Improving Traditional Registrational Trial End Points: Development and Application of a Desirability of Outcome Ranking End Point for Complicated Urinary Tract Infection Clinical Trials
Abstract Background Traditional end points used in registrational randomized, controlled trials (RCTs) often do not allow for complete interpretation of the full range of potential clinical outcomes. Desirability of outcome ranking (DOOR) is an approach to the design and analysis of clinical trials...
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| Veröffentlicht in: | Clinical infectious diseases 2023-02, Vol.76 (3), p.e1157-e1165 |
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| creator | Howard-Anderson, Jessica Hamasaki, Toshimitsu Dai, Weixiao Collyar, Deborah Rubin, Daniel Nambiar, Sumathi Kinamon, Tori Hill, Carol Gelone, Steven P Mariano, David Baba, Takamichi Holland, Thomas L Doernberg, Sarah B Chambers, Henry F Fowler, Vance G Evans, Scott R Boucher, Helen W |
| description | Abstract
Background
Traditional end points used in registrational randomized, controlled trials (RCTs) often do not allow for complete interpretation of the full range of potential clinical outcomes. Desirability of outcome ranking (DOOR) is an approach to the design and analysis of clinical trials that incorporates benefits and risks of novel treatment strategies and provides a global assessment of patient experience.
Methods
Through a multidisciplinary committee of experts in infectious diseases, clinical trial design, drug regulation, and patient experience, we developed a DOOR end point for infectious disease syndromes and demonstrated how this could be applied to 3 registrational drug trials (ZEUS, APEKS-cUTI, and DORI-05) for complicated urinary tract infections (cUTIs). ZEUS compared fosfomycin to piperacillin/tazobactam, APEKS-cUTI compared cefiderocol to imipenem, and DORI-05 compared doripenem to levofloxacin. Using DOOR, we estimated the probability of a more desirable outcome with each investigational antibacterial drug.
Results
In each RCT, the DOOR distribution was similar and the probability that a patient in the investigational arm would have a more desirable outcome than a patient in the control arm had a 95% confidence interval containing 50%, indicating no significant difference between treatment arms. DOOR facilitated improved understanding of potential trade-offs between clinical efficacy and safety. Partial credit and subgroup analyses also highlight unique attributes of DOOR.
Conclusions
DOOR can effectively be used in registrational cUTI trials. The DOOR end point presented here can be adapted for other infectious disease syndromes and prospectively incorporated into future clinical trials.
A multidisciplinary committee developed an infectious diseases desirability of outcome ranking end point and demonstrated how this could be applied to 3 registrational trials for complicated urinary tract infections, allowing for improved understanding of risks and benefits with each treatment. |
| doi_str_mv | 10.1093/cid/ciac692 |
| format | Article |
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Background
Traditional end points used in registrational randomized, controlled trials (RCTs) often do not allow for complete interpretation of the full range of potential clinical outcomes. Desirability of outcome ranking (DOOR) is an approach to the design and analysis of clinical trials that incorporates benefits and risks of novel treatment strategies and provides a global assessment of patient experience.
Methods
Through a multidisciplinary committee of experts in infectious diseases, clinical trial design, drug regulation, and patient experience, we developed a DOOR end point for infectious disease syndromes and demonstrated how this could be applied to 3 registrational drug trials (ZEUS, APEKS-cUTI, and DORI-05) for complicated urinary tract infections (cUTIs). ZEUS compared fosfomycin to piperacillin/tazobactam, APEKS-cUTI compared cefiderocol to imipenem, and DORI-05 compared doripenem to levofloxacin. Using DOOR, we estimated the probability of a more desirable outcome with each investigational antibacterial drug.
Results
In each RCT, the DOOR distribution was similar and the probability that a patient in the investigational arm would have a more desirable outcome than a patient in the control arm had a 95% confidence interval containing 50%, indicating no significant difference between treatment arms. DOOR facilitated improved understanding of potential trade-offs between clinical efficacy and safety. Partial credit and subgroup analyses also highlight unique attributes of DOOR.
Conclusions
DOOR can effectively be used in registrational cUTI trials. The DOOR end point presented here can be adapted for other infectious disease syndromes and prospectively incorporated into future clinical trials.
