Abstract
In the last decade, many disease-focused foundations and patient advocacy organizations that support biomedical research have created patient registries and biobanks. This article reviews the motivations behind the creation of those biobanks and how they are different from biobanks sponsored by government or industry. It also discusses some of the different funding models being employed by these organizations. Finally, it highlights some of the unique challenges faced by disease-focused foundations and advocacy organizations that sponsor biobanks, and how they are overcoming those challenges to achieve both financial and operational sustainability.
Introduction
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The biobanks created by disease-focused foundations and patient advocacy organizations differ in many ways from traditional academic or government collections. First, they are created to provide a disease-specific open resource for the biomedical research community and are prospective in design to be a durable resource for both current and future research needs, when open source government collections do not exist or when access to academic collections is restricted. Second, recruitment and participation is not limited to a single investigator or limited group of investigators, institutions, or local patient populations, but can be open to any patient who wants to participate. Third, to minimize start-up time, operating costs and maximize quality and reliability, they typically rely on third parties to provide most, if not all, of the necessary biobanking services, including database hosting, software, sample collection, processing, storage, and distribution.
The purpose of this article is to review how several forward thinking disease-focused foundations and patient advocacy organizations have designed, funded, and are operating biobanks for the benefit of patients. We provide examples of how different organizations have approached each step in the process and focus on how they achieve financial sustainability. We have tried to highlight the sustainability challenges that are unique to these different operating models, in addition to challenges to sustainability that are common to all biobanks.
Operational Considerations
Recruitment and collection
Disease-focused foundations and patient advocacy organizations who wish to establish biobanks typically do not have the medical operating infrastructure to identify potential subjects, obtain their consent, and collect their biosamples. This operational limitation has been addressed in a number of ways. The Cystic Fibrosis Foundation supports a network of clinical treatment centers across the United States, where the vast majority of cystic fibrosis (CF) patients are able to consent, enroll, and donate samples for CF research. This is a very expensive resource to maintain, but the incremental cost of recruitment and sample acquisition is modest. Others such as the Accelerated Cure Project for Multiple Sclerosis and Vascular Cures have created clinical networks to collect patient data and associated samples. Maintaining these networks for longitudinal studies frequently requires sustained reimbursement for personal costs, in addition to transaction costs associated with enrollment and sample collection. When biobanks need maximum geographic and socioeconomic diversity, or involve rare diseases when the patient population is small, recruitment at clinical centers may not be practical or cost effective.
A third alternative that is being used extensively by disease foundations and advocacy organizations is direct recruitment of subjects. Many disease-focused foundations and patient advocacy organizations have extensive databases of patients and family members who are candidates for participation in a disease-focused biobank. They also have mechanisms for outreach to a significant portion of their target patient populations. Patients view these organizations as a trusted third party who will provide ethical stewardship of their data and samples. This model has the added advantage of low recruitment costs, as participants will often take an active role in recruiting other subjects, as well as geographic and familial controls. With this recruiting method, subjects are largely self-selecting, however prescreening on-line or by phone is frequently used to confirm diagnosis. Consent can be obtained on-line, as well as collection of the data necessary to annotate samples. Screening surveys use standardized demographic elements coupled with clinically validated survey instruments. Typically patient-reported data is curated by a biobank coordinator. This is a relatively low cost model but sample collection can be operationally challenging.
While it is relatively easy to obtain saliva or cheek swabs collected by the patient, collection of blood or other tissue requires that the subject to go to their doctor or a local phlebotomy clinic, outpatient surgery center, or hospital, with a doctor's order for sample collection. The Solve ME/CFS Initiative has overcome this hurdle through the use of mobile phlebotomy services for blood collection. However, these services are not available in all locations. When longitudinal samples must be collected, or the tissue samples required for the biobank can only be secured via surgical procedures or other invasive procedures (e.g., lumbar puncture), disease-focused foundations and advocacy organizations can partner with practice management organizations for clinical access.
