GP referrals for suspected cancer in Ireland: protocol for a cross-sectional study (GRACCHUS)

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Murphy" }, { "@type": "Person", "name": "Benjamin Jacob" }, { "@type": "Person", "name": "Yiren Yin" }, { "@type": "Person", "name": "Heather Burns" }, { "@type": "Person", "name": "Kathleen Bennett" }, { "@type": "Person", "name": "Patrick Redmond" } ], "publisher": { "@type": "Organization", "name": "HRB Open Research", "logo": { "@type": "ImageObject", "url": "https://hrbopenresearch.org/img/AMP/HRB_image.png", "height": 566, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://hrbopenresearch.org/img/AMP/HRB_image.png", "height": 1200, "width": 127 }, "description": " Background Cancer is a leading cause of mortality in Ireland, accounting for approximately 30% of deaths annually. Early diagnosis improves survival, reduces treatment burden, and enhances patient outcomes. Rapid Access Clinics (RACs) were introduced to facilitate expedited diagnosis of suspected lung, prostate, and breast cancers, as well as malignant melanoma. However, the extent to which Irish general practitioners (GPs) utilise RAC pathways, and the subsequent diagnostic outcomes, remain poorly understood. Methods This retrospective repeated cross-sectional study will analyse electronic health records from Irish general practices (2013–2024). Phase 1 will assess trends in RAC referrals, including volume, cancer type, and inter-practice variation, alongside demographic, geographic, and clinical factors influencing referral rates. Phase 2 will evaluate cancer conversion rates, time to diagnosis, stage at diagnosis, treatment received, and cancer-specific mortality. Data collection will use a validated extraction tool, and analysis will follow STROBE guidelines for observational studies. Expected Outcomes This study will quantify RAC referral patterns and identify factors influencing variability in GP referral behaviour. It will also assess diagnostic yield and cancer outcomes associated with RAC referrals. Findings will inform quality improvement initiatives and policy development to optimise cancer diagnostic pathways in Ireland. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://hrbopenresearch.org/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://hrbopenresearch.org/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://hrbopenresearch.org/articles/8-52", "name": "GP referrals for suspected cancer in Ireland: protocol for a cross-sectional..." } } ] } Home Browse GP referrals for suspected cancer in Ireland: protocol for a cross-sectional... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Killeen K, O'Regan S, Murphy CF et al. GP referrals for suspected cancer in Ireland: protocol for a cross-sectional study (GRACCHUS) [version 2; peer review: 2 approved] . HRB Open Res 2025, 8 :52 ( https://doi.org/10.12688/hrbopenres.14109.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Study Protocol Revised GP referrals for suspected cancer in Ireland: protocol for a cross-sectional study (GRACCHUS) [version 2; peer review: 2 approved] Katie Killeen 1 , Sean O'Regan 1 , Conor F. Murphy https://orcid.org/0009-0003-1166-0207 1 , [...] Benjamin Jacob https://orcid.org/0000-0003-1119-064X 1 , Yiren Yin 1 , Heather Burns 2 , Kathleen Bennett https://orcid.org/0000-0002-2861-7665 3 , Patrick Redmond 1 Katie Killeen 1 , Sean O'Regan 1 , [...] Conor F. Murphy https://orcid.org/0009-0003-1166-0207 1 , Benjamin Jacob https://orcid.org/0000-0003-1119-064X 1 , Yiren Yin 1 , Heather Burns 2 , Kathleen Bennett https://orcid.org/0000-0002-2861-7665 3 , Patrick Redmond 1 PUBLISHED 01 Aug 2025 Author details Author details 1 Department of General Practice, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland 2 National Cancer Control Programme, Health Service Executive, Dublin, Ireland 3 Data Science Centre, School of Population Health, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland Katie Killeen Roles: Investigation, Project Administration, Writing – Original Draft Preparation Sean O'Regan Roles: Conceptualization, Investigation, Methodology, Software, Writing – Original Draft Preparation Conor F. Murphy Roles: Conceptualization, Methodology, Project Administration, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Benjamin Jacob Roles: Conceptualization, Investigation, Methodology, Software, Supervision, Writing – Review & Editing Yiren Yin Roles: Investigation, Writing – Original Draft Preparation Heather Burns Roles: Conceptualization, Methodology, Writing – Review & Editing Kathleen Bennett Roles: Methodology, Writing – Review & Editing Patrick Redmond Roles: Conceptualization, Investigation, Methodology, Project Administration, Resources, Supervision, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Background Cancer is a leading cause of mortality in Ireland, accounting for approximately 30% of deaths annually. Early diagnosis improves survival, reduces treatment burden, and enhances patient outcomes. Rapid Access Clinics (RACs) were introduced to facilitate expedited diagnosis of suspected lung, prostate, and breast cancers, as well as malignant melanoma. However, the extent to which Irish general practitioners (GPs) utilise RAC pathways, and the subsequent diagnostic outcomes, remain poorly understood. Methods This retrospective repeated cross-sectional study will analyse electronic health records from Irish general practices (2013–2024). Phase 1 will assess trends in RAC referrals, including volume, cancer type, and inter-practice variation, alongside demographic, geographic, and clinical factors influencing referral rates. Phase 2 will evaluate cancer conversion rates, time to diagnosis, stage at diagnosis, treatment received, and cancer-specific mortality. Data collection will use a validated extraction tool, and analysis will follow STROBE guidelines for observational studies. Expected Outcomes This study will quantify RAC referral patterns and identify factors influencing variability in GP referral behaviour. It will also assess diagnostic yield and cancer outcomes associated with RAC referrals. Findings will inform quality improvement initiatives and policy development to optimise cancer diagnostic pathways in Ireland. READ ALL READ LESS Keywords Primary Health Care; Early Detection of Cancer; Referral and Consultation; Diagnostic Services; Cross-Sectional Studies; Ireland. Corresponding Author(s) Conor F. Murphy ( [email protected] ) Close Corresponding author: Conor F. Murphy Competing interests: No competing interests were disclosed. Grant information: Health Research Board [APA-2024-001]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2025 Killeen K et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Killeen K, O'Regan S, Murphy CF et al. GP referrals for suspected cancer in Ireland: protocol for a cross-sectional study (GRACCHUS) [version 2; peer review: 2 approved] . HRB Open Res 2025, 8 :52 ( https://doi.org/10.12688/hrbopenres.14109.2 ) First published: 09 Apr 2025, 8 :52 ( https://doi.org/10.12688/hrbopenres.14109.1 ) Latest published: 01 Aug 2025, 8 :52 ( https://doi.org/10.12688/hrbopenres.14109.2 ) Revised Amendments from Version 1 In response to the valuable peer review feedback we received, the following changes were made to the manuscript: 1. Text in first section of the introduction entitled Cancer burden and the importance of early diagnosis was updated to highlight the beneficial impact early detection of cancer can have on reducing treatment burden and complexity. 2. Statistics cited in this paragraph were updated to include figures for prostate cancer 5-year survival and stage at diagnosis. Figures were taken from a more recent report from the National Cancer Registry of Ireland, and as such updates were also made to 5-year survival and staging statistics for the other cancer types. This reference has all been added to our list of references. In response to the valuable peer review feedback we received, the following changes were made to the manuscript: 1. Text in first section of the introduction entitled Cancer burden and the importance of early diagnosis was updated to highlight the beneficial impact early detection of cancer can have on reducing treatment burden and complexity. 