Biomedical subjects

Vincent Haudiquet

Publications and source records attributed to Vincent Haudiquet.

5 recordsLinked to original sources

PubMed2003

ICH E9 guideline 'Statistical principles for clinical trials': a case study.

The International Conference on Harmonization (ICH) E9 guideline 'Statistical principles for clinical trials' was adopted by the Committee for Proprietary Medicinal Products in March 1998, and consequently is operational in Europe. It has also been adopted in the U.S.A. and Japan. The aim of this paper is to relate the problems encountered during a recent regulatory submission to those discussed in the ICH E9 guideline. Statistical principles discussed in the guideline, but not comprehensively addressed when the clinical development programme was initiated in the mid-1990s, will be reviewed. The impact of each issue on the approvability of the dossier will be discussed, together with recommendations on how to avoid such problems with other ongoing clinical development programmes.

Data Interpretation, Statistical↗

PubMed2003

A method for controlling for a high placebo response rate in a comparison of venlafaxine XR and diazepam in the short-term treatment of patients with generalised anxiety disorder.

This randomised, double-blind, placebo-controlled study compared the efficacy of venlafaxine XR (75 or 150 mg/d) with diazepam (15 mg/d) over an 8-week treatment period in 540 non-depressed outpatients with generalised anxiety disorder (GAD). At week 8, significant improvements from baseline were observed in the venlafaxine XR, diazepam and placebo groups. Although these improvements were higher in the first two groups than in the placebo group for each of the primary efficacy variables (Hamilton Rating Scale for Anxiety (HAM-A) total, HAM-A psychic anxiety factor, Hospital Anxiety and Depression Scale (HAD) anxiety sub-scale and Clinical Global Impression (CGI) improvement), there were no statistically significant differences between groups. These non-positive results were thought to be due to the very high placebo response observed in some centres. To understand the variability of the study, a secondary preplanned analysis was performed. This involved sub-dividing the study centres according to their ability to detect a two-point mean difference between diazepam and placebo at week 8 on the HAM-A total score. Centres able to show such a difference were termed verum-sensitive. Improvements from baseline to week 8 in venlafaxine XR-treated patients from verum-sensitive centres were significantly greater than in placebo on each of the primary efficacy measures (P </= 0.05). This suggests that those centres able to detect an anxiolytic effect of diazepam were also able to detect an anxiolytic effect of venlafaxine XR. Significant differences in baseline demographics, rates of adverse event reporting and rates of patient discontinuations were noted between patients enrolled at verum-sensitive and verum-insensitive sites. These results reflect the importance of study centre selection in accurately determining efficacy in placebo-controlled trials.

Adult↗

PubMed2002

Achieving remission with venlafaxine and fluoxetine in major depression: its relationship to anxiety symptoms.

Venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI), produces significantly higher remission rates in depressed patients than do the selective serotonin reuptake inhibitors (SSRIs). In this analysis of pooled data, we explored the relationship between differences in treatment efficacy, early improvement of symptoms, and severity of baseline anxiety in depressed patients treated with either venlafaxine or fluoxetine. A pooled analysis was performed on data from 1,454 outpatients with major depression from five double-blind, randomized studies comparing the 6-week efficacy of venlafaxine (542 patients) with fluoxetine (555 patients). The Hamilton rating scale for depression (HAM-D) total and item scores were analyzed at different treatment times up to 6 weeks. Venlafaxine and fluoxetine both produced statistically significant higher response and remission rates compared with placebo starting from week 2 for response and weeks 3 to 4 for remission. Venlafaxine was statistically significantly superior to fluoxetine from week 3 until week 6 in respect of response rate, and from week 2 until week 6 for remission rate. After 1 week of treatment, greater improvement in individual symptoms was observed in the depressed mood, suicide, and psychic anxiety items of the HAM-D scale for both venlafaxine- and fluoxetine-treated patients compared with placebo. Improvement in psychic anxiety was statistically significantly greater with venlafaxine than with fluoxetine. The presence of baseline psychic anxiety correlated significantly to treatment outcome when analyzing the remission rates. In depressed patients with moderate anxiety (HAM-D psychic anxiety score < or = 2), venlafaxine statistically significantly increased remission rates compared with placebo from week 4 until week 6, while a significant effect of fluoxetine on remission rates was observed starting at week 6. Remission rates in the severely anxious depressed patients (score > 2) were statistically significantly higher with venlafaxine than placebo starting from week 3 until the end of the study period, but no difference could be observed between fluoxetine and placebo. Baseline severity of psychic anxiety had a significant impact on remission rates after treatment of patients diagnosed with depression. Venlafaxine's superior remission rates in the more severely anxious patients and its ability to improve psychic anxiety as early as week 1 compared with fluoxetine suggest that venlafaxine's early efficacy on anxiety symptoms may be the basis for its superior efficacy in depression.

