Pregabalin for hot flashes in women: NCCTG trial N07C1

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9513-9513
Author(s):  
C. L. Loprinzi ◽  
R. Qin ◽  
P. J. Stella ◽  
K. M. Rowland ◽  
D. L. Graham ◽  
...  
Keyword(s):  
Information Quality ◽  
Type I Error ◽  
Treatment Options ◽  
Hot Flashes ◽  
Baseline Period ◽  
Type I ◽  
Hot Flash ◽  
Double Blinded ◽  
Oral Doses

9513 Background: Hot flashes are a major problem in many women for which better treatment options are needed. Given the known efficacy of gabapentin for decreasing hot flashes, it was decided to evaluate pregabalin, with hopes that it would work better and/or with fewer toxicities. Methods: A three-arm, double-blinded, placebo-controlled randomized trial was developed. Women with bothersome hot flashes (at least 28/week) were randomized to receive either a placebo or target pregabalin oral doses of 75 mg bid or 150 mg bid (starting at 50 mg/d and then increasing the dose at weekly intervals to 50 mg bid, then 75 mg bid, and then, in the higher dose arm, 150 mg bid); patients were treated for 6 weeks. Hot flash numbers and scores (hot flash number times mean severity) were measured using a validated daily hot flash diary. A one-week baseline period preceded initiation of study tablets. The primary endpoint was the average intra-patient difference in hot flash score between baseline and week six, comparing the higher dose pregabalin arm and the placebo arm. With the planned sample size of 55 patients per arm, there was an 80% power and two-sided 5% Type I error rate to detect a difference of 0.54 standard deviations, or 1.08 hot flashes per day, or 2.7 units of hot flash score per day. Results: 207 patients were randomized between 6/20/2008 and 8/21/2008. The study arms were well balanced. Mean/median daily hot flash scores and frequencies for all pts at baseline were 15.7/13.4 and 8.3/7.7, respectively. The table shows the decreases in hot flashes from the baseline to the sixth treatment week. Larger numbers illustrate greater hot flash reductions. Toxicity information, quality of life information, and information regarding the effects of hot flashes on subjective symptoms will be available at the meeting time. Conclusions: Pregabalin reduces hot flashes in women. There appears to be similar effects with both studied doses. [Table: see text] No significant financial relationships to disclose.

Gabapentin for hot flashes in men: NCCTG trial N00CB

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9005-9005 ◽  
Author(s):  
C. L. Loprinzi ◽  
B. S. Khoyratty ◽  
A. Dueck ◽  
D. L. Barton ◽  
S. Jafar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Hot Flashes ◽  
Baseline Period ◽  
Androgen Deprivation ◽  
Hot Flash ◽  
Treatment Termination ◽  
Patient Reported ◽  
Double Blinded ◽  
To Receive

9005 Background: Hot flashes can be a major problem in men with prostate cancer; effective non-hormonal options are needed. Methods: A four-arm, double-blinded, placebo-controlled randomized trial was developed to evaluate gabapentin for hot flashes. Men with bothersome hot flashes (at least 14/week) related to androgen deprivation therapy were randomized to receive either a placebo or gabapentin doses of 300 mg qd, 300 mg bid or 300 mg tid; men were treated for 4 weeks. Hot flashes numbers and scores (hot flash number times mean severity) were measured using a validated daily hot flashes diary. A one-week baseline period preceded initiation of study tablets. The primary endpoint was the average intrapatient difference in hot flash score between baseline and treatment termination. With the planned sample size of 50 evaluable patients per arm, the study provided 80% power to detect a difference in change from baseline at 4 weeks between each gabapentin arm and the placebo arm of 1.3 hot flashes per day or 3.3 points in hot flash score. Results: 223 patients were randomized between 12/21/2001 and 11/10/2006. The study arms were well balanced. The following table illustrates the percentage of baseline hot flash scores and frequencies during the fourth treatment week, compared to the baseline week for 179 eligible patients, utilizing the data available at time of this abstract preparation. Patients receiving 900 mg/d dose of gabapentin also reported significantly less hot flash distress and more hot flash control satisfaction than did the placebo group. The gabapentin was remarkably well tolerated, without any statistically significantly worse patient-reported side effects on the gabapentin arms. Conclusion: Gabapentin at the 900 mg/d dose can reduce hot flashes, in men receiving androgen deprivation therapy for prostate cancer. No significant financial relationships to disclose. [Table: see text]

scholarly journals A comparative analysis of cell-type adjustment methods for epigenome-wide association studies based on simulated and real data sets

