Our Research

Background and Objectives 

For over two decades, recombinant human granulocyte colony-stimulating factors (G-CSFs) have been used to treat and prevent chemotherapy-induced neutropenia. Currently two biosimilar products to reference filgrastim (filgrastim-sndz, filgrastim-aafi), and two biosimilars to reference pegfilgrastim (pegfilgrastim-jmdb, pegfilgrastim-cbqv) are approved in the US with adequate utilization through mid-2020. G-CSFs, including filgrastim and pegfilgrastim originator and biosimilar products, are used as primary prophylaxis of febrile neutropenia (FN), a potentially fatal side effect associated with myelosuppressive chemotherapy. BBCIC is conducting a descriptive and exploratory comparative safety and effectiveness study of G-CSF use in breast, lung, colon, ovarian, pancreatic, testicular, cervical, uterine, or non-Hodgkin lymphoma cancers. 

Current Status 

Update – October 2023: This study is complete and the study report and final manuscripts are in preparation.

To date, one manuscript has been accepted for publication:

Lockhart CM, McDermott CL, Mendelsohn A, Marshall J, McBride A, Yee G, Li S, Jamal-Allial A, Djibo DA, Vazquez-Benitez G, DeFor TA, Pawloski PA. Identification of cancer chemotherapy regimens and patient cohorts in administrative claims: challenges, opportunities, and a proposed algorithm. Journal of Medical Economics, 2023;26(1):403-410, DOI: 10.1080/13696998.2023.2187196.

We presented four posters related to this work in 2022:

Lockhart CM, McDermott CL, Vazquez Benitez G, DeFor T, Mendelsohn A, Marshall J, McBride A, Moyneur E, Pawloski PA; on behalf of the BBCIC G-CSF Comparative Effectiveness Research Team. Challenges to Identification of Cancer Chemotherapy Regimens and Patient Cohorts in Administrative Claims. Poster presentation at ISPOR 2022, National Harbor, MD, May 15-18, 2022.

Pawloski PA, Lockhart CM, Vazquez-Benitez G, DeFor TA, Mendelsohn AB, Marshall J, Moyneur E, McDermott CL, on behalf of the BBCIC G-CSF Comparative Effectiveness Research Team. An exploratory comparative effectiveness analysis of febrile neutropenia incidence among patients with cancer receiving granulocyte colony stimulating factors. Poster presentation at ASCO Quality Care Symposium, Chicago, IL, September 30-October 1, 2022.

Pawloski PA, McDermott CL, Vazquez-Benitez G, DeFor TA, Mendelsohn AB, Marshall J, Moyneur E, Bosco J, Bottorff M, Djibo DA, Engelhardt E, Jamal-Allial A, Kline A, Li E, Li S, Lin N, McBride A, McMahill-Walraven C, Yee G, Lockhart CM. Changes in G-CSF biosimilar and originator use over time. Poster presentation at ACCP 2022, San Francisco, CA, October 16-19, 2022.

Pawloski PA, McDermott CL, Vazquez Benitez G, DeFor TA, Mendelsohn A, Marshall J, Moyneur E, Lockhart CM, on behalf of the G-CSF Comparative Effectiveness Research Team. A population-based analysis of prophylactic G-CSF biosimilar and originator administration over time among patients diagnosed with breast cancer. Poster presentation at San Antonio Breast Cancer Symposium, San Antonio, TX, December 6-10, 2022.

Research Team 

• Co-Principal Investigator: Pamala A. Pawloski, PharmD, BCOP, FCCP, Senior Research Investigator, HealthPartners Institute 
• Co-Principal Investigator: Cara McDermott, PharmD, PhD, Research Consultant, BBCIC 
• Jaclyn Bosco, PhD, MPH, Senior Director, Global Head, Epidemiology & Outcomes Research, IQVIA 
• Maria Bottorff, Oncology Pharmacist, Loyola University Medical Center
• Terese A. Defor, Senior Manager, Research Informatics, HealthPartners Institute for Education and Research 
• Audrey Djibo, PhD, Lead Epidemiologist, CVS Health
• Ed Li, PharmD, MPH, BCOP, Associate Director, HEOR & RWE, Sandoz 
• Sam Li, PhD, Assistant Professor, Health Outcomes and Policy Research, University of Tennessee 
• Nancy Lin, ScD, Principal, Epidemiology and Drug Safety, Real World Evidence Solutions, IQVIA 
• James Marshall, Senior Research Associate, Harvard Pilgrim Health Care Institute
• Ali McBride, PharmD, MS, BCOP, FAzPA, FASHP, Clinical Coordinator Hematology/Oncology, University of Arizona 
• Aaron B. Mendelsohn, PhD, MPH, Senior Health Services Researcher, Department of Population Medicine, Harvard Pilgrim Health Care Institute 
• Cheryl Walraven, MSW, PhD, Executive Director, CVS Health
• Gary C. Yee, PharmD, FCCP, BCOP, Professor and Associate Dean, College of Pharmacy, University of Nebraska College 
• BBCIC Staff: Cate Lockhart, PharmD, PhD, Executive Director, BBCIC

