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 – January 2022: The data are coming! The code has been distributed to all participating Research Partners in the BBCIC network and data will be compiled into our study dataset for analysis. 

Update – October 2021: Our de novo program designed to identify patient cohorts and extract de-identified person-level data according to the protocol is undergoing testing with the lead study partner data with promising results from an initial test run. Once testing is complete, we will distribute the finalized code to BBCIC Research Partners to extract data and build the full data set. Meanwhile, we will finalize the manuscript describing the challenges we faced and solutions we implemented to accurately identify the study cohorts. This manuscript will be submitted to Medical Care or another journal with health-services or methodology-based readership. 

Update – June 2021: A scoping review of the observational literature and a manuscript describing the study protocol are undergoing peer-review. We knew this study would be complex and have encountered several challenges in cohort and chemotherapy regimen identifications due to some known and some unexpected limitations of claims data and of our algorithms. A manuscript is in preparation to describe these challenges and solutions identified and implemented to overcome them. 

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 
• Terese A. Defor, Senior Manager, Research Informatics, HealthPartners Institute for Education and Research 
• 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 
• Ali McBride, PharmD, MS, BCOP, FAzPA, FASHP, Clinical Coordinator Hematology/Oncology, University of Arizona 
• Cheryl N. McMahill-Walraven, PhD, Director – Safety Surveillance & Collaboration, CVS Health Clinical Trial Services 
• 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

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.  

There is limited information available on the utilization of biosimilars versus the originator bevacizumab. The Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) will conduct a descriptive study using claims data from the five participating Research Partners to characterize the utilization patterns and patient characteristics of the bevacizumab originator and biosimilar users. The objective of this study is to evaluate utilization patterns and patient sociodemographic and clinical characteristics for the originator bevacizumab relative to its biosimilars within labeled and off-label oncology and ophthalmology conditions for which bevacizumab is used.  

Current Status 

Update – January 2022: The study protocol was reviewed and approved by the BBCIC Science Committee, and we are finalizing code lists and specifications to modify the query program for distribution to BBCIC Research Partners.  

Update – October 2021: a workgroup has begun designing a study of utilization patterns and characteristics of patients treated with bevacizumab for both cancer (on-label) and ophthalmology (off-label) indications. The study plan is near final and data specifications are in preparation. 

Research Team 

• Principal Investigator: Jenice Ko, Department of Population Medicine, Harvard Pilgrim Health Care Institute 
• TBD 

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 – January 2022: The BBCIC Science Committee reviewed and approved the study protocol so we are beginning partner contracting and code identification to inform de novo program development. 

Update – October 2021: A workgroup has been convened to plan a descriptive analysis of treatment patterns and switching among RA patients treated with immunomodulating biologics (e.g., TNFi, JAKi). We are finalizing the study proposal for Science Committee review, followed by development of a detailed protocol. 

Research Team 

• Principal Investigator: Aaron B. Mendelsohn, PhD, MPH, Senior Health Services Researcher, Department of Population Medicine, Harvard Pilgrim Health Care Institute 
• Anna Hyde, Arthritis Foundation 
• Jaclyn Bosco, PhD, MPH, Senior Director, Global Head, Epidemiology & Outcomes Research, IQVIA 
• Cara McDermott, PharmD, PhD, Research Consultant, BBCIC 
• Jerry Clewell, PharmD, MBA, Scientific Director, Immunology – Medical Payor Strategy, Abbvie 
• Hillel Cohen, PhD, Executive Director, Scientific Affairs, Sandoz 
• Seoyoung Kim, MD, ScD, MSCE, Director, Program in Rehumatologic, Immunologic, and Musculoskeletal PharmacoEpidemiology, Associate Professor of Medicine, Brigham & Women’s Hospital, Harvard Medical School 
• 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, PhD, Senior Manager, Observational Research, Amgen 
• Dottie McCabe, PhD, FCP, Executive Director, Specialty Pharmaceuticals, Clinical Development & Medical Affairs, Immunology and Biosimilars, Boehringer Ingelheim 
• Manish Mittal, PhD, Director Immunoscience, External Strategies, HEOR, Abbvie 
• Pamala A. Pawloski, PharmD, BCOP, FCCP, Senior Research Investigator, HealthPartners Institute 
• 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 – January 2022: Protocols are in development with our Italian collaborators to align as closely as possible to allow comparable data and results from our two countries. This will enable us to compare our data resources, methods, as well as clinical outcomes of interest. 

Research Team 

• Principal Investigator: Cate Lockhart, PharmD, PhD, Executive Director, BBCIC 
• TBD 

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 – January 2022: A re-run of the query is planned for mid-2022 to supplement the preliminary analysis with more recent data. 

Update – October 2021: a preliminary analysis has been completed describing utilization patterns of HER2-inhibitor products and two abstracts were accepted for poster presentation at ASCO Quality Care 2021 and AMCP Nexus 2021. The abstract accepted at AMCP Nexus received a PLATINUM RIBBON and was one of only five abstracts selected for podium presentation during the meeting!! 

Research Team 

• Principal Investigator: Young Hee Nam, PhD, Department of Population Medicine, Harvard Pilgrim Health Care Institute 

Documents 

• Study Protocol (coming soon)

Background and Objectives 

In anticipation of future BBCIC research questions, a workgroup surveyed and assessed the availability, fitness, and completeness of data from several sources not currently in the existing BBCIC network of partners. The goal was to identify opportunities to enrich current BBCIC data to better answer research questions around clinical outcomes that may not be readily available in administrative claims. This is a continuation of Phase I completed in early 2021 to gain deeper knowledge of the data resources available both within the existing BBCIC network, and to further explore the external sources we engaged with for Phase I of this study. 

Current Status 

Update – January 2022: The BBCIC Science Committee will be reviewing the draft survey soon, and once all feedback is incorporated we will begin distributing the survey and scheduling interviews with responding organizations to take a more granular look into our data resources. 

Update – October 2021: A survey is in preparation to take a deeper dive into existing network partner data resources that extend beyond the Sentinel Common Data Model, and follow-up evaluation of the external data sources who responded to the initial workgroup questionnaire. 

Research Team 

• Principal Investigator: Cara McDermott, PharmD, PhD, Research Consultant, BBCIC 
• TBD 

Documents 

• Full Study Report (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 – January 2022: In planning. 

Research Team 

• Principal Investigator: TBD 
• TBD 

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 mid-2022 with a comprehensive literature review followed by protocol development and approval by the end of 2022 or early 2023. 

Current Status 

Update – January 2022: 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)

Background and Objective 

BBCIC is excited to begin developing a strategy to engage patients throughout all aspects of our research. With guidance from two of our patient advocacy representatives, a team of BBCIC volunteers will begin preparing a plan to build our network of patients and patient groups and identify opportunities to include those important voices in our work. This effort will also identify appropriate dissemination channels for BBCIC research results and educational materials. 

Current Status 

Update – January 2022: In planning. 

Research Team 

• Co-Lead: Rebekah Angove, PhD, Vice President, Patient Experience and Program Evaluation, Patient Advocate Foundation 
• Co-Lead: Anna Hyde, Vice President of Advocacy and Access, Arthritis Foundation 
• TBD 

Documents 

• Engagement Guide (coming soon) 

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
• 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).