Early Detection Initiative: A randomized controlled trial of algorithm-based screening in patients with new onset hyperglycemia and diabetes for early detection of pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the only leading cause of cancer death without an early detection strategy. In retrospective studies, 0.5-1% of subjects >50 years of age who newly develop biochemically-defined diabetes have been diagnosed with PDAC within 3 years of meeting new onset hyperglycemia and diabetes (NOD) criteria. The Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) algorithm further risk stratifies NOD subjects based on age and changes in weight and diabetes parameters. We present the methodology for the Early Detection Initiative (EDI), a randomized controlled trial of algorithm-based screening in patients with NOD for early detection of PDAC. We hypothesize that study interventions (risk stratification with ENDPAC and imaging with Computerized Tomography (CT) scan) in NOD will identify earlier stage PDAC. EDI uses a modified Zelen's design with post-randomization consent. Eligible subjects will be identified through passive surveillance of electronic medical records and eligible study participants randomized 1:1 to the Intervention or Observation arm. The sample size is 12,500 subjects. The ENDPAC score will be calculated only in those randomized to the Intervention arm, with 50% (n = 3125) expected to have a high ENDPAC score. Consenting subjects in the high ENDPAC group will undergo CT imaging for PDAC detection and an estimate of potential harm. The effectiveness and efficacy evaluation will compare proportions of late stage PDAC between Intervention and Observation arm per randomization assignment or per protocol, respectively, with a planned interim analysis. The study is designed to improve the detection of sporadic PDAC when surgical intervention is possible.

Trial registration: ClinicalTrials.gov NCT04662879 NCT03731637.

Keywords: Cancer early detection; Modified Zelen's design; New onset diabetes mellitus; Pancreatic ductal adenocarcinoma; Post-randomization consent.

Conflict of interest statement

Declaration of interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Copyright © 2021. Published by Elsevier Inc.

Figures

Figure 1:. EDI organizational structure.

The entities that govern (top medium grey box), advise (medium grey) and execute (light grey) the EDI study are indicated. Members of the Executive, Steering, and Operations committees are representatives of the organizations indicated in their respective boxes.

Figure 2:. EDI study design.

Individuals eligible for the EDI study are identified through electronic medical record algorithms at participating sites. Randomization and ENDPAC scoring steps occur at the DMCC, with information flow back to the participating sites to identify individuals to be approached for informed consent. Individuals that agree to imaging and blood collection are included in the efficacy analysis, and individuals that agree or decline informed consent are included in the effectiveness analysis.