Background Simple blood tests can play an important role in identifying patients for cancer investigation. The current evidence base is limited almost entirely to tests used in isolation. However, recent evidence suggests combining multiple types of blood tests and investigating trends in blood test results over time could be more useful to select patients for further cancer investigation. Such trends could increase cancer yield and reduce unnecessary referrals. We aim to explore whether trends in blood test results are more useful than symptoms or single blood test results in selecting primary care patients for cancer investigation. We aim to develop clinical prediction models that incorporate trends in blood tests to identify risk of cancer. Methods Primary care electronic health records data from the English Clinical Practice Research Datalink Aurum primary care database will be accessed and linked to cancer registrations and secondary care datasets. Using a cohort study design, we will describe patterns in blood testing (Aim 1) and explore associations between covariates and trends in blood tests with cancer using mixed-effects, Cox, and joint models (Aim 2). To build the predictive models for risk of cancer, we will use multivariate joint modelling and machine-learning, incorporating simultaneous trends in multiple blood tests, together with other covariates (Aim 3). Model performance will be assessed using various performance measures, including c-statistic and calibration plots. Discussion These models will form decision rules to help general practitioners find patients who need referral for further investigation of cancer. This could increase cancer yield, reduce unnecessary referrals, and give more patients the opportunity for treatment and improved outcomes.

The authors have declared no competing interest.

Brian D. Nicholson is the Principal Investigator for this study, funded by a Cancer Research UK Population Research Committee Postdoctoral Fellowship (RCCPDF\100005).

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The eRAP committee of the Clinical Practice Research Datalink (on behalf of the Health Research Authority) gave ethical approval for this work.

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