Use of funded multicenter prospective longitudinal databases to inform clinical trials in rare diseases—Examination of cholestatic liver disease in Alagille syndrome
dc.contributor.author | Shneider, Benjamin L. | |
dc.contributor.author | Kamath, Binita M. | |
dc.contributor.author | Magee, John C. | |
dc.contributor.author | Goodrich, Nathan P. | |
dc.contributor.author | Loomes, Kathleen M. | |
dc.contributor.author | Ye, Wen | |
dc.contributor.author | Spino, Cathie | |
dc.contributor.author | Alonso, Estella M. | |
dc.contributor.author | Molleston, Jean P. | |
dc.contributor.author | Bezerra, Jorge A. | |
dc.contributor.author | Wang, Kasper S. | |
dc.contributor.author | Karpen, Saul J. | |
dc.contributor.author | Horslen, Simon P. | |
dc.contributor.author | Guthery, Stephen L. | |
dc.contributor.author | Rosenthal, Philip | |
dc.contributor.author | Squires, Robert H. | |
dc.contributor.author | Sokol, Ronald J. | |
dc.date.accessioned | 2022-08-02T18:59:24Z | |
dc.date.available | 2023-09-02 14:59:22 | en |
dc.date.available | 2022-08-02T18:59:24Z | |
dc.date.issued | 2022-08 | |
dc.identifier.citation | 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. (2022). "Use of funded multicenter prospective longitudinal databases to inform clinical trials in rare diseases—Examination of cholestatic liver disease in Alagille syndrome." Hepatology Communications (8): 1910-1921. | |
dc.identifier.issn | 2471-254X | |
dc.identifier.issn | 2471-254X | |
dc.identifier.uri | https://hdl.handle.net/2027.42/173149 | |
dc.description.abstract | 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.Prospective multi-center longitudinal databases, which may require significant funding, provide critical biomedical information. It is possible to adapt entry criteria for completed and on-going clinical trials to the participants in these registries, thereby generating a similar natural history cohort. Investment in prospective databases affords unique and invaluable real world data, serving as important comparators in the assessment of the safety and efficacy of novel agents investigated in rare diseases as demonstrated by this study in Alagille syndrome. | |
dc.publisher | Wiley Periodicals, Inc. | |
dc.title | Use of funded multicenter prospective longitudinal databases to inform clinical trials in rare diseases—Examination of cholestatic liver disease in Alagille syndrome | |
dc.type | Article | |
dc.rights.robots | IndexNoFollow | |
dc.subject.hlbsecondlevel | Internal Medicine | |
dc.subject.hlbtoplevel | Health Sciences | |
dc.description.peerreviewed | Peer Reviewed | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/173149/1/hep41970.pdf | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/173149/2/hep41970_am.pdf | |
dc.identifier.doi | 10.1002/hep4.1970 | |
dc.identifier.source | Hepatology Communications | |
dc.identifier.citedreference | Shah KK, Kogut S, Slitt A. Challenges in evaluating safety and efficacy in drug development for rare diseases: a review for pharmacists. J Pharm Pract. 2021; 34: 472 – 79. | |
dc.identifier.citedreference | Miller KL, Mueller C, Liu G, Miller Needleman KI, Maynard J. FDA orphan products clinical trial grants: assessment of outcomes and impact on rare disease product development. Orphanet J Rare Dis. 2020; 15: 234. | |
dc.identifier.citedreference | Kamath BM, Yin W, Miller H, Anand R, Rand EB, Alonso E, et al. Outcomes of liver transplantation in alagille syndrome: the split experience. Liver Transpl. 2012; 18: 940 – 8. | |
dc.identifier.citedreference | Kohut TJ, Gilbert MA, Loomes KM. Alagille syndrome: a focused review on clinical features, genetics, and treatment. Semin Liver Dis. 2021; 41: 525 – 37. | |
dc.identifier.citedreference | Kamath BM, Spino C, McLain R, Magee JC, Fredericks EM, Setchell KD, et al. Unraveling the relationship between itching, scratch scales, and biomarkers in children with Alagille syndrome. Hepatol Commun. 2020; 4: 1012 – 8. | |