2. Statistics cited in this paragraph were updated to include figures for prostate cancer 5-year survival and stage at diagnosis. Figures were taken from a more recent report from the National Cancer Registry of Ireland, and as such updates were also made to 5-year survival and staging statistics for the other cancer types. This reference has all been added to our list of references. See the authors' detailed response to the review by Alexander Ross Kerr See the authors' detailed response to the review by Hein Van Poppel READ REVIEWER RESPONSES Introduction Cancer burden and the importance of early diagnosis Cancer remains a leading cause of mortality worldwide, accounting for one in six deaths 1 . In Ireland, approximately 43,000 people are diagnosed with cancer each year, with over 9,000 cancer-related deaths, representing nearly one-third of all national mortality 2 . Lung cancer is the most common cause of cancer death in Ireland, responsible for 20% of cancer-related mortality, followed by breast cancer in women, prostate cancer in men, and colorectal cancer in both sexes 2 . Cancer survival is influenced by multiple factors, including tumour biology, patient comorbidities, and access to effective treatments. However, for most tumour types, stage at diagnosis is the strongest predictor of survival 3 . In Ireland, 30% of lung cancers are diagnosed at stage I or II, compared to 41% of colorectal cancers, 65% of prostate cancers and 76% of breast cancers. Five-year net survival for lung cancer is just 24%, compared to 66% for colorectal cancer, 93% for prostate cancers and 88% for breast cancer 4 , 5 . Given that early-stage cancers are more amenable to less complex and curative treatment, strategies that facilitate timely diagnosis are critical for improving patient outcomes and reducing healthcare and treatment burden 3 , 6 , 7 . Rapid Access Clinics in Ireland: structure, utilisation, and limitations The National Cancer Control Programme (NCCP) was established in 2007 as a directorate of the Health Service Executive (HSE) to coordinate cancer services, standardise care, and improve survival rates. A key initiative has been the development of Rapid Access Clinics (RACs), specialist-led services designed to expedite diagnosis and specialist assessment for suspected breast, lung, prostate cancer, and melanoma—the four most commonly diagnosed cancers in Ireland 8 . RACs operate within designated cancer centres, with defined targets for appointment scheduling, aiming to ensure timely evaluation following GP referral 5 . International evidence suggests that structured pathways such as RACs improve access to diagnostic services, reduce diagnostic delays, and increase the proportion of cancers diagnosed at an early stage 6 , 9 . Despite this, Irish data suggest that diagnostic pathways may not be fully optimised, as a significant proportion of cancers continue to be diagnosed at an advanced stage 5 . Variation in GP referral behaviour and patient outcomes General practitioners (GPs) are central to early cancer detection, with the majority of symptomatic cancer patients initially presenting in primary care 9 . However, referral pathways are complex, and the decision to refer is influenced by clinical guidelines, GP experience, patient characteristics, and healthcare system constraints 10 , 11 . While RACs provide an expedited pathway for specialist assessment, referral decisions are complex, and substantial variation in GP referral behaviour has been documented in international studies 12 . In Denmark, where structured urgent referral pathways have been in place since 2008, approximately 27% of lung cancer diagnoses occur via fast-track pathways 9 . However, GP referral rates for suspected cancer vary significantly between practices, even after adjusting for case-mix, practice size, and patient demographics 12 – 14 . Notably, higher referral rates are associated with lower emergency presentation rates and improved cancer survival 15 . These findings suggest that greater utilisation of structured referral pathways may contribute to earlier cancer detection and better patient outcomes. In contrast, there is limited evidence on the extent of referral variation within Ireland and its impact on cancer diagnosis and outcomes. The "Cancer Care in Ireland 2020" report recorded 44,245 new attendances at RACs for breast, prostate, and lung cancers in a single year 16 . However, the conversion rate (proportion of referrals resulting in a cancer diagnosis) remains unclear, making it difficult to assess the efficiency of the RAC system. Additionally, how referral rates vary by patient demographics, GP practice characteristics, and geographic location has not been explored, limiting opportunities for targeted improvements in diagnostic pathways. Given the established link between referral patterns and cancer outcomes 6 , 15 , a detailed examination of RAC referral trends is necessary to identify potential barriers to timely cancer diagnosis. These may include regional disparities in access to diagnostic services, differences in GP decision-making and adherence to referral guidelines, and variations in patient presentation, such as symptom severity and comorbidities. Furthermore, analysing the relationship between referral rates and conversion rates will provide a clearer picture of how effectively RAC pathways function in practice. Identifying patterns of under-referral or over-referral will be essential for improving diagnostic efficiency, ensuring that referral decisions align with clinical need. This evidence will inform GP education and the refinement of clinical guidelines to promote appropriate referrals, support policy interventions aimed at addressing gaps in cancer diagnostic services, and enhance quality improvement initiatives to optimise the equitable and efficient use of RACs. This study is the first in Ireland to propose a comprehensive, retrospective cross-sectional analysis of RAC referrals, using electronic health records (EHRs) from general practice. By quantifying referral trends, identifying predictive factors, and assessing diagnostic outcomes, this research will generate critical evidence to strengthen RAC pathways and improve early cancer detection. Aims and objectives This study aims to examine general practice referrals to RACs for suspected cancer in Ireland, evaluating referral patterns, variation across practices, and the impact on cancer diagnosis and outcomes. Specific objectives include: • To characterise RAC referral patterns by cancer type, volume, and inter-practice variability over time. • To examine demographic, geographic, and clinical factors influencing referral rates. • To determine the diagnostic conversion rate, time from referral to diagnosis, and stage at diagnosis for patients referred to RACs. • To assess cancer treatment and survival outcomes following RAC referral. Methods Study design This is a retrospective study that will analyse electronic health record (EHR) data from Centric Health’s network of general practices in Ireland. Specifically, we will examine electronic rapid access cancer referrals for breast, prostate, lung cancer, and melanoma, by GPs in Ireland from 2013–2024. The data collection and analysis for the study will be conducted throughout 2025. The study will be conducted in two phases. The first phase has three steps: 1) a descriptive analysis of utilisation of RAC pathways over time and how this varies by GP practice; 2) a series of descriptive analyses, which, for each referral type, examines how the prevalence or degree of a referral characteristic varies over time, and 3) a series of negative binomial regression analyses which seek to explain the variation in the number of referrals (of a particular type) from a GP practice varies as a function of GP practice characteristics, patients characteristics and time. The second phase involves: 1) a descriptive analysis of outcomes of RAC referrals over time, and 2) an exploration and analysis of characteristics predictive of cancer diagnosis and outcomes over time. We will adhere to the SPIROS (Standardized Protocol Items Recommendations for Observational Studies) and STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) Checklist for reporting protocols and cross-sectional studies, respectively 17 , 18 . Study setting & participants The setting includes GP practices from the Centric Health practice network. Eligible participating practices are GP practices utilising the Socrates patient management system (Socrates Healthcare Ltd. Sligo, Ireland; https://www.socrates.ie/ ). Participation will be discussed with practices from the targeted networks after outlining the study's scope and significance. These inclusion criteria are designed to ensure a reliable dataset and consistency in data collection methods. Sample size As this is an observational study of a general practice population that aims to characterise current practice, and generate hypotheses for further investigation, there is no intent to conduct inferential analyses beyond the studied population. As such, a sample size calculation is not necessary. Variables The primary outcome variable for phase 1 is: 1) The RAC pathway referral volume & rate, standardised for age and sex distribution, by cancer type, and variation over time and between practices. 