{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:33:11Z","timestamp":1790476391532,"version":"4.1.0"},"reference-count":33,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Otolaryngol Head Neck Surg"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"\n Importance<\/jats:title>\n Innovative clinical trials (CTs) are needed to address the rising incidence of head and neck squamous cell carcinoma (HNSCC). Despite adequate trial initiation, HNSCC CTs experience high failure rates, and the factors driving these trends remain unclear.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To assess the characteristics associated with failure (termination or withdrawal) in CTs for the treatment of HNSCC.<\/jats:p>\n <\/jats:sec>\n \n Design and Setting<\/jats:title>\n HNSCC CTs were identified on ClinicalTrials.gov from January 1, 2000, to December 31, 2024, and trial failures were defined as early termination or withdrawal. Trial characteristics were compared between failed CTs and completed CT controls. Data were analyzed from June to August 2025.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was trial failure. The association between failure and CT characteristics, including phase, enrollment, funding source, intervention type, and age-eligibility criteria, was analyzed using descriptive statistics and multivariable regression models.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 692 matched trials were analyzed, including 346 trial failures and 346 completed control trials. The overall leading reasons for failure were strategic decisions (defined as nonscientific, sponsor-driven choices; 102 trials [29.5%]) and poor recruitment (90 trials [26.0%]). The reasons for failure varied by trial characteristics. Strategic decisions were the predominant reason for failure in phase 1 trials, industry-sponsored trials, and immunotherapy and targeted therapy trials. In contrast, poor recruitment was a more common reason in later-phase trials, non\u2013industry-sponsored trials, and trials investigating chemotherapy, radiation, chemoradiation, combination treatments, and supportive care. Temporal analysis revealed a growing failure rate among CTs since 2000. Increased log-transformed actual enrollment safeguarded against trial failure, whereas industry funding was an independent risk factor.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this study, HNSCC CTs were terminated early or withdrawn for a variety of reasons, most commonly due to strategic decisions or poor recruitment. Careful attention to trial characteristics associated with early failure is needed to overcome new barriers to drug development and adapt trial design to common reasons for failure.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoto.2025.4766","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T16:30:59Z","timestamp":1767371459000},"page":"242","source":"Crossref","is-referenced-by-count":5,"title":["Clinical Trial Termination or Withdrawal in Head and Neck Squamous Cell Carcinoma"],"prefix":"10.1001","volume":"152","author":[{"given":"Janice J.","family":"Huang","sequence":"first","affiliation":[{"name":"Medical Scientist Training Program, University of Miami Miller School of Medicine, Miami, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex S.","family":"Reznik","sequence":"additional","affiliation":[{"name":"Medical Scientist Training Program, University of Miami Miller School of Medicine, Miami, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Sonis","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts"},{"name":"Division of Oral Medicine and Dentistry, Brigham and Women\u2019s Hospital, Boston, Massachusetts"},{"name":"Division of Oral Medicine and Oral Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts"},{"name":"Biomodels LLC, Waltham, Massachusetts"},{"name":"Primary Endpoint Solutions, Waltham, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Franzmann","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, University of Miami Miller School of Medicine, Miami, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Villa","sequence":"additional","affiliation":[{"name":"Oral Medicine, Oral Oncology, and Dentistry, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida"},{"name":"Department of Orofacial Sciences, University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"9","key":"ooi250084r1","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1038\/s41415-022-5166-x","article-title":"Reviewing the epidemiology of head and neck cancer: definitions, trends and risk factors.","volume":"233","author":"Gormley","year":"2022","journal-title":"Br Dent J"},{"issue":"2","key":"ooi250084r2","first-page":"39","article-title":"Update on oral and oropharyngeal cancers: a guide for oral health care providers.","volume":"98","author":"Johnson","year":"2024","journal-title":"J Dent Hyg"},{"issue":"1","key":"ooi250084r3","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and