In January 2003, Dr. Harvey G. Klein helped ring the opening bell at the New York Stock Exchange.
He was joined by his fellow board members of Haemonetics Corp., a Massachusetts company that markets blood-filtering equipment. A color photo of Klein and the directors at the exchange's lectern, smiling with upraised thumbs, was published in the company's annual report.
As the top expert on blood transfusion at the National Institutes of Health, Klein is in an excellent position to ring the bell for many companies that make blood products.
A Harvard University graduate with a medical degree from Johns Hopkins University, he was hired by the NIH in 1973. A decade later, he was named chief of the agency's Clinical Center blood bank. Now 61, he earns $215,000 a year as director of the NIH's Department of Transfusion Medicine.
Along the way, Klein joined the coterie of NIH scientists who won approval from the agency to consult for industry.
Confidential income disclosure documents that the NIH recently surrendered to the House Energy and Commerce Committee and other records examined by the Los Angeles Times show that from 1999 to this year Klein received $240,200 in consulting fees and 76,000 stock options from five blood products companies. Klein acknowledged in written responses for this article that several other firms also had paid him fees; he said that he properly reported the compensation to the NIH.
While taking industry's money and also working for the government, Klein helped shape policies and practices that directly affected his industry clients and patients. He participated as an expert at dozens of federal meetings that focused on uses of new blood- related products but did not publicly acknowledge his role as a paid consultant to any company, records show. Other experts did so voluntarily.
Klein also wrote an article for a major medical journal whose editors now say they would not have published if they had known about his company ties.
Blood experts have had a long debate over whether white cells should be filtered from blood for all transfusions. Proponents say such "universal" filtering would protect against infection and other complications. Opponents say it would squander hundreds of millions of dollars a year while benefiting companies that sell the filters. Hospitals already filter white cells for the most vulnerable patients.
At public meetings in 1999 and 2001 that led to a federal recommendation on the issue, Klein backed universal filtering.
At the 1999 session, sponsored by the Food and Drug Administration, Klein said universal filtering was "a better product.... So let's get on with it, with all appropriate speed." An FDA medical officer who chaired the session introduced Klein as "the spokesperson for today's workshop."
At the 2001 meeting, convened by the U.S. Health and Human Services Advisory Committee on Blood Safety and Availability, participants were asked at the outset to announce their industry ties.
Dr. Edward Snyder, director of the blood bank at Yale University, said, "I think it's particularly important, considering what I've been doing for the 22 [to] 23 years of my academic career, to state up front clearly my conflicts of interest." He named four companies, including a firm that was in a partnership with Haemonetics.
Klein, who along with Snyder was among six invited experts, identified himself as an NIH employee and as president of the American Assn. of Blood Banks. He did not mention that, since 1998, he had been on the board of directors of Haemonetics, which makes blood-collection systems with a built-in white-cell filter. The company paid him $60,000 in fees and 33,000 stock options from 1999 through 2003.
During the meeting, Dr. S. Breanndan Moore, a transfusion specialist at the Mayo Clinic, called for independent judgment. "Should we permit the suppliers of a product with a potential for an enormous financial windfall to unduly sway government? ... What has happened to protection from conflict of interest?"
The federal advisory committee ultimately voted 10 to 3 to recommend that universal filtering of white cells "should be implemented as soon as feasible." On its website, Haemonetics says that the FDA expects the process "to become industry standard."
"As far as I'm concerned, this whole controversy has nothing to do with blood safety," said Dr. Lawrence Goodnough, director of the blood transfusion department at Barnes-Jewish Hospital in St. Louis, in comments published in October 2000 by the College of American Pathologists. "This is a business plan implemented by the blood centers and commercial [blood-filtering] companies."
Klein told The Times in written comments: "To the best of my knowledge I did not make any statement at the January 2001 meeting, or at any other time, that would assist the sale of any of Haemonetics' products."
Artificial blood could be a blessing to trauma patients and hospitals where blood is in short supply. But the safety of such temporary substitutes remains in doubt.
In September 1999, Klein served as co-chairman for half of a two-day federal workshop convened to evaluate blood substitutes.
The workshop -- sponsored by the FDA, the NIH and the U.S. Army -- had significant implications for companies seeking to produce substitutes. Policymakers needed to decide what scientific evidence should be relied upon as proof that a blood substitute was safe enough for testing, or for broader use, in humans.
The stakes were highlighted the year before when one company, Baxter Healthcare, halted testing of a blood substitute after trauma patients who received it died at a far higher rate than the company had expected.
Klein told the federal workshop, held at the NIH, that he favored developing blood substitutes in part as a way to ensure adequate quantities of blood for transfusion. He did not reveal that he was a consultant to three companies that were developing substitutes.
Interviews and company records show that Klein had been a paid consultant within the preceding year to Biopure Corp., which was testing its product in patients in the U.S., South Africa and Europe. He was also a paid consultant to Alliance Pharmaceuticals Corp., whose blood substitute was in clinical trials, Klein acknowledged in response to questions from The Times. Also in 1999, Klein had joined the advisory board of Sangart Inc., which was trying to bring such products to market. Sangart that year granted Klein 20,000 stock options, according to company and government disclosure records.
