Medical ethics requires that in any research involving human beings, "the benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best current proven intervention." Declaration of Helsinki (latest revision, Principle 32)
Severely ill patients undergoing surgery at prestigious medical centers in the U.S.—including the National Heart, Blood and Lung Institute —have been subjected to increased risk testing experimental interventions without a proven safe comparator as a control.
Such research designs violate medical ethics: failure to include current practice as a comparator increases the likelihood of preventable patient harm. Patients and families are often not informed about the risks or the true purpose of the research. Whereas such explorative experiments may (or may not) be acceptable in animal research, such research is unacceptable in human beings.
An investigative report in TRUTHOUT is about an unethical blood experiment (Protocol #9256) conducted on patients undergoing cardiac surgery at Columbia University (1999-2001). The University’s administrators have managed to cover-up the nature of the experiment and the harm to patients for ten years.
An earlier report by Jeanne Lenzer and Shannon Brownlee appeared in Huffington Post (October, 2009)
"Protocol #9256 is not just a story about a wrong-headed clinical trial, ethical failures or even about harm to patients, as serious as that might be. For nearly a decade, Columbia has manifested a form of "institutional denial" by engaging in a widespread program of obscuring the reasons for the study, the harm actually done, the results of internal analyses and the behind-the-scenes influences that were doubtless necessary to induce sophisticated academics and administrators to ignore both the facts and the unambiguous conclusions of some of their peers."
The study, titled "Effect of Different Intravenous Fluids on Thromboelastography [TEG] During Cardiac Surgery," was presented as "minimal risk" for patients. In fact, the study posed major risks for patients: the study design included an intervention known to pose serious risks—Hespan—and it failed to include a control–i.e., current standard of practice.
The primary objective of Protocol #9256 was not disclosed either to patients or to the institutional review board. The primary objective was to document differences in clinical outcomes–i.e., bleeding, returns to the operating room, and kidney complications associated with each of four fluids.
The study design radically departed from standard hospital practice without regard for patient welfare:
"In order to make definitive comparisons, the protocol required each of the more than two-hundred patients randomly assigned to one of four study sub-groups to receive only one fluid during their bypass or heart valve replacement surgery, a departure from standard hospital procedure that called for a combination of fluids."
The principle investigator, Dr. Elliott Bennett-Guerrero, was Columbia’s chief of cardiothoracic anesthesia, had a financial conflict of interest in Hextend, one of the tested "blood expansion" fluids. He was a past consultant and paid speaker for BioTime Inc. – developer of Hextend, and a paid speaker for Abbott Laboratories, which is Hextend’s distributor, and pharmaceutical company that had indirectly sponsored the Columbia study with an unrestricted grant.
TRUTHOUT reports that one of the study fluids used in the experiment was Hespan, whose side effects "were sufficiently worrying that a "routine safe practice" had evolved to limit high-volume use of Hespan, especially in cardiac surgery. In Columbia’s operating rooms, as in most other hospitals, the simple rule of thumb was never to administer more than 1.5 liters of Hespan to patients."
"Nevertheless, by design Protocol #9256 placed no limits on the amount of any of the study fluids that could be given, including Hespan. In some cases, over three times the normal safe limit was administered, potentially a massive overdose."
So, patients who were randomized to Hespan in the study were put at KNOWN increased risk of harm. In fact, a number of patients in the Hespan group developed complications, and two died. There were no deaths in the study’s other sub-groups. The chart of one such victimized patient acknowledged that this was a "medical disaster."
By 2006, after years of denials and obfuscations, after three internal administrative investigations, many of the concerns about the study that were raised by two Columbia physicians, Dr. Mark Heath and Dr. Marc Dickstein, had largely been confirmed. Columbia had acknowledged that it had failed to inform patients of either the study’s true purpose or its inherent risks.
“By Columbia’s own written admissions, patients in the Hespan group did suffer a number of adverse clinical outcomes at rates significantly greater than other groups, and it is precisely these outcomes that the 2007 committee had established as its criteria for patient harm.
Yet Steven Shea, M.D. senior vice dean, Columbia University Medical Center, wrote to the federal Office for Human Research Protections (OHRP) that the conditions for harm had not been met.
In a letter (June 8, 2009) to Columbia University, OHRP disputes the dean, stating:
there was “a statistically significant higher rate” of “negative clinical outcomes, including bleeding events (requiring use of transfusions) and decreases in renal [kidney] function among study participants who received hetastarch. Beyond that, there was the trend toward increased need for re-operation.”
Since the study’s risks were not disclosed to patients, they were denied the human right to choose whether they wished to accept the risks.
Unlike patients who voluntarily accept risks in the hope of gaining some medical benefit not otherwise available in normal clinical practice, patients who were enrolled in Protocol #9256 were enrolled in the trial without their informed consent. Therefore, Columbia University bears full responsibility for any adverse outcomes affecting patients enrolled in protocol #9256 without their informed consent .
