dispersion	Type: Value:
	Estimation Comments	Proportion = Numerator / Denominator. 95% confidence interval on the proportion is calculated by using the exact (Clopper-Pearson) method.

2. Secondary Outcome

Title	Number of Men That Are Confirmed to Have BPH Based on Full Urologist Assessment of Diagnostic Test Results Among Men With a Positive Result on the IPSS, BPE/BPO and IPSS, and BPE/BPO or IPSS Screening Tools and Serum PSA >=2 ng/mL
Description	Confirmed diagnosis of BPH was based on full urologist diagnostic testing with a positive result on the IPSS, BPE/BPO and IPSS, BPE/BPO or IPSS screening tools and serum PSA >=2 ng/mL. The BPE/BPO questionnaire consists of three questions each with a score ranging from 0= never experienced to 5= almost always experienced. IPSS tool is used to assess the severity of LUTS symptoms with a score ranging from 0= never experienced to 5= almost always experienced. Participants with probable BPH underwent full urologist diagnostic testing, which included review of medical history, symptoms and previous tests, brief physical examination, DRE. Proportion of participants was calculated by dividing number of participants with a positive result on the screening tool and a diagnosis of BPH by the urologist (Numerator) by number of participants with a positive result on the screening tool and a BPH assessment by the urologist(Denominator).
Time Frame	Up to 6 weeks

Outcome Measure Data

Analysis Population Description

All Evaluable Subjects Population

Arm/Group Title	IPSS >=8	IPSS >=8 and BPE/BPO >=3	IPSS >=8 or BPE/BPO >=3
Arm/Group Description	Participants were screened using the IPSS screening tool. Participants with a positive response to this tool (i.e. Participants met entry criteria, including a positive IPSS score >=8) were enrolled and proceeded to Part I (GP Assessment) of the study. Participants with probable BPH (PSA >=2 ng/mL) proceeded to Part II and were scheduled for the urologist assessment to confirm diagnosis of BPH and to estimate whether the participant was at risk of progression of BPH.	Participants were screened using the BPE/BPO and IPSS screening tools. Participants with positive responses to these tools (i.e. Participants met entry criteria, including a positive IPSS score >=8 and BPE/BPO score >=3) were enrolled and proceeded to Part I (GP Assessment) of the study. Participants with probable BPH (PSA >=2 ng/mL) proceeded to Part II and were scheduled for the urologist assessment to confirm diagnosis of BPH and to estimate whether the participant was at risk of progression of BPH	Participants were screened using the BPE/BPO and IPSS screening tools. Participants with positive responses to these tools (i.e. Participants met entry criteria, including a positive IPSS score >=8 or BPE/BPO score >=3) were enrolled and proceeded to Part I (GP Assessment) of the study. Participants with probable BPH (PSA >=2 ng/mL) proceeded to Part II and were scheduled for the urologist assessment to confirm diagnosis of BPH and to estimate whether the participant was at risk of progression of BPH
Measure Participants	1558	1149	1658
Numerator	471 28.4%	367 NaN	490 NaN
Denominator	537 32.4%	413 NaN	561 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BPE/BPO >=3
	Comments	For Arm IPSS >=8
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	0.877
	Confidence Interval	(2-Sided) 95%; 0.846 to 0.904
	Parameter Dispersion	Type: Value:
	Estimation Comments	Proportion = Numerator / Denominator. 95% confidence interval on the proportion is calculated by using the exact (Clopper-Pearson) method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IPSS >=8 and BPE/BPO >=3
	Comments	For Arm IPSS >=8 and BPE/BPO >=3
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	0.889
	Confidence Interval	(2-Sided) 95%; 0.854 to 0.917
	Parameter Dispersion	Type: Value:
	Estimation Comments	Proportion = Numerator / Denominator. 95% confidence interval on the proportion is calculated by using the exact (Clopper-Pearson) method.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	IPSS >=8 or BPE/BPO >=3
	Comments	For Arm IPSS >=8 or BPE/BPO >=3
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	0.873
	Confidence Interval	(2-Sided) 95%; 0.843 to 0.900
	Parameter Dispersion	Type: Value:
	Estimation Comments	Proportion = Numerator / Denominator. 95% confidence interval on the proportion is calculated by using the exact (Clopper-Pearson) method.

