{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:47:47Z","timestamp":1785523667719,"version":"3.56.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C18081\/A31373"],"award-info":[{"award-number":["C18081\/A31373"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C18081\/A18180"],"award-info":[{"award-number":["C18081\/A18180"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["EDDCPJT\/100018"],"award-info":[{"award-number":["EDDCPJT\/100018"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"crossref","award":["EDDAPA-2022\/100002"],"award-info":[{"award-number":["EDDAPA-2022\/100002"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosdigitalhealth.org"],"crossmark-restriction":false},"short-container-title":["PLOS Digit Health"],"abstract":"<jats:p>Early diagnosis of cancer relies on accurate assessment of cancer risk in patients presenting with symptoms, when screening is not appropriate. But recorded symptoms in cancer patients pre-diagnosis may vary between different sources of electronic health records (EHRs), either genuinely or due to differential completeness of symptom recording. To assess possible differences, we analysed primary care EHRs in the year pre-diagnosis of cancer in UK Biobank and Clinical Practice Research Datalink (CPRD) populations linked to cancer registry data. We developed harmonised phenotypes in Read v2 and CTV3 coding systems for 21 symptoms and eight blood tests relevant to cancer diagnosis. Among 22,601 CPRD and 11,594 UK Biobank cancer patients, 54% and 36%, respectively, had at least one consultation for possible cancer symptoms recorded in the year before their diagnosis. Adjusted comparisons between datasets were made using multivariable Poisson models, comparing rates of symptoms\/tests in CPRD against expected rates if cancer site-age-sex-deprivation associations were the same as in UK Biobank. UK Biobank cancer patients compared with those in CPRD had lower rates of consultation for possible cancer symptoms [RR: 0.61 (0.59\u20130.63)], and lower rates for any primary care consultation [RR: 0.86 (95%CI 0.85\u20130.87)]. Differences were larger for \u2018non-alarm\u2019 symptoms [RR: 0.54 (0.52\u20130.56)], and smaller for \u2018alarm\u2019 symptoms [RR: 0.80 (0.76\u20130.84)] and blood tests [RR: 0.93 (0.90\u20130.95)]. In the CPRD cohort, approximately representative of the UK population, half of cancer patients had recorded symptoms in the year before diagnosis. The frequency of non-specific presenting symptoms recorded in the year pre-diagnosis of cancer was substantially lower among UK Biobank participants. The degree to which results based on highly selected biobank cohorts are generalisable needs to be examined in disease-specific contexts.<\/jats:p>","DOI":"10.1371\/journal.pdig.0000383","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T21:02:20Z","timestamp":1702674140000},"page":"e0000383","update-policy":"https:\/\/doi.org\/10.1371\/journal.pdig.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Phenotypes and rates of cancer-relevant symptoms and tests in the year before cancer diagnosis in UK Biobank and CPRD Gold"],"prefix":"10.1371","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1148-1922","authenticated-orcid":true,"given":"Matthew","family":"Barclay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Renzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonis","family":"Antoniou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spiros","family":"Denaxas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Ip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Pashayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Torralbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8501-2531","authenticated-orcid":true,"given":"Juliet","family":"Usher-Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Wood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Lyratzopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"key":"pdig.0000383.ref001","unstructured":"World Health Organisation. Guide to cancer early diagnosis. 2017 [cited 27 Jan 2022]. https:\/\/apps.who.int\/iris\/handle\/10665\/254500."},{"key":"pdig.0000383.ref002","doi-asserted-by":"crossref","first-page":"S92","DOI":"10.1038\/bjc.2015.48","article-title":"Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review","volume":"112","author":"RD Neal","year":"2015","journal-title":"Br J Cancer"},{"key":"pdig.0000383.ref003","doi-asserted-by":"crossref","first-page":"e171","DOI":"10.3399\/bjgp16X683977","article-title":"Pre-referral GP consultations in patients subsequently diagnosed with rarer cancers: a study of patient-reported data","volume":"66","author":"SC Mendonca","year":"2016","journal-title":"Br J Gen Pract"},{"key":"pdig.0000383.ref004","doi-asserted-by":"crossref","first-page":"e566","DOI":"10.3399\/BJGP.2022.0268","article-title":"National Cancer Diagnosis Audits for England 2018 versus 2014: a comparative analysis","volume":"73","author":"R Swann","year":"2023","journal-title":"Br J Gen Pract"},{"key":"pdig.0000383.ref005","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1158\/1940-6207.CAPR-20-0115","article-title":"A Proposal to Improve the Early Diagnosis of Symptomatic Cancers in the United States","volume":"13","author":"EA Sarma","year":"2020","journal-title":"Cancer Prev Res"},{"key":"pdig.0000383.ref006","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1038\/bjc.2012.408","article-title":"Routes to diagnosis for cancer\u2014determining the patient journey using multiple routine data sets","volume":"107","author":"L Elliss-Brookes","year":"2012","journal-title":"Br J Cancer"},{"key":"pdig.0000383.ref007","unstructured":"National Institute for Health and Care Excellence. Suspected cancer: recognition and referral. NICE Guidel. 