Documents 

• Study Protocol (coming soon)

Background and Objectives 

To provide a landscape of patient characteristics and treatment patterns using biologic products of interest, including biosimilars, BBCIC conducts periodic analyses of utilization in our distributed research network. This initiative provides informative data on trends over time in a large patient population in the BBCIC network and is essential for planning future descriptive and comparative analyses. 

Avastin® (bevacizumab), an anti-angiogenic therapy, was licensed in the United States (US) in February 2004 for treatment of metastatic colorectal cancer in combination with intravenous fluororacil-based chemotherapy in individuals aged 18 years and older. Since 2004, Avastin has been approved for other conditions such as advanced lung, kidney, breast and brain cancers. In 2011, the approval of the metastatic breast cancer indication for Avastin was withdrawn. Avastin is indicated for continuous use throughout the period of chemotherapy, delivered intravenously every two weeks. In September of 2017, the first biosimilar for Avastin, Mvasi® (bevacizumab-awwb) was approved for the treatment of adult patients with certain colorectal, lung, brain, kidney and cervical cancers. A second biosimilar, Zirabev® (bevacizumab-bvzr) was approved in June 2019 for the treatment of metastatic colorectal cancer, recurrent or metastatic nonsquamous non-small cell lung cancer (NSCLC), recurrent glioblastoma, metastatic renal cell carcinoma, and persistent, recurrent, or metastatic cervical cancer. Bevacizumab products are used off-label for ophthalmologic conditions such as neovascular age-related macular degeneration, macular edema, and retinal vein occlusion.  

Current Status 

Update – October 2023: This study is complete and a manuscript is in preparation.

Research Team 

• Principal Investigator: Jenice Ko, Department of Population Medicine, Harvard Pilgrim Health Care Institute 
• Kimberly Daniels, PhD, MS, Researcher, Safety & Epidemiology, HealthCore
• Ainhoa Gomez-Lumbreras, MD, PhD, Post Doc Fellow, Department of Pharmacotherapy, Skaggs College of Pharmacy, University of Utah
• Cara McDermott, PharmD, PhD, Research Consultant, BBCIC
• Aaron B. Mendelsohn, PhD, MPH, Senior Health Services Researcher, Department of Population Medicine, Harvard Pilgrim Health Care Institute
• Pamala A. Pawloski, PharmD, BCOP, FCCP, Senior Research Investigator, HealthPartners Institute
• Gary C. Yee, PharmD, FCCP, BCOP, Professor and Associate Dean, College of Pharmacy, University of Nebraska College
• BBCIC Staff: Cate Lockhart, PharmD, PhD, Executive Director, BBCIC

Documents 

• Study Protocol (coming soon)

Background and Objectives 

Switching between different originator biologics, biosimilars and originator biologics, or different medication classes, is a challenge in post-marketing comparative effectiveness research (CER) studies as it introduces potential bias and complicates the study design. The Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) previously convened a Workgroup (Switching Methods Workgroup) charged with developing best practice recommendations for the conduct of innovator and biosimilar switching studies, including treating switching/sequencing as a covariate/confounder in CER studies, and describing valid approaches to compare outcomes between switchers and non-switchers.  Building upon this Workgroup’s recommendations, study designs and methods for handling switching as a confounder or covariate will be tested in the BBCIC Distributed Research Network (DRN) with anti-inflammatory agents being used to treat RA as a test case.  As a next step, we will conduct a descriptive analysis to better understand anti-inflammatory medication treatment patterns in patients with RA.   

