{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:49:55Z","timestamp":1791578995035,"version":"4.3.4"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Alexion, AstraZeneca Rare Disease"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Res Involv Engagem"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Meaningful patient engagement requires understanding lived disease and healthcare experiences. This patient-centric approach is especially valuable when applied to the design and execution of clinical trials, as participation barriers may hinder trial recruitment, retention, and detection of meaningful outcomes. Patient engagement is particularly important in the study of treatments for rare diseases, where populations are small and geographically dispersed and there are few sites with relevant clinical expertise. Additionally, protocol amendments to address hurdles are expensive and can cause delays in trial activities, which can affect downstream regulatory approvals and access to treatments. Alexion, AstraZeneca Rare Disease, worked with patients and their stakeholders to identify points of additional trial burden and enable patient-driven changes before clinical trial protocol finalization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients, parents of pediatric patients, and patient advocacy group representatives with diverse experiences participated in virtual, study-specific perspective exchange sessions on 4 protocols (adults with generalized myasthenia gravis, pediatric patients with generalized myasthenia gravis, adults with antibody-mediated rejection after kidney transplantation, and adults with transthyretin amyloid cardiomyopathy). Participants discussed their disease journey, the protocol, and perceived barriers to clinical trial awareness, enrollment, participation, and follow-up through semistructured interviews.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Participants raised points about the eligibility criteria, study drug self-administration, visit frequency, participant mental health, and the relevance of specific outcome measures. In response, the study sponsor proactively changed the clinical trial protocols when feasible. Changes included expanding the eligibility criteria, developing an instructional video on self-administration of the study drug, and reducing the frequency of clinic visits. In addition, the sponsor created appreciation cards and trained trial sites on a standardized approach to help participants understand the goals of specific outcome measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These insights led to demonstrable, advocate-recommended changes in rare disease clinical trial protocols before study delivery, underscoring how early patient-partnered drug development can be meaningfully applied to research in rare diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>NCT05556096, NCT06607627, NCT06744647, and NCT06183931.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial number<\/jats:title>\n                    <jats:p>Not applicable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40900-026-00985-3","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T08:04:14Z","timestamp":1791533054000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Patient engagement in protocol development for rare disease clinical trials: a framework"],"prefix":"10.1186","volume":"12","author":[{"given":"Janella","family":"Beltran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Bolton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pesh","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6361-0004","authenticated-orcid":false,"given":"Rohita","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"985_CR1","unstructured":"21st Century Cures Act, HR 6, 114th Cong. [Internet]. 2015 [cited 2025 Jan 28]. Available from: https:\/\/www.congress.gov\/bill\/114th-congress\/house-bill\/6."},{"key":"985_CR2","unstructured":"European Medicines Agency. Science medicines health. Engagement framework: EMA and patients, consumers and their organisations; 2022 [cited 2025 Jan 24]. Available from: https:\/\/www.ema.europa.eu\/en\/documents\/other\/engagement-framework-european-medicines-agency-and-patients-consumers-and-their-organisations_en.pdf."