{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T07:22:31Z","timestamp":1777879351939,"version":"3.51.4"},"reference-count":49,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Drug Safety"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>In tissue regenerative trials, investigators operate in the intersection of routine clinical care and research. Often, clinical trials are the only option to introduce innovative treatments to disadvantaged populations in safety-net hospitals (SNHs). It is necessary to maintain a balance between efficient study conduct and patient safety. Social determinants play a role in medication adherence in clinical trials and chronic disease management that may increase risks if not managed correctly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>We aimed to assess the safety of patients in tissue regenerative clinical trials while examining underlying causes to develop proactive risk mitigation strategies for high-risk patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>A single-center, retrospective study was conducted for clinical trials with tissue regenerative products for chronic wounds at an SNH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Data obtained from 186 subjects were analyzed retrospectively for correlation between social determinants of health and adverse events by using Spearman correlation and Kruskal\u2013Wallis tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Wound healing was achieved in 41.94% of patients who received investigational products. Overall, the diabetic foot ulcer group was noted to have a higher prevalence of serious adverse events (SAEs; 22.8% of enrolled subjects) and adverse events (78.3% of enrolled subjects) as compared to the venous stasis ulcer group, with 12.4% of SAEs and 71.0% adverse events observed in the study population. Kruskal\u2013Wallis test demonstrated statistically significant correlation between polypharmacy (\u2a7e5 drugs) and a higher number of adverse events (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0016). A Spearman correlation test showed that a higher number of comorbidities was associated with a higher number of adverse events (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0007).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>These findings in polypharmacy and comorbidities being associated with a higher number of adverse events highlighted the importance of safety monitoring of patients with high disease burden in clinical trials. Understanding the frequency\/types of adverse events can provide important insights for those conducting trials in a particular indication. In addition, monitoring can help to address social determinants that contribute to higher numbers of adverse events, and proactively address disease burden with appropriate medical management to minimize risks in tissue regenerative clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/20420986251385861","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T10:37:23Z","timestamp":1767868643000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and risk management in clinical trials for chronic wounds with tissue regenerative products"],"prefix":"10.1177","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1370-187X","authenticated-orcid":false,"given":"Marina Alexandra","family":"Malikova","sequence":"first","affiliation":[{"name":"Department of Surgery, Chobanian and Avedisian School of Medicine, Boston Medical Center, Boston University, 85 East Concord Street, Boston, MA 02118, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Connor Michael","family":"Roddy","sequence":"additional","affiliation":[{"name":"Department of Surgery, Chobanian and Avedisian School of Medicine, Boston Medical Center, Boston University, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nolan Patrick","family":"Joyce","sequence":"additional","affiliation":[{"name":"Department of Surgery, Chobanian and Avedisian School of Medicine, Boston Medical Center, Boston University, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine Nicole","family":"Cilley","sequence":"additional","affiliation":[{"name":"Department of Surgery, Chobanian and Avedisian School of Medicine, Boston Medical Center, Boston University, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1994.01690040093015"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.200223"},{"key":"e_1_3_4_4_2","volume-title":"Wound healing phases","author":"Wallace HA","year":"2022","unstructured":"Wallace HA, Basehore BM, Zito PM. Wound healing phases. Treasure Island, FL: StatPearls, 2022."},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2021.0026"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13047-020-00383-2"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.12683"},{"key":"e_1_3_4_8_2","first-page":"61","article-title":"Quality of life and psychological aspects in patients with chronic leg ulcer","volume":"70","author":"Situm M","year":"2016","unstructured":"Situm M, Kolic M, Spoljar S. Quality of life and psychological aspects in patients with chronic leg ulcer. Acta Med Croatica 2016; 70: 61\u201363.","journal-title":"Acta Med Croatica"},{"key":"e_1_3_4_9_2","first-page":"199","volume-title":"Wound care essentials","author":"Baranoski SAE.","year":"2020","unstructured":"Baranoski SAE. Wound treatment options. In: Wound care essentials. 5th ed. Philadelphia, PA: Wolters Kluwer, 2020, p. 199.","edition":"5"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASW.0000288217.83128.f3"},{"key":"e_1_3_4_11_2","unstructured":"Centers for Medicare & Medicaid Services. Skin substitute grafts\/cellular and tissue-based products for the treatment of diabetic foot ulcers and venous leg ulcers. Document Information LCD ID: L3504 https:\/\/www.cms.gov\/medicare-coverage-database\/view\/lcd.aspx?LCDId=35041 (2025 accessed 12 May 2025)."},{"key":"e_1_3_4_12_2","unstructured":"Code of Federal Regulations. Title 21. \u00a7 1271.10. Are my HCT\/P's regulated solely under section 361 of the PHS Act and the regulations in this part and if so what must I do? https:\/\/www.ecfr.gov\/current\/title-21\/chapter-I\/subchapter-L\/part-1271\/subpart-A\/section-1271.10 (2025 accessed 12 May 2025)."