3. Secondary Outcome

Title	Number of Men That Are Confirmed to be at Risk for BPH Progression Based Upon Full Urologist Assessment Among Men With a Positive Result on the BPE/BPO, IPSS, BPE/BPO and IPSS, and BPE/BPO or IPSS Screening Tools and Serum PSA >=2 ng/mL
Description	Confirmed risk for BPH was based on full urologist diagnostic testing with a positive result on the BPE/BPO and/or IPSS screening tool and probable GP BPH diagnosis. The BPE/BPO questionnaire consists of 3 questions each with a score from 0= never experienced to 5= almost always experienced. IPSS tool is used to assess the severity of LUTS symptoms with a score from 0= never experienced to 5= almost always experienced. Participants with probable BPH underwent full urologist diagnostic testing, which included review of medical history, symptoms and previous tests, physical examination, DRE. Participants with PSA >=2.0 ng/mL and other tests were considered as at risk for BPH. Proportion of participants was calculated by dividing number of participants with a positive result on the screening tool and diagnosis of BPH progression risk (Numerator) by number of participants with a positive result on the screening tool and a BPH progression risk assessment by the urologist (Denominator).
Time Frame	Up to 6 weeks

Outcome Measure Data

Analysis Population Description

All Evaluable Subjects Population

Arm/Group Title	IPSS >=8	BPE/BPO >=3	IPSS >=8 and BPE/BPO >=3	IPSS >=8 or BPE/BPO >=3
Arm/Group Description	Participants were screened using the IPSS screening tool. Participants with a positive response to this tool (i.e. Participants met entry criteria, including a positive IPSS score >= 8) were enrolled and proceeded to Part I (GP Assessment) of the study. Participants with probable BPH (PSA >= 2 ng/mL) proceeded to Part II and were scheduled for the urologist assessment to confirm diagnosis of BPH and to estimate whether the participant was at risk of progression of BPH.	Participants were screened using BPE/BPO screening tool. Participants with a positive response to this tool (i.e. Participants met entry criteria, including a positive BPE/BPO score >=3) were enrolled and proceeded to Part I (GP Assessment) of the study. Participants with probable BPH (PSA >=2 ng/mL) proceeded to Part II and were scheduled for the urologist assessment to confirm diagnosis of BPH and to estimate risk of progression of BPH	Participants were screened using the BPE/BPO and IPSS screening tools. Participants with positive responses to these tools (i.e. Participants met entry criteria, including a positive IPSS score >= 8 and BPE/BPO score >= 3) were enrolled and proceeded to Part I (GP Assessment) of the study. Participants with probable BPH (PSA >= 2 ng/mL) proceeded to Part II and were scheduled for the urologist assessment to confirm diagnosis of BPH and to estimate whether the participant was at risk of progression of BPH	Participants were screened using the BPE/BPO and IPSS screening tools. Participants with positive responses to these tools (i.e. Participants met entry criteria, including a positive IPSS score >= 8 or BPE/BPO score >= 3) were enrolled and proceeded to Part I (GP Assessment) of the study. Participants with probable BPH (PSA >= 2 ng/mL) proceeded to Part II and were scheduled for the urologist assessment to confirm diagnosis of BPH and to estimate whether the participant was at risk of progression of BPH
Measure Participants	1558	1249	1149	1658
Numerator	424 25.6%	350 NaN	333 NaN	441 NaN
Denominator	471 28.4%	386 NaN	367 NaN	490 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BPE/BPO >=3
	Comments	For Arm IPSS >=8
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	0.900
	Confidence Interval	(2-Sided) 95%; 0.870 to 0.926
	Parameter Dispersion	Type: Value:
	Estimation Comments	Proportion = Numerator / Denominator. 95% confidence interval on the proportion is calculated by using the exact (Clopper-Pearson) method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IPSS >=8 and BPE/BPO >=3
	Comments	For Arm BPE/BPO >=3
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	0.907
	Confidence Interval	(2-Sided) 95%; 0.873 to 0.934
	Parameter Dispersion	Type: Value:
	Estimation Comments	Proportion = Numerator / Denominator. 95% confidence interval on the proportion is calculated by using the exact (Clopper-Pearson) method.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	IPSS >=8 or BPE/BPO >=3
	Comments	For Arm IPSS >=8 and BPE/BPO >=3
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	0.907
	Confidence Interval	(2-Sided) 95%; 0.873 to 0.935
	Parameter Dispersion	Type: Value:
	Estimation Comments	Proportion = Numerator / Denominator. 95% confidence interval on the proportion is calculated by using the exact (Clopper-Pearson) method.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	IPSS >=8 or BPE/BPO >=3
	Comments	For Arm PSS >=8 or BPE/BPO >=3
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	0.900
	Confidence Interval	(2-Sided) 95%; 0.870 to 0.925
	Parameter Dispersion	Type: Value:
	Estimation Comments	Proportion = Numerator / Denominator. 95% confidence interval on the proportion is calculated by using the exact (Clopper-Pearson) method.