2) Secondary outcomes will include exploration of practice and patient characteristics that predict referral rates over time. The primary outcome variable for phase 2 is: 1) The conversion rate, defined as the proportion of referrals resulting in a cancer diagnosis, by cancer type, and variation over time and between practices. 2) Secondary outcomes will include cancer stage at diagnosis, time from referral to diagnosis, treatment received, and mortality for each cancer diagnosis, as well as characterisation of practice and patient factors that predict conversion rate for each cancer type. Data collection and management Data extraction tool A data extraction tool, based on the Visual Basic for Applications (VBA) language was designed for phase 1 of this study (Microsoft. (2025). Microsoft Office [Visual Basic for Applications]. Available from https://www.microsoft.com/en-us/microsoft-365 ). It was designed to extract data in Extensible Markup Language, which is the output produced for referrals in some EHRs in Ireland. It then converts this data into a format suitable for tabulation and analysis in Microsoft Excel. It will collect variables as outlined in Table 1 . The tool will be refined through a trial run of pilot practices with iterative debugging. Validity of the data extracted will be determined by comparing the proportion of records extracted relative to the known number of records. A successful extraction rate, indicating adequate completeness of data, namely complete extraction of information from a referral file, will be defined as exceeding a threshold of 95%. Table 1. Overview of planned data collection & data source. Data Item Description Format/Type Source Patient Characteristics Patient Age/DOB Age & DOB of the patient Numerical/Date GP records Referral Type Type of cancer referral Categorical GP records Sex Gender of the patient Categorical GP records Clinical Info Relevant clinical information Text GP records Referral Date Date when the referral was made Date GP records GMS Status Private or General Medical Services card holder (GMS) Categorical GP records Practice Characteristics Practice Location Geographic location of the practice Categorical Eircode.ie Practice Size Number of GP sessions per week worked in the practice Numerical Practice records Practice Size Number of patients registered to the practice Numerical Practice records GMS List size Proportion of GMS patients relative to total active patients Numerical Practice records Deprivation index Quantitative measure of socioeconomic status of population Numerical Pobal HP deprivation index based on Eircode Practice population density Urban vs rural Categorical Pobal HP / Practice Eircode Patient Outcomes Cancer diagnosis Was there an ultimate cancer diagnosis? Categorical GP records Cancer investigations and diagnosis timeline Date of RACC investigations and cancer diagnosis. Freetext GP records Cancer stage Stage of cancer at diagnosis Categorical GP records Cancer treatment Type of treatment received. Date of treatment commencement. Categorical GP records Cancer mortality Did the patient die of cancer? Date of death. Categorical GP records Electronic Health Record chart review Patient EHRs will be manually searched by the study team and medical students under the supervision of Centric Health in each practice to extract the data for phase 2, specifically extraction the information listed in Table 1 . The list of patient charts to review will be produced from the phase 1 data extraction process. Researchers will login to the EHR using a specific temporary login provided by the Practice Manager. This will have an associated audit log providing oversight of the data viewed during the chart review process. A Standard Operating Procedure (SOP) for the data collection process will be developed and used to train the relevant personnel, ensuring consistency and quality of data throughout phase 2. Sample data collection spreadsheets will be freely available via Open Science Framework. Data governance Data will be pseudonymised following extraction from the clinical records in Phase 1, ensuring the removal of identifiable personal information. The pseudonymised data will remain on the same secure server in a password-protected document with access strictly limited to authorised members of the research team. The unique identifier linking this data to identifiable patient information will be stored separately in a secure, password-protected file. Bias Potential sources of bias include recruitment from a specific network of practices, and exclusion of non-Centric health practices. These will be addressed and quantified by ensuring a range of practices are included and by analysing the representativeness of participating practices. Efforts to mitigate bias will be documented and discussed in the study's findings. Ethics Ethical approval for the study was granted by the Irish College of General Practitioners Research Ethics Committee (REC) on 12th December 2024 (reference no. 2662). According to the Amendments (January 2021) to the Health Research Regulations 2018, individual consent is not required for a low risk, retrospective chart review that has gained approval by the appropriate REC and is conducted by authorised parties 17 . There is low risk of potential harm to participants of the study. There is no intent to involve the patients or the public in the design of this study protocol. Statistical approach Data analysis for phase 1 of the study consists of three parts focusing on GP practice characteristics, referral volume trends and clinical information trends respectively. 1) Initially, the characteristics of GP practices will be summarised, specifically the number of patients, age-sex distribution of patients, proportion of General Medical Services (GMS) patients, and the deprivation index and rurality of the practice location. 2) Referral trends between practices will be assessed by characterising the referral volume distribution across practices, year of referral, and time of year. Additionally, these results will be stratified by cancer type and adjusted first for GP practice size, and for age and sex, to investigate further associations or trends. 3) Clinical information of referred patients from all practices will be summarised, stratified by cancer type and year of referral to map trends for the population over time. Any inter-practice variation will then be characterised. Data analysis for phase 2 of the study will focus on conversion rates for referrals as well as cancer stage at diagnosis and time from referral to diagnosis. First, conversion rates for all referrals over the study period will be presented by cancer type. Then rates will additionally be stratified by year of referral. The timeline from referral to diagnosis including pertinent investigations will be described for each cancer type for each practice. Finally, conversion rates will be characterised by all of cancer type, year of referral, and GP practice. The (TNM and/or Gleason) stage of cancer at diagnosis will be summarised for each cancer type. Discussion This study aims to explore patterns in GP referrals for suspected cancer, stratified by practice characteristics, patient demographics and clinical features. It then aims to determine the rate of cancer diagnosis and to characterise diagnostic timelines and cancer outcomes. We anticipate that our findings will provide a detailed understanding of referral behaviours across various GP practices in Ireland and how these relate to cancer diagnosis and outcomes. By identifying specific trends and deviations, we will contribute