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August 03, 2017

Barriers in Biobanking

Obstacles Remain in Connecting Researchers with the Right Specimens for Their Work

Barriers in Biobanking

While biorepostitories and commercial specimen-researcher matchmakers are working to improve access to biopspecimens, uniform and consistent clinical annotation remains a significant hurdle for researchers looking to gather multiple specimens from multiple sources. [Mayo Clinic]

  • All around the world, human samples are stored in laboratories, hospitals, and specialized facilities. These collections vary significantly in size—from single labs housing specimens for individual projects, to large, university-based biobanks. In the United States alone, there are thousands of such facilities. “Anybody that’s systemically collecting samples is considered a biobank,” said Andrew Brooks, Ph.D., COO at RUCDR Infinite Biologics, a Rutgers University-based biorepository. “There are biobanks all over the place, and [there is] a huge, growing community.”

    Despite the growth in biorepositories, technical and operational hurdles still stand in the way of investigators procuring the right samples for their research. In a 2011 National Cancer Institute (NCI) survey of 727 cancer researchers, 47 percent reported having difficulty obtaining quality biospecimens. And as the field of precision medicine continues to accelerate, the demand for high-quality samples will likely continue to grow.

    “Many investigators are constantly looking for access to biosamples,” said Stephen Thibodeau, Ph.D., a co-director of the biorepositories program at the Mayo Clinic. “Because it’s just really hard to get good samples that are well annotated and meet the specific criteria that you want to have large enough numbers.”

    Big repositories, such as those established by RUCDR Infinite Biologics and the Mayo Clinic, are trying to respond to these demands by providing access to samples, as well as the facilities to process, store and manage them. Often, these facilities also provide access to researchers outside of their respective institutions.

    “Right now, there are lots of large programs that exist academically and commercially that are doing prospective collections, like us [at RUCDR],” Dr. Brooks said. “People are generating biological assets for future use to help decrease or to make the hurdle a bit lower to get access to samples.” 

  • Improving Annotation

    While many biorepostitories and commercial specimen-researcher matchmakers are working to improve access to biospecimens, uniform and consistent clinical annotation remains a significant hurdle for researchers looking to gather multiple specimens from multiple sources for their work.

    “In order to get pathologists, radiologists, oncologists and surgeons to produce data that can be used to annotate tissue, there need to be standards that are adopted across all fields and across the entire nation,” Mary E. Edgerton, a pathology professor at the MD Anderson Cancer Center in Houston, told Clinical OMICs. “While pathology leads in this area, only 5 to 10% of pathology laboratories are actually collecting the data in a discretized format.”

    Though samples collected at university hospitals are usually annotated, this is not always the case in smaller community hospitals—and even at the large centers, this process is not yet completely standardized. “Until we’re all hooked up in electronic health records, that are compatible to each other and that people can query, I think it will continue to be challenging,” said Kay Washington, M.D., Ph.D., director of the Western division of the Cooperative Human Tissue Network (CHTN), an organization established by the NCI to meet the increasing demands for human tissue. “I think we need better electronic tools all around.”

    This is one of the focuses of the CHTN. “We do simple things like download the schedule for the operating rooms onto our system to flag potential patient cases,” Dr. Washington says. “Some of the sites are developing tools to allow investigators outside their institutions to look at what they have in the bank at the moment and pick specimens that might suit their needs.”

  • Short Supply

    Some areas of research face a bigger supply shortage than others. Though paraffin blocks are widely available, they cannot be applied across all experiments. Fresh or frozen tissues, on the other hand, are much more expensive to handle and store, and require more specialized expertise to collect. “The paraffin blocks have been attractive because many academic [repositories] have warehouses full of blocks, so you can do a retrospective study pretty easily with them,” Dr. Washington says.

    However, Michael Roehrl, director of the Precision Pathology Biobanking Center at Memorial Sloan Kettering Cancer Center (MSKCC), says that paraffin-embedded tissues have limited utility because these samples often come with fragmented genomes, altered proteomes and metabolomes, processing and fixation differences, and inherent biomolecular variability. This makes them suboptimal for certain applications, such as whole genome sequencing or protein phosphorylation analysis, which requires “ultra-fresh, rapidly frozen tissues from an operating room where everything is controlled,” he said.   

    This is especially true for newly burgeoning fields of precision medicine, such as immuno-oncology, a hot area of translational research that requires scientists to study not only the tumor itself, but also the surrounding dynamic microenviroment and the patient’s immune system. “One of the main reasons why we don’t quite understand how immunotherapy actually works is because the therapies are on the market faster than an actual good precision assay to assess the functional changes induced by the therapy,” Dr. Roehrl noted. “That’s why there is an enormous interest to obtain samples from wide categories to characterize what’s happening with patients on these therapies.”

    Dr. Roehrl believes sample collection should be driven by the underlying scientific questions, rather than “collecting samples and later hoping for an idea of what to do with them.” The main reason for this, he says, is that “the types of specimens, as well as how you acquire them and extract molecular information from them, depends so much on the question you’re asking.”

    In order to achieve this, he added, researchers in both academia and industry need to collaborate closely with physician scientists with expertise in pathology and laboratory medicine who can help pinpoint optimal specimens and provide insights into the best ways to sample and analyze them. MSKCC’s precision pathology biobanking is currently working to help develop these relationships.

    Biobanking is a rapidly growing field—however, overcoming these obstacles are crucial for good precision medicine to move forward. “Garbage in, garbage out,” Dr. Roehrl says. “You can do wonderfully extensive research, but if your input sample is suboptimal, you’re producing inaccurate data even if you spend a lot of money and use very high-end instrumentation.” 

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