Methodologic considerations for noninterventional studies of switching from reference biologic to biosimilars

Abstract

Purpose: As more biosimilars become available in the United States, postapproval noninterventional studies describing biosimilar switching and comparing effectiveness and/or safety between switchers and nonswitchers will play a key role in generating real-world evidence to inform clinical practices and policy decisions. Ensuring sound methodology is critical for making valid inferences from these studies. Methods: The Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) convened a workgroup consisting of academic researchers, industry scientists, and practicing clinicians to establish best practice recommendations for the conduct of noninterventional studies of biosimilar and reference biologic switching. The workgroup members participated in eight teleconferences between August 2017 and February 2018 to discuss specific topics and build consensus. Results: This report provides workgroup recommendations covering five main considerations relating to noninterventional studies describing reference biologic to biosimilar switching and comparing reference biologic to biosimilars for safety and effectiveness in the presence of switching at treatment initiation and during followup: (a) selecting appropriate data sources from a range of available options including insurance claims, electronic health records, and registries; (b) study designs; (c) outcomes of interest including health care utilization and clinical endpoints; (d) analytic approaches including propensity scores, disease risk scores, and instrumental variables; and (e) special considerations including avoiding designs that ignore history of biologic use, avoiding immortal time bias, exposure misclassification, and accounting for postindex switching. Conclusion: Recommendations provided in this report provide a framework that may be helpful in designing and critically evaluating postapproval noninterventional studies involving reference biologic to biosimilar switching.

Flares after hydroxychloroquine reduction or discontinuation: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort

“…This approach balances the groups on the length of previous treatment at the beginning of follow‐up and avoids immortal person-time. 12 …”

“…This approach balances the groups on the length of previous treatment at the beginning of follow-up and avoids immortal person-time. 12 Patients who discontinued HCQ but started chloroquine immediately were not included in the discontinuation cohort, as they were still on an antimalarial; these were censored at the time of switching.…”

Discontinuation of infliximab treatment in patients with inflammatory bowel disease who retransitioned to originator and those who remained on biosimilar

“… 19 Retransitioned patients who could not be matched were excluded. Matching was performed based on the following criteria: (i) treatment in the same hospital, as treatment policies may differ between hospitals; (ii) transition date in the same 6-month calendar period, accounting for changes in treatment policies and treatment options over time; and (iii) duration of biosimilar use from transition date: patients were matched on the duration of biosimilar use, 20 defined as the time from transition date until the match date, as depicted in Figure 1 where patient 2 is matched with patient 1. Patient 1 received infliximab on the index date, thus the patient cannot discontinue infliximab for the next 8 weeks (standard infliximab dosing interval 21 ).…”

Impact of Infliximab-dyyb (Infliximab Biosimilar) on Clinical and Patient-Reported Outcomes: 1-Year Follow-up Results from an Observational Real-World Study Among Patients with Inflammatory Bowel Disease in the US and Canada (the ONWARD Study)

“…To date, only limited real-world data have been published on the use of infliximab-dyyb, and the clinical and patient-reported outcomes in IBD patients treated with infliximab-dyyb, in the North American population. Post-approval non-interventional studies evaluating comparative outcomes can play a key role in building a real-world evidence base to help inform clinical practices and policy decisions [18]. Therefore, the goal of this study was to understand realworld treatment patterns of infliximab-dyyb and to assess its effects on clinical outcomes, patient-reported outcomes (PROs), and healthcare resource use in adult UC and CD patients treated with infliximab-dyyb in a real-world North American setting.…”