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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2023-11-01
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| Series: | Lupus Science and Medicine |
| Online Access: | https://lupus.bmj.com/content/10/2/e000890.full |
| _version_ | 1797366335243550720 |
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| author | Joan T Merrill Kenneth Kalunian Sandra Garces Anca D Askanase Elaine Karis May Mo Cassandra E Milmont |
| author_facet | Joan T Merrill Kenneth Kalunian Sandra Garces Anca D Askanase Elaine Karis May Mo Cassandra E Milmont |
| author_sort | Joan T Merrill |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-08T17:03:43Z |
| format | Article |
| id | doaj.art-2fa9074c62ef463690b0a0c71f60cdae |
| institution | Directory Open Access Journal |
| issn | 2053-8790 |
| language | English |
| last_indexed | 2024-03-08T17:03:43Z |
| publishDate | 2023-11-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Lupus Science and Medicine |
| spelling | doaj.art-2fa9074c62ef463690b0a0c71f60cdae2024-01-04T06:35:08ZengBMJ Publishing GroupLupus Science and Medicine2053-87902023-11-0110210.1136/lupus-2022-000890Improving resource utilisation in SLE drug development through innovative trial designJoan T Merrill0Kenneth Kalunian1Sandra Garces2Anca D Askanase3Elaine Karis4May Mo5Cassandra E Milmont65Oklahoma Medical Research Foundation, Oklahoma City, USA4Division of Rheumatology, Allergy and Immunology, University of California San Diego, CA, USAAmgen Inc, Thousand Oaks, California, USAMedicine, Columbia University College of Physicians and Surgeons, New York, New York, USAAmgen Inc, Thousand Oaks, California, USAAmgen Inc, Thousand Oaks, California, USAAmgen Inc, Thousand Oaks, California, USASLE 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.https://lupus.bmj.com/content/10/2/e000890.full |
| spellingShingle | Joan T Merrill Kenneth Kalunian Sandra Garces Anca D Askanase Elaine Karis May Mo Cassandra E Milmont Improving resource utilisation in SLE drug development through innovative trial design Lupus Science and Medicine |
| 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 |
| url | https://lupus.bmj.com/content/10/2/e000890.full |
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