A framework for N-of-1 trials of individualized gene-targeted therapies for genetic diseases
Individualized genetic therapies - medicines that precisely target a genetic variant that may only be found in a small number of individuals, as few as only one - offer promise for addressing unmet needs in genetic disease, but present unique challenges for trial design. By nature these new individu...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
12 November 2024
|
| In: |
Nature Communications
Year: 2024, Jahrgang: 15, Pages: 1-5 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-024-54077-5 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-024-54077-5 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41467-024-54077-5 
|
| Verfasserangaben: | Olivia Kim-McManus, Joseph G. Gleeson, Laurence Mignon, Amena Smith Fine, Winston Yan, Nicole Nolen, Scott Demarest, Elizabeth Berry-Kravis, Richard Finkel, Stefanie Leonard, Samuel Finlayson, Erika Augustine, Gholson J. Lyon, Rebecca Schule & Timothy Yu |
MARC
| LEADER | 00000naa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1932496068 | ||
| 003 | DE-627 | ||
| 005 | 20250805104526.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 250805s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-024-54077-5 |2 doi | |
| 035 | |a (DE-627)1932496068 | ||
| 035 | |a (DE-599)KXP1932496068 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Kim-McManus, Olivia |e VerfasserIn |0 (DE-588)1373174838 |0 (DE-627)193249667X |4 aut | |
| 245 | 1 | 2 | |a A framework for N-of-1 trials of individualized gene-targeted therapies for genetic diseases |c Olivia Kim-McManus, Joseph G. Gleeson, Laurence Mignon, Amena Smith Fine, Winston Yan, Nicole Nolen, Scott Demarest, Elizabeth Berry-Kravis, Richard Finkel, Stefanie Leonard, Samuel Finlayson, Erika Augustine, Gholson J. Lyon, Rebecca Schule & Timothy Yu |
| 246 | 3 | 3 | |a A framework for N-of-one trials of individualized gene-targeted therapies for genetic diseases |
| 264 | 1 | |c 12 November 2024 | |
| 300 | |a 5 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 05.08.2025 | ||
| 520 | |a Individualized genetic therapies - medicines that precisely target a genetic variant that may only be found in a small number of individuals, as few as only one - offer promise for addressing unmet needs in genetic disease, but present unique challenges for trial design. By nature these new individualized medicines require testing in individualized N-of-1 trials. Here, we provide a framework for maintaining scientific rigor in N-of-1 trials. Building upon best practices from traditional clinical trial design, recent guidance from the United States Food and Drug Administration, and our own clinical research experience, we suggest key considerations including comprehensive baseline natural history, selection of appropriate clinical outcome assessments (COAs) individualized to the patient genotype-phenotype for safety and efficacy assessment over time, and specific statistical considerations. Standardization of N-of-1 trial designs in this fashion will maximize efficient learning from this next generation of targeted individualized therapeutics. | ||
| 650 | 4 | |a Antisense oligonucleotide therapy | |
| 650 | 4 | |a Clinical trials | |
| 650 | 4 | |a Drug discovery | |
| 650 | 4 | |a Gene therapy | |
| 650 | 4 | |a Personalized medicine | |
| 700 | 1 | |a Gleeson, Joseph G. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mignon, Laurence |e VerfasserIn |4 aut | |
| 700 | 1 | |a Smith Fine, Amena |e VerfasserIn |4 aut | |
| 700 | 1 | |a Yan, Winston |e VerfasserIn |4 aut | |
| 700 | 1 | |a Nolen, Nicole |e VerfasserIn |4 aut | |
| 700 | 1 | |a Demarest, Scott |e VerfasserIn |4 aut | |
| 700 | 1 | |a Berry-Kravis, Elizabeth |e VerfasserIn |4 aut | |
| 700 | 1 | |a Finkel, Richard |e VerfasserIn |4 aut | |
| 700 | 1 | |a Leonard, Stefanie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Finlayson, Samuel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Augustine, Erika |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lyon, Gholson J. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schüle-Freyer, Rebecca |d 1975- |e VerfasserIn |0 (DE-588)137544472 |0 (DE-627)695848283 |0 (DE-576)30411118X |4 aut | |