This study will provide foundational data regarding patterns of care for anti-inflammatory medications among commercially insured adults in the United States with a recorded diagnosis of RA.  Specifically, this study will involve an examination of patterns of medication use by demographics and clinical comorbidities, plus switching between and within medication classes. Switching events of interest will be dependent upon the clinical significance of a given switch, as well as the frequency of use of the individual products involved.  The findings from this study will be used to inform the design and conduct of inferential analyses of medications in this therapeutic area, e.g., to examine the comparative effectiveness and safety across products for which switching may have occurred; to compare outcomes among patients treated according to clinical guidelines versus those treated based upon other regimens.     

The objective of this study is to examine treatment patterns for anti-inflammatory agents, namely targeted immunomodulators (i.e., biologics and Janus Kinase [JAK] inhibitors), used in the treatment of RA, with particular focus on switching of medications. 

Current Status 

Update – October 2023: Initial data analysis is complete. A number of additional analyses are in preparation. Data have been collected and analysis is underway. Two abstracts have been accepted for poster presentation at AMCP Nexus 2023 (October 16-19, Orlando, FL) and ISPOR Europe 2023 (November 12-15, Copenhagen, Denmark):

Djeneba Audrey Djibo, Erick Moyneur, Jonathan P. DeShazo, Jennifer L. Pigoga, Cheryl N. McMahill-Walraven, Aaron B. Mendelsohn, Catherine M. Lockhart. Describing medication switching patterns in adults with rheumatoid arthritis from 2016-2022: A real-world data study. Submitted to AMCP Nexus 2023, Orlando, FL, October 16-19, 2023.

Djeneba Audrey Djibo, Erick Moyneur, Jonathan P. DeShazo, Jennifer L. Pigoga, Cheryl N. McMahill-Walraven, Aaron B. Mendelsohn, Catherine M. Lockhart. Describing Medication Switching Patterns Among Adults With Rheumatoid Arthritis From 2016-2022 Using Real-World Data. Submitted to ISPOR Europe 2023, Cophenhagen, Denmark, November 12-15, 2023.

Research Team 

• Principal Investigator: Cheryl Walraven, MSW, PhD, Executive Director, CVS Health
• Jaclyn Bosco, PhD, MPH, Senior Director, Global Head, Epidemiology & Outcomes Research, IQVIA
• Anna Chen, Associate Director, HEOR/RWE, Sandoz
• Hillel Cohen, PhD, Executive Director, Scientific Affairs, Sandoz
• Johnathan Deshazo, PhD, MPH, Lead Decision Scientist: Epidemiology, Safety, Surveillance & Collaboration, CVS Health
• Audrey Djibo, PhD, Lead Epidemiologist, CVS Health Clinical Trial Services
• Anna Hyde, Vice President of Advocacy and Access, Arthritis Foundation
• Ran Jin, Observational Research Senior Manager, Amgen
• Ed Li, PharmD, MPH, BCOP, Associate Director, HEOR & RWE, Sandoz
• Nancy Lin, ScD, Principal, Epidemiology and Drug Safety, Real World Evidence Solutions, IQVIA
• Junjie Ma, Observational Research Senior Manager, Amgen
• James Marshall, Senior Research Associate, Harvard Pilgrim Health Care Institute
• Dottie McCabe, PhD, FCP, Executive Director, BI
• Aaron B. Mendelsohn, PhD, MPH, Senior Health Services Researcher, Department of Population Medicine, Harvard Pilgrim Health Care Institute
• Erick Moyneur, Managing Partner – Economist, StatLog Inc.
• BBCIC Staff: Cate Lockhart, PharmD, PhD, Executive Director, BBCIC 

Documents 

• Study Protocol

Background and Objectives 

As the COVID-19 pandemic has disrupted nearly every aspect of life since early 2020, as researchers it is important to understand the effect of the pandemic on treatment patterns for other chronic and acute conditions. This is important both to understand the impact of COVID-19 on non-COVID related health concerns and outcomes, but also to understand how to interpret results from longitudinal databases that span the pandemic timeline. 

The purpose of this study is to describe utilization and treatment patterns, along with selected clinical outcomes and adverse events, of patients diagnosed with inflammatory bowel disease (Crohn’s disease or ulcerative colitis) as a test case to evaluate the influence of the COVID-19 pandemic on trends in treatment and outcomes in the United States. This work is essential in continuing our research to include data more recent than mid-2020 (or the beginning of the pandemic in the US). 

We have engaged in a collaborative partnership with a group from Italy (the VALORE Project) to align our protocols and provide the opportunity to both compare the COVID experience in Italy vs the US, but also to compare our data and approaches to observational research with the goal of future collaborations. 

