Pathology (January 2015) 47(1), pp. 4–6
EDITORIAL
Institutional biobanking: an integral part of contemporary pathology practice GILLIAN M. SCOTT1, ANUSHA HETTIARATCHI1, ELIZABETH SALISBURY2, ROBYN L. WARD1,3 NICHOLAS J. HAWKINS4
AND
1Prince of Wales Clinical School, UNSW, Sydney, 2Anatomical Pathology Department, South Eastern Area Laboratory Services (SEALS), NSW Health Pathology, 3POW Cancer Centre, Prince of Wales Hospital, Sydney, and 4School of Medical Sciences, UNSW, Sydney, NSW, Australia
Lack of access to quality biospecimens and associated health data is a major roadblock to clinical and translational research. While major advances have been achieved in the emerging field of personalised medicine, significantly more research is required to understand the genomic and proteomic factors underlying many diseases including cancer.1 The establishment of large repositories of annotated biospecimens is considered by many the only way to meet the current and future demands of translational medicine.1–3 We are addressing the deficiency in biospecimen availability through establishment of the Health Science Alliance (HSA) Biobank, an institutional biobank implemented within South Eastern Sydney Local Health District (SESLHD) hospitals and the University of New South Wales (UNSW) Australia. As an institutional biobank, the processes of HSA biobank consent, biospecimen and data collection are integrated within the hospital patient care pathway. In this way, the biobank is sustained by ongoing collaboration between patients, clinicians, nurses, hospital support staff, researchers and pathologists. The HSA Biobank began collection in April 2012 of solid organ tissues, bone marrow, matched blood or buccal swab, and associated health data, with participant consent. The intersections between the patient care pathway in the hospital and the processes of the HSA Biobank are outlined in Fig. 1. Our aim is to have biobank processes embedded across all hospital practices, while ensuring minimal impact to staff workloads and patient care workflows. The ultimate goal is that biobanking becomes a routine part of patient care. In two years of operation, this set-up has provided over 2650 biobank specimens from over 1400 consenting participants who have had a recent diagnosis of cancer. Clinicians and researchers see value in institutional biobanking.4 However, hospital-wide uptake of HSA Biobank practices, as well as researcher use of biobank resources, relies on the implementation of collection processes that are appropriate, routine and trustworthy. Hence, diagnostic pathology plays a central role in the collection of tissue and data for the HSA Biobank. In the HSA model it is pathologists and haematologists, rather than surgeons, who are responsible for the allocation of tissues and bone marrow to the biobank. The expertise and discretion of specialist pathologists ensures that the diagnostic integrity of tissue is maintained and that the optimal quality and quantity of banked specimens is achieved (Table 1). While in some cases, biobank tissue is allocated by pathologists without prior knowledge of HSA Biobank consent status, the long-term storage of tissue and receipt of patient health data by the HSA Biobank only occurs when consent to do so is obtained from participants. Any tissue for which participant consent is Print ISSN 0031-3025/Online ISSN 1465-3931 DOI: 10.1097/PAT.0000000000000185
#
refused, revoked or unlikely to be obtained is returned to pathology or destroyed. Implementation of innovative IT and bioinformatics systems for secure data and information retrieval, transfer and storage is an important feature of the HSA Biobank. Electronic transfer of pathology reports is achieved by HL7 messaging to protected HSA Biobank databases maintained on secure UNSW servers. Systems are also in place for secure storage of demographic, clinical and epidemiological data on consenting participants. Information can be provided to appropriately authorised researchers through electronically-generated pathology reports and data files, from which personal health information has been removed to ensure de-identification. Integration of biobanking practices within the pathology service has benefits for research, hospital services and ultimately, patient outcomes. The benefits to research of a wellresourced tissue and data biobank are clear. Researchers continue to value biobanks that provide access to large numbers of formalin fixed tissue for standard immunohistochemistry and other in situ detection techniques.5 However, biobanks must also be capable of adapting to new technologies and changing trends in research methodology, and the resultant changes in demand for various tissue types (e.g., fresh tissue) and linked data. This capacity can only be provided through integration of the biobanking process with diagnostic pathology services. This linkage also provides significant benefit to the diagnostic laboratory (Table 1). Two clear benefits that pathologyresearch linkages provide are the creation of opportunities for improved diagnosis and the rapid uptake of new techniques and systems. An example of this is the increased use of next generation sequencing for identification of BRAC1/2 and other genetic mutations, which can inform clinicians of an individual’s risk of disease and potential treatment options. These advances in technology have also pushed the development of institutional protocols that provide access to adequate health data and different tissue types (diseased and normal fresh tissue or blood). With this comes renewed concern for data security, biospecimen quality and experimental variability. The robust data storage and transfer systems developed for the HSA Biobank are of practical use to hospital systems seeking to securely and efficiently share health and personal data. Institutional biobanking also provides a vehicle for the advancement of biospecimen science, leading to improvements in biospecimen handling that can minimise variation in gene expression or other biological markers.6–8 In this way, institutional biobanking provides a conduit for knowledge transfer between the diagnostic and research domains.
