{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T07:49:39Z","timestamp":1779176979284,"version":"3.51.4"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T00:00:00Z","timestamp":1633737600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T00:00:00Z","timestamp":1633737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Blueprint Medicines"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Advanced systemic mastocytosis (AdvSM), indolent systemic mastocytosis (ISM), and smoldering systemic mastocytosis (SSM) are rare diseases characterized by neoplastic mast cell infiltration of more than one organ. A content-valid patient-reported outcome (PRO) questionnaire that assesses relevant signs and symptoms that are important and understandable to individuals with a condition is critical for assessing new treatment benefit as well as supporting product labeling claims. Notably, no such PRO questionnaire has been developed in accordance with regulatory and scientific guidelines for use in AdvSM, ISM, and SSM patient populations. To fill that gap, this study documents the development and content validity of instruments evaluating signs and symptoms of systemic mastocytosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A review of peer-reviewed literature, advice meetings with clinical therapeutic area experts, patient concept elicitation interviews, concept selection and questionnaire construction meetings, and patient cognitive debriefing interviews were conducted, and regulatory feedback was incorporated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>For AdvSM, 26 sign- and symptom-level concepts were identified in literature, 39 by clinicians, and 33 by patients. For ISM\/SSM, 38 sign- and symptom-level concepts were identified in the literature, 39 by clinicians, and 57 by patients. Two patient-reported instruments, the Advanced Systemic Mastocytosis Symptom Assessment Form (AdvSM-SAF) and Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF)(\u00a9Blueprint Medicines Corporation), were developed based on consolidated findings. Cognitive debriefing interviews with AdvSM and ISM patients showed the AdvSM-SAF and ISM-SAF were understood and interpreted as intended by the majority of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The AdvSM-SAF and ISM-SAF are content-valid tools measuring symptoms from AdvSM and ISM patients\u2019 perspective.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13023-021-02035-5","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T19:35:43Z","timestamp":1633894543000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Development of symptom-focused outcome measures for advanced and indolent systemic mastocytosis: the AdvSM-SAF and ISM-SAF\u00a9"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6474-4314","authenticated-orcid":false,"given":"Fiona","family":"Taylor","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cem","family":"Akin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger E.","family":"Lamoureux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brad","family":"Padilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanya","family":"Green","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony L.","family":"Boral","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iyar","family":"Mazar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenton","family":"Mar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan L.","family":"Shields","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Siebenhaar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,9]]},"reference":[{"issue":"8","key":"2035_CR1","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1038\/modpathol.2015.72","volume":"28","author":"M Jara-Acevedo","year":"2015","unstructured":"Jara-Acevedo M, Teodosio C, Sanchez-Mu\u00f1oz L, \u00c1lvarez-Twose I, Mayado A, Caldas C, et al. Detection of the KIT D816V mutation in peripheral blood of systemic mastocytosis: diagnostic implications. Mod Pathol. 2015;28(8):1138\u201349.","journal-title":"Mod Pathol"},{"issue":"3","key":"2035_CR2","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/ajh.25371","volume":"94","author":"A Pardanani","year":"2019","unstructured":"Pardanani A. Systemic mastocytosis in adults: 2019 update on diagnosis, risk stratification and management. Am J Hematol. 2019;94(3):363\u201377.","journal-title":"Am J Hematol"},{"issue":"11","key":"2035_CR3","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1182\/blood-2016-09-731893","volume":"129","author":"P Valent","year":"2017","unstructured":"Valent P, Akin C, Metcalfe DD. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood. 2017;129(11):1420\u20137.","journal-title":"Blood"},{"issue":"2","key":"2035_CR4","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1056\/NEJMra1409760","volume":"373","author":"TC Theoharides","year":"2015","unstructured":"Theoharides TC, Valent P, Akin C. Mast cells, mastocytosis, and related disorders. N Engl J Med. 2015;373(2):163\u201372.","journal-title":"N Engl J Med"},{"issue":"9","key":"2035_CR5","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1016\/0959-8049(94)90182-1","volume":"30A","author":"RK Portenoy","year":"1994","unstructured":"Portenoy RK, Thaler HT, Kornblith AB, Lepore JM, Friedlander-Klar H, Kiyasu E, et al. The Memorial Symptom Assessment Scale: an instrument for the evaluation of symptom prevalence, characteristics and distress. EurJ Cancer. 