2018 ◽  
Vol 20 (6) ◽  
pp. 2055-2065 ◽  
Author(s):  
Johannes Brägelmann ◽  
Justo Lorenzo Bermejo
Keyword(s):  
Statistical Power ◽  
Type I Error ◽  
Association Studies ◽  
Real Data ◽  
Error Rates ◽  
Data Sets ◽  
Type I ◽  
Cell Type ◽  
Type I Error Rates

Abstract Technological advances and reduced costs of high-density methylation arrays have led to an increasing number of association studies on the possible relationship between human disease and epigenetic variability. DNA samples from peripheral blood or other tissue types are analyzed in epigenome-wide association studies (EWAS) to detect methylation differences related to a particular phenotype. Since information on the cell-type composition of the sample is generally not available and methylation profiles are cell-type specific, statistical methods have been developed for adjustment of cell-type heterogeneity in EWAS. In this study we systematically compared five popular adjustment methods: the factored spectrally transformed linear mixed model (FaST-LMM-EWASher), the sparse principal component analysis algorithm ReFACTor, surrogate variable analysis (SVA), independent SVA (ISVA) and an optimized version of SVA (SmartSVA). We used real data and applied a multilayered simulation framework to assess the type I error rate, the statistical power and the quality of estimated methylation differences according to major study characteristics. While all five adjustment methods improved false-positive rates compared with unadjusted analyses, FaST-LMM-EWASher resulted in the lowest type I error rate at the expense of low statistical power. SVA efficiently corrected for cell-type heterogeneity in EWAS up to 200 cases and 200 controls, but did not control type I error rates in larger studies. Results based on real data sets confirmed simulation findings with the strongest control of type I error rates by FaST-LMM-EWASher and SmartSVA. Overall, ReFACTor, ISVA and SmartSVA showed the best comparable statistical power, quality of estimated methylation differences and runtime.

Hot flash placebo responses: Related to baseline hot flash frequency?

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9628-9628
Author(s):  
J. M. Jones ◽  
C. L. Loprinzi ◽  
R. Qin ◽  
D. L. Barton
Keyword(s):  
Significant Positive Correlation ◽  
Hot Flashes ◽  
Placebo Response ◽  
Correlation Coefficients ◽  
Baseline Period ◽  
Percent Reduction ◽  
Hot Flash ◽  
Positive Correlation ◽  
Pubmed Search ◽  
Multiple Treatments

9628 Background: As multiple treatments have been studied for the management of hot flashes in randomized, controlled trials, hot flash placebo responses have been quite variable across trials. Based on observations of trial reports, it was hypothesized that the magnitude of placebo effect might correlate with the number of baseline hot flashes in different studies. The current project examines the effect of the baseline hot flash frequency required for study participation and also the actual number of baseline hot flashes observed as these individually relate to the eventual reductions of hot flash frequency observed in patients receiving placebos. Methods: Data were collected from placebo-controlled, double-blinded, randomized trials, identified by a PubMed search, which reported hot flash frequency at baseline, 4–6 weeks and 12 weeks. Trials were excluded if they had less than 20 participants completing the placebo arm. Data gathered, in each study, included the number of hot flashes required to enroll in the study, the average hot flash number during the baseline period, and the hot flash changes in the placebo arms of each study (percent reduction from the baseline period). A simple statistical analysis was conducted in a descriptive fashion since standard deviation was not available in many trials. Scatter plots and Pearson's correlation coefficients demonstrated the relationships between the placebo hot flash percent reduction from baseline and both the minimum required number of hot flashes at baseline, and the mean number of hot flashes at baseline. Results: 45 trials with 49 placebo arms were included in this analysis. A significant positive correlation was seen between the number of hot flashes required to enroll in a study and the percent reduction of hot flashes from baseline at 4–6 weeks (Rho = 0.481, p = 0.003). There was also a significant positive correlation between the number of hot flashes at baseline and the percent reduction of hot flashes from baseline at 4–6 weeks (Rho = 0.481, p= 0.002) and at 12 weeks (Rho = 0.573, p= 0.003). Conclusions: These data support that higher baseline hot flash enrollment requirements and also higher baseline hot flash frequencies are associated with an increased placebo response. No significant financial relationships to disclose.