to a nuanced understanding of how different factors, including geography, patient age, gender, and clinical presentations, influence the referral process and cancer outcomes. Implications for practice and policy The anticipated results of this study are expected to provide a foundation for future research and inform policy and practice surrounding cancer diagnosis – particularly in primary care - in Ireland. We expect that the insights gained will be crucial in guiding population health policy, particularly in improving early detection strategies for cancer. By understanding referral patterns and associated cancer outcomes, participating GP practices can benchmark their behaviours against wider trends, potentially leading to quality improvement initiatives or an informed audit cycle. Limitations While aiming for comprehensive and representative findings, we acknowledge potential limitations in our study. These may include the representativeness of the sample and inherent biases in referral practices. Moreover, the reliance on retrospective data from practices might introduce variability in the data quality. We plan to address these limitations through rigorous study design and transparent reporting of our methods and findings. Finally, while rapid access pathways are viewed as the primary route for referring patients with these suspected cancers, there are other potential routes of referral (paper-based or private referral pathways) that may not be captured in this dataset. However, the focus of this analysis is on the use of rapid access pathways rather than other routes to diagnosis. Dissemination We plan a comprehensive dissemination strategy, targeting both academic and healthcare professional audiences. Findings will be submitted to peer-reviewed journals, presented at relevant conferences, and shared with healthcare policy makers. Additionally, we aim to engage with the wider public through media releases and open-access publications to ensure the study's implications are communicated broadly. Artificial Intelligence Artificial intelligence (AI) assisted technologies have not been used in the preparation of this protocol and there is no intent to use them in the execution of this study. Conclusion This study protocol describes an ambitious proposal to explore referral patterns for suspected cancer in Ireland and associated cancer outcomes. By providing a detailed and representative analysis, it aims to contribute valuable insights that will enhance understanding and inform practices and policies for better health outcomes. Ethics and consent Ethical approval for the study was granted by the Irish College of General Practitioners Research Ethics Committee (REC) on 12th December 2024 (reference no. 2662). According to the Amendments (January 2021) to the Health Research Regulations 2018, individual consent is not required for a low risk, retrospective chart review that has gained approval by the appropriate REC and is conducted by authorised parties 17 . There is low risk of potential harm to participants of the study. There is no intent to involve the patients or the public in the design of this study protocol. Data availability Underlying data No data are associated with this article. Extended data OSF: GP Referrals for Suspected Cancer in Ireland: Protocol for a Cross-Sectional Study (GRACCHUS) DOI: https://doi.org/10.17605/OSF.IO/3S4P9 19 The project contains the following extended data: GRACCHUS_EHR_DataExtraction_Tool.xlsx Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Reporting guidelines OSF: SPIROS checklist for ‘GP Referrals for Suspected Cancer in Ireland: Protocol for a Cross-Sectional Study (GRACCHUS)’ DOI: https://doi.org/10.17605/OSF.IO/3S4P9 19 GRACCHUS_Protocol_SPIROS_checklist.pdf Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Software availability N/A Acknowledgments Nandita Devaraj for their work on the VBA Tiberius Audit Tool. Ming Chuen Chong for contributions to initial drafts of the protocol. Faculty Opinions recommended References 1. 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Round T, Gildea C, Ashworth M, et al. : Association between use of urgent suspected cancer referral and mortality and stage at diagnosis: a 5–year national cohort study. Br J Gen Pract. 2020; 70 (695): e389–e398. PubMed Abstract | Publisher Full Text | Free Full Text 7. Neal RD, Allgar VL, Ali N, et al. : Stage, survival and delays in lung, colorectal, prostate and ovarian cancer: comparison between diagnostic routes. Br J Gen Pract. 2007; 57 (536): 212–9. PubMed Abstract | Free Full Text 8. Department of Health, Ireland: National cancer strategy 2017–2026. 2017. Reference Source 9. Guldbrandt LM, Fenger-Grøn M, Rasmussen TR, et al. : The role of general practice in routes to diagnosis of lung cancer in Denmark: a population-based study of general practice involvement, diagnostic activity and diagnostic intervals. BMC Health Serv Res. 2015; 15 : 21. PubMed Abstract | Publisher Full Text | Free Full Text 10. Baughan P, Keatings J, O’Neill B: Urgent suspected cancer referrals from general practice: audit of compliance with guidelines and referral outcomes. Br J Gen Pract. 2011; 61 (592): e700–e706. PubMed Abstract | Publisher Full Text | Free Full Text 11. Green T, Atkin K, Macleod U: Cancer detection in primary care: insights from general practitioners. Br J Cancer. 2015; 112 Suppl 1 (Suppl 1): S41–9. PubMed Abstract | Publisher Full Text | Free Full Text 12. Zhou Y, Mendonca SC, Abel GA, et al. : Variation in ‘fast-track’ referrals for suspected cancer by patient characteristic and cancer diagnosis: evidence from 670 000 patients with cancers of 35 different sites. Br J Cancer. 2018; 118 (1): 24–31. PubMed Abstract | Publisher Full Text | Free Full Text 13. Round T, Ashworth M, L’Esperance V, et al. : Cancer detection via primary care urgent referral and association with practice characteristics: a retrospective cross-sectional study in England from 2009/2010 to 2018/2019. Br J Gen Pract. 2021; 71 (712): e826–e835. PubMed Abstract | Publisher Full Text | Free Full Text 14. Meechan D, Gildea C, Hollingworth L, et al. : Variation in use of the 2–week referral pathway for suspected cancer: a cross-sectional analysis. Br J Gen Pract. 2012; 62 (602): e590–7. PubMed Abstract | Publisher Full Text | Free Full Text 15. Møller H, Gildea C, Meechan D, et al. : Use of the English urgent referral pathway for suspected cancer and mortality in patients with cancer: cohort study. BMJ. 2015; 351 : h5102. PubMed Abstract | Publisher Full Text | Free Full Text 16. Cancer care in Ireland in 2020: the impact of the COVID-19 pandemic. Royal College of Physicians of Ireland. [cited 2024 Sep 26]. Reference Source 17. Vandenbroucke JP, von Elm E, Altman DG, et al. : Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Epidemiology. 2007; 18 (6): 805–35. PubMed Abstract | Publisher Full Text 18. Mahajan R, Burza S, Bouter LM, et al. : Standardized Protocol Items Recommendations for Observational Studies (SPIROS) for observational study protocol reporting guidelines: protocol for a Delphi study. JMIR Res Protoc. 2020; 9 (10): e17864. PubMed Abstract | Publisher Full Text | Free Full Text 19. Murphy CF, Killeen K: GP referrals for suspected cancer in Ireland: protocol for a cross-sectional study (GRACCHUS). OSF. 2025. https://osf.io/3s4p9 Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 09 Apr 2025 ADD YOUR COMMENT Comment Author details Author details 1 Department of General Practice, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland 2 National Cancer Control Programme, Health Service Executive, Dublin, Ireland 3 Data Science Centre, School of Population Health, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland Katie Killeen Roles: Investigation, Project Administration, Writing – Original Draft Preparation Sean O'Regan Roles: Conceptualization, Investigation, Methodology, Software, Writing – Original Draft Preparation Conor F. Murphy Roles: Conceptualization, Methodology, Project Administration, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Benjamin Jacob Roles: Conceptualization, Investigation, Methodology, Software, Supervision, Writing – Review & Editing Yiren Yin Roles: Investigation, Writing – Original Draft Preparation Heather Burns Roles: Conceptualization, Methodology, Writing – Review & Editing Kathleen Bennett Roles: Methodology, Writing – Review & Editing Patrick Redmond Roles: Conceptualization, Investigation, Methodology, Project Administration, Resources, Supervision, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information Health Research Board [APA-2024-001]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (2) version 2 Revised Published: 01 Aug 2025, 8:52 https://doi.org/10.12688/hrbopenres.14109.2 version 1 Published: 09 Apr 2025, 8:52 https://doi.org/10.12688/hrbopenres.14109.1 Copyright © 2025 Killeen K et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics VIEWS $counts.viewCount downloads Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Killeen K, O'Regan S, Murphy CF et al. GP referrals for suspected cancer in Ireland: protocol for a cross-sectional study (GRACCHUS) [version 2; peer review: 2 approved] . HRB Open Res 2025, 8 :52 ( https://doi.org/10.12688/hrbopenres.14109.