title: Evaluating adverse cardiovascular effects of drug treatment for benign prostatic hyperplasia (BPH): methodological considerations.
abstract: When studying the effects of drug exposure in diseases with a long asymptomatic clinical course, exposure classification may be biased by the gradually developing "visibility" of the disease. Benign prostatic hyperplasia (BPH) is such a disease. We found that cardiovascular morbidity is two times more prevalent in patients starting drug treatment for BPH when compared to age-matched population controls. This resulted in a difference of cardiovascular prognostic factors between the exposed and non-exposed. This feature can jeopardize the validity of non-randomized comparisons of drug effects. Moreover, the existence of non-treatment strategies, disease under-reporting, and an elderly population with a high baseline risk of experiencing (cardiovascular) outcome events were encountered as methodological problems. When studying adverse cardiovascular effects in patients using BPH products in a non-randomized fashion, an important question is whether we can measure in the database all relevant prognostic factors and use the information for statistical adjustment. This question is an important challenge to observational research and once again stresses the need for control of possible biases in choosing an appropriate study design.
authors.affiliation: Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht, The Netherlands. p.c.souverein@pharm.uu.nl
authors.forename: P C
authors.initials: PC
authors.lastname: Souverein
authors.forename: R M
authors.initials: RM
authors.lastname: Herings
authors.forename: J J
authors.initials: JJ
authors.lastname: De la Rosette
authors.forename: A J
authors.initials: AJ
authors.lastname: Man in 't Veld
authors.forename: R D
authors.initials: RD
authors.lastname: Farmer
authors.forename: H G
authors.initials: HG
authors.lastname: Leufkens
mesh_terms: D058891:5-alpha Reductase Inhibitors; D000317:Adrenergic alpha-Antagonists / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D015982:Bias; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D016022:Case-Control Studies; D018120:Finasteride / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D009426:Netherlands / Q000453:epidemiology; D011224:Prazosin / Q000009:adverse effects / Q000031:analogs & derivatives*; D011379:Prognosis; D011470:Prostatic Hyperplasia / Q000188:drug therapy*; D011799:Quinazolines / Q000009:adverse effects; D012107:Research Design; D012307:Risk Factors; D013449:Sulfonamides / Q000009:adverse effects; D000077409:Tamsulosin
chemical_list: D058891:5-alpha Reductase Inhibitors; D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; D013449:Sulfonamides; D018120:Finasteride; C041226:Terazosin; C047638:alfuzosin; D000077409:Tamsulosin; D011224:Prazosin