A multidisciplinary committee developed an infectious diseases desirability of outcome ranking end point and demonstrated how this could be applied to 3 registrational trials for complicated urinary tract infections, allowing for improved understanding of risks and benefits with each treatment.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1093/cid/ciac692</identifier><identifier>PMID: 36031403</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Anti-Bacterial Agents - therapeutic use ; Doripenem - therapeutic use ; Editor's Choice ; Humans ; Imipenem ; Levofloxacin - therapeutic use ; Major ; Urinary Tract Infections - drug therapy ; Urinary Tract Infections - microbiology</subject><ispartof>Clinical infectious diseases, 2023-02, Vol.76 (3), p.e1157-e1165</ispartof><rights>The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2022</rights><rights>The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-857d4ccc21dcea6ab0f0278e7a1b79cae479dea1270c0274d37e95641c36020d3</citedby><cites>FETCH-LOGICAL-c440t-857d4ccc21dcea6ab0f0278e7a1b79cae479dea1270c0274d37e95641c36020d3</cites><orcidid>0000-0001-9924-0458 ; 0000000199240458</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36031403$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/1888831$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Howard-Anderson, Jessica</creatorcontrib><creatorcontrib>Hamasaki, Toshimitsu</creatorcontrib><creatorcontrib>Dai, Weixiao</creatorcontrib><creatorcontrib>Collyar, Deborah</creatorcontrib><creatorcontrib>Rubin, Daniel</creatorcontrib><creatorcontrib>Nambiar, Sumathi</creatorcontrib><creatorcontrib>Kinamon, Tori</creatorcontrib><creatorcontrib>Hill, Carol</creatorcontrib><creatorcontrib>Gelone, Steven P</creatorcontrib><creatorcontrib>Mariano, David</creatorcontrib><creatorcontrib>Baba, Takamichi</creatorcontrib><creatorcontrib>Holland, Thomas L</creatorcontrib><creatorcontrib>Doernberg, Sarah B</creatorcontrib><creatorcontrib>Chambers, Henry F</creatorcontrib><creatorcontrib>Fowler, Vance G</creatorcontrib><creatorcontrib>Evans, Scott R</creatorcontrib><creatorcontrib>Boucher, Helen W</creatorcontrib><title>Improving Traditional Registrational Trial End Points: Development and Application of a Desirability of Outcome Ranking End Point for Complicated Urinary Tract Infection Clinical Trials</title><title>Clinical infectious diseases</title><addtitle>Clin Infect Dis</addtitle><description>Abstract
Background
Traditional end points used in registrational randomized, controlled trials (RCTs) often do not allow for complete interpretation of the full range of potential clinical outcomes. Desirability of outcome ranking (DOOR) is an approach to the design and analysis of clinical trials that incorporates benefits and risks of novel treatment strategies and provides a global assessment of patient experience.
Methods
Through a multidisciplinary committee of experts in infectious diseases, clinical trial design, drug regulation, and patient experience, we developed a DOOR end point for infectious disease syndromes and demonstrated how this could be applied to 3 registrational drug trials (ZEUS, APEKS-cUTI, and DORI-05) for complicated urinary tract infections (cUTIs). ZEUS compared fosfomycin to piperacillin/tazobactam, APEKS-cUTI compared cefiderocol to imipenem, and DORI-05 compared doripenem to levofloxacin. Using DOOR, we estimated the probability of a more desirable outcome with each investigational antibacterial drug.
Results
In each RCT, the DOOR distribution was similar and the probability that a patient in the investigational arm would have a more desirable outcome than a patient in the control arm had a 95% confidence interval containing 50%, indicating no significant difference between treatment arms. DOOR facilitated improved understanding of potential trade-offs between clinical efficacy and safety. Partial credit and subgroup analyses also highlight unique attributes of DOOR.
Conclusions
DOOR can effectively be used in registrational cUTI trials. The DOOR end point presented here can be adapted for other infectious disease syndromes and prospectively incorporated into future clinical trials.
