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Published on: June 21, 2018
Analysis of drug combinations: current methodological landscape
Julie Foucquier1, Mickael Guedj1
1Department of Bioinformatics and Biostatistics, Pharnext Issy-Les-Moulineaux, France.
Abstract:
Combination therapies exploit the chances for better efficacy, decreased toxicity, and reduced development of drug resistance and owing to these advantages, have become a standard for the treatment of several diseases and continue to represent a promising approach in indications of unmet medical need. In this context, studying the effects of a combination of drugs in order to provide evidence of a significant superiority compared to the single agents is of particular interest. Research in this field has resulted in a large number of papers and revealed several issues. Here, we propose an overview of the current methodological landscape concerning the study of combination effects. First, we aim to provide the minimal set of mathematical and pharmacological concepts necessary to understand the most commonly used approaches, divided into effect-based approaches and dose-effect-based approaches, and introduced in light of their respective practical advantages and limitations. Then, we discuss six main common methodological issues that scientists have to face at each step of the development of new combination therapies. In particular, in the absence of a reference methodology suitable for all biomedical situations, the analysis of drug combinations should benefit from a collective, appropriate, and rigorous application of the concepts and methods reviewed here.
Insights
Combination therapies offer improved efficacy and reduced toxicity, making them crucial for treating diseases. This review clarifies methods for studying drug combinations to ensure rigorous and effective therapeutic development.
Area of Science:
- Pharmacology
- Biostatistics
- Drug Development
Background:
- Combination therapies are increasingly vital for treating complex diseases, offering enhanced efficacy and reduced toxicity.
- Despite their advantages, challenges in studying drug combination effects persist, necessitating methodological clarity.
Purpose of the Study:
- To provide an overview of the current methodological landscape for studying drug combination effects.
- To elucidate essential mathematical and pharmacological concepts underpinning common combination study approaches.
- To identify and discuss key methodological issues in developing new combination therapies.
Main Methods:
- Review and synthesis of existing literature on combination therapy study methodologies.
- Categorization of approaches into effect-based and dose-effect-based methods.
- Discussion of practical advantages, limitations, and common challenges.
Main Results:
- Established foundational concepts for understanding combination effect analyses.
- Detailed comparison of effect-based and dose-effect-based approaches.
- Identified six critical methodological issues encountered in combination therapy development.
Conclusions:
- A standardized, universally applicable methodology for all biomedical situations is currently absent.
- Rigorous and collective application of reviewed concepts and methods is essential for advancing drug combination studies.
- Improved methodological understanding can accelerate the development of superior combination therapies.
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