scholarly journals Newer Antidepressants and Gabapentin for Hot Flashes: An Individual Patient Pooled Analysis

2009 ◽  
Vol 27 (17) ◽  
pp. 2831-2837 ◽  
Author(s):  
Charles L. Loprinzi ◽  
Jeff Sloan ◽  
Vered Stearns ◽  
Rebecca Slack ◽  
Malini Iyengar ◽  
...  
Keyword(s):  
Treatment Options ◽  
Hot Flashes ◽  
Clinical Problem ◽  
Pooled Analysis ◽  
Double Blind ◽  
Hot Flash ◽  
Study Results ◽  
Study Heterogeneity ◽  
Study Characteristics ◽  
Major Clinical Problem

Purpose Nonhormonal treatment options have been investigated as treatments for hot flashes, a major clinical problem in many women. Starting in 2000, a series of 10 individual double-blind placebo-controlled studies has evaluated newer antidepressants and gabapentin for treating hot flashes. This current project was developed to conduct an individual patient pooled analysis of the data from these published clinical trials. Patients and Methods Individual patient data were collected from the various study investigators who published their study results between 2000 and 2007. Between-study heterogeneity for study characteristics and patient populations was tested via χ2 tests before a pooled analysis. The primary end point, the change in hot flash activity from baseline to week 4, for each agent was calculated via both weighted and unweighted approaches, using the size of the study as the weight. Basic summary statistics were produced for hot flash score and frequency using the following three statistics: raw change, percent reduction, and whether or not a 50% reduction was achieved. Results This study included seven trials of newer antidepressants and three trials of gabapentin. The optimal doses (defined by individual study results) of the newer antidepressants paroxetine, venlafaxine, fluoxetine, and sertraline decreased hot flash scores by 41%, 33%, 13%, and 3% to 18% compared with the corresponding placebo arms, respectively. The three gabapentin trials decreased hot flashes by 35% to 38% compared with the corresponding placebo arms. Conclusion Some newer antidepressants and gabapentin, within 4 weeks of therapy initiation, decrease hot flashes more than placebo.

Prioritizing hypothesis tests for high throughput data

2015 ◽  
Vol 32 (6) ◽  
pp. 850-858 ◽  
Author(s):  
Sangjin Kim ◽  
Paul Schliekelman
Keyword(s):  
High Throughput ◽  
Correction Factor ◽  
Type I Error ◽  
Supplementary Information ◽  
Type I ◽  
Hypothesis Tests ◽  
High Throughput Data ◽  
Independent Information ◽  
Discovery Probability

Abstract Motivation: The advent of high throughput data has led to a massive increase in the number of hypothesis tests conducted in many types of biological studies and a concomitant increase in stringency of significance thresholds. Filtering methods, which use independent information to eliminate less promising tests and thus reduce multiple testing, have been widely and successfully applied. However, key questions remain about how to best apply them: When is filtering beneficial and when is it detrimental? How good does the independent information need to be in order for filtering to be effective? How should one choose the filter cutoff that separates tests that pass the filter from those that don’t? Result: We quantify the effect of the quality of the filter information, the filter cutoff and other factors on the effectiveness of the filter and show a number of results: If the filter has a high probability (e.g. 70%) of ranking true positive features highly (e.g. top 10%), then filtering can lead to dramatic increase (e.g. 10-fold) in discovery probability when there is high redundancy in information between hypothesis tests. Filtering is less effective when there is low redundancy between hypothesis tests and its benefit decreases rapidly as the quality of the filter information decreases. Furthermore, the outcome is highly dependent on the choice of filter cutoff. Choosing the cutoff without reference to the data will often lead to a large loss in discovery probability. However, naïve optimization of the cutoff using the data will lead to inflated type I error. We introduce a data-based method for choosing the cutoff that maintains control of the family-wise error rate via a correction factor to the significance threshold. Application of this approach offers as much as a several-fold advantage in discovery probability relative to no filtering, while maintaining type I error control. We also introduce a closely related method of P-value weighting that further improves performance. Availability and implementation: R code for calculating the correction factor is available at http://www.stat.uga.edu/people/faculty/paul-schliekelman. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.

