Browsing by Author "Spino, Cathie"

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    Guidance for biostatisticians on their essential contributions to clinical and translational research protocol review
    (Cambridge University Press, 2021-07-12) Ciolino, Jody D.; Spino, Cathie; Ambrosius, Walter T.; Khalatbari, Shokoufeh; Messinger Cayetano, Shari; Lapidus, Jodi A.; Nietert, Paul J.; Oster, Robert A.; Perkins, Susan M.; Pollock, Brad H.; Pomann, Gina-Maria; Price, Lori Lyn; Rice, Todd W.; Tosteson, Tor D.; Lindsell, Christopher J.; Spratt, Heidi; Biostatistics and Health Data Science, School of Medicine
    Rigorous scientific review of research protocols is critical to making funding decisions, and to the protection of both human and non-human research participants. Given the increasing complexity of research designs and data analysis methods, quantitative experts, such as biostatisticians, play an essential role in evaluating the rigor and reproducibility of proposed methods. However, there is a common misconception that a statistician’s input is relevant only to sample size/power and statistical analysis sections of a protocol. The comprehensive nature of a biostatistical review coupled with limited guidance on key components of protocol review motived this work. Members of the Biostatistics, Epidemiology, and Research Design Special Interest Group of the Association for Clinical and Translational Science used a consensus approach to identify the elements of research protocols that a biostatistician should consider in a review, and provide specific guidance on how each element should be reviewed. We present the resulting review framework as an educational tool and guideline for biostatisticians navigating review boards and panels. We briefly describe the approach to developing the framework, and we provide a comprehensive checklist and guidance on review of each protocol element. We posit that the biostatistical reviewer, through their breadth of engagement across multiple disciplines and experience with a range of research designs, can and should contribute significantly beyond review of the statistical analysis plan and sample size justification. Through careful scientific review, we hope to prevent excess resource expenditure and risk to humans and animals on poorly planned studies.
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    Use of funded multicenter prospective longitudinal databases to inform clinical trials in rare diseases-Examination of cholestatic liver disease in Alagille syndrome
    (Wolters Kluwer, 2022) Shneider, Benjamin L.; Kamath, Binita M.; Magee, John C.; Goodrich, Nathan P.; Loomes, Kathleen M.; Ye, Wen; Spino, Cathie; Alonso, Estella M.; Molleston, Jean P.; Bezerra, Jorge A.; Wang, Kasper S.; Karpen, Saul J.; Horslen, Simon P.; Guthery, Stephen L.; Rosenthal, Philip; Squires, Robert H.; Sokol, Ronald J.; Childhood Liver Disease Research Network (ChiLDReN); Pediatrics, School of Medicine
    The conduct of long-term conventional randomized clinical trials in rare diseases is very difficult, making evidenced-based drug development problematic. As a result, real-world data/evidence are being used more frequently to assess new therapeutic approaches in orphan diseases. In this investigation, inclusion and exclusion criteria from a published trial of maralixibat in Alagille syndrome (ALGS, ITCH NCT02057692) were applied to a prospective longitudinal cohort of children with cholestasis (LOGIC NCT00571272) to derive contextual comparator data for evolving clinical trials of intestinal bile acid transport inhibitors in ALGS. A natural history/clinical care cohort of 59 participants who met adapted inclusion and exclusion criteria of ITCH was identified from 252 LOGIC participants with ALGS with their native liver. Frequency weighting was used to match the age distribution of ITCH and yielded a cohort (Alagille Syndrome Natural History [ALGS NH]) that was very similar to the baseline status of ITCH participants. During a 2-year prospective follow-up there was a significant reduction in pruritus in the weighted ALGS NH cohort as assessed by the clinician scratch score (-1.43 [0.28] -1.99, -0.87; mean [SEM] 95% confidence interval). During the same time period, the total bilirubin, albumin, and alanine aminotransferase levels were unchanged, whereas platelet count dropped significantly (-65.2 [16.2] -98.3, -32.1). Weighted survival with native liver was 91% at 2 years in the ALGS NH. These investigations provide valuable real-world data that can serve as contextual comparators to current clinical trials, especially those without control populations, and highlight the value and importance of funded multicenter, prospective, natural history studies.