2014 Royal College of Pathologists of Australasia
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
INSTITUTIONAL BIOBANKING
Pre-admission consultation
5
Pre-operative ward
Consent to HSA Biobank
Consent to surgery
Yes
Eligible for biobanking?
No
No HSA Biobank 10 mL EDTA
Pre-surgery blood
No further action
Yes No further action
Removed tissue sent to anatomical pathology
Surgery
No
Check consent status
Specimen destroyed
Pending Post-operative ward - consent checked on rutine ward round
Specimen holding bay
Consent to HSA Biobank
Yes
Consent confirmed Medical record containing consent form
Medical records department
Lowy biorepository HSA Biobank HSA Biobank consent form collection
Fig. 1 HSA Biobank workflow for collection of participant consent, resected tissue, matched blood and data. Biobank consent, tissue and data collection processes are carried out alongside routine pre- and post-admission procedures that occur within the hospital patient care pathway. Consent collection is decoupled from tissue collection to aid workflow, with SEALS Anatomical Pathology responsible for allocation of tissue to the HSA Biobank. Table 1
Advantages and disadvantages of institutional biobanking
Advantages
No need to track participant consent to tissue donation Avoids disputes regarding tissue access for researchers and clinicians Reliable storage of archival tissue and retrieval for future diagnosis if necessary
Avoids ’sampling’ of tissue prior to receipt in anatomical pathology and haematology
Maintenance of tissue integrity and biospecimen quality for research and diagnosis
Standardised and contemporary approach to tissue collection Drives advancements in tissue collection, diagnosis and data transfer technology Potential or perceived disadvantages
Can be resolved by:
Delays/impediments to
Tissue banking built around routine
diagnosis
workflows
Tissue always readily available for new testing
Increased staff workload and time
Staffing costs Consumable costs
Integration within routine practices Automation Improved efficiency Professional development and training Integration within routine practices Supply of additional reagents by biobank
Not surprisingly, the integration of tissue and data banking practices within pathology services is recognised internationally as providing benefits across the hospital setting.2,3,9,10 Institutional biobanks can inform best practice in consent and tissue collection, drive advancements in information storage and data transfer technology, and improve patient care through better diagnosis and personalisation of therapy. More generally, the intersections between treatment, diagnosis and research that occur as a result of institutional biobanking build collaborative networks that foster rapid improvements in patient care. This is the ultimate aim of biobanking – to contribute to research in a way that effectively leads to health improvements for the community. The large majority of people will consent to participation in research when invited,9,11 and they typically report a positive experience from their involvement in research, even if it is limited to a single event of tissue donation.12 The integration of banking into routine clinical practice, as attempted through the HSA Biobank, can provide all patients with the opportunity to participate in research in an efficient and minimally intrusive manner. It also provides a mechanism to honour the commitment of those donors to future biomedical research. We believe that the implementation strategy of the HSA Biobank has strengthened the perception of biobanking as a worthwhile endeavour in patient care at SESLHD hospitals (Table 1). This acceptance has occurred despite initial concerns regarding increased staff workloads, disruption of work
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
6
SCOTT et al.