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 01 Aug 2025 Revised Views 0 Cite How to cite this report: Van Poppel H. Reviewer Report For: GP referrals for suspected cancer in Ireland: protocol for a cross-sectional study (GRACCHUS) [version 2; peer review: 2 approved] . HRB Open Res 2025, 8 :52 ( https://doi.org/10.21956/hrbopenres.15647.r48712 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-52/v2#referee-response-48712 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 30 Aug 2025 Hein Van Poppel , KU Leuven, Leuven, Flanders, Belgium Approved VIEWS 0 https://doi.org/10.21956/hrbopenres.15647.r48712 no further comments, ... Continue reading READ ALL no further comments, happy with revised draft Competing Interests: No competing interests were disclosed. Reviewer Expertise: Reduces Treatment Burden: It would be beneficial to state explicitly that early diagnosis enables earlier, less complicated, and less toxic treatment.Cancer Burden: While figures for lung, colorectal, and breast cancer are provided, it would enhance completeness to include corresponding data for prostate cancer, given its relevance to the studyVariation in GP Referral Behaviour: For prostate cancer, it should be clarified that in its curable stages, the disease is typically asymptomatic. Voiding symptoms are more commonly associated with benign prostatic hyperplasia (BPH), which affects referral behaviour differently than cancers presenting with clear symptoms.Limitations: The manuscript correctly highlights sample representativeness as a key limitation. However, further detail is needed on how the exclusion of handwritten referral letters will be mitigated, as this could significantly influence the national and international applicability of the findings. This is potentially a serious flaw, which could limit the usefulness of the data obtained in Phase 1 nationally and internationally in efforts to improve GP referrals and awareness of early cancer detection.Thank you for the opportunity to review this important work. I look forward to seeing how the project progresses. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Van Poppel H. Reviewer Report For: GP referrals for suspected cancer in Ireland: protocol for a cross-sectional study (GRACCHUS) [version 2; peer review: 2 approved] . HRB Open Res 2025, 8 :52 ( https://doi.org/10.21956/hrbopenres.15647.r48712 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-52/v2#referee-response-48712 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 09 Apr 2025 Views 0 Cite How to cite this report: Kerr AR. Reviewer Report For: GP referrals for suspected cancer in Ireland: protocol for a cross-sectional study (GRACCHUS) [version 2; peer review: 2 approved] . HRB Open Res 2025, 8 :52 ( https://doi.org/10.21956/hrbopenres.15506.r46763 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-52/v1#referee-response-46763 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 10 May 2025 Alexander Ross Kerr , New York University, New York, New York, USA Approved VIEWS 0 https://doi.org/10.21956/hrbopenres.15506.r46763 This retrospective cross-sectional study to review EHR data for selected GP practices to evaluate the efficiency of rapid access clinics for the early detection of the 4 most prevalent cancers in Ireland is well designed and an important study. One ... Continue reading READ ALL This retrospective cross-sectional study to review EHR data for selected GP practices to evaluate the efficiency of rapid access clinics for the early detection of the 4 most prevalent cancers in Ireland is well designed and an important study. One small criticism would be to focus on cancers with the poorest outcomes rather than the most common. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Yes Are the datasets clearly presented in a useable and accessible format? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Oral cancer I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Kerr AR. Reviewer Report For: GP referrals for suspected cancer in Ireland: protocol for a cross-sectional study (GRACCHUS) [version 2; peer review: 2 approved] . HRB Open Res 2025, 8 :52 ( https://doi.org/10.21956/hrbopenres.15506.r46763 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-52/v1#referee-response-46763 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 10 Sep 2025 Conor Murphy , Department of General Practice, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland 10 Sep 2025 Author Response The authors would like to thank the reviewer for their kind comments. This study focuses solely on the available Rapid Access Clinics for cancer referrals in Ireland. Pathways are ... Continue reading The authors would like to thank the reviewer for their kind comments. This study focuses solely on the available Rapid Access Clinics for cancer referrals in Ireland. Pathways are currently only established for the four cancers described - lung, prostate, breast and malignant melanoma. Lung cancer is the leading cause of cancer death in Ireland, accounting for 20% of all cancer-related deaths annually. With a five-year net survival rate of just 21%, the 4th lowest for cancers, it is Ireland’s most common poor-prognosis cancer. At present there are no dedicated referral pathways for other less common cancers or those presenting with ‘non-specific’ cancer symptoms. We believe these alternative pathways would be valuable for General Practice in Ireland to increase early diagnoses and reduce overall mortality, and it is an area we are actively exploring alongside this work. Kind regards, GRACCHUS study team The authors would like to thank the reviewer for their kind comments. This study focuses solely on the available Rapid Access Clinics for cancer referrals in Ireland. Pathways are currently only established for the four cancers described - lung, prostate, breast and malignant melanoma. Lung cancer is the leading cause of cancer death in Ireland, accounting for 20% of all cancer-related deaths annually. With a five-year net survival rate of just 21%, the 4th lowest for cancers, it is Ireland’s most common poor-prognosis cancer. At present there are no dedicated referral pathways for other less common cancers or those presenting with ‘non-specific’ cancer symptoms. We believe these alternative pathways would be valuable for General Practice in Ireland to increase early diagnoses and reduce overall mortality, and it is an area we are actively exploring alongside this work. Kind regards, GRACCHUS study team Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 10 Sep 2025 Conor Murphy , Department of General Practice, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland 10 Sep 2025 Author Response The authors would like to thank the reviewer for their kind comments. This study focuses solely on the available Rapid Access Clinics for cancer referrals in Ireland. Pathways are ... Continue reading The authors would like to thank the reviewer for their kind comments. This study focuses solely on the available Rapid Access Clinics for cancer referrals in Ireland. Pathways are currently only established for the four cancers described - lung, prostate, breast and malignant melanoma. Lung cancer is the leading cause of cancer death in Ireland, accounting for 20% of all cancer-related deaths annually. With a five-year net survival rate of just 21%, the 4th lowest for cancers, it is Ireland’s most common poor-prognosis cancer. At present there are no dedicated referral pathways for other less common cancers or those presenting with ‘non-specific’ cancer