Assessing the Financial,Operational,and Social Sustainability of a Biobank: The Wales Cancer Bank Case Study

Abstract

Biobank sustainability is a multi-faceted concept that many biobanks are wrestling with to justify their continued existence. After 10 years of operation, the Wales Cancer Bank is faced with a potential reduction in grant funding that will result in the need for a restructured approach to patient consenting, sample collection, and sample issue. A review is currently in progress, using evidence from the last 12 months, to inform the decisions that will be taken at the end of 2014 regarding the biobank's future. The information presented details the areas under consideration for revision with the perceived costs and benefits associated with the amendment. Not all outcomes are currently known, and some decisions will be made once the level of future funding is confirmed. The process of assessment has proved to be a valuable exercise and has highlighted the need for biobanks to regularly evaluate strategic principles and operating procedures using sustainability as a denominator.

Introduction

The Wales Cancer Bank (WCB), which has operated under the same principles and processes for 10 years, is currently analyzing its core areas of operation. The strategic principles and operational processes of the biobank are being reviewed to assess sustainability and evaluate the impact on the future structure of the repository. The sustainability of the WCB is assessed by examining its value to the research community, the patients, and the healthcare system, as well as its continued funding. The dictionary definition of sustainability is “to keep in existence, to maintain” and “able to be upheld or defended.”¹ The information gained through this analysis will be utilized in the submission for continued funding of the biobank.

The WCB collects disease-specific samples that are made available for general use by cancer researchers worldwide. As described previously, the three main sustainability dimensions relevant to biobanking (operational, financial, and social) are not mutually exclusive.^2,3 For the purposes of this discussion, social sustainability includes acceptability by the research community, the public/patient community and other non-funder stakeholders. There is overlap with operational sustainability, as efficiency of operation is vital to maintain the confidence of the researchers. Financial sustainability is a more difficult concept to delineate as it depends upon the structure, operational strategies, and long-term objectives of an individual biobank.

The Wales Cancer Bank

Background

The WCB is a research tissue bank in the United Kingdom (UK) that collects biosamples from cancer patients in eleven National Health Service hospitals around Wales. [Wales covers an area of 20,782 sq kms (8,024 sq miles) and has a population of approximately 3 million, with an annual incidence of cancer diagnoses of approximately 16,000.]

The WCB receives core funding from the devolved Government of Wales via the National Institute for Social Care and Health Research (NISCHR), as well as grant funding from Cancer Research Wales (CRW), a cancer charity based solely in Wales. The WCB is licensed by the Human Tissue Authority (HTA) under the UK's Human Tissue Act (2004), and it has ethics approval from the UK National Research Ethics Service as a research tissue bank to collect samples and issue them to researchers. Cardiff University hosts the biobank.

Under the current operational model, tissue and blood samples are collected from patients in Wales with a confirmed or suspected cancer diagnosis. Patients with any tumor type are consented by research nurses and the samples are stored for future, as yet unknown, research. The samples are available to cancer researchers worldwide via an application system, and a contribution towards cost recovery is collected. The core funding from the Welsh Government supports the central administration office, IT staff, research nurses, and laboratory-based staff, as well as non-staff-related costs such as consumables, training, and equipment. Initially, four hospitals in Wales were involved in the sample collection that gradually expanded to eleven hospital sites. In 2004, this equated to 10 full-time equivalent (FTE) staff and core funding of £459,000 (approximately $735,000) per year; in 2013 there were 20 FTE staff and the core funding was £840,000 (approximately $1,345,000). The capital investment profile shown in Figure 1 follows the expected pattern as described by Vaught et al.⁴ when illustrating a model of total cost of ownership for a biobank; the increasing staff costs reflect the addition of new collection sites as the project expanded.

FIG. 1.

Expenditures on the Core Grant from the Welsh Government From 2004–2009, the IT costs were contained within the staff costs until a dedicated IT contract was initiated. Non-staff recurring costs include consumables, maintenance contracts, legal (licensing) fees, office expenses, and costs for travel and training. The spike in capital costs in 2010 represents technology and equipment upgrades or replacement costs.

