{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:13:18Z","timestamp":1789427598498,"version":"build-2803163510"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"name":"ibsa institut biochimique sa, pambio-noranco, switzerland"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Drug Investig"],"published-print":{"date-parts":[[2022,1]]},"DOI":"10.1007\/s40261-021-01101-x","type":"journal-article","created":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T12:02:43Z","timestamp":1637928163000},"page":"43-51","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Safety and Efficacy of the FLECTOR (Diclofenac Epolamine) Topical System in Children with Minor Soft Tissue Injuries: A Phase IV Non-randomized Clinical Trial"],"prefix":"10.1007","volume":"42","clinical-trial-number":[{"clinical-trial-number":"nct02132247","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Christopher A.","family":"Jones","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred K.","family":"Hoehler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Frangione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert","family":"Ledesma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Paul P.","family":"Wisman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarence","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"1101_CR1","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.pmr.2020.02.002","volume":"31","author":"S Stanos","year":"2020","unstructured":"Stanos S. Topical analgesics. Phys Med Rehabil Clin N Am. 2020;31:233\u201344. https:\/\/doi.org\/10.1016\/j.pmr.2020.02.002.","journal-title":"Phys Med Rehabil Clin N Am"},{"issue":"Suppl 1","key":"1101_CR2","doi-asserted-by":"publisher","first-page":"S35","DOI":"10.1111\/pme.12288","volume":"14","author":"ML McPherson","year":"2013","unstructured":"McPherson ML, Cimino NM. Topical NSAID formulations. Pain Med. 2013;14(Suppl 1):S35\u20139. https:\/\/doi.org\/10.1111\/pme.12288.","journal-title":"Pain Med"},{"key":"1101_CR3","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD008609.pub2","volume":"5","author":"S Derry","year":"2017","unstructured":"Derry S, Wiffen PJ, Kalso EA, Bell RF, Aldington D, Phillips T, et al. Topical analgesics for acute and chronic pain in adults\u2014an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2017;5: CD008609. https:\/\/doi.org\/10.1002\/14651858.CD008609.pub2.","journal-title":"Cochrane Database Syst Rev"},{"key":"1101_CR4","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s40266-019-00661-0","volume":"36","author":"G Honvo","year":"2019","unstructured":"Honvo G, Leclercq V, Geerinck A, Thomas T, Veronese N, Charles A, et al. Safety of topical non-steroidal anti-inflammatory drugs in osteoarthritis: outcomes of a systematic review and meta-analysis. Drugs Aging. 2019;36:45\u201364. https:\/\/doi.org\/10.1007\/s40266-019-00661-0.","journal-title":"Drugs Aging"},{"key":"1101_CR5","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.3899\/jrheum.090935","volume":"37","author":"UE Makris","year":"2010","unstructured":"Makris UE, Kohler MJ, Fraenkel L. Adverse effects of topical nonsteroidal antiinflammatory drugs in older adults with osteoarthritis: a systematic literature review. J Rheumatol. 2010;37:1236\u201343. https:\/\/doi.org\/10.3899\/jrheum.090935.","journal-title":"J Rheumatol"},{"key":"1101_CR6","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1080\/03007995.2020.1716703","volume":"36","author":"PJ Wiffen","year":"2020","unstructured":"Wiffen PJ, Xia J. Systematic review of topical diclofenac for the treatment of acute and chronic musculoskeletal pain. Curr Med Res Opin. 2020;36:637\u201350. https:\/\/doi.org\/10.1080\/03007995.2020.1716703.","journal-title":"Curr Med Res Opin"},{"key":"1101_CR7","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1185\/03007995.2010.550606","volume":"27","author":"RS Taylor","year":"2011","unstructured":"Taylor RS, Fotopoulos G, Maibach H. Safety profile of topical diclofenac: a meta-analysis of blinded, randomized, controlled trials in musculoskeletal conditions. Curr Med Res Opin. 2011;27:605\u201322. https:\/\/doi.org\/10.1185\/03007995.2010.550606.","journal-title":"Curr Med Res Opin"},{"key":"1101_CR8","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/978-981-13-3642-3_8","volume-title":"Novel drug delivery technologies","author":"AK Seth","year":"2019","unstructured":"Seth AK. Transdermal drug therapy: emerging techniques and improved patient compliance. In: Misra A, Shahiwala A, editors. Novel drug delivery technologies. Singapore: Springer Nature; 2019. p. 261\u201389."