Pilot evaluation of venlafaxine hydrochloride for the therapy of hot flashes in cancer survivors.

1998 ◽  
Vol 16 (7) ◽  
pp. 2377-2381 ◽  
Author(s):  
C L Loprinzi ◽  
T M Pisansky ◽  
R Fonseca ◽  
J A Sloan ◽  
K M Zahasky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Survivors ◽  
Breast Cancer Survivors ◽  
Low Dose ◽  
Hot Flashes ◽  
Daily Diary ◽  
Clinical Problem ◽  
Baseline Period ◽  
Hot Flash ◽  
Venlafaxine Hydrochloride

PURPOSE Hot flashes can be a prominent clinical problem for breast cancer survivors and men who undergo androgen-deprivation therapy. Anecdotal information suggested a low dose of a relatively new antidepressant, venlafaxine, could abrogate this clinical problem. MATERIALS AND METHODS This study included 28 consecutive assessable patients entered onto a phase II clinical trial. Hot flash data were collected by daily diary questionnaires during a 1-week baseline period and then for 4 weeks, during which time patients received venlafaxine 12.5 mg orally twice daily. RESULTS Fifty-eight percent of patients who completed the study had a greater than 50% reduction in hot flash scores (frequency times severity) during the fourth treatment week as compared with the baseline week. Median weekly hot flash scores were reduced by 55% from baseline during the fourth week of venlafaxine therapy. Therapy was generally well tolerated and appeared to alleviate fatigue, sweating, and trouble sleeping. CONCLUSION Venlafoxine appears to represent an efficacious new method to alleviate hot flashes. Further evaluation of this compound for alleviating hot flashes is indicated.

Impact of FOLFOXIRI and bevacizumab (bev) compared to FOLFOX and bev on health related quality of life (HRQOL) in patients with metastatic colorectal cancer (MCRC): Analysis of the CHARTA-AIO 0209 trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3544-3544 ◽  
Author(s):  
Julia Quidde ◽  
Hans-Joachim Schmoll ◽  
Benjamin Garlipp ◽  
Christian Junghanss ◽  
Malte Leithaeuser ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Type I Error ◽  
Compliance Rate ◽  
Induction Treatment ◽  
Type I ◽  
Mean Values ◽  
Deterioration Rate ◽  
Global Quality Of Life ◽  
The Impact