The core grant funding from the Welsh Government as provided in 3- or 5-year blocks (2004–2007, 2007–2010, 2010–2015), with the current grant ending on March 31, 2015. In 2006, CRW awarded the project a 3-year grant of £500,000 to support the further processing of tissue samples to make DNA and RNA available to researchers. Two additional 5-year grants of £600,000 and £1,500,000 were also awarded by CRW in 2007 and 2012, respectively, to continue the previous support and to use Next Generation Sequencing to characterize 3000 tumor samples and enrich sample annotation. WCB has also received funding from the Velindre Cancer Centre Fundraising fund through the Stepping Stones Appeal and from Cancer Research UK (CRUK), via the Cardiff University Experimental Cancer Medicine Centre funding (these are shown as “Grants-Others” in Fig. 2).

FIG. 2.

Annual grant funding, number of staff employed, and number of consenting patients.

The WCB employs research nurses to consent patients for access to tissue that is surplus to diagnostic requirements, and to request additional blood samples. WCB-funded laboratory staff are embedded in the histology departments of the National Health Service hospitals and research-specific, formalin-fixed paraffin-embedded tissue samples are sourced via routine hospital procedure once a pathologist has confirmed tissue can be taken for the biobank. All samples are barcoded and quality assured, either at the source or prior to issue, to ensure all samples are fit for the intended purpose. Pathology, treatment, outcome, and molecular genotyping information are collected to provide well-annotated samples.

Income Generation

WCB has two main income streams other than grant funding—cost recovery and the provision of additional services to the research community.

Cost recovery

The WCB charges researchers a fee to access samples as a contribution towards cost recovery following a satisfactory scientific review by an external panel. All researchers, regardless of sector or institution, are subject to the same cost recovery fee for equivalent samples and/or data. Differential charging could not be implemented as it was found to be in contravention of the EU competition policy and viewed as State Aid (the core funding is from a government source) and therefore illegal. The use of public funding cannot give a recipient an advantage on a selective basis. Therefore, local or academic researchers cannot be charged less than academic researchers outside Wales or researchers from biotechnology or pharmaceutical companies.

Thus far, the majority of samples have been issued to research groups outside Wales. Although there is local, high-quality, cancer-related research, the WCB has struggled to persuade some of the local research groups that despite the fee, the service provided is good value for the money. Many local researchers feel that they should have free access to samples and are unhappy or unwilling to meet the assessed fee. However, sample-related income has risen markedly since 2011 (Fig. 3) due to participation as one of seven clinical hubs chosen to collect samples for genetic analysis in phase one of the CRUK Stratified Medicine Programme (SMP). In phase two of the program, sample collection will be reduced and income is, therefore, expected to be reduced by 80% in 2014.

FIG. 3.

Number of samples issued and related income. Service-related income includes hosting clinical trial samples and access to analytical technologies.

Provision of additional services

Hosting clinical trial samples

Since the HTA was passed in 2004, WCB has stored approximately 18,000 samples for 13 clinical trials originating from three UK clinical trial units. A hosting arrangement is provided for these samples under the Human Tissue Act license for a fee that is related to the number and type of samples, and length of storage required. Sample processing is also provided if required by the trial management group, who retain complete control over the samples. In 2012, the volume of work increased to such a level that it became necessary to employ a dedicated curator for these samples.

Access to analytical technologies

Using grant money, various pieces of equipment (e.g., digital imager, tissue microarray, laser capture microdissector) have been purchased to enhance the operational capability of the biobank. Analyses using this equipment is now offered as a service to researchers to further supplement income. A cost model with the WCB as a small research facility within Cardiff University was implemented.

The income generated through these additional services has funded the replacement of several pieces of equipment as well as provided support for staff while grant funding was pending. Although this additional income has not been sufficient to reduce the need for grant funding to support operations, it has allowed reduction of requests for external funds by approximately £120,000 over the last 3 years, as well as retention of three staff members during a gap in grant funding.

Over the life of the biobank, the income generated from sources other than grant funding accounts for approximately 5% of the total and is highly dependent upon the number, size, and length of individual contracts.

Sustainability Analysis

WCB recognizes that a leaner, smarter operating model is necessary; the implementation of a re-focused model is dependent upon the level of funding available after April 2015. This reorganization will result in a departure from the original model where disease-specific samples are collected and made available for general use. However, without this restructuring, the biobank is highly unlikely to ever become financially self-supporting, and grant funding will continue to be necessary.

Three areas with the potential to increase the social, operational and financial sustainability of the biobank were identified:

1) Tumor and sample types collected

2) Informed consent process

3) Cost recovery and marketing

For each of the three areas, analysis of the current protocols was undertaken and changes recommended with the goal of increasing efficiency and decreasing costs. While the outcome of all the analysis is not yet complete, the evidence presented provides a good indication of the likely conclusions.

