DOI: 10.25934/pr00007785
title: Using Norwegian real world data to emulate and reproduce results from oncology clinical trials

description: Cancer clinical trials can be slow and costly, often produce results with limited external validity, and are difficult for patients to participate in. Recent technological advances and a gradually more dynamic policy landscape in the United States and Europe have created a fertile ground for the use of real-world data (RWD) to improve current methods of clinical evidence generation. In recent years, many new efforts have emerged that try to maximize the value of data collected during clinical trials (RCT). Secondary analyses of individual trials or aggregated meta-analyses of multiple comparable trials can generate additional clinical discoveries or lead to novel hypotheses. Modern trials include patient consent to generate de-identified patient-level datasets at the trial completion and making this data available for secondary research use. Thus, easier access to RCT data, in platforms like Vivli, can be used for comparison with RWD generated from ordinary clinical practice.

The company's goal is to develop population-based external control arms (ECA) that reflect standard of care and can be used to interpret and contextualize the results from phase II-III oncology trials and potentially, at a later stage, being able to serve as a full external control arm for single-arm oncology trials. As a first step towards this goal, and the basis for this concrete data request proposal, Vivli RCT data will be used as a proof-of-concept to emulate the trial population in completed lung cancer RCTs with Norwegian RWD and investigate if the outcomes in the RCTs can be reproduced using Norwegian RWD. If successful, this proof-of-concept study will provide evidence that Norwegian RWD is fit-for-purpose and can produce trustworthy results for regulatory decision-making.

Included in this Vivli proposal are six completed lung cancer trials from Roche/Genentech. Five studies with PD-L1 immunotherapy in both small-cell and non-small cell lung cancer (PD-L1 Immunotherapy is a therapy that boosts your immune system to help it recognize and fight cancer cells that contain high levels of the protein PD-L1, which is a protein that normally helps keep immune cells from attacking nonharmful cells in the body) and one targeted therapy trial on NSCLC ALK positive patients [ALK-positive lung cancer is a type of non-small cell lung cancer (NSCLC) in which the cancer cells have mutations in the anaplastic lymphoma kinase (ALK) gene]. The research will emulate and reproduce both the standard-of-care (placebo) arm and the experimental arm in these studies. For emulation we will use nation-wide mandatory registries in Norway, including the Cancer Registry of Norway, the Hospital registry, the Drug prescription database and the Cause of death registry. For replication we will examine different endpoints, focusing first on overall and cancer-specific survival, and in later steps also progression free survival, time to treatment discontinuation and other efficacy outcomes. Statistical balancing of baseline characteristics via propensity scores will be applied as the preferred method for emulation and the Cox proportional hazard model will be used to compare event rates between groups.

This research is funded by a grant from the Research Council of Norway (grant no. 327887)