Incidence of Serious Infections and Design of Utilization and Safety Studies for Biologic and Biosimilar Surveillance.

BACKGROUND: There is a need for postmarketing evidence generation for novel biologics and biosimilars. OBJECTIVE: To assess the feasibility, strengths, and limitations of the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) Distributed Research Network (DRN) to examine the utilization and comparative safety of immune-modulating agents among patients with autoimmune diseases. METHODS: We conducted a retrospective cohort study among patients enrolled in health insurance plans participating in the BBCIC DRN between January 1, 2006, and September 30, 2015. Eligible patients were adult (≥18 years) new users of a disease-modifying nonbiologic and/or biologic agent with a prior diagnosis of rheumatoid arthritis (RA), other inflammatory conditions (psoriasis, psoriatic arthritis, ankylosing spondylitis), or inflammatory bowel disease (IBD). Follow-up started at treatment initiation and ended at the earliest of outcome occurrence (serious infection); treatment discontinuation; or switching, death, disenrollment, or end of study period. The study leveraged the FDA Sentinel System infrastructure for data management and analysis; descriptive statistics of patient characteristics and unadjusted incidence rates of study outcomes during follow-up were calculated. RESULTS: Eligible patient drug episodes included 111,611 with RA (75% female), 61,050 with other inflammatory conditions (51% female), and 30,628 with IBD (52% female). Across all 3 cohorts, approximately half of the patient drug episodes initiated a biologic (50% in RA; 60% in psoriasis, psoriatic arthritis, ankylosing spondylitis; and 55% in IBD). The crude incidence rate of serious infection was 9.8 (9.5-10.0) cases per 100 person-years in RA, 7.1 (6.8-7.5) in other inflammatory conditions, and 14.2 (13.6-14.8) in IBD patients. CONCLUSIONS: This study successfully identified large numbers of new users of biologics and produced results that were consistent with those from earlier published studies. The BBCIC DRN is a potential resource for surveillance of biologics. DISCLOSURES: This study was funded by the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC). HealthCore conducted this study in collaboration with Harvard Pilgrim Health Care. Zhang and Sridhar were employed by HealthCore at the time of this study. Haynes is employed by HealthCore funded by PCORI, the NIH, and the FDA. Barr and Eichelberger were employed by AMCP at the time of this study. Lockhart is employed by the BBCIC. Holmes and Clewell are employed by AbbVie. Accrott is an employee of and shareholder in Amgen. Marshall and Brown are employed by Harvard Pilgrim Health Care. Barr is a shareholder in Roche/Genentech. Curtis has received research grants from and consults with the following: Amgen, AbbVie, BMS, CORRONA, Lilly, Janssen, Myriad, Pfizer, Roche, Regeneron, and UCB. Brown has received research grants from GSK and Pfizer and consulting fees from Bayer, Roche, and Jazz Pharmaceuticals, along with funding from the Reagan-Udall Foundation for the FDA to conduct studies for medical product manufacturers, including Eli Lilly, Novartis, Abbvie, and Merck. Brown is also funded by PCORI, the NIH, and the FDA. McMahill-Walraven subcontracts with Harvard Pilgrim Health Care Institute for public health and safety surveillance distributed data network activtities and with the FDA, GSK, and Pfizer. She also reports fees from Reagan Udall Foundation for the FDA and the Patient Centered Outcomes Research Institute.

Harnessing the Biologics and Biosimilars Collective Intelligence Consortium to Evaluate Patterns of Care.

INTRODUCTION: As clinical trials test efficacy rather than effectiveness of medications, real-world effectiveness data often vary from clinical trial data. Given the recent market entry of multiple biologics and biosimilars, a dedicated assessment of these diverse agents is needed to build the evidence base regarding efficacy and safety of innovator biologics and biosimilars. PROGRAM DESCRIPTION: The Academy of Managed Care Pharmacy's Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) was convened to address the lack of real-world, postmarket outcome evidence generation for innovator biologics and corresponding biosimilars. The BBCIC is a multistakeholder scientific research consortium whose participants prioritize topics and collaboratively conduct research studies. The BBCIC conducts a wide range of analyses, including population characterization, epidemiologic studies, and active observational studies, and develops best practices for conducting large-scale studies to provide real-world evidence. OBSERVATIONS: Over the past 3 years, we undertook multiple descriptive analyses with the goal of characterizing data availability and demonstrating the feasibility and efficacy of using the BBCIC distributed research network (DRN), which includes commercial claims data from 2008-2018 covering approximately 100 million lives, with approximately 20 million active members in 2017 from 2 major U.S. health plans and 3 regional integrated delivery networks. We analyzed 4 medication classes of particular interest to biologics and biosimilars development: insulins, granulocyte colony-stimulating factors, erythropoietic-stimulating agents, and anti-inflammatories. We were able to identify exposures and user characteristics in all 4 categories. Herein we describe the successes and challenges of conducting some of our analyses, specifically among insulin users with type 1 diabetes mellitus. IMPLICATIONS: Our results demonstrate the BBCIC DRN's ability to identify and characterize exposures, cohorts, and outcomes that can contribute to more sophisticated comparative surveillance of biosimilars and innovator biologics in the future. Additional linkages to laboratory data and a wider range of insurance carriers will further strengthen the BBCIC DRN. DISCLOSURES: This study was coordinated and funded by the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) and represents the independent findings of the BBCIC Insulins Principal Investigator and the BBCIC Insulins Research Team. Lockhart is employed by the BBCIC; Eichelberger was employed by the BBCIC at the time of this study. McMahill-Walraven is employed by Aetna, a CVS Health business. Panozzo, Marshall, and Brown are employed by Harvard Pilgrim Healthcare Institute. Aetna receives external funding through research grants and subcontracts with Harvard Pilgrim Healthcare Institute, which are funded by the FDA, NIH, PCORI, BBCIC, Pfizer, and GSK; the Reagan-Udall Foundation for IMEDS; and PCORI for the ADAPTABLE Study. Aetna was reimbursed for data and analytic support from Harvard Pilgrim Healthcare Institute and the Reagan Udall Foundation for the U.S. Food and Drug Administration. This work was presented as a poster at AMCP Nexus 2018; October 22-25, 2018; in Orlando, FL.

