Investigating the Safety Profile of Fast‐Track COVID‐19 Drugs Using the FDA Adverse Event Reporting System Database: A Comparative Observational Study

{ 'indexed': { 'date-parts': [[2024, 11, 14]], 'date-time': '2024-11-14T05:23:16Z', 'timestamp': 1731561796346, 'version': '3.28.0'}, 'reference-count': 55, 'publisher': 'Wiley', 'issue': '11', 'license': [ { 'start': { 'date-parts': [[2024, 11, 12]], 'date-time': '2024-11-12T00:00:00Z', 'timestamp': 1731369600000}, 'content-version': 'vor', 'delay-in-days': 11, 'URL': 'http://creativecommons.org/licenses/by-nc-nd/4.0/'}], 'funder': [ { 'DOI': '10.13039/501100003625', 'name': 'Ministry of Health and Welfare', 'doi-asserted-by': 'publisher', 'id': [{'id': '10.13039/501100003625', 'id-type': 'DOI', 'asserted-by': 'publisher'}]}, { 'DOI': '10.13039/501100002701', 'name': 'Ministry of Education', 'doi-asserted-by': 'publisher', 'id': [{'id': '10.13039/501100002701', 'id-type': 'DOI', 'asserted-by': 'publisher'}]}], 'content-domain': {'domain': ['onlinelibrary.wiley.com'], 'crossmark-restriction': True}, 'published-print': {'date-parts': [[2024, 11]]}, 'abstract': '<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The US ' 'Food and Drug Administration (US FDA) granted emergency use authorization (EUA) for multiple ' 'coronavirus disease 2019 (COVID‐19) drugs as a medical countermeasure during the COVID‐19 ' "pandemic. Despite these drugs' fast‐track nature, concerns persist regarding their efficacy " 'and potential adverse effects. Thus, the continuous surveillance and understanding of these ' "drugs' safety profiles are crucial in such " 'scenarios.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>Using the ' 'FDA Adverse Event Reporting System (FAERS) database, we aimed to compare the adverse drug ' 'reactions (ADRs) of four fast‐track COVID‐19 drugs to explore the potential of real‐world ' 'data for providing prompt feedback in clinical ' 'settings.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>To evaluate ' 'the post‐marketing safety of fast‐track COVID‐19 drugs, we descriptively evaluated the ADRs ' 'of four COVID‐19 drugs (bebtelovimab, molnupiravir, nirmatrelvir/ritonavir, and remdesivir) ' 'using FAERS data reported from January 2020 to June 2022. We examined FAERS case records of ' 'COVID‐19 drugs reported as the “primary suspect drug” as a case group and the records of ' 'other drugs as the control. “Serious adverse drug reactions (SADRs)” were defined based on ' 'FDA guidelines. Using reporting odds ratios, disproportionality analysis was conducted to ' 'determine significant signals for ADRs related to each of the four drugs compared with those ' 'of others, both at the preferred term (PT) and system organ class (SOC) levels. To explore ' 'the occurrence of reporting each serious outcome reported to the four drugs, we fitted ' 'logistic regression models, adjusting for age and ' 'sex.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>During the study ' 'period, 5\u2009248\u2009221 cases were submitted to FAERS, including 17\u2009275 cases of the ' 'four COVID‐19 drugs: bebtelovimab (532 cases), molnupiravir (1106 cases), ' 'nirmatrelvir/ritonavir (9217 cases), and remdesivir (6420 cases). A total of 64, 46, 116, and ' '207 PTs with significant disproportionality were identified for each drug, respectively. ' '“Infusion‐related reaction” (18.4%), “diarrhea” (7.4%), “dysgeusia” (11.4%), and “increased ' 'alanine aminotransferase” (14.5%) were the most frequently reported SADRs for bebtelovimab, ' 'molnupiravir, nirmatrelvir/ritonavir, and remdesivir, respectively. Among the 27 SOCs, ' 'statistically significant signals were observed in 10, 3, 0, and 8 SOCs for bebtelovimab, ' 'molnupiravir, nirmatrelvir/ritonavir, and remdesivir, respectively. Remdesivir showed a ' 'higher occurrence for the reporting of death or life‐threatening ADRs compared with the ' 'control (adjusted odds ratio (OR)\u2009=\u20092.44, 95% confidence interval (CI)\u2009=\u2009' '2.23–2.59; adjusted OR\u2009=\u20091.82, 95% CI\u2009=\u20091.64–2.02, ' 'respectively).