A simulation study using the hybrid statistic and the meta-analysis t-test for data with matched and unmatched subjects in the interim analysis of clinical trials

An interim analysis is usually applied in later phase II or phase III trials to find convincing evidence of a significant treatment difference that may lead to trial termination at an earlier point than planned at the beginning. This can result in the saving of patient resources and shortening of drug development and approval time. In addition, ethics and economics are also the reasons to stop a trial earlier. In clinical trials of eyes, ears, knees, arms, kidneys, lungs, and other clustered treatments, data may include distribution-free random variables with matched and unmatched subjects in one study. It is important to properly include both subjects in the interim and the final analyses so that the maximum efficiency of statistical and clinical inferences can be obtained at different stages of the trials. So far, no publication has applied a statistical method for distribution-free data with matched and unmatched subjects in the interim analysis of clinical trials. In this simulation study, the hybrid statistic was used to estimate the empirical powers and the empirical type I errors among the simulated datasets with different sample sizes, different effect sizes, different correlation coefficients for matched pairs, and different data distributions, respectively, in the interim and final analysis with 4 different group sequential methods. Empirical powers and empirical type I errors were also compared to those estimated by using the meta-analysis t-test among the same simulated datasets. Results from this simulation study show that, compared to the meta-analysis t-test commonly used for data with normally distributed observations, the hybrid statistic has a greater power for data observed from normally, log-normally, and multinomially distributed random variables with matched and unmatched subjects and with outliers. Powers rose with the increase in sample size, effect size, and correlation coefficient for the matched pairs. In addition, lower type I errors were observed estimated by using the hybrid statistic, which indicates that this test is also conservative for data with outliers in the interim analysis of clinical trials.^

Implementation of an Anthropomorphic Phantom for the Evaluation of Proton Therapy Treatment Procedures

With an increasing number of institutions offering proton therapy, the number of multi-institutional clinical trials involving proton therapy will also increase in the coming years. The Radiological Physics Center monitors sites involved in clinical trials through the use of site visits and remote auditing with thermoluminescent dosimeters (TLD) and mailable anthropomorphic phantoms. Currently, there are no heterogeneous phantoms that have been commissioned to evaluate proton therapy. It was hypothesized that an anthropomorphic pelvis phantom can be designed to audit treatment procedures (patient simulation, treatment planning and treatment delivery) at proton facilities to confirm agreement between the measured dose and calculated dose within 5%/3mm with a reproducibility of 3%. A pelvis phantom originally designed for use with photon treatments was retrofitted for use in proton therapy. The relative stopping power (SP) of each phantom material was measured. Hounsfield Units (HU) for each phantom material were measured with a CT scanner and compared to the relative stopping power calibration curve. The tissue equivalency for each material was calculated. Two proton treatment plans were created; one which did not correct for material SP differences (Plan 1) and one plan which did correct for SP differences (Plan 2). Film and TLD were loaded into the phantom and the phantom was irradiated 3 times per plan. The measured values were compared to the HU-SP calibration curve and it was found that the stopping powers for the materials could be underestimated by 5-10%. Plan 1 passed the criteria for the TLD and film margins with reproducibility under 3% between the 3 trials. Plan 2 failed because the right-left film dose profile average displacement was -9.0 mm on the left side and 6.0 mm on the right side. Plan 2 was intended to improve the agreements and instead introduced large displacements along the path of the beam. Plan 2 more closely represented the actual phantom composition with corrected stopping powers and should have shown an agreement between the measured and calculated dose within 5%/3mm. The hypothesis was rejected and the pelvis phantom was found to be not suitable to evaluate proton therapy treatment procedures.

Relating one's social support network to one's mid term grade

Much has been written about the relation of social support to health outcomes. Support networks were found to be predictive of health status. Not so clear was the manner in which social support helped the individual to avoid health complications. Whereas some aspects of the support network were protective, others were burdensome. Duties to one's network could serve as a stressor and duties outside one's network might stress the support system itself. Exposure to one's network was associated with certain health risks while disruption in one's social support network was associated with other health risks.^ Many factors contributed to the impact of a social support network upon the individual member: the characteristics of the individual, the individual's role or position within the network, qualities of the network and duties or indebtedness of the individual to the network. This investigation considered the possibility that performance could serve as a stressor in a fashion similar to an exposure to a health hazard.^ Because the literature includes many examples of studies in which the subjects were college students, academic progress is a performance common to most subjects. A profile of the support networks of successful students was contrasted with those of less successful students in this correlational study.^ What was uncovered in this investigation was a very complex web of interrelated constructs. Most aspects of the social support network did not significantly predict academic performance. Only a limited number of characteristics were associated with academic success: the frequency of support, student age, the existence of a 'mentor' within one' s network, and the extent to which one received a predominant source of support. Other factors had a tendency to be negatively correlated with midterm grade, suggesting those factors may impede academic performance.^ Medical status did not predict grades, but was correlated with many aspects of the network. Disruptions in particular parts of one's network were correlated with particular health categories. In fact, disruption in social support was more predictive of academic outcomes than medical complications. Whereas the individual's values were related to the contributing factors, only the individual's satisfaction with certain aspects of the support network were predictive of higher midterm grades in a psychology class. Dissatisfaction was associated with lower grades, suggesting a disruptive effect within the network. Associations among the features of support networks which predicted academic progress were considered. ^