Current Status 

Update – October 2023: Initial data describing three study cohorts have been collected and analysis is underway. Preliminary results were presented to BBCIC Participants at our Annual Workshop in June.  

Research Team 

• Principal Investigator: Cate Lockhart, PharmD, PhD, Executive Director, BBCIC 
• Analyst: Scott Myers, Senior Research Scientist, PearlDiver Technologies™
• Rebekah Angove, PhD, Executive Vice President, Research and Evaluation, Patient Advocate Foundation
• Jaclyn Bosco, PhD, MPH, Senior Director, Global Head, Epidemiology & Outcomes Research, IQVIA
• Audrey Djibo, PhD, Lead Epidemiologist, CVS Health
• Ran Jin, Observational Research Senior Manager, Amgen
• Nancy Lin, ScD, Principal, Epidemiology and Drug Safety, Real World Evidence Solutions, IQVIA

Documents 

• Study Protocol (coming soon)

Background and Objectives 

To provide a landscape of patient characteristics and treatment patterns using biologic products of interest, including biosimilars, BBCIC conducts periodic analyses of utilization in our distributed research network. This initiative provides informative data on trends over time in a large patient population in the BBCIC network and is essential for planning future descriptive and comparative analyses. 

There are five trastuzumab biosimilar products currently available in the United States. This study was conducted to assess utilization and characteristics of patients treated with HER2-inhibitor products, including all five biosimilar trastuzumab products, in the BBCIC data network. This analysis is intended to follow-up the preliminary analysis completed in early 2021 to capture complete data at least through mid-2020. 

Current Status 

Update – October 2023: This study is complete and a manuscript is in preparation. An abstract was presented at ICPE 2023 (August 23-27, Halifax, Nova Scotia, Canada): 

Xiaodan (Melody) Mai, Aaron B. Mendelsohn, James Marshall, Nancy Lin, Cara L. McDermott, Pamala A. Pawloski, Aziza Jamal-Allial, Kimberly Daniels, Cheryl N McMahill-Walraven, Djeneba Audrey Djibo, Catherine M. Lockhart. Utilization and patient characteristics for the trastuzumab reference and biosimilars, and other HER2 inhibitors in the United States. Poster presentation at ICPE 2023, Halifax, Nova Scotia, Canada, August 23-27, 2023.

Research Team 

• Principal Investigator: Xiaodan (Melody) Mai, PhD, MBBS, Therapeutics Research & Infectious Disease Epidemiology (TIDE), Department of Population Medicine, Harvard Pilgrim Health Care Institute 
• Aziza Jamal-Allial, PhD, MS, Research Scientist of Epidemiology, Carelon Research
• Nancy Lin, ScD, Principal, Epidemiology and Drug Safety, Real World Evidence Solutions, IQVIA
• James Marshall, Senior Research Associate, Harvard Pilgrim Health Care Institute
• Cara McDermott, PharmD, PhD, Research Consultant, BBCIC
• Aaron B. Mendelsohn, PhD, MPH, Senior Health Services Researcher, Department of Population Medicine, Harvard Pilgrim Health Care Institute
• Pamala A. Pawloski, PharmD, BCOP, FCCP, Senior Research Investigator, HealthPartners Institute
• Cheryl Walraven, MSW, PhD, Executive Director, CVS Health
• BBCIC Staff: Cate Lockhart, PharmD, PhD, Executive Director, BBCIC

Documents 

• Study Protocol (coming soon)

Background and Objectives 

Adherence is an important construct to consider in evaluating product utilization.  As the BBCIC begins to perform inferential analyses (e.g., comparative effectiveness and safety studies), it will be necessary to consider medication adherence and how this influences product risk and benefit outcomes.  However, measuring adherence is highly nuanced, particularly when relying on secondary data, namely administrative claims data.  Further, this is complicated by the variety of medications that might be involved in a given analysis, both in terms of product class as well as mode and frequency of administration of these products.  

As this topic was conceived through work currently being performed for the Switching Descriptive analysis that is focused on rheumatoid arthritis (RA), we will focus on this therapeutic area as a case example, i.e., measuring adherence for immunomodulators (biologics and JAK inhibitors) used in the treatment of RA; however, these findings should also help inform research for other disease areas. 

The goal is a methods-based project to develop best practices for measuring adherence (and related concepts, e.g., persistence) for medicinal products when using claims data for novel biologics and biosimilar products, as well as how to optimally include covariates for adherence-related measures in inferential analyses. The WorkGroup will follow the model of the Switching Methods WorkGroup convened by the BBCIC to propose best practices for handling switching of medications in non-interventional research. 

