Bias in observational studies on the effectiveness of in hospital use of hydroxychloroquine in COVID-19

DOI record: { "DOI": "10.1002/pds.5632", "ISSN": [ "1053-8569", "1099-1557" ], "URL": "http://dx.doi.org/10.1002/pds.5632", "abstract": "<jats:title>Abstract</jats:title><jats:sec><jats:title>Purpose</jats:title><jats:p>During the first waves of the coronavirus pandemic, evidence on potential effective treatments was urgently needed. Results from observational studies on the effectiveness of hydroxychloroquine (HCQ) were conflicting, potentially due to biases. We aimed to assess the quality of observational studies on HCQ and its relation to effect sizes.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>PubMed was searched on 15 March 2021 for observational studies on the effectiveness of in‐hospital use of HCQ in COVID‐19 patients, published between 01/01/2020 and 01/03/2021 on. Study quality was assessed using the ROBINS‐I tool. Association between study quality and study characteristics (journal ranking, publication date, and time between submission and publication) and differences between effects sizes found in observational studies compared to those found in RCTs, were assessed using Spearman's correlation.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Eighteen of the 33 (55%) included observational studies were scored as critical risk of bias, eleven (33%) as serious risk and only four (12%) as moderate risk of bias. Biases were most often scored as critical in the domains related to selection of participants (<jats:italic>n</jats:italic> = 13, 39%) and bias due to confounding (<jats:italic>n</jats:italic> = 8, 24%). There were no significant associations found between the study quality and the characteristics nor between the study quality and the effect estimates.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>Overall, the quality of observational HCQ studies was heterogeneous. Synthesis of evidence of effectiveness of HCQ in COVID‐19 should focus on RCTs and carefully consider the added value and quality of observational evidence.</jats:p></jats:sec>", "alternative-id": [ "10.1002/pds.5632" ], "assertion": [ { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Received", "name": "received", "order": 0, "value": "2022-06-10" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Accepted", "name": "accepted", "order": 1, "value": "2023-04-14" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Published", "name": "published", "order": 2, "value": "2023-04-24" } ], "author": [ { "ORCID": "https://orcid.org/0000-0003-0223-4815", "affiliation": [ { "name": "Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands" } ], "authenticated-orcid": false, "family": "Hempenius", "given": "Mirjam", "sequence": "first" }, { "affiliation": [ { "name": "Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands" } ], "family": "Bots", "given": "Sophie H.", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Clinical Epidemiology Leiden University Medical Center Leiden The Netherlands" } ], "family": "Groenwold", "given": "Rolf H. H.", "sequence": "additional" }, { "affiliation": [ { "name": "Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands" } ], "family": "de Boer", "given": "Anthonius", "sequence": "additional" }, { "affiliation": [ { "name": "Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands" }, { "name": "Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht The Netherlands" } ], "family": "Klungel", "given": "Olaf H.", "sequence": "additional" }, { "affiliation": [ { "name": "Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands" }, { "name": "Department of Clinical Pharmacy, Division Laboratory and Pharmacy University Medical Center Utrecht Utrecht The Netherlands" }, { "name": "Faculty of Pharmaceutical Sciences University of Iceland Reykjavik Iceland" } ], "family": "Gardarsdottir", "given": "Helga", "sequence": "additional" } ], "container-title": "Pharmacoepidemiology and Drug Safety", "container-title-short": "Pharmacoepidemiology and Drug", "content-domain": { "crossmark-restriction": true, "domain": [ "onlinelibrary.wiley.com" ] }, "created": { "date-parts": [ [ 2023, 4, 18 ] ], "date-time": "2023-04-18T12:09:42Z", "timestamp": 1681819782000 }, "deposited": { "date-parts": [ [ 2023, 8, 18 ] ], "date-time": "2023-08-18T06:09:42Z", "timestamp": 1692338982000 }, "indexed": { "date-parts": [ [ 2025, 6, 4 ] ], "date-time": "2025-06-04T04:23:20Z", "timestamp": 1749011000430, "version": "3.40.5" }, "is-referenced-by-count": 3, "issue": "9", "issued": { "date-parts": [ [ 2023, 4, 24 ] ] }, "journal-issue": { "issue": "9", "published-print": { "date-parts": [ [ 2023, 9 ] ] } }, "language": "en", "license": [ { "URL": "http://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 4, 24 ] ], "date-time": "2023-04-24T00:00:00Z", "timestamp": 1682294400000 } } ], "link": [ { "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1002/pds.5632", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "311", "original-title": [], "page": "1001-1011", "prefix": "10.1002", "published": { "date-parts": [ [ 2023, 4, 24 ] ] }, "published-online": { "date-parts": [ [ 2023, 4, 24 ] ] }, "published-print": { "date-parts": [ [ 2023, 9 ] ] }, "publisher": "Wiley", "reference": [ { "DOI": "10.1056/nejme2015903", "doi-asserted-by": "publisher", "key": "e_1_2_9_2_1" }, { "DOI": "10.1016/j.ijantimicag.2020.105960", "doi-asserted-by": "publisher", "key": "e_1_2_9_3_1" }, { "DOI": "10.1016/j.tmaid.2020.101663", "doi-asserted-by": "publisher", "key": "e_1_2_9_4_1" }, { "DOI": "10.1002/pds.5029", "doi-asserted-by": "publisher", "key": "e_1_2_9_5_1" }, { "DOI": "10.1093/ajhp/zxab056", "doi-asserted-by": "publisher", "key": "e_1_2_9_6_1" }, { "DOI": "10.1016/j.tmaid.2020.101791", "doi-asserted-by": "publisher", "key": "e_1_2_9_7_1" }, { "DOI": "10.1136/BMJOS‐2021‐100202", "doi-asserted-by": "publisher", "key": "e_1_2_9_8_1" }, { "DOI": "10.1016/j.ijid.2020.06.099", "doi-asserted-by": "publisher", "key": "e_1_2_9_9_1" }, { "DOI": "10.1111/cts.12860", "doi-asserted-by": "publisher", "key": "e_1_2_9_10_1" }, { "DOI": "10.1016/j.ijid.2020.06.095", "doi-asserted-by": "publisher", "key": "e_1_2_9_11_1" }, { "DOI": "10.1056/NEJMoa2022926", "doi-asserted-by": "publisher", "key": "e_1_2_9_12_1" }, { "DOI": "10.1056/nejmoa2023184", "doi-asserted-by": "publisher", "key": "e_1_2_9_13_1" }, { "DOI": "10.1136/bmj.m2980", "doi-asserted-by": "publisher", "key": "e_1_2_9_14_1" }, { "DOI": "10.7326/M20‐1223", "doi-asserted-by": "publisher", "key": "e_1_2_9_15_1" }, { "DOI": "10.1016/j.cmi.2020.08.022", "doi-asserted-by": "publisher", "key": "e_1_2_9_16_1" }, { "DOI": "10.1093/aje/kwab028", "doi-asserted-by": "publisher", "key": "e_1_2_9_17_1" }, { "DOI": "10.1016/j.cmi.2021.03.003", "doi-asserted-by": "publisher", "key": "e_1_2_9_18_1" }, { "key": "e_1_2_9_19_1", "unstructured": "Clarivate.InCites Journal Citation Reports.2021Accessed August 4 2021.https://jcr.clarivate.com" }, { "DOI": "10.1136/bmj.i4919", "doi-asserted-by": "publisher", "key": "e_1_2_9_20_1" }, { "key": "e_1_2_9_21_1", "unstructured": "RECOVERY trial to stop enrolling patients to “ineffective” hydroxychloroquine arm – The Pharmaceutical Journal. 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