{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:49:58Z","timestamp":1792093798362,"version":"4.4.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Crinetics","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Patient Rep Outcomes"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Patient-reported outcome (PRO) measures are important to consider when evaluating treatments, yet there are no PRO measures for patients with acromegaly that have been developed in accordance with US Food and Drug Administration guidance. Acromegaly is a rare, chronic condition caused by hypersecretion of growth hormone. Disease activity is monitored by measurement in serum of growth hormone and insulin-like growth factor-I. The objectives of this research were to develop the Acromegaly Symptom Diary (ASD), establish a scoring algorithm, and evaluate the psychometric measurement properties of the ASD.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Semistructured interviews consisting of concept elicitation and cognitive debriefing components were conducted with 16 adult participants with acromegaly. The concept elicitation component identified symptoms important to individuals with acromegaly. The cognitive debriefing component gathered information about the participants\u2019 experience with each proposed item of the ASD, their thought process for answering each question, and their interpretation of the items. The psychometric properties of the draft ASD were then evaluated using data from the ACROBAT Evolve (NCT03792555; n\u2009=\u200913) and ACROBAT Edge (NCT03789656; n\u2009=\u200947) clinical trials.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The 16 participants from the interviews described ongoing symptoms, with the most frequently reported being joint pain (n\u2009=\u200913) and fatigue (n\u2009=\u200912), followed by swelling (n\u2009=\u20098), headache (n\u2009=\u20097), and mood swings (n\u2009=\u20096), and were able to interpret and understand the ASD items and had no issues with the 24-hour recall period. From data collected in the clinical studies, the psychometric properties of internal consistency (0.91\u2009\u2212\u20090.80), test-retest reliability with item-level and total ASD scores (&gt;\u20090.70), baseline construct validity (r \u2265 |0.38|) across scales, and responsiveness to change (r\u2009=\u20090.52\u20130.56) were supported for the ASD. The proposed preliminary threshold range to characterize a meaningful change from the patients\u2019 perspective for the ASD total is a 4- to 6-point change for improvement or worsening out of a total score of 70.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>These findings provide qualitative and quantitative evidence to support the ASD as fit for the purpose of evaluating the symptom experience of patients with acromegaly in clinical trials.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s41687-023-00541-7","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T17:04:08Z","timestamp":1676480648000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Development and evaluation of the Acromegaly Symptom Diary"],"prefix":"10.1186","volume":"7","author":[{"given":"Susan","family":"Martin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall H.","family":"Bender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Krasner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonya","family":"Marmon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Monahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"issue":"11","key":"541_CR1","doi-asserted-by":"publisher","first-page":"3189","DOI":"10.1172\/JCI39375","volume":"119","author":"S Melmed","year":"2009","unstructured":"Melmed S (2009) Acromegaly pathogenesis and treatment. J Clin Invest 119(11):3189\u20133202. doi:https:\/\/doi.org\/10.1172\/JCI39375","journal-title":"J Clin Invest"},{"issue":"1","key":"541_CR2","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1210\/er.2002-0022","volume":"25","author":"A Colao","year":"2004","unstructured":"Colao A, Ferone D, Marzullo P et al (2004) Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 25(1):102\u2013152. doi:https:\/\/doi.org\/10.1210\/er.2002-0022","journal-title":"Endocr Rev"},{"key":"541_CR3","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1159\/000486001","volume":"49","author":"M Mercado","year":"2018","unstructured":"Mercado M, Ramirez-Renteria C (2018) Metabolic complications of acromegaly. Front Horm Res 49:20\u201328. doi:https:\/\/doi.org\/10.1159\/000486001","journal-title":"Front Horm Res"},{"issue":"2","key":"541_CR4","doi-asserted-by":"publisher","first-page":"64","DOI":"10.14797\/mdcj-13-2-64","volume":"13","author":"MD