APPENDIX A: Methods for Evidence Synthesis 

Literature Search 

To identify relevant citations, we searched Ovid MEDLINE (1966 to July 2006.) For Key 

Question #1 we used the following search strategy: 

1. exp Adrenergic alpha-Antagonists/ad, ae, cl, tu, ct, du [Administration & Dosage, Adverse 

Effects, Classification, Therapeutic Use, Contraindications, Diagnostic Use] 

2. exp Prostatic Hyperplasia/mo, cl, co, di, pc, dh, dt, ep, su, th, ge [Mortality, Classification, 

Complications, Diagnosis, Prevention & Control, Diet Therapy, Drug Therapy, 

Epidemiology, Surgery, Therapy, Genetics] 

3. 1 and 2 

4. limit 3 (humans and male and "all adult (19 plus years)" and (clinical trial, phase i or 

clinical trial, phase ii or clinical trial, phase iii or clinical trial, phase iv or clinical trial or 

controlled clinical trial or evaluation studies or multicenter study or randomized controlled 

trial or technical report)) 

5. explode Finasteride 

6. 3 and 5 

For Key Questions #2 and #3, we used steps 1 to 4 of the same search string. We searched the 

Cochrane Database of Systematic Reviews (2nd quarter, 2006) but did not identify any additional 

systematic reviews. 

All citations were imported into an electronic database (EndNote 9.0).

Study Selection 

One reviewer assessed abstracts of citations identified from literature searches for inclusion, using 

the criteria described above. Full-text articles of potentially relevant abstracts were retrieved and a 

second review for inclusion was conducted by reapplying the inclusion criteria. 

Data Abstraction 

The following data were abstracted from included trials: study design, setting, population 

characteristics (including sex, age, ethnicity, diagnosis), eligibility and exclusion criteria, 

interventions (dose and duration), comparisons, numbers screened, eligible, enrolled, and lost to 

follow-up, method of outcome ascertainment, and results for each outcome. We recorded 

intention-to-treat results when reported. In cases where only per-protocol results were reported, 

we calculated intention-to-treat results if the data for these calculations were available. In trials 

with crossover, outcomes for the first intervention were recorded if available. This was because of 

the potential for differential withdrawal prior to crossover biasing subsequent results and the 

possibility of either a “carryover effect” (from the first treatment) in studies without a washout 

period, or “rebound” effect from withdrawal of the first intervention. 

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Data abstracted from observational studies included design, eligibility criteria duration, 

interventions, concomitant medication, assessment techniques, age, gender, ethnicity, number of 

patients screened, eligible, enrolled, withdrawn, or lost to follow-up, number analyzed, and results. 

Quality Assessment 

We assessed the internal validity (quality) of trials based on the predefined criteria listed in 

Appendix B. These criteria are based on the U.S. Preventive Services Task Force and the National 

Health Service Centre for Reviews and Dissemination (U.K.) criteria.22, 23 We rated the internal 

validity of each trial based on the methods used for randomization, allocation concealment, and 

blinding; the similarity of compared groups at baseline; maintenance of comparable groups; 

adequate reporting of dropouts, attrition, crossover, adherence, and contamination; loss to followup; and the use of intention-to-treat analysis. Trials that had a fatal flaw in one or more categories 

were rated “poor-quality”; trials that met all criteria were rated “good-quality”; the remainder were 

rated “fair-quality.” A fatal flaw occurs when there is evidence of bias or confounding in the trial, 

for example when randomization and concealment of allocation of random order are not reported 

and baseline characteristics differ significantly between the groups. In this case, randomization 

has apparently failed and for one reason or another bias has been introduced. 

As the fair-quality category is broad, studies with this rating vary in their strengths and 

weaknesses: the results of some fair-quality studies are likely to be valid, while others are only 

probably valid. Those studies considered only probably valid are indicated as such using a “fairpoor” rating. A poor-quality trial is not valid—the results are at least as likely to reflect flaws in 

the study design as the true difference between the compared drugs. External validity of trials was 

assessed based on whether the publication adequately described the study population, how similar 

patients were to the target population in whom the intervention will be applied, and whether the 

treatment received by the control group was reasonably representative of standard practice. We 

also recorded the role of the funding source. 

Appendix B also shows the criteria we used to rate observational studies. These criteria reflect 

aspects of the study design that are particularly important for assessing adverse event rates. We 

rated observational studies as good-quality for adverse event assessment if they adequately met six 

or more of the seven predefined criteria, fair-quality if they met three to five criteria and poorquality if they met two or fewer criteria. 

Included systematic reviews were also rated for quality based on pre-defined criteria (see 

Appendix B), based on a clear statement of the questions(s), inclusion criteria, adequacy of search 

strategy, validity assessment and adequacy of detail provided for included studies, and 

appropriateness of the methods of synthesis. 

Overall quality ratings for the individual study were based on internal and external validity ratings 

for that trial. A particular randomized trial might receive two different ratings: one for 

effectiveness and another for adverse events. The overall strength of evidence for a particular key 

question reflects the quality, consistency, and power of the set of studies relevant to the question. 