Regardless of the site of collection or mechanism, data collection and sampling methods must be simple, robust, and consistent across the collection. In the case of ad hoc clinical networks, partnerships with practice management organizations or when local phlebotomy services are utilized, ensuring that all personnel are adequately trained can be challenging. The costs of on-going collection site training, along with data curation, are significant sustainability considerations for any disease-focused foundation or advocacy organization considering creating a biobank.
Data collection and registries
While a registry is not essential to the creation of a biobank, it is a very useful tool for advancing research sponsored by disease-focused foundations and advocacy organizations and is frequently used as a precursor to a biobank. Registries enable patient engagement and allow collection of the data necessary to annotate the samples properly in a prospective collection. In addition, a well-designed registry database can be a valuable tool for in silico research and optimizing the selection of samples and subjects for both laboratory and clinical research. There are several successful approaches to creating registries and the amount of data they collect can be extensive. The Foundation Fighting Blindness utilizes a registration survey that includes over 170 data elements from genomic diagnosis to quality of life measures and is being expanded to incorporate physician-reported clinical data. The quality of data in this registry is enhanced by utilizing standardized data elements from the NIH and clinically validated survey instruments along with active curation.
The value of a prospective biobank to serve future research needs is enhanced by the richness of the associated database. Web-enabled registries allow longitudinal data collection, without extensive transcription, from both subjects and clinicians. Tools such as REDCap allow rapid creation and testing of data collection instruments for clinical networks and can be very cost effective. There are public registries such as Connect from Patient Crossroads and Registries4All from the Genetic Alliance that are available to disease-focused foundations and advocacy organizations. There are also federal grants available from the Patient-Centered Outcomes Research Institute (PCORI) that can catalyze this process.
The key to a biobank's utility is linking the data from a registry to samples that are available to investigators. To protect participants' privacy, this is typically done via export of deidentified data that is linked with the samples through the use of a unique subject identification number. Since a subject may have data and samples in more than one biobank, the National Institute of Mental Health's National Database for Autism Research (NDAR) created an algorithm to generate a Global User ID number (GUID). This algorithm is publically available for use in registries and biobanks sponsored by nonprofit organizations to help facilitate comparison of data between diseases and databases.
Most disease-focused foundations and advocacy organizations rely on outside software, and service providers, for their registry and biobank databases. Identifying suppliers that meet both current and future needs is a challenge. Developing well-thought out requirements documents, testing various platforms for their abilities to meet those requirements, and checking references from other organizations using these services and providers, are critical elements of the start-up process and have a significant impact on both start-up and long-term operating costs. However, using off the shelf technology solutions is almost always faster and less costly that designing and implementing custom databases.
Sample recovery, processing, storage and distribution
Since most disease-focused foundations and advocacy organizations have limited in house scientific facilities, they will contract for sample recovery, processing, storage, and distribution services. Fortunately, over the last decade, all of these services have become available from a number of capable companies, in addition to several academic institutions. In most cases disease-focused foundations and advocacy organizations are looking for “turn-key” services that include:
• sample kit preparation (including collection instructions and return shipping documents), • kit distribution and recovery, • incoming integrity inspection and quality control, • processing and aliquoting of samples, • archival storage at appropriate temperature to maintain long term sample integrity, • sample inventory control, • distribution of samples in investigator defined configurations for research use, • well documented operating procedures (SOPs) including training records, • adherence to standards (e.g., CAP certifications).
The gamut of services available ranges from simple inventory and storage of samples as they are received to comprehensive genomic analysis after processing. A number of nonprofit and commercial biorepositories such as the Coriell Institute, RUDCR Infinite Biologics, Fisher BioServices, Precision Biosciences, and others have established excellent reputations for providing reliable, cost effective biobank services for government agencies, as well as disease-focused foundations and advocacy organizations. Use of these services enables rapid start-up with no capital investment. It also provides lower operating costs through economies of scale and fee-for-service pricing. Most of these organizations employ quality and sample control systems that exceed the capabilities of most individual labs to ensure every investigator receives samples that meet their specific needs in terms of quality, quantity and format.
