Multi-omics investigation on the prognostic and predictive factors in metastatic breast cancer using data from Phase III ribociclib clinical trials: A statistical and machine learning analysis plan

In 2020, Novartis Pharmaceuticals Corporation and the U.S. Food and Drug Administration (FDA) started a 4-year scientific collaboration to find novel radiogenomics-based prognostic and predictive factors for HR+/HER2-metastatic breast cancer under a Research Collaboration Agreement. This manuscript aims to detail the guiding principles and methodology for this study. We include a discussion of internal and external clinical, genomics, imaging datasets, data processing workflows, and machine learning model development strategies. We also prospectively define our success criteria to ensure robust scientific outputs. Disclosure This publication reflects the views of the authors and should not be construed to represent FDA’s views or policies. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT01958021, [NCT02422615][1], [NCT02278120][2] ### Clinical Protocols ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics Committee from Novartis gave ethical approval for the MONALEESA trials I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data for the MONALEESA studies are available at clinicaltrials.gov and Kisqali USPI. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02422615&atom=%2Fmedrxiv%2Fearly%2F2023%2F08%2F31%2F2023.08.30.23294367.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02278120&atom=%2Fmedrxiv%2Fearly%2F2023%2F08%2F31%2F2023.08.30.23294367.atom