Implementing pharmacogenetics in clinical trials: considerations about current methodological, ethical, and regulatory challenges

ABSTRACT

Introduction

The implementation of pharmacogenetic analysis within clinical trials faces methodological, ethical, and regulatory challenges, as well as tackling the difficulty in obtaining actionable information with a sufficient level of evidence to enable its integration into routine clinical practice.

Areas covered

We discuss the current status of pharmacogenetics integration in clinical trials, underscore the associated challenges, and make some suggestions on the aspects to address in any clinical trial including a pharmacogenetic evaluation. We conducted a literature review, thoroughly reviewed the applicable regulations and available guidelines, and assessed the application dossiers submitted for evaluation to the Ethics committee of Hospital La Paz (Madrid, Spain) to extract information related to inclusion of pharmacogenetics evaluations.

Expert opinion

The integration of pharmacogenetics into clinical trials is becoming increasingly common. However, several regulatory, methodological and ethical aspects involved are insufficiently addressed. There is a need for specific and transparent guidelines that establish unified and compliant criteria for methodology, proper handling of samples in compliance with regulations, and the protection of data privacy and confidentiality. Participants should receive complete and appropriate information regarding the purpose, handling, storage, and transfer of their samples and data, and should have the right to decide about their processing.

KEYWORDS:

• Pharmacogenetics
• clinical trials
• methodological challenges
• regulatory challenges
• ethical considerations
• privacy and confidentiality

Article highlights

• The integration of pharmacogenetics into clinical trials is becoming increasingly common and could potentially lead to drug costs reduction by minimizing the size and duration of clinical trials and enabling earlier decisions in the development process.

• Applicable European regulations offer limited specificity regarding the prerequisites for incorporating pharmacogenetics into clinical trial designs, allowing for a broad scope of interpretation and action which results in the collection and used of data and samples without clearly specifying the purpose or how they will be managed and stored.

• Establishing an appropriate methodology in advance is essential to make the most of pharmacogenetic research.

• The performance of pharmacogenetic analysis within clinical trials necessarily implies the collection of biological samples from participating subjects and the handling of personal data, which is associated with a range of ethical implications.

• There is a need for specific and transparent guidelines that establish unified criteria for methodology, proper handling of samples in compliance with regulations, and the protection of data privacy and confidentiality.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Acknowledgement

We would like to thank Emma Fernández de Uzquiano, Head of the Technical Secretariat of the Clinical Research Ethics Committee of Hospital La Paz, and Elena García Méndez, Member of the Technical Secretariat, for granting access to the documents of the clinical trials evaluated and for providing support during the data collection, as well as facilitating the preparation of this manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.