Peter Robinson is a Medical Student at Newcastle University. He has completed a project looking at the clinical trial activity by the Department of Cellular Pathology at Newcastle Hospitals using SPIRIT-Path guidelines, which has been published in the Journal of Pathology: Clinical Research.
Last summer I took part in a research project with support from the Pathological Society of Great Britain and Ireland, as part of their undergraduate bursary scheme. The project was ‘An assessment of clinical trial activity by the Department of Cellular Pathology at Newcastle Hospitals’, which allowed me to explore my interest in clinical trials and the integration of P4 (predictive, personalised, preventive, participatory) medicine into clinical research(1). The discipline of pathology is fundamental to contemporary clinical trials as pathologists can utilise their latest understanding of disease mechanisms and diagnostic technology to stratify patients for interventions. The speed of the COVID-19 vaccine development and approval amazed me and the resilience of Katalin Karikó to continue to investigate mRNA technology despite setbacks inspired me to explore clinical research(2,3).
Clinical trial protocols are key documents that outline the ‘study rationale, proposed methods, organisation and ethical considerations’ of a trial(4). A comprehensive well-written protocol is essential for approval by ethical and regulatory agencies, fulfilment of trial objectives, reproducibility of trial data and participant safety(5). The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement is a 33-item checklist providing evidence-based recommendations for the minimum content of clinical trial protocols and is widely endorsed by academia and industry(4,6). Since the publication of SPIRIT there have been extensions to address specific protocol elements not fully addressed by the original guidelines. The SPIRIT-Path extension provides 14 additional items that specifically address the minimum pathology content for clinical trials(7).
Clinical trial activity at Newcastle University
The project was based on activity at the Newcastle upon Tyne Hospitals NHS Foundation Trust as it has an important role in clinical trial delivery as one of five National Institute for Health Research (NIHR) Patient Recruitment Centres (PRCs)(8). PRCs have been established to ‘increase the UK’s capacity to deliver late-phase commercial clinical research’, facilitate ‘commercial clinical research in the National Health Service’ and provide ‘opportunities for patients to benefit from early access to innovation’(9).
The project had four aims:
- Identify the clinical trials that the Department of Cellular Pathology at Newcastle Hospitals is currently supporting.
- Assess clinical trial protocols against the SPIRIT-Path checklist.
- Outline the pathology activities supporting the trials.
- Establish the funding arrangements for the pathology activities.
Increasing understanding of pathology-related clinical trial activities
Taking part in this project has been rewarding and has made me aware of the challenges of research, such as responding and reacting to new information and time constraints. Throughout the project I have had numerous opportunities to receive feedback on my work from SPIRIT-Path core members. This has highlighted the importance of collaboration with experts to maximise the information gained from a study.
At the end of the project, I had the opportunity to present my findings to a SPIRIT-Path core group member which improved my confidence in presenting information in a clear and concise manner. Drafting a manuscript for the investigator helped me to develop my academic writing skills and taught me the importance of scrutinising and critically appraising information when finding references to support my work. The paper has subsequently been published in the Journal of Pathology Clinical Research(10).
During the eight week project I had the opportunity to speak to scientists and pathologists about their involvement in clinical trials. I gained an appreciation of the importance of laboratory processes and how pathologists contribute to the assessment of patient inclusion criteria, evaluate the response to interventions and support quality assurance procedures. I was invited to listen to Trial Management Group (TMG) meetings which helped me appreciate the challenges in co-ordinating multi-centre clinical trials. Particularly for non-commercial trials there were issues in obtaining funding for exploratory research and shipment of tissue for bio-banking. I gained an insight into the multidisciplinary nature of clinical trials and the importance of involving patient advocates to assess the acceptability of trial design and ensure transparency in reporting trial outcomes(11).
It was exciting to explore first-hand pathology-related clinical trial activities in the clinical laboratory, such as slide production and immunohistochemistry testing, which made me appreciate the work of laboratory staff in the smooth running of clinical trials. The experience had added value, as during COVID I did not have many opportunities to speak to clinicians in person; most of the first-year medical course at Newcastle University was delivered online. The positive experience of this project has motivated me to conduct another project through Newcastle University’s Climate Leadership Scholarship which will explore sustainability in surgery. I am looking forwards to building on these experiences in medical school and throughout my future career.
- Hood L, Friend SH. Predictive, personalized, preventive, participatory (P4) cancer medicine. Nat Rev Clin Oncol. 2011;8:184-187.
- Dolgin E. The tangled history of mRNA vaccines. 2021;597:318-324.
- Standage T. Gamechangers: Don’t shoot the messenger [Internet]. The Economist; 2021. Available from: https://www.economist.com/podcasts/2021/07/19/dont-shoot-the-messenger-the-pioneers-of-mrna [Accessed: 20/09/2021]
- Chan A-W, Tetzlaff JM, Gøtzsche PC, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. 2013;346:e7586.
- Chan A-W,Tetzlaff JM, Altman DG, et al. SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials. Ann Intern Med. 2013;158(3):200-207.
- Endorsement. Available from: https://www.spirit-statement.org/about-spirit/spirit-endorsement/ [Accessed: 20/09/2021].
- Kendall TJ, Robinson M, Brierley DJ, et al. Guidelines for cellular and molecular pathology content in clinical trial protocols: the SPIRIT-Path extension. Lancet Oncol. 2021;22(10):435-445.
- National Institute for Health Research. Patient Recruitment Centre: Newcastle. Available from: https://local.nihr.ac.uk/prc/newcastle/ [Accessed: 20/09/2021]
- National Institute for Health Research. National Patient Recruitment Centres. Available from: https://www.nihr.ac.uk/explore-nihr/support/national-patient-recruitment-centres.htm [Accessed: 20/09/2021]
- Robinson P, Bacon CM, Lim SJ, et al. Assessment of clinical trial protocols for pathology content using the SPIRIT-Path guidelines highlights areas for improvement. J Pathol Clin Res. 2022 May 31; in press. doi: 10.1002/cjp2.274.
- Batten LM, Bhattacharya IS, Moretti L, et al. Patient advocate involvement in the design and conduct of breast cancer clinical trials requiring the collection of multiple biopsies. Res Involv Engagem. 2018;4:22.