CEO SUMMARY: Reporting in The Wall Street Journal shows that some physicians in Arizona were concerned about the harm from erroneous test results from Theranos Inc. But those physicians who expressed concern may have been only a small set of the number of physicians who were worried about patient harm. After reviewing the concerns about patient harm published by the Journal reporter, an expert in clinical lab quality issues said there may be no way to know how many patients were harmed.
DESPITE ALL THE FAVORABLE PRESS COVERAGE Theranos Inc. received in the fall of 2015, many in the clinical laboratory industry were concerned about the science behind Theranos’ blood testing methods. In a new book out this month, investigative journalist John Carreyrou of The Wall Street Journal showed that many patients were harmed as a result of that lab testing.
“From his reporting, we can assume that many more patients were harmed,” said George Cembrowski, MD, an expert in lab utilization and quality control. The former Director, Medical Biochemistry, at the University of Alberta Hospital in Edmonton, Canada, has followed the Theranos saga closely.
“What we learned from the story about Theranos is something we all knew earlier, and it bears repeating now: Before anyone puts huge amounts of money into new methods for clinical laboratory testing, they should do all of the required and rigorous methods of evaluation that are possible,” he said.
“As the laboratory profession saw with Theranos, when you rely on unvalidated testing methods and untested machines, the result will be losses for investors and harm for patients,” commented Cembrowski.
“Certainly when big investors lose money, it may not be a significant problem because they always seem to have more money,” he added. “But the larger issue involves patient harm. And, for many of the patients harmed by Theranos’ testing methods, that harm is lasting, whether it’s financial or physical.”
Faulty Test Results
In addition to financial and physical harm, patients who get faulty test results also may worry needlessly while they are taken on a diagnostic odyssey. “If results are flawed, then it leads a patient on this journey of more testing and overtesting to make sure the initial results were correct,” stated Cembrowski.
“In many cases, abnormal results lead to overdiagnosis, overtreatment, and ultimately to significant morbidity and even mortality.
“Most clinical lab directors are happy the FDA and CMS have stringent quality standards in place because those standards are designed to ensure patient safety,” he said. “But in this case, Theranos was doing whatever it could to get around those regulations.
Tip of the Iceberg
“We could also argue that what has been reported about patient harm is just the tip of the iceberg,” Cembrowski added. “We know some physicians were using independent laboratories to verify the lab test results reported by Theranos on their patients. It’s likely that other physicians were doing the same because they were puzzled or concerned about the results they got from Theranos.
“Some physicians agonized over the data they got, especially if a particular result showed the potential for patient harm,” he said. “Take, for example, the prothrombin time and International Normalized Ratio (INR) test, which shows the action of warfarin, an important anticoagulant. In either direction, if the INR is too high or too low, it can indicate serious patient bleeding or clotting issues.
Mixing Distilled Water with Red Blood Cells Is Bad Idea
ONE ADVANTAGE TO ITS DIAGNOSTIC TECHNOLOGY THAT THERANOS TOUTED in its marketing and media interviews was its use of blood samples collected by fingerstick collections. Using fingersticks allowed the company to advertise itself as being patient friendly because its technology would allow it to avoid the need for venous blood draws.
News reports indicate that Theranos had been adding distilled water to these capillary blood samples in order to have enough specimen volume to run those samples on standard blood analyzers.
Problems arise, however, if there is insufficient blood volume for some tests, said George Cembrowski, MD. “Depending on how much water gets added to the blood sample, you could have a significant problem,” he said. “In short, this is a really bad practice when testing clinical specimens.
“For example, consider how red blood cells react with distilled water,” continued Cembrowski. “The red cells would swell up as more water is added and eventually break apart (lyse), thus releasing everything in the red cell into the plasma, which is then measured in addition to what was already in the plasma.
“When red cells break apart like this, it is called hemolysis and hemolysis is an issue which labs try hard to avoid when they collect and handle blood specimens,” he added. “Many papers have been written on the effects of hemolysis. The basic issue is that, as the red cell contents leak out, that increases their apparent concentrations, which, in turn, affects all kinds of clinical laboratory tests.
“Sometimes, the test results decrease,” added Cembrowski. “One example is when a lab tests for troponin in a patient suspected of having a heart attack. With hemolysis, on certain instruments, the troponin levels decline.”
“Or, consider if a test result shows a problem with a patient’s sodium,” he added. “In most patients, the body regulates sodium flawlessly, and most lab instruments measure it well. But if sodium or any electrolytes are out of range in just a couple of patients the physician should be thinking that the lab has defective testing.
“In almost all healthy patients, if clinicians suspect sodium or electrolytes are out of range, they would be highly bothered because there’s so little deviation in normal healthy people,” he explained. “That alone could lead a physician to question almost all results from that lab.
“If a doctor gets a high frequency of clinically important outliers and reports those results to the lab, then the lab might need to suspend testing and identify the problem,” Cembrowski said.
“I would guess that physicians saw the outliers and reported those outliers, but it looks like Theranos’ response was poor at best,” he added. “It looks as if Theranos went into a mode designed to elude everybody. And they did a great job in eluding almost everyone.
Good Laboratory Practices
“What we don’t know is how much self-delusion or group-think went on with the lab and executive teams at Theranos,” Cembrowski concluded. “It could be there was a way of thinking in the lab that was counter to good laboratory practices, particularly if one or two people at the top were saying the system works fine. That can create a kind of a mass hypnosis. When that happens, everybody simply follows the leader.
“Just by the fact that Theranos had some of their proprietary Edison instruments in one place and other Siemens production instruments in a different place, implies that they were attempting to deceive inspectors or to keep employees in the dark,” he said.
Potential for Patient Harm
The potential for significant patient harm was an issue that went unaddressed by nearly all the media accounts about Theranos and its founder Elizabeth Holmes during the years when it was being touted as the next Silicon Valley success story, a company likely to succeed on the same scale as Amazon, Google, or Apple, for example.
After Theranos began offering testing through Walgreens pharmacies in Palo Alto, Calif., and Phoenix, consumer review websites, such as Yelp, had postings from patients who reported serious issues with clinical laboratory test results they had recieved from Theranos and what they learned when they had the same tests repeated by another clinical laboratory.
During this time, did state and federal regulators of clinical laboratories fail patients in the regions where Theranos was offering lab testing services? It is not known how many physicians and patients may have complained to their state CLIA offices or CMS about discordant lab test results. But it is reasonable to expect that some medical professionals reported incidents of seriously-discordant lab test results to government bodies.
In several important ways, the story of Theranos’ rise to fame and its subsequent collapse demonstrate why innovations in diagnostic technologies must be thoroughly vetted before they are used in patient care.
Response to Bad Test Results Offer to Retest for Free
ONE FACTOR SHOWS CLEARLY how Theranos was less than upfront in its dealings with regulators, referring physicians, patients, and the public, said George Cembrowski, MD. An expert in lab utilization and quality control, Cembrowski found it troubling that Theranos did not offer to retest patients when informed about bad test results.
“If Theranos truly wanted to improve, then when physicians had questions about test results, Theranos should have offered to do retesting for free,” he stated. “The honorable way to respond to questionable results is to pay another clinical laboratory to do the retesting.
“As far as we know, that didn’t happen,” he said. “Instead, we know that Theranos voided the millions of blood test results.”
In May 2016, reporter John Carreyrou reported in The Wall Street Journal that Theranos told federal regulators it had voided two years of results from its Edison blood-testing devices. But there is no evidence that Theranos provided or offered retesting to these patients.
Contact George Cembrowski, MD, at 780-407-3185 or Cembr001@gmail.com.