How well do randomized controlled trial data generalize to 'real-world' clinical practice settings? A comparison of two generalized anxiety disorder studies.

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.

The best next drug in the course of generalized anxiety disorders: the "PN-GAD-algorithm".

OBJECTIVE: Today, there are many pharmacotherapeutic options for generalized anxiety disorder (GAD). The question is, which is the best medication for a particular patient at a particular moment? This is especially challenging because GAD is by definition a chronic disorder and new interventions should learn from earlier experiences. An algorithm which can help to use pretreatment information for drug selection is the "Pretreatment - Next Treatment (PN) - Algorithm". This article introduces an PN-algorithm for GAD. METHODS AND RESULTS: For the development of a GAD-specific PN-algorithm, all possible pharmacological options for GAD are reviewed and brought into a rank order on the basis of scientific evidence regarding efficacy, tolerability, or price: (1) pregabalin, (2) venlafaxine XR, (3) selective serotonin reuptake inhibitors, (4) tricyclic antidepressants, (5) buspirone, (6) antipsychotics, (7) benzodiazepines, and (8) hydroxyzine. Based on this hierarchy and patient-specific information, a decision algorithm is derived, which allows to assess and evaluate pretreatment and to select the drug with no contraindications, limited negative or convincing positive effects, or the option which has not been used so far but which is the next compound in the hierarchy. CONCLUSIONS: The "PN-GAD-algorithm" can be easily translated into a checklist to support clinical decision-making. It can also help to increase patient empowerment and cooperation in long-term treatment.

Efficacy and safety of pregabalin in patients with diabetic peripheral neuropathy or postherpetic neuralgia: Open-label, non-comparative, flexible-dose study.

We assessed the efficacy and safety of a flexible-dose pregabalin regimen in patients with diabetic peripheral neuropathy (DPN) or postherpetic neuralgia (PHN) under clinical practice conditions. Further, the trial investigated the correlation of unspecific measures of change (patient and physician global impression of change, PGIC and CGIC) and specific measures of morbidity. The primary outcomes of this prospective, open-label, non-controlled study were the correlation between global status (PGIC and CGIC) and changes in pain, sleep, and anxiety scores as assessed on numerical or visual rating scales. A total of 217 outpatients were included in 53 centres. The most frequently used dosing regimen involved a starting dose of 150mg/d and dose escalation to 300mg/d after one week (mean: 301mg/d, administered in two doses). The significant changes on pain, sleep and anxiety scales (-40%, -43%, -42%) between baseline and study end after 4-week pregabalin treatment were paralleled by the changes in ratings in both the PGIC and CGIC. The correlation with both PGIC and CGIC was 0.60 for pain, 0.51 for sleep and 0.20 or 0.13 for the correlation of anxiety with PGIC and CGIC, respectively. All correlations with exception of the pair CGIC/anxiety reached statistical significance. In conclusion, pregabalin in a flexible-dose regimen improved pain, sleep, anxiety and general state, and was well tolerated. The efficacy and safety profile of pregabalin was consistent with the data from the controlled clinical trials. The PGIC and CGIC and the specific pain and sleep scores, but not the anxiety score were generally well correlated but not synonymous.