Current Status 

Update – October 2023: A structured literature review is underway to identify how other investigators have defined adherence and to assess any proposed algorithms or methods for measuring adherence in claims. 

Research Team 

• Samantha Smith, BU Student, Harvard Pilgrim Research Assistant
• Kim Campbell, Medical Director, Sandoz
• Audrey Djibo, PhD, Lead Epidemiologist, CVS Health Clinical Trial Services
• Megan Fesinmeyer, PhD, MPH, Observational Research Sr. Manager, Amgen
• Jim Kenney, RPh, MBA, Founder and President, JTKenney, LLC
• Sam Li, PhD, Assistant Professor, Health Outcomes and Policy Research, University of Tennessee
• Aaron B. Mendelsohn, PhD, MPH, Senior Health Services Researcher, Department of Population Medicine, Harvard Pilgrim Health Care Institute
• Pamala A. Pawloski, PharmD, BCOP, FCCP, Senior Research Investigator, HealthPartners Institute
• Gary C. Yee, PharmD, FCCP, BCOP, Professor and Associate Dean, College of Pharmacy, University of Nebraska College
• BBCIC Staff: Cate Lockhart, PharmD, PhD, Executive Director, BBCIC

Documents 

• Study Protocol (coming soon)

Background and Objectives 

Conducting observational research using administrative claims is both powerful and challenging. One challenge is in identifying patient cohorts, clinical outcomes, and treatment regimens using data collected for purposes of billing and reimbursement. There is a need in the observational research community for robust, validated algorithms to reliably identify those elements that are so essential to conducting meaningful research.  

The goal of this initiative is to contribute to observational science methodology by developing, validating, and publishing algorithms of high relevance to BBCIC research. The specific algorithm topics will be determined by the Research Team of BBCIC volunteers. This project will begin in with a comprehensive literature review followed by protocol development and approval by the BBCIC Science Committee.

Current Status 

Update – June 2023: In planning. 

Research Team 

• Principal Investigator: TBD
• Kimberly Daniels, PhD, MS, Researcher, Safety & Epidemiology, HealthCore
• Audrey Djibo, PhD, Epidemiologist – Lead Data Scientist, CVS Health Clinical Trial Services
• Rochelle Henderson, Vice President, Clinical Research, Evernorth
• Jim Kenney, RPh, MBA, Founder and President, JTKenney, LLC
• Annemarie Klein, MS, CHES, Manager, Common Data Model Analytics, CVS Health Clinical Trial Services
• Ed Li, PharmD, MPH, BCOP, Associate Director, HEOR & RWE, Sandoz
• Aaron B. Mendelsohn, PhD, MPH, Senior Health Services Researcher, Department of Population Medicine, Harvard Pilgrim Health Care Institute
• BBCIC Staff: Cate Lockhart, PharmD, PhD, Executive Director, BBCIC

Documents 

• Study Protocol(coming soon) 

Project Title: Patient access to biologics and the impact of biosimilars

Study Objective(s) 

• Determine the uptake of biosimilars and how biosimilar availability has impacted patient access to biologic treatment
• Identify the impact of additional biosimilar options of a reference molecule on biosimilar utilization and patient access to treatment
• Measure the impact of biosimilar availability on healthcare resource utilization
• Identify reasons for observed utilization and uptake levels (qualitative?)

Background and Significance 

Data from Europe show that availability of biosimilars has led to increased use of a given molecule (either originator or biosimilars). Moreover, there is evidence that the molecule is being used earlier in the disease cycle. Biosimilars can potentially expand patient access to biologic therapies by providing more treatment options, but limited studies have been conducted to understand the potential changes in access over time with biosimilar market being rapidly evolved. The successful deliverables of this project will fill in such knowledge gap.

Study Design or Approach 

A retrospective, observational cohort study with the following steps:

1. Perform a longitudinal utilization/descriptive analysis of biologics, including biosimilars, including assessment of time from diagnosis to first biologic treatment.
2. Evaluate incremental changes in utilization parsed at the time of product availability in the US.
3. Merge utilization data with publicly available fee schedules (e.g. Medicare, Federal Supply Schedule) and using available reimbursement records.
4. Perform a qualitative study of key biosimilars stakeholders to understand barriers to adoption, key knowledge gaps etc.

