BBCIC Range of Research
The BBCIC will conduct a range of analyses from population characterization, epidemiologic studies, and active observational sequential analysis of biologics/biosimilars using a distributed network of healthcare organizations.
Specific observational research activities may include, but are not limited to:
- Population characterization and natural history, for example:
- Disease prevalence
- Product exposure
- Product utilization, switching and adherence
- Characterization of subpopulations or cohorts
- Safety (with and without the comparative dimension), for example:
- Detecting frequency of events
- Assessing clinical loss of efficacy over time
- Comparing among products’ acute reactions such as anaphylaxis, injection site reactions and flu-like symptoms
- Effectiveness (with and without the comparative dimension), for example:
- Focusing on clinical endpoints/measurable efficacy
- Assessing real-world dosing
- Assessing compliance and gaps in therapy
BBCIC 2017-2018 Research Plan
Specific Research Plans and Protocols are posted at www.clinicaltrials.gov once they are written and approved by the BBCIC Science Committee and Planning Board. The 2019-2020 Research plan covers:
Comparative Effectiveness Research (CER). The goal of this research is to generate real-world information from observational data on the comparative safety and effectiveness between biosimilars and their reference biologics. These protocols will characterize patient populations, exposures, outcomes, treatment patterns, and will identify differences based on treatment regimen. Utilization is increasing and research will commence for each biosimilar product as sufficient exposure is captured in the BBCIC DRN.
- Granulocyte Colony Stimulating Factors (G-CSF). The first CER team is being convened in Q1 2019 to focus on G-CSF. Outcomes of interest will include 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 the white cells are low. All filgrastim products available in the U.S. will be included in this study.
- Long- and Intermediate-Acting Insulins. There is sufficient exposure in the BBCIC DRN to insulin glargine and the available follow-on biologic to begin a CER study in Q3 2019. Outcomes of interest will include control of blood sugar and the incidence of hypoglycemia and major cardiac events in patients with Type 1 and Type 2 diabetes. A Patient Reported Outcome (PRO) element will also be included in this study to capture the patient experience through a mobile phone app.
Descriptive Analysis Studies. A precursor to actual observational research studies, these protocols establish indicators to be measured by characterizing patient populations, identifying exposures and outcomes, as well as patterns of use and clinical risk factors that may influence patient response. The following descriptive studies are planned to convene in 2019:
- Oncology Data Fitness and Descriptive Analysis. To prepare the BBCIC to conduct CER in oncology, the current data capabilities of the BBCIC DRN will be evaluated, in addition to identification of additional data sources to enrich BBCIC capabilities in measures relevant to oncology outcomes including cancer stage, and some effectiveness measures that may not be readily available in standard administrative claims data sets. This work will establish the BBCIC DRN to conduct future product- or disease-specific CER.
- Switching Patterns Descriptive Analysis. Switching between biosimilars and reference biologics, or between different classes medication, is a challenge in CER studies as it introduces potential bias and complicates the study design. Building upon the Switching Methods Workgroup recommendations, study designs and methods for handling switching as a confounder or covariate will be tested in the BBCIC DRN. Anti-Inflammatory agents will be used as a test case.
Four descriptive analysis studies have been completed and manuscripts are expected to be published in 2019. The following descriptive analyses have been completed:
- Biologic Anti-inflammatory Therapies (AI): 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: 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): 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 the white cells are low. (NCT 02922192)
- Erythropoietin Stimulating Agents (ESAs): Chronicity of hemodialysis (HD) and important covariates and confounders for the HD populations will be identified among the selected BBCIC data partners. We will assess whether we have a sufficiently similar population of HD patients to that described by the USRDS.
Data and Standards Working Groups. As we wait for adequate biosimilar utilization in the U.S. to conduct CER studies, four working groups were convened in 2017 and 2018 to address known or newly identified methodologic challenges and gaps in existing data sources, and to develop solutions to support future CER work. This work has concluded, and publications are expected in 2019.
- 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. This included discussion of design and analytic options (e.g., propensity score methods, discontinuity or instrumental variables, difference-in-difference) and identification of options for supplemental analyses to address the potential alternate explanations for observed effects.
- ICD9 to ICD10 Mapping. To prepare to conduct CER, all ICD9 criteria from current Descriptive Analysis Protocols have been converted 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. For optimal product identification of biologics and biosimilars, NDCs are recommended for all physician office claims. A research team conducted a descriptive analysis of occurrence of NDCs and J-codes in the Procedure Table of the common data model (CDM). We also explored capture of NDC in data partner claims data warehouses.
- Switching Pattern Workgroup. As we wait for sufficient infliximab biosimilar exposures to conduct CER, we are conducted an initial descriptive analysis work on innovator switching patterns. The purpose of this Workgroup 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. Recommendations used anti-inflammatory agents as a case study but will include considerations for switching studies in other biologic classes.
Monitoring Queries. To take advantage of the uniquely large data network in the BBCIC, we are conducting routine data queries across the BBCIC DRN to identify biosimilar and reference biologic utilization patterns, and to define the baseline and demographic characteristics of the populations of interest.