A multidisciplinary committee developed an infectious diseases desirability of outcome ranking end point and demonstrated how this could be applied to 3 registrational trials for complicated urinary tract infections, allowing for improved understanding of risks and benefits with each treatment.</description><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Doripenem - therapeutic use</subject><subject>Editor's Choice</subject><subject>Humans</subject><subject>Imipenem</subject><subject>Levofloxacin - therapeutic use</subject><subject>Major</subject><subject>Urinary Tract Infections - drug therapy</subject><subject>Urinary Tract Infections - microbiology</subject><issn>1058-4838</issn><issn>1537-6591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kl1rFDEUhgex2Fq98l6CFyLI1GQyn95IWatdKFTK9jpkM2e2R2eSaZJZ6E_z33m2Oy5604R8nTx58yacJHkj-JngjfxksKWmTdlkz5ITUcgqLYtGPKc5L-o0r2V9nLwM4SfnQtS8eJEcy5JLkXN5kvxeDqN3W7QbtvK6xYjO6p7dwAZD9HperjxSf2Fb9sOhjeEz-wpb6N04gI1MU_x8HHs0jzxzHdMEBPR6jT3Gh13keorGDcButP21u-0gxjrn2cIN-_PQsluPVvuHnR8T2dJ2YB5lFz1aQmY34VVy1NEAr-fxNLn9drFaXKZX19-Xi_Or1OQ5j2ldVG1ujMlEa0CXes07nlU1VFqsq8ZoyKumBS2yihvayFtZQVOUuTD0SRlv5WnyZa87TusBSMTSv_Rq9DiQS-U0qv93LN6pjdsqwUXZyCYnhXd7BRciqmAwgrkzzlp6mBI1FSkI-jBf4939BCGqAYOBvtcW3BQU-atqqk1N6Mc9arwLwUN3MCO42qWEopRQc0oQ_fZf_wf2bw4Q8H62N41PKv0BGXvEiA</recordid><startdate>20230208</startdate><enddate>20230208</enddate><creator>Howard-Anderson, Jessica</creator><creator>Hamasaki, Toshimitsu</creator><creator>Dai, Weixiao</creator><creator>Collyar, Deborah</creator><creator>Rubin, Daniel</creator><creator>Nambiar, Sumathi</creator><creator>Kinamon, Tori</creator><creator>Hill, Carol</creator><creator>Gelone, Steven P</creator><creator>Mariano, David</creator><creator>Baba, Takamichi</creator><creator>Holland, Thomas L</creator><creator>Doernberg, Sarah B</creator><creator>Chambers, Henry F</creator><creator>Fowler, Vance G</creator><creator>Evans, Scott R</creator><creator>Boucher, Helen W</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>OTOTI</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9924-0458</orcidid><orcidid>https://orcid.org/0000000199240458</orcidid></search><sort><creationdate>20230208</creationdate><title>Improving Traditional Registrational Trial End Points: Development and Application of a Desirability of Outcome Ranking End Point for Complicated Urinary Tract Infection Clinical Trials</title><author>Howard-Anderson, Jessica ; Hamasaki, Toshimitsu ; Dai, Weixiao ; Collyar, Deborah ; Rubin, Daniel ; Nambiar, Sumathi ; Kinamon, Tori ; Hill, Carol ; Gelone, Steven P ; Mariano, David ; Baba, Takamichi ; Holland, Thomas L ; Doernberg, Sarah B ; Chambers, Henry F ; Fowler, Vance G ; Evans, Scott R ; Boucher, Helen W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-857d4ccc21dcea6ab0f0278e7a1b79cae479dea1270c0274d37e95641c36020d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Doripenem - therapeutic use</topic><topic>Editor's Choice</topic><topic>Humans</topic><topic>Imipenem</topic><topic>Levofloxacin - therapeutic use</topic><topic>Major</topic><topic>Urinary Tract Infections - drug therapy</topic><topic>Urinary Tract Infections - microbiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Howard-Anderson, Jessica</creatorcontrib><creatorcontrib>Hamasaki, Toshimitsu</creatorcontrib><creatorcontrib>Dai, Weixiao</creatorcontrib><creatorcontrib>Collyar, Deborah</creatorcontrib><creatorcontrib>Rubin, Daniel</creatorcontrib><creatorcontrib>Nambiar, Sumathi</creatorcontrib><creatorcontrib>Kinamon, Tori</creatorcontrib><creatorcontrib>Hill, Carol</creatorcontrib><creatorcontrib>Gelone, Steven P</creatorcontrib><creatorcontrib>Mariano, David</creatorcontrib><creatorcontrib>Baba, Takamichi</creatorcontrib><creatorcontrib>Holland, Thomas L</creatorcontrib><creatorcontrib>Doernberg, Sarah B</creatorcontrib><creatorcontrib>Chambers, Henry F</creatorcontrib><creatorcontrib>Fowler, Vance G</creatorcontrib><creatorcontrib>Evans, Scott