New Guidance Offered for Inclusion of Pathology in Clinical Trial Protocols

Tim Kendall, BM, PhD, FRCPath, Senior Clinical Fellow in Pathology, University of Edinburgh

An international group of cancer researchers led by the National Cancer Research Institute’s (NCRI’s) Cellular Molecular Pathology Initiative (CMPath) has published guidance to address the variability in how pathology (the study of the causes and effects of disease or injury) is planned and delivered in clinical trials.

The guidance, published this week in The Lancet Oncology, was produced through the development of international consensus, drawing on expertise from Africa, Asia, Australasia, Europe, and North America and from all sectors of the clinical trials community, including funders, regulators, statisticians and data managers, patient advocates, industry representatives, laboratory scientists, medical publishing representatives, and clinicians.

This guidance, called SPIRIT-Path, was developed as an extension to the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement, which provides evidence-based recommendations to address the variability in quality and content of clinical trial protocols. The SPIRIT Statement is widely endorsed by medicines developers, academia, regulators, and medical journals.

According to Dr. Tim Kendall, co-chair of the NCRI’s SPIRIT-Path working group, “Pathology is an integral component in the planning and delivery of clinical trials. To ensure methodological rigor in trials requiring pathology evaluation, for trial eligibility or outcome assessment, there is increasing recognition of the need for pathologists to be involved early in trial planning and design. However, this is not always the case. The SPIRIT-Path extension will allow investigators to comprehensively address the cellular and molecular pathology aspects of trial protocols, ensuring adequate skills and resources are available at trial commencement and [full leveraging of] the value of biospecimens for translational research.”

Dr. Max Robinson, another co-chair of the working group, added, “The SPIRIT-Path extension was conceived as a means of both maximizing the value of pathology content of clinical trial protocols and facilitating its execution. This guidance is the first international consensus project to formalize pathology input into clinical trials and is the necessary first step toward enabling next-generation pathology that fully meets the needs of precision medicine.”

SPIRIT-Path recommends that protocols should document the individuals, processes, and standards for all cellular and molecular pathology components of the trial protocol, including all stages of the specimen pathway, any digital pathology methods, and with specific consideration of the value of trial data and tissue samples for additional translational studies.

The CMPath team is now embarking on a follow-on project to develop guidelines for the reporting of pathology-related activities to complement the SPIRIT-Path extension. It is also developing a Good Clinical Practice training module in “Trials Pathology” with the intention that completion of the training by interested members of staff, irrespective of the nature or location of their department, will build a community of research-ready clinical trial pathologists.

Edited by Gary Cramer