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Evidence Synthesis 

An evidence report pays particular attention to the generalizability of efficacy studies performed in 

controlled or academic settings. Efficacy studies provide the best information about how a drug 

performs in a controlled setting that allow for better control over potential confounding factors and 

bias. However, efficacy studies have some limitations, as the results are not always applicable to 

many, or to most, patients seen in everyday practice. This is because most efficacy studies use 

strict eligibility criteria which may exclude patients based on their age, sex, medication 

compliance, or severity of illness. For many drug classes severely impaired patients are often 

excluded from trials. Often, efficacy studies also exclude patients who have “comorbid” diseases, 

meaning diseases other than the one under study. Efficacy studies may also use dosing regimens 

and follow up protocols that may be impractical in other practice settings. They often restrict 

options, such as combining therapies or switching drugs, that are of value in actual practice. They 

often examine the short-term effects of drugs that, in practice, are used for much longer periods of 

time. Finally, they tend to use objective measures of effect that do not capture all of the benefits 

and harms of a drug or do not reflect the outcomes that are most important to patients and their 

families. 

Data Presentation 

We constructed evidence tables showing the study characteristics, quality ratings, and results for 

all included studies. Studies that evaluated one macrolide against another provided direct evidence 

of comparative benefits and harms. Outcomes of changes in symptom measured using scales or 

tools with good validity and reliability are preferred over scales or tools with low 

validity/reliability or no reports of validity/reliability testing. Where possible, head-to-head data 

are the primary focus of the synthesis. No meta-analyses were conducted in this review due to 

heterogeneity in treatment regimens, use of concomitant medications, outcome reporting and 

patient populations. 

In theory, trials that compare these drugs to other interventions or placebos can also provide 

evidence about effectiveness. This is known as an indirect comparison and can be difficult to 

interpret for a number of reasons, primarily issues of heterogeneity between trial populations, 

interventions, and assessment of outcomes. Indirect data are used to support direct comparisons, 

where they exist, and are also used as the primary comparison where no direct comparisons exist. 

Such indirect comparisons should be interpreted with caution. 
Appendix B: Trials comparing alpha antagonists 

Clinical Trial Inclusion Criteria/Pt. 

Population 

Intervention Results Safety/Com

Cam et al 2003 Prospective clinical study 178 patients doxazosin 4 mg 24 months no financial disclosure Turkish 

Men > 50 years old IPSS 18-35 Attendance to a urology department due to: -LUTS -age > 50 -unremarkable medical hx in terms of LUTS -no definitive need for surgery 

Doxazosin 1 mg titrated to 4 mg 

Reduction in symptom scores from 24 (SD 

+7.4) before medication to 17 (SD 

+8.4) after 

3 months of treatment 

In the patients reporting doxazosin as ineffective, no change, or effective, 93%, 59% and 15% respectively underwent surgery. Of the 178 patients enrolled 47% underwent surgery. 

Evaluation determined regarding ttreatment i

Ichioka et al 2004 Prospective 123 patients 43 months Tamsulosin (n = 123) No financial disclosure Japanese 

Men 53-88 years old Dx BPH Treated with tamsulosin >12 months 

Tamsulosin 0.2 mg titrated up to 0.4 mg as needed to relieve sx. 

Predictive for treatment failure: baseline IPSS 

> 15, months 0-12 lowest IPSS 

> 13, lowest 

QoL score of 

> 3 and lowest BPH impact 

score of 

> 4. 

Roehrborn et al 1996 Prospective, placebo controlled, randomized, double-blinded 2084 patients 1 year (Terazosin n = 1053 Placebo n = 1031) Funding: Abbot Labratorie American 

Men 

> 55 years old 

Moderate-severe BPH AUA-Symptom Score (SS) 

>

13 

AUA-Bother Score (BS) 

> 8 

PUF 

< 15 mL/sec. 

Voided volume = 150 mL 

Terazosin 1 mg x 3 days, 2 mg x 25 days, ↑

5 mg or 10 mg as tolerated 

Placebo 

Statistically superior improvements were observed in regard to AUA-BS, BPH impact index and the QoL score in terazosin-treated patients. PUF improved Treatment failure was higher in placebo 

Withdraw in terazosin 

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Okada et al 

2000 Single-blind, randomized 61 patients 4 weeks Japanese 

Symptomatic BPH Terazosin 1-2 mg 

Tamsulosin 0.2 mg 

Both meds significantly improved the total IPSS, irritative and obstructive symptom score, and quality of life. There was no significant difference for these variables between groups. There was no significant improvements between groups. 

Incidence odifferent beNeither mediastolic bl

Lee et al 1997 Single-blind 98 patients randomized 8 weeks Korean 

Moderate to severe BPH Tamsulosin 0.2 mg 

Terazosin 1 mg ↑ 5 mg 

Both medications similarly improved IPSS and Increased Qmax 

Terazosin: -systolic ansignificant-dizziness, 

Tsuiji et al 2000 Open-label 105 patietns Randomized (Prazosin n= 32, Terazosin n=35, Tamsulosin n=38) 4 weeks 

LUTS associated with BPH Prazosin 1 mg ↑ 2 mg 

Terazosin 1 mg ↑ 2 mg Tamsulosin 0.1 mg ↑ 0.2 mg 

All significantly reduced subjective symptom scores from baseline. Terazosin significantly better improvement than Tamsulosin in 4 of 9 symptom scores (urgency, sense of residual urine, prolonged micturition, intermittency) Significant increase in flow with prazosin 

ADR whicPrazosin = Terazosin = Tamsulosin 

Na et al 1998 Single-blinded, randomized 212 Patients Randomized 4 weeks Chinese 

BPH Terazosin 2 mg 

Tamsulosin 0.2 mg 

Tamsulosin and terazosin: significant improvement in IPSS, Qmax and average urinary flow rate from baseline 

Dizziness, more frequ

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