Sharma","year":"2017","unstructured":"Sharma MD, Nguyen AV, Brown S et al (2017) Cardiovascular disease in acromegaly. Methodist Debakey Cardiovasc J 13(2):64\u201367. doi:https:\/\/doi.org\/10.14797\/mdcj-13-2-64","journal-title":"Methodist Debakey Cardiovasc J"},{"key":"541_CR5","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.ghir.2016.08.002","volume":"30\u201331","author":"F Hannah-Shmouni","year":"2016","unstructured":"Hannah-Shmouni F, Trivellin G, Stratakis CA (2016) Genetics of gigantism and acromegaly. Growth Horm IGF Res 30\u201331:37\u201341. doi:https:\/\/doi.org\/10.1016\/j.ghir.2016.08.002","journal-title":"Growth Horm IGF Res"},{"issue":"4","key":"541_CR6","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1007\/s11102-016-0725-2","volume":"19","author":"A Abreu","year":"2016","unstructured":"Abreu A, Tovar AP, Castellanos R et al (2016) Challenges in the diagnosis and management of acromegaly: a focus on comorbidities. Pituitary 19(4):448\u2013457. doi:https:\/\/doi.org\/10.1007\/s11102-016-0725-2","journal-title":"Pituitary"},{"issue":"3","key":"541_CR7","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1530\/EJE-15-1042","volume":"174","author":"CJ Strasburger","year":"2016","unstructured":"Strasburger CJ, Karavitaki N, Stormann S et al (2016) Patient-reported outcomes of parenteral somatostatin analogue injections in 195 patients with acromegaly. Eur J Endocrinol 174(3):355\u2013362. doi:https:\/\/doi.org\/10.1530\/EJE-15-1042","journal-title":"Eur J Endocrinol"},{"issue":"4","key":"541_CR8","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1007\/s11102-020-01038-y","volume":"23","author":"M Fleseriu","year":"2020","unstructured":"Fleseriu M, Fogelfeld L, Gordon MB et al (2020) An evaluation of the Acromegaly treatment satisfaction questionnaire (Acro-TSQ) in adult patients with acromegaly, including correlations with other patient-reported outcome measures: data from two large multicenter international studies. Pituitary 23(4):347\u2013358. doi:https:\/\/doi.org\/10.1007\/s11102-020-01038-y","journal-title":"Pituitary"},{"key":"541_CR9","unstructured":"US Food and Drug Administration (2009) Patient-reported outcome measures: use in medical product development to support labeling claims. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/patient-reported-outcome-measures-use-medical-product-development-support-labeling-claims"},{"key":"541_CR10","unstructured":"US Food and Drug Administration. Patient-focused drug development guidance: methods to identify what is important to patients and select, develop or modify fit-for-purpose clinical outcome assessments (2018) https:\/\/www.fda.gov\/drugs\/news-events-human-drugs\/patient-focused-drug-development-guidance-methods-identify-what-important-patients-and-select"},{"key":"541_CR11","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1477-7525-2-13","volume":"2","author":"X Badia","year":"2004","unstructured":"Badia X, Webb SM, Prieto L et al (2004) Acromegaly Quality of Life Questionnaire (AcroQoL). Health Qual Life Outcomes 2:13. doi:https:\/\/doi.org\/10.1186\/1477-7525-2-13","journal-title":"Health Qual Life Outcomes"},{"issue":"16","key":"541_CR12","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1056\/NEJM200004203421604","volume":"342","author":"PJ Trainer","year":"2000","unstructured":"Trainer PJ, Drake WM, Katznelson L et al (2000) Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 342(16):1171\u20131177 2000\/04\/20 [Epub ahead of print]. doi:https:\/\/doi.org\/10.1056\/NEJM200004203421604","journal-title":"N Engl J Med"},{"key":"541_CR13","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab874","author":"M van der Meulen","year":"2021","unstructured":"van der Meulen M, Zamanipoor Najafabadi AH, Broersen LHA et al (2021) State of the art of patient-reported outcomes in acromegaly or GH deficiency: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2021\/12\/07 [Epub ahead of print] doi:https:\/\/doi.org\/10.1210\/clinem\/dgab874","journal-title":"J Clin Endocrinol Metab"},{"key":"541_CR14","doi-asserted-by":"publisher","first-page":"627711","DOI":"10.3389\/fendo.2021.627711","volume":"12","author":"M Fleseriu","year":"2021","unstructured":"Fleseriu M, Molitch M, Dreval A et al (2021) Disease and treatment-related burden in patients with acromegaly who are biochemically controlled on injectable somatostatin receptor ligands. Front Endocrinol (Lausanne) 12:627711. doi:https:\/\/doi.org\/10.3389\/fendo.2021.627711","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"6","key":"541_CR15","doi-asserted-by":"publisher","first-page":"3337","DOI":"10.1210\/jc.2004-1565","volume":"90","author":"SV