Exposures 

All approved indications for bevacizumab, trastuzumab and rituximab biosimilars, with specific focus on metastatic colorectal cancer (mCRC), non-small cell lung cancer (NSCLC), breast cancer, non-Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL). 

Outcomes/Measures of Interest 

Changes in following variables over time, specifically prior to and following the market availability of biosimilars, will be assessed.

• Number of treated patients (originator, biosimilar(s), or both)
• Treatment length (e.g., number of cycles received)
• Time to treatment initiation
• Healthcare resource utilization, including total spend (reimbursement) for biologics
• Select patient outcomes (TBD)

Study Population  

Adult patients (age 18+ years) diagnosed with mCRC, NSCLC, breast cancer, NHL, and CLL and treated with bevacizumab, trastuzumab, and/or rituximab products.  

Current Status 

Update – June 2023: In planning. 

Research Team 

• Principal Investigator: TBD
• Anna Chen, Associate Director, HEOR/RWE, Sandoz
• Bahar Coley, Project Manager, Carelon Research
• Mitch DeKoven, MHSA, Practice Leader – US Retrospective Research, IQVIA
• Katherine Harris, Principal Scientist, Carelon Research
• David Hughes, PharmD, BCOP, Director, Field Medical, Pfizer
• Ran Jin, Observational Research Senior Manager, Amgen
• Jim Koeller, UT Health Science Center at San Antonio
• Sam Li, PhD, Assistant Professor, Health Outcomes and Policy Research, University of Tennessee
• Aaron B. Mendelsohn, PhD, MPH, Senior Health Services Researcher, Department of Population Medicine, Harvard Pilgrim Health Care Institute
• Pamala A. Pawloski, PharmD, BCOP, FCCP, Senior Research Investigator, HealthPartners Institute 
• Gary C. Yee, PharmD, FCCP, BCOP, Professor and Associate Dean, College of Pharmacy, University of Nebraska College
• BBCIC Staff: Cate Lockhart, PharmD, PhD, Executive Director, BBCIC

Project Title: Trastuzumab descriptive and comparative safety and effectiveness analyses

Study Objective(s) 

• To better understand patterns of utilization over time; e.g., the proportion of patients that use trastuzumab products in sequential/multiple treatment lines (e.g., 1st, 2nd, and 3rd) over time.
• To understand safety outcomes such as cardiotoxicity (infusion reactions, pulmonary toxicity, etc.) as a benchmark for rates observed in our clinical trials and in the postmarking setting, and as an important additional source of safety data.
• To understand clinical response rates (e.g., overall survival (OS), overall response rate (ORR), progression free survival (PFS), time to progression (TTP), pathologic complete response (pCR), etc.) as a benchmark for rates observed in our clinical trials and in the post-marketing setting.
• Disparities and other covariates/confounders: For example, to understand the impact of racial, socioeconomic (e.g., patient insurance status, patient out of pocket information) and age disparities, to the extent measurable and available in our data, and if this correlates with utilization. Can also explore whether underutilization due to disparity leads to relatively worse effectiveness outcome in these sub-populations compared to populations without these disparities. If there is underuse, there is an opportunity for biosimilar adoption with more affordability to address these gaps. Other covariates to consider pre-existing renal, liver, cardiac, pulmonary disease.
• To assess the comparative safety and effectiveness across available trastuzumab products

Background and Significance 

There are now multiple trastuzumab biosimilars available in the US, and utilization of biosimilars relative to the originator product has been rapidly increasing, but there is limited information regarding treatment patterns and comparisons across available products. BBCIC has conducted a utilization analysis of trastuzumab and other HER2-inhibitors in breast cancer, and this work is intended to expand on these prior studies.

Study Design or Approach 

A retrospective, observational cohort study will be conducted in the following phases:

1. Descriptive analysis to thoroughly understand patterns of care, confounders, and algorithms or other data elements needed for a comparative analysis
2. Exploratory comparative safety and effectiveness analysis

Exposures 

All available trastuzumab products. 

