At Vanderbilt, NCI’s Cooperative Human Tissue Network Relies On Lean Principles For Efficiency

By Allison Proffitt  

September 7, 2017 | Turns out, the Western Division of the National Cancer Institute’s Cooperative Human Tissue Network (CHTN) isn’t actually all that far West. But Vanderbilt University in Nashville, Tenn., which took over the Western Division in 2001 is at least further West than its predecessor in Cleveland, Ohio, Kerry Wiles told me.

Wiles is the program director for the Cooperative Human Tissue Network (CHTN), Western Division, one of six institutions that are part of the network funded by the National Cancer Institute to procure and distribute remnant human tissues and fluids to biomedical researchers throughout the United States, Canada, and now internationally.

The CHTN provides human tissues and fluids from routine procedures to investigators who use human biospecimens in their research. Unlike tissue banks, the CHTN works prospectively with each investigator to tailor specimen acquisition and processing to meet their specific project requirements.

CHTN operations are all run with NCI funds; Vanderbilt competes for a grant—and the right to be part of the network—every five years. CHTN Western’s samples come from Vanderbilt University Hospital and other hospitals in Nashville. All samples are clinical remnants collected with patient consent or under a waiver of consent and anonymized. The biobank can use anything not needed by pathology to accurately diagnose the patient, as long as disease staging and grading are not compromised.

Right now, shipping is brisk. “Any given day we may ship 50-500 samples,” Wiles explained.

Sample Collection

CHTN Western collects high quality biospecimens from surgeries, autopsies, and routine procedures representing malignant, benign, diseased, and normal tissues and biofluids including urine, serum, plasma, and buffy coat. Samples may be fresh, frozen, paraffin embedded, or as unstained slides.

Tissue and fluids are available to any researcher with a scientifically-valid research project, but NCI dictates that samples aren’t to be used for teaching. Wiles said the CHTN Western declines requests about once a year. Usually, she explained, the invalid requests are for samples to be used for demonstration or perhaps a company wants to commercialize the biospecimen, which is not allowed. Use of CHTN Western samples requires a “scientific justification,” Wiles explained.

Often, investigators start their project at the biobank, Wiles said. The interaction with CHTN Western is very personal, she explained. “We talk about expectations, and what’s reasonable.” Sometimes a researcher may have envisioned a project that requires a sample type or volume that isn’t likely to be available. CHTN Western explains what types of biospecimens are available and how quickly a researcher might expect to access them. Once the researcher has outlined a project that CHTN expects to be able to support, the biobank writes a letter of support that the researcher can use to apply for funding. Later, Wiles said, the biobank will hear from researchers looking for advice on how to work with a particular tissue type.

CHTN Western delivers not only the samples, but also final pathology reports and age, sex, and race details of patients. Other medical history is available if a researcher needs to ask specific questions. The samples are anonymized or coded, depending on the collection protocol, Wiles said, but researchers can fill in holes specifically for their research project, for example asking if a sample came from a patient who was a smoker, or had prior history of disease.

The National Cancer Institute determines the distribution priority of samples, Wiles explained. Vanderbilt researchers get priority; then other academic, peer-reviewed research; then free-standing cancer centers, and finally commercial biotech or pharmaceutical companies.

Lean Machine

Recognizing the need to operate in a more streamlined fashion in response to diminishing federal research dollars, CHTN Western has been using a Lean Six Sigma (LSS) approach to operations since 2007. LSS has assisted in increasing customer satisfaction, streamlined operations, and reduced overall operating costs, Wiles believes.

The IT system that runs the moving parts is one that Wiles designed herself and had built in house. The system is built of a series of modules replete with checks and balances: Consent; Procurement; Quality Control and Data Entry; Quality Assurance and Quality Control; and Shipping or Banking.

Consent records the type and scope of consent. Can tissue be collected? Both tissue and fluids? “We operate under a waiver of consent,” Wiles explained. Any tissue or fluid samples are anonymized before they leave Vanderbilt, but CHTN Western maintains detailed records.

Procurement covers gross diagnosis, collection from the operating room, and chain of custody for samples. CHTN Western does not have a direct connection to Vanderbilt Hospital’s electronic medical records for clinical data, so Quality Control and Data Entry personnel extracts pathology reports and conducts medical chart reviews. Quality Assurance and Quality Control includes independent pathology review. Kay Washington, the PI for CHTN Western, is also a board certified GI pathologist at Vanderbilt, so in some cases she is reviewing her own work. In other cases, she’s double-checking the work of colleagues. Finally, samples are either shipped to researchers or banked in the CHTN Western lab.

For the most part, Wiles said, CHTN Western is a prospective procurement service. Samples are generally collected after an agreement is in place with a researcher. But the National Cancer Institute recognizes that there are rare tissues or, alternatively, commonly-requested tissues for which banking samples would be wise. The biobank has about 30,000 frozen tissue specimens, Wiles said, and about 200,000 paraffin-imbedded samples. CHTN Western has recently added tissue microarrays to the sample type it can provide, and the paraffin blocks have been banked in anticipation of high demand.

A staff of 12, including Wiles and Washington, moves samples through the workflow. The process is created with many checks and balances, Wiles said, and has caught a few diagnostic or filing errors over the years. Whenever a sample is different from its labeling, CHTN Western immediately sends the sample back to the hospital pathologist.

Internal System

CHTN Western has a homegrown IT system supporting the process. Out-of-the-box solutions usually require a lot of build-out, Wiles explained. “To build what we need would have cost a tremendous amount of money.” Even if an off-the-shelf sample management and procurement system cost $45,000, customizing it to the needs of CHTN Western would require additional use-case writers, programmers, and project managers. “By the time you’ve gotten the system to do what you need, you’ve spent $250,000 she said.” It can take a year to get a commercial solution set up especially if changes or build-out is required, Wiles said. “With our IT solution, it may take a few weeks to make changes or upgrades.”

Instead, Wiles hired a programmer to build the system she envisioned with LSS principles. The system is built on an Oracle database within Vanderbilt’s two levels of firewalls. A principal investigator portal delivers only de-identified data. Any changes that need to be made can be done almost immediately.

The system uses NCI and ISBER—International Society for Biological and Environmental Repositories—best practices. It’s a topic Wiles wishes more researchers would take time to understand.

“A lot of people have misconceptions about biorepositories,” she said. “At the academic level, people don't think they're a biorepository but they are. Any time you collect, process, and store samples you are a biorepository.”

Whether a researcher has a few dozen samples in the lab freezer or thousands in the cold room, Wiles encourages the use of best practices for annotating, processing, and storing data about those samples. It can save a repository and researchers a great deal of headache, she said.

To help other biorepositories and research laboratories implement the LSS philosophy, Wiles and the CHTN Western team makes portions of its project management and LSS workbooks available to the scientific community.