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SPIRIT-Path: International Guidance on the Inclusion of Pathology in Clinical Trial Protocols

SPIRIT-Path: International Guidance on the Inclusion of Pathology in Clinical Trial Protocols

Our international group of researchers, led by the National Cancer Research Institute’s (NCRI) Cellular Molecular Pathology Initiative (CMPath), has published guidance in The Lancet Oncology to address the variability in how pathology is planned and delivered in clinical trials(1).

This guidance, called SPIRIT-Path, was developed by a Core SPIRIT-Path Group in the UK and supported by an international SPIRIT-Path Advisory Group as an extension to the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement(2) that provides evidence-based recommendations to address the variability in quality and content of clinical trial protocols.

The development of the guidance has been supported from inception by the Pathological Society. 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, aligning with the Society’s focus on understanding disease through encouraging research into disease mechanisms for patient benefit and developing partnerships with other organisations in pursuit of that goal. 

The development process

Our systematic review(3) published in ‘The Journal of Pathology: Clinical Research’ (JPCR) identified and rationalised existing pathology-specific protocol guidance. The review identified 40 sources of guidance that were used to develop the candidate items for an international Delphi process. Four of these were themselves published in the Society’s journals(4–7), three of which were earlier NCRI CMPath outputs published as a series by JPCR.

Invited panellists from Africa, Asia, Australasia, Europe and North America participated in the Delphi process. This group included representatives from all sectors of the clinical trial community, including funders, regulators, statisticians and data managers, patient advocates, industry representatives, laboratory scientists, medical publishing representatives, and clinicians.

A rationalisation and consensus meeting was held with members of the international SPIRIT-Path Advisory Group to synthesise the outcomes of the Delphi process and agree upon the final extension items.

The SPIRIT-Path guidance

The SPIRIT-Path guidelines recommend 14 additional items (7 extensions to the SPIRIT checklist and 7 elaborations) regarding pathology content that should be addressed in trial protocols alongside the existing SPIRIT 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.

Maximising the value of pathology

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 fully leverage the value of biospecimens for translational research.

Dr Tim Kendall

Co-Chair and Pathological Society representative, SPIRIT-Path group

Senior Clinical Research Fellow in Pathology, University of Edinburgh

Consultant Histopathologist, NHS Lothian

1.           Kendall TJ, Robinson M, Brierley DJ, Lim SJ, O’Connor DJ, Shaaban AM, et al. Guidelines for cellular and molecular pathology content in clinical trial protocols: the SPIRIT-Path extension. Lancet Oncol. 2021 Oct 1;22(10):e435–45.

2.           Chan A-W, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, et al. SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials. Ann Intern Med. 2013 Feb 5;158(3):200–7.

3.           Lim SJ, Gurusamy K, O’Connor D, Shaaban AM, Brierley D, Lewis I, et al. Recommendations for cellular and molecular pathology input into clinical trials: a systematic review and meta-aggregation. J Pathol Clin Res. 2021;7(3):191–202.

4.           Nagtegaal ID, West NP, Krieken JHJ van, Quirke P. Pathology is a necessary and informative tool in oncology clinical trials. J Pathol. 2014;232(2):185–9.

5.           Pell R, Oien K, Robinson M, Pitman H, Rajpoot N, Rittscher J, et al. The use of digital pathology and image analysis in clinical trials. J Pathol Clin Res. 2019;5(2):81–90.

6.           Rees G, Salto‐Tellez M, Lee JL, Oien K, Verrill C, Freeman A, et al. Training and accreditation standards for pathologists undertaking clinical trial work. J Pathol Clin Res. 2019 Apr;5(2):100.

7.           Robinson M, James J, Thomas G, West N, Jones L, Lee J, et al. Quality assurance guidance for scoring and reporting for pathologists and laboratories undertaking clinical trial work. J Pathol Clin Res. 2019 Apr;5(2):91.


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