Use of funded multicenter prospective longitudinal databases to inform clinical trials in rare diseases-Examination of cholestatic liver disease in Alagille syndrome.
Use of funded multicenter prospective longitudinal databases to inform clinical trials in rare diseases-Examination of cholestatic liver disease in Alagille syndrome.
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DOI：
10.1002/hep4.1970
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发表时间：
2022-08
影响因子：
5.1
通讯作者：
Sokol, Ronald J.
中科院分区：
文献类型：
--
作者：
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.
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.
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影响因子：
29.4
作者：
WHITINGTON, PF;WHITINGTON, GL
通讯作者：
WHITINGTON, GL
影响因子：
168.9
作者：
Gonzales, Emmanuel;Hardikar, Winita;Jacquemin, Emmanuel
通讯作者：
Jacquemin, Emmanuel
影响因子：
5.1
作者：
Kamath, Binita M.;Spino, Cathie;Shneider, Benjamin L.
通讯作者：
Shneider, Benjamin L.
DOI：
10.1002/hep.29019
发表时间：
2017-05
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Wang KS;Tiao G;Bass LM;Hertel PM;Mogul D;Kerkar N;Clifton M;Azen C;Bull L;Rosenthal P;Stewart D;Superina R;Arnon R;Bozic M;Brandt ML;Dillon PA;Fecteau A;Iyer K;Kamath B;Karpen S;Karrer F;Loomes KM;Mack C;Mattei P;Miethke A;Soltys K;Turmelle YP;West K;Zagory J;Goodhue C;Shneider BL;Childhood Liver Disease Research Network (ChiLDReN)
通讯作者：
Childhood Liver Disease Research Network (ChiLDReN)
DOI：
10.1007/s40271-017-0266-4
发表时间：
2018-03
期刊：
The patient
影响因子：
--
作者：
Kamath BM;Abetz-Webb L;Kennedy C;Hepburn B;Gauthier M;Johnson N;Medendorp S;Dorenbaum A;Todorova L;Shneider BL
通讯作者：
Shneider BL