Tumor and sample types collected

Collecting samples from a representative population in Wales for future, unknown research projects has resulted in sizeable collections representing the most common cancers, as well as several collections of between 10 and 100 patients. The utility of multiple small collections is greatly reduced and the time and cost invested in collecting these samples is far greater than the financial return. A review of the tumor samples issued showed a good correlation with the tumor types stored (Table 1) for the three tumor types with the greatest number of registered consents (breast, colorectal, and prostate).

Table 1.

Percentage of Tumor Types Stored and Samples Issued in 2013/2014 ¹

Tumor type	% of total collection ¹	% of total tumor samples issued
Breast	23.6	25.8
Colorectal	18.7	21.8
Prostate	15.6	25.2
Renal	8.3	2.1
Lung	6.7	10.5
Head and neck	5.2	0.8
Ovarian	4.8	1.6
Endometrial	4.1	1.0
Pancreatic	2.1	0.7
Skin	1.4	1.9
Gastric	0.3	8.6

These eleven tumor types are a subset of all tumor types in the biobank; therefore this column does not total 100%.

During the 2013/14 analysis period, 8653 samples were collected and stored, and 2755 samples (31.8%) were issued; the breakdown by sample type is provided in Table 2. Over the 10 years of the project, 34% of patients have had at least one donated sample used in a research project and 13% of samples collected have been used.

Table 2.

Comparison of Sample Types Collected and Issued During 2013/2014

Parent sample type	% of total samples collected	Sample type issued	% of total sample types issued
Whole blood	29.5	Whole blood	17.2
		DNA from blood	0.9
Serum	46.0	Serum	19.7
Paraffin blocks	21.5	Paraffin tissue (tumor, normal)	47.0
Fresh, frozen blocks	3.0	Fresh or frozen tissue	6.3
		Nucleic acids from frozen tissue	8.9

A cost/benefit analysis was carried out to evaluate the impact of introducing proposed changes to the tumor and sample types collection policies (Table 3). This analysis suggests that those actions with an impact score of 4 or 5 should be implemented to enhance financial or operational sustainability. These are:

Table 3.

Cost/Benefit Analysis of Proposed Changes to the Tumor and Sample Types Collected ¹

Action	Cost	Benefit	Impact score ²
Reduce primary collection to 4 or 5 most commonly used tumor types	• Unable to supply requests for all tumor types	• Reduces the number of clinics for consent• Reduces the number of samples stored• Reduces the number of unused samples	3 - Increased financial sustainability
Collect primary tumors only for known projects	• Extends time to fulfill project requests• Difficult to start/stop presence in clinics	• Always able to supply requests• Reduces storage requirements• Eliminates unused samples	4 - Increased financial and operational sustainability
Stop collecting frozen tissue	• Reduces range of available samples	• Eliminates reliance on immediate pathology presence• Reduces staff time performing nucleic acid extractions• Reduces freezer requirements	4 - Increased financial and operational sustainability
Stop reviewing slides for quality assurance	• Reduces ability to accurately record samples in database• Onus on researchers to review sections for acceptability	• Eliminates requirement for pathologist input• Increased use of existing digital imaging and remote pathology software• Researchers can select samples they consider acceptable for projects• Reduces staff time	3 - Increased financial sustainability
Increase metastatic and longitudinal sampling	• Requires good patient tracking	• Provides more useful sample sets• Reduces number of patients for follow up	4 - Increased financial and operational sustainability

For each proposed action the costs and benefits were evaluated and balanced to produce an overall perceived impact score on biobank sustainability.

Impact was rated on a scale of 0 to 5 with 0 having a negative impact on sustainability, 1 having no impact on sustainability, and 5 having a large positive impact on sustainability.

• Confine future primary tumor collection to known projects rather than prospective collection.

• Suspend collection and storage of frozen tissues.

• Expand metastatic and longitudinal sampling for identified patient cohorts.

The two areas with an impact score of 3 (reduce primary collection to the four or five most commonly used tumor types and stop reviewing slides for quality assurance) require further discussion and evaluation. The decision to provide well-annotated and quality-assured samples for research requires enormous staff input and makes the supply of samples extremely labor intensive. The time and effort required to make samples ready for issue was under-estimated. The elimination of this process is under consideration as all slides are imaged and software is in place to allow researchers to view slides and annotation remotely. Pathology services could be obtained and a charge assessed for those researchers without the expertise to choose relevant samples.

