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By ANDREW POLLACK
Published: January 7, 2009
LOS ANGELES — The nation’s largest medical laboratory company provided possibly erroneous results to thousands of people who had their vitamin D levels tested in the last two years, the company has acknowledged.

The company, Quest Diagnostics, has already sent letters to thousands of doctors listing the patients who might have received “questionable” test results and offering free re-tests. Typically the test costs $100 to $200 or more.

An erroneously high result might mean patients would not take vitamin D supplements when perhaps they should, doctors said. And an erroneously low test result might lead in rare instances to a toxic overdose of vitamin D. When the Quest tests have been inaccurate, the reading has typically been too high, although not in all cases.

Quest’s action represents “the largest patient test recall I’m aware of in my 20 years in the business,” said Robert L. Michel, editor of The Dark Report, a newsletter for pathologists that first reported on Quest’s action.

The incident could raise calls for more regulation of diagnostic testing at a time when diagnostics are playing an increasingly crucial role in guiding medical treatment. Many laboratory tests, including Quest’s vitamin D test, do not require approval from the Food and Drug Administration.

The incident also raises questions about vitamin D testing, which has surged because studies have suggested that a deficiency of the nutrient raises the risk of bone weakness, cancer, heart attacks, autoimmune diseases and other diseases. Propelled by such research, Quest and other major laboratory companies have reported test volumes roughly doubling from one year to the next.

But experts say that so far there is no standardization of the tests, meaning that results can differ considerably from one laboratory to another. That can make it hard for doctors to decide on treatment and difficult for experts to compare studies aimed at determining what the optimal level of vitamin D in the blood should be. “If you get your vitamin D level measured in the Mayo Clinic, the Cleveland Clinic and the Timbuktu Clinic, it would be nice if it came out the same value,” said Dr. Neil Binkley, associate professor of medicine at the University of Wisconsin.

Dr. Binkley said that a few years ago he sent a sample of his blood to six different laboratories and got results that ranged from 14 nanograms a milliliter, which would be a deficient level, to 41 nanograms — a level three times as high and considered adequate. While the tests have improved since then and there are efforts under way to standardize them, there can still be substantial variability, he said.

And yet, many experts say that even if the tests were accurate, there would still be uncertainty in how to treat patients. There is considerable debate about how much vitamin D is needed and whether vitamin D supplements even prevent various diseases. Vitamin D is usually made by the body when the skin is exposed to sunlight and is also contained in oily fish and some fortified drinks like milk.

Quest’s problems began when it started shifting to a new test at the same time demand for testing was rising rapidly. The new test promised to be more accurate and offer more detailed information, Quest executives said. But the test relied on a sophisticated instrument called a mass spectrometer, which can be tricky to use, especially for high-volume testing.

Dr. Wael A. Salameh, the medical director for endocrinology at Quest’s most sophisticated laboratory, in San Juan Capistrano, Calif., said some materials used to calibrate test results were faulty. And four of Quest’s seven testing laboratories around the country did not follow proper procedures for some period of time, he said.

Quest would not say how many patients were affected. But a spokesman did not deny that thousands of doctors were sent letters in October. Each doctor had at least one patient, and in many cases dozens of patients, who had the possibly inaccurate test results.

Dr. Salameh said the inaccurate results represented fewer than 10 percent of all the vitamin D tests done by the Quest from early 2007 to mid 2008. And even many of the possibly inaccurate results were probably accurate, he said, because Quest sent letters even if there was only a remote chance that the test was erroneous.

“We are kind of being penalized for going the extra mile,” he said.

Dr. Ronald Hoffman, a clinical nutritionist in Manhattan, said his letter from Quest mentioned about two dozen of his patients.

“There was a patient we put on vitamin D and all of a sudden, for the first time ever, the patient came back with what seemed to be a toxic level of vitamin D,” said Dr. Hoffman, who is also host of a radio program on health, on WOR, in New York. When the patient was given a different vitamin D test, the value was considerably lower.

Dr. Lawrence Rosen, a pediatrician in Oradell, N.J., who treats many autistic children, said his letter named more than 20 patients and that re-testing was an inconvenience. “A lot of these kids, especially if they’re autistic, it’s a big deal for parents to have their blood drawn,” he said.

One question is why Quest’s problems took so long to discover. Some doctors who advocate vitamin D use said they began noticing some unusually high test results in 2007 and began complaining publicly in the summer of 2008.

One of them was Dr. John Cannell, a psychiatrist at a California hospital for the criminally insane who started the Vitamin D Council to promote use of the vitamin. He said that after the test was introduced, he started noticing some patients having normal levels of vitamin D, a departure from the past, when the levels have often been low.

“A black man coming from solitary confinement on C.D.C.R. food cannot have a normal level of vitamin D,” he said, referring to the California Department of Corrections and Rehabilitation. People with dark skin do not convert sunlight to vitamin D as easily as those with lighter skin.

Quest executives say they dismissed the concerns of Dr. Cannell because he was a paid consultant to DiaSorin, a company that makes a rival test.

They said the company’s review of its testing results was instead prompted by questions from other doctors. Also, they said, in preparing a report from its data on national health trends, the company noticed an unusual rise in average vitamin D levels.

Meanwhile the F.D.A. is considering increasing its role in regulating diagnostic tests. Right now test kits sold to labs, hospitals and doctor’s offices have to be approved by the agency. But tests developed and offered by a single laboratory, like the Quest vitamin D test, do not.

Quest and many other laboratories argue that lab quality is already regulated through Medicare and that having to win approval for each new test would slow innovation and raise costs.

A public company, Quest had sales of about $5 billion for the first nine months of 2008.

Source: New York Times