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.^

Improving disclosure of medical errors: Including patients and family members in the disclosure process

Over the last decade, adverse events and medical errors have become a main focus of interest for the standards of quality and safety in the U.S. healthcare system (Weinstein & Henderson, 2009). Particularly when a medical error occurs, the disclosure of medical errors and its practices have become a focal point of the healthcare process. Patients and family members who have experienced a medical error might be able to provide knowledge and insight on how to improve the disclose process. However, patient and family member are not typically involved in the disclosure process, thus their experiences go unnoticed. ^ The purpose of this research was to explore how best to include patients and family members in the disclosure process regarding a medical error. The research consisted of 28 qualitative interviews from three stakeholder groups: Hospital Administrators, Clinical Service Providers, and Patients and Family Members. They were asked for their ideas and suggestions on how best to include patients and family members in the disclosure process. Framework Analysis was used to analyze this data and find prevalent themes based on the primary research question. A secondary aim was to index categories created based on the interviews that were collected. Data was used from the Texas Disclosure and Compensation Study with Dr. Eric Thomas as the Principal Investigator. Full acknowledgement of access to this data is given to Dr. Thomas. ^ The themes from the research revealed that each stakeholder group was interested and open to including patients and family members in the disclosure process and that the disclosure process should not be a "one-way" avenue. The themes gave many suggestions regarding how to best include patients and family members in the disclosure process of a medical error. Secondary aims revealed several ways to assess the ideas and suggestion given by the stakeholders. Overall, acceptability of getting the perspective of patients and family members was the most common theme. Comparison of each stakeholder group revealed that including patients and family members would be beneficial to improving hospital disclosure practices. ^ Conclusions included a list of recommendations and measureable appropriate strategies that could provide hospital with key stakeholders insights on how to improve their disclosure process. Sharing patients and family members experience with healthcare providers can encourage a shift in culture where patients are valued and active in participating in hospital practices. To my knowledge, this research is the very first of its kind and moves the disclosure process conversation forward in a patient-family member inclusion direction that will assist in improving disclosure practices. Future research should implement and evaluate the success of the various inclusion strategies.^