Factors associated with potentially serious incidental findings and with serious final diagnoses on multi-modal imaging in the UK Biobank Imaging Study: A prospective cohort study.

Background: Feedback of potentially serious incidental findings (PSIFs) to imaging research participants generates clinical assessment in most cases. Understanding the factors associated with increased risks of PSIFs and of serious final diagnoses may influence individuals' decisions to participate in imaging research and will inform the design of PSIFs protocols for future research studies. We aimed to determine whether, and to what extent, socio-demographic, lifestyle, other health-related factors and PSIFs protocol are associated with detection of both a PSIF and a final diagnosis of serious disease.
Methods and Findings: Our cohort consisted of all UK Biobank participants who underwent imaging up to December 2015 (n = 7334, median age 63, 51.9% women). Brain, cardiac and body magnetic resonance, and dual-energy x-ray absorptiometry images from the first 1000 participants were reviewed systematically by radiologists for PSIFs. Thereafter, radiographers flagged concerning images for radiologists' review. We classified final diagnoses as serious or not using data from participant surveys and clinical correspondence from GPs up to six months following imaging (either participant or GP correspondence, or both, were available for 93% of participants with PSIFs). We used binomial logistic regression models to investigate associations between age, sex, ethnicity, socio-economic deprivation, private healthcare use, alcohol intake, diet, physical activity, smoking, body mass index and morbidity, with both PSIFs and serious final diagnoses. Systematic radiologist review generated 13 times more PSIFs than radiographer flagging (179/1000 [17.9%] versus 104/6334 [1.6%]; age- and sex-adjusted OR 13.3 [95% confidence interval (CI) 10.3-17.1] p<0.001) and proportionally fewer serious final diagnoses (21/179 [11.7%]; 33/104 [31.7%]). Risks of both PSIFs and of serious final diagnoses increased with age (sex-adjusted ORs [95% CI] for oldest [67-79 years] versus youngest [44-58 years] participants for PSIFs and serious final diagnoses respectively: 1.59 [1.07-2.38] and 2.79 [0.86 to 9.0] for systematic radiologist review; 1.88 [1.14-3.09] and 2.99 [1.09-8.19] for radiographer flagging). No other factor was significantly associated with either PSIFs or serious final diagnoses. Our study is the largest so far to investigate the factors associated with PSIFs and serious final diagnoses, but despite this, we still may have missed some associations due to sparsity of these outcomes within our cohort and small numbers within some exposure categories.
Conclusion: Risks of PSIFs and serious final diagnosis are substantially influenced by PSIFs protocol and to a lesser extent by age. As only 1/5 PSIFs represent serious disease, evidence-based PSIFs protocols are paramount to minimise over-investigation of healthy research participants and diversion of limited health services away from patients in need.
Competing Interests: The authors have the following competing interests: L.M. Gibson: Member of the UK Biobank Imaging Working Group. UK Biobank Imaging; Consultant, University of Edinburgh; J. Nolan: UK Biobank Data Analyst, University of Edinburgh; E. Mathieu: Former UK Biobank Data Analyst, University of Oxford; T.J. Littlejohns: UK Biobank Epidemiologist, University of Oxford; S. Garratt: Member of the UK Biobank Imaging Working Group. Senior Project Manager of UK Biobank Imaging Study; N. Doherty: UK Biobank Senior Clinical Study Administrator; S. Petersen: Member of the UK Biobank Imaging Working Group; N.C.W. Harvey: Member of the UK Biobank Imaging Working Group; J. Sellors: UK Biobank legal counsel; N.E. Allen: Member of UK Biobank Steering Committee, UK Biobank Imaging, Enhancements, Follow-up and Outcomes and Infectious Diseases Working Groups. UK Biobank Senior Epidemiologist; J.M. Wardlaw: Advised on imaging protocols for the UK Biobank imaging study, currently analysing UK Biobank brain imaging and numeric data; C.A. Jackson: None; C.L.M. Sudlow: Member of UK Biobank Steering Committee, and UK Biobank Imaging, Enhancements, and Follow-up and Outcomes Working Groups. UK Biobank Chief Scientist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.