{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T07:38:12Z","timestamp":1769153892264,"version":"3.49.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research and Development, LLC","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ther Innov Regul Sci"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Patient-Focused Drug Development initiative of the U.S. Food and Drug Administration (FDA) aims to ensure that the patient experience of disease and treatment is an integral component of the drug development process. The 21st Century Cures Act and Prescription Drug User Fee Act (PDUFA) VI require the FDA to publicly report the type of patient-experience data reviewed in a new drug application (NDA) to inform regulatory decision-making. This report describes a recent approach adopted at Janssen of integrating patient-experience data into the NDA for esketamine (SPRAVATO\u00ae) nasal spray with a newly initiated oral antidepressant (esketamine\u2009+\u2009AD) for treatment-resistant depression. During the development of esketamine\u2009+\u2009AD, patient-experience data were collected using several patient-reported outcomes, including the Sheehan Disability Scale and 9-item Patient Health Questionnaire\u00a0(PHQ-9). Additionally, a patient-preference study assessed the relative importance of benefits and harms that patients allocated to different attributes of treatment. Preferences were collected from patients enrolled in phase 3 esketamine trials and from an online panel of primarily ketamine-naive patients. Patient-experience data were integrated into the esketamine NDA, the FDA advisory committee meeting briefing document, and the Sponsor\u2019s presentation. The FDA acknowledged reviewing the patient-experience data and determined that they supported esketamine\u2009+\u2009AD for treatment-resistant depression. This report highlights the importance of integrating patient-experience methods early in drug development, their impact on assessing patient-relevant benefits and risks, and how they can help improve clinical program design.<\/jats:p>","DOI":"10.1007\/s43441-021-00340-6","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T02:34:31Z","timestamp":1633833271000},"page":"38-46","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["U.S. Food and Drug Administration\u2019s Patient-Focused Drug Development Initiative: Experience with Integration of Patient-Experience Data in a New Drug Application for Esketamine Nasal Spray Plus a Newly Initiated Oral Antidepressant for Treatment-Resistant Depression"],"prefix":"10.1007","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6293-1674","authenticated-orcid":false,"given":"Eva G.","family":"Katz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pauline","family":"McNulty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bennett","family":"Levitan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Treichler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jadwiga","family":"Martynowicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol","family":"Jamieson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,8]]},"reference":[{"key":"340_CR1","unstructured":"US Food and Drug Administration. Patient-Focused Drug Development guidance series for enhancing the incorporation of the patient\u2019s voice in medical product development and regulatory decision making 2019. Available from: https:\/\/www.fda.gov\/drugs\/development-approval-process-drugs\/fda-patient-focused-drug-development-guidance-series-enhancing-incorporation-patients-voice-medical. Accessed 5 Apr 2021."},{"key":"340_CR2","unstructured":"114th U.S. Congress. 21st Century Cures Act 2016. Available from: https:\/\/www.congress.gov\/114\/plaws\/publ255\/PLAW-114publ255.pdf. Accessed 5 Apr 2021."},{"key":"340_CR3","unstructured":"US Food and Drug Administration. Benefit-risk assessment in drug regulatory decision-making: draft PDUFA VI Implementation Plan (FY 2018-2022) 2018. Available from: https:\/\/www.fda.gov\/media\/112570\/download. Accessed 5 Apr 2021."},{"key":"340_CR4","unstructured":"US Food and Drug Administration. eCTD Technical conformance guide 2020. Available from: https:\/\/www.fda.gov\/media\/93818\/download. Accessed 5 Apr 2021."},{"key":"340_CR5","unstructured":"US Food and Drug Administration. Patient-Focused Drug Development: collecting comprehensive and representative input. Guidance for industry, Food and Drug Administration staff, and other stakeholders 2020. Available from: https:\/\/www.fda.gov\/media\/139088\/download. Accessed 5 Apr 2021."