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

1. To gain an understanding of biologics including biosimilars and on the related regulatory landscape
2. To learn how to design real-world studies for studying comparative benefit-risk profile of biologics in post-marketing setting in different therapeutic areas
3. 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 and clinical considerations for biologicals, including biosimilars
This presentation will discuss the regulatory requirements for biologicals, including biosimilars. Specific emphasis will be placed on the post-marketing requirements, including the Risk Management Plan, and the specific challenges in the design and conduct of post-marketing studies for biologicals, including biosimilars. The added value of switching studies (originator  biosimilar) and the regulatory, clinical and methodological challenges for the conduct of switching studies will also be discussed.

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.

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.