3544 Background: FOLFOXIRI/bev is a highly efficacious first line regimen in MCRC. Despite higher rates of neutropenia, diarrhea and stomatitis, FOLFOXIRI/bev is tolerable and feasible in MCRC patients. To date nothing is known about the impact of this regimen on HRQOL. Methods: 250 patients were randomized to FOLFOX/bev (arm A) or FOLFOXIRI/bev (arm B). HRQOL were assessed at baseline, every 8 weeks during induction treatment (6 months) and every 12 weeks during maintenance treatment, using the EORTC QLQ-C30, QLQ-CR29 and QLQ-CIPN20. The mean values of every score were calculated as the average of week 8, 16 and 24 assessment. Test concerning mean values were performed as t-test, with global type I error set at 0.05. HRQOL deterioration and improvement rates were analyzed and compared between treatment groups using chi² tests. Results: For HRQOL analysis, 237 patients were eligible (arm A: 118; arm B: 119). Compliance rate with the HRQOL questionnaires was 95.4% at baseline, 72.6% at week 8, 59.5 % at week 16 and 43.5% at week 24. Whereas mean global quality of life score (GHS/QOL) was similar between arm A and B (59.8 vs. 58.8; p = 0.726), mean scores for nausea/vomiting (9.4 vs. 16.0; p = 0.015) and diarrhea (23.7 vs. 32.1; p = 0.051) significantly or borderline significantly favored arm A during induction period. Furthermore, at week 8 scores of nausea/vomiting (9.2 versus 17.3, p = 0.006) appetite loss (19.5 vs. 29.4; p = 0.035) and financial problems (18.3 vs. 29.5; p = 0.021) and at the end of treatment physical functioning (75.0 vs. 65.8; p = 0.048) were significantly better for arm A compared to arm B. No significant differences were observed in the remaining EORTC scores. The rates of deterioration and improvement between baseline and week 8 of at least 10 points in the EORTC scores were similar (e.g. deterioration-rate GHS/QOL score 21.5% vs. 26.5% for arm A vs. B; p = 0.461). Conclusions: Although no remarkable detriment in HRQOL was noted, the better efficacy of FOLFOXIRI/bev compared to FOLFOX/bev is associated with a decrease in mainly gastrointestinal QOL scores. Further subgroup-analyses will be presented at the meeting. Clinical trial information: NCT01321957.

Multicenter, Randomized, Cross-Over Clinical Trial of Venlafaxine Versus Gabapentin for the Management of Hot Flashes in Breast Cancer Survivors

2010 ◽  
Vol 28 (35) ◽  
pp. 5147-5152 ◽  
Author(s):  
Louise Bordeleau ◽  
Kathleen I. Pritchard ◽  
Charles L. Loprinzi ◽  
Marguerite Ennis ◽  
Olivera Jugovic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Survivors ◽  
Patient Preference ◽  
Breast Cancer Survivors ◽  
Negative Mood ◽  
Hot Flashes ◽  
Baseline Period ◽  
Open Label ◽  
Group Sequential ◽  
Hot Flash

Purpose Nonhormonal pharmacologic interventions are recommended for the treatment of hot flashes in breast cancer survivors. Antidepressants and gabapentin have been shown to be both effective and well tolerated; however, it is not clear which is preferred. Patients and Methods This was a group-sequential, open-label, randomized, cross-over trial of 4 weeks of venlafaxine (37.5 mg daily for 7 days followed by 75 mg daily for 21 days) versus gabapentin (300 mg once per day for 3 days, then 300 mg twice per day for 3 days, then 300 mg three times per day for 22 days), with patient preference as the primary outcome. Postmenopausal women with at least 14 bothersome hot flashes per week for the prior month were eligible. A 2-week baseline period and a 2-week tapering/washout time was used before the first and second treatment periods, respectively. Diaries were used to measure hot flashes and potential toxicities throughout the study. Participants completed a preference questionnaire at the end of the study. A predefined Pocock stopping rule was applied. Patient preference and hot flash and toxicity outcomes were compared between treatments. Results Sixty-six patients were randomly assigned, 56 of whom provided a preference (eight dropped out and two had no preference); 18 (32%) preferred gabapentin and 38 (68%) preferred venlafaxine (P = .01). Both agents reduced hot flash scores to a similar extent (66% reduction). Venlafaxine was associated with increased nausea, appetite loss, constipation, and reduced negative mood changes compared with gabapentin, whereas gabapentin was associated with increased dizziness and appetite compared with venlafaxine (all P < .05). Conclusion Breast cancer survivors prefer venlafaxine over gabapentin for treating hot flashes.

