1. Testing for Verification Bias in Reported Malignancy Risks for Side-Branch Intraductal Papillary Mucinous Neoplasms: A Simulation Modeling Approach
- Author
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Davis T. Weaver, Alec J. Megibow, Brian M. Wolpin, Lincoln L. Berland, Anna P. Lietz, Chin Hur, Pari V. Pandharipande, Chung Yin Kong, Sarah F Mercaldo, Amy B. Knudsen, and Mary Linton B. Peters
- Subjects
Male ,medicine.medical_specialty ,genetic structures ,endocrine system diseases ,Malignancy ,Article ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Bias ,Side branch ,Pancreatic cancer ,Prevalence ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Computer Simulation ,Intraductal papillary mucinous neoplasm ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Pancreatic Neoplasms ,Adenocarcinoma, Papillary ,030220 oncology & carcinogenesis ,Verification bias ,Pancreatic cyst ,Female ,Radiology ,business ,Carcinoma, Pancreatic Ductal - Abstract
OBJECTIVE. The objective of our study was to test for the possibility that published malignancy risks for side-branch intraductal papillary mucinous neoplasms (IPMNs) are overestimates, likely due to verification bias. MATERIALS AND METHODS. We tested for possible verification bias using simulation modeling techniques. First, in age-defined hypothetical cohorts of 10 million persons, we projected the frequency of pancreatic ductal adenocarcinoma (PDAC) arising from side-branch IPMNs over 5 years using published estimates of their prevalence (4.4%) and rate of malignant transformation (1.9%). Second, we projected the total number of PDAC cases in corresponding cohorts over the same time horizon using national cancer registry data. For each cohort, we determined whether the percentage of all PDAC cases that arose from side-branch IPMNs (i.e., side-branch IPMN–associated PDAC cases) was clinically plausible using an upper limit of 10% to define plausibility, as estimated from the literature. Model assumptions and parameter uncertainty were evaluated in sensitivity analysis. RESULTS. Across all cohorts, percentages of side-branch IPMN–associated PDACs greatly exceeded 10%. In the base case (mean age = 55.7 years), 80% of PDAC cases arose from side-branch IPMNs (7877/9786). In the oldest cohort evaluated (mean age = 75 years), this estimate was 76% (14,227/18,714). In a secondary analysis, we found that if an upper limit threshold of 10% for side-branch IPMN–associated PDAC was imposed, the model-predicted rate of malignancy for side-branch IPMNs would be less than 0.24% over a 5-year time horizon, substantially lower than most literature-based estimates. CONCLUSION. Our results suggest that reported malignancy risks associated with side-branch IPMNs are likely to be overestimates and imply the presence of verification bias.
- Published
- 2019