Clinical Study Data Request Registered Users, Please Login


Proposal 1660

Title of the Proposed Research

Assessing the generalizability of all-cause mortality from the MOSAIC trial to older adults diagnosed with stage II and III colon cancer in SEER-Medicare

Lead Researcher

Jennifer L. Lund

Affiliation

University of North Carolina at Chapel Hill, Department of Epidemiology, Gillings School of Global Public Health

Funding Source

None

Potential Conflicts of Interest

Dr. Lund receives research funding through the UNC Oncology Clinical Translational Research Training Program (K12 CA120780).Dr. Sanoff has received research funding paid to the University of North Carolina from Bayer, Novartis, Merck, and Precision Biologics. Dr. Meyer has received honorarium from the National Cancer Institute, the American Society for Clinical Oncology, and Merck.TS receives investigator-initiated research funding and support as Principal Investigator (R01 AG023178) from the National Institute on Aging (NIA), and as Co-Investigator (R01 CA174453; R01 HL118255, R21-HD080214), National Institutes of Health (NIH). He also receives salary support as Director of the Comparative Effectiveness Research (CER) Strategic Initiative, NC TraCS Institute, UNC Clinical and Translational Science Award (UL1TR001111) and as Director of the Center for Pharmacoepidemiology (current members: GlaxoSmithKline, UCB BioSciences, Merck) and research support from pharmaceutical companies (Amgen, AstraZeneca) to the Department of Epidemiology, University of North Carolina at Chapel Hill. Dr. Stürmer does not accept personal compensation of any kind from any pharmaceutical company. He owns stock inNovartis, Roche, BASF, AstraZeneca, and Johnsen & Johnsen.

Data Sharing Agreement Date

22 February 2017

Lay Summary

Underrepresentation in RCTs may be problematic when patient subgroups experience different harms and benefits from treatment but there are too few patients within subgroups to accurately estimate treatment effects. Older adults may experience different treatment effects (compared with younger adults). Underrepresentation of older adults in cancer trials is of concern, as the median age at diagnosis is 67 and adults over 65 represent 60% of cancer diagnoses and 70% of cancer deaths. Despite this, a 2006 study found that those participating in cancer trials were generally younger and had better performance status than those that did not enroll.

As a result, substantial interest has focused on developing ways to estimate how treatment outcomes (e.g., risk of mortality) and effects (e.g., outcomes comparing one treatment to another) may differ when given to older adults treated in routine clinical practice versus the clinical trial setting – i.e., generalizability of trial findings. In the past, researchers have tried to evaluate the generalizability of trial findings of older metastatic cancer patients with solid tumors by directly comparing their outcomes to older patients treated in routine clinical practice (e.g., using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database). However, due to the small numbers of older adults enrolled in the specific RCTs, these researchers were unable to account for differences between RCT participants and cancer patients treated in community settings with respect to variables like age and sex, which might plausibly influence outcomes and treatment effects. A new statistical method to address this shortcoming involves the use of weighting techniques similar to survey sampling weights (i.e., generalizability weights).

In this study, we propose to apply these generalizability weighting methods using data from older adults (age 65-75 years) enrolled in the MOSAIC randomized controlled trial (RCT) and SEER-Medicare observational cohort (a linkage of cancer registry and Medicare enrollment and claims data). Specifically, we aim to: (1) estimate the expected effects of adjuvant chemotherapy with oxaliplatin versus 5-fluorouracil (5-FU) alone in routine care populations of older adults (age 65-75 years) diagnosed with stage II and III colon cancer and (2) assess whether we can use the MOSAIC data to predict all-cause mortality in an observational SEER-Medicare cohort of older adults.

We will conduct a cohort study using patient-level MOSAIC trial data and aggregated information from the SEER-Medicare database, providing the unique opportunity to pursue our aims. The results of this study will be used to inform policymakers about the population-level impact of adjuvant chemotherapy with oxaliplatin (versus 5-FU alone) among older adults treated in routine care settings. We will plan to present our research findings at scientific conferences and publish our results in a peer-reviewed journal.

Study Data Provided

SANOFI-EFC3313: Multicenter International Study of Oxaliplatin/ 5FU-LV in the Adjuvant Treatment of Colon Cancer

Statistical Analysis Plan

Publication Citation

The publication citation will be added after the research is published.

Summary Results

Results summary or link will be posted when available.