Sequential Experimentation in Clinical Trials

Bartroff, Jay; Lai, Tze Leung; Shih, Mei‐Chiung

doi:10.1007/978-1-4614-6114-2

Cited by 64 publications

(72 citation statements)

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“…16 Similarly, MaxSPRT has approximate optimality of EST under its composite alternative hypothesis, again under the condition of indefinite trial size. 3,17 However, as mentioned earlier, the unknown and truncated end of the trial collapses their assumptions and optimality. Although our method does not have any theoretical optimality, it is still as efficient as other applications of Bayesian methods 18,19 as we illustrated in the WORTH trial example.…”

Section: Discussionmentioning

confidence: 95%

A Bayesian Stopping Rule for Sequential Monitoring of Serious Adverse Events

Kashiwabara

Matsuyama

Ohashi

2014

Ther Innov Regul Sci

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In an ongoing clinical trial, there will always be a risk for unanticipated critical safety problems, such as excessive occurrence of serious adverse events. When such a problem arises, the trial administrators must conduct an immediate evaluation to determine whether the trial should be terminated to protect patients. This decision is complicated but may be aided by statistical stopping rules. Sequential stopping rules are appropriate for immediate decisions, but frequentist approaches may not be useful because the unknown truncated end of the trial makes it impossible to define type I errors. Thus, a Bayesian stopping rule is proposed that is based on the posterior distribution with an informative prior distribution, and a guideline to construct this stopping rule is presented. Some operating characteristics are evaluated and compared with those of the modified sequential probability ratio test (SPRT), the maximized SPRT, and Pocock's test. The proposed method has flexibility for construction and could provide a more desirable performance than the other compared methods.

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Section: Discussionmentioning

confidence: 95%

A Bayesian Stopping Rule for Sequential Monitoring of Serious Adverse Events

Kashiwabara

Matsuyama

Ohashi

2014

Ther Innov Regul Sci

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“…The treatment of the experimental data was carried out by methods of variation statistics [16] using the software package SPSS 16.0: the data were tested for normality of distribution using the Kolmogorov-Smirnov Z-test, intergroup comparison was performed by one-way analysis of variance (ANOVA) with the use of posteriori multiple comparisons of Bonferroni test, and using U-Mann-Whitney test. The difference between the values of the parameters was compared, it was considered significant at p≤0.05.…”

Section: Discussionmentioning

confidence: 99%

“…The histological examinations were performed using rectal segments, which were fixed in 10 % neutral formalin saline, paraffin sections were prepared and stained with hematoxylin-eosin according to the standard procedure [15,16]. The preparations were analyzed at the light-optical level using the microscope Bresser Researcher Trino (100, 400 magnification) (Bresser, Germany), coloured microphotographs were obtained using the digital camera Delta Optical CCD HDCE 5.0 (Delta Optical, Poland) and the above mentioned microscope.…”

Section: Tissue Preparationmentioning

confidence: 99%

Effect of Pyrrole Derivative on the Rat Colonic Mucosa Compared to 5-Fluorouracil

Yena

Dzyubenko

2016

EUREKA: Life Sciences

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Prevention the development of malignant tumors and treatment of cancer patients remains an important problem today. In spite of substantive progress in the cancer diagnostics and treatment cancer occupies one of the main places in human morbidity and mortality in the World. Targeted therapy is an alternative to traditional one through targeted action on tumor cells and relatively low toxicity. Inhibitor of membrane tyrosine kinases dihydropyrrole derivative 5-amino-4-(1,3-benzothiazole-2-yl)-1-(3- methoxyphenyl)-1,2-dihydro-3Н-pyrrol-3-one (D-1) has significant antitumor activity on colorectal cancer and low toxicity acting in effective dose. However, to assess the D-1 therapeutic gap the investigation of its higher doses is necessary. The investigation was aimed at D-1 effects applied at different doses compared to 5-fluorouracil one on rats ascending colon mucosa. The research has found out that the dihydropyrrole derivative has no damaging effect on the colon of rats, whereas the administration of 5-fluorouracil causes marked mucosal lesion of the ascending colon. Hereby D-1 low toxicity to ascending colon mucosa compared to 5-FU and wide therapeutic gap of the first was concluded.

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“…The observed effect size may differ substantially from the assumed effect size during the course of the trial. This has led to adaptive designs with mid-course sample size re-estimation; see Chapter 8 of [7]. Since our design also allows treatment comparisons over smaller patient subgroups and there is usually little information at the beginning of the trial from previous studies about the effect sizes in the subgroups, an adaptive design that can both choose the patient subgroup and re-estimate the sample size is particularly attractive.…”

Section: Basic Theory In Prototypical Normal Settingmentioning

confidence: 99%

“…Hence, the probabilities P 1 b and P 1 c can be computed by the recursive numerical integration [7, p.86] using the joint normal density of {

Z_{J}^{ℓ}

, 1 ≤ ℓ ≤ 3}.…”

Section: Basic Theory In Prototypical Normal Settingmentioning

confidence: 99%

Adaptive choice of patient subgroup for comparing two treatments

Lai¹,

Lavori²,

Liao³

2014

Contemporary Clinical Trials

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This paper is motivated by a randomized controlled trial to compare an endovascular procedure with conventional medical treatment for stroke patients, in which the endovascular procedure may be effective only in a subgroup of patients. Since the subgroup is not known at the design stage but can be learned statistically from the data collected during the course of the trial, we develop a novel group sequential design that incorporates adaptive choice of the patient subgroup among several possibilities which include the entire patient population as a choice. We define the type I and type II errors of a test in this design and show how a prescribed type I error can be maintained by using the closed testing principle in multiple testing. We also show how asymptotically optimal tests can be constructed by using generalized likelihood ratio statistics for parametric problems and analogous standardized or Studentized statistics for nonparametric tests such as Wilcoxon’s rank sum test commonly used for treatment comparison in stroke patients.

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Sequential Experimentation in Clinical Trials

Cited by 64 publications

References 0 publications

A Bayesian Stopping Rule for Sequential Monitoring of Serious Adverse Events

A Bayesian Stopping Rule for Sequential Monitoring of Serious Adverse Events

Effect of Pyrrole Derivative on the Rat Colonic Mucosa Compared to 5-Fluorouracil

Adaptive choice of patient subgroup for comparing two treatments

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