neck squamous cell carcinoma.","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"ooi250084r4","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3322\/caac.21871","article-title":"Cancer statistics, 2025.","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J Clin"},{"issue":"9","key":"ooi250084r5","doi-asserted-by":"publisher","first-page":"E300","DOI":"10.1002\/lary.25942","article-title":"Characteristics of NIH- and industry-sponsored head and neck cancer clinical trials.","volume":"126","author":"Devaiah","year":"2016","journal-title":"Laryngoscope"},{"issue":"4","key":"ooi250084r6","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1097\/COC.0000000000001160","article-title":"Geospatial mapping of head and neck cancer research: assessing access, disparities, and characteristics of head and neck cancer clinical trials across the United States.","volume":"48","author":"Glehan","year":"2025","journal-title":"Am J Clin Oncol"},{"issue":"3","key":"ooi250084r7","doi-asserted-by":"publisher","DOI":"10.1016\/j.adro.2020.10.021","article-title":"Head and neck cancer clinical research on ClinicalTrials.gov: an opportunity for radiation oncologists.","volume":"6","author":"Muralidhar","year":"2020","journal-title":"Adv Radiat Oncol"},{"issue":"7","key":"ooi250084r8","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1001\/jamaoto.2022.0890","article-title":"Comparison of patients with head and neck cancer in randomized clinical trials and clinical practice: a systematic review.","volume":"148","author":"Kaanders","year":"2022","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"issue":"2","key":"ooi250084r9","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1001\/jamaoto.2019.3967","article-title":"Rates of discontinuation and nonpublication of head and neck cancer randomized clinical trials.","volume":"146","author":"Johnson","year":"2020","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"issue":"4","key":"ooi250084r10","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2013-002625","article-title":"Barriers to recruitment for surgical trials in head and neck oncology: a survey of trial investigators.","volume":"3","author":"Kaur","year":"2013","journal-title":"BMJ Open"},{"issue":"7","key":"ooi250084r11","doi-asserted-by":"publisher","first-page":"E596","DOI":"10.1097\/BSD.0000000000001323","article-title":"Analysis of the frequency, characteristics, and reasons for termination of spine-related clinical trials.","volume":"35","author":"Caruana","year":"2022","journal-title":"Clin Spine Surg"},{"key":"ooi250084r12","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.ijcard.2017.06.020","article-title":"Discontinuation and non-publication of clinical trials in cardiovascular medicine.","volume":"244","author":"Roddick","year":"2017","journal-title":"Int J Cardiol"},{"issue":"1","key":"ooi250084r13","doi-asserted-by":"publisher","DOI":"10.1017\/cts.2025.65","article-title":"Characterization of terminated and withdrawn clinical trials for the treatment and prevention of oral mucositis.","volume":"9","author":"Reznik","year":"2025","journal-title":"J Clin Transl Sci"},{"issue":"11","key":"ooi250084r14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002966","article-title":"Noncompletion and nonpublication of trials studying rare diseases: a cross-sectional analysis.","volume":"16","author":"Rees","year":"2019","journal-title":"PLoS Med"},{"issue":"10","key":"ooi250084r15","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1001\/jama.2014.1361","article-title":"Prevalence, characteristics, and publication of discontinued randomized trials.","volume":"311","author":"Kasenda","year":"2014","journal-title":"JAMA"},{"issue":"6","key":"ooi250084r16","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1111\/cts.12577","article-title":"The current status of drug discovery and development as originated in United States academia: the influence of industrial and academic collaboration on drug discovery and development.","volume":"11","author":"Takebe","year":"2018","journal-title":"Clin Transl Sci"},{"key":"ooi250084r17","doi-asserted-by":"publisher","first-page":"d7373","DOI":"10.1136\/bmj.d7373","article-title":"Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study.","volume":"344","author":"Prayle","year":"2012","journal-title":"BMJ"},{"key":"ooi250084r18","doi-asserted-by":"publisher","first-page":"d7292","DOI":"10.1136\/bmj.d7292","article-title":"Publication of NIH funded trials registered in ClinicalTrials.gov: cross sectional analysis.","volume":"344","author":"Ross","year":"2012","journal-title":"BMJ"},{"issue":"1","key":"ooi250084r19","doi-asserted-by":"publisher","first-page":"3446","DOI":"10.1038\/s41598-021-82840-x","article-title":"Predictive modeling of clinical trial terminations using feature engineering and embedding learning.","volume":"11","author":"Elkin","year":"2021","journal-title":"Sci