symptoms. We believe these alternative pathways would be valuable for General Practice in Ireland to increase early diagnoses and reduce overall mortality, and it is an area we are actively exploring alongside this work. Kind regards, GRACCHUS study team The authors would like to thank the reviewer for their kind comments. This study focuses solely on the available Rapid Access Clinics for cancer referrals in Ireland. Pathways are currently only established for the four cancers described - lung, prostate, breast and malignant melanoma. Lung cancer is the leading cause of cancer death in Ireland, accounting for 20% of all cancer-related deaths annually. With a five-year net survival rate of just 21%, the 4th lowest for cancers, it is Ireland’s most common poor-prognosis cancer. At present there are no dedicated referral pathways for other less common cancers or those presenting with ‘non-specific’ cancer symptoms. We believe these alternative pathways would be valuable for General Practice in Ireland to increase early diagnoses and reduce overall mortality, and it is an area we are actively exploring alongside this work. Kind regards, GRACCHUS study team Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Van Poppel H. Reviewer Report For: GP referrals for suspected cancer in Ireland: protocol for a cross-sectional study (GRACCHUS) [version 2; peer review: 2 approved] . HRB Open Res 2025, 8 :52 ( https://doi.org/10.21956/hrbopenres.15506.r46756 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-52/v1#referee-response-46756 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 29 Apr 2025 Hein Van Poppel , KU Leuven, Leuven, Flanders, Belgium Approved with Reservations VIEWS 0 https://doi.org/10.21956/hrbopenres.15506.r46756 I have reviewed the manuscript examining referral patterns from primary care to rapid access clinics for early cancer diagnosis. I would like to commend the team for addressing an important and underexplored area in Irish healthcare. All this is worthy ... Continue reading READ ALL I have reviewed the manuscript examining referral patterns from primary care to rapid access clinics for early cancer diagnosis. I would like to commend the team for addressing an important and underexplored area in Irish healthcare. All this is worthy of analysis and hasn’t been performed in Ireland. However I would like to raise a few points that may help strengthen the work further: Reduces Treatment Burden : It would be beneficial to state explicitly that early diagnosis enables earlier, less complicated, and less toxic treatment. Cancer Burden : While figures for lung, colorectal, and breast cancer are provided, it would enhance completeness to include corresponding data for prostate cancer, given its relevance to the study. Variation in GP Referral Behaviour : For prostate cancer, it should be clarified that in its curable stages, the disease is typically asymptomatic. Voiding symptoms are more commonly associated with benign prostatic hyperplasia (BPH), which affects referral behaviour differently than cancers presenting with clear symptoms. Limitations : The manuscript correctly highlights sample representativeness as a key limitation. However, further detail is needed on how the exclusion of handwritten referral letters will be mitigated, as this could significantly influence the national and international applicability of the findings. This is potentially a serious flaw, which could limit the usefulness of the data obtained in Phase 1 nationally and internationally in efforts to improve GP referrals and awareness of early cancer detection. Thank you for the opportunity to review this important work. I look forward to seeing how the project progresses. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Partly Are the datasets clearly presented in a useable and accessible format? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Reduces Treatment Burden: It would be beneficial to state explicitly that early diagnosis enables earlier, less complicated, and less toxic treatment.Cancer Burden: While figures for lung, colorectal, and breast cancer are provided, it would enhance completeness to include corresponding data for prostate cancer, given its relevance to the studyVariation in GP Referral Behaviour: For prostate cancer, it should be clarified that in its curable stages, the disease is typically asymptomatic. Voiding symptoms are more commonly associated with benign prostatic hyperplasia (BPH), which affects referral behaviour differently than cancers presenting with clear symptoms.Limitations: The manuscript correctly highlights sample representativeness as a key limitation. However, further detail is needed on how the exclusion of handwritten referral letters will be mitigated, as this could significantly influence the national and international applicability of the findings. This is potentially a serious flaw, which could limit the usefulness of the data obtained in Phase 1 nationally and internationally in efforts to improve GP referrals and awareness of early cancer detection.Thank you for the opportunity to review this important work. I look forward to seeing how the project progresses. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Van Poppel H. Reviewer Report For: GP referrals for suspected cancer in Ireland: protocol for a cross-sectional study (GRACCHUS) [version 2; peer review: 2 approved] . HRB Open Res 2025, 8 :52 ( https://doi.org/10.21956/hrbopenres.15506.r46756 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-52/v1#referee-response-46756 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 10 Sep 2025 Conor Murphy , Department of General Practice, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland 10 Sep 2025 Author Response Thank you for reviewing this article and providing your valuable feedback. It is greatly appreciated. The authors acknowledge the recommendations and have updated the manuscript to reflect those ... Continue reading Thank you for reviewing this article and providing your valuable feedback. It is greatly appreciated. The authors acknowledge the recommendations and have updated the manuscript to reflect those given regarding treatment burden and prostate cancer statistics. Regarding variation in GP referrals to Rapid Access Clinics (RACs) for prostate cancer, we accept the point made in relation to asymptomatic early-stage disease, which could in fact be extended to other cancers, including lung cancer. However, we are not comparing referral behaviours between cancer types as these are influenced by many factors, such as clinical presentation and referral criteria. Rather, we are interested in variability amongst GP practices in their use of the referral pathways within each cancer type. As the limited symptomatology in early disease is a common challenge for all GPs, it should not in itself influence referral variability between practices. Notwithstanding this, depending on our findings with regards to suspected prostate cancer referral, this may be an important discussion point for our final manuscript. Regarding the exclusion of handwritten referral letters in this study, there are a several points to consider. The primary purpose of this study is to describe healthcare service utilisation i.e. referrals specifically to RACs. These referrals are done electronically by GPs and have been for a number of years at least, so any contribution via handwritten letters within the specified study timeframe (2013-2024) would be very minimal. Moreover, the included practices have used Electronic Health Records for the duration of the study period and are therefore likely to consistently have made these referrals electronically. It is important to reiterate that a limitation of this study is that it does not capture all suspected cancer referrals for each cancer type, only those referred electronically via the RAC pathways. We note this in our limitations section. Kind regards, GRACCHUS study team Thank you for reviewing this article and providing your valuable feedback. It is greatly appreciated. The authors acknowledge the recommendations and have updated the manuscript to reflect those given regarding treatment burden and prostate cancer statistics. Regarding variation in GP referrals to Rapid Access Clinics (RACs) for prostate cancer, we accept the point made in relation to asymptomatic early-stage disease, which could in fact be extended