Sample Size Determination in Clinical Trials with an Emphasis on Exponentially Distributed Responses

Aj, Gross; Hh, Hunt; Ab, Cantor; Bc, Clark

doi:10.2307/2531541

Cited by 16 publications

(11 citation statements)

References 13 publications

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“…A trauma dose of 40 g-cm is at the appropriate place on the trauma dose-response curve and appears optimal for assessment of therapeutic effect on mortality rate. For a therapeutic agent to reduce the severity of spinal cord injury from the equivalent of 40 g-cm to 30 g-cm, a reduction of mortality rate by approximately one-half (from 27% to 14%) is expected at a significance level of 0.05 (a) with a power of 0.8 (1 -B) if 30 rats each are included in both the treatment and control groups (26).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Model for Experimental Spinal Cord Injury in the Rat: I. Mortality and Motor Deficit

Perot¹,

Lee²,

Hsu

et al. 1987

Central Nervous System Trauma

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In the course of establishing a therapeutic model for experimental spinal cord injury in the rat, we determined the effects of trauma dose (20, 30, 40, 50, and 60 g-cm) on the mortality and motor deficit in the 4 weeks following injury. Mortality was dependent upon the trauma dose: 20 g-cm, 11%; 30 g-cm, 14%; 40 g-cm, 27%; 50 g-cm, 32%; 60 g-cm, 41%. Statistical analysis by linear regression is highly significant for increasing mortality with increasing trauma dose. The motor deficit determined by a modified Tarlov scale also was dependent upon trauma dose. A trauma dose-response curve based on this study indicates that a drug which reduces the motor deficit from that found at 40 g-cm to that at 30 g-cm may be detected at a significant level of 0.05 with a power of 0.8 if 30 rats are included in each of placebo and treated groups. The same sample size would detect a significant reduction of mortality from that of 40 g-cm to 30 g-cm.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Model for Experimental Spinal Cord Injury in the Rat: I. Mortality and Motor Deficit

Perot¹,

Lee²,

Hsu

et al. 1987

Central Nervous System Trauma

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“…Typically, for the purposes of calculating N, the time to an outcome event is assumed to be exponentially distributed, though other, non-parametric methods are available [8][9][10]. In addition, the accrual pattern is usually assumed to be smooth, with patient entry times following a Uniform distribution over the accrual period (0, A) [11][12][13]. Under these assumptions it has been shown that…”

Section: A Brief Comment On Nmentioning

confidence: 99%

Back to basics: explaining sample size in outcome trials, are statisticians doing a thorough job?

Carroll

2009

Pharmaceutical Statistics

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Time to event outcome trials in clinical research are typically large, expensive and high-profile affairs. Such trials are commonplace in oncology and cardiovascular therapeutic areas but are also seen in other areas such as respiratory in indications like chronic obstructive pulmonary disease. Their progress is closely monitored and results are often eagerly awaited. Once available, the top line result is often big news, at least within the therapeutic area in which it was conducted, and the data are subsequently fully scrutinized in a series of high-profile publications. In such circumstances, the statistician has a vital role to play in the design, conduct, analysis and reporting of the trial. In particular, in drug development it is incumbent on the statistician to ensure at the outset that the sizing of the trial is fully appreciated by their medical, and other non-statistical, drug development team colleagues and that the risk of delivering a statistically significant but clinically unpersuasive result is minimized. The statistician also has a key role in advising the team when, early in the life of an outcomes trial, a lower than anticipated event rate appears to be emerging. This paper highlights some of the important features relating to outcome trial sample sizing and makes a number of simple recommendations aimed at ensuring a better, common understanding of the interplay between sample size and power and the final result required to provide a statistically positive and clinically persuasive outcome.

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“…In normal skin, similar amounts of CD4 + and CD8 + T cells are found in the dermis (13,14). T cells on the leading edge of the vitiligo lesion are homing lymphocytes, which specifically recognize autologous melanocytes (11,12,15).…”

Section: Introductionmentioning

confidence: 96%

CD8+ T cells from vitiligo perilesional margins induce autologous melanocyte apoptosis

Wu¹,

Zhou²,

Wan³

et al. 2012

Molecular Medicine Reports

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Cell-mediated autoimmunity has been suggested to be involved in the melanocyte apoptosis that occurs in vitiligo. We investigated the cytotoxicity to autologous melanocytes of CD8+ T cells from the perilesional margins and peripheral blood samples of vitiligo patients. CD8+ T cells isolated from skin biopsied from the edges of depigmented skin patches of vitiligo patients or from peripheral blood samples of the same donors were proliferated in culture medium. The primary cultures of CD8+ T cells and autologous melanocytes were mixed at ratios of 1:1, 1:2 or 1:5 and incubated for 3 days. The apoptosis of the melanocytes was analyzed by flow cytometry. Secreted cytokines in selected samples were measured by cytokine arrays. The results show that the CD8+ T cells were successfully isolated from the vitiligo perilesional margins. This cell population showed a significantly higher percentage of CD69 expression (56.13±3.55 versus 29.93±2.35%, p<0.01) and CD137 expression (41.74±1.06 versus 25.97±1.63%, p<0.01) compared with CD8+ T cells in peripheral blood from the same donors. The co-culturing of CD8+ T cells from lesional skin with autologous melanocytes induced apoptosis in the melanocytes (16.63±1.21, 16.71±0.63 and 18.32±1.60% for CD8+ T cells and autologous melanocytes at ratios of 1:1, 1:2 and 1:5, respectively). IL-6 levels were much higher in the co-culture (3.01-fold higher than in a melanocyte monoculture and 17.32-fold higher than in a CD8+ T-cell monoculture). The CD8+ T cells were also demonstrated to secrete more IL-13. Taken together, our data demonstrate that the infiltration of active CD8+ T cells takes place in the vitiligo perilesional margins. Those CD8+ T cells present significantly higher activation levels and higher cytotoxicity to autologous melanocytes than their counterparts from peripheral blood samples. These data suggest that CD8+ T cells are likely to be involved in the pathogenesis of vitiligo.

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Sample Size Determination in Clinical Trials with an Emphasis on Exponentially Distributed Responses

Cited by 16 publications

References 13 publications

Therapeutic Model for Experimental Spinal Cord Injury in the Rat: I. Mortality and Motor Deficit

Therapeutic Model for Experimental Spinal Cord Injury in the Rat: I. Mortality and Motor Deficit

Back to basics: explaining sample size in outcome trials, are statisticians doing a thorough job?

CD8+ T cells from vitiligo perilesional margins induce autologous melanocyte apoptosis

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