{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T15:11:16Z","timestamp":1789830676100,"version":"4.0.1"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Pfizer Inc","award":["Pfizer Inc"],"award-info":[{"award-number":["Pfizer Inc"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Patient Rep Outcomes"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>During a phase 2\/3 study of twice-daily nirmatrelvir 300\u00a0mg coadministered with ritonavir 100\u00a0mg versus placebo for 5 days (NCT05011513), participants reported presence and severity of COVID-19 symptoms using a COVID-19 symptom diary in accordance with FDA guidance. Here, we aimed to evaluate the content validity of the COVID-19 symptom diary and global impression items through qualitative interviews as recommended by the FDA. Study participants kept a daily electronic diary to record the presence and severity of 14 COVID-19 symptoms (stuffy or runny nose, sore throat, shortness of breath, cough, low energy or tiredness, muscle or body aches, headache, chills\/shivering, feeling hot or feverish, nausea, frequency of vomiting, frequency of diarrhea, sense of smell, and sense of taste). They also answered questions regarding 3 global impression items (return to health, return to usual activities, and overall symptom severity). A subset of clinical trial participants was interviewed at study completion to assess content validity of the diary. Overall, 25 participants were interviewed across 10 clinical sites. Each of the 14 symptoms included in the diary were reported by \u2265\u20091 participant, with low energy\/tiredness being reported most frequently (88.0%). Twelve participants (48.0%) reported\u2009\u2265\u20091 symptom that was not captured by the diary, with dizziness being the most common (12.0%). Rates of these symptoms were lower (\u2264\u200912.0%) than the 14 prespecified symptoms included in the diary (16.0\u221288.0%). Based on participant feedback, all 14 diary items were clear and generally easy to answer using the response scales, and all were interpreted as intended. The 3 global items received similar feedback, although a few participants noted that there were challenges in interpreting the items, describing questions as \u201cvague\u201d and \u201cconfusing\u201d, or that responses were too limited; one-third reported having difficulty calculating overall symptom experience for multiple symptoms. Participants reported that the electronic application for the diary and global items was easy to use and enabled the items to be easily completed. Exit interview results support the content validity of the COVID-19 symptom diary and global impression items, with the 14 symptoms included in the diary reflecting the most commonly experienced COVID-19 symptoms. NCT05011513; <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/classic.clinicaltrials.gov\/ct2\/show\/NCT05011513\" ext-link-type=\"uri\">https:\/\/classic.clinicaltrials.gov\/ct2\/show\/NCT05011513<\/jats:ext-link>.<\/jats:p>","DOI":"10.1186\/s41687-025-00901-5","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T10:26:54Z","timestamp":1754908014000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Assessing participants\u2019 experiences with the COVID-19 symptom diary in a clinical trial"],"prefix":"10.1186","volume":"9","author":[{"given":"T. Michelle","family":"Brown","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisom","family":"Kanu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Harrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"901_CR1","unstructured":"Centers for Disease Control and Prevention. COVID Data Tracker (2024) Available at: https:\/\/covid.cdc.gov\/covid-data-tracker\/#datatracker-home. Accessed May 23"},{"key":"901_CR2","volume-title":"Ritonavir tablets). Full prescribing information","author":"Paxlovid (nirmatrelvir tablets","year":"2023","unstructured":"Paxlovid (nirmatrelvir tablets; ritonavir tablets) (2023) Full prescribing information. Pfizer Inc, New York, NY"},{"key":"901_CR3","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1056\/NEJMoa2309003","volume":"390","author":"J Hammond","year":"2024","unstructured":"Hammond J, Fountaine RJ, Yunis C et al (2024) Nirmatrelvir for vaccinated or unvaccinated adult outpatients with COVID-19. N Engl J Med 390:1186\u20131195","journal-title":"N Engl J Med"},{"key":"901_CR4","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1056\/NEJMoa2118542","volume":"386","author":"J Hammond","year":"2022","unstructured":"Hammond J, Leister-Tebbe H, Gardner A et al (2022) Oral nirmatrelvir for high-risk, nonhospitalized adults with COVID-19. N Engl J Med 386:1397\u20131408","journal-title":"N Engl J Med"},{"key":"901_CR5","unstructured":"US Food & Drug Administration (2024) Assessing COVID-19-Related Symptoms in Outpatient Adult and Adolescent Subjects in Clinical Trials of Drugs and Biological Products for COVID-19 Prevention or Treatment: Guidance for Industry. Available at: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/assessing-covid-19-related-symptoms-outpatient-adult-and-adolescent-subjects-clinical-trials-drugs. Accessed May 6"},{"key":"901_CR6","first-page":"e33190","volume":"14","author":"M Jacobs","year":"2022","unstructured":"Jacobs M, Karp A, Alessandro C et al (2022) SARS-CoV-2 infection in winter 2021\/2022: the association of varying clinical manifestations with and without prior vaccination. Cureus 14:e33190","journal-title":"Cureus"},{"key":"901_CR7","doi-asserted-by":"publisher","first-page":"385","DOI":"10.3201\/eid2702.203729","volume":"27","author":"Vahey","year":"2021","unstructured":"Vahey GM, Marshall KE, McDonald E et al (2021) Symptom profiles and progression in hospitalized and nonhospitalized patients with coronavirus disease, Colorado, USA, 2020. Emerg Infect Dis 27:385\u2013395","journal-title":"Emerg Infect Dis"},{"key":"901_CR8","doi-asserted-by":"publisher","first-page":"904","DOI":"10.15585\/mmwr.mm6928a2","volume":"69id","author":"RM Burke","year":"2020","unstructured":"Burke RM, Killerby ME, Newton S et al (2020) Symptom profiles of a convenience sample of patients with COVID-19 - United States, January-April 2020. MMWR Morb Mortal Wkly Rep 69id:904\u2013908","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"901_CR9","doi-asserted-by":"publisher","first-page":"3941","DOI":"10.2147\/IJGM.S313486","volume":"14","author":"N Dreyer","year":"2021","unstructured":"Dreyer N, Petruski-Ivleva N, Albert L et al (2021) Identification of a vulnerable group for post-acute sequelae of SARS-CoV-2 (PASC): people with autoimmune diseases recover more slowly from COVID-19. Int J Gen Med 14:3941\u20133949","journal-title":"Int J Gen Med"},{"key":"901_CR10","first-page":"1267","volume":"12","author":"M Andre","year":"2023","unstructured":"Andre M, Lau LS, Pokharel MD et al (2023) From alpha to Omicron: how different variants of concern of the SARS-coronavirus-2 impacted the world. Biology (Basel) 12:1267","journal-title":"Biology (Basel)"},{"key":"901_CR11","unstructured":"Centers for Disease Control and Prevention (2024) Long COVID or Post-COVID Conditions. Available at: https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/long-term-effects\/index.html. Accessed May 7"},{"key":"901_CR12","unstructured":"Centers for Disease Control and Prevention (2024) Symptoms of COVID-19. Available at: https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/symptoms-testing\/symptoms.html. Accessed May 7"}],"container-title":["Journal of Patient-Reported Outcomes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41687-025-00901-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s41687-025-00901-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41687-025-00901-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T23:14:52Z","timestamp":1757373292000},"score":1,"resource":{"primary":{"URL":"https:\/\/jpro.springeropen.com\/articles\/10.1186\/s41687-025-00901-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,11]]},"references-count":12,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["901"],"URL":"https:\/\/doi.org\/10.1186\/s41687-025-00901-5","relation":{},"ISSN":["2509-8020"],"issn-type":[{"value":"2509-8020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,11]]},"assertion":[{"value":"24 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All participants consented to trial participation (qualitative interviews were included in overall study consent). As previously reported [], the trial was conducted in accordance with consensus ethical principles from international guidelines including the Declaration of Helsinki, Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines, International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines, as well as applicable laws and regulations. The protocol and related documents were approved by an institutional review board\/ethics committee before study start.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MB and CK have nothing to declare. MH is an employee of Pfizer Inc and may hold stock or stock options.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"99"}}