Rowles","year":"2005","unstructured":"Rowles SV, Prieto L, Badia X et al (2005) Quality of life (QOL) in patients with acromegaly is severely impaired: use of a novel measure of QOL: acromegaly quality of life questionnaire. J Clin Endocrinol Metab 90(6):3337\u20133341. doi:https:\/\/doi.org\/10.1210\/jc.2004-1565","journal-title":"J Clin Endocrinol Metab"},{"key":"541_CR16","unstructured":"ClinicalTrials.gov (2021) A study to evaluate the safety and efficacy of paltusotine for the treatment of acromegaly (ACROBAT Evolve). https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03792555"},{"key":"541_CR17","unstructured":"ClinicalTrials.gov (2021) An study to evaluate the safety and efficacy of paltusotine for the treatment of acromegaly (ACROBAT edge). https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03789656"},{"key":"541_CR18","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac643","author":"MR Gadelha","year":"2022","unstructured":"Gadelha MR, Gordon MB, Doknic M et al (2021) Safety and efficacy of switching injected peptide long-acting somatostatin receptor ligands to once daily oral paltusotine: ACROBAT Edge phase 2 study. J Endocr Soc 5(Supplement1):A526\u2013A527. https:\/\/doi.org\/10.1210\/jendso\/bvab048.1073","journal-title":"J Clin Endocrinol Metab"},{"key":"541_CR19","unstructured":"National Institute of Mental Health. Patient Global Impressions scale - Change, Improvement, Severity (PGI-C, PGI-I, PGI-S) (2021) https:\/\/eprovide.mapi-trust.org\/instruments\/patient-global-impressions-scale-change-improvement-severity"},{"key":"541_CR20","unstructured":"EuroQol Research Foundation. About the EQ-5D (2021) https:\/\/euroqol.org\/eq-5d-instruments\/"},{"key":"541_CR21","unstructured":"US Food and Drug Administration (2018) Methods to identify what is important to patients & select, develop or modify fit-for-purpose clinical outcomes assessments. https:\/\/www.fda.gov\/media\/116281\/download"},{"key":"541_CR22","doi-asserted-by":"crossref","unstructured":"Streiner DL, Norman GR, Cairney J (2015) Health measurement scales: a practical guide to their development and use. Oxford University Press","DOI":"10.1093\/med\/9780199685219.001.0001"},{"issue":"3","key":"541_CR23","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/BF02310555","volume":"16","author":"LJ Cronbach","year":"1951","unstructured":"Cronbach LJ (1951) Coefficient alpha and the internal structure of tests. Psychometrika 16(3):297\u2013334. doi:https:\/\/doi.org\/10.1007\/BF02310555","journal-title":"Psychometrika"},{"issue":"1","key":"541_CR24","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1037\/1082-989X.1.1.30","volume":"1","author":"KO McGraw","year":"1996","unstructured":"McGraw KO, Wong SP (1996) Forming inferences about some intraclass correlation coefficients. Psychol Methods 1(1):30\u201346. doi:https:\/\/doi.org\/10.1037\/1082-989X.1.1.30","journal-title":"Psychol Methods"},{"key":"541_CR25","volume-title":"Psychometric theory 3ed","author":"J Nunnally","year":"1994","unstructured":"Nunnally J (1994) Psychometric theory 3ed. McGraw-Hill Humanities\/Social Sciences\/Languages, New York, New York"},{"issue":"1","key":"541_CR26","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1037\/\/0033-2909.112.1.155","volume":"112","author":"J Cohen","year":"1992","unstructured":"Cohen J (1992) A power primer. Psychol Bull 112(1):155\u2013159. doi:https:\/\/doi.org\/10.1037\/\/0033-2909.112.1.155","journal-title":"Psychol Bull"},{"issue":"1","key":"541_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11136-013-0443-4","volume":"23","author":"PM Fayers","year":"2014","unstructured":"Fayers PM, Hays RD (2014) Don\u2019t middle your MIDs: regression to the mean shrinks estimates of minimally important differences. Qual Life Res 23(1):1\u20134. doi:https:\/\/doi.org\/10.1007\/s11136-013-0443-4","journal-title":"Qual Life Res"},{"issue":"1","key":"541_CR28","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1081\/copd-200050663","volume":"2","author":"RD Hays","year":"2005","unstructured":"Hays RD, Farivar SS, Liu H (2005) Approaches and recommendations for estimating minimally important differences for health-related quality of life measures. COPD 2(1):63\u201367. doi:https:\/\/doi.org\/10.1081\/copd-200050663","journal-title":"COPD"},{"issue":"2","key":"541_CR29","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.jclinepi.2007.03.012","volume":"61","author":"D Revicki","year":"2008","unstructured":"Revicki D, Hays RD, Cella D et al (2008) Recommended methods for determining responsiveness and minimally important differences for patient-reported outcomes. J Clin