SPIRIT-Path is a project to develop international consensus guidance on the inclusion of pathology in clinical trial protocols. NCRI’s Cellular Molecular Pathology Initiative (CMPath) has set up a steering committee in order to develop an extension to the SPIRIT statement.

As part of this work, Dr Shujing Jane Lim, Newcastle upon Tyne Hospitals NHS Foundation Trust, led a systematic review to identify all pathology-specific clinical trial recommendations available in current literature and critically examine the quality and content of the advice.

Clinical trials are regarded as the “gold standard” in medical research. Yet, few are aware that the reliability of the evidence drawn from trials is highly dependent upon the robustness of the study design and methodology, which is lacking in areas where pathology input is required.

Involving pathology in clinical trial planning and design

Pathology is often an integral component in the planning and delivery of clinical trials.(1) To ensure methodological rigour in trials requiring pathology evaluation, for trial eligibility or outcome assessment, there is increasing recognition for the need for pathologists to be involved early in trial planning and design.(1-4) This is not always the case; there are low levels of engagement of pathologists in clinical trials.(2) When clinical trials are set up, the specifics of standardisation for the processing and evaluation of pathological samples is often overlooked. Investigators writing trial protocols typically have little understanding of the laboratory and pathologist’s role in their studies and may overlook key issues that need to be addressed during the design phase. The lack of standardisation of pathology-related parameters can have significant implications on trial results, leading to misleading findings and wasted resources, and can potentially pose unethical harm to patients if findings were implemented in clinical practice.

This raises the question, “What pathology-related issues should be considered when planning and carrying out clinical trials involving pathology assessment?”

Lack of single comprehensive guidance

Numerous pathologists and biomedical scientists have published their views on different specific aspects of the laboratory workflow that could improve clinical trial quality. However, there is no single comprehensive guidance document covering all aspects of pathology workflow feeding into various stages of the clinical trial process.

Identifying existing recommendations

NCRI’s CMPath has undertaken a systematic review to identify all pathology-specific clinical trial recommendations available in current literature and critically examine the quality and content of the advice. This review confirmed the current best practice and addressed any variation in pathology practice within clinical trials.

The results from the systematic review provide comprehensive guidance covering all aspects of pathology input in various stages of the clinical trial process. Seven key recommendations statements were synthesised, guiding pathology-specific parameters on the following areas of clinical trials:

  1. Multidisciplinary collaboration in trial design with early involvement of pathologists, particularly concerning the use of biospecimens and associated biomarker/analytical assays and in the evaluation of pathology-related parameters
  2. Funding and training for personnel undertaking trial work
  3. Selection of an accredited laboratory with suitable facilities to undertake scheduled work
  4. Quality assurance of pathology-related parameters
  5. Transparent reporting of pathology-related parameters
  6. Policies regarding informatics and tracking biospecimens across trial sites
  7. Informed consent for specimen collection and retention for future research

Where do we go from here?

These recommendations provide evidence for many key clinical trials stakeholders to guide decision-making when considering pathology-specific clinical trial protocol design issues. Everyone involved in clinical trials research prides themselves on evidence-based practice to provide the best for our patients. There is a vested interest for us all to implement these evidence-based recommendations into our clinical trial practice to enhance our clinical trials’ methodological rigour and reliability for the benefit of our patients worldwide.


  1. Nagtegaal ID, West NP, van Krieken JHJM, Quirke P. Pathology is a necessary and informative tool in oncology clinical trials. J Pathol. 2014;232(2):185–9.
  2. Rees G, Salto-Tellez M, Lee J, Oien K, Verrill C, Freeman A, et al. Training and accreditation standards for pathologists undertaking clinical trial work. J Pathol Clin Res. 2019;5(2):100–7.
  3. Röcken C. Quality assurance in clinical trials—the role of pathology. Vol. 468, Virchows Archiv. Springer Verlag; 2016. p. 83–92.
  4. Provenzano E, Driskell OJ, ‘O’Connor DJ, Rodriguez‐Justo M, McDermott J, Wong N, et al. The important role of the histopathologist in clinical trials: challenges and approaches to tackle them. Histopathology. 2020;235:942–9.