Got CER? Educating Pharmacists for Practice in the Future: New Tools for New Challenges.

BACKGROUND: Understanding how treatments work in the real world and in real patients is an important and complex task. In recent years, comparative effectiveness research (CER) studies have become more available for health care providers to inform evidence-based decision making. There is variability in the strengths and limitations of this new evidence, and researchers and decision makers are faced with challenges when assessing the quality of these new methods and CER studies. OBJECTIVES: To (a) describe an online tool developed by the CER Collaborative, composed of the Academy of Managed Care Pharmacy, the International Society for Pharmacoeconomics and Outcomes Research, and the National Pharmaceutical Council, and (b) provide an early evaluation of the training program impact on learners' self-reported abilities to evaluate and incorporate CER studies into their decision making. METHODS: To encourage greater transparency, consistency, and uniformity in the development and assessment of CER studies, the CER Collaborative developed an online tool to assist researchers, new and experienced clinicians, and decision makers in producing and evaluating CER studies. A training program that supports the use of the online tool was developed to improve the ability and confidence of individuals to apply CER study findings in their daily work. Seventy-one health care professionals enrolled in 3 separate cohorts for the training program. Upon completion, learners assessed their abilities to interpret and apply findings from CER studies by completing on online evaluation questionnaire. RESULTS: The first 3 cohorts of learners to complete the training program consisted of 71 current and future health care practitioners and researchers. At completion, learners indicated high confidence in their CER evidence assessment abilities (mean = 4.2). Learners reported a 27.43%-59.86% improvement in capabilities to evaluate various CER studies and identify study design flaws (mean evaluation before CER Certificate Program [CCP] scores = 1.86-3.14 and post-CCP scores = 3.92-4.24). Additionally, 63% of learners indicated that they expected to increase their use of evidence from CER studies in at least 1-2 problem decisions per month. CONCLUSIONS: The CER Collaborative has responded to the need for increased practitioner training to improve understanding and application of new CER studies. The CER Collaborative tool and certificate training program are innovative solutions to help decision makers meet the challenges they face in honing their skills to best incorporate credible and relevant CER evidence into their decision making. DISCLOSURES: The CER Collaborative, the development of the questionnaires and web-based tool, and the development of the CER Certificate Program were supported by grants and in-kind contributions from the Academy of Managed Care Pharmacy (AMCP), the International Society for Pharmacoeconomics and Outcomes Research (ISPOR), and the National Pharmaceutical Council (NPC). The University of Maryland School of Pharmacy conducted its work under a contract with the AMCP Foundation and grant funding from the NPC. Perfetto is employed by the University of Maryland and the National Health Council and serves as assistant editor for the Journal of Managed Care & Specialty Pharmacy, consults for Avelere, and serves as a member of advisory boards for the PQA and CMTP. Pickering received support from the NPC for activities related to this research. Eichelberger is employed by the Academy of Managed Care Pharmacy. Eichelberger and Graff are with the CER Collaborative. Graff is employed by the National Pharmaceutical Council. Study concept and design were primarily contributed by Perfetto, Graff, and Eichelberger, along with Anyanwu and assisted by Pickering and Ward Zaghab. Pickering and Ward Zaghab took the lead in data collection, with assistance from the other authors, and data interpretation was performed by Perfetto, Graff, Pickering, and Ward Zaghab, with assistance from the other authors. The manuscript was written by Perfetto and Anyanwu, with assistance from the other authors, and revised by Graff, Perfetto, Anyanwu, and Pickering, assisted by Eichelberger and Ward Zaghab.

Utilizing data consortia to monitor safety and effectiveness of biosimilars and their innovator products.

BACKGROUND: The Biologics Price Competition and Innovation Act, introduced as part of the Affordable Care Act, directed the FDA to create an approval pathway for biologic products shown to be biosimilar or interchangeable with an FDA-approved innovator drug. These biosimilars will not be chemically identical to the reference agent. Investigational studies conducted with biosimilar agents will likely provide limited real-world evidence of their effectiveness and safety. How do we best monitor effectiveness and safety of biosimilar products once approved by the FDA and used more extensively by patients? OBJECTIVE: To determine the feasibility of developing a distributed research network that will use health insurance plan and health delivery system data to detect biosimilar safety and effectiveness signals early and be able to answer important managed care pharmacy questions from both the government and managed care organizations. METHODS: Twenty-one members of the AMCP Task Force on Biosimilar Collective Intelligence Systems met November 12, 2013, to discuss issues involved in designing this consortium and to explore next steps. RESULTS: The task force concluded that a managed care biosimilars research consortium would be of significant value. Task force members agreed that it is best to use a distributed research network structurally similar to existing DARTNet, HMO Research Network, and Mini-Sentinel consortia. However, for some surveillance projects that it undertakes, the task force recognizes it may need supplemental data from managed care and other sources (i.e., a "hybrid" structure model). CONCLUSIONS: The task force believes that AMCP is well positioned to lead the biosimilar-monitoring effort and that the next step to developing a biosimilar-innovator collective intelligence system is to convene an advisory council to address organizational governance.