Early detection of pancreatic cancer: Study design and analytical considerations in biomarker discovery and early phase validation studies

Lynette M Smith¹, Douglas W Mahoney², William R Bamlet², Fang Yu¹, Suyu Liu³, Michael G Goggins⁴, Sourat Darabi⁵, Shounak Majumder⁶, Qiao-Li Wang⁷, Gregory A Coté⁸, Michael J Demeure⁵, Zhen Zhang⁴, Sudhir Srivastava⁹, Akhil Chawla¹⁰, Grant Izmirlian⁹, Janet E Olson², Brian M Wolpin⁷, Jeanine M Genkinger¹¹, Kenneth S Zaret¹², Randall Brand¹³, Eugene J Koay¹⁴, Ann L Oberg¹⁵

Affiliations

¹ Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, USA.
² Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
³ Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Departments of Pathology and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Hoag Family Cancer Institute, Newport Beach, CA, USA.
⁶ Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
⁷ Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
⁸ Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
⁹ Division of Cancer Prevention, NCI, NIH, Bethesda, MD, USA.
¹⁰ Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹¹ Department of Epidemiology, Mailman School of Public Health, Columbia University, NY, NY, USA.
¹² Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹³ Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁴ Department of Gastrointestinal Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁵ Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA. Electronic address: oberg.ann@mayo.edu.

PMID: 39516175
PMCID: PMC11780679 (available on 2025-12-01)
DOI: 10.1016/j.pan.2024.10.012

Review

Early detection of pancreatic cancer: Study design and analytical considerations in biomarker discovery and early phase validation studies

Lynette M Smith et al. Pancreatology. 2024 Dec.

. 2024 Dec;24(8):1265-1279.

doi: 10.1016/j.pan.2024.10.012. Epub 2024 Oct 29.

Authors

Affiliations

¹ Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, USA.
² Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
³ Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Departments of Pathology and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Hoag Family Cancer Institute, Newport Beach, CA, USA.
⁶ Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
⁷ Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
⁸ Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
⁹ Division of Cancer Prevention, NCI, NIH, Bethesda, MD, USA.
¹⁰ Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹¹ Department of Epidemiology, Mailman School of Public Health, Columbia University, NY, NY, USA.
¹² Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹³ Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁴ Department of Gastrointestinal Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁵ Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA. Electronic address: oberg.ann@mayo.edu.

PMID: 39516175
PMCID: PMC11780679 (available on 2025-12-01)
DOI: 10.1016/j.pan.2024.10.012

Abstract

Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease that is challenging to detect at an early stage. Biomarkers are needed that can detect PDAC early in the course of disease when interventions lead to the best outcomes. We highlight study design and statistical considerations that inform pancreatic cancer early detection biomarker evaluation.

Methods: We describe experimental design strategies in this setting useful for streamlining biomarker evaluation at each Early Detection Research Network (EDRN) phase of biomarker development. We break the early EDRN phases into sub-phases, proposing objectives, study design strategies, and biomarker performance benchmarks.

Results: The goal of early detection in populations at high-risk of PDAC is described. Evaluating biomarker behavior in patients under surveillance without disease can winnow candidate biomarkers. Potential resources for biomarker validation studies are described.

Conclusions: Multisite and multidisciplinary collaboration can facilitate study design strategies in this lethal but low incidence disease and streamline the path from biomarker discovery to clinical use. Improvements in analytical and experimental design methods could help accelerate biomarker evaluation through the phases of biomarker development.

Keywords: Biomarker development; Early detection; Experimental design; Pancreatic cancer; Validation.

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References

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Early detection of pancreatic cancer: Study design and analytical considerations in biomarker discovery and early phase validation studies

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Early detection of pancreatic cancer: Study design and analytical considerations in biomarker discovery and early phase validation studies

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