},{"issue":"4","key":"985_CR3","first-page":"265","volume":"37","author":"R Sharma","year":"2023","unstructured":"Sharma R, Ahmed S, Campagnari J, Huff W, Lloyd L. Embedding patient-centricity by collaborating with patients to transform the rare disease ecosystem. Pharmaceut Med. 2023;37(4):265\u201373.","journal-title":"Pharmaceut Med"},{"key":"985_CR4","doi-asserted-by":"publisher","first-page":"631","DOI":"10.2147\/PPA.S104259","volume":"10","author":"JA Sacristan","year":"2016","unstructured":"Sacristan JA, Aguaron A, Avendano-Sola C, Garrido P, Carrion J, Gutierrez A, et al. Patient involvement in clinical research: why, when, and how. Patient Prefer Adherence. 2016;10:631\u201340.","journal-title":"Patient Prefer Adherence"},{"issue":"3","key":"985_CR5","doi-asserted-by":"publisher","first-page":"bjgpopen20X1010","DOI":"10.3399\/bjgpopen20X101056","volume":"4","author":"MJ van den Brink","year":"2020","unstructured":"van den Brink MJ, Hummel M, Lemstra M, Berger MY, Dekker JH, Blanker MH. Factors affecting patient recruitment to trials: qualitative research in general practice. BJGP Open. 2020;4(3):bjgpopen20X101056.","journal-title":"BJGP Open"},{"key":"985_CR6","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.conctc.2018.08.001","volume":"11","author":"DB Fogel","year":"2018","unstructured":"Fogel DB. Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: a review. Contemp Clin Trials Commun. 2018;11:156\u201364.","journal-title":"Contemp Clin Trials Commun"},{"issue":"6","key":"985_CR7","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1007\/s10928-023-09859-7","volume":"50","author":"JS Barrett","year":"2023","unstructured":"Barrett JS, Betourne A, Walls RL, Lasater K, Russell S, Borens A, et al. The future of rare disease drug development: the rare disease cures accelerator data analytics platform (RDCA-DAP). J Pharmacokinet Pharmacodyn. 2023;50(6):507\u201319.","journal-title":"J Pharmacokinet Pharmacodyn"},{"issue":"1","key":"985_CR8","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1007\/s43441-020-00207-2","volume":"55","author":"J Lai","year":"2021","unstructured":"Lai J, Forney L, Brinton DL, Simpson KN. Drivers of start-up delays in global randomized clinical trials. Ther Innov Regul Sci. 2021;55(1):212\u201327.","journal-title":"Ther Innov Regul Sci"},{"issue":"9","key":"985_CR9","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1177\/0883073813495959","volume":"28","author":"EF Augustine","year":"2013","unstructured":"Augustine EF, Adams HR, Mink JW. Clinical trials in rare disease: challenges and opportunities. J Child Neurol. 2013;28(9):1142\u201350.","journal-title":"J Child Neurol"},{"key":"985_CR10","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/1472-6963-14-89","volume":"14","author":"JP Domecq","year":"2014","unstructured":"Domecq JP, Prutsky G, Elraiyah T, Wang Z, Nabhan M, Shippee N, et al. Patient engagement in research: a systematic review. BMC Health Serv Res. 2014;14:89.","journal-title":"BMC Health Serv Res"},{"issue":"1","key":"985_CR11","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s13063-022-06989-0","volume":"24","author":"S Joshi","year":"2023","unstructured":"Joshi S. Common clinical trial amendments, why they are submitted and how they can be avoided: a mixed methods study on NHS UK sponsored research (amendments assemble). Trials. 2023;24(1):10.","journal-title":"Trials"},{"issue":"4","key":"985_CR12","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1177\/2168479016632271","volume":"50","author":"KA Getz","year":"2016","unstructured":"Getz KA, Stergiopoulos S, Short M, Surgeon L, Krauss R, Pretorius S, et al. The impact of protocol amendments on clinical trial performance and cost. Ther Innov Regul Sci. 2016;50(4):436\u201341.","journal-title":"Ther Innov Regul Sci"},{"issue":"8","key":"985_CR13","doi-asserted-by":"publisher","first-page":"e150","DOI":"10.1016\/j.clinthera.2020.06.015","volume":"42","author":"D Cameron","year":"2020","unstructured":"Cameron D, Willoughby C, Messer D, Lux M, Aitken M, Getz K. Assessing participation burden in clinical trials: introducing the patient friction coefficient. Clin Ther. 2020;42(8):e150\u20139.","journal-title":"Clin Ther"},{"key":"985_CR14","unstructured":"Alexion Pharmaceuticals Inc. Safety and efficacy of ALXN1720 in adults with generalized myasthenia gravis [Internet]. 