},{"key":"1101_CR9","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1001\/jama.2016.0249","volume":"315","author":"S Derry","year":"2016","unstructured":"Derry S, Wiffen P, Moore A. Topical nonsteroidal anti-inflammatory drugs for acute musculoskeletal pain. JAMA. 2016;315:813\u20134. https:\/\/doi.org\/10.1001\/jama.2016.0249.","journal-title":"JAMA"},{"key":"1101_CR10","unstructured":"US Food and Drug Administration (FDA). Flector patch (diclofenac epolamine topical patch) 1.3%. Approved product label. 2007"},{"key":"1101_CR11","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/s0885-3924(00)00125-1","volume":"19","author":"BS Galer","year":"2000","unstructured":"Galer BS, Rowbotham M, Perander J, Devers A, Friedman E. Topical diclofenac patch relieves minor sports injury pain: results of a multicenter controlled clinical trial. J Pain Symptom Manage. 2000;19:287\u201394. https:\/\/doi.org\/10.1016\/s0885-3924(00)00125-1.","journal-title":"J Pain Symptom Manage"},{"key":"1101_CR12","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3810\/psm.2011.02.1857","volume":"39","author":"J Gimbel","year":"2011","unstructured":"Gimbel J, Jacobs D, Pixton G, Paterson C. Effectiveness and safety of diclofenac epolamine topical patch 1.3% for the treatment of acute pain due to back strain: an open-label, uncontrolled study. Phys Sportsmed. 2011;39:11\u20138. https:\/\/doi.org\/10.3810\/psm.2011.02.1857.","journal-title":"Phys Sportsmed"},{"key":"1101_CR13","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1055\/s-0031-1275359","volume":"32","author":"K Kuehl","year":"2011","unstructured":"Kuehl K, Carr W, Yanchick J, Magelli M, Rovati S. Analgesic efficacy and safety of the diclofenac epolamine topical patch 1.3% (DETP) in minor soft tissue injury. Int J Sports Med. 2011;32:635\u201343. https:\/\/doi.org\/10.1055\/s-0031-1275359.","journal-title":"Int J Sports Med"},{"key":"1101_CR14","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1185\/03007995.2010.493099","volume":"26","author":"J Yanchick","year":"2010","unstructured":"Yanchick J, Magelli M, Bodie J, Sjogren J, Rovati S. Time to significant pain reduction following DETP application vs placebo for acute soft tissue injuries. Curr Med Res Opin. 2010;26:1993\u20132002. https:\/\/doi.org\/10.1185\/03007995.2010.493099.","journal-title":"Curr Med Res Opin"},{"key":"1101_CR15","first-page":"275","volume":"53","author":"T Polieri","year":"2000","unstructured":"Polieri T, Saponati G. Minor sport injuries in children: a new, safe, topical preparation containing DHEP (Diclofenac Epolamine). Med Sport (Roma). 2000;53:275\u20138.","journal-title":"Med Sport (Roma)."},{"key":"1101_CR16","doi-asserted-by":"publisher","first-page":"15","DOI":"10.2165\/11585890-000000000-00000","volume":"31","author":"C Costantino","year":"2011","unstructured":"Costantino C, Kwarecki J, Samokhin AV, Mautone G, Rovati S. Diclofenac epolamine plus heparin plaster versus diclofenac epolamine plaster in mild to moderate ankle sprain: a randomized, double-blind, parallel-group, placebo-controlled, multicentre, phase III trial. Clin Drug Investig. 2011;31:15\u201326. https:\/\/doi.org\/10.2165\/11585890-000000000-00000.","journal-title":"Clin Drug Investig"},{"key":"1101_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2165\/0044011-200929010-00001","volume":"29","author":"B Petersen","year":"2009","unstructured":"Petersen B, Rovati S. Diclofenac epolamine (Flector) patch: evidence for topical activity. Clin Drug Investig. 