This story is enough to strike terror into our hearts.  Literally.  If you happen to be a medical researcher, it’s even more troubling, because anytime you have patients dying during clinical trials, researchers  investigated by their employers, lawsuits launched against hospitals by their own doctors, drug companies funding research into products that kill people, patients misinformed about what studies would do to them, and world-famous heart institutes trying to sweep all of it under the rug – well, it looks bad.

The non-profit Huffington Post Investigative Fund obtained government documents last week about a two-year drug study undertaken at Columbia University Medical Center between 1999 and 2001 that was so badly mismanaged, it will likely be used as a case study in future PR classes.

This study focused on four fluids called ‘blood expanders’ that are administered by anaesthesiologists and combat medics when patients/soldiers have lost significant quantities of blood. Blood expanders are frequently needed during over half a million cardiac surgeries performed each year in North America alone.

Trouble was: two of the study’s four blood expanders contained hetastarch, which two previous studies dating back to 1981 had already warned would prevent blood from clotting at high dosages, and one of the two, Hextend, was manufactured by drug giant Abbott Laboratories – coincidentally one of the funders of the study.  Abbott’s interest was in boosting its share of the blood expander business with Hextend if the Columbia study results were favourable.

But by 2000, two Columbia anesthesiologists, Dr. Marc Dickstein and Dr. Mark Heath,  had officially raised concerns about the safety of the 200 patients enrolled in this study, known as Protocol #9256. These concerns triggered the hospital’s first of three internal reviews of the study and its lead author, cardiothoracic anaesthesiologist Dr. Elliott Bennett-Guerrero (whose face might be familiar to you because over the past two decades, the cameras of the PBS science program Nova have been following him since his Harvard med school days starting in 1987, as part of its Doctors’ Diaries show).

The two whistleblowers reported that they had been in the O.R. when a number of the study’s heart patients had hemorrhaged, and feared that the study’s design virtually guaranteed that more patients would also hemorrhage.

By 2001, the study’s lead author – who was also running 25 other simultaneous clinical trials at Columbia – was ordered to stop recruiting new patients for the blood expander study. Just a few months later, Bennett-Guerrero reported the first of two deaths among his study patients. Both died shortly after being given one of the hetastarch fluids. Another two dozen patients hemorraghed so severely after receiving hetastarch that they required emergency transfusions. Some patients had received up to three times the hetastarch level recommended by manufacturers.

In 2002, Columbia disciplined the doctor for not properly reporting “a substantial number of medical complications” that were emerging in his study.

He was also barred from conducting further research, relieved of his senior post in cardiothoracic anaesthesiology, and taken off Columbia’s tenure track. The doctor responded by filing a lawsuit against his employer, and then quitting his anaesthesiology job there for another at Duke University Health System.

In spite of a letter from Columbia University Medical Center to federal government regulators admitting that …

• they had not acted on the warnings of their two whistleblowers
• their researchers had “failed to convey” the purpose of the study to both the hospital’s research review board and to patients
• the hospital’s review board had approved the terms of the study even though no members of the board were trained in the subject
• they had not informed the patients of the risks
• they had not appropriately reported serious medical complications
• the fluids prepared for the study had allegedly been mixed in an unsanitary blood-spattered room

… Columbia’s internal review decided that the patients’ medical outcomes did not meet the definition of ‘harm’ and that they had not found a causal relationship between the blood expander fluids and the two patient deaths.

Oddly, Columbia officials came to this conclusion even though they had reviewed only 14 of the 200 patient charts, according to the released documents. In 2003, government regulators recommended that Columbia contact all surviving study patients to re-disclose the risks that not been made clear to them.

Meanwhile, despite the bad news at Columbia and the sudden loss of their lead study author, over at Abbott Laboratories, officials sent a letter to the FDA in May of 2002 requesting 30 minutes on their upcoming June 14th meeting agenda to “make recommendations for the unwarranted need for warning statements on Hextend package inserts about risks of excessive bleeding during cardiac surgery.”

Huffpost documents also show that the two whistleblowers repeatedly asked government regulators to re-examine the study and its outcomes, and to warn the surviving study participants of the risks of hetastarch. By 2006, a compliance officer with the Office of Human Research Protections finally responded via e-mail that his agency would not challenge Columbia again, adding:

“Failing to disclose risks to subjects in completed research was a very common deficiency.”

But for some reason, Columbia began yet another internal investigation of the blood expander study in 2007, this time admitting to the Feds that there were indeed some “deficiencies”. But this time, regulators sat up and paid attention, concluding that, among the patients who had received hetastarch:

• there was a “statistically significant higher rate of negative clinical outcomes including bleeding events requiring use of transfusions and decreases in renal (kidney) function”
• there was an “increased need for re-operation”
• patients did worse than other patients who did not receive hetastarch

The government’s new verdict: this study was carried out with both ethical and regulatory mistakes, and Columbia University Medical Center must now track down all surviving study patients and their families – the same instructions that Columbia had failed to carry out back in 2003.

All of this makes you wonder: who’s minding the store here, when patients are clearly placed in harm’s way with impunity so that Big Pharma can increase sales?

In spite of both regulatory and hospital acknowledgement of the flawed research, in 2001, Bennett-Guerrero had two articles about his study accepted for publication by the medical journals Anesthesiology and Anesthesia and Analgesia. Funny, though – he left out the part about the “statistically significant higher rates of negative clinical outcomes” for those study patients given hetastarch.

UPDATE December 13, 2010: Bennett-Guerrero continues to add to his list of published “research” as recently as October 2010 in this study submitted successfully to the Journal of the American Medical Association, which indicates the lax standards of JAMA editors in accepting papers despite both regulatory and hospital acknowledgements of his flawed research methodology at Columbia.

And according to Dr. Marc Gerstein of the Office of Medical And Scientific Justice, when Protocol #9256 was being designed in 1999 – and two years after the blood expander’s manufacturers had identified increased sales potential as the reason for the study – it seems likely that Bennett-Guerrero knew precisely what the corporate funders of his research expected from him.

As an expert in this field, and a paid speaker and consultant for Abbott, Bennett-Guerrero would have been well aware of the company’s marketing hopes for its new product. See also: “Columbia’s 10-Year Cover-Up Killed Patients“.

Since my own heart attack, I’ve been tirelessly advocating for women to participate in cardiac research (where women are woefully under-represented despite the fact that more women than men die from heart disease each year).  But when I hear stories like this Columbia fiasco, I despair.

It makes me wonder if any of us are truly safe in the greedy  hands of clinical researchers and the drug companies that control them.