practices, compromise of patient care, or ethical considerations.4 These concerns have been largely overcome by making disease diagnosis, patient care and privacy a priority when establishing biobanking processes. Consultation, training and adaptability of processes to differing situations have also ensured minimal disruptions to workflows within individual units. Significant milestones have been met in the two years of operation of the HSA Biobank, including implementation of pre-admission consent processes, establishment of routine tissue banking procedures and the use of biobank tissue in current research projects. We have shown that institutional biobanking, when based on the routine workflows of a busy diagnostic pathology service, is cost-effective and sustainable, and can be established in ways that are innovative and minimally intrusive. This biobank-hospital interaction is a symbiotic relationship that benefits stakeholders in terms of research and patient care outcomes, and importantly places pathology services at the centre of this important initiative. It has significant value for individual participants, health service providers, researchers and community. The HSA Biobank has demonstrated the pursuit of institutional biobanking is worthwhile within public hospital services, and expansion to further sites is encouraged. Acknowledgements: We gratefully acknowledge the expertise and input of Ms Nicki Meagher, HSA Biobank Project Manager, in establishment of HSA Biobank processes, and the efforts of the staff of SEALS pathology in supporting their implementation. Conflicts of interest and sources of funding: The authors state that there are no conflicts of interest to disclose. The HSA Biobank is a flagship project of the Translational Cancer Research Network, which is funded by Cancer Institute
Pathology (2015), 47(1), January
NSW. HSA Biobank implementation was in part supported by funding from NSW Health Pathology. Address for correspondence: Professor Nicholas Hawkins, School of Medical Sciences, UNSW, Sydney, NSW 2052, Australia. E-mail: [email protected]
References 1. Scolyer RA, Thompson JF. Biospecimen banking: the pathway to personalized medicine for patients with cancer. J Surg Oncol 2013; 107: 681–2. 2. Watson PH, Wilson-McManus JE, Barnes RO, et al. Evolutionary concepts in biobanking – the BC BioLibrary. J Transl Med 2009; 7: 95. 3. McKeon S, Alexander E, Brodaty H, Ferris W, Frazer I, Little M. Strategic Review of Health and Medical Research in Australia – Better Health Through Research. February 2013. Canberra: Department of Health and Aging; 2013. 4. Wyld L, Smith S, Hawkins NJ, Long J, Ward RL. Introducing research initiatives into healthcare: what do doctors think? Biopreserv Biobank 2014; 12: 91–8. 5. Sadanandam A, Lyssiotis CA, Homicsko K, et al. A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nat Med 2013; 19: 619–25. 6. Ransohoff DF, Gourlay ML. Sources of bias in specimens for research about molecular markers for cancer. J Clin Oncol 2010; 28: 698–704. 7. Hatzis C, Sun H, Yao H, et al. Effects of tissue handling on RNA integrity and microarray measurements from resected breast cancers. J Natl Cancer Inst 2011; 103: 1871–83. 8. Dev H, Rickman D, Sooriakumaran P, et al. Biobanking after roboticassisted radical prostatectomy: a quality assessment of providing prostate tissue for RNA studies. J Transl Med 2011; 9: 121. 9. Platell C, Zeps N, Joseph D, Spry N, Iacopetta B, Caruso V. Tumour banking as part of routine clinical practice. ANZ J Surg 2010; 80: 203–4. 10. Brisson AR, Matsui D, Rieder MJ, Fraser DD. Translational research in pediatrics: tissue sampling and biobanking. Pediatrics 2012; 129: 153–62. 11. Thomas G. Tissue banking for research: connecting the disconnected. Cell Tissue Bank 2011; 12: 29–30. 12. Cervo S, Rovina J, Talamini R, et al. An effective multisource informed consent procedure for research and clinical practice: an observational study of patient understanding and awareness of their roles as research stakeholders in a cancer biobank. BMC Med Ethics 2013; 14: 30.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
EDITORIAL
Institutional biobanking: an integral part of contemporary pathology practice GILLIAN M. SCOTT1, ANUSHA HETTIARATCHI1, ELIZABETH SALISBURY2, ROBYN L. WARD1,3 NICHOLAS J. HAWKINS4
AND
1Prince of Wales Clinical School, UNSW, Sydney, 2Anatomical Pathology Department, South Eastern Area Laboratory Services (SEALS), NSW Health Pathology, 3POW Cancer Centre, Prince of Wales Hospital, Sydney, and 4School of Medical Sciences, UNSW, Sydney, NSW, Australia