Since the majority of the cost is in initial sample acquisition and processing, critical design criteria include:
• the type and quantity of patient sample to be collected, • how the samples must be processed and stored, • how many daughter samples and what type will be included in the collection, • how the samples may be used in the future and how long they will be stored.
Sample type is generally driven by what currently funded investigators require or are requesting. Because these collections are prospective, careful consideration must be given to emerging techniques and future requirements so patients do not have to provide additional samples. However, consent for resampling is an important design criterion. Sample collection kits may be configured so that cells and tissue are collected in sufficient quantities, processed and preserved for a range of future analyses, to provide enough aliquots to meet the anticipated lifetime of the collection. All of these factors must be incorporated in the biobanks design and budget in order to achieve financial sustainability. Since biobanks sponsored by disease-focused foundations and advocacy organizations are not tied to a specific project, design and financial modeling are particularly challenging and are often driven by financial constraints.
A number of on-line resources are available to assist organizations wishing to create new biobanks using contracted resources. The Genetic Alliance provides an excellent Registry and Repository Vendor Assessment Worksheet in their resource repository http://resourcerepository.org/documents/1865/registryandrepositoryvendorasse%20ssmentworksheet/. The Accelerated Cure Project for MS also provides an outstanding resource by making all of the documentation regarding their biobank available on their web site at http://www.acceleratedcure.org/impact/repository/documents.
Promoting utilization of these collections
In many cases, creation of these biobanks is in response to demand from investigators who have been funded by disease-focused foundations and advocacy organizations, or commercial entities who want to develop new therapies for the disease. This is especially true for rare diseases where it is difficult to find suitable subjects. Several of the organizations who have created biobanks give preference to funding research that utilizes the collections in their biobanks. Other methods of promoting these collections to the biomedical research community include appearing at scientific meetings, literature citations, and outreach to known investigators in the field.
There are two principal hurdles to utilization of biobanks created by disease-focused foundations and advocacy organizations. First, investigators frequently want to have complete control of the entire research process and tend to distrust the quality of samples collected or processed by third parties. The reality is that well-designed, “industrialized” processes utilized by disease-focused foundations and advocacy organizations via competent third party service providers often have superior quality control and traceability systems. And they can provide sample quality that meets or exceeds what can be achieved locally. Second is the misperception that it is less costly to collect and process samples in-house. The cost per sample from a foundation or advocacy organization is generally far less than the cost of local collection, processing, and storage. These costs do not include the time savings by utilizing an existing collection rather than developing protocols, obtaining IRB approvals and recruiting new subjects.
If a disease-focused foundation or advocacy organization is collecting the type of sample a researcher requires, the cost of accessing these samples is typically 2%–5% of the cost of local collection and processing. Gaining visibility within the research community will remain a significant challenge for these biobanks in the near future.
Financial Models for Sustainability
Disease-focused foundations and advocacy organizations derive financial support of their biobanks from a broad range of sources. This includes traditional sources such as grants from government and philanthropic support from patients and other donors. However, since the goal of many of these biobanks is to create a durable resource for research, grant funding with a limited duration is typically only available during the start-up phase or to expand the collection in conjunctions with a specific project. Availability of grants to disease-focused foundations and advocacy organizations for biobanks has been extremely limited since they frequently do not conform to the traditional eligibility requirements for government funding. Therefore they have had to turn to other models to achieve financial sustainability.