2009;29:1\u20139. https:\/\/doi.org\/10.2165\/0044011-200929010-00001.","journal-title":"Clin Drug Investig"},{"key":"1101_CR18","first-page":"9","volume":"14","author":"DL Wong","year":"1988","unstructured":"Wong DL, Baker CM. Pain in children: comparison of assessment scales. Pediatr Nurs. 1988;14:9\u201317.","journal-title":"Pediatr Nurs"},{"key":"1101_CR19","doi-asserted-by":"publisher","first-page":"2967","DOI":"10.1185\/03007990802381364","volume":"24","author":"KD Rainsford","year":"2008","unstructured":"Rainsford KD, Kean WF, Ehrlich GE. Review of the pharmaceutical properties and clinical effects of the topical NSAID formulation, diclofenac epolamine. Curr Med Res Opin. 2008;24:2967\u201392. https:\/\/doi.org\/10.1185\/03007990802381364.","journal-title":"Curr Med Res Opin"},{"key":"1101_CR20","unstructured":"Pediatric Exclusivity Study Age Group. Available from URL: https:\/\/www.fda.gov\/drugs\/data-standards-manual-monographs\/pediatric-exclusivity-study-age-group. Accessed 18 Nov 2021."},{"key":"1101_CR21","doi-asserted-by":"publisher","first-page":"168","DOI":"10.3810\/pgm.2011.07.2316","volume":"123","author":"AR Brewer","year":"2011","unstructured":"Brewer AR, Pierchala LA, Yanchick JK, Magelli M, Rovati S. Gastrointestinal tolerability of diclofenac epolamine topical patch 13%: a pooled analysis of 14 clinical studies. Postgrad Med. 2011;123:168\u201376. https:\/\/doi.org\/10.3810\/pgm.2011.07.2316.","journal-title":"Postgrad Med"},{"key":"1101_CR22","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1111\/bcp.12268","volume":"79","author":"HK Batchelor","year":"2015","unstructured":"Batchelor HK, Marriott JF. Formulations for children: problems and solutions. Br J Clin Pharmacol. 2015;79:405\u201318. https:\/\/doi.org\/10.1111\/bcp.12268.","journal-title":"Br J Clin Pharmacol"}],"container-title":["Clinical Drug Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40261-021-01101-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40261-021-01101-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40261-021-01101-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T11:19:06Z","timestamp":1641986346000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40261-021-01101-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,26]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["1101"],"URL":"https:\/\/doi.org\/10.1007\/s40261-021-01101-x","relation":{},"ISSN":["1173-2563","1179-1918"],"issn-type":[{"value":"1173-2563","type":"print"},{"value":"1179-1918","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,26]]},"assertion":[{"value":"1 November 2021","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 November 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This clinical trial was financially supported by IBSA Institut Biochimique SA, Pambio-Noranco, Switzerland.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"FH is an IBSA consultant. At the time of the study, CAJ and CJ were employees of IBSA Pharma Inc., a wholly-owned subsidiary of IBSA. VF is an employee of IBSA CH. GL and PPW have no financial interests in either FDETS or IBSA CH or its affiliate.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The datasets used and\/or analyzed during the current study are available from the corresponding author on reasonable request.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of data and material"}},{"value":"CAJ: contributed to protocol design and study management, reviewed study data, authored the CSR, and reviewed\/revised the manuscript. FH: prepared the study statistical analysis plan (SAP), oversaw study data management and analysis, provided additional statistical analysis for the manuscript, and reviewed\/revised the manuscript. VF: reviewed the manuscript. GL and PPW: reviewed and executed the protocol and reviewed the manuscript. CJ: contributed to protocol design and study management, reviewed study data and the clinical study report (CSR), and reviewed\/revised the manuscript.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author contributions"}},{"value":"A central institutional review board approved the protocol at each participating site, and the study was conducted according to the ethical principles of human research established by the Declaration of Helsinki and its amendments.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent by way of a Parental Permission Form was obtained in writing from parents\/legally authorized representatives and, in addition, children aged 10\u201316 years were required to sign a Children\u2019s Assent Form, before the commencement of study procedures.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}