Epidemiol 61(2):102\u2013109. doi:https:\/\/doi.org\/10.1016\/j.jclinepi.2007.03.012","journal-title":"J Clin Epidemiol"},{"issue":"5","key":"541_CR30","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1097\/01.MLR.0000062554.74615.4C","volume":"41","author":"GR Norman","year":"2003","unstructured":"Norman GR, Sloan JA, Wyrwich KW (2003) Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care 41(5):582\u2013592","journal-title":"Med Care"},{"issue":"9","key":"541_CR31","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/s0895-4356(99)00071-2","volume":"52","author":"KW Wyrwich","year":"1999","unstructured":"Wyrwich KW, Tierney WM, Wolinsky FD (1999) Further evidence supporting an SEM-based criterion for identifying meaningful intra-individual changes in health-related quality of life. J Clin Epidemiol 52(9):861\u2013873. doi:https:\/\/doi.org\/10.1016\/s0895-4356(99)00071-2","journal-title":"J Clin Epidemiol"},{"issue":"2","key":"541_CR32","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1586\/erp.11.12","volume":"11","author":"LD McLeod","year":"2014","unstructured":"McLeod LD, Coon CD, Martin SA et al (2014) Interpreting patient-reported outcome results: US FDA guidance and emerging methods. Exp Rev Pharmacoecon Outcomes Res 11(2):163\u2013169. doi:https:\/\/doi.org\/10.1586\/erp.11.12","journal-title":"Exp Rev Pharmacoecon Outcomes Res"},{"issue":"5","key":"541_CR33","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/s0895-4356(03)00044-1","volume":"56","author":"RD Crosby","year":"2003","unstructured":"Crosby RD, Kolotkin RL, Williams GR (2003) Defining clinically meaningful change in health-related quality of life. J Clin Epidemiol 56(5):395\u2013407. doi:https:\/\/doi.org\/10.1016\/s0895-4356(03)00044-1","journal-title":"J Clin Epidemiol"},{"issue":"4","key":"541_CR34","doi-asserted-by":"publisher","first-page":"R59","DOI":"10.1530\/EC-15-0064","volume":"4","author":"JM Silverstein","year":"2015","unstructured":"Silverstein JM (2015) Need for improved monitoring in patients with acromegaly. Endocr Connect 4(4):R59\u201367. doi:https:\/\/doi.org\/10.1530\/EC-15-0064","journal-title":"Endocr Connect"},{"issue":"2","key":"541_CR35","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1111\/j.1365-2265.2009.03556.x","volume":"71","author":"PU Freda","year":"2009","unstructured":"Freda PU (2009) Monitoring of acromegaly: what should be performed when GH and IGF-1 levels are discrepant? Clin Endocrinol (Oxf) 71(2):166\u2013170. doi:https:\/\/doi.org\/10.1111\/j.1365-2265.2009.03556.x","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"1","key":"541_CR36","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1007\/s11102-016-0754-x","volume":"20","author":"A Lavrentaki","year":"2017","unstructured":"Lavrentaki A, Paluzzi A, Wass JA et al (2017) Epidemiology of acromegaly: review of population studies. Pituitary 20(1):4\u20139. doi:https:\/\/doi.org\/10.1007\/s11102-016-0754-x","journal-title":"Pituitary"}],"container-title":["Journal of Patient-Reported Outcomes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41687-023-00541-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s41687-023-00541-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41687-023-00541-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T17:04:17Z","timestamp":1676480657000},"score":1,"resource":{"primary":{"URL":"https:\/\/jpro.springeropen.com\/articles\/10.1186\/s41687-023-00541-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,15]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["541"],"URL":"https:\/\/doi.org\/10.1186\/s41687-023-00541-7","relation":{},"ISSN":["2509-8020"],"issn-type":[{"value":"2509-8020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,15]]},"assertion":[{"value":"26 May 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 February 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the RTI\nInstitutional Review Board, and all participants provided verbal informed\nconsent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable as data was anonymized.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"SM, LN, and RB are full-time employees of RTI Health Solutions, an independent nonprofit research organization, which was retained by Crinetics\u00a0Pharmaceuticals, Inc. to conduct the research, which is the subject of this manuscript. Their compensation is unconnected to the studies on which they work. AK and MM are employees of Crinetics\u00a0Pharmaceuticals, Inc. and may hold shares and\/or stock options in the company.\u00a0TM\u00a0has\u00a0received consulting fees from Crinetics Pharmaceuticals, Inc.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15"}}