Last week, my son, a second-year university student reading microbiology, approached me very excited indeed. He had come across an article on his mobile news feed that was related to mum’s work! He asked, “This blood test described as inadequate and inaccurate, isn’t it a medical device?” Yes, I answered. “If it never worked effectively, how and why did the FDA approve it?” Son have a seat.

The new year began with the news that Elizabeth Homes, billionaire former CEO and founder of Theranos, was found guilty of wire fraud and conspiracy to commit wire fraud.

Theranos developed a diagnostic test, which the company claimed was able to perform a full range of clinical tests using very small blood samples drawn from a single finger stick.  The analyzer was publicly presented to investors, health professionals and patients with the ability to produce results that were more accurate and reliable than those yielded by conventional methods—all at a faster speed than previously possible. Brilliant, everyone said. The wealthy invested, health clinics wanted to partner and the famous were on the board of directors.

However, the criminal investigation revealed that CEO Holmes knew about accuracy and reliability problems, limitations for the number of tests performed, slow speed, and, overall, could not compete with more conventional technologies.  Evidence presented showed that Theranos’ ultimate solution was to utilize equipment bought from third parties to perform the blood testing. Certainly not the golden panacea as promised.

The term Laboratory Developed Test (LDT) is used to describe a certain class of in vitro diagnostics (IVDs) that are designed, manufactured, and used within a single laboratory, often in a hospital and are not distributed or sold to any other labs or health care facilities. Also note that any FDA-approved commercial test that is modified in any way by a testing lab is considered to be an LDT.

In the United States, LDTs are regulated under the Clinical Laboratory Improvements Amendments (CLIA) program. (For more information https://www.cdc.gov/clia/law-regulations.html)

LDTs are not centrally registered or tracked, therefore no one knows precisely how many are used, when and why they are used, or how their performance compares with FDA-reviewed diagnostics.

Oversight Comparison Table:

The above table illustrates a fragmented surveillance system, whereby tests are regulated according to where they are developed and used rather than their risk to patients and their outcomes.

Critics say the lack of FDA regulation is a loophole that allows laboratories to perform unproven tests with dubious claims. As per the Medical Device Amendment of 1976, LDTs were intended as limited exceptions to FDA medical device oversight as their application was to be generally low risk, short term for simple analysis.

Every year in the United States an estimated 3.3 billion in vitro diagnostic tests performed, impossible to determine how many are LDTs. Without oversight, LDTs can be high-risk and give the health care providers who rely on them inaccurate information which may potentially pose dangers to general public health via misdiagnoses.

As Theranos did not release the LDT test kit to the commercial market, the fraud remained safely under the FDA radar for many years.

“The FDA’s Office of Criminal Investigations (OCI) will continue to investigate and help bring to justice individuals and companies responsible for putting the public health at risk,” said FDA Assistant Commissioner for Criminal Investigations Catherine A. Hermsen in relation to the Theranos case.

In 2010, the FDA announced its intent to reconsider its policy of enforcement discretion for LDTs. But not much regulatory progress has been made since publication of an FDA discussion paper on 13 January 2017. The efforts to pass any stringent legislation has stalled and the fate of LDT regulation has met with opposition from various political and healthcare fractions and appears to have an uncertain future under the current administration.

So, darling son, the FDA did not approve the Theranos blood testing regime because current legislation does not require FDA review.

Next week: How IVDR legislation may close this legislative gap for the European market.

K Young

kimyoung@instem.com

References

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