},{"key":"e_1_3_4_13_2","unstructured":"U.S. Food & Drug Adminstration. Guidance for industry and food and drug administration staff regulatory considerations for human cells tissues and cellular and tissue-based products: minimal manipulation and homologous use https:\/\/www.fda.gov\/downloads\/BiologicsBloodVaccines\/GuidanceComplianceRegulatoryInformation\/Guidances\/CellularandGeneTherapy\/UCM585403.pdf (2020)."},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.12968\/jowc.2017.26.Sup4.S4"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.suc.2020.05.002"},{"key":"e_1_3_4_16_2","unstructured":"Leg Ulcers Clinical Trials.Gov. Clinical Trials https:\/\/clinicaltrials.gov\/ct2\/results?cond=leg+ulcersterm=cntry=state=city=dist= (2025 accessed 9 May 2025)."},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-023-02492-3"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.332.7537.347"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-791-0_7"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1525\/maq.2004.18.2.258"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.5034\/inquiryjrnl_46.01.7"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1475-6773.2005.00430.x"},{"key":"e_1_3_4_23_2","unstructured":"World Health Organization. Social determinants of health https:\/\/www.who.int\/health-topics\/social-determinants-of-health#tab=tab_1 (accessed 12 May 2025)."},{"key":"e_1_3_4_24_2","unstructured":"U.S. Food & Drug Adminstration. Reporting serious adverse events to FDA https:\/\/www.fda.gov\/safety\/reporting-serious-problems-fda\/what-serious-adverse-event (2025 accessed 12 May 2025)."},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1177\/2042098620909614"},{"key":"e_1_3_4_26_2","unstructured":"US Food & Drug Administration. Guidance for industry and investigators safety reporting requirements for INDs and BA\/BE studies https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/safety-reporting-requirements-inds-investigational-new-drug-applications-and-babe (2012 accessed 12 May 2025)."},{"key":"e_1_3_4_27_2","unstructured":"US Census Bureau. Income by zip code\u2014Census Bureau Search https:\/\/data.census.gov\/all?q=income%20by%20zip%20code (accessed 25 September 2024)."},{"key":"e_1_3_4_28_2","unstructured":"National Heart Lung and Blood Institute. Calculate your BMI\u2014standard BMI calculator. US Department of Health and Human Services www.nhlbi.nih.gov\/health\/educational\/lose_wt\/BMI\/bmicalc.htm (2025 accessed 30 September 2024)."},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjem.2018.08.001"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-08-102474-4.00004-2"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e3181577511"},{"key":"e_1_3_4_32_2","volume-title":"23rd ISoP annual meeting \u201cGlobal perspectives on pharmacovigilance in the digital age and advanced therapeutics,\u201d","author":"Joyce NP","unstructured":"Joyce NP, Roddy CM, Malikova MA. Safety and risk-management in clinical trials with tissue regenerative products. In: 23rd ISoP annual meeting \u201cGlobal perspectives on pharmacovigilance in the digital age and advanced therapeutics,\u201d Montreal, QC, Canada, 1\u20135 October 2024."},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1154567"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3643"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2011.10.032"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2007.00221.x"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63482-7"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007-0226"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-006-0270-9"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.11072"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v037a14"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1212-2"},{"issue":"1","key":"e_1_3_4_43_2","first-page":"51","article-title":"Mesenchymal stromal cell therapy alone does not lead to complete restoration of skin parameters in diabetic foot patients within a 3-year follow-up period","volume":"12","author":"Maksimova NV","year":"2022","unstructured":"Maksimova NV, Michenko AV, Krasilnikova OA, et al. Mesenchymal stromal cell therapy alone does not lead to complete restoration of skin parameters in diabetic foot patients within a 3-year follow-up period. Bioimpacts 2022; 12(1): 51\u201355.","journal-title":"Bioimpacts"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/hsr2.2036"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.21037\/sci-2022-025"},{"key":"e_1_3_4_46_2","unstructured":"Vogel G. Macchiarini guilty of misconduct but whistleblowers share blame new Karolinska Institute verdict finds. Science Insider https:\/\/www.science.org\/content\/article\/macchiarini-guilty-misconduct-whistleblowers-share-blame-new-karolinska-institute (2018 accessed 15 May 2025)."},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpcardiol.2020.100647"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-020-06447-0"},{"key":"e_1_3_4_49_2","article-title":"Deprescribing in older adults with polypharmacy","volume":"385","author":"Hung A","year":"2024","unstructured":"Hung A, Kim YH, Pavon JM. Deprescribing in older adults with polypharmacy. BMJ 2024; 385: e074892.","journal-title":"BMJ"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/1475-6773.13567"}],"container-title":["Therapeutic Advances in Drug Safety"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20420986251385861","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/20420986251385861","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20420986251385861","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:41:08Z","timestamp":1777592468000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/20420986251385861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":49,"alternative-id":["10.1177\/20420986251385861"],"URL":"https:\/\/doi.org\/10.1177\/20420986251385861","relation":{},"ISSN":["2042-0986","2042-0994"],"issn-type":[{"value":"2042-0986","type":"print"},{"value":"2042-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"article-number":"20420986251385861"}}