Outcomes/Measures of Interest 

• Exploratory analyses in the following 4 areas: (if feasible)
  - Descriptive analysis of trastuzumab usage patterns across invasive breast cancer,
  - by HR-/HER2+ disease
  - by HR+/HER2+ disease, and
  - by various lines of therapy (e.g., NCCN “preferred” vs. “Other regimens”)
• Evaluate trastuzumab patient use of sequential /multiple treatment cancer stage or treatment indication lines (e.g., 1st,2nd and 3rd) over time
• Evaluate frequency of switching from other oncology biologics (i.e., baseline prior to trastuzumab index by HR-/HER2+ and by HR+/HER2+ disease, by cancer stage, by endocrine therapy or preoperative/adjuvant chemotherapy, by NCCN preferred vs Other regimen)
• Evaluate baseline potential covariates and confounders [e.g., Charlson comorbidity index, cardiac events, age, gender, health service utilization (e.g., number unique drug classes, ER visits, inpatient hospitalizations, ambulatory encounters, ED visits), G-CSF use, hospitalizations for febrile neutropenia, radiation exposure, metastatic sites]
• Evaluate frequency of switching to other oncology biologics (i.e., post trastuzumab cycles by HR-/HER2+ and by HR+/HER2+ disease, by cancer stage, by endocrine therapy or preoperative/adjuvant chemotherapy, by NCCN preferred vs Other regimen)
• Evaluate duration (doses, days, cycles) of trastuzumab therapy by HR-/HER2+ and by HR+/HER2+ disease, by cancer stage, by endocrine therapy or preoperative/adjuvant chemotherapy, by NCCN preferred vs Other regimen)
• Evaluate utilization of non-biologic chemotherapy or other agents such as hormone therapy, etc. (baseline prior, during trastuzumab episodes and post-trastuzumab cycles).
• Impact of disparity factors, to the extent measurable and available in our data, in the treatment of metastatic HER2-positive breast cancer (e.g., racial, socioeconomic [e.g., patient insurance status, patient out of pocket information] and age, and the impact of disparity on effectiveness response rates
• Descriptive analysis of drug-specific adverse events incidence of cardiotoxicity (CHF grade) and other important safety events (i.e., infusion reactions, pulmonary toxicity, etc.) by
• Descriptive analysis of effectiveness response rates in standard of care regimens.
  - Evaluate the effectiveness response rates such as OS, ORR, PFS, pCR, etc.
  - Evaluate use/availability/harmonization of other Recist 1.1 data in trastuzumab exposed patients: cell type, recurrence, tumor measurement)
• Descriptive analysis of trastuzumab cycles and dosing (mg/m2) regimens.

Study Population  

Female and male adults (age 18+ years) diagnosed with breast cancer.  

Current Status 

Update – June 2023: In planning. 

Project Title: Descriptive analysis of utilization, patient characteristics, and outcomes in people treated with adalimumab

Study Objective(s) 

• To understand patterns of utilization and treatment, including observed place of adalimumab in therapy, persistence, and patient adherence.
• To understand what outcomes are measurable in our existing data, such as disease severity, and identify surrogate endpoints or algorithms that may be used to identify unmeasurable outcomes.
• Compare our real-world results with those observed in clinical trials as a benchmark for assessing how real-world data can be incorporated into treatment and coverage decisions.
• Explore our ability to measure disparities (e.g., race, ethnicity, socioeconomics, etc.) and the impact on treatment patterns and outcomes.

Background and Significance 

We anticipate multiple biosimilars to reference adalimumab (Humira) will become available in the US starting in 2023. Now is a good time to prepare for future comparative studies by conducting a detailed descriptive analysis of current adalimumab use and clinical outcomes. This study will build on past BBCIC work on switching patterns and methods for measuring adherence in inflammatory diseases.

Study Design or Approach 

A retrospective, observational, longitudinal, descriptive cohort study.

Exposures 

Any adalimumab product. 

Outcomes/Measures of Interest 

• Utilization patterns
• Patient characteristics
• Safety events
• Clinical outcomes
• Time from diagnosis to first biologic treatment
• Persistence and adherence of adalimumab
• Confounders
• Average resource utilization or overall healthcare costs

Study Population  

People diagnosed with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, or uveitis will be included. Cohorts will be stratified by age, including pediatric populations, and diagnosis where appropriate. 

Current Status 

Update – June 2023: In planning. 

Project Title: Descriptive analysis of utilization, patient characteristics, and outcomes in people treated with bevacizumab

Study Objective(s) 

• To understand patterns of utilization and treatment, observed place of bevacizumab in therapy.
• To understand what outcomes are measurable in our existing data, such as disease severity and clinical outcomes, and identify surrogate endpoints or algorithms that may be used to identify unmeasurable outcomes.
• Compare our real-world results with those observed in clinical trials as a benchmark for assessing how real-world data can be incorporated into treatment and coverage decisions.
• Explore our ability to measure disparities (e.g., race, ethnicity, socioeconomics, etc.) and the impact on treatment patterns and outcomes.

