title: How well do randomized controlled trial data generalize to 'real-world' clinical practice settings? A comparison of two generalized anxiety disorder studies.
abstract: The aim of this post-hoc comparison is to compare efficacy and tolerability results from two generalized anxiety disorder (GAD) studies: a placebo-controlled, randomized controlled trial (RCT) and a study conducted in the clinical practice setting, and to evaluate the extent to which results from RCTs in GAD patients can be generalized to clinical practice. In the clinical practice study, GAD outpatients (n=578) were treated with 4 weeks of pregabalin 150-600mg/day. In the double-blind placebo-controlled RCT, GAD outpatients (n=249) were randomized to 8 weeks of pregabalin (300-600mg/day), or placebo (only the first 4 weeks are included in the current analysis). Efficacy measures included the Hospital Anxiety and Depression Scale - Anxiety and Depression subscales (HADS-A; HADS-D), a visual analogue anxiety scale (VAS-Anxiety), and the Medical Outcomes Study Sleep Problems Index (MOS-SPI). Baseline HADS-A and HADS-D scores were both higher in the clinical practice study vs. the RCT. In the RCT, treatment with pregabalin resulted in significantly greater Week 4 change vs. placebo in the HADS-A (-5.3 vs. -3.9; P<0.005), VAS-Anxiety (-24.0 vs. -13.3; P<0.02), MOS-SPI (-19.1 vs. -9.5; P<0.01), and HADS-D (-2.7 vs. -1.4; P<0.05). The magnitude of Week 4 improvement on pregabalin in the clinical practice study was numerically larger on the HADS-A (-5.9), VAS-Anxiety (-36.0), MOS-SPI (-22.7), and HADS-D (-5.1), despite use of lower doses. These results suggest that clinical practice patients with GAD may achieve comparable efficacy on lower doses of pregabalin than tested in RCTs, despite having comparable levels of anxiety symptom severity at baseline. The current exploratory comparison also suggests that results from RCTs in patients with GAD may not be directly generalizable to clinical practice.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: sci-biolpsy@meduniwien.ac.at.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.affiliation: Medical Department, Pfizer Pharma GmbH, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Brasser
authors.affiliation: Paladin Consulting Group, Princeton, NJ, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Schweizer
authors.affiliation: Pfizer Ltd, Tadworth, Surrey, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Lyndon
authors.affiliation: Pfizer EuCan, Madrid, Spain.
authors.forename: Rita
authors.initials: R
authors.lastname: Prieto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000700:Analgesics / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D010147:Pain Measurement; D010818:Practice Patterns, Physicians'; D000069583:Pregabalin; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid
keywords: Generalized anxiety disorder; Hospital Anxiety and Depression Scale; Pregabalin; Randomized controlled trial