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Improving resource utilisation in SLE drug development through innovative trial design
SLE is a complex autoimmune disease with considerable unmet need. Numerous clinical trials designed to investigate novel therapies are actively enrolling patients straining limited resources and creating inefficiencies that increase enrolment challenges. This has motivated investigators developing n...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373732/ https://www.ncbi.nlm.nih.gov/pubmed/37491104 http://dx.doi.org/10.1136/lupus-2022-000890 |
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author | Garces, Sandra Karis, Elaine Merrill, Joan T Askanase, Anca D Kalunian, Kenneth Mo, May Milmont, Cassandra E |
author_facet | Garces, Sandra Karis, Elaine Merrill, Joan T Askanase, Anca D Kalunian, Kenneth Mo, May Milmont, Cassandra E |
author_sort | Garces, Sandra |
collection | PubMed |
description | SLE is a complex autoimmune disease with considerable unmet need. Numerous clinical trials designed to investigate novel therapies are actively enrolling patients straining limited resources and creating inefficiencies that increase enrolment challenges. This has motivated investigators developing novel drugs and treatment strategies to consider innovative trial designs that aim to improve the efficiency of generating evidence; these strategies propose conducting fewer trials, involving smaller numbers of patients, while maintaining scientific rigour in safety and efficacy data collection and analysis. In this review we present the design of two innovative phase IIb studies investigating efavaleukin alfa and rozibafusp alfa for the treatment of SLE which use an adaptive study design. This design was selected as a case study, investigating efavaleukin alfa, in the Food and Drug Administration’s Complex Innovative Trial Design Pilot Program. The adaptive design approach includes prospectively planned modifications at predefined interim timepoints. Interim assessments of futility allow for a trial to end early when the investigational therapy is unlikely to provide meaningful treatment benefits to patients, which can release eligible patients to participate in other—potentially more promising—trials, or seek alternative treatments. Response-adaptive randomisation allows randomisation ratios to change based on accumulating data, in favour of the more efficacious dose arm(s), while the study is ongoing. Throughout the trial the placebo arm allocation ratio is maintained constant. These design elements can improve the statistical power in the estimation of treatment effect and increase the amount of safety and efficacy data collected for the optimal dose(s). Furthermore, these trials can provide the required evidence to potentially serve as one of two confirmatory trials needed for regulatory approval. This can reduce the need for multiple phase III trials, the total patient requirements, person-exposure risk, and ultimately the time and cost of investigational drug development programmes. |
format | Online Article Text |
id | pubmed-10373732 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-103737322023-07-28 Improving resource utilisation in SLE drug development through innovative trial design Garces, Sandra Karis, Elaine Merrill, Joan T Askanase, Anca D Kalunian, Kenneth Mo, May Milmont, Cassandra E Lupus Sci Med Review SLE is a complex autoimmune disease with considerable unmet need. Numerous clinical trials designed to investigate novel therapies are actively enrolling patients straining limited resources and creating inefficiencies that increase enrolment challenges. This has motivated investigators developing novel drugs and treatment strategies to consider innovative trial designs that aim to improve the efficiency of generating evidence; these strategies propose conducting fewer trials, involving smaller numbers of patients, while maintaining scientific rigour in safety and efficacy data collection and analysis. In this review we present the design of two innovative phase IIb studies investigating efavaleukin alfa and rozibafusp alfa for the treatment of SLE which use an adaptive study design. This design was selected as a case study, investigating efavaleukin alfa, in the Food and Drug Administration’s Complex Innovative Trial Design Pilot Program. The adaptive design approach includes prospectively planned modifications at predefined interim timepoints. Interim assessments of futility allow for a trial to end early when the investigational therapy is unlikely to provide meaningful treatment benefits to patients, which can release eligible patients to participate in other—potentially more promising—trials, or seek alternative treatments. Response-adaptive randomisation allows randomisation ratios to change based on accumulating data, in favour of the more efficacious dose arm(s), while the study is ongoing. Throughout the trial the placebo arm allocation ratio is maintained constant. These design elements can improve the statistical power in the estimation of treatment effect and increase the amount of safety and efficacy data collected for the optimal dose(s). Furthermore, these trials can provide the required evidence to potentially serve as one of two confirmatory trials needed for regulatory approval. This can reduce the need for multiple phase III trials, the total patient requirements, person-exposure risk, and ultimately the time and cost of investigational drug development programmes. BMJ Publishing Group 2023-07-25 /pmc/articles/PMC10373732/ /pubmed/37491104 http://dx.doi.org/10.1136/lupus-2022-000890 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Review Garces, Sandra Karis, Elaine Merrill, Joan T Askanase, Anca D Kalunian, Kenneth Mo, May Milmont, Cassandra E Improving resource utilisation in SLE drug development through innovative trial design |
title | Improving resource utilisation in SLE drug development through innovative trial design |
title_full | Improving resource utilisation in SLE drug development through innovative trial design |
title_fullStr | Improving resource utilisation in SLE drug development through innovative trial design |
title_full_unstemmed | Improving resource utilisation in SLE drug development through innovative trial design |
title_short | Improving resource utilisation in SLE drug development through innovative trial design |
title_sort | improving resource utilisation in sle drug development through innovative trial design |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373732/ https://www.ncbi.nlm.nih.gov/pubmed/37491104 http://dx.doi.org/10.1136/lupus-2022-000890 |
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