2022 [last updated 2025 Jun 12. Available from: https:\/\/clinicaltrials.gov\/study\/NCT05556096.\u00a0Accessed 7 August 2025."},{"key":"985_CR15","unstructured":"Alexion Pharmaceuticals Inc. PK, PD, safety, and efficacy study of gefurulimab in pediatric patients with AChR+ generalized myasthenia gravis [Internet]. 2024 [last updated 2025 Jul 10. Available from: https:\/\/clinicaltrials.gov\/study\/NCT06607627.\u00a0Accessed 7 August 2025."},{"key":"985_CR16","unstructured":"Alexion Pharmaceuticals Inc. Phase 2 study of ALXN2030 in patients with antibody-mediated rejection after kidney transplantation (CONCORD) [Internet]. 2024 [last updated 2025 Jun 22. Available from: https:\/\/clinicaltrials.gov\/study\/NCT06744647.\u00a0Accessed 7 August 2025."},{"key":"985_CR17","unstructured":"Alexion Pharmaceuticals Inc. Study of ALXN2220 versus placebo in adults with ATTR-CM (DepleTTR-CM) [Internet]. 2024 [last updated 2025 Jul 1. Available from: https:\/\/clinicaltrials.gov\/study\/NCT06183931.\u00a0Accessed 7 August 2025."},{"issue":"3","key":"985_CR18","first-page":"256","volume":"49","author":"LP Wong","year":"2008","unstructured":"Wong LP. Focus group discussion: a tool for health and medical research. Singap Med J. 2008;49(3):256\u201360. quiz 61.","journal-title":"Singap Med J"},{"issue":"6","key":"985_CR19","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1177\/2168479015580384","volume":"49","author":"A Hoos","year":"2015","unstructured":"Hoos A, Anderson J, Boutin M, Dewulf L, Geissler J, Johnston G, et al. Partnering with patients in the development and lifecycle of medicines: a call for action. Ther Innov Regul Sci. 2015;49(6):929\u201339.","journal-title":"Ther Innov Regul Sci"},{"issue":"11","key":"985_CR20","doi-asserted-by":"publisher","first-page":"e1002966","DOI":"10.1371\/journal.pmed.1002966","volume":"16","author":"CA Rees","year":"2019","unstructured":"Rees CA, Pica N, Monuteaux MC, Bourgeois FT. Noncompletion and nonpublication of trials studying rare diseases: A cross-sectional analysis. PLoS Med. 2019;16(11):e1002966.","journal-title":"PLoS Med"},{"issue":"1","key":"985_CR21","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s40900-025-00755-7","volume":"11","author":"SC Tscherning","year":"2025","unstructured":"Tscherning SC, Jensen AL, Bekker HL, Vedelo TW, Finderup J, Rasmussen GS, et al. How are patient partners involved in health service research? A scoping review of reviews. Res Involv Engagem. 2025;11(1):78.","journal-title":"Res Involv Engagem"},{"issue":"4","key":"985_CR22","doi-asserted-by":"publisher","first-page":"809","DOI":"10.3233\/JPD-230444","volume":"14","author":"ML Zeissler","year":"2024","unstructured":"Zeissler ML, Bakshi N, Bartlett M, Batla A, Byrom D, Chapman R, et al. Patient and public involvement and engagement in the development of a platform clinical trial for Parkinson\u2019s disease: An evaluation protocol. J Parkinsons Dis. 2024;14(4):809\u201321.","journal-title":"J Parkinsons Dis"},{"issue":"6","key":"985_CR23","doi-asserted-by":"publisher","first-page":"e094788","DOI":"10.1136\/bmjopen-2024-094788","volume":"15","author":"A Bangiri","year":"2025","unstructured":"Bangiri A, Horobin A, Baker J, Pszczolkowski S, Thust S, Morgan PS. Outcomes of patient and public involvement in the development of the Cognitive Decline after Brain Radiosurgery (CoDe B-Rad) study: refining the research question and methodology. BMJ Open. 2025;15(6):e094788.","journal-title":"BMJ Open"},{"issue":"1","key":"985_CR24","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s40900-023-00536-0","volume":"10","author":"C Ryf","year":"2024","unstructured":"Ryf C, Hofstetter L, Clack L, Hincapie CA. Involving patients and clinicians in the development of a randomised clinical trial protocol to assess spinal manual therapy versus nerve root injection for patients with lumbar radiculopathy: a patient and public involvement project to inform the SALuBRITY trial design. Res Involv Engagem. 