How Do Differences in Inclusion Criteria in Emulation Studies Impact the Outcome of Overall Survival? Emulating an Ovarian Cancer Clinical Trial in Norwegian Registries

OBJECTIVES: Our study has used a published protocol for a novel second line treatment of ovarian cancer and have studied how choices regarding inclusion criteria affects the overall survival in a RWD population.

METHODS: This study is a retrospective registry-based study of patients with advanced (FIGO stage 3-4) high-grade serous ovarian cancer in Norway. Patients with ovarian cancer in 2015-2021 were included in the study population. Data came from the Cancer Registry of Norway and the Norwegian Patient Registry containing hospital data. We emulated the inclusion and exclusion criteria used in a 2nd line clinical trial (CT) on a new therapeutic cancer vaccine using registry data. A key inclusion criterion was that the patients should have used platinum drugs in combination with taxanes in 5 or 6 courses during first line treatment. We emulated different ways of relaxing this assumption. We allowed platinum to be used alone or in combination with another chemotherapy drug and we allowed for varying ranges of treatment courses given (any, 3-7, 4-7 as well as 5-6). The proportion who died within one year of end of treatment was calculated for each of these combinations.

RESULTS: There were 3350 ovarian cancer patients in Norway in 2015-2021. In the widest group, any use of platinum in any number of courses, 542 patients were included and 5.2 % died within one year. In the strictest group, platinum+taxanes in 5 or 6 courses, 181 patients were included and 2.2 %.

CONCLUSIONS: Different implementations of CT inclusion criteria related to first line treatment in ovarian cancer led to varying number of patients included and differences in one year survival. Our findings highlight the importance of doing sensitivity analyses for crucial choices in emulation studies to show how these choices impact the size of the study population and clinical endpoints.