{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:43:48Z","timestamp":1788263028972,"version":"build-2803163510"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Theravance Biopharma"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin. Auton. Res."],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Establish the minimally clinically important difference (MCID) for the Orthostatic Hypotension Questionnaire (OHQ).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neurogenic orthostatic hypotension (nOH) causes disabling symptoms that impair daily function and quality of life. The OHQ is a validated patient-reported outcome with a symptom assessment (OHSA) and daily activity scale (OHDAS), widely used in clinical trials, despite the MCID being unestablished.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed data from two phase 3, randomized placebo-controlled trials (SEQUOIA and REDWOOD), evaluating ampreloxetine for symptomatic nOH in patients with Parkinson disease, multiple system atrophy, and pure autonomic failure. Using anchor-based and distribution-based methods, we calculated the MCID for the total OHQ score, OHSA and OHDAS composite subscales, and for the single dizziness\/lightheadedness question (OHSA1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The analysis included 184 subjects from SEQUOIA and 128 from REDWOOD. The total OHQ MCID for improvement was a reduction of 0.9\u20131.2 points and for worsening was an increase of 0.7\u20131.1 points. The MCID for the OHSA composite ranged from a reduction of 0.9\u20131.3 points for improvement and an increase of 0.7\u20131.1 points for worsening. For the single-item OHSA1, the MCID was a reduction of 2.0\u20133.0 points for improvement and an increase of 1.0 point for worsening. Owing to poor correlation with the symptom-based anchors, a reliable MCID for the OHDAS component was not established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These MCID thresholds for the OHQ, OHSA and OHSA item 1 alone, enhance the interpretability of scores and support their use in evaluating clinical benefit.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10286-025-01168-y","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T03:58:45Z","timestamp":1761278325000},"page":"103-111","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Establishing minimally clinically important differences for the orthostatic hypotension questionnaire (OHQ)"],"prefix":"10.1007","volume":"36","author":[{"given":"Horacio","family":"Kaufmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose-Alberto","family":"Palma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross","family":"Vickery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Norcliffe-Kaufmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beiyao","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lewin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadhg","family":"Guerin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"1168_CR1","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1056\/NEJMra1509723","volume":"382","author":"H Kaufmann","year":"2020","unstructured":"Kaufmann H, Norcliffe-Kaufmann L, Palma JA (2020) Baroreflex dysfunction. N Engl J Med 382:163\u2013178","journal-title":"N Engl J Med"},{"key":"1168_CR2","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/S1474-4422(22)00169-7","volume":"21","author":"W Wieling","year":"2022","unstructured":"Wieling W, Kaufmann H, Claydon VE, van Wijnen VK, Harms MPM, Juraschek SP, Thijs RD (2022) Diagnosis and treatment of orthostatic hypotension. Lancet Neurol 21:735\u2013746","journal-title":"Lancet Neurol"},{"key":"1168_CR3","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s10286-017-0437-3","volume":"27","author":"H Kaufmann","year":"2017","unstructured":"Kaufmann H, Palma JA (2017) Neurogenic orthostatic hypotension: the very basics. Clin Auton Res 27:39\u201343","journal-title":"Clin Auton Res"},{"key":"1168_CR4","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1002\/mdc3.12478","volume":"4","author":"JA Palma","year":"2017","unstructured":"Palma JA, Kaufmann H (2017) Epidemiology, diagnosis, and management of neurogenic orthostatic hypotension. Mov Disord Clin Pract 4:298\u2013308","journal-title":"Mov Disord Clin Pract"},{"key":"1168_CR5","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1212\/CON.0000000000000816","volume":"26","author":"JA Palma","year":"2020","unstructured":"Palma JA, Kaufmann H (2020) Management of orthostatic hypotension. Continuum 26:154\u2013177","journal-title":"Continuum"},{"key":"1168_CR6","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s12883-017-0867-5","volume":"17","author":"I Biaggioni","year":"2017","unstructured":"Biaggioni I, Arthur Hewitt L, Rowse GJ, Kaufmann H (2017) Integrated analysis of droxidopa trials for neurogenic orthostatic hypotension. BMC Neurol 17:90","journal-title":"BMC Neurol"},{"key":"1168_CR7","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1161\/HYPERTENSIONAHA.114.04035","volume":"65","author":"I Biaggioni","year":"2015","unstructured":"Biaggioni I, Freeman R, Mathias CJ, Low P, Hewitt LA, Kaufmann H, Droxidopa\u00a0302 Investigators (2015) Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa. Hypertension 65:101\u2013107","journal-title":"Hypertension"},{"key":"1168_CR8","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1111\/ggi.12553","volume":"16","author":"J Frith","year":"2016","unstructured":"Frith J, Newton JL (2016) Validation of a questionnaire for orthostatic hypotension