Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC): External validation using English sentinel network

Claire A Price; Hugh Claridge; Simon de Lusignan; Natalia Khalaf; Freda Mold; Nadia A. S. Smith; Martyn Winn; Agnieszka Lemanska

doi:10.3399/BJGP.2024.0253

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Beyond risk stratification: defining the diagnostic pathway after a positive ENDPAC score
Muhammad Mukarrum Saleh and Mehak Fatima

Published on: 24 August 2026

Published on: (24 August 2026)
Page navigation anchor for Beyond risk stratification: defining the diagnostic pathway after a positive ENDPAC score
Beyond risk stratification: defining the diagnostic pathway after a positive ENDPAC score
Muhammad Mukarrum Saleh, General Physician, Sharifa Bibi Memorial Hospital
Other Contributors:
Mehak Fatima, General Physician, Sharifa Bibi Memorial Hospital
Price and colleagues provide an important external validation of the Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) score in UK primary care.¹ In more than 70,000 adults aged ≥50 years with new-onset diabetes, an ENDPAC score ≥3 identified 27.6% as high risk, with 62.6% sensitivity and 72.3% specificity. However, the positive predictive value was only 0.6%, despite a negative predictive value of 99.9%.¹ These findings raise an important question for clinical implementation: what should happen after a patient is classified as high risk?

The low positive predictive value has practical consequences. If ENDPAC were applied broadly, a substantial proportion of patients with new-onset diabetes could be flagged for further assessment while the vast majority would not ultimately have pancreatic cancer. Immediate cross-sectional imaging for every positive score could therefore increase imaging burden, incidental findings, patient anxiety, and downstream investigations without clearly establishing clinical benefit.

The authors appropriately position ENDPAC as the first stage of a sequential diagnostic pathway rather than a stand-alone screening test.¹ The critical next step is therefore to define and validate that second stage. Additional clinical features, biomarkers, or targeted imaging may further enrich risk before referral for more invasive or resource-intensive investigations. This may be particularly important because we...
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Price and colleagues provide an important external validation of the Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) score in UK primary care.¹ In more than 70,000 adults aged ≥50 years with new-onset diabetes, an ENDPAC score ≥3 identified 27.6% as high risk, with 62.6% sensitivity and 72.3% specificity. However, the positive predictive value was only 0.6%, despite a negative predictive value of 99.9%.¹ These findings raise an important question for clinical implementation: what should happen after a patient is classified as high risk?

The low positive predictive value has practical consequences. If ENDPAC were applied broadly, a substantial proportion of patients with new-onset diabetes could be flagged for further assessment while the vast majority would not ultimately have pancreatic cancer. Immediate cross-sectional imaging for every positive score could therefore increase imaging burden, incidental findings, patient anxiety, and downstream investigations without clearly establishing clinical benefit.

The authors appropriately position ENDPAC as the first stage of a sequential diagnostic pathway rather than a stand-alone screening test.¹ The critical next step is therefore to define and validate that second stage. Additional clinical features, biomarkers, or targeted imaging may further enrich risk before referral for more invasive or resource-intensive investigations. This may be particularly important because weight loss and worsening glycaemia—the core features contributing to ENDPAC—can also accompany several non-pancreatic conditions.

Future prospective studies should consequently evaluate ENDPAC not only by discrimination statistics, but by its performance within a complete diagnostic pathway. Outcomes should include cancers detected at a resectable stage, number of imaging studies required per cancer detected, false-positive investigations, incidental findings, time to diagnosis, and cost-effectiveness.

ENDPAC offers an attractive opportunity to identify pancreatic cancer earlier through routinely available primary-care data. Its clinical value, however, will ultimately depend less on generating a high-risk flag than on establishing a safe, efficient, and evidence-based pathway for what follows that flag.

Reference

1. Price CA, Claridge H, de Lusignan S, Khalaf N, Mold F, Smith NAS, Winn M, Lemanska A. Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC): external validation using English sentinel network. Br J Gen Pract. 2026. doi:10.3399/BJGP.2024.0253.

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Competing Interests: None declared.