Lack of access to quality biospecimens and associated health data is a major roadblock to clinical and translational research. While major advances have been achieved in the emerging field of personalised medicine, significantly more research is required to understand the genomic and proteomic factors underlying many diseases including cancer.1 The establishment of large repositories of annotated biospecimens is considered by many the only way to meet the current and future demands of translational medicine.1–3 We are addressing the deficiency in biospecimen availability through establishment of the Health Science Alliance (HSA) Biobank, an institutional biobank implemented within South Eastern Sydney Local Health District (SESLHD) hospitals and the University of New South Wales (UNSW) Australia. As an institutional biobank, the processes of HSA biobank consent, biospecimen and data collection are integrated within the hospital patient care pathway. In this way, the biobank is sustained by ongoing collaboration between patients, clinicians, nurses, hospital support staff, researchers and pathologists. The HSA Biobank began collection in April 2012 of solid organ tissues, bone marrow, matched blood or buccal swab, and associated health data, with participant consent. The intersections between the patient care pathway in the hospital and the processes of the HSA Biobank are outlined in Fig. 1. Our aim is to have biobank processes embedded across all hospital practices, while ensuring minimal impact to staff workloads and patient care workflows. The ultimate goal is that biobanking becomes a routine part of patient care. In two years of operation, this set-up has provided over 2650 biobank specimens from over 1400 consenting participants who have had a recent diagnosis of cancer. Clinicians and researchers see value in institutional biobanking.4 However, hospital-wide uptake of HSA Biobank practices, as well as researcher use of biobank resources, relies on the implementation of collection processes that are appropriate, routine and trustworthy. Hence, diagnostic pathology plays a central role in the collection of tissue and data for the HSA Biobank. In the HSA model it is pathologists and haematologists, rather than surgeons, who are responsible for the allocation of tissues and bone marrow to the biobank. The expertise and discretion of specialist pathologists ensures that the diagnostic integrity of tissue is maintained and that the optimal quality and quantity of banked specimens is achieved (Table 1). While in some cases, biobank tissue is allocated by pathologists without prior knowledge of HSA Biobank consent status, the long-term storage of tissue and receipt of patient health data by the HSA Biobank only occurs when consent to do so is obtained from participants. Any tissue for which participant consent is Print ISSN 0031-3025/Online ISSN 1465-3931 DOI: 10.1097/PAT.0000000000000185
#
refused, revoked or unlikely to be obtained is returned to pathology or destroyed. Implementation of innovative IT and bioinformatics systems for secure data and information retrieval, transfer and storage is an important feature of the HSA Biobank. Electronic transfer of pathology reports is achieved by HL7 messaging to protected HSA Biobank databases maintained on secure UNSW servers. Systems are also in place for secure storage of demographic, clinical and epidemiological data on consenting participants. Information can be provided to appropriately authorised researchers through electronically-generated pathology reports and data files, from which personal health information has been removed to ensure de-identification. Integration of biobanking practices within the pathology service has benefits for research, hospital services and ultimately, patient outcomes. The benefits to research of a wellresourced tissue and data biobank are clear. Researchers continue to value biobanks that provide access to large numbers of formalin fixed tissue for standard immunohistochemistry and other in situ detection techniques.5 However, biobanks must also be capable of adapting to new technologies and changing trends in research methodology, and the resultant changes in demand for various tissue types (e.g., fresh tissue) and linked data. This capacity can only be provided through integration of the biobanking process with diagnostic pathology services. This linkage also provides significant benefit to the diagnostic laboratory (Table 1). Two clear benefits that pathologyresearch linkages provide are the creation of opportunities for improved diagnosis and the rapid uptake of new techniques and systems. An example of this is the increased use of next generation sequencing for identification of BRAC1/2 and other genetic mutations, which can inform clinicians of an individual’s risk of disease and potential treatment options. These advances in technology have also pushed the development of institutional protocols that provide access to adequate health data and different tissue types (diseased and normal fresh tissue or blood). With this comes renewed concern for data security, biospecimen quality and experimental variability. The robust data storage and transfer systems developed for the HSA Biobank are of practical use to hospital systems seeking to securely and efficiently share health and personal data. Institutional biobanking also provides a vehicle for the advancement of biospecimen science, leading to improvements in biospecimen handling that can minimise variation in gene expression or other biological markers.6–8 In this way, institutional biobanking provides a conduit for knowledge transfer between the diagnostic and research domains.