2015;NG12. https:\/\/www.nice.org.uk\/guidance\/ng12."},{"key":"pdig.0000383.ref008","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1038\/s41416-021-01541-4","article-title":"The impact of changing risk thresholds on the number of people in England eligible for urgent investigation for possible cancer: an observational cross-sectional study","volume":"125","author":"SF Moore","year":"2021","journal-title":"Br J Cancer"},{"key":"pdig.0000383.ref009","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1186\/1471-2407-14-636","article-title":"Cancer suspicion in general practice, urgent referral and time to diagnosis: a population-based GP survey and registry study","volume":"14","author":"H Jensen","year":"2014","journal-title":"BMC Cancer"},{"key":"pdig.0000383.ref010","doi-asserted-by":"crossref","first-page":"h3044","DOI":"10.1136\/bmj.h3044","article-title":"Suspected cancer (part 2\u2014adults): reference tables from updated NICE guidance","volume":"350","author":"W Hamilton","year":"2015","journal-title":"Bmj"},{"key":"pdig.0000383.ref011","doi-asserted-by":"crossref","first-page":"e366","DOI":"10.3399\/bjgp10X515412","article-title":"Positive predictive values of \u22655% in primary care for cancer: systematic review","volume":"60","author":"M Shapley","year":"2010","journal-title":"Br J Gen Pract"},{"key":"pdig.0000383.ref012","article-title":"Predictive value of the official cancer alarm symptoms in general practice\u2014a systematic review","volume":"62","author":"IK Huggenberger","year":"2015","journal-title":"Dan Med J"},{"key":"pdig.0000383.ref013","unstructured":"Hippisley-Cox J, Coupland C. QCancer. 2013 [cited 27 Jul 2023]. https:\/\/www.qcancer.org\/."},{"key":"pdig.0000383.ref014","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.3399\/bjgp13X660733","article-title":"Symptoms and risk factors to identify women with suspected cancer in primary care: derivation and validation of an algorithm","volume":"63","author":"J Hippisley-Cox","year":"2013","journal-title":"Br J Gen Pract"},{"key":"pdig.0000383.ref015","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.3399\/bjgp13X660724","article-title":"Symptoms and risk factors to identify men with suspected cancer in primary care: derivation and validation of an algorithm","volume":"63","author":"J Hippisley-Cox","year":"2013","journal-title":"Br J Gen Pract"},{"key":"pdig.0000383.ref016","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1136\/bmj.39171.637106.AE","article-title":"Alarm symptoms in early diagnosis of cancer in primary care: cohort study using General Practice Research Database","volume":"334","author":"R Jones","year":"2007","journal-title":"BMJ"},{"key":"pdig.0000383.ref017","doi-asserted-by":"crossref","first-page":"e1003708","DOI":"10.1371\/journal.pmed.1003708","article-title":"Predictive values for different cancers and inflammatory bowel disease of 6 common abdominal symptoms among more than 1.9 million primary care patients in the UK: A cohort study","volume":"18","author":"A Herbert","year":"2021","journal-title":"PLOS Med"},{"key":"pdig.0000383.ref018","article-title":"Red-flag signs and symptoms for earlier diagnosis of early-onset colorectal cancer","author":"CDL Fritz","year":"2023","journal-title":"JNCI J Natl Cancer Inst"},{"key":"pdig.0000383.ref019","doi-asserted-by":"crossref","DOI":"10.1093\/ije\/dyv098","article-title":"Data Resource Profile: Clinical Practice Research Datalink (CPRD)","volume":"44","author":"E Herrett","year":"2015","journal-title":"Int J Epidemiol"},{"key":"pdig.0000383.ref020","article-title":"Comparison of risk factor associations in UK Biobank against representative, general population based studies with conventional response rates: prospective cohort study and individual participant meta-analysis","volume":"368","author":"GD Batty","year":"2020","journal-title":"BMJ"},{"key":"pdig.0000383.ref021","doi-asserted-by":"crossref","first-page":"e1003931","DOI":"10.1371\/journal.pmed.1003931","article-title":"Associations between multimorbidity and adverse health outcomes in UK Biobank and the SAIL Databank: A comparison of longitudinal cohort studies","volume":"19","author":"P Hanlon","year":"2022","journal-title":"PLOS Med"},{"key":"pdig.0000383.ref022","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1093\/aje\/kwx246","article-title":"Comparison of Sociodemographic and Health-Related Characteristics of UK Biobank Participants With Those of the General Population","volume":"186","author":"A Fry","year":"2017","journal-title":"Am J Epidemiol"},{"key":"pdig.0000383.ref023","unstructured":"NHS Digital. Read Codes. 2022 [cited 12 Jan 2023]. https:\/\/digital.nhs.uk\/services\/terminology-and-classifications\/read-codes."