A conceptual model and practical guidance for the development, administration, and evaluation of individualized therapies
Bespoke therapies represent a promising tool to address a diverse range of genetic and acquired conditions, offering new hope where conventional treatments have fallen short. With the rapid rise of bespoke therapies, profound ethical and regulatory challenges emerge, making it crucial to establish a...
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| Language: | English |
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2025.1493832/full |
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| author | Lucie Perillat Lucie Perillat Andrew McFadyen Andrew McFadyen Andrew McFadyen Patricia Furlong James Anderson James Anderson James Anderson |
| author_facet | Lucie Perillat Lucie Perillat Andrew McFadyen Andrew McFadyen Andrew McFadyen Patricia Furlong James Anderson James Anderson James Anderson |
| author_sort | Lucie Perillat |
| collection | DOAJ |
| description | Bespoke therapies represent a promising tool to address a diverse range of genetic and acquired conditions, offering new hope where conventional treatments have fallen short. With the rapid rise of bespoke therapies, profound ethical and regulatory challenges emerge, making it crucial to establish a comprehensive framework that ensures these treatments reach clinical settings and meet patients’ needs as quickly as possible while protecting all parties involved. Although current guidelines are continually evolving to address the range of ethical tensions raised by these therapies, several gaps remain. A significant unresolved question is determining where personalized interventions fall on the research-care continuum and understanding the institutional, regulatory, and ethical implications when custom therapies are classified as research, care, or a mix of both. To address these questions, we introduce a conceptual model alongside practical guidance for the development, administration, and evaluation of individualized therapies, using CRISPR/Cas9-based interventions for Duchenne Muscular Dystrophy as a case study. We argue that the goals of an intervention should be as individualized as the bespoke product itself, tailored to the specifics of each case. Rather than attempting to pinpoint the exact location of an intervention on the continuum, which may be hard to operationalize and have limited utility, our approach focuses on the practical details of how such interventions are administered and the individual component parts of an intervention. It advocates for transparent discussions among all partners to anticipate and adjust various components/parameters along the process of administering individualized interventions. Our paper highlights the most critical of these parameters in (1) the planning and development of individualized therapies in laboratory settings, (2) their regulatory oversight, and (3) evaluation. By discussing these stages and parameters in detail, we aim to provide guidance on how to navigate the ethical complexities inherent to individualized interventions and offer a preliminary framework for balancing the interplay between research objectives and patient care needs. Acknowledging that the scientific rigor and adequacy of any new model must be evaluated, we also identify the types of evidence that are required to validate that our model effectively meets individual and societal needs. |
| format | Article |
| id | doaj-art-d36c4bfa4281401b9893474f1d4af437 |
| institution | Kabale University |
| issn | 2296-858X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj-art-d36c4bfa4281401b9893474f1d4af4372025-02-05T17:36:56ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-01-011210.3389/fmed.2025.14938321493832A conceptual model and practical guidance for the development, administration, and evaluation of individualized therapiesLucie Perillat0Lucie Perillat1Andrew McFadyen2Andrew McFadyen3Andrew McFadyen4Patricia Furlong5James Anderson6James Anderson7James Anderson8Department of Molecular Genetics, University of Toronto, Toronto, ON, CanadaProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, CanadaPrecision Child Health, The Hospital for Sick Children, Toronto, ON, CanadaDivision of Clinical Public Health, University of Toronto, Toronto, ON, CanadaDepartment of Bioethics, The Hospital for Sick Children, Toronto, ON, CanadaParent Project Muscular Dystrophy, Washington, DC, United StatesDepartment of Bioethics, The Hospital for Sick Children, Toronto, ON, CanadaInstitute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, CanadaAI at SickKids, The Hospital for Sick Children, Toronto, ON, CanadaBespoke therapies represent a promising tool to address a diverse range of genetic and acquired conditions, offering new hope where conventional treatments have fallen short. With the rapid rise of bespoke therapies, profound ethical and regulatory challenges emerge, making it crucial to establish a comprehensive framework that ensures these treatments reach clinical settings and meet patients’ needs as quickly as possible while protecting all parties involved. Although current guidelines are continually evolving to address the range of ethical tensions raised by these therapies, several gaps remain. A significant unresolved question is determining where personalized interventions fall on the research-care continuum and understanding the institutional, regulatory, and ethical implications when custom therapies are classified as research, care, or a mix of both. To address these questions, we introduce a conceptual model alongside practical guidance for the development, administration, and evaluation of individualized therapies, using CRISPR/Cas9-based interventions for Duchenne Muscular Dystrophy as a case study. We argue that the goals of an intervention should be as individualized as the bespoke product itself, tailored to the specifics of each case. Rather than attempting to pinpoint the exact location of an intervention on the continuum, which may be hard to operationalize and have limited utility, our approach focuses on the practical details of how such interventions are administered and the individual component parts of an intervention. It advocates for transparent discussions among all partners to anticipate and adjust various components/parameters along the process of administering individualized interventions. Our paper highlights the most critical of these parameters in (1) the planning and development of individualized therapies in laboratory settings, (2) their regulatory oversight, and (3) evaluation. By discussing these stages and parameters in detail, we aim to provide guidance on how to navigate the ethical complexities inherent to individualized interventions and offer a preliminary framework for balancing the interplay between research objectives and patient care needs. Acknowledging that the scientific rigor and adequacy of any new model must be evaluated, we also identify the types of evidence that are required to validate that our model effectively meets individual and societal needs.https://www.frontiersin.org/articles/10.3389/fmed.2025.1493832/fullethical challengesregulatory implicationsCRISPR/Cas9 therapeuticsresearch-care dichotomybespoke therapyNof1 |
| spellingShingle | Lucie Perillat Lucie Perillat Andrew McFadyen Andrew McFadyen Andrew McFadyen Patricia Furlong James Anderson James Anderson James Anderson A conceptual model and practical guidance for the development, administration, and evaluation of individualized therapies Frontiers in Medicine ethical challenges regulatory implications CRISPR/Cas9 therapeutics research-care dichotomy bespoke therapy Nof1 |
| title | A conceptual model and practical guidance for the development, administration, and evaluation of individualized therapies |
| title_full | A conceptual model and practical guidance for the development, administration, and evaluation of individualized therapies |
| title_fullStr | A conceptual model and practical guidance for the development, administration, and evaluation of individualized therapies |
| title_full_unstemmed | A conceptual model and practical guidance for the development, administration, and evaluation of individualized therapies |
| title_short | A conceptual model and practical guidance for the development, administration, and evaluation of individualized therapies |
| title_sort | conceptual model and practical guidance for the development administration and evaluation of individualized therapies |
| topic | ethical challenges regulatory implications CRISPR/Cas9 therapeutics research-care dichotomy bespoke therapy Nof1 |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1493832/full |
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