2014 Royal College of Pathologists of Australasia
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
INSTITUTIONAL BIOBANKING
Pre-admission consultation
5
Pre-operative ward
Consent to HSA Biobank
Consent to surgery
Yes
Eligible for biobanking?
No
No HSA Biobank 10 mL EDTA
Pre-surgery blood
No further action
Yes No further action
Removed tissue sent to anatomical pathology
Surgery
No
Check consent status
Specimen destroyed
Pending Post-operative ward - consent checked on rutine ward round
Specimen holding bay
Consent to HSA Biobank
Yes
Consent confirmed Medical record containing consent form
Medical records department
Lowy biorepository HSA Biobank HSA Biobank consent form collection
Fig. 1 HSA Biobank workflow for collection of participant consent, resected tissue, matched blood and data. Biobank consent, tissue and data collection processes are carried out alongside routine pre- and post-admission procedures that occur within the hospital patient care pathway. Consent collection is decoupled from tissue collection to aid workflow, with SEALS Anatomical Pathology responsible for allocation of tissue to the HSA Biobank. Table 1
Advantages and disadvantages of institutional biobanking
Advantages
No need to track participant consent to tissue donation Avoids disputes regarding tissue access for researchers and clinicians Reliable storage of archival tissue and retrieval for future diagnosis if necessary
Avoids ’sampling’ of tissue prior to receipt in anatomical pathology and haematology
Maintenance of tissue integrity and biospecimen quality for research and diagnosis
Standardised and contemporary approach to tissue collection Drives advancements in tissue collection, diagnosis and data transfer technology Potential or perceived disadvantages
Can be resolved by:
Delays/impediments to
Tissue banking built around routine
diagnosis
workflows
Tissue always readily available for new testing
Increased staff workload and time
Staffing costs Consumable costs
Integration within routine practices Automation Improved efficiency Professional development and training Integration within routine practices Supply of additional reagents by biobank
Not surprisingly, the integration of tissue and data banking practices within pathology services is recognised internationally as providing benefits across the hospital setting.2,3,9,10 Institutional biobanks can inform best practice in consent and tissue collection, drive advancements in information storage and data transfer technology, and improve patient care through better diagnosis and personalisation of therapy. More generally, the intersections between treatment, diagnosis and research that occur as a result of institutional biobanking build collaborative networks that foster rapid improvements in patient care. This is the ultimate aim of biobanking – to contribute to research in a way that effectively leads to health improvements for the community. The large majority of people will consent to participation in research when invited,9,11 and they typically report a positive experience from their involvement in research, even if it is limited to a single event of tissue donation.12 The integration of banking into routine clinical practice, as attempted through the HSA Biobank, can provide all patients with the opportunity to participate in research in an efficient and minimally intrusive manner. It also provides a mechanism to honour the commitment of those donors to future biomedical research. We believe that the implementation strategy of the HSA Biobank has strengthened the perception of biobanking as a worthwhile endeavour in patient care at SESLHD hospitals (Table 1). This acceptance has occurred despite initial concerns regarding increased staff workloads, disruption of work
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
6
SCOTT et al.
