{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T10:25:43Z","timestamp":1768818343271,"version":"3.49.0"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Gene therapy offers an etiologically targeted treatment for genetic disorders. Little is known about the acceptance of mortality risk among patients with progressive, fatal conditions. We assessed patients\u2019 and caregivers\u2019 maximum acceptable risk (MAR) of mortality for gene therapy when used to treat Duchenne muscular dystrophy (DMD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The threshold technique was used to assess tolerance for mortality risks using a hypothetical vignette. Gene therapy was described as non\u2010curative and resulting in a slowing of progression and with a 10\u2010year benefit duration. MAR was analyzed using interval regression for gene therapy initiated \u201cnow\u201d; in the last year of walking well; in the last year of being able to bring arms to mouth; and in newborns (for caregivers only).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two hundred eighty\u2010five caregivers and 35 patients reported the greatest MAR for gene therapy initiated in last year of being able to lift arms (mean MAR 6.3%), followed by last year of walking well (mean MAR 4.4%), when used \u201cnow\u201d (mean MAR 3.5%), and when used in the newborn period (mean MAR 2.1%, caregivers only). About 35% would accept \u2265200\/2000 risk in the last year of being able to lift arms. Non\u2010ambulatory status predicted accepting 1.8 additional points in MAR \u201cnow\u201d compared with ambulatory status (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.010). Respondent type (caregiver or patient) did not predict MAR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this first quantitative study to assess MAR associated with first\u2010generation DMD gene therapy, we find relatively high tolerance for mortality risk in response to a non\u2010curative treatment scenario. Risk tolerance increased with disease progression. Patients and caregivers did not have significantly different MAR. These results have implications for protocol development and shared decision making.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1664","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T11:52:32Z","timestamp":1616500352000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Patients\u2019 and caregivers\u2019 maximum acceptable risk of death for non\u2010curative gene therapy to treat Duchenne muscular dystrophy"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3053-7453","authenticated-orcid":false,"given":"Holly L.","family":"Peay","sequence":"first","affiliation":[{"name":"RTI International Research Triangle Park NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Fischer","sequence":"additional","affiliation":[{"name":"Parent Project Muscular Dystrophy Hackensack NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brennan","family":"Mange","sequence":"additional","affiliation":[{"name":"RTI Health Solutions Research Triangle Park NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan S.","family":"Paquin","sequence":"additional","affiliation":[{"name":"RTI International Research Triangle Park NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Duke University Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alesia","family":"Sadosky","sequence":"additional","affiliation":[{"name":"Pfizer, Inc New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo","family":"Russo","sequence":"additional","affiliation":[{"name":"Pfizer, Inc New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Ricotti","sequence":"additional","affiliation":[{"name":"Solid Biosciences Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin","family":"Rensch","sequence":"additional","affiliation":[{"name":"Parent Project Muscular Dystrophy Hackensack NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl","family":"Morris","sequence":"additional","affiliation":[{"name":"Solid Biosciences Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy Strong","family":"Martin","sequence":"additional","affiliation":[{"name":"UCLA Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annie","family":"Ganot","sequence":"additional","affiliation":[{"name":"Solid Biosciences Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Beaverson","sequence":"additional","affiliation":[{"name":"Pfizer, Inc New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol","family":"Mansfield","sequence":"additional","affiliation":[{"name":"RTI Health Solutions Research Triangle Park NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,3,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2016.0657"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30024-3"},{"key":"e_1_2_9_4_1","volume-title":"Microeconometrics using stata","author":"Cameron A.","year":"2010"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.02.019"},{"issue":"3","key":"e_1_2_9_6_1","first-page":"21","article-title":"The control preferences scale","volume":"29","author":"Degner L. 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