Pharmacodynamic and clinical endpoints for functional colonic disorders: statistical considerations.
Pharmacodynamic and clinical endpoints for functional colonic disorders: statistical considerations.
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DOI：
10.1007/s10620-012-2369-z
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发表时间：
2013-02
影响因子：
3.1
通讯作者：
Camilleri, Michael
中科院分区：
文献类型：
--
作者：
Zinsmeister, Alan R.;Burton, Duane;Camilleri, Michael
扫描结肠过境（SCT）的主体内和主体间变异系数（COV）得到了很好的表征。SCT对治疗的反应预测实验性药物治疗低功能胃肠道疾病（FGID）的临床疗效。比较低FGID研究中cov与药效学（PD）结肠运输几何中心（GC）作为终点的肠功能。我们评估了来自安慰剂组的9个IIA期平行组临床试验的数据，即利那洛肽、dexloxiglumide、renzapride、elobixbat、ROSE 010和chenodeoxycholate在伴便秘的较低FGID和腹泻的较低FGID中的PD效果，以及pexacerafont、VSL#3和colesevelam。患者每天完成至少7天的排便次数、一致性（布里斯托尔大便形式7分量表）和便利性（从手动排便到尿失禁的7分量表）的日记。在两项独立的研究中，17名患者接受了安慰剂，以评估患者内冠状病毒。我们计算了证明低FGID合并便秘和腹泻患者结肠运输、大便频率、一致性和通过便利性的30%效应量所需的样本量。报告了87例患者的COVinter和17例患者的COVintra。一般来说，COVintra略大于COVinter。PD终点的cov低于临床终点；然而，使用平行组设计研究，可以通过适度（~50%）增加样本量来确定临床相关效应。纳入临床和PD终点的IIA期研究对于与便秘或腹泻相关的低FGID是可行的。与平行组研究相比，交叉设计对大多数终点的样本量要求更低。
Intra- and inter-subject coefficients of variation (COV) of scintigraphic colonic transit (SCT) are well characterized. SCT response to therapy predicts clinical efficacy of experimental medications in lower functional gastrointestinal disorders (FGID). To compare COVs for bowel function with pharmacodynamic (PD) colonic transit geometric center (GC) as endpoints in lower FGID studies. We evaluated data from placebo arm of 9 phase IIA, parallel-group, clinical trials of PD effects of linaclotide, dexloxiglumide, renzapride, elobixibat, ROSE 010, and chenodeoxycholate in lower FGID with constipation, and pexacerafont, VSL#3, and colesevelam in lower FGID with diarrhea. Patients completed daily diaries for at least 7 days of stool frequency, consistency (7-point Bristol Stool Form Scale), and ease of passage (7-point scale from manual disimpaction to incontinence). Seventeen patients received placebo in 2 separate studies allowing assessment of intra-patient COVs. We calculated sample sizes required to demonstrate a 30% effect size for colonic transit, stool frequency, consistency and ease of passage for patients with lower FGID with constipation and, separately, diarrhea. COVinter from 87 patients and COVintra from 17 patients are reported. Generally, COVintra is somewhat greater than COVinter. The COVs for PD endpoints are lower than for clinical endpoints; however, clinically relevant effects can be identified with modest (~50%) increases in the sample size using parallel-group design studies. Phase IIA studies that incorporate clinical and PD endpoints are feasible in lower FGID associated with constipation or diarrhea. Crossover design would require lower sample size for most endpoints compared to parallel-group studies.
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影响因子：
29.4
作者：
Rao AS;Wong BS;Camilleri M;Odunsi-Shiyanbade ST;McKinzie S;Ryks M;Burton D;Carlson P;Lamsam J;Singh R;Zinsmeister AR
通讯作者：
Zinsmeister AR
DOI：
10.1016/j.cgh.2009.10.020
发表时间：
2010-02
期刊：
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
影响因子：
--
作者：
Odunsi-Shiyanbade ST;Camilleri M;McKinzie S;Burton D;Carlson P;Busciglio IA;Lamsam J;Singh R;Zinsmeister AR
通讯作者：
Zinsmeister AR
DOI：
10.1152/ajpgi.00076.2012
发表时间：
2012-07-01
影响因子：
4.5
作者：
Camilleri, Michael;Vazquez-Roque, Maria;Zinsmeister, Alan R.
通讯作者：
Zinsmeister, Alan R.
影响因子：
9.7
作者：
Adams, CP;Brantner, VV
通讯作者：
Brantner, VV
影响因子：
29.4
作者：
CAMILLERI, M;ZINSMEISTER, AR
通讯作者：
ZINSMEISTER, AR