practices, compromise of patient care, or ethical considerations.4 These concerns have been largely overcome by making disease diagnosis, patient care and privacy a priority when establishing biobanking processes. Consultation, training and adaptability of processes to differing situations have also ensured minimal disruptions to workflows within individual units. Significant milestones have been met in the two years of operation of the HSA Biobank, including implementation of pre-admission consent processes, establishment of routine tissue banking procedures and the use of biobank tissue in current research projects. We have shown that institutional biobanking, when based on the routine workflows of a busy diagnostic pathology service, is cost-effective and sustainable, and can be established in ways that are innovative and minimally intrusive. This biobank-hospital interaction is a symbiotic relationship that benefits stakeholders in terms of research and patient care outcomes, and importantly places pathology services at the centre of this important initiative. It has significant value for individual participants, health service providers, researchers and community. The HSA Biobank has demonstrated the pursuit of institutional biobanking is worthwhile within public hospital services, and expansion to further sites is encouraged. Acknowledgements: We gratefully acknowledge the expertise and input of Ms Nicki Meagher, HSA Biobank Project Manager, in establishment of HSA Biobank processes, and the efforts of the staff of SEALS pathology in supporting their implementation. Conflicts of interest and sources of funding: The authors state that there are no conflicts of interest to disclose. The HSA Biobank is a flagship project of the Translational Cancer Research Network, which is funded by Cancer Institute
Pathology (2015), 47(1), January
NSW. HSA Biobank implementation was in part supported by funding from NSW Health Pathology. Address for correspondence: Professor Nicholas Hawkins, School of Medical Sciences, UNSW, Sydney, NSW 2052, Australia. E-mail: [email protected]
References 1. Scolyer RA, Thompson JF. Biospecimen banking: the pathway to personalized medicine for patients with cancer. J Surg Oncol 2013; 107: 681–2. 2. Watson PH, Wilson-McManus JE, Barnes RO, et al. Evolutionary concepts in biobanking – the BC BioLibrary. J Transl Med 2009; 7: 95. 3. McKeon S, Alexander E, Brodaty H, Ferris W, Frazer I, Little M. Strategic Review of Health and Medical Research in Australia – Better Health Through Research. February 2013. Canberra: Department of Health and Aging; 2013. 4. Wyld L, Smith S, Hawkins NJ, Long J, Ward RL. Introducing research initiatives into healthcare: what do doctors think? Biopreserv Biobank 2014; 12: 91–8. 5. Sadanandam A, Lyssiotis CA, Homicsko K, et al. A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nat Med 2013; 19: 619–25. 6. Ransohoff DF, Gourlay ML. Sources of bias in specimens for research about molecular markers for cancer. J Clin Oncol 2010; 28: 698–704. 7. Hatzis C, Sun H, Yao H, et al. Effects of tissue handling on RNA integrity and microarray measurements from resected breast cancers. J Natl Cancer Inst 2011; 103: 1871–83. 8. Dev H, Rickman D, Sooriakumaran P, et al. Biobanking after roboticassisted radical prostatectomy: a quality assessment of providing prostate tissue for RNA studies. J Transl Med 2011; 9: 121. 9. Platell C, Zeps N, Joseph D, Spry N, Iacopetta B, Caruso V. Tumour banking as part of routine clinical practice. ANZ J Surg 2010; 80: 203–4. 10. Brisson AR, Matsui D, Rieder MJ, Fraser DD. Translational research in pediatrics: tissue sampling and biobanking. Pediatrics 2012; 129: 153–62. 11. Thomas G. Tissue banking for research: connecting the disconnected. Cell Tissue Bank 2011; 12: 29–30. 12. Cervo S, Rovina J, Talamini R, et al. An effective multisource informed consent procedure for research and clinical practice: an observational study of patient understanding and awareness of their roles as research stakeholders in a cancer biobank. BMC Med Ethics 2013; 14: 30.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