Rep"},{"issue":"3","key":"ooi250084r20","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.oraloncology.2014.12.007","article-title":"Barriers to clinical trial recruitment in head and neck cancer.","volume":"51","author":"Haddad","year":"2015","journal-title":"Oral Oncol"},{"key":"ooi250084r21","doi-asserted-by":"publisher","DOI":"10.2196\/42123","article-title":"Recruitment of patients with cancer for a clinical trial evaluating a web-based psycho-oncological intervention: secondary analysis of a diversified recruitment strategy in a randomized controlled trial.","volume":"9","author":"Tsiouris","year":"2023","journal-title":"JMIR Cancer"},{"issue":"2","key":"ooi250084r22","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1007\/s00520-012-1553-1","article-title":"Nurse-led follow-up care for head and neck cancer patients: a quasi-experimental prospective trial.","volume":"21","author":"de Leeuw","year":"2013","journal-title":"Support Care Cancer"},{"issue":"9","key":"ooi250084r23","doi-asserted-by":"publisher","first-page":"2430","DOI":"10.1158\/1078-0432.CCR-20-3857","article-title":"Impact of broadening trial eligibility criteria for patients with advanced non-small cell lung cancer: real-world analysis of select ASCO-Friends recommendations.","volume":"27","author":"Harvey","year":"2021","journal-title":"Clin Cancer Res"},{"issue":"9","key":"ooi250084r24","doi-asserted-by":"publisher","first-page":"e160","DOI":"10.1016\/j.clon.2019.05.003","article-title":"Generalisability of common oncology clinical trial eligibility criteria in the real world.","volume":"31","author":"Karim","year":"2019","journal-title":"Clin Oncol (R Coll Radiol)"},{"issue":"33","key":"ooi250084r25","doi-asserted-by":"publisher","first-page":"3737","DOI":"10.1200\/JCO.2017.73.7916","article-title":"Broadening eligibility criteria to make clinical trials more representative: American Society of Clinical Oncology and Friends of Cancer Research joint research statement.","volume":"35","author":"Kim","year":"2017","journal-title":"J Clin Oncol"},{"issue":"33","key":"ooi250084r26","doi-asserted-by":"publisher","first-page":"3917","DOI":"10.1200\/JCO.24.00843","article-title":"Patient enrollment to industry-sponsored versus federally-sponsored cancer clinical trials.","volume":"42","author":"Unger","year":"2024","journal-title":"J Clin Oncol"},{"key":"ooi250084r27","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.jhealeco.2016.01.012","article-title":"Innovation in the pharmaceutical industry: new estimates of R&D costs.","volume":"47","author":"DiMasi","year":"2016","journal-title":"J Health Econ"},{"issue":"9","key":"ooi250084r28","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1001\/jama.2020.1166","article-title":"Estimated research and development investment needed to bring a new medicine to market, 2009-2018.","volume":"323","author":"Wouters","year":"2020","journal-title":"JAMA"},{"issue":"6","key":"ooi250084r29","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/d41573-020-00093-1","article-title":"Impact of COVID-19 on oncology clinical trials.","volume":"19","author":"Upadhaya","year":"2020","journal-title":"Nat Rev Drug Discov"},{"issue":"3","key":"ooi250084r30","doi-asserted-by":"publisher","first-page":"e222","DOI":"10.1097\/SLA.0000000000004113","article-title":"The impact of COVID-19 on clinical trials.","volume":"272","author":"Asaad","year":"2020","journal-title":"Ann Surg"},{"issue":"2","key":"ooi250084r31","doi-asserted-by":"publisher","DOI":"10.1111\/cts.70117","article-title":"Decentralized clinical trials in the era of real-world evidence: a statistical perspective.","volume":"18","author":"Chen","year":"2025","journal-title":"Clin Transl Sci"},{"issue":"4","key":"ooi250084r32","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1001\/jamaoncol.2023.6565","article-title":"Decentralized clinical trials as a new paradigm of trial delivery to improve equity of access.","volume":"10","author":"Underhill","year":"2024","journal-title":"JAMA Oncol"},{"issue":"1","key":"ooi250084r33","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1056\/NEJMra1510061","article-title":"Adaptive designs for clinical trials.","volume":"375","author":"Bhatt","year":"2016","journal-title":"N Engl J Med"}],"container-title":["JAMA Otolaryngology\u2013Head & Neck Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaotolaryngology\/articlepdf\/2843111\/jamaotolaryngology_huang_2026_oi_250084_1771965327.2938.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T15:00:30Z","timestamp":1773327630000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaotolaryngology\/fullarticle\/2843111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,1]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaoto.2025.4766","relation":{},"ISSN":["2168-6181"],"issn-type":[{"value":"2168-6181","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3,1]]}}}