},{"key":"pdig.0000383.ref024","doi-asserted-by":"crossref","first-page":"e1001779","DOI":"10.1371\/journal.pmed.1001779","article-title":"UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age","volume":"12","author":"C Sudlow","year":"2015","journal-title":"PLOS Med"},{"key":"pdig.0000383.ref025","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1136\/bmj.m2651","article-title":"Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study","volume":"370","author":"BD Nicholson","year":"2020","journal-title":"BMJ"},{"key":"pdig.0000383.ref026","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1038\/s41416-022-01733-6","article-title":"Risk of cancer following primary care presentation with fatigue: a population-based cohort study of a quarter of a million patients","volume":"126","author":"B White","year":"2022","journal-title":"Br J Cancer"},{"key":"pdig.0000383.ref027","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1093\/jamiaopen\/ooaa047","article-title":"A semi-supervised approach for rapidly creating clinical biomarker phenotypes in the UK Biobank using different primary care EHR and clinical terminology systems","volume":"3","author":"S Denaxas","year":"2021","journal-title":"JAMIA Open"},{"key":"pdig.0000383.ref028","unstructured":"NHS Digital. NHS TRUD. [cited 13 Oct 2022]. https:\/\/isd.digital.nhs.uk\/trud\/user\/guest\/group\/0\/home."},{"key":"pdig.0000383.ref029","article-title":"Primary care blood tests before cancer diagnosis: National Cancer Diagnosis Audit data","author":"B Cranfield","year":"2022","journal-title":"Br J Gen Pract"},{"key":"pdig.0000383.ref030","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2016-011664","article-title":"Is omission of free text records a possible source of data loss and bias in Clinical Practice Research Datalink studies? A case-control study","volume":"6","author":"SJ Price","year":"2016","journal-title":"BMJ Open"},{"key":"pdig.0000383.ref031","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S1470-2045(19)30595-9","article-title":"Presenting symptoms of cancer and stage at diagnosis: evidence from a cross-sectional, population-based study","volume":"21","author":"MM Koo","year":"2020","journal-title":"Lancet Oncol"},{"key":"pdig.0000383.ref032","doi-asserted-by":"crossref","first-page":"101805","DOI":"10.1016\/j.canep.2020.101805","article-title":"Trends in time to cancer diagnosis around the period of changing national guidance on referral of symptomatic patients: A serial cross-sectional study using UK electronic healthcare records from 2006\u201317","volume":"69","author":"S Price","year":"2020","journal-title":"Cancer Epidemiol"},{"key":"pdig.0000383.ref033","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1038\/bjc.2013.569","article-title":"Emergency presentation of cancer and short-term mortality","volume":"109","author":"S McPhail","year":"2013","journal-title":"Br J Cancer"},{"key":"pdig.0000383.ref034","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1038\/sj.bjc.6605383","article-title":"Delay in diagnosis: the experience in Denmark","volume":"101","author":"F Olesen","year":"2009","journal-title":"Br J Cancer"},{"key":"pdig.0000383.ref035","first-page":"652","article-title":"Do presenting symptoms, use of pre-diagnostic endoscopy and risk of emergency cancer diagnosis vary by comorbidity burden and type in patients with colorectal cancer?","volume":"126","author":"SB Majano","year":"2021","journal-title":"Br J Cancer 2021 1264"},{"key":"pdig.0000383.ref036","doi-asserted-by":"crossref","first-page":"e806","DOI":"10.3399\/BJGP.2021.0301","article-title":"Clinical coding of long COVID in English primary care: a federated analysis of 58 million patient records in situ using OpenSAFELY","volume":"71","author":"AJ Walker","year":"2021","journal-title":"Br J Gen Pract"},{"key":"pdig.0000383.ref037","doi-asserted-by":"crossref","first-page":"S92","DOI":"10.7326\/M19-0879","article-title":"A Sociotechnical Framework for Safety-Related Electronic Health Record Research Reporting: The SAFER Reporting Framework","volume":"172","author":"H Singh","year":"2020","journal-title":"Ann Intern Med"},{"key":"pdig.0000383.ref038","doi-asserted-by":"crossref","first-page":"i5515","DOI":"10.1136\/bmj.i5515","article-title":"Can safety-netting improve cancer detection in patients with vague symptoms?","author":"BD Nicholson","year":"2016","journal-title":"BMJ"},{"key":"pdig.0000383.ref039","article-title":"Progress and priorities in reducing the time to cancer diagnosis","author":"BD Nicholson","year":"2022","journal-title":"Br J Cancer"},{"key":"pdig.0000383.ref040","doi-asserted-by":"crossref","first-page":"e2015437","DOI":"10.1001\/jamanetworkopen.2020.15437","article-title":"Association of Self-reported Presenting Symptoms With Timeliness of Help-Seeking Among Adolescents and Young Adults With Cancer in the BRIGHTLIGHT Study","volume":"3","author":"MM Koo","year":"2020","journal-title":"JAMA Netw Open"}],"container-title":["PLOS Digital Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pdig.0000383","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T21:02:48Z","timestamp":1702674168000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pdig.0000383"}},"subtitle":[],"editor":[{"given":"Benjamin P.","family":"Geisler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,12,15]]},"references-count":40,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pdig.0000383","relation":{},"ISSN":["2767-3170"],"issn-type":[{"value":"2767-3170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,15]]}}}