Executives from Biopure and Alliance Pharmaceuticals addressed the federal workshop that Klein led.
On June 1, 2000, the New England Journal of Medicine published an editorial by Klein which, without naming any company, concluded that blood substitutes would "probably reduce or eliminate the need for transfused blood in some patients.... If the problems of their high cost and [perishability in the body] can be solved, these drugs will save countless lives in the developing world."
Klein's editorial, commissioned by the journal because the same issue carried a "case report" on the experimental use of Biopure's product, did not reveal his connections to Biopure, Alliance or Sangart.
In response to questions from The Times, Klein said that while leading the workshop, he "did not refer to any Alliance product nor did I even mention Alliance Pharmaceuticals." As for Biopure, Klein said he did not disclose his consulting role at the public meeting because at the time he "had no ongoing relationship with that company." Klein said that he did not acknowledge his position with Sangart because it was "a research company" that did not yet have a product.
He also said that he "complied fully with the disclosure policy of each journal."
However, editors responsible for the June 1, 2000, issue of the New England Journal of Medicine said that Klein's editorial would not have been published if they had known he was a paid consultant to a maker of a blood substitute.
"We do not allow editorialists who have a financial connection with a relevant company," said the editor who handled the editorial, Dr. Robert S. Schwartz.
The journal's editor in chief, Dr. Jeffrey M. Drazen, said a standard form signed by Klein in early 2000 reported that he had no ongoing "equity interest" or "consultancies ... with a company that stands to gain from the use of a product (or its competitor) discussed in the editorial." By signing, Klein also affirmed that he had not conducted any related consulting "within the past two years."
Drazen said that Klein added a note to the form: "I have in the past consulted for a number of companies."
"But he didn't say what 'the past' was," Drazen said. Nor, Drazen said, did Klein identify as a current or past client Sangart, the blood substitute company that had granted him 20,000 stock options the previous year.
"We should have checked the information that Klein had sent to us," Drazen said. "We made a mistake when we published this piece."
Blood in the U.S. is typically screened for five types of viral and bacterial infections before transfusions. New infectious contaminants, such as West Nile virus, continue to emerge, forcing public health officials to weigh the risks and benefits of so-called pathogen-reduction products.
In August 2002, Klein participated in an FDA workshop on whether and how to treat blood for rare contaminants without damaging red cells, platelets and other essential components.
At the time, three companies that were testing pathogen-reduction products in humans or were preparing related applications for FDA review had Klein on their payrolls, records show.
Five of the other panelists at the workshop publicly acknowledged their financial ties to companies developing the products.
One panelist, Dr. Walter Dzik, co-director of the blood bank at Massachusetts General Hospital, announced that he was chairman of the scientific advisory board for Vitex and a paid consultant to the company.
In a news release the month before the workshop, Vitex said that it hoped to become the first company to win FDA approval to market a product to inactivate contaminants in blood. A Vitex executive spoke at the workshop about the company's product.
Klein, who company records show had become a member of Vitex's scientific advisory board a year earlier, said nothing about his role with the firm.
Another company, Gambro BCT, summarized its product development plans at the workshop. Klein did not reveal that he was serving on Gambro's medical advisory board. From 2000 through 2003, Gambro paid him fees totaling $20,000, according to NIH records. A third client of Klein's, Haemonetics, also had an application pending at the FDA on human testing of a pathogen-reduction product.
Near the conclusion of the two-day workshop, Klein presented an analysis regarding the safety, effectiveness and need for a product that could remove infectious contaminants from blood. In his remarks, Klein pointed out risks, benefits and uncertainties. He did not endorse any product but noted that "certainly, pathogen reduction could provide an additional layer of safety."
Asked why he did not announce his private consulting at the meeting, Klein told The Times that he did not recall "speaking about or discussing" any specific company or its products.
As of November, Klein was listed on the advisory boards of five biomedical companies. The websites of the companies, including Vitex, ViaCell Inc., Navigant Biotechnologies Inc. (a wholly owned subsidiary of Gambro) and Verax Biomedical Inc., identified Klein by his NIH title. Klein remained on the Haemonetics board until the end of July.
In his written comments this month to The Times, Klein said that he had stopped accepting payments for his consulting and that all of his previous arrangements were approved as required. "At no time have my prior outside consultant arrangements resulted in a conflict of interest with my official duty at the Department of Transfusion Medicine at NIH," Klein said.
In January, NIH Director Elias A. Zerhouni appointed Klein to the NIH Ethics Advisory Committee, a new panel the director said would provide "independent peer review" of scientists' deals with industry.
Zerhouni hoped the committee would show that the NIH could police itself without the need for banning paid arrangements.
No transcripts or minutes of the advisory committee's proceedings are available for public review. A hint of the panel's deliberations can be found in materials for mandatory ethics training, which were distributed this fall within the agency.
According to the materials, ethics committee members typically have four "issues of concern" when they review colleagues' requests to consult for pay outside of the NIH. Among the issues: "subject matter overlap with substance of official duties" and "use of NIH title or affiliation."
As of midyear, the committee had recommended approval for 234 of 317, or 74%, of all outside arrangements proposed by NIH employees. With three exceptions, the recommendations were accepted by the NIH director's office.