regulation

Pharmacogenomic testing, or PGx, is considered low-hanging fruit, a no-brainer for the application of genetic testing in the clinic. And some may think it is small fruit. Not so, says today’s guest, Kristine Ashcraft.

"Currently we lose a life every two minutes in the United States to non-optimized medications,” says Kristine in today’s show. She has spent over twenty years working to see pharmacogenomic testing adopted into standard-of-care medicine. Kristine serves today as the Medical Affairs Director for PGx at the genetic testing company Invitae.

“In 2016, we spent $528 billion on non-optimized medications. That is more than we spend on the drugs themselves or on any chronic disease. Pharmacogenomics will not solve that on its own, but it is a major piece we do not consider.”

There are some big questions here. The FDA has not regulated genetic testing, for the most part. Has this been a hindrance to the adoption of PGx into medicine? Does the industry want the FDA to take a larger role? There are some informal regulatory groups, such as AMP and CPIC putting out guidance. Is Kristine happy with the system as it currently is?

Let’s take it out to you the listener. Have you been pharmacogenomically tested? Why or why not? When or how does one decide to be tested?

Kristine has some ideas. And Invitae, who recently bought her company YouScript, is the place where the rubber meets the road in genetic testing. Are we at the tipping point for PGx?

"DTC is now too big of an arena to put everything in the same bucket.”

This was a line from Laura Hercher, one of our monthly commentators a couple shows back. The statement made its way around Twitter, so we thought we’d have Laura back to the program and ask her to come up with some more buckets.

It turns out it’s not that easy.  Direct-to-consumer genetic testing is a dynamic and complex space in 2019, a mishmash that quite defies easy categorization.

But if anyone can do it, it's Laura.  She's the Director of Research, Human Genetics at Sarah Lawrence College, a fearless genetic counselor. And she hosts our sister podcast, The Beagle Has Landed, devoted to the topic of genetic counseling.

We set up the conversation with a short history of DTC testing and end with a question about whether the consumer is becoming more savvy, more knowledgeable about genetic tests.  Yes, she says, but warns that the disinformation campaigns are becoming equally sophisticated.

With her characteristic cut-the-crap style, it’s Laura Hercher talking the world of DTC testing, past, present, and a little into the future.

Our two favorite commentators are back for our February 2019 month-in-review show, and to give our own twist to Valentine's Day celebrations we take on the topic of family surprises due to DNA testing. This is a phenomenon taking the world by storm in 2019. The Boston Globe had a great headline this past week, "First came the home DNA kits. Now come the support groups."

The month began with the New York Times's Editorial Board issuing a rebuke of 23andMe's cancer genetics testing. Nathan says it's similar to the paper's tech consumer reports section giving a bad grade. Theral says, no, it's the press filling in for a lax FDA.

Laura joins her colleagues, the authors of a STAT opinion piece, in raising alarm over the possibility of companies soon profiling for high IQ in the preimplantation genetics arena. She also questions whether Thermo's move to stop selling sequencers to one small region in China to protest surveillance by the state can be anything more than a PR stunt. "Don't they have trucks in China?"

Join us for another monthly romp through the genomics headlines.

We ran a series this summer highlighting one of the major issues in biomedical research: that the collection, storage, and procurement of biospecimen samples lacks any across-the-board governing standards. Various institutions adopt their own regulations resulting in a checkerboard of quality assurance, and by extension, an unknown effect on the outcomes of research. Our first guest called it “garbage in, garbage out.” (See links below.) This should send shudders through anyone doing research with any human tissue sample.

We also highlighted some of the proposed solutions, from the accreditation of bio repositories that CAP is offering (the same guest thinks biobanks should come under CLIA as laboratories do) to hearing how they handle the problem in the U.K. with their Human Tissue Authority, a light regulation at the government level.

Today we talk with Matt McLoughlin, the V.P. of Compliance at Scientist.com, the rapidly growing online research marketplace (last month they were listed No. 9 on Inc Magazine’s list of the fastest growing companies in the U.S.). Because of the large amount of human tissue samples acquired through their marketplace, Scientist has the chance to implement a market solution to the sample quality problem that makes a real difference. And they are. Think of the Fair Trade certification in the coffee or clothing industries.

“We’ve been in a unique position to do it because we’re agnostic. We’re not a supplier of human samples, nor are we a research organization using those samples. We can take a step back and act as a third party facilitator,” says Matt.

Just how does this private market system work? And does Matt think such a major problem can be fully tackled without any federal government oversight?