Background and Significance 

We anticipate increased utilization of bevacizumab biosimilars as multiple products enter the US market. This study builds on prior studies evaluating the longitudinal product utilization of bevacizumab in both oncology and off-label ophthalmology use. This descriptive analysis will focus on oncology only.

Study Design or Approach 

A retrospective, observational, longitudinal, descriptive cohort study.

Exposures 

Any bevacizumab product. 

Outcomes/Measures of Interest 

• Utilization patterns
• Patient characteristics
• Safety events
• Clinical outcomes
• Time from diagnosis to first biologic treatment
• Length of therapy (e.g., number of cycles, regimens)
• Confounders
• Average resource utilization or overall healthcare costs

Study Population  

• Patients will be required to have a diagnosis of one of the following cancers: colorectal, non-squamous non-small cell lung cancer, renal cell carcinoma, or cervical cancer.
• All patients treated with at least one dose of bevacizumab during the study period will be included in the analysis.
• Patients with more than 1 cancer diagnosis (except for non-melanomatous skin cancer or carcinoma in situ) treated during the study period will be excluded from analysis.

Current Status 

Update – June 2023: In planning. 

Background and Purpose 

To provide a landscape of patient characteristics and treatment patterns using biologic products of interest, including biosimilars, BBCIC conducts periodic analyses of product utilization in our distributed research network. This initiative provides informative data on trends over time in a large patient population in the BBCIC network and is essential for planning future descriptive and comparative analyses.

• Insulins
• Trastuzumab
• Bevacizumab
• Anti-Inflammatories
• G-CSF

• CER Statistical Approach Workgroup. To reduce rework by each CER team on statistical design, the BBCIC convened a workgroup to develop recommendations on a standard methodologic approach to conducting BBCIC CER studies. The workgroup discussed design and analytic options (e.g., propensity score methods, discontinuity or instrumental variables, difference-in-difference) and identified options for supplemental analyses to address the potential alternate explanations for observed effects.
• ICD9 to ICD10 Mapping Workgroup. To prepare to conduct CER, BBCIC convened a workgroup to convert all ICD9 criteria from current Descriptive Analysis Protocols to ICD10. This is a complex process that requires significant work beyond simple backward/forward mapping including developing the best criteria for actual phenotyping.
• Improving Capture of NDC on Physician Office Claims Workgroup. For optimal product identification of biologics including biosimilars, NDCs are recommended for all physician office claims. BBCIC convened a research workgroup to conduct a descriptive analysis of occurrence of NDCs and J-codes in the Procedure Table of the common data model (CDM). The workgroup also explored NDCs captured in data partner claims data warehouses.
• Switching Pattern Workgroup. As we wait for sufficient infliximab biosimilar exposures to conduct CER, BBCIC convened a workgroup to conduct an initial descriptive analysis on innovator switching patterns. The Switching Patterns Workgroup’s purpose was to improve the conduct of biosimilar switching studies by establishing recommendations for best practices for the conduct of innovator and biosimilar switching studies and for treating switching/sequencing as a covariate/confounder in CER studies. The workgroup’s recommendations used anti-inflammatory agents as a case study but will include considerations for switching studies in other biologic classes.

• Biologic anti-inflammatory (AI) therapies and incidence of hospitalizations for serious infections among patients with autoimmune diseases (e.g., rheumatoid arthritis, psoriasis, or inflammatory bowel disease such as Crohn’s disease) being treated with AI. Several biologics are approved to treat all or some of these conditions, three of which have FDA- approved biosimilars (i.e., Remicade/Inflectra, Enbrel/ Erelzi, and Humira/Amjevita). (NCT 02922192)
• Long-acting insulins and control of blood sugar and the incidence of hypoglycemia and major cardiac events in patients with Type 1 and Type 2 diabetes. (NCT 02922179)
• Colony stimulating factors (CSFs) and incidence of hospitalizations for febrile neutropenia in breast and lung cancer patients. Some chemotherapy agents create potentially life-threatening infections in part because they reduce white cells. CSFs help reduce the likelihood of these infections by shortening the time white cells are low. (NCT 02922192)
• Erythropoietin Stimulating Agents (ESAs) and chronicity of hemodialysis (HD) and important covariates and confounders for HD populations among selected BBCIC data partners. BBCIC assessed whether we have a sufficiently similar population of HD patients to that described by the United States Renal Data System (USRDS).