Theranos exploited black box medicineBMJ 2022; 379 doi: https://doi.org/10.1136/bmj.o3003 (Published 14 December 2022) Cite this as: BMJ 2022;379:o3003
Elizabeth Holmes, the 38 year old founder of failed diagnostic start-up Theranos, was sentenced to more than 11 years in prison this November.1 The sentence was handed down nearly a year after she was found guilty of defrauding investors about her finger prick blood testing devices, and seven years after the Wall Street Journal published its first investigation exposing the company’s struggles.23 Her co-conspirator and ex-boyfriend Ramesh “Sunny” Balwani was also convicted this summer and sentenced to almost 13 years in prison.4
“It’s been a long road of hardship for her,” Holmes’ husband, Billy Evans, wrote in a support letter pleading for a lenient sentence.5 Theranos’ customers, arguably, had it harder. Some received false laboratory test results indicating life threatening conditions such as cancer and HIV.6 Patients were left to wait anxiously while traditional laboratories repeated the tests, and at least one customer stopped taking his medication on the basis of erroneous results.7 In 2016, United States government inspectors concluded that technical defects in Theranos’ operations had placed patients in “immediate jeopardy.”8
Holmes was ultimately not convicted of charges relating to patient harm, instead she will be locked up for misleading wealthy investors. Yet it wasn’t her youthful charm alone that enabled this deception. Financiers, journalists, and patients couldn’t rely on regulators to vet her claims that Theranos’ proprietary technology produced accurate results from a single drop of blood.9 Just one of Theranos’ assays was formally approved by the US Food and Drug Administration, it tested for herpes.10 Many of the company’s other offerings were considered “laboratory developed tests.” This regulatory framework bypasses pre-authorisation from the FDA.11 Instead, laboratory developed tests are self-validated, and the laboratory’s paperwork is only reviewed later, during routine inspections. These tests have become common in the US, and most laboratories performing these diagnostics are legitimate.
Theranos’ use of laboratory developed tests was far from legitimate. The company produced two so called “innovations:” an error prone portable testing device and a set of commercial blood analysers that had been hacked to run finger prick samples. These off-the-shelf machines typically required large venous blood volumes. Theranos was secretly diluting the few drops of capillary blood it collected to fit its samples to the instruments, a process that led to unreliable results. Ironically, Timothy Cooper, a former Theranos vice president, wrote “central to Elizabeth’s beliefs is that you must never dilute or compromise on your purpose and vision” in his letter of support before Holmes’ sentencing.5
The laboratory developed test framework allows patients easier access to new and specialised diagnostic technologies. Most of these tests are more innovative than a simple dilution, but lack of FDA oversight opens the possibility for promises to exceed supporting evidence. Non-invasive prenatal testing to detect common fetal abnormalities like Down’s syndrome, for example, has become standard in recent years. Because these tests are being offered as laboratory developed tests, the FDA does not pre-approve their methods or advertising. Some companies have expanded their offerings to identify much rarer genetic disorders, and the technology is leading to a raft of agonising false positives, according to a report by the New York Times.12 All the FDA has been able to do in response is issue a toothless safety warning.13
US legislators want to put a stop to this diagnostic free for all. A set of proposed regulations, called the VALID Act, is being debated in Congress.14 Advocates claim the bill would finally tackle the “Theranos problem”15 for good. The bill’s fate remains uncertain, but industry lobbyists are pressuring the government to pass it by the end of the year.16 VALID would provide the FDA with new authority to oversee custom laboratory tests. Many high risk technologies would require the agency’s review before coming to market. However, the medical community is divided over the merits of the bill. Different pathology groups, for instance, have expressed opposing positions on it.1718 Those speaking out against the regulations feel their cost and complexity would limit the number of tests available and make those that do come to market less innovative. Supporters of the bill feel that tighter government oversight is inevitable, and VALID would provide enough exemptions to minimise industry disruption.
Stringent regulations will not eliminate the risks associated with introducing new diagnostics. Laboratory tests largely remain a black box to patients and physicians alike. Body fluids go in, then results mysteriously come out. Ignorance is fertile ground for error and fraud. Even an analytically sound method can produce undesired outcomes if ordered indiscriminately or interpreted incorrectly. The best guard against another Theranos, then, is an inquisitive mind and sceptical outlook. Doctors and patients must demand evidence. Doctors will need to think carefully about whether a test should even be ordered in the first place. Holmes is facing years in prison partly because of how easily she convinced the public to believe her lies.
Competing interests: I have read and understood the BMJ Group policy on declaration of interests and declare the following interests: Volunteer for the College of American Pathologists. This article represents the author’s personal views only.
Commissioned, not externally peer reviewed