Informed consent process

The model of using dedicated research nurses to consent patients is reliable but expensive, utilizing 29% of the total budget and just over a third of the budget for staff salaries (Fig. 4).

FIG. 4.

Allocation of staff budget. The staff budget for WCB is 82% of the overall budget.

The consenting process currently takes place in 11 hospitals, grouped into six operational sites that were assessed to ascertain performance levels during the 2013/2014 analysis period (Table 4 and Fig. 5). Retrospective consenting in tertiary referral centers such as Site F has resulted in a greater consent return but it has proven harder and more resource intensive to source tissue samples post routine processing. To demonstrate cost effectiveness, sites should have equivalent or increased percentage output (number of consents and number of samples) compared to the percentage of income received (Fig. 5). This assessment shows that some sites are less financially viable than others. The lower consent, collection and usage rates, and concomitant higher cost per consent and sample at some sites may be due to lack of engagement and integration into the routine hospital departments. While annual audits have identified the need for some training at these sites, which has been implemented, the sites continue to operate at a reduced level compared to others. This assessment will be taken into consideration when contemplating the possible reduction in the number of collection sites and incorporating different consenting models in the remaining centers.

FIG. 5.

Comparison of funding, consents, samples received and issued, and cancer incidence data, by site, for the analysis period 2013/2014. LHB, Local Health Board. Site F is a tertiary referral center that routinely sources blood only.

Table 4.

Collection Activity by Site During 2013/2014 ¹

Site	FTE nurses	Consents per FTE nurse	Number of samples recorded per: donation FTE nurse		Site funding £	Cost per consent £	Cost per sample £
Site A	2.7	252	6.9	1,738.9	174,200.00	255.80	37.10
Site B	0.45	251	8.6	2155.6	46,200.00	408.85	47.63
Site C	0.7	122	5.7	701.5	45,150.00	543.98	94.65
Site D	2.8	136	7.4	1,005.0	160,180.00	420.42	56.92
Site E	1.2	137	6.2	845.0	59,750.00	364.33	58.93
Site F	1.0	418	1.1	462.0	40,400.00	96.65	87.45
Average		219	6.0	1,151.3	87,646.67	348.34	63.78

The cost per consent and cost per individual sample at each site was calculated using data from the 2013/2014 analysis period. The number of consents and samples per donation per full-time equivalent (FTE) nurse were used against the amount of funding received by each site for the staff directly involved in consent and sample acquisition.

Attempts have been made in numerous clinics to integrate the consent process into the patient pathway facilitated by the clinical team. This has varied in effectiveness but in general has had limited success. Until consent for research is integrated with consent for surgery, the process will still need to be funded but examples of models from other biobanks, such as volunteer consenting,⁵ are being considered.

A cost/benefit analysis was also carried out to evaluate the impact of proposed changes to the consenting policy (Table 5). From this analysis, it is suggested that those changes with an impact of 4 should be implemented to enhance operational, social or financial sustainability. These are:

Table 5.

Cost/Benefit Analysis of Changes Proposed to the Consenting Process ¹

Action	Cost	Benefit	Impact score ²
Reduce the number of collection sites	• Loss of pan- Wales coverage – political implications• Loss of public support in closed centers• Decreases ability to support researchers with local collections	• More concentrated geographic area of operation• Diversion of funding to more productive sites• Reduces administration• Reduces licensing costs	4 - Increased financial and operational sustainability but decreased social sustainability
Rely on clinical teams to consent patients	• Loss of reliability• Need for a coordinator to ensure compliance across teams	• Reduces requirement for WCB-funded nurses• Ability to consent in a larger number of clinics	2 - Increased financial and operational sustainability
Introduce volunteer consenting	• Need for extensive training and supervision	• Supplements clinician and/or nurse consenting• Increases patient/public involvement	4 - Increased social sustainability

For each proposed action the costs and benefits were evaluated and balanced to produce an overall perceived impact score on biobank sustainability.

Impact was rated on a scale of 0 to 5 with 0 having a negative impact on sustainability, 1 having no impact on sustainability, and 5 having a large positive impact on sustainability.

• Reduce the number of collection sites

• Introduce volunteer consenting

Cost recovery and marketing

In order to increase financial stability, better use of the biobank resources must be made, and a marketing strategy was introduced in 2013 to investigate possible opportunities. To inform the strategy, two electronic surveys (SurveyMonkey) were undertaken. Recipients had 4 weeks to complete the surveys, with reminders at the end of Weeks 3 and 4.