4. Secondary Outcome

Title	Number of Men That Are Diagnosed With Probable BPH as Assessed by the GP Among Men With a Positive Result on the BPE/BPO, IPSS, BPE/BPO and IPSS, and BPE/BPO or IPSS Screening Tools
Description	Diagnosis of probable BPH was based on GP assessment among men with a positive result on the BPE/BPO and/or IPSS screening tool. The BPE/BPO questionnaire consists of 3 questions each with a score from 0= never experienced to 5= almost always experienced. IPSS tool is used to assess the severity of LUTS symptoms with a score from 0= never experienced to 5= almost always experienced. Probable BPH is the presumptive diagnosis of urinary tract obstruction from an enlarged prostate based on clinical symptoms and findings where urinary symptoms are not apparently related to any other cause. Participants underwent GP assessment and lab result review by GP. Participants with PSA >=2 ng/mL were assessed for probable BPH. Proportion of participants was calculated by dividing number of participants with a positive result on the screening tool and diagnosis of probable BPH (Numerator) by number of participants with a positive result on the screening tool and a BPH assessment by GP (Denominator).
Time Frame	Up to 6 weeks

Outcome Measure Data

Analysis Population Description

All Evaluable Subjects Population

Arm/Group Title	IPSS >=8	BPE/BPO >=3	IPSS >=8 and BPE/BPO >=3	IPSS >= 8 or BPE/BPO >=3
Arm/Group Description	Participants were screened using the IPSS screening tool. Participants with a positive response to this tool (i.e. Participants met entry criteria, including a positive IPSS score >=8) were enrolled and proceeded to Part I (GP Assessment) of the study. Participants with probable BPH (PSA >=2 ng/mL) proceeded to Part II and were scheduled for the urologist assessment to confirm diagnosis of BPH and to estimate whether the participant was at risk of progression of BPH.	Participants were screened using BPE/BPO screening tools. Participants with a positive response to this tool (i.e. Participants met entry criteria, including a positive BPE/BPO score >=3) were enrolled and proceeded to Part I (GP Assessment) of the study. Participants with probable BPH (PSA >=2 ng/mL) proceeded to Part II and were scheduled for the urologist assessment to confirm diagnosis of BPH and to estimate risk of progression of BPH	Participants were screened using the BPE/BPO and IPSS screening tools. Participants with positive responses to these tools (i.e. Participants met entry criteria, including a positive IPSS score >=8 and BPE/BPO score >=3) were enrolled and proceeded to Part I (GP Assessment) of the study. Participants with probable BPH (PSA >=2 ng/mL) proceeded to Part II and were scheduled for the urologist assessment to confirm diagnosis of BPH and to estimate whether the participant was at risk of progression of BPH	Participants were screened using the BPE/BPO and IPSS screening tools. Participants with positive responses to these tools (i.e. Participants met entry criteria, including a positive IPSS score >=8 or BPE/BPO score >=3) were enrolled and proceeded to Part I (GP Assessment) of the study. Participants with probable BPH (PSA >=2 ng/mL) proceeded to Part II and were scheduled for the urologist assessment to confirm diagnosis of BPH and to estimate whether the participant was at risk of progression of BPH
Measure Participants	1558	1249	1149	1658
Numerator	556 33.5%	453 NaN	428 NaN	581 NaN
Denominator	1538 92.8%	1232 NaN	1135 NaN	1635 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BPE/BPO >=3
	Comments	For Arm IPSS >=8
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	0.362
	Confidence Interval	(2-Sided) 95%; 0.337 to 0.386
	Parameter Dispersion	Type: Value:
	Estimation Comments	Proportion = Numerator / Denominator. 95% confidence interval on the proportion is calculated by using the exact (Clopper-Pearson) method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IPSS >=8 and BPE/BPO >=3
	Comments	For Arm BPE/BPO >=3
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	0.368
	Confidence Interval	(2-Sided) 95%; 0.341 to 0.395
	Parameter Dispersion	Type: Value:
	Estimation Comments	Proportion = Numerator / Denominator. 95% confidence interval on the proportion is calculated by using the exact (Clopper-Pearson) method.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	IPSS >=8 or BPE/BPO >=3
	Comments	For Arm IPSS >=8 and BPE/BPO >=3
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	0.377
	Confidence Interval	(2-Sided) 95%; 0.349 to 0.406
	Parameter Dispersion	Type: Value:
	Estimation Comments	Proportion = Numerator / Denominator. 95% confidence interval on the proportion is calculated by using the exact (Clopper-Pearson) method.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	IPSS >=8 or BPE/BPO >=3
	Comments	For Arm IPSS >=8 or BPE/BPO >=3
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	0.355
	Confidence Interval	(2-Sided) 95%; 0.332 to 0.379
	Parameter Dispersion	Type: Value:
	Estimation Comments	Proportion = Numerator / Denominator. 95% confidence interval on the proportion is calculated by using the exact (Clopper-Pearson) method.