Adult↗

PubMed2002

Effectiveness of venlafaxine, extended release formulation, in the short-term and long-term treatment of generalized anxiety disorder: results of a survival analysis.

A survival analysis of data from two placebo-controlled, randomized, long-term (6-month) studies was used to examine the effectiveness of venlafaxine, extended release (XR) formulation, in patients with generalized anxiety disorder (GAD). Patients in a placebo-controlled, flexible-dose study received 75 to 225 mg/day venlafaxine XR, while patients in a placebo-controlled, fixed-dose study received once-daily venlafaxine XR doses of 37.5 mg, 75 mg, or 150 mg. The survival analysis was based on the clinician's decision to discontinue treatment in a placebo-controlled study and incorporated data from all patients who were randomized. In each study, placebo-treated patients discontinued treatment due to lack of efficacy more frequently and earlier than those receiving venlafaxine XR (p < 0.001, log-rank test). A dose-response relationship was apparent, with the lowest rate of withdrawal seen at the highest venlafaxine XR dose. Survival curves for discontinuations due to adverse events did not differ significantly in either study. These results were consistent with the conventional intent-to-treat efficacy assessments of changes in anxiety severity, highlighting the superiority of venlafaxine XR over placebo in the long-term treatment of GAD. Overall, these results demonstrate the clinical effectiveness of venlafaxine XR in the short-term and long-term treatment of GAD.

Antidepressive Agents, Second-Generation↗

PubMedDate not supplied

Characterization of the longitudinal course of improvement in generalized anxiety disorder during long-term treatment with venlafaxine XR.

OBJECTIVE: To characterize the response to the serotonin and norepinephrine reuptake inhibitor, venlafaxine extended release (XR), during the long-term treatment of generalized anxiety disorder. METHODS: Data from two double-blind, placebo-controlled, 6-month trials of venlafaxine XR for the treatment of generalised anxiety disorder were pooled. Criteria for response (> or = 50% improvement from baseline HAM-A score) and remission (HAM-A score < or = 7) and their temporal profile were used to characterize patient improvement over 6 months of treatment with venlafaxine XR and placebo. RESULTS: Venlafaxine XR was associated with significantly (P<0.001) higher response and remission rates (66 and 43%, respectively) compared with placebo (39 and 19%), regardless of the level of baseline anxiety. In the venlafaxine XR group, 61% of the patients who had responded but not remitted by week 8 showed remission by the end of 6 months. In comparison, only 39% of placebo responders who did not qualify for remission at the end of the first 8 weeks of therapy remitted by the end of the 6 months (P=0.007). Relapse occurred in 6% of venlafaxine XR-treated patients and 15% of placebo-treated patients (P<0.01). CONCLUSION: This analysis provides further insight into the outcome of long-term treatment of generalised anxiety disorder with venlafaxine XR and shows for the first time that long-term treatment might be necessary to achieve and maintain remission of symptoms.

Adult↗