Donations
Because of their link to patients and other philanthropic supporters, disease focus foundations and advocacy organizations can create biobank specific fundraising campaigns and endowments. The success of this approach is dependent on educating their audience about the importance of a biobank for advancing research related to the focus disease, but the appeal of contributing to something as understandable and durable as a biobank is very appealing. A biobank is something a patient can physically and financially contribute to and feel as if they are making a significant personal contribution to the research process. Vascular Cures has employed a two-pronged approach to funding its biobank. At its annual fundraising dinner, during the live auction it incorporates a “fund a need” where donors can fund the addition of one or more subjects to the biobank. The amount is sufficient to cover the direct costs of subject enrollment, sample processing, and storage. Vascular Cures has also created an endowment for its biobank that is named in honor of the organizations founder. This endowment is intended to cover the annual operating cost of maintaining the biobank in perpetuity.
One especially unique model for personal philanthropy is charging subjects who want to contribute samples to a biobank, in conjunction with participation in other diagnostic testing. Since a single blood draw for genetic testing will yield enough material for several hundred tests, participants may be asked if they are willing to contribute the excess material to a biobank. The Foundation Fighting Blindness has taken that process one step further and asked subjects to provide modest donation to cover the costs of maintaining their sample in the biobank.
Sample Cost Reimbursement
Disease research foundations and advocacy organizations are increasingly charging investigators for the samples they want to draw from the biobank. Since operating costs for these biobanks are front-end loaded, this source of revenue is not significant in the early stages but can be a significant contributor to offsetting long-term operating costs. Unfortunately, today many investigators balk at the idea of paying for samples from a biobank. Typically they include the cost of sample acquisition in the cost of their grant and will work through their institution to recruit the necessary subjects and bank the samples. Historically this has been because there was no other way to access the necessary samples. The advent of disease-focused collections that are open to the research community significantly alters this dynamic. Today when a biobank sponsored by a disease-focused foundation or advocacy organization with suitable samples is available, the cost of drawing prepared samples from the biobank is 1%–10% of the cost of de novo collection. The added benefit to researchers is speed of acquisition, since the time required for sample acquisition can be reduced from months to days. It is critical that the scientific community be educated about the availability and benefits of these collections.
Most of the organizations mentioned in this review expect researchers who want samples from their collections to pay for the direct cost of those samples. While each organization may calculate those direct costs slightly differently most would include:
• A portion of the sample collection and processing cost based on the number of daughter samples resulting from the collection event, • The storage cost for that sample, • The cost of assembling the requested samples, performing viability checks, repackaging the samples in the requested format, and the shipping cost to the researcher.
Many organizations have a two-tiered reimbursement system, with one price for academic and other nonprofit investigators and another price for commercial investigators, which reflect the differences in acquisition cost and patient access. Since it is uncertain how much any collection will be used, it is unlikely that sample reimbursement alone will ever be sufficient to ensure the long-term viability of a biobank.
One especially unique approach to sample cost reimbursement is being used by the Solve ME/CFs Initiative. It has consented over 800 people with chronic fatigue syndrome, their family members and geographically proximal healthy controls, and collected enrollment data, but has not collected samples from most of these subjects. When an investigator submits a study requesting samples, the subjects will be contacted, necessary samples collected in their home or by a local phlebotomist, and shipped to their biobank to be processed and stored. The investigator pays for the samples they receive, but at a cost that is significantly lower than recruiting the subjects and collecting the sample themselves. This process avoids the Solve ME/CFS Initiative having to make a significant up-front investment in collection and processing of samples that may never be used.
Corporate Partnerships
As open access, disease-focused collections grow, they often attract the interest of pharmaceutical and biotechnology companies. Companies understand the real cost of creating well-annotated collections, especially from subjects who have agreed to be re-contacted for research. These companies are willing to pay for access to data, samples, and select patients that meet their research needs. This possibility should be considered during the development of the patient consent process and incorporated for biobanks that wish to tap this source of funding. Developing effective corporate partnerships is of growing interest among disease-focused foundations and advocacy organizations, since it is well aligned with their mission and becoming more expected by their patients. Because of the stringent sample and data quality requirements of industry, utilization of these collections by industry is a key measure of success and can be a significant contributor to long-term financial sustainability.
