biospecimens


The Sad State of Biospecimen Science with David Rimm, Yale

Guest:

David Rimm, Professor of Pathology, Yale University School of Medicine Bio and Contact Info

Listen (4:16) An unsexy science

Listen (5:36) A lack of certifications

Listen (6:20) Most pathologists not aware of the problem

Listen (2:48) Pathologists not reimbursed for providing research samples

Listen (7:44) Still no Tissue Quality Index

The next stop in our journey to better understand the impact of poor biospecimens on biomedical research takes us to Yale where we talk with pathology professor, David Rimm, about the new science of biospecimens.

In past interviews we’ve established the importance of better standards in the collection, handling and storage of biospecimens. David has developed some rare and unique training at Yale for the students of pathology, but still, he says that biospecimen science has not really taken off.

“Most scientists and pathologists are not aware of this problem,” says David, referring to the issue of sample degradation.

How is it the case that billions of dollars are spent studying samples that were not collected with any standards? Why are there no certifications for pathologists in this regard?

One thing that would help immensely and has been long hoped for is an assay that would tell whether a sample is still good, what David calls a Tissue Quality Index. Perhaps a researcher or pathologist does’t know where a sample came from or how long it’s been in storage. This Tissue Quality Index would be a scoring system for determining whether the sample could still be used for an application. David got a grant to develop the score, but didn’t quite get there with the one grant. He applied for another grant, but it was turned down. Regrettably, he says, it’s just not an important topic for traditional funders.

The holy grail of biospecimen science, a Tissue Quality Index, remains still to be grasped.

Podcast brought to you by: Quintiles - bringing people and knowledge together for a healthier world.

And by: Fluidigm - Make your biobank a quality research partner. Download the Evolution of Biobanking whitepaper today.

Cancer 2014: The Year in Review with Anna Barker

Guest:

Anna Barker, Co-Director, Complex Adaptive Systems Center, ASU Bio and Contact Info

Listen (3:21) Andy's challenge

Listen (4:39) The year of immunotherapy

Listen (4:53) iSpy 2 and a new approach to clinical trials

Listen (6:42) The swan

Listen (6:35) A coalition of the willing

Listen (5:14) Six reasons biomarkers fail

In 2003, the then Director of the National Cancer Insitute, Andrew von Eschenbach, issued a challenge: “to eliminate the suffering and death from cancer, and to do so by 2015.”

Anna Barker is the former Deputy Director of the National Cancer Insitute, and she was at the meeting when Dr. von Eschenbach issued his challenge. Now at the end of 2014, we talk with Anna about the challenge and how far we have come. She offers her vote for the three most important developments in cancer this past year.

The Impact of Biospecimens on Clinical Study Design

We perform therapeutic and diagnostic clinical trials to learn the safety and efficacy of drugs and tests in a clinical setting.  Typically, we think about the biospecimens in a clinical study in terms of operational requirements such as sample collection, processing, storage and analysis.  Our ability to obtain and test high quality patient samples is an important consideration during the design of clinical research programs and may significantly limit the questions that we can ask in trials. 

For example, our ability to develop drugs for precision medicine in diseases such as cancer depends on access to high quality samples.  The fundamental elements of a trial are the objectives--what questions we intend to address--and the endpoints--what will be measured to answer those questions.   Trials are also defined by the patient population or the inclusion and exclusion criteria determining who is enrolled.   Successful clinical studies require careful planning and design of the study protocol to ensure that the study is feasible and that we capture the lessons learned.  Often, endpoints rely on patient samples for laboratory testing. 

Patient enrollment may require rapid laboratory testing for a molecular or genetic alteration to meet the inclusion criteria.  Researchers also collect patient samples for long term storage for future analysis in the hope that advances in technologies and disease knowledge will open new opportunities.  These study endpoints require robust biospecimen planning during the early development of research programs all the way through to the medical writing of the study protocol.   Study planning is typically based upon experience and expertise.  However, the industry is more frequently utilizing best practices and data-driven analytics and modeling. These tools will improve our planning and preparations for biomarker-driven trials that require biospecimens.

Targeted therapeutics and drug candidates that will rely on patient laboratory test results are becoming common in oncology and other diseases.  Diseases are also being reclassified by molecular biomarkers and complex laboratory tests.  As a result, the biospecimen considerations that have been discussed in the ongoing Biospecimen Series at Mendelspod are becoming critical success factors for drug development. 

In the planning stages we often would like to target a small patient population who may greatly benefit from a new drug compared to the general population.  We then have to ask if we can identify, test and enroll those patients if the samples for testing are difficult to obtain or unstable for shipment and testing.  Similarly, we may have a novel drug with a new mechanism of action that promises to address a critical clinical need.  In this situation we are often limited by the test to certain sample types that may cause a great deal of patient inconvenience or duress.   Difficulties in obtaining  repeated tumor biopsies is one example that has resulted in the development of tests that rely on surrogate samples that may be obtained from the blood.  These considerations often restrict many of our options for study designs include choice of diseases, patient populations and regions or clinical sites. These restrictions also impact the patient journey in the trial. 

Trial protocols summarize the collection and use of samples in a table or schedule of events or assessments.  What may appear to be a simple table, ultimately impacts the patient experience and determines trial feasibility and success.  Researchers must balance the potential knowledge gained, time, cost and risk to maximize the benefit of the study to current and future patients.  Biospecimen planning is increasingly an important part of this equation.  The Mendelspod series Back to Basics: Improving Biospecimens supports a greater understanding of the challenges and opportunities for improving how we utilize critical patient samples.  These improvements will also enable more powerful clinical studies, addressing challenging clinical questions and advancing novel drugs and diagnostics.

Historic Consensus Reached on Biospecimen Standards: Carolyn Compton, NBDA

Guest:

Carolyn Compton, Professor of Pathology, ASU Bio and Contact Info

Listen (4:54) A historic new consensus

Listen (6:33) CAP committed to enforcement

Listen (2:50) Five core variables

Listen (5:16) Non-governmental leadership

Listen (4:20) Problem unique to biomedicine

Listen (3:25) Ramifications for our audience

Listen (4:48) Does this mean more work and higher prices?

A unique event happened at ASU last week that has the potential to positively impact all of biomedical research and therefore patients.

Carolyn Compton has been a tireless crusader for higher standards in biospecimen collection, handling, and storage. (See our interview earlier this year with Carolyn here where she argues that uneven sample quality is a major reason that biomedical research has such poor reproducibility rates.) Beginning as a pathologist herself, Carolyn has served at various organizations, including a stint at the National Cancer Insitute, which have prepared her for a special leadership role on the topic of biosamples. Last week she saw her long time dream come true.

“I’m delighted to report that we did in fact come to consensus after four days of discussion on what standards would be needed to raise the quality of ALL biospecimens from ALL patients to a standard that would be acceptable—perhaps not optimized—transparent and of known quality level for all patient samples. This is huge!” Carolyn exclaims in today’s show.

What does Carolyn mean by consensus? As we’ve been uncovering in our recent series on the topic, there have been no uniform standards in the collection, handling, and storage of biospecimens. It’s all been done with “poetic license” Caroly says. Until now. Last week Carolyn and a very special organization at ASU known as the National Biomarker Development Alliance put on two “convergence conferences” back-to-back that brought the major stakeholders—pathologists, physicians, patients, tool makers, and regulators—together AND found broad agreement on five basic standards to improve biospecimen handling.

This is indeed huge. Because the President and President Elect of the College of American Pathologists attended the conferences and committed to enforce these five basic standards in all of the labs which they accredit.

In her ebullience, Carolyn is careful to say that this is just the beginning, that the standards must now be written out and optimized. But it’s a very strong beginning which will have ramifications throughout the industry.

Who will be most affected? Patients, Carolyn says. Because tests, such as the popular HER2 assay for breast cancer, will be more accurate.

This story is not only unique in how it will change the course of the industry, but a powerful example of how non-governmental leadership can effect much needed change.

Podcast brought to you by: Quintiles - bringing people and knowledge together for a healthier world.

And by: Fluidigm - Make your biobank a quality research partner. Download the Evolution of Biobanking whitepaper today.

The Daunting Task of Managing Biospecimens at the World's Largest CRO: Diane Farhi, Quintiles

Guest:

Diane C. Farhi,, MD, Senior Medical Director, Quintiles Laboratories Bio and Contact Info

Listen (6:37) Tracking clinical samples around the world

Listen (5:34) How to measure sample stability

Listen (3:37) New software needed

Listen (5:07) Challenges from the increase in DNA sequencing

As we’ve been uncovering in our special series, Back to Basics: Improving Biospecimens, the issues around biosample collection, storage, and delivery here in the U.S. can be overwhelming. But Diane Farhi and her team have to manage on a global scale at Quintiles, the world's largest CRO. Who better to take us into the practical issues around sampling?

'Harmonization' is the name of the game in dealing with a global laboratory, says Diane, the Senior Medical Director at Quintiles. Diane and her team are dependent on a world wide delivery system, and that can bring with it many variables which impact samples.

“The whole issue of transport--how long it takes, what the temperature variability is within the package, impacts of alterations in flight schedules due to natural disasters and strikes and other event--all impacts the quality of our specimens when they finally arrive at one of our global laboratories,” she says.

In today’s interview, Diane shares some of the ways that the team at Quintiles mitigates the sampling issues that lie beyond their control. She also details some of the new challenges that have come with the dramatic increase in RNA and DNA sequencing.

Podcast brought to you by: Fluidigm - Make your biobank a quality research partner. Download the Evolution of Biobanking whitepaper today.

Biosampling Basics with Scott Jewell, Van Andel Institute

Guest:

Scott Jewell, Senior Scientific Investigator and Director of Program for Biospecimen Science, Van Andel Institute Bio and Contact Info

Listen (3:30) Do you see more creativity in the sample consent area?

Listen (7:08) Sample collection - the operating room

Listen (6:52) Sample storage - keeping analytes viable

Listen (7:49) Are researchers becoming more discriminating in their choice of samples?

Listen (4:39) A gold mine

Listen (3:21) How did you get into this?

Scott Jewell joins us from the Van Andel Institute today to walk through some of the basic issues involved with the procurement, storage, and processing of biosamples.

This is the second part of our series on biospecimens, and Scott too will leave you wondering if more focus on sampling might just improve your research dramatically. Scott argues that as biomedical research has developed, "we’ve cherry picked the best things potentially out of what we could gain from science that were robust and that didn’t need to have the perfectly preserved samples.” But those days are passing and now there’s “a lot that doesn’t stand up because there are not appropriate measurements.”

It’s an overlooked area that could well offer a gold mine of solutions for biomedical research.

Podcast brought to you by: Quintiles - bringing people and knowledge together for a healthier world.

And by: Fluidigm - Make your biobank a quality research partner. Download the Evolution of Biobanking whitepaper today.

Are We Driving Innovation without the Quality? Pete Kissinger, Purdue

Guest:

Pete Kissinger, Chemist, Purdue University
Bio and Contact Info

Listen (4:43) Many problems in life science traced back to poor measurements

Listen (2:50) Innovation without quality

Listen (4:37) Metabolome closer to reality than genome

Listen (7:46) Too focused on questions of reimbursement and regulation

Listen (3:34) Smartphone bio sample collection not there yet

Listen (10:35) Does the new Emerald Cloud Lab have a future?

Pete Kissinger is one of those who can discuss just about any area in the life sciences, often with humor. Pete's a professor of analytical chemistry at Purdue and founder of a drug development company, Bioanalytical Systems.

When I first chatted with Pete, our discussion went to every corner of the industry and back again. If Pete were a football player, he'd be comfortable in any position from quarterback to front linesman to safety.
For today's show, Pete and I tried to stick to a common theme--the importance of quality measurements.

Pete ties many of the problems we have in the life sciences--issues of reproducibility, failed clinical trials, an over emphasis on genomics--to low quality measurements. When asked why that is, Pete turns to funding, arguing that we are prioritizing the new over the reproducible.

"Often there isn't the funding to validate sufficient numbers of samples . . . We fund innovative academic science. We don't fund the routine blocking and tackling required to get quality data from a sufficient number of subjects," he says in today's interview.

At the end, I ask Pete what he thinks about the new Emerald Cloud Lab, a remote lab offering basic biology experiments accessible to anyone through the cloud. Will this impact the integrity of the scientific method?

But often we get off track. Pete is too fun a guest not to loosen the reins a bit.

Podcast brought to you by: See your company name here. - Promote your organization by aligning it with today's latest trends.

Raising the Standards of Biomarker Development - A New Series

We talk a lot on this show about the potential of personalized medicine. Never before have we learned at such breakneck speed just how our bodies function. The pace of biological research staggers the mind and hints at a time when we will “crack the code” of the system that is homo sapiens, going from picking the low hanging fruit to a more rational approach. The high tech world has put at the fingertips of biologists just the tools to do it. There is plenty of compute, plenty of storage available to untangle, or decipher the human body. Yet still, we talk of potential.




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