How to Design a Real-World Study of Biologics Including Biosimilars

‎1. Course Aim ‎

This workshop will provide participants with information on the following topics:‎
‎•‎ Background on originator biologics, biosimilars and differences from small molecules ‎
‎•‎ Naming and traceability issues for biologics including biosimilars
‎•‎ Interchangeability, switching, and automatic substitution of originator and biosimilars from a regulatory, ‎methodological, and clinical perspective
‎•‎ How to design a real-world study to explore pattern of use, comparative effectiveness and safety of ‎biologics including biosimilars through interactive case study discussion
‎•‎ Selecting the most suitable source of real-world data for observational studies of biologics, including ‎either primary data collection or secondary use of available data sources such as registries, claims data ‎and electronic medical records
‎•‎ Special emphasis will be given to the methodological issues such as concerning post-marketing ‎assessment of the interchangeability of originator biologics and corresponding biosimilars ‎

‎2. Requisites Statement ‎
Entry level. Fundamental understanding of pharmacoepidemiology required, but biologic-related topics will start ‎from the basics.‎

‎3. Course Objectives
‎a. To gain an understanding of biologics including biosimilars and on the related regulatory ‎landscape
‎b.‎ To learn how to design real-world studies for studying comparative benefit-risk profile of ‎biologics in post-marketing setting in different therapeutic areas
‎c.‎ To learn specifically how to explore the interchangeability of originator biologics and ‎respective biosimilars in the real-world setting

‎4. Syllabus Outline‎

‎1.‎ Biologics: The Basics
Students will be introduced to biologics/biosimilars terminology, the big picture, complexities in the ‎marketplace that challenge researchers. Some recommended tips regarding planning ‎pharmacoepidemiologic research studies will also be described. ‎

‎2.‎ Regulatory requirements and considerations for biologicals and biosimilars ‎
This presentation will discuss the regulatory requirements for biologicals, including biosimilars. Students will be introduced to regulatory pathways for "stand-alone" biologics and biosimilars, as well as, their unique safety issues for post-marketing monitoring. Specific ‎emphasis will be placed on where real-world data/evidence may help to inform gaps in knowledge of the safety or effectiveness of biologicals, including biosimilars, from a regulatory point of view.

‎3.‎ Methodological considerations for using prospective data and multiple data sources to generate evidence
This presentation will discuss stakeholder needs to generate fit-for-purpose evidence. Students will learn ‎about different study design options and specific considerations when designing a ‎pharmacoepidemiologic study of biologics The presentation will include examples from published ‎literature.‎

‎4.‎ Methodological challenges when studying biologics/biosimilars using U.S. secondary data sources ‎
This presentation will focus on the use of U.S. secondary data sources, including administrative claims ‎and electronic health records, for conducting comparative effectiveness and safety studies of biologics / ‎biosimilars. The role of confounding by indication and misclassification biases will be discussed, ‎leveraging examples from published literature.‎

‎5.‎ Requirements and potential limitations of observational studies of biosimilars in real world settings ‎through secondary use of healthcare databases in Europe. ‎
Overview of observational studies on originator biologics and biosimilars that have been carried out or ‎are actually ongoing in Europe also through large-scale distributed claims database network and linkage ‎with clinical registries will be given. In particular, potential limitations of different data sources (e.g. ‎claims databases and electronic medical records from various EU countries in terms of addressing ‎clinically relevant questions concerning originator biologics and biosimilars will be discussed. Specific ‎issues to consider will include interchangeability of biological originator and biosimilar products, and ‎immunogenicity associated with switching between biological medicines. Some examples of database ‎studies will be provided. Finally, it will be discussed the potential impact of the COVID19 pandemic on ‎the conduct and interpretation of observational studies using large database network and clinical ‎registries in Europe.‎

‎6.‎ Interactive Case Study activity ‎
We will have two interactive case studies to apply learnings from the course lectures. Case study #1 will ‎be presented with a problem and task. Participants will be asked to answer a series of questions using ‎the polling system to prompt group discussion. For case study #2, participants will break up into smaller ‎teams and be provided instructions to tackle a research problem. Teams will have 15 minutes to design a ‎study concept. Teams will present back to the group for discussion.