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Overhype And PAMA Panic

By Benjamin Ross

January 22, 2018 | What’s overhyped?

This broad question was posed to Nickolas Papadopoulos, Professor of Oncology and Pathology at Johns Hopkins University; Victoria Pratt, Director of the Pharmacogenomics Lab at Indiana University School of Medicine; and Nathan Ledeboer, Associate Professor of Pathology at the Medical College of Wisconsin. Each of these experts served as panelists at the “Key Trends In Diagnostics and Lifesciences: Promise, Reality, Reimbursement” session of the 2018 JP Morgan Healthcare Conference in San Francisco.

Each panelist gave an answer unique to their field, but the theme of their responses was unified: current technologies are unable to perform optimal diagnostics for patients, despite their initial promise.

Papadopoulos called out liquid biopsy for early cancer detection as perhaps getting more credit than it should. “It’s not that it’s not necessarily going to work,” Papadopoulos said. “What I think is overhyped is how people claim it’s going to work, either how successful or how specific it’s going to be.”

People ignore the biology, Papadopoulos said, and several important questions need to be addressed for liquid biopsies to work: Can we actually detect certain tumors in plasma? How sensitive are these assays? “Older people, like me, sometimes have mutations in their plasma, but that doesn’t necessarily mean they have cancer.”

Despite innovations in the technology, including the novel blood test recently revealed by Papadopoulos’ research group at Johns Hopkins, researchers are still not able to diagnosing cancers from blood tests in otherwise healthy people.

Good algorithms are the key to increasing the sensitivity of diagnostic tools, Papadopoulos said. “If your test is not sensitive, you’re going to have a lot of false-positives. This means, on top of the psychological issues for the patient, a lot of follow ups costing a lot of money and leading to unnecessary procedures that aren’t advantageous to anybody.”

Victoria Pratt, of Indiana University, said next generation sequencing (NGS) is overhyped. “I love it. I use it. It’s great,” she said. “But they’re a lot of genes for genetic disorders or even pharmacogenetics that you can’t do very well with NGS and NGS platforms.”

Certain forms of mental retardation are examples of genetic disorders that may not benefit from NGS, Pratt says. A lot of those genes have pseudo-genes and so when researchers try to capture and analyze a specific gene they might capture the pseudo-gene as well, meaning that researchers are unable to determine whether or not that are looking at a real gene or a “fake” gene, as Pratt put it.

Nathan Ledeboer of the Medical College of Wisconsin says that “rapid diagnostics” is perhaps the most overhyped term, especially when it comes to microbial resistance and infectious diseases. He said there’s a problem when the diagnostics community has the mindset of: “We can do it faster, therefore it’s better.”

“The problem with [that mindset] is that we’ve not built any of the downstream decision support processes to help providers make decisions based upon a rapid diagnostic,” Ledeboer said. “It’s great that you can give a rapid urine result at two in the morning, but is there actually anyone there to listen to it and do anything with it?”

If we’re going to use rapid diagnostics, we have to build the case support for why they should be used, and build the decision support for providers to be comfortable to be able to use that information, said Ledeboer.

Preparing for PAMA

A piece of legislation hindering the industry from building up their current diagnostics technologies is the 2014 Protecting Access to Medicare Act (PAMA), which set all tests on the Clinical Laboratory Fee Schedule (CLFS) to a market-based rate.

Through PAMA, the Centers for Medicare & Medicaid Services (CMS) is able to designate which labs are applicable by developing a low volume or low expenditure threshold. CMS has stated that it will generally exclude a laboratory from being an applicable laboratory, and thus from having its private payor data reported, if it is paid less than $12,500 under the CLFS during a data collection period. 

According to Pratt, researchers would originally bring new diagnostic tests to CMS and would try to crosswalk their test to an existing test based on cost and value.

“Now, CMS defined what was an ‘applicable laboratory’ by a weighted median that was set for all the lab systems and their data,” Pratt said. “But most of this data that was submitted, and where they put the cutoffs, reflected two of the largest laboratories in the country, [Quest Diagnostics and LabCorp].”

Where this weighted median hits hardest is with hospitals because hospital contracts and pricing are significantly more than one would get from the larger laboratories, Pratt said. He expects hospitals and hospital reimbursement to take a huge hit in 2018.

Ledeboer agreed with Pratt’s pessimism towards the regulation, saying that he has already seen reductions in reimbursements, which he thinks will add significant challenge to the justification of both new diagnostic tests and even tests that are in current practice.

The effects of the regulations hit perhaps harder than they should have because, according to Ledeboer, very few healthcare systems prepared for the regulations until it was too late.

“It wasn’t until we started our 2018 budgeting that we started to look at what the financial impact was going to be,” he said. Overall, the Medical College of Wisconsin has seen a $800,000-$1 million hit in terms of reimbursement on a yearly basis.

“Up until three years ago, we focused a lot on outpatients because we got paid for everything we got done,” said Ledeboer. “Now, it’s much easier if I just bring a test in on an inpatient because if we can show that we can get [the patients] out of the hospital faster, that’s an easy way that we can justify the test.”

As for liquid biopsies, Papadopoulos believes the tests are still too far removed from real world use to even fret about PAMA.

“We’re not even there yet,” Papadopoulos said. “We, as a community, are trying to understand what is going to be required besides clinical integrity. How we prepare for that is engaging with bodies like the FDA and CMS, and working together to find out what needs to be done in order to one day, hopefully soon, have a test for reimbursement that’s going to be useful to the clinician and patient.”