},{"key":"340_CR6","doi-asserted-by":"crossref","unstructured":"Contesse MG, Valentine JE, Wall TE, Leffler MG. The case for the use of patient and caregiver perception of change assessments in rare disease clinical trials: a methodologic overview. Adv Ther. 2019;36(5):997\u20131010. https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30879250","DOI":"10.1007\/s12325-019-00920-x"},{"key":"340_CR7","unstructured":"US Food and Drug Administration. Collecting patient experience data: how you can best help FDA 2018. Available from: https:\/\/www.fda.gov\/media\/112163\/download. Accessed 5 Apr 2021."},{"key":"340_CR8","unstructured":"US Food and Drug Administration. FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor\u2019s office or clinic. March 5, 2019 [press release]. https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-new-nasal-spray-medication-treatment-resistant-depression-available-only-certified. Accessed 5 Apr 2021."},{"key":"340_CR9","unstructured":"SPRAVATO\u00ae (esketamine) nasal spray, CIII [Prescribing Information]. Titusville: Janssen Pharmaceuticals, Inc; 2020."},{"key":"340_CR10","unstructured":"Janssen Research & Development, LLC. Advisory Committee Briefing Document. Esketamine nasal spray for patients with treatment-resistant depression [press release]; 2019. https:\/\/www.fda.gov\/media\/121377\/download. Accessed 24 May 2021."},{"key":"340_CR11","unstructured":"US Food and Drug Administration. Janssen presentations for the February 12, 2019 joint meeting of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee 2019. Available from: https:\/\/www.fda.gov\/media\/121379\/download. Accessed 5 Apr 2021."},{"key":"340_CR12","doi-asserted-by":"crossref","unstructured":"Fedgchin M, Trivedi M, Daly EJ, Melkote R, Lane R, Lim P, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22(10):616\u201330. https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31290965","DOI":"10.1093\/ijnp\/pyz039"},{"key":"340_CR13","doi-asserted-by":"crossref","unstructured":"Popova V, Daly EJ, Trivedi M, Cooper K, Lane R, Lim P, et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study. Am J Psychiatry. 2019;176(6):428\u201338. https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31109201","DOI":"10.1176\/appi.ajp.2019.19020172"},{"key":"340_CR14","doi-asserted-by":"crossref","unstructured":"Daly EJ, Trivedi MH, Janik A, Li H, Zhang Y, Li X, et al. Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2019;76(9):893\u2013903. https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31166571","DOI":"10.1001\/jamapsychiatry.2019.1189"},{"key":"340_CR15","doi-asserted-by":"crossref","unstructured":"Wajs E, Aluisio L, Holder R, Daly EJ, Lane R, Lim P, et al. Esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: assessment of long-term safety in a phase 3, open-label study (SUSTAIN-2). J Clin Psychiatry. 2020;81(3):19m12891. https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/32316080","DOI":"10.4088\/JCP.19m12891"},{"key":"340_CR16","unstructured":"Clinical protocol: a randomized, double-blind, multicenter, active-controlled study to evaluate the efficacy, safety, and tolerability of fixed doses of intranasal esketamine plus an oral antidepressant in adult subjects with treatment-resistant depression (TRANSFORM-1); 2016. Available from: https:\/\/clinicaltrials.gov\/ProvidedDocs\/64\/NCT02417064\/Prot_000.pdf. Accessed 26 May 2021."},{"key":"340_CR17","unstructured":"Statistical analysis plan: a randomized, double-blind, multicenter, active-controlled study to evaluate the efficacy, safety, and tolerability of fixed doses of intranasal esketamine plus an oral antidepressant in adult subjects with treatment-resistant depression (TRANSFORM-1); 2017. Available from: https:\/\/clinicaltrials.gov\/ProvidedDocs\/64\/NCT02417064\/SAP_001.pdf. Accessed 26 May 2021."},{"key":"340_CR18","unstructured":"Clinical protocol: a randomized, double-blind, multicenter, active-controlled study to evaluate the efficacy, safety, and tolerability of flexible doses of intranasal esketamine plus an oral antidepressant in adult subjects with treatment-resistant depression (TRANSFORM-2); 2016. Available from: https:\/\/clinicaltrials.gov\/ProvidedDocs\/85\/NCT02418585\/Prot_000.pdf. Accessed 26 May 2021."},{"key":"340_CR19","unstructured":"Statistical analysis plan: a randomized, double-blind, multicenter, active-controlled study to evaluate the efficacy, safety, and tolerability of flexible doses of intranasal esketamine plus an oral antidepressant in adult subjects with treatment-resistant depression (TRANSFORM-2); 2017. Available from: https:\/\/clinicaltrials.gov\/ProvidedDocs\/85\/NCT02418585\/SAP_001.pdf. Accessed 26 May 2021."