Statistical approaches in oncology clinical development: Current paradigm and methodological advancement. Satrajit Roychoudhury and Soumi Lahiri. Boca Raton: Chapman and Hall/CRC.

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151915/1/biom13129.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151915/2/biom13129_am.pd

Survival Analysis of Shared-Path Adaptive Treatment Strategies

Adaptive treatment strategies closely mimic the reality of a physician's prescription process where the physician prescribes a medication to his/her patient and based on that patient's response to the medication, modifies the treatment. Two-stage randomization designs, more generally, sequential multiple assignment randomization trial (SMART) designs, are useful to assess adaptive treatment strategies where the interest is in comparing the entire sequence of treatments, including the patient's intermediate response. In this dissertation, we introduce the notion of shared-path and separate-path adaptive treatment strategies and propose weighted log-rank statistics to compare overall survival distributions of two shared-path or multiple two-stage adaptive treatment strategies. Large sample properties of the statistics are derived and the type I error rate and power of the tests are compared to standard statistics through simulation. We also propose a sample size equation to power a two-stage SMART comparing the overall survival of multiple adaptive treatment strategies. Public health significance: The treatment of many diseases and illnesses, especially those which are chronic (cancer, AIDS, depression, substance abuse, ADHD), includes sequences of treatments based on the individual's characteristics, behaviors, and responses. Treatment is inherently dynamic, but often, clinical trials are not designed or analyzed to take this dynamic feature into account. We present methods to adequately power and analyze clinical trials with time-to-event data which aim to compare these individualized sequences of treatments or adaptive treatment strategies. Through these methods and by comparing adaptive treatment strategies, patient outcomes can be operationalized and improved over time

Inference for the median residual life function in sequential multiple assignment randomized trials

In survival analysis, median residual lifetime is often used as a summary measure to assess treatment effectiveness; it is not clear, however, how such a quantity could be estimated for a given dynamic treatment regimen using data from sequential randomized clinical trials. We propose a method to estimate a dynamic treatment regimen‐specific median residual life (MERL) function from sequential multiple assignment randomized trials. We present the MERL estimator, which is based on inverse probability weighting, as well as, two variance estimates for the MERL estimator. One variance estimate follows from Lunceford, Davidian and Tsiatis' 2002 survival function‐based variance estimate and the other uses the sandwich estimator. The MERL estimator is evaluated, and its two variance estimates are compared through simulation studies, showing that the estimator and both variance estimates produce approximately unbiased results in large samples. To demonstrate our methods, the estimator has been applied to data from a sequentially randomized leukemia clinical trial. Copyright © 2013 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106925/1/sim6042.pd

A Bayesian analysis of small n sequential multiple assignment randomized trials (snSMARTs)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146269/1/sim7900.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146269/2/sim7900_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146269/3/A_Bayesian_Analysis_of_snSMART_Revision_Supplimentary.pd

Weighted Log-rank Statistic to Compare Shared-Path Adaptive Treatment Strategies

Abstract Adaptive treatment strategies more closely mimic the reality of a physician's prescription process where the physician prescribes a medication to his/her patient and based on that patient's response to the medication, modifies the treatment. Two-stage randomization designs, more generally, sequential multiple assignment randomization trial (SMART) designs, are useful to assess adaptive treatment strategies where the interest is in comparing the entire sequence of treatments, including the patient's intermediate response. In this paper, we introduce the notion of shared-path and separate-path adaptive treatment strategies and propose weighted log-rank statistics to compare overall survival distributions of two or more two-stage, shared-path adaptive treatment strategies. Large sample properties of the statistics are derived and the type I error rate and power of the tests are compared to standard statistics through simulation

Using an interactive water bottle to target fluid adherence in pediatric kidney transplant recipients: A pilot study

Hydration is important post‐renal transplant to maintain adequate renal perfusion and graft function. Adherence to fluid recommendations is challenging given barriers to staying hydrated. There are no studies of adherence to fluid intake recommendations following pediatric renal transplant. Through this pilot study, we sought to determine whether the use of a commercially available interactive water bottle would lead to better adherence to recommended fluid intake and improved kidney functioning post‐transplant relative to standard of care. Participants included 32 youth ages 7–19 ≥1 month post‐kidney transplant randomized to the intervention (HydraCoach ® water bottle) or standard education control group. Laboratory records were reviewed for serum chemistries (Na, BUN , creatinine) at baseline and one‐month follow‐up, and participants recorded daily fluid intake for 28 days. Those in the intervention group were significantly more likely to meet or exceed their fluid target, but this did not translate into better kidney functioning. Participants in the intervention group largely reported satisfaction with the water bottle and were likely to continue its use. While an interactive water bottle providing real‐time feedback may be a promising intervention to help pediatric kidney transplant patients meet fluid goals, it did not appear to impact kidney function.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109912/1/petr12385.pd

Improving nutritional status in a pediatric cystic fibrosis center

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111789/1/ppul23128.pd

Perceptions of 24/7 In‐house Attending Coverage on Fellow Education and Autonomy in a Pediatric Cardiothoracic Intensive Care Unit

BackgroundThe 24/7 in‐house attending coverage is emerging as the standard of care in intensive care units. Implementation costs, workforce feasibility, and patient outcomes resulting from changes in physician staffing are widely debated topics. Understanding the impact of staffing models on the learning environment for medical trainees and faculty is equally warranted, particularly with respect to trainee education and autonomy.ObjectiveThis study aims to elicit the perceptions of pediatric cardiology fellows and attendings toward 24/7 in‐house attending coverage and its effect on fellow education and autonomy.MethodsWe surveyed pediatric cardiology fellows and attendings practicing in the pediatric cardiothoracic intensive care unit (PCTU) of a large, university‐affiliated medical center, using structured Likert response items and open‐ended questions, prior to and following the transition to 24/7 in‐house attending coverage.ResultsAll (100%) trainees and faculty completed all surveys. Both prior to and following transition to 24/7 in‐house attending coverage, all fellows, and the majority of attendings agreed that the overnight call experience benefited fellow education. At baseline, trainees identified limited circumstances in which on‐site attending coverage would be critical. Preimplementation concerns that 24/7 in‐house attending coverage would negatively affect the education of fellows were not reflected following actual implementation of the new staffing policy. However, based upon open‐ended questions, fellow autonomy was affected by the new paradigm, with fellows and attendings reporting decreased “appropriateness” of autonomy after implementation.ConclusionsOur prospective study, showing initial concerns about limiting the learning environment in transitioning to 24/7 in‐house attending coverage did not result in diminished perceptions of the educational experience for our fellows but revealed an expected decrease in fellow autonomy. The study indirectly facilitated open discussions about methods to preserve fellow education and warranted autonomy in our PCTU; however, continued efforts are needed to achieve the optimal balance between supervised training and the transition to autonomous practice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111990/1/chd12261.pd

Statistical competencies for medical research learners: What is fundamental?

IntroductionIt is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from 'fundamental' (necessary for all) to 'specialized' (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.MethodsWe surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by 'fundamental' and 'specialized.'ResultsThere were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one's own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).ConclusionWe have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature