Our Research

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 – July 2025: 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. This project is continuing into 2025 with examining the impact of adherence to medications on clinical and other outcomes (e.g., cost, HCRU).

• So far, for 2025, one manuscript is in preparation.
• In 2024, we also presented one poster related to this work:

Smith S, Mendelsohn AB, Abente E, Djibo A, Kenney J, Yee GC, Lockhart CM. A Targeted Literature Review on Medication Adherence: A Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) Study. Poster presentation at ISPOR 2024, Atlanta, GA, May 6-8, 2024.

Research Team 

• Samantha Smith, BU Student, Harvard Pilgrim Research Assistant
• Audrey Djibo, PhD, Lead Epidemiologist, CVS Health Clinical Trial Services
• Megan Fesinmeyer, PhD, MPH, Observational Research Sr. Manager, Amgen
• Shellie Keast, PharmD, PhD, Mgr, Health Economics and Outcomes, MedImpact Healthcare Systems, Inc. 
• Jim Kenney, RPh, MBA, Founder and President, JTKenney, LLC
• Sam Li, PhD, Assistant Professor, Health Outcomes and Policy Research, University of Tennessee
• Charron Long, PharmD, Associate Director, Medical Value and Access, Astellas
• 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
  • Pam Pawloski, PharmD, BCOP, FCCP, Principal Research Scientist, BBCIC
  • Aaron B. Mendelsohn, PhD, MPH, Research Consultant, BBCIC

Background and Objectives 

Vascular endothelial growth factor (VEGF) plays a role in the angiogenic growth of new blood vessels by stimulating proliferation, migration, and tube formation. VEGF has been in numerous retinal diseases like age-related macular degeneration (AMD) and diabetic retinopathy. These conditions leave those affected with severely impaired vision. In 2019, about 12.6% of Americans 40 years and older were living with AMD. The economic impact of late-stage AMD was about 49.1 billion dollars in the United States. This shows both the disease and economic burden for those dealing with just AMD. The addition of other VEGF-related diseases would potentially benefit more individuals who live with these disease burdens and the financial weight they hold.

Anti-VEGF therapies have shown effective clinical outcomes in patients with wet AMD in controlled clinical trials. While these studies have provided information regarding the safety and efficacy of the medications, they do not reflect real-world usage. There is a need to understand how clinical trial information translates into real-world applications. Real-world studies allow insights into utilization patterns and potential concerns and provide perspective on the unmet need. A comprehensive understanding of the real-world evidence will allow the identification of knowledge gaps and help steer future researchers to improve these therapies for further improved outcomes for patients. This review aims to systematically examine the current, real-world evidence for anti-VEGF therapies approved in the United States for wet AMD to help provide insight into its applications to aid in better-informed clinical decision-making.

Study Design or Approach 

To map the landscape of real-world research on anti-VEGF therapies in wet AMD, this review will address the following questions:

1. Utilization Patterns: How are the anti-VEFG therapies utilized in wet AMD in real-world settings? What is the common patient population, treatment duration, and dosing frequency for each therapy? What are the utilization patterns for each of the therapies compared to each other?

2. Clinical Outcomes: What are the reported real-world outcomes for each anti-VEGF therapy in wet AMD in a real-world setting and how do they differ from each other?

3. Safety Profiles: o What adverse events are associated with each anti-VEGF therapy in real-world settings for wet AMD, and how might these differ from clinical trial data?

4. Research Landscape:

• Data Sources & Methods: What types of real-world data sources and observational study designs are used in anti-VEGF therapies in wet AMD?
• Strengths & Weaknesses: What are the advantages and limitations of the methodologies utilized in these studies?
• Knowledge Gaps: What aspect of anti-VEGF therapies use, outcomes, or study designs in wet AMD require further investigation due to lack of data?

Current Status 

Update – July 2025: A protocol for a scoping review of the literature to evaluate the landscape of real-world research focused on anti-VEGF treatment in ophthalmology.

To date, we have presented one poster related to this work:

Tran T, Yoon, J, Pawloski PA, Lockhart CM. Understanding Real-World Evidence for Safety, Efficacy, and Adherence of Anti-Vascular Endothelial Growth Factor in Wet Age-Related Macular Degeneration: A Scoping Review. Poster presentation at AMCP 2025, Houston, TX, March 31-April 2, 2025.

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 – July 2025: Our colleagues at Carelon are leading this study in which we are exploring the impact of biosimilar availability on treatment patterns, utilization, and outcomes in patients treated with bevacizumab or trastuzumab. The data analysis is complete and a manuscript is in preparation.

To date, we have presented one poster related to this work:

Dixon R, Venkataraman M, Barron J, Harris K, Pithua P, Roth J, Mendelsohn A, Yee G, Li MS, Lockhart CM. Real-world bevacizumab biosimilar uptake from 2018–2023 and outcomes among patients with NSCLC and mCRC using commercial and Medicare Advantage claims in the US. Poster presentation at AMCP 2025, Houston, TX, March 31-April 2, 2025.

Research Team 

• Principal Investigator: Ruth Dixon, PhD, Senior Researcher, Carelon Research
• Anna Chen, Associate Director, HEOR/RWE, Sandoz
• Mitch DeKoven, MHSA, Practice Leader – US Retrospective Research, IQVIA
• Katherine Harris, Principal Scientist, Carelon Research
• Kaitlyn Hopkins, BSc, Project Manager, Carelon
• David Hughes, PharmD, BCOP, Director, Field Medical, Pfizer
• Argentina Servin, Global Biosimilar Lead, Amgen
• Jim Koeller, UT Health Science Center at San Antonio
• Sam Li, PhD, Assistant Professor, Health Outcomes and Policy Research, University of Tennessee
• 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
  • Aaron B. Mendelsohn, PhD, MPH, Research Consultant, BBCIC

Background and Objectives 

Osteoporosis, hypercalcemia, and bone metastasis are significant health concerns worldwide due to their association with increased morbidity and mortality [1]. These conditions can result in severe complications, including fractures, renal dysfunction, and a reduced quality of life. It is estimated that 2 million osteoporosis-related fractures occur in the United States annually, costing over $20 billion in direct medical costs and this burden is expected to rise significantly in the coming decades due to the aging population [2].

Denosumab, a monoclonal antibody targeting the Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) protein has emerged as a vital treatment option for these conditions due to its ability to inhibit bone resorption [3]. Approved indications for Denosumab include the treatment of osteoporosis in postmenopausal women and men at high risk of fractures, treatment of bone loss in patients undergoing hormone ablation therapy for prostate or breast cancer, management of hypercalcemia of malignancy, and prevention of skeletal-related events in patients with bone metastases from solid tumors [4,5]. Despite its effectiveness, understanding the real-world utilization, outcomes, and safety profile of Denosumab is critical, especially with the introduction of interchangeable biosimilars Jubbonti (denosumab-bbdz) and Wyost (denosumab-bbdz), which could impact treatment accessibility and affordability [6].

This is a new therapeutic area for BBCIC research.

To map the landscape of real-world research on Denosumab, this review will address the following questions:

1. Utilization Patterns: How is Denosumab used in real-world settings across its indications (osteoporosis, hypercalcemia, and bone metastasis-related fracture prevention)? What are the common patient populations, treatment durations, and dosage patterns?

2. Clinical Outcomes: What are the reported effectiveness measures (e.g., changes in BMD, fracture rates, hypercalcemia control) in real-world practice, and how do they compare across different indications?

3. Safety Profiles: What adverse events are associated with Denosumab use in real-world settings, and how might these differ from clinical trial data?

4. Research Landscape:

• Data Sources & Methods: What types of real-world data sources (e.g., healthcare databases, registries, electronic health records or claims) and observational study designs are used in Denosumab research?
• Strengths & Weaknesses: What are the advantages and limitations of the methodological approaches used in these studies?
• Knowledge Gaps: What aspects of Denosumab use, outcomes, or study designs remain under-researched or require further investigation?

References 

1. Salari N, Ghasemi H, Mohammadi L, Behzadi MH, Rabieenia E, Shohaimi S, Mohammadi M. The global prevalence of osteoporosis in the world: a comprehensive systematic review and meta-analysis. J Orthop Surg Res. 2021 Oct 17;16(1):609. doi: 10.1186/s13018-021-02772-0. PMID: 34657598; PMCID: PMC8522202.
2. Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007 Mar;22(3):465-75. doi: 10.1359/jbmr.061113. PMID: 17144789.
3. Zhu Y, Huang Z, Wang Y, Xu W, Chen H, Xu J, Luo S, Zhang Y, Zhao D, Hu J. The efficacy and safety of denosumab in postmenopausal women with osteoporosis previously treated with bisphosphonates: A review. J Orthop Translat. 2019 Sep 9;22:7-13. doi: 10.1016/j.jot.2019.08.004. PMID: 32440494; PMCID: PMC7231967
4. Zaheer S, LeBoff M, Lewiecki EM. Denosumab for the treatment of osteoporosis. Expert Opin Drug Metab Toxicol. 2015 Mar;11(3):461-70. doi: 10.1517/17425255.2015.1000860. Epub 2015 Jan 22. PMID: 25614274; PMCID: PMC4480604.
5. Imre A, Zoltán S, Miklós S. Current indications for denosumab in benign bone tumours. EFORT Open Rev. 2023 Dec 1;8(12):895-905. doi: 10.1530/EOR-23-0138. PMID: 38038377; PMCID: PMC10714381.
6. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-interchangeable-biosimilars-prolia-and-xgeva-treat-certain-types-osteoporosis-and

Current Status 

Update – July 2025: A protocol for a scoping review of the literature is in preparation to evaluate the landscape of real-world research focused on denosumab.

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 – July 2025: Initial data describing three study cohorts have been collected and analysis is underway. 

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
• Argentina Servin, Global Biosimilar Lead, Amgen
• Nancy Lin, ScD, Principal, Epidemiology and Drug Safety, Real World Evidence Solutions, IQVIA
• BBCIC Staff:
  • Pam Pawloski, PharmD, BCOP, FCCP, Principal Research Scientist, BBCIC

Study Objective 

The proposed study will use qualitative methods to better understand patients’ knowledge of, experiences with, access to and decision-making surrounding the use of biologics and biosimilars among patients with inflammatory bowel disease (IBD), with a focus on the two primary types: ulcerative colitis (UC) and Crohn’s disease (CD), from different racial/ethnic groups. The results of this study will expand our understanding of challenges, trade-offs, and preferences among patients with IBD from underserved communities and inform the development and dissemination of patient communication strategies around the accessibility, safety, and effectiveness of biologic and biosimilar treatments for IBDs.

A patient advisory council (PAC) will be formed (see description below) to identify the most relevant topics for individuals with IBD lived experience who are taking biologics or biosimilars. A list of potential topics that may be explored are below. Additional topics may be identified and included based on feedback from the PAC. These topics could include:

• Patients’ experiences regarding the adequacy of information on IBD disease symptoms prognosis and treatment options including the use of biologics and biosimilars
• Patient preferences and knowledge about benefit/risk trade-offs regarding the use of biologics/biosimilars
• Patient definition of treatment success and how that definition impacts treatment decisions
• Patient perspective and experience with shared treatment decision-making
• Patient experience accessing biologics and/or biosimilars
• Patient experience with physician management of prescribed biologic/biosimilar treatment and switching

The PAC will consist of at least three individuals who have direct experience with biologics and/or biosimilar treatment for an IBD and reflect diverse sociodemographic and clinical backgrounds. Patient advisors will be compensated for their time. Total patient advisor time commitments are estimated to be 8-10 hours.

Background and Significance 

Inflammatory bowel disease (IBD), consisting of Crohn’s Disease (CD) and ulcerative colitis (UC), causes chronic inflammation and damage in the gastrointestinal (GI) tract (Crohn’s and Colitis Foundation of America, 2014). Although IBD has been more prevalent in white populations, it is becoming more common in other races and ethnicities leading to a projected increased health economic burden in the future (Aniwan, et al., 2019). There is a need to ensure broad access to appropriate IBD treatments and improved health outcomes across all racial and ethnic groups.

Biosimilars can offer an affordable, effective alternative to originator biologics (Quinn, 2024); however, barriers remain for their access and use in underserved communities (Santoro, 2024a; 2024b). Biosimilars may improve access and reduce costs, although their adoption in clinical practice has been slow, despite multiple available IBD biosimilars (Angyal et al., 2024). While clinician knowledge and comfort with biosimilars have improved in recent years, doubts about safety (Angyal et al., 2024; Sarnola et al., 2020) and gaps in knowledge remain (Angyal et al., 2024; Stevenson, et al., 2023). Moreover, patients have reported dissatisfaction with the information they received at diagnosis about treatment options and side effects (Al Khoury, et al., 2022) suggesting the shared decision-making process may lack key elements that support the achievement of patient treatment goals. Reasons for provider and patient hesitancy to initiate or switch to biosimilars have not been well-studied among various racial and ethnic groups. At the same time, little has been published on how clinicians engage with patients from other races and ethnicities about their IBD treatment options, including biosimilars (Feuerstein, et al., 2021). This qualitative study aims to examine the role of race and ethnicity in patients' experiences with IBD biological/biosimilar treatment decision-making and use through a pharmacoequity lens.

Study Design or Approach 

In addition to contributing new insights on patient access and decision making around the use of biotherapy treatment in UC and CD by race and ethnicity, the study will provide preliminary data that will inform the development of future claims-based research to understand patient preferences and experiences using larger, more representative samples of patients.

We will collect qualitative data by conducting one-on-one semi-structured telephone interviews lasting approximately 60 minutes that will explore the questions in Section 1 among four groups of patients using an interview discussion guide that will be developed specifically for use with this study: Patients with UC currently using a biologic treatment, Patients with UC currently using a biosimilar treatment, Patients with CD currently using a biologic treatment, and Patients with CD currently using a biosimilar treatment.

Study eligible patients will be identified from claims in the Healthcare Integrated Research Database (HIRD), a large administrative claims database maintained by Carelon Research for research purposes. The study population will consist of survey-eligible patients, age 18 years and older, with Commercial or Medicare Advantage health insurance and at least one medical claim with an ICD-10-CM diagnosis code for UC or CD and at least one pharmacy claim for a biologic or biosimilar during the patient identification period (PIP) from April 1, 2023 through March 31, 2024, or the most recent 12 months of HIRD data at the time the patient sample is identified.

Patient-level race and ethnicity data are available for HIRD patients and will be used to ensure that at least 4 groups of 10-12 individuals are included from the following racial / ethnic backgrounds: Black, Hispanic, Asian/Pacific Islander, and White. We will finalize recruitment targets for the planned groups in collaboration with the BBCIC using information about the financial resources available to the project and preliminary IBD patient counts in the HIRD.

Update – July 2025: Our colleagues at Carelon are leading this study. The work group is currently being assembled and an orientation meeting will be held in August.  

Study Objectives 

The U.S. biosimilar market is in a relatively early phase of development, and the economic benefits may not fully be realized unless sustainable market conditions are established. Current challenges to sustainability include, but are not limited to: (1) substantial price volatility that introduces uncertainty and economic challenges for all stakeholders; (2) perverse economic incentives that encourage providers to use more expensive reference products because reimbursement dynamics make them more profitable; (3) complex rebate structures that create barriers to biosimilar access; and (4) ongoing changes to the legal and regulatory environment, including evidence requirements to gain “interchangeable” status.

Developing evidence to better understand these challenges through the lens of key stakeholders can help to identify the most pertinent issues, raise awareness among government and other decision-makers who are positioned to intervene, and ultimately design and implement policy changes that support long-term market sustainability. BBCIC is particularly well-suited to pursue this research topic because the organization sits at the intersection of all the key stakeholder groups and has the scientific expertise to conduct a methodologically rigorous and representative survey.

The primary audience for the research findings should be U.S. government decision-makers in the House, Senate, CMS, and FDA who can implement legal/regulatory policy change to support a more sustainable biosimilar market. BBCIC is also well-positioned to communicate findings to these decision-makers given existing connections and positioning as a trusted policy-making partner.

Current Status 

Update – July 2025: The Research Team has been assembled, and the group is starting to develop the survey questions.  