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>We ' 'identified potential ADRs associated with COVID‐19 drugs and provided insights into their ' 'real‐world safety. This study demonstrated that real‐world data and real‐time safety reviews ' 'could be effective methods for the timely detection of ADR signals of drugs that have ' 'received fast‐track approval, as exemplified by COVID‐19 drugs. These findings underscore the ' 'importance of the continued surveillance, efficient data processing, and establishment of ' 'automated pipelines for real‐time safety reviews.</jats:p></jats:sec>', 'DOI': '10.1002/pds.70043', 'type': 'journal-article', 'created': { 'date-parts': [[2024, 11, 13]], 'date-time': '2024-11-13T12:25:18Z', 'timestamp': 1731500718000}, 'update-policy': 'http://dx.doi.org/10.1002/crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Investigating the Safety Profile of Fast‐Track <scp>COVID</scp>‐19 Drugs Using the ' '<scp>FDA</scp> Adverse Event Reporting System Database: A Comparative Observational Study', 'prefix': '10.1002', 'volume': '33', 'author': [ { 'ORCID': 'http://orcid.org/0000-0001-9555-0926', 'authenticated-orcid': False, 'given': 'Hyo Jung', 'family': 'Kim', 'sequence': 'first', 'affiliation': [ { 'name': 'Department of Digital Health, Samsung Advanced Institute for ' 'Health Science and Technology Sungkyunkwan University Seoul ' 'Korea'}, { 'name': 'Center of Research Resource Standardization Research Institution ' 'for Future Medicine, Samsung Medical Center Seoul Korea'}]}, { 'ORCID': 'http://orcid.org/0000-0002-9150-3732', 'authenticated-orcid': False, 'given': 'Jeong‐Hwa', 'family': 'Yoon', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Big Data Research Center, Medical Research Center Seoul ' 'National University Seoul Korea'}]}, { 'ORCID': 'http://orcid.org/0000-0002-7593-7020', 'authenticated-orcid': False, 'given': 'Kye Hwa', 'family': 'Lee', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Information Medicine, Asan Medical Center Seoul ' 'Korea'}, { 'name': 'Department of Digital Medicine Ulsan University College of ' 'Medicine Seoul Korea'}]}], 'member': '311', 'published-online': {'date-parts': [[2024, 11, 12]]}, 'reference': [ {'key': 'e_1_2_14_2_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMp2118468'}, {'key': 'e_1_2_14_3_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s40290‐021‐00397‐6'}, { 'key': 'e_1_2_14_4_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jamainternmed.2021.7257'}, { 'key': 'e_1_2_14_5_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jamainternmed.2020.2402'}, { 'key': 'e_1_2_14_6_1', 'unstructured': 'U.S. Food and Drug Administration “FDA Announces Bebtelovimab is Not ' 'Currently Authorized in Any US Region ”(2020) accessed March 16 2023 ' 'https://www.fda.gov/drugs/drug‐safety‐and‐availability/fda‐announces‐bebtelovimab‐not‐currently‐authorized‐any‐us‐region.'}, { 'key': 'e_1_2_14_7_1', 'unstructured': 'US Food and Drug Administration “Request for Emergency Use Authorization ' 'for Use of Chloroquine Phosphate or Hydroxychloroquine Sulfate Supplied ' 'From the Strategic National Stockpile for Treatment of 2019 Coronavirus ' 'Disease ”(2020) accessed July 23 2022 ' 'https://www.fda.gov/media/136534/download.'}, { 'key': 'e_1_2_14_8_1', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.7573/dic.2020-4-14', 'article-title': 'The Journey of Remdesivir: From Ebola to COVID‐19', 'volume': '9', 'author': 'Pardo J.', 'year': '2020', 'journal-title': 'Drugs in Context'}, { 'key': 'e_1_2_14_9_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S1473‐3099(20)30200‐0'}, {'key': 'e_1_2_14_10_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2007016'}, { 'key': 'e_1_2_14_11_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0140‐6736(20)31022‐9'}, { 'issue': '23', 'key': 'e_1_2_14_12_1', 'first-page': '2365', 'article-title': 'Emergency Use Authorization of Remdesivir: The Need for a Transparent ' 'Distribution Process', 'volume': '323', 'author': 'Ison M. 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