to other cancers, including lung cancer. However, we are not comparing referral behaviours between cancer types as these are influenced by many factors, such as clinical presentation and referral criteria. Rather, we are interested in variability amongst GP practices in their use of the referral pathways within each cancer type. As the limited symptomatology in early disease is a common challenge for all GPs, it should not in itself influence referral variability between practices. Notwithstanding this, depending on our findings with regards to suspected prostate cancer referral, this may be an important discussion point for our final manuscript. Regarding the exclusion of handwritten referral letters in this study, there are a several points to consider. The primary purpose of this study is to describe healthcare service utilisation i.e. referrals specifically to RACs. These referrals are done electronically by GPs and have been for a number of years at least, so any contribution via handwritten letters within the specified study timeframe (2013-2024) would be very minimal. Moreover, the included practices have used Electronic Health Records for the duration of the study period and are therefore likely to consistently have made these referrals electronically. It is important to reiterate that a limitation of this study is that it does not capture all suspected cancer referrals for each cancer type, only those referred electronically via the RAC pathways. We note this in our limitations section. Kind regards, GRACCHUS study team Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 10 Sep 2025 Conor Murphy , Department of General Practice, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland 10 Sep 2025 Author Response Thank you for reviewing this article and providing your valuable feedback. It is greatly appreciated. The authors acknowledge the recommendations and have updated the manuscript to reflect those ... Continue reading Thank you for reviewing this article and providing your valuable feedback. It is greatly appreciated. The authors acknowledge the recommendations and have updated the manuscript to reflect those given regarding treatment burden and prostate cancer statistics. Regarding variation in GP referrals to Rapid Access Clinics (RACs) for prostate cancer, we accept the point made in relation to asymptomatic early-stage disease, which could in fact be extended to other cancers, including lung cancer. However, we are not comparing referral behaviours between cancer types as these are influenced by many factors, such as clinical presentation and referral criteria. Rather, we are interested in variability amongst GP practices in their use of the referral pathways within each cancer type. As the limited symptomatology in early disease is a common challenge for all GPs, it should not in itself influence referral variability between practices. Notwithstanding this, depending on our findings with regards to suspected prostate cancer referral, this may be an important discussion point for our final manuscript. Regarding the exclusion of handwritten referral letters in this study, there are a several points to consider. The primary purpose of this study is to describe healthcare service utilisation i.e. referrals specifically to RACs. These referrals are done electronically by GPs and have been for a number of years at least, so any contribution via handwritten letters within the specified study timeframe (2013-2024) would be very minimal. Moreover, the included practices have used Electronic Health Records for the duration of the study period and are therefore likely to consistently have made these referrals electronically. It is important to reiterate that a limitation of this study is that it does not capture all suspected cancer referrals for each cancer type, only those referred electronically via the RAC pathways. We note this in our limitations section. Kind regards, GRACCHUS study team Thank you for reviewing this article and providing your valuable feedback. It is greatly appreciated. The authors acknowledge the recommendations and have updated the manuscript to reflect those given regarding treatment burden and prostate cancer statistics. Regarding variation in GP referrals to Rapid Access Clinics (RACs) for prostate cancer, we accept the point made in relation to asymptomatic early-stage disease, which could in fact be extended to other cancers, including lung cancer. However, we are not comparing referral behaviours between cancer types as these are influenced by many factors, such as clinical presentation and referral criteria. Rather, we are interested in variability amongst GP practices in their use of the referral pathways within each cancer type. As the limited symptomatology in early disease is a common challenge for all GPs, it should not in itself influence referral variability between practices. Notwithstanding this, depending on our findings with regards to suspected prostate cancer referral, this may be an important discussion point for our final manuscript. Regarding the exclusion of handwritten referral letters in this study, there are a several points to consider. The primary purpose of this study is to describe healthcare service utilisation i.e. referrals specifically to RACs. These referrals are done electronically by GPs and have been for a number of years at least, so any contribution via handwritten letters within the specified study timeframe (2013-2024) would be very minimal. Moreover, the included practices have used Electronic Health Records for the duration of the study period and are therefore likely to consistently have made these referrals electronically. It is important to reiterate that a limitation of this study is that it does not capture all suspected cancer referrals for each cancer type, only those referred electronically via the RAC pathways. We note this in our limitations section. Kind regards, GRACCHUS study team Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 09 Apr 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 2 (revision) 01 Aug 25 read Version 1 09 Apr 25 read read Hein Van Poppel , KU Leuven, Leuven, Belgium Alexander Ross Kerr , New York University, New York, USA Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Van Poppel H. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 30 Aug 2025 | for Version 2 Hein Van Poppel , KU Leuven, Leuven, Flanders, Belgium 0 Views copyright © 2025 Van Poppel H. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions no further comments, happy with revised draft Competing Interests No competing interests were disclosed. Reviewer Expertise Reduces Treatment Burden: It would be beneficial to state explicitly that early diagnosis enables earlier, less complicated, and less toxic treatment.Cancer Burden: While figures for lung, colorectal, and breast cancer are provided, it would enhance completeness to include corresponding data for prostate cancer, given its relevance to the studyVariation in GP Referral Behaviour: For prostate cancer, it should be clarified that in its curable stages, the disease is typically asymptomatic. Voiding symptoms are more commonly associated with benign prostatic hyperplasia (BPH), which affects referral behaviour differently than cancers presenting with clear symptoms.Limitations: The manuscript correctly highlights sample representativeness as a key limitation. However, further detail is needed on how the exclusion of handwritten referral letters will be mitigated, as this could significantly influence the national and international applicability of the findings. This is potentially a serious flaw, which could limit the usefulness of the data obtained in Phase 1 nationally and internationally in efforts to improve GP referrals and awareness of early cancer detection.Thank you for the opportunity to review this important work. I look forward to seeing how the project progresses. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Van Poppel H. Peer Review Report For: GP referrals for suspected cancer in Ireland: protocol for a cross-sectional study (GRACCHUS) [version 2; peer review: 2 approved] . HRB Open Res 2025, 8 :52 ( https://doi.org/10.21956/hrbopenres.15647.r48712) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://hrbopenresearch.org/articles/8-52/v2#referee-response-48712 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Kerr A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 10 May 2025 | for Version 1 Alexander Ross Kerr , New York University, New York, New York, USA 0 Views copyright © 2025 Kerr A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This retrospective cross-sectional study to review EHR data for selected GP practices to evaluate the efficiency of rapid access clinics for the early detection of the 4 most prevalent cancers in Ireland is well designed and an important study. One small criticism would be to focus on cancers with the poorest outcomes rather than the most common. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Yes Are the datasets clearly presented in a useable and accessible format? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Oral cancer I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (1) Author Response 10 Sep 2025 Conor Murphy, Department of General Practice, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland The authors would like to thank the reviewer for their kind comments. This study focuses solely on the available Rapid Access Clinics for cancer referrals in Ireland. Pathways are currently only established for the four cancers described - lung, prostate, breast and malignant melanoma. Lung cancer is the leading cause of cancer death in Ireland, accounting for 20% of all cancer-related deaths annually. With a five-year net survival rate of just 21%, the 4th lowest for cancers, it is Ireland’s most common poor-prognosis cancer. At present there are no dedicated referral pathways for other less common cancers or those presenting with ‘non-specific’ cancer symptoms. We believe these alternative pathways would be valuable for General Practice in Ireland to increase early diagnoses and reduce overall mortality, and it is an area we are actively exploring alongside this work. Kind regards, GRACCHUS study team View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Kerr AR. Peer Review Report For: GP referrals for suspected cancer in Ireland: protocol for a cross-sectional study (GRACCHUS) [version 2; peer review: 2 approved] . HRB Open Res 2025, 8 :52 ( https://doi.org/10.21956/hrbopenres.15506.r46763) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://hrbopenresearch.org/articles/8-52/v1#referee-response-46763 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Van Poppel H. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 29 Apr 2025 | for Version 1 Hein Van Poppel , KU Leuven, Leuven, Flanders, Belgium 0 Views copyright © 2025 Van Poppel H. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I have reviewed the manuscript examining referral patterns from primary care to rapid access clinics for early cancer diagnosis. I would like to commend the team for addressing an important and underexplored area in Irish healthcare. All this is worthy of analysis and hasn’t been performed in Ireland. However I would like to raise a few points that may help strengthen the work further: Reduces Treatment Burden : It would be beneficial to state explicitly that early diagnosis enables earlier, less complicated, and less toxic treatment. Cancer Burden : While figures for lung, colorectal, and breast cancer are provided, it would enhance completeness to include corresponding data for prostate cancer, given its relevance to the study. Variation in GP Referral Behaviour : For prostate cancer, it should be clarified that in its curable stages, the disease is typically asymptomatic. Voiding symptoms are more commonly associated with benign prostatic hyperplasia (BPH), which affects referral behaviour differently than cancers presenting with clear symptoms. Limitations : The manuscript correctly highlights sample representativeness as a key limitation. However, further detail is needed on how the exclusion of handwritten referral letters will be mitigated, as this could significantly influence the national and international applicability of the findings. This is potentially a serious flaw, which could limit the usefulness of the data obtained in Phase 1 nationally and internationally in efforts to improve GP referrals and awareness of early cancer detection. Thank you for the opportunity to review this important work. I look forward to seeing how the project progresses. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Partly Are the datasets clearly presented in a useable and accessible format? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Reduces Treatment Burden: It would be beneficial to state explicitly that early diagnosis enables earlier, less complicated, and less toxic treatment.Cancer Burden: While figures for lung, colorectal, and breast cancer are provided, it would enhance completeness to include corresponding data for prostate cancer, given its relevance to the studyVariation in GP Referral Behaviour: For prostate cancer, it should be clarified that in its curable stages, the disease is typically asymptomatic. Voiding symptoms are more commonly associated with benign prostatic hyperplasia (BPH), which affects referral behaviour differently than cancers presenting with clear symptoms.Limitations: The manuscript correctly highlights sample representativeness as a key limitation. However, further detail is needed on how the exclusion of handwritten referral letters will be mitigated, as this could significantly influence the national and international applicability of the findings. This is potentially a serious flaw, which could limit the usefulness of the data obtained in Phase 1 nationally and internationally in efforts to improve GP referrals and awareness of early cancer detection.Thank you for the opportunity to review this important work. I look forward to seeing how the project progresses. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 10 Sep 2025 Conor Murphy, Department of General Practice, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland Thank you for reviewing this article and providing your valuable feedback. It is greatly appreciated. The authors acknowledge the recommendations and have updated the manuscript to reflect those given regarding treatment burden and prostate cancer statistics. Regarding variation in GP referrals to Rapid Access Clinics (RACs) for prostate cancer, we accept the point made in relation to asymptomatic early-stage disease, which could in fact be extended to other cancers, including lung cancer. However, we are not comparing referral behaviours between cancer types as these are influenced by many factors, such as clinical presentation and referral criteria. Rather, we are interested in variability amongst GP practices in their use of the referral pathways within each cancer type. As the limited symptomatology in early disease is a common challenge for all GPs, it should not in itself influence referral variability between practices. Notwithstanding this, depending on our findings with regards to suspected prostate cancer referral, this may be an important discussion point for our final manuscript. Regarding the exclusion of handwritten referral letters in this study, there are a several points to consider. The primary purpose of this study is to describe healthcare service utilisation i.e. referrals specifically to RACs. These referrals are done electronically by GPs and have been for a number of years at least, so any contribution via handwritten letters within the specified study timeframe (2013-2024) would be very minimal. Moreover, the included practices have used Electronic Health Records for the duration of the study period and are therefore likely to consistently have made these referrals electronically. It is important to reiterate that a limitation of this study is that it does not capture all suspected cancer referrals for each cancer type, only those referred electronically via the RAC pathways. We note this in our limitations section. Kind regards, GRACCHUS study team View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Van Poppel H. Peer Review Report For: GP referrals for suspected cancer in Ireland: protocol for a cross-sectional study (GRACCHUS) [version 2; peer review: 2 approved] . HRB Open Res 2025, 8 :52 ( https://doi.org/10.21956/hrbopenres.15506.r46756) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://hrbopenresearch.org/articles/8-52/v1#referee-response-46756 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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