for routine clinical use. Geriatr Gerontol Int 16:785\u2013790","journal-title":"Geriatr Gerontol Int"},{"key":"1168_CR9","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1002\/mds.26086","volume":"30","author":"RA Hauser","year":"2015","unstructured":"Hauser RA, Isaacson S, Lisk JP, Hewitt LA, Rowse G (2015) Droxidopa for the short-term treatment of symptomatic neurogenic orthostatic hypotension in Parkinson\u2019s disease (nOH306B). Mov Disord 30:646\u2013654","journal-title":"Mov Disord"},{"key":"1168_CR10","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1212\/WNL.0000000000000615","volume":"83","author":"H Kaufmann","year":"2014","unstructured":"Kaufmann H, Freeman R, Biaggioni I, Low P, Pedder S, Hewitt LA, Mauney J, Feirtag M, Mathias CJ, NOH301 Investigators (2014) Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology 83:328\u2013335","journal-title":"Neurology"},{"key":"1168_CR11","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/s10286-011-0146-2","volume":"22","author":"H Kaufmann","year":"2012","unstructured":"Kaufmann H, Malamut R, Norcliffe-Kaufmann L, Rosa K, Freeman R (2012) The orthostatic hypotension questionnaire (OHQ): validation of a novel symptom assessment scale. Clin Auton Res 22:79\u201390","journal-title":"Clin Auton Res"},{"key":"1168_CR12","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1586\/14779072.2015.1057504","volume":"13","author":"H Kaufmann","year":"2015","unstructured":"Kaufmann H, Norcliffe-Kaufmann L, Palma JA (2015) Droxidopa in neurogenic orthostatic hypotension. Expert Rev Cardiovasc Ther 13:875\u2013891","journal-title":"Expert Rev Cardiovasc Ther"},{"key":"1168_CR13","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1007\/s10286-021-00827-0","volume":"31","author":"H Kaufmann","year":"2021","unstructured":"Kaufmann H, Vickery R, Wang W, Kanodia J, Shibao CA, Norcliffe-Kaufmann L, Haumann B, Biaggioni I (2021) Safety and efficacy of ampreloxetine in symptomatic neurogenic orthostatic hypotension: a phase 2 trial. Clin Auton Res 31:699\u2013711","journal-title":"Clin Auton Res"},{"key":"1168_CR14","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1055\/s-0040-1713846","volume":"40","author":"JA Palma","year":"2020","unstructured":"Palma JA, Kaufmann H (2020) Clinical trials for neurogenic orthostatic hypotension: a comprehensive review of endpoints, pitfalls, and challenges. Semin Neurol 40:523\u2013539","journal-title":"Semin Neurol"},{"key":"1168_CR15","unstructured":"US Food and Drug Administration (2023) Patient-focused drug development: Incorporating clinical outcome assessments into endpoints for regulatory decision-making. Accessed October 17, 2025. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/patient-focused-drug-development-incorporating-clinical-outcome-assessments-endpoints-regulatory"},{"key":"1168_CR16","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s10286-021-00800-x","volume":"31","author":"A Lo","year":"2021","unstructured":"Lo A, Norcliffe-Kaufmann L, Vickery R, Bourdet D, Kanodia J (2021) Pharmacokinetics and pharmacodynamics of ampreloxetine, a novel, selective norepinephrine reuptake inhibitor, in symptomatic neurogenic orthostatic hypotension. Clin Auton Res 31:395\u2013403","journal-title":"Clin Auton Res"},{"key":"1168_CR17","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1136\/bmj.m1714","volume":"369","author":"T Devji","year":"2020","unstructured":"Devji T (2020) Evaluating the credibility of anchor based estimates of minimal important differences for patient reported outcomes: instrument development and reliability study. BMJ 369:1714. https:\/\/doi.org\/10.1136\/bmj.m1714","journal-title":"BMJ"}],"container-title":["Clinical Autonomic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10286-025-01168-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10286-025-01168-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10286-025-01168-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T08:37:57Z","timestamp":1773304677000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10286-025-01168-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,24]]},"references-count":17,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["1168"],"URL":"https:\/\/doi.org\/10.1007\/s10286-025-01168-y","relation":{},"ISSN":["0959-9851","1619-1560"],"issn-type":[{"value":"0959-9851","type":"print"},{"value":"1619-1560","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,24]]},"assertion":[{"value":"6 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"H. Kaufmann is Editor-in-Chief of\n                      Clinical Autonomic Research\n                      , published by Springer-Nature, and serves as PI of studies sponsored by Biogen MA Inc. (TRACK MSA, S19-01846) and Vaxxinity Inc. (UB-312, S22-01332). He has received consultant fees from Takeda Pharmaceutical Company Ltd, Ono Pharma UK Ltd, Theravance Biopharma US LLC., and Parexel. He receives royalties from UpToDate. He receives research support from NIH-NINDS, the Food and Drug Administration, the Familial Dysautonomia Foundation, and the HSAN IV Foundation. J.-A. Palma reports research funding from the NIH. R. Vickery is an employee of Theravance Biopharma Ireland Limited and is a shareholder. L. Norcliffe-Kaufmann and B. Zheng are employees of Theravance Biopharma US, LLC and are shareholders. D. Lewin is a contractor for Theravance Biopharma Ireland Limited. T. Guerin is an employee of Theravance Biopharma Ireland Limited and is a shareholder.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}