dc.identifier.citedreference | Whitington PF, Whitington GL. Partial external diversion of bile for the treatment of intractable pruritus associated with intrahepatic cholestasis. Gastroenterology. 1988; 95: 130 – 6. | |
dc.identifier.citedreference | Kamath BM, Abetz-Webb L, Kennedy C, Hepburn B, Gauthier M, Johnson N, et al. Development of a novel tool to assess the impact of itching in pediatric cholestasis. Patient. 2018; 11: 69 – 82. | |
dc.identifier.citedreference | Sherman RE, Anderson SA, Dal Pan GJ, Gray GW, Gross T, Hunter NL, et al. Real-world evidence—what is it and what can it tell us? N Engl J Med. 2016; 375: 2293 – 7. | |
dc.identifier.citedreference | Schurman B. The framework for FDA’s Real World Evidence Program. Appl Clin Trials. 2019; 28: 15 – 7. | |
dc.identifier.citedreference | van Laarhoven AI, van der Sman-Mauriks IM, Donders AR, Pronk MC, van de Kerkhof PC, Evers AW. Placebo effects on itch: a meta-analysis of clinical trials of patients with dermatological conditions. J Invest Dermatol. 2015; 135: 1234 – 43. | |
dc.identifier.citedreference | Gonzales E, Hardikar W, Stormon M. ICONIC. Efficacy and safety of maralixibat treatment in patients with Alagille syndrome and cholestatic pruritus (ICONIC): a randomized phase 2 study. Lancet. 2021; 398: 1581 – 92. | |
dc.identifier.citedreference | Shneider BL, Spino C, Kamath BM, Magee JC, Sokol RJ, et al. Impact of long-term Administration of Maralixibat on children with cholestasis secondary to Alagille syndrome. Hepatol Commun. 2022. [Submitted]. | |
dc.identifier.citedreference | Shneider BL, Spino C, Kamath BM, Magee JC, Bass LM, Setchell KD, et al. Placebo-controlled randomized trial of an intestinal bile salt transport inhibitor for pruritus in Alagille syndrome. Hepatol Commun. 2018; 2: 1184 – 98. | |
dc.identifier.citedreference | Karpen SJ, Kelly D, Mack C, Stein P. Ileal bile acid transporter inhibition as an anticholestatic therapeutic target in biliary atresia and other cholestatic disorders. Hepatol Int. 2020; 14: 677 – 89. | |
dc.identifier.citedreference | Kamath BM, Ye W, Goodrich NP, Loomes KM, Romero R, Heubi JE, et al. Outcomes of childhood cholestasis in Alagille syndrome: results of a multicenter observational study. Hepatol Commun. 2020; 4: 387 – 98. | |
dc.identifier.citedreference | Kamath BM, Stein P, Houwen RHJ, Verkade HJ. Potential of ileal bile acid transporter inhibition as a therapeutic target in Alagille syndrome and progressive familial intrahepatic cholestasis. Liver Int. 2020; 40: 1812 – 22. | |
dc.identifier.citedreference | Neimark E, Shneider B. Novel surgical and pharmacological approaches to chronic cholestasis in children: partial external biliary diversion for intractable pruritus and xanthomas in Alagille syndrome. J Pediatr Gastroenterol Nutr. 2003; 36: 296 – 7. | |
dc.identifier.citedreference | Wang KS, Tiao G, Bass LM, Hertel PM, Mogul D, Kerkar N, et al. Analysis of surgical interruption of the enterohepatic circulation as a treatment for pediatric cholestasis. Hepatology. 2017; 65: 1645 – 54. | |
dc.identifier.citedreference | Kamath BM, Baker A, Houwen R, Todorova L, Kerkar N. Systematic review: the epidemiology, natural history, and burden of Alagille syndrome. J Pediatr Gastroenterol Nutr. 2018; 67: 148 – 56. | |
dc.identifier.citedreference | Mitchell E, Gilbert M, Loomes KM. Alagille syndrome. Clin Liver Dis. 2018; 22: 625 – 41. | |
dc.identifier.citedreference | Stockler-Ipsiroglu S, Potter BK, Yuskiv N, Tingley K, Patterson M, van Karnebeek C. Developments in evidence creation for treatments of inborn errors of metabolism. J Inherit Metab Dis. 2021; 44: 88 – 98. | |
dc.working.doi | NO | en |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.