Research Team 

• Anna Hyde, Vice President of Advocacy and Access, Arthritis Foundation
• Jim Kenney, RPh, MBA, Founder and President, JTKenney, LLC
• Tianze Jiao, PhD, Assistant Professor, College of Pharmacy University of Florida
• Ed Li, PharmD, MPH, Head, HEOR and Oncology, Sandoz
• Charron Long, PharmD, Associate Director, Medical Value and Access, Astellas
• Kevin Lu, PhD, FISPE, Associate Professor, College of Pharmacy University of South Carolina
• Josh Roth, PhD, MHA, Director, HTA, Value & Evidence, Biosimilars, Pfizer Inc.
• BBCIC Staff:
  • Cate Lockhart, PharmD, PhD, Executive Director, BBCIC
  • Pam Pawloski, PharmD, BCOP, FCCP, Principal Research Scientist, BBCIC
  • Aaron B. Mendelsohn, PhD, MPH, Research Consultant, BBCIC

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 

This study is complete and a manuscript has been published to the Journal of Managed Care + Specialty Pharmacy. 

To date, one manuscript has been accepted for publication:

Ko J, Mendelsohn A, Daniels K, Gomez-Lumbreras A, Marshall J, McDermott CL, Pawloski PA, Yee G, Lockhart CM. Patient characteristics and use for bevacizumab in ophthalmology and oncology in a distributed research network. J Manag Care Spec Pharm. 2025;31(2):157-166.

We have presented two posters related to this work:

Ko J, Mendelsohn A, Daniels K, Gomez-Lumbreras A, Marshall J, McDermott C, Pawloski P, Yee G, Lockhart. Patient characteristics and utilization for bevacizumab in ophthalmology and oncology in a distributed research network. Poster presentation at AMCP Nexus 2022, National Harbor, MD, October 11-14, 2022.

Ko J, Mendelsohn A, Daniels K, Gomez-Lumbreras A, Marshall J, McDermott C, Pawloski P, Yee G, Lockhart. Utilization, user characteristics, and adverse outcomes of bevacizumab products in oncology in a distributed research network. Poster presentation at ASCO Quality Care Symposium 2022, Chicago, IL, September 30-October 1, 2022.

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
• Ed Li, Head, HEOR and Oncology, Sandoz
• 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
• 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

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 

This study is complete and the 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 have presented five posters related to this work:

Lockhart CM, McDermott CL, Vazquez Benitez G, DeFor T, Mendelsohn A, Marshall J, Moyneur E, Pawloski PA; on behalf of the BBCIC G-CSF Comparative Effectiveness Research Team. Studying medications to lower the risk of infections during chemotherapy for cancers. Poster presentation at Patient Insight Congress 2024, Atlanta, GA, April 8-10, 2024.

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: 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

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 

This study is complete and the final manuscripts are in preparation. 

To date, we have presented four posters related to this work:

Jonathan Deshazo, Djeneba Audrey Djibo, Erick Moyneur, Cheryl N McMahill-Walraven, Aaron B. Mendelsohn, Cate Lockhart. Adherence Differences Between Self-Administered and Provider-Administered Biologics Among Patients with Rheumatoid Arthritis During the COVID-19 National Emergency. Poster presentation at ICPE 2024 [Spotlight Poster], Berlin, Germany, August 24-28, 2024.

Jonathan Deshazo, Djeneba Audrey Djibo, Erick Moyneur, Cheryl N McMahill-Walraven, Aaron B. Mendelsohn, Cate Lockhart. Medication Adherence Among Moderate to Severe Rheumatoid Arthritis Patients with Similarly Treated Inflammatory Autoimmune Comorbidities. Poster presentation at AcademyHealth 2024 Annual Research Meeting, Baltimore, MD, June 29-July 2, 2024.

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. Poster presentation at 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. Poster presentation at 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
• 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
• 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 

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 

This study is complete.

To date, one manuscript has been accepted for publication:

Xiaodan Mai, Aaron B. Mendelsohn, James Marshall, Nancy D. Lin, Cara L. McDermott, Jenice S. Ko, 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 human epidermal growth factor receptor 2 inhibitors in the United States. J Manag Care Spec Pharm. 2024;30(10):1160-66.

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
• Ed Li, Head, HEOR and Oncology, Sandoz
• 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
• Cheryl Walraven, MSW, PhD, Executive Director, CVS Health
• BBCIC Staff: Cate Lockhart, PharmD, PhD, Executive Director, BBCIC

• 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).