2024;10(1):8.","journal-title":"Res Involv Engagem"},{"issue":"2","key":"985_CR25","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1111\/cts.12910","volume":"14","author":"MF Dockendorf","year":"2021","unstructured":"Dockendorf MF, Hansen BJ, Bateman KP, Moyer M, Shah JK, Shipley LA. Digitally Enabled, Patient-Centric Clinical Trials: Shifting the Drug Development Paradigm. Clin Transl Sci. 2021;14(2):445\u201359.","journal-title":"Clin Transl Sci"},{"issue":"4","key":"985_CR26","first-page":"e58352","volume":"16","author":"K Vats","year":"2024","unstructured":"Vats K. Navigating the digital landscape: Embracing innovation, addressing challenges, and prioritizing patient-centric care. Cureus. 2024;16(4):e58352.","journal-title":"Cureus"},{"issue":"5","key":"985_CR27","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1007\/s43441-020-00115-5","volume":"54","author":"E Manning","year":"2020","unstructured":"Manning E, Herndon M, Frye W, Ice TS, Thyssen N, Pushparajah DS, et al. Giving voice to clinical study participants: development and deployment of sequential patient experience surveys for global clinical studies. Ther Innov Regul Sci. 2020;54(5):1001\u20139.","journal-title":"Ther Innov Regul Sci"},{"issue":"6","key":"985_CR28","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1007\/s43441-020-00176-6","volume":"54","author":"BT TransCelerate","year":"2020","unstructured":"TransCelerate Biopharma Toolkits Core Team; Elmer M, Florek C, Gabryelski L, Greene A, Inglis AM, Johnson KL, et al. Amplifying the voice of the patient in clinical research: development of toolkits for use in designing and conducting patient-centered clinical studies. Ther Innov Regul Sci. 2020;54(6):1489\u2013500.","journal-title":"Ther Innov Regul Sci"}],"container-title":["Research Involvement and Engagement"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40900-026-00985-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40900-026-00985-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40900-026-00985-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:03:10Z","timestamp":1791576190000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40900-026-00985-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,9]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["985"],"URL":"https:\/\/doi.org\/10.1186\/s40900-026-00985-3","relation":{},"ISSN":["2056-7529"],"issn-type":[{"value":"2056-7529","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,9]]},"assertion":[{"value":"7 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","label":"Human ethics and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The first draft of the plain English summary was generated using a generative AI model that distills scientific publications into easy-to-understand summaries. The first draft was reviewed, revised, and approved by the authors. As part of AstraZeneca's commitment to innovation and ethical AI use, this summary was generated within the secure confines of AstraZeneca's infrastructure, ensuring both data privacy and adherence to copyright laws. The authors are accountable for the accuracy and integrity of the final draft of the plain language summary.","order":2,"name":"Ethics","label":"Generative AI","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"S.B. and P.P are patient participants.","order":3,"name":"Ethics","label":"Author's Information","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":4,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"J.B. is an employee of Alexion, AstraZeneca Rare Disease. S.B. received compensation for participating in an Alexion, AstraZeneca Rare Disease, patient engagement discussion. P.P. received compensation for participating in an Alexion, AstraZeneca Rare Disease, patient engagement discussion. R.S. is an employee of Alexion, AstraZeneca Rare Disease and holds stock in AztraZeneca.","order":5,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"167"}}