| 700 | 1 | |a Yu, Timothy |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature Communications |d [London] : Springer Nature, 2010 |g 15(2024), Artikel-ID 9802, Seite 1-5 |h Online-Ressource |w (DE-627)626457688 |w (DE-600)2553671-0 |w (DE-576)331555905 |x 2041-1723 |7 nnas |a A framework for N-of-1 trials of individualized gene-targeted therapies for genetic diseases |
| 773 | 1 | 8 | |g volume:15 |g year:2024 |g elocationid:9802 |g pages:1-5 |g extent:5 |a A framework for N-of-1 trials of individualized gene-targeted therapies for genetic diseases |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41467-024-54077-5 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.nature.com/articles/s41467-024-54077-5 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20250805 | ||
| 993 | |a Article | ||
| 994 | |a 2024 | ||
| 998 | |g 137544472 |a Schüle-Freyer, Rebecca |m 137544472:Schüle-Freyer, Rebecca |d 910000 |d 911100 |e 910000PS137544472 |e 911100PS137544472 |k 0/910000/ |k 1/910000/911100/ |p 14 | ||
| 999 | |a KXP-PPN1932496068 |e 4753201163 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"language":["eng"],"note":["Gesehen am 05.08.2025"],"type":{"bibl":"article-journal","media":"Online-Ressource"},"titleAlt":[{"title":"A framework for N-of-one trials of individualized gene-targeted therapies for genetic diseases"}],"name":{"displayForm":["Olivia Kim-McManus, Joseph G. Gleeson, Laurence Mignon, Amena Smith Fine, Winston Yan, Nicole Nolen, Scott Demarest, Elizabeth Berry-Kravis, Richard Finkel, Stefanie Leonard, Samuel Finlayson, Erika Augustine, Gholson J. Lyon, Rebecca Schule & Timothy Yu"]},"person":[{"given":"Olivia","display":"Kim-McManus, Olivia","family":"Kim-McManus","role":"aut"},{"display":"Gleeson, Joseph G.","given":"Joseph G.","family":"Gleeson","role":"aut"},{"given":"Laurence","display":"Mignon, Laurence","family":"Mignon","role":"aut"},{"family":"Smith Fine","role":"aut","display":"Smith Fine, Amena","given":"Amena"},{"role":"aut","family":"Yan","given":"Winston","display":"Yan, Winston"},{"role":"aut","family":"Nolen","given":"Nicole","display":"Nolen, Nicole"},{"given":"Scott","display":"Demarest, Scott","family":"Demarest","role":"aut"},{"display":"Berry-Kravis, Elizabeth","given":"Elizabeth","family":"Berry-Kravis","role":"aut"},{"given":"Richard","display":"Finkel, Richard","role":"aut","family":"Finkel"},{"display":"Leonard, Stefanie","given":"Stefanie","family":"Leonard","role":"aut"},{"role":"aut","family":"Finlayson","given":"Samuel","display":"Finlayson, Samuel"},{"given":"Erika","display":"Augustine, Erika","family":"Augustine","role":"aut"},{"role":"aut","family":"Lyon","given":"Gholson J.","display":"Lyon, Gholson J."},{"family":"Schüle-Freyer","role":"aut","given":"Rebecca","display":"Schüle-Freyer, Rebecca"},{"role":"aut","family":"Yu","display":"Yu, Timothy","given":"Timothy"}],"recId":"1932496068","title":[{"title":"A framework for N-of-1 trials of individualized gene-targeted therapies for genetic diseases","title_sort":"framework for N-of-1 trials of individualized gene-targeted therapies for genetic diseases"}],"id":{"eki":["1932496068"],"doi":["10.1038/s41467-024-54077-5"]},"physDesc":[{"extent":"5 S."}],"relHost":[{"language":["eng"],"part":{"year":"2024","volume":"15","pages":"1-5","extent":"5","text":"15(2024), Artikel-ID 9802, Seite 1-5"},"note":["Gesehen am 13.06.24"],"pubHistory":["2010-"],"type":{"media":"Online-Ressource","bibl":"periodical"},"disp":"A framework for N-of-1 trials of individualized gene-targeted therapies for genetic diseasesNature Communications","recId":"626457688","title":[{"title":"Nature Communications","title_sort":"Nature Communications"}],"physDesc":[{"extent":"Online-Ressource"}],"id":{"zdb":["2553671-0"],"issn":["2041-1723"],"eki":["626457688"]},"origin":[{"publisherPlace":"[London] ; [London]","dateIssuedDisp":"[2010]-","publisher":"Springer Nature ; Nature Publishing Group UK"}]}],"origin":[{"dateIssuedKey":"2024","dateIssuedDisp":"12 November 2024"}]} | ||
| SRT | |a KIMMCMANUSFRAMEWORKF1220 | ||