5. Secondary Outcome

Title	Summary of Agreement Between BPE/BPO and IPSS Screening Tools
Description	Agreement between the IPSS and BPE/BPO tools had to utilize the screened population, as the evaluable population did not include any participants with IPSS <8 and BPE/BPO<3. All screened participants with IPSS and BPE/BPO results were utilized (2327 of the 2343 participants had IPSS and BPE/PO results). There were 16 participants (2343 minus 2327) in the screened population without IPSS and BPE/BPO results, and hence were not included in the calculation of the Kappa statistic. Kappa statistic values of <0 were characterized as no agreement, 0 to 0.20 as slight, 0.21 to 0.40 as fair, 0.41 to 0.60 as moderate, 0.61 to 0.80 as substantial, and 0.81 to 1.00 as almost perfect agreement. The 95% confidence interval for the Kappa statistic is based on the asymptotic standard error.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

All Screened Subjects Population comprised of all participants who were screened for eligibility. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Arm/Group Title	All Screened Subjects
Arm/Group Description	All the participants who signed informed consent form and were screened for eligibility were included in this arm
Measure Participants	2327
Count of Participants [Participants]	1812 109.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BPE/BPO >=3
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Kappa statistic
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; 0.51 to 0.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse events (AEs) and serious adverse events (SAEs) were collected from screening (Visit 1) through 6 weeks
Adverse Event Reporting Description	On-therapy SAEs and non-serious AEs are reported for members of All Evaluable Subjects Population which comprised of all participants who met the entry criteria, including a positive IPSS screening result (score >=8) and/or a positive BPE/BPO screening result (score >=3)
Arm/Group Title	IPSS >= 8 or BPE/BPO >= 3
Arm/Group Description	Participants were screened using the BPE/BPO and IPSS screening tools. Participants with positive responses to these tools (i.e. Participants met entry criteria, including a positive IPSS score >= 8 or BPE/BPO score >= 3) were enrolled and proceeded to Part I (GP Assessment) of the study. Participants with probable BPH (PSA >= 2 ng/mL) proceeded to Part II and were scheduled for the urologist assessment to confirm diagnosis of BPH and to estimate whether the participant was at risk of progression of BPH
All Cause Mortality
	IPSS >= 8 or BPE/BPO >= 3
	Affected / at Risk (%)	# Events
Total	1/1658 (0.1%)
Serious Adverse Events
	IPSS >= 8 or BPE/BPO >= 3
	Affected / at Risk (%)	# Events
Total	9/1658 (0.5%)
Cardiac disorders
Atrial flutter	1/1658 (0.1%)
Myocardial infarction	1/1658 (0.1%)
General disorders
Sudden death	1/1658 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	6/1658 (0.4%)
Other (Not Including Serious) Adverse Events
	IPSS >= 8 or BPE/BPO >= 3
	Affected / at Risk (%)	# Events
Total	0/1658 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.