Paroxetine Is an Effective Treatment for Hot Flashes: Results From a Prospective Randomized Clinical Trial

2005 ◽  
Vol 23 (28) ◽  
pp. 6919-6930 ◽  
Author(s):  
Vered Stearns ◽  
Rebecca Slack ◽  
Nancy Greep ◽  
Ronda Henry-Tilman ◽  
Michael Osborne ◽  
...  
Keyword(s):  
Effective Treatment ◽  
Controlled Trial ◽  
Hot Flashes ◽  
Composite Score ◽  
Open Label ◽  
Double Blind ◽  
Hot Flash ◽  
Secondary Objective ◽  
Open Label Trial

Purpose In an open-label trial we have previously demonstrated that paroxetine reduces hot flashes. We initiated a stratified, randomized, double-blind, cross-over, placebo-controlled trial to investigate the efficacy of paroxetine 10 mg and 20 mg compared to placebo in reducing hot flash frequency and composite score. A secondary objective was to evaluate quality of life (QOL) parameters. Patients and Methods Women who suffered at least two hot flashes a day for 1 month or longer were eligible. Women were randomly assigned to 4 weeks of paroxetine 10 mg or 20 mg followed by placebo for 4 weeks, or placebo for 4 weeks followed by paroxetine 10 mg or 20 mg for 4 weeks. Participants completed baseline daily hot flash diaries for one week prior to the start of the study and throughout the study, and QOL questionnaires at baseline, week 5 and week 9. Results 279 women were screened, and 151 were randomly assigned. Paroxetine 10 mg reduced hot flash frequency and composite score by 40.6% and 45.6%, respectively, compared to 13.7% and 13.7% for placebo (P = .0006 and P = .0008, respectively). Paroxetine 20 mg reduced hot flash frequency and composite score by 51.7% and 56.1%, respectively, compared with 26.6% and 28.8% for placebo (P = .002 and P = .004, respectively). Efficacy was similar between the two doses, but women were less likely to discontinue low-dose paroxetine. Paroxetine 10 mg was associated with a significant improvement in sleep compared with placebo (P = .01). Conclusion Paroxetine is an effective treatment for hot flashes in women with or without a prior breast cancer.

An Evaluation of the Quality of Clinical Trials in Anesthesia

2001 ◽  
Vol 95 (5) ◽  
pp. 1068-1073 ◽  
Author(s):  
Hwee Leng Pua ◽  
Jerrold Lerman ◽  
Mark W. Crawford ◽  
James G. Wright
Keyword(s):  
Clinical Trials ◽  
Sample Size ◽  
Type I Error ◽  
Sample Size Calculation ◽  
Adverse Outcomes ◽  
Random Allocation ◽  
Type I ◽  
Trial Methodology ◽  
Eligibility Criteria

Background The authors evaluated the quality of clinical trials published in four anesthesia journals during the 20-yr period from 1981-2000. Methods Trials published in four major anesthesia journals during the periods 1981-1985, 1991-1995, and the first 6 months of 2000 were grouped according to journal and year. Using random number tables, four trials were selected from all of the eligible clinical trials in each journal in each year for the periods 1981-1985 and 1991-1995, and five trials were selected from all of the trials in each journal in the first 6 months of 2000. Methods and results sections from the 160 trials from 1981-1985 and 1991-1995 were randomly ordered and distributed to three of the authors for blinded review of the quality of the study design according to 10 predetermined criteria (weighted equally, maximum score of 10): informed consent and ethics approval, eligibility criteria, sample size calculation, random allocation, method of randomization, blind assessment of outcome, adverse outcomes, statistical analysis, type I error, and type II error. After these trials were evaluated, 20 trials from the first 6 months of 2000 were randomly ordered, distributed, and evaluated as described. Results The mean (+/- SD) analysis scores pooled for the four journals increased from 5.5 +/- 1.4 in 1981-1985 to 7.0 +/- 1.1 in 1991-1995 (P &lt; 0.00001) and to 7.8 +/- 1.5 in 2000. For 7 of the 10 criteria, the percentage of trials from the four journals that fulfilled the criteria increased significantly between 1981-1985 and 1991-1995. During the 20-yr period, the reporting of sample size calculation and method of randomization increased threefold to fourfold, whereas the frequency of type I statistical errors remained unchanged. Conclusion Although the quality of clinical trials in four major anesthesia journals has increased steadily during the past two decades, specific areas of trial methodology require further attention.

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