},{"key":"340_CR20","unstructured":"Clinical protocol: a randomized, double-blind, multicenter, active-controlled study of intranasal esketamine plus an oral antidepressant for relapse prevention in treatment-resistant depression (SUSTAIN-1); 2017. Available from: https:\/\/clinicaltrials.gov\/ProvidedDocs\/68\/NCT02493868\/Prot_000.pdf. Accessed 26 May 2021."},{"key":"340_CR21","unstructured":"Statistical analysis plan: a randomized, double-blind, multicenter, active-controlled study of intranasal esketamine plus an oral antidepressant for relapse prevention in treatment-resistant depression (SUSTAIN-1); 2018. Available from: https:\/\/clinicaltrials.gov\/ProvidedDocs\/68\/NCT02493868\/SAP_001.pdf. Accessed 26 May 2021."},{"key":"340_CR22","unstructured":"Clinical protocol: an open-label, long-term, safety and efficacy study of intranasal esketamine in treatment-resistant depression (SUSTAIN-2); 2016. Available from: https:\/\/clinicaltrials.gov\/ProvidedDocs\/87\/NCT02497287\/Prot_000.pdf. Accessed 26 May 2021."},{"key":"340_CR23","unstructured":"Statistical analysis plan: an open-label, long-term, safety and efficacy study of intranasal esketamine in treatment-resistant depression (SUSTAIN-2); 2017. Available from: https:\/\/clinicaltrials.gov\/ProvidedDocs\/87\/NCT02497287\/SAP_001.pdf. Accessed 26 May 2021."},{"key":"340_CR24","unstructured":"US Food and Drug Administration. Center for Drug Evaluation and Research. Application No. 211243Orig1s000: clinical reviews; pp 1\u2013285: p22 (Patient Experience Data checklist), pp35\u201343 (Table 2: Listing of Clinical Trials), pp 105\u2013108 (Efficacy Results\u2014Secondary and other relevant endpoints), pp 108\u2013111 (Other Secondary Endpoints), pp 170\u2013171 (Efficacy Results\u2014Secondary and other relevant endpoints), pp 187\u2013188 (Patient Preference Study Results), pp 192\u2013193 (Summary) 2019. Available from: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2019\/211243Orig1s000MedR.pdf. Accessed 5 Apr 2021."},{"key":"340_CR25","doi-asserted-by":"crossref","unstructured":"Lewis S, Romano C, De Bruecker G, Murrough JW, Shelton R, Singh JB, et al. Analysis of clinical trial exit interview data in patients with treatment-resistant depression. 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Benefit-risk assessment of esketamine nasal spray vs. placebo in treatment-resistant depression. Clin Pharmacol Ther. 2021;109(2):536\u201346. https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/32860422","DOI":"10.1002\/cpt.2024"},{"key":"340_CR32","unstructured":"The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. M4: the common technical document; 2016. Available from: https:\/\/www.ich.org\/page\/ctd. Accessed 5 Apr 2021."},{"key":"340_CR33","doi-asserted-by":"crossref","unstructured":"Reardon S. Antidepressant based on party drug gets backing from FDA advisory group (News Article). Nature. https:\/\/www.nature.com\/articles\/d41586-019-00559-2. Accessed 13 Feb 2019.","DOI":"10.1038\/d41586-019-00559-2"},{"key":"340_CR34","doi-asserted-by":"crossref","unstructured":"Kim J, Farchione T, Potter A, Chen Q, Temple R. Esketamine for treatment-resistant depression - first FDA-approved antidepressant in a new class. 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Ther Innov Regul Sci. 2019. https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31597462","DOI":"10.1177\/2168479019871519"}],"container-title":["Therapeutic Innovation &amp; Regulatory Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-021-00340-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43441-021-00340-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-021-00340-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T22:49:48Z","timestamp":1640040588000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43441-021-00340-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,8]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["340"],"URL":"https:\/\/doi.org\/10.1007\/s43441-021-00340-6","relation":{},"ISSN":["2168-4790","2168-4804"],"issn-type":[{"value":"2168-4790","type":"print"},{"value":"2168-4804","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,8]]},"assertion":[{"value":"7 April 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":"8 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":"All authors are employees of Janssen Research & Development and may own stock and\/or stock options. BL has a stocks portfolio that at times includes other pharmaceutical and health care-related companies.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}