Oct 2020: EDM Data Dictionary and Release Notesastrazeneca_commercial

Flatiron R Packages

We’ve released a new version (0.2.0) of our cohort selection R package, rwdplyr, that includes:

• Updates to the summarize_patient_biomarker_status to align with the recent guidance released in the related tutorial, including new select methods and arguments
• Warnings in derive_age_at_event if a negative age is calculated
• Helper functions count_rows and count_patients for sizing remote and local tables
• New summarize_and_apply_gap_rule to calculate patient activity and filter patients in a single function call
• More detail can be found in the release notes in the repository

If you do not have access to rwdplyr and would like to, please submit the form on this webpage and Flatiron will follow up with further information.

COVID Updates

We’ve updated the Impact of COVID-19 on Flatiron Datasets section of the Knowledge Center for August 2020, including an update to our monthly observations of trends seen in Flatiron EDMs (incorporating data through July 2020), as well as a short explanation of ICD codes relating to COVID-19 in Flatiron EDMs.

Ovarian Cancer

Flatiron’s LineOfTherapy (LOT) table is created through code-based algorithms that apply disease-specific clinical rules to each patient’s treatment data. We are currently in the process of completing a series of LOT code refactoring efforts to:

1. Improve the functionality of our code base to ensure that future LOT updates are more efficient to potentially implement
2. Ensure that our LOT rules, such as maintenance line rules, line start date triggers, and line name conventions, are functioning appropriately as documented on the Knowledge Center for all patient IDs and LOTs
3. Implement a limited number of rule changes (in select disease models) that are essential for code health and consistency across disease models

The four Ovarian LOT rule changes are summarized below:

1. We added a number of additional requirements (in bold) related to maintenance lines (LOT rule #5):
   1. Bevacizumab must have been given in combination with other drugs for at least 30 days and continued for at least 21 days after all non-maintenance drugs are dropped
   2. Olaparib, rucaparib, and/or niraparib must be used in combination with other drugs for at least 30 days and continued for at least 28 days after all non-maintenance drugs are dropped
   3. Paclitaxel and gemcitabine must be used in combination with other drugs for at least 30 days and continued for at least 28 days after all non-maintenance drugs are dropped
      1. Bevacizumab in combination with either a PARP inhibitor, paclitaxel, or gemcitabine must be started within 90 days of previous treatment and continued for at least 28 days after all non-maintenance drugs are dropped
2. Added the rule that substitution of olaparib, rucaparib, or niraparib as maintenance therapy does not advance the LOT, and the line will be named according to all drugs used within the maintenance line. Previously, changing from one PARP inhibitor to another would end the maintenance line. (LOT rule #7)
3. Added the rule that substitution of a biosimilar or vice versa does not advance the line for the following biosimilars. The line will be named according to the drug used for the longest duration within a line (LOT rule #7)
   1. Bevacizumab, bevacizumab-awwb, bevacizumab-bvzr
   2. Rituximab, rituximab-abbs
   3. Trastuzumab, trastuzumab-anns, trastuzumab-dkst, trastuzumab-pkrb

Added the rule that lines with the following substitutions will be named according to the drug given for the longest within the line:

1. Cisplatin for carboplatin or vice-versa
2. Paclitaxel, nab-paclitaxel, or docetaxel

Impact for Ovarian EDM:

16.0% of patient records experienced a change in number of lines and/or a change in line startdate, enddate, or linename, as a result of code refactoring and rule changes.

Most observable differences include:

• Changes to maintenance start date due to updates to code logic to ensure that start of maintenance therapy aligns with the first eligible drug episode (~16% of patients have a maintenance line and 40% of maintenance lines had a change in startdate)
• Changes to linenames for (3% of lines) due in part to:
  • New rules for line naming when equivalent drugs are substituted within a line and refactoring efforts to ensure that, in these situations, the drug that was used for the longest duration within the line is used in the linename
  • New requirements for maintenance lines described in rule changes above

While our teams found no statistically significant difference when comparing overall survival between the prior LOT and updated LOT, indexed to the start of first, second, or third line, the impact of these changes may vary widely by use case. Please reach out to your dedicated Flatiron Life Sciences team with your use case for guidance.

Small Cell Lung Cancer

As part of Flatiron’s broader efforts to refactor our LineofTherapy rules, we have added a new rule in the SCLC EDM, specifying that substitution of the following biosimilars will not advance line numbers:

• Bevacizumab, bevacizumab-awwb, bevacizumab-bvzr
• Rituximab, rituximab-abbs
• Trastuzumab, trastuzumab-anns, trastuzumab-dkst, trastuzumab-pkrb

  Disease	Total EDM Patients (October 2020)	Academic Patients (October 2020)
  Chronic Lymphocytic Leukemia	12236	895
  Advanced Non-Small Cell Lung Cancer	64553	6104
  Ovarian Cancer	7476	1001
  Advanced Melanoma	10418	1760
  Small-Cell Lung Cancer	7350	506
  Advanced Endometrial Cancer	4297	943
  Metastatic Breast Cancer	23485	1732