1994;30A(9):1326\u201336.","journal-title":"EurJ Cancer"},{"key":"2035_CR6","doi-asserted-by":"crossref","unstructured":"Gotlib J, Kluin-Nelemans HC, George TI, Akin C, Sotlar K, Hermine O, et al. Durable Responses and Improved Quality of Life with Midostaurin (PKC412) in Advanced Systemic Mastocytosis (SM): Updated Stage 1 Results of the Global D2201 Trial. Blood2013. p. 106.","DOI":"10.1182\/blood.V122.21.106.106"},{"issue":"6","key":"2035_CR7","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1111\/all.12842","volume":"71","author":"F Siebenhaar","year":"2016","unstructured":"Siebenhaar F, von Tschirnhaus E, Hartmann K, Rabenhorst A, Staubach P, Peveling-Oberhag A, et al. Development and validation of the mastocytosis quality of life questionnaire: MC-QoL. Allergy. 2016;71(6):869\u201377.","journal-title":"Allergy"},{"issue":"7","key":"2035_CR8","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1111\/all.13425","volume":"73","author":"F Siebenhaar","year":"2018","unstructured":"Siebenhaar F, Sander B, Ho LHT, Ellrich A, Maurer M, Weller K. Development and validation of the mastocytosis activity score. Allergy. 2018;73(7):1489\u201396.","journal-title":"Allergy"},{"key":"2035_CR9","unstructured":"US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Center for Devices and Radiological Health. Guidance for Industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. Silver Spring, MD: Office of Communications, Division of Drug Information, 2009."},{"issue":"8","key":"2035_CR10","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1016\/j.jval.2011.06.014","volume":"14","author":"DL Patrick","year":"2011","unstructured":"Patrick DL, Burke LB, Gwaltney CJ, Leidy NK, Martin ML, Molsen E, et al. Content validity-establishing and reporting the evidence in newly developed patient-reported outcomes (PRO) instruments for medical product evaluation: ISPOR PRO good research practices task force report: part 1-eliciting concepts for a new PRO instrument. Value in Health. 2011;14(8):967\u201377.","journal-title":"Value in Health"},{"issue":"8","key":"2035_CR11","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1111\/j.1524-4733.2009.00603.x","volume":"12","author":"M Rothman","year":"2009","unstructured":"Rothman M, Burke L, Erickson P, Leidy NK, Patrick DL, Petrie CD. Use of existing patient-reported outcome (PRO) instruments and their modification: the ISPOR Good research practices for evaluating and documenting content validity for the use of existing instruments and their modification PRO task force report. Value Health. 2009;12(8):1075\u201383.","journal-title":"Value Health"},{"key":"2035_CR12","unstructured":"US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Patient-Focused Drug Development: Methods to Identify What Is Important to Patients\u2014Guidance for Industry, Food and Drug Administration Staff, and Other Stakeholders. Draft Guidance. Silver Spring, MD: Office of Communications, Division of Drug Information, 10\/2019."},{"key":"2035_CR13","doi-asserted-by":"crossref","unstructured":"Lamoureux R, Galipeau N, Yaworsky A, Stokes J, Shields A. How many subjects are enough for symptom-focused concept elicitation studies? A retrospective analysis of saturation across twenty-six studies. the 20th Annual International Meeting of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR); Philadelphia PA, USA (2015).","DOI":"10.1016\/j.jval.2015.03.198"},{"key":"2035_CR14","doi-asserted-by":"crossref","unstructured":"Mazar I, Evans E, Taylor F, Patki A, Ojo O, Lamoureux R, et al. Development and content validity of the advanced systemic mastocytosis symptom assessment form (AdvSM-SAF). In: ISPOR 19th annual european congress, 29 October\u20132 November 2016; Vienna, Austria.","DOI":"10.1016\/j.jval.2016.09.224"},{"issue":"7","key":"2035_CR15","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/j.jval.2017.11.014","volume":"21","author":"DM Turner-Bowker","year":"2018","unstructured":"Turner-Bowker DM, Lamoureux RE, Stokes J, Litcher-Kelly L, Galipeau N, Yaworsky A, et al. Informing a priori sample size estimation in qualitative concept elicitation interview studies for clinical outcome assessment instrument development. Value Health. 2018;21(7):839\u201342.","journal-title":"Value Health"},{"key":"2035_CR16","unstructured":"Mazar I, Stokes J, Shields AL. Saturation of sign and symptom concepts in concept elicitation studies with rare disease and vulnerable patient populations. In 22nd Annual international meeting of the international society for pharmacoeconomics and outcomes research; May 20\u201324; Boston, MA, USA (2017)."}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-02035-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-021-02035-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-02035-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T19:54:47Z","timestamp":1699646087000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-021-02035-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,9]]},"references-count":16,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2035"],"URL":"https:\/\/doi.org\/10.1186\/s13023-021-02035-5","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,9]]},"assertion":[{"value":"26 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Participants were recruited through an advocacy group or clinical sites in the US and Germany with study materials approved by a centralized independent review board (IRB), Copernicus Group IRB, and, for clinical-site interviews, through local ethics committees associated with Stanford University in the US and Mannheim University in Germany.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"FT, REL, BP, IM, and ALS are, or were at the time of the research, employees of Adelphi Values, which conducted research on behalf of Blueprint Medicines. CA received research funding and consultancy fees from Blueprint Medicines. TG, ALB, and BM are employees of Blueprint Medicines and own stock in the company. FS is or recently was a speaker and\/or advisor for and\/or has received research funding from Allakos, Blueprint, Celldex, Genentech, Moxie, Novartis, and Uriach.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"414"}}