Here are the links to our summer series on the topic:

I Won't Rest Until We Have Quality Standards in Place for Biospecimens, Says Carolyn Compton, ASU, Guest #1

Should Biobanking Come Under CLIA? Asks Shannon McCall, Duke, Guest #2

An International Perspective on How to Improve Biobanking with Kiristin Goldring, Guest #3

The Personalized Medicine Coalition advocates for a wide group of constituents, including scientists, health care providers, entrepreneurs, payers, and patients. Which is why we’ve often wondered how the organization can be absolutely clear in their priorities.

Today, PMC President Edward Abrahams joins us to answer that question.

For example, take the topic of laboratory developed tests. The country is currently experimenting with an anti-regulatory political direction. Is Ed happy that the FDA has dropped their guidance for LDT regulation? With such a disparate constituency, what does he think is the best way forward? What about the CMS announcement recently that there wouldn’t be any reimbursement for diagnostic tests that weren’t FDA approved (isn’t this at odds with anti-regulatory policies?)—does Ed have any insight here? Also, is the current boom in direct-to-consumer testing a boon or bane for the industry?

When Obama’s Precision Medicine Initiative was launched, many organizations which had been using “personalized medicine” in their nomenclature were pressured to change their names. Ed says he’s still happy with the old term and in fact is working in congress to create the first Personalized Medicine Caucus.

We come in at around 27 min today with one of those unique industry veterans who can talk science with scientists, can talk real with patients, and carries clout on The Hill.

We set up an interview with David Spetzler, the CSO of Caris Life Sciences, to hear about some promising new liquid biopsy tests they are developing. And we do that in today’s show. But first, the interview takes a turn toward the regulation of molecular tests. Spetzler says that Caris is already doing as many quality certifications as possible short of FDA oversight.

“We are actually quite favorable to increases in regulation,” he says, “We think there’s a lot of bad science being done, quite honestly, because it’s expensive to take the additional steps to insure that high quality work is being performed. And we’re doing those steps, so we might as well get credit for it.”

At the same time, Spetzler says that an appropriate framework to evaluate the utility of molecular profiling is missing. Traditional blind trials don’t work for molecular tests, he warns. The studies must be more longitudinal and be focused on more than just one biomarker at a time. Caris is currently running a study that “backs away from individual biomarker validation and focuses on process validation to identify underlying treatment opportunities for patients with particular molecular profiles.”

We do get to a discussion of Caris’ upcoming liquid biopsy tests, such as one that screens for breast cancer. This past year we’ve seen an explosion in the industry of these new non-invasive, blood-based tests. But whereas most companies are looking at cell free DNA (cfDNA) or circulating tumor cells (CTCs), Caris has come up with a novel platform using exosomes. These are small vesicles that handle intracellular communication and are not only present in all biological fluids but much more ubiquitous than cfDNA or CTCs.

As the FDA works away on final guidance for regulating LDTs, various professional groups unhappy with the course of the FDA have put together and hurried their own proposals up to Captiol Hill. The Diagnostic Testing Working Group (DTWG) has had their proposal drafted into legislation which has already been revised once in the House Energy and Commerce Committeee, while proposals from the College of American Pathologists (CAP) and the Association of Molecular Pathology (AMP) have been presented to both the Senate and the House. Various other groups, including the American Medical Association (AMA) and the American College of Medical Genetics (ACMG), have either signed on in support of one of these proposals or are independently lobbying Congress as well.

What chance do these organizations have at persuading Congress to step in and change the course of LDT regulation?

Here to help us parse through these options and get a sense of congressional reception is Scott McGoohan, the new Director of Science and Regulatory Affairs at BIO. Scott says that all of the proposals fit into “three buckets:”

First, there’s the guidance that the FDA is working on which will bring regulatory oversight to thousands of tests which heretofore have not been regulated.

Second, there’s the CAP and AMP proposals which call for the modernization of CLIA which will include increased oversight of laboratory developed tests. These proposals reserve a small set of high risk tests for FDA oversight.

And third, there’s the DTWG who are hoping to get Congress to establish a new center at the FDA for all in vitro diagnostics.

One thing is for sure, says Scott. Whichever proposal wins out, “the general sense is that there will be a change coming with increased regulatory standards for laboratory developed tests.”

Scott joins BIO at a very busy time in Washington for biotech policy. The House has passed the 21st Century Cures Initiative and the Senate Help Committee is doing active work on their health innovation agenda.

“It is an incredible time [in Washington] and an incredible opportunity for transformative regulatory change,” says Scott.

Certainly not all regulatory change is transformative, as Scott reminds at the conclusion of today's show with a story about a crazy bill in Wisconsin.