R</creatorcontrib><creatorcontrib>Boucher, Helen W</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Howard-Anderson, Jessica</au><au>Hamasaki, Toshimitsu</au><au>Dai, Weixiao</au><au>Collyar, Deborah</au><au>Rubin, Daniel</au><au>Nambiar, Sumathi</au><au>Kinamon, Tori</au><au>Hill, Carol</au><au>Gelone, Steven P</au><au>Mariano, David</au><au>Baba, Takamichi</au><au>Holland, Thomas L</au><au>Doernberg, Sarah B</au><au>Chambers, Henry F</au><au>Fowler, Vance G</au><au>Evans, Scott R</au><au>Boucher, Helen W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improving Traditional Registrational Trial End Points: Development and Application of a Desirability of Outcome Ranking End Point for Complicated Urinary Tract Infection Clinical Trials</atitle><jtitle>Clinical infectious diseases</jtitle><addtitle>Clin Infect Dis</addtitle><date>2023-02-08</date><risdate>2023</risdate><volume>76</volume><issue>3</issue><spage>e1157</spage><epage>e1165</epage><pages>e1157-e1165</pages><issn>1058-4838</issn><eissn>1537-6591</eissn><abstract>Abstract
Background
Traditional end points used in registrational randomized, controlled trials (RCTs) often do not allow for complete interpretation of the full range of potential clinical outcomes. Desirability of outcome ranking (DOOR) is an approach to the design and analysis of clinical trials that incorporates benefits and risks of novel treatment strategies and provides a global assessment of patient experience.
Methods
Through a multidisciplinary committee of experts in infectious diseases, clinical trial design, drug regulation, and patient experience, we developed a DOOR end point for infectious disease syndromes and demonstrated how this could be applied to 3 registrational drug trials (ZEUS, APEKS-cUTI, and DORI-05) for complicated urinary tract infections (cUTIs). ZEUS compared fosfomycin to piperacillin/tazobactam, APEKS-cUTI compared cefiderocol to imipenem, and DORI-05 compared doripenem to levofloxacin. Using DOOR, we estimated the probability of a more desirable outcome with each investigational antibacterial drug.
Results
In each RCT, the DOOR distribution was similar and the probability that a patient in the investigational arm would have a more desirable outcome than a patient in the control arm had a 95% confidence interval containing 50%, indicating no significant difference between treatment arms. DOOR facilitated improved understanding of potential trade-offs between clinical efficacy and safety. Partial credit and subgroup analyses also highlight unique attributes of DOOR.
Conclusions
DOOR can effectively be used in registrational cUTI trials. The DOOR end point presented here can be adapted for other infectious disease syndromes and prospectively incorporated into future clinical trials.
A multidisciplinary committee developed an infectious diseases desirability of outcome ranking end point and demonstrated how this could be applied to 3 registrational trials for complicated urinary tract infections, allowing for improved understanding of risks and benefits with each treatment.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>36031403</pmid><doi>10.1093/cid/ciac692</doi><orcidid>https://orcid.org/0000-0001-9924-0458</orcidid><orcidid>https://orcid.org/0000000199240458</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1058-4838 |
| ispartof | Clinical infectious diseases, 2023-02, Vol.76 (3), p.e1157-e1165 |
| issn | 1058-4838 1537-6591 |
| language | eng |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Anti-Bacterial Agents - therapeutic use Doripenem - therapeutic use Editor's Choice Humans Imipenem Levofloxacin - therapeutic use Major Urinary Tract Infections - drug therapy Urinary Tract Infections - microbiology |
| title | Improving Traditional Registrational Trial End Points: Development and Application of a Desirability of Outcome Ranking End Point for Complicated Urinary Tract Infection Clinical Trials |
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