Financial Modeling for Success
Since biobanking is not a core competency for most disease-focused foundations and advocacy organizations, having a well-designed business strategy is critical. This strategy must include the purpose and goals of the biobank along with the resulting operational and financial requirements. Decisions made during the planning process will have significant downstream implications on cost, quality, utility, and sustainability. Fortunately, as mentioned above, a number of good resources are available from the Genetic Alliance2 and the Accelerated Cure Project3 to assist in the planning process. Based on our recent experience at Vascular Cures, and years of industry experience in financial modeling by the leadership team, we recommend including the following considerations when building financial models for biobanks.
• Identify the key drivers of cost
• Size of the collection • Mix of patients and controls • Duration of the collection and individual sample storage • Quantity and types of samples to be collected and stored • Method of enrollment • Speed of enrollment • Location of sample collection • Choice of shipping vendor (UPS vs. FedEx) • Timing of sample collection—weekends and holidays are more expensive • Difference in cost for type of site, area of country • Services required by biorepository • Start-up costs vs continuing operating costs • Fixed costs (personnel, licenses, physical assets, etc.) vs variable costs (i.e. cost per patients or per sample)
• Create robust financial projections
• Draw form the experience and expertise of your service providers • Reality test assumptions with patient, medical, scientific advisers • Revisit assumptions once actual data is available • Review actual vs budget at least quarterly • Ask questions!
• Be creative about ways to control costs
• Consent patient but wait to collect samples until they are needed • Discounts for longer term contracts • Lower pricing in early stage vs after pass a volume threshold • “Barter”—what can you do for them?
Once projected costs are determined, it is critical to match them with anticipated revenue, keeping in mind differences in duration. As described above, different sources of funding should be considered for start-up cost and sustaining costs. Multi-year grants for start-up provide a window to develop additional revenue streams to support sustainability such as sample cost reimbursement and corporate partnerships. Solid financial modeling is critical to sustainability. A sound business plan is a powerful tool for attracting financial support from all of the sources enumerated above, at every stage of a biobank's life cycle. It also enables rapid response when conditions change which is essential to maintaining viability over the long term.
Conclusions
Biobanks sponsored by disease-focused foundations and advocacy organizations fill an important and growing role in the biomedical research ecosystem. They emerged based on the demand by patients to accelerate disease-focused research and recognition that limited access to well annotated biosamples was a major impediment to progress in many diseases. Creation of these biobanks and related patient registries has been accelerated by the proliferation of capable service providers, creation of operational standards by ISBER and certification processes. As a result of these developments, access to high quality, low cost biorepository service has never been greater. Patients are beginning to understand the importance of biobanks and supporting foundation and advocacy based biobanks by contributing data, samples, and donations. Some foundations are tying grant funding to investigators to the use of samples in their biobanks. Industry has recognized the ability of patient advocacy organizations to rapidly attract a diverse group of patients within a specific disease space. Finally, investigators are beginning to appreciate the time and cost savings of using these biobanks to reduce their cost and increase the speed of their research.
There are two principal challenges to the financial sustainability of biobanks sponsored by disease-focused foundation and advocacy organizations. First, can they attract the grants or large donations (seed capital) necessary to cover the start-up costs associated with establishing a biobank? Second, can they attract sufficient continued support (operating revenue) to maintain and grow the collection? Fortunately there is a broad, and growing, range of potential funding sources available to these biobanks that should help ensure their long-term financial viability. The success of this model has been demonstrated by several organizations, focused on both common and rare diseases, for the last decade, and the number of disease-focused foundations and advocacy organizations sponsoring biobanks continues to grow each year.
Footnotes
Acknowledgments
The author gratefully recognizes many helpful contributions to this paper from Sara Loud, MS Repository Director at the Accelerated Cure Project for MS, Suzanne D. Vernon, PhD, Scientific Director of the Solve ME/CFS Initiative, Elizabeth Horn, PhD, of Liz Horn Consulting, and Wendy Hitchcock, CEO of Vascular Cures.
Author Disclosure Statement
No competing financial interests exist.
