Figure 1 (A) Incidence and timing of common

presenting symptoms in 100 matched controls 1 year before a normally random consultation. (B) Incidence and timing of common presenting symptoms in 100 randomly selected patients with pancreatic cancer in the year prior … The control sample contained randomly selected patients without a diagnosis of PDAC or BTC. Stratified sampling within the same GP practices from where patients with a cancer diagnosis were identified was used to ensure control patients had similar characteristics to those with a cancer diagnosis in terms of age, sex, practice and equivalent year of consultation (control group) to year of diagnosis (cancer group). Up to six control patients were selected per patient with a cancer diagnosis. Outcomes Alarm symptoms and laboratory tests were selected based on clinical knowledge

and the existing literature.6 7 22–31 To ensure that no symptoms had been missed by the literature review, Read codes for 10% of patients with PDAC (n=296) were reviewed in their entirety to identify any additional common or biologically plausible symptoms (table 1). For each individual symptom, frequency, median onset and average number of presentations were recorded. Symptoms were grouped according to pathological aetiology and onset (greater or less than 6 months prior to diagnosis). All symptoms with a frequency of greater than 5% were identified as potential alarm symptoms and included in the subsequent case–control study (table 1). Table 1 Frequency and onset of common and biologically plausible symptoms in a 10% cohort of patients with pancreatic ductal adenocarcinoma Laboratory tests were restricted to routinely performed tests to ensure adequate numbers were recorded for the control population and included haemoglobin and liver function tests: serum bilirubin, alkaline

phosphatase (ALP), alanine aminotransferase (ALT). Covariates Age, gender, time period and Townsend score, smoking status and BMI were selected as potential confounders. Where multiple measures of BMI and smoking status were recorded, the earliest Cilengitide record in the 2-year time frame from the index date was selected. Deprivation was examined using quintiles of Townsend score from ‘one’ (least deprived) to ‘five’ (most deprived). The Townsend score is a combined measure of owner occupation, car ownership, overcrowding and unemployment based on a patient’s postcode and linkage to population census data for 2001 for approximately 150 households in that postal area. Statistical analyses Multivariable logistic regression was used to estimate the ORs for symptoms in the 2 years prior to PDAC or BTC diagnosis versus the 2 years prior to the index date in patients with and without cancer. Linear regression was used to estimate adjusted mean differences in clinical measures between patients with and without cancer.