Guidelines for cellular and molecular pathology content in clinical trial protocols: the SPIRIT-Path extension


Session type:

Ian Lewis1, Max Robinson2, Timothy J. Kendall3, Daniel J. Brierley4, Shujing Jane Lim2, Daniel O’Connor5, Abeer Shaaban6, An-Wen Chan7, David Harrison8
1National Cancer Research Institute (NCRI), 2Newcastle upon Tyne Hospitals NHS Foundation Trust, 3University of Edinburgh, 4University of Sheffield, 5Other, 6Queen Elizabeth Hospital Birmingham, 7University of Toronto, 8University of St Andrews



Despite the importance of trial protocols, their quality and content are known to be variable. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement provides evidence-based recommendations for the minimum content of clinical trial protocols to address this variability and is widely endorsed by medicines developers, academia, regulators and medical journals.

SPIRIT-Path is an international project coordinated by the National Cancer Research Institute’s (NCRI) Cellular and Molecular Pathology Initiative (CMPath) that has now extended the SPIRIT 2013 Statement for trials that include cellular and molecular pathology protocol content.

The extension offers guidance to authors of clinical trial protocols to ensure all possible steps, including aspects of specimen handling and reporting, are identified at trial inception.



The SPIRIT-Path Extension was developed using an international Delphi process assessing candidate items generated from a prior systematic review, followed by an expert consensus meeting.  74 selected individuals from five continents responded, including clinicians, statisticians, laboratory scientists, patient advocates, funders, industry representatives, journal editors, and regulators.


The SPIRIT-Path guidelines recommend 14 additional items, 7 extensions to the SPIRIT checklist and 7 elaborations, that should be addressed in trial protocols with pathology content alongside the SPIRIT 2013 Statement items. 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 for additional translational studies.


The SPIRIT-Path extension will allow trial protocols to comprehensively address cellular and molecular pathology aspects, ensuring adequate skills and resources are available at trial commencement to facilitate the smooth running of laboratory-based components of the trial and fully leverage the value of biospecimens for translational research.

Impact statement

The SPIRIT-Path extension was conceived as a means of both maximising the value of pathology content of clinical trial protocols and facilitating its execution. We believe that this guidance is the necessary first step towards enabling an international next-generation approach to pathology that fully meets the needs of precision medicine.