In the first survey, awareness of the WCB within the cancer research community based in Wales was assessed. Sixty-eight out of 169 researchers (40%) completed the survey, with 46 confirming that they have used, or may have need of, human samples for their research. Of these, 46 were aware of the WCB, from various sources: colleague (10), conference (1), email (1), poster/flyer (1), press (1), WCB newsletter/leaflet (2), WCB website (1), word of mouth (7), workplace (9), and other (13). Fifty-two percent of respondents indicated they would consider using WCB samples in the future, 13% said they would not, 33% said maybe, and 2% did not know.

In the second survey, researchers who have previously sourced biosamples from WCB were asked to rate specific aspects of the sample application and supply process, to comment upon the likelihood of using WCB in the future, and to provide their perceptions of the costs involved in procuring the samples (Table 6). Results of the user survey suggested general acceptance of the process and service supplied, but it also highlighted some areas of concern. Some researchers suggested that the application form is too long and they viewed the process as overly complex. Some felt the cost of samples was prohibitive, with 68% indicating they would be more encouraged to use the service if the cost of samples was reduced. The question of discounting or even discontinuing the cost recovery fee is completely at odds with a drive to achieve financial sustainability. However, if the legal position remains that differential charging cannot be implemented, then the cost will remain prohibitive for local and academic researchers. Processing and service charges could be introduced, which would be much lower for large sample requests than the cost recovery contribution. This would allow the income stream to continue, albeit it reduced, rather than offering completely free samples.

Table 6.

Survey of Previous Users of Samples from WCB ¹

Application and supply process rated	Good	Average	Poor	Don't know or N/A
Application process	12	7	0	5
Communication	17	5	0	2
Turnaround time of application	9	9	1	5
Cost of samples	9	6	2	7
Quality of samples	17	1	2	4
Type of tissue available	17	3	2	2
Overall service	17	5	1	1

The survey was sent to 51 researchers around the world using the e-mail addresses registered at the time of application. There were 5 e-mail delivery failures. Responses were received from 24 researchers (47%); 77% indicated they would use WCB again, and 19% said maybe they would. One respondent (4%) said they would not use WCB again as they no longer worked with human biosamples.

The user survey will now be routinely sent to researchers 3 months after sample supply to ensure constant feedback is received.

Conclusion

The WCB has the opportunity to re-model itself and learn from the last 10 years. Although the original plan was ideologically and scientifically sound, it has proven resource heavy and impractical and would require substantially greater funding to reach its original aim. The WCB has been a success, but in the current format it is financially unsustainable without continued, significant grant funding. A change in the operating model is inevitable and the areas analyzed and reported here will be central to the new structure to maintain and enhance social and operational sustainability. Savings could be found to reduce the required grant funding, but some changes will reduce the available pool of samples and potentially the quality assurances currently supplied with the samples. If this has the effect of reducing sample income, then there will be no gain in financial sustainability. But sustainability of the biobank as a core principle will be enhanced.

Biobanks should regularly audit and review processes and policies to ensure they remain fit-for-purpose, cost effective, and scientifically relevant. Unless specific operational parameters are mandated by the funding bodies or host institution, the fundamental premise of the biobank, such as what to collect, where to collect, and how to collect, should be included in the review process to keep the biobank current and sustainable. It is difficult to compare biobank self-sufficiency models, since running costs are diverse and the baseline calculations will depend upon the structure and purpose of the biobank. Where processes are integrated into the host institution, there are a varying number of costs (e.g., rent, electricity, histology processing, staff time, consumables) that may be absorbed by the hospital or university and not included in the financial sustainability consideration for the biobank, making it appear more viable than the reality. Cost recovery income can be highly variable, dependent upon the size and number of contracts in place, and mid-term business planning and marketing must be thorough to avoid over reliance on lucrative contracts.

A biobank should be viewed as infrastructure, as it is there to support others and facilitate research on good quality human tissue and blood samples. This in turn encourages investment in research. The Strategic Tissue Repository Alliances Through Unified Methods (STRATUM) work package on cost models for biobanks suggested that there is a “requirement for public funding of biobanking” and that public funding for research such as biobanking is “critical”.⁵ Future gains for the health service from research done on tissue bank samples are becoming increasingly important with the advent of stratified medicine. But tangible gains that arise from tissue banking, in terms of patient impact, reduced drug costs, impact on the health service etc., are not short-term gains but mid- to long-term gains. Continued investment in tandem with leaner, smarter operating models remains necessary.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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