Dr. Bennett-Guerrero, the study’s architect and principal investigator, had been sanctioned by Columbia and removed from his supervisory position and tenure track.)"
"Overall, the story suggests that Columbia has been covering up a guilty secret, acting more like a malfeasant corporate enterprise than a center of higher learning. Viewed through a larger lens, Columbia’s behavior also illustrates the limitations of self-policing. Despite extensive federal regulations and the university’s impeccably high standards of scientific conduct, faced with potential legal liabilities, Columbia compromised its principles, dragged its feet investigating charges of whistleblower retaliation), and held fast to its denials of patient harm for nearly a decade."
Below, we excerpt Marc Gerstein’s psychological analysis as to why Columbia expended so much effort to avoid acknowledging patient harm. Marc Gerstein, Ph.D., is an organizational psychologist who sheds light on organizational behavior. He is the author of "Flirting With Disaster: Why Accidents Are Rarely Accidental" with Michael Ellsberg and Daniel Ellsberg (2008).
1. Red Cell Storage Duration Study (RECESS). Sponsored by NHLBI is currently recruiting patients. See: http://clinicaltrials.gov/ct2/show/NCT00991341
See also: Unethical US Gov Blood Experiment vs. Canadian Version http://www.ahrp.org/cms/content/view/660/111/
Vera Hassner Sharav
Blood Simple : Columbia University’s Ten-Year-Cover-Up of Patient Harm: Conflicts of Interest and Administrative Misconduct By Marc Gerstein, PhD
Why Has Columbia Expended So Much Effort to Avoid the Conclusion of Patient Harm?
The deep involvement of Ms. Catapano and Jane Booth, Columbia’s general counsel, throughout this decade-long controversy suggests that the university’s legal position was of ongoing concern to Columbia’s top administration. It is not difficult to see that if harm were established, and especially since the only deaths occurred in the Hespan group, that there was a possibility of litigation as well as damage to the university’s reputation and to the reputations of those members of the Medical Center staff who had misrepresented the study’s risks, biased its three investigations and misrepresented known facts about patient harm to OHRP in violation of federal regulations.
One possible explanation for Columbia’s behavior is that it was hoped that if the inquiry could be dragged out long enough the controversy would eventually disappear. In fact, in 2003 OHRP accepted both the university’s admissions of procedural and ethical violations and its proposed administrative remedies, putting the matter to rest until Dickstein and Heath raised the issue of patient harm again in 2006 after the arrival of Dean Goldman.
Despite Columbia’s admissions of administrative failure, however, its investigations were never led by independent parties, and were not, until 2007, based upon a review of all the pertinent clinical outcome data. Even putting all such questionable actions to one side, the most visible indication of systematic, self-serving bias was the administration’s drawing of bottom-line conclusions that were inconsistent with the evidence, a clear breach of scientific ethics.
The 2002 Committee and Ms. Catapano refer to examining the harm to the "study population as a whole." Applying the criterion of harm done to the entire population guaranteed a no-harm conclusion. It was the statistical equivalent of "cooking the books."
A similar misrepresentation arises from the question of whether bleeding could be attributed to the study for any individual patient. While such causal determinations often confound many individual medical liability cases, such those related to Merck’s Vioxx, an argument of individual harm was never made here, nor is one necessary. By Columbia’s own written admissions, patients in the Hespan group did suffer a number of adverse clinical outcomes at rates significantly greater than other groups, and it is precisely these outcomes that the 2007 committee had established as its criteria for patient harm. The conclusion of harm should therefore have been automatic, yet Dean Shea wrote to OHRP that the conditions for harm had not been met.
Beyond this, to determine whether patients were harmed as a result of the study, we need go no further than Kristina Borror’s simple argument: Since the study’s risks were not disclosed, patients could not choose whether they wished to accept them. Consequently, any avoidable adverse outcomes that affected groups of patients at higher than the rates of Columbia’s normal clinical practice were the result of the study’s design. This is fundamentally different from cases in which patients voluntarily accept risks in the hope of some otherwise unobtainable medical benefit.
Conclusions and Implications
Protocol #9256 is not just a story about a wrong-headed clinical trial, ethical failures or even about harm to patients, as serious as that might be. For nearly a decade, Columbia has manifested a form of "institutional denial" by engaging in a widespread program of obscuring the reasons for the study, the harm actually done, the results of internal analyses and the behind-the-scenes influences that were doubtless necessary to induce sophisticated academics and administrators to ignore both the facts and the unambiguous conclusions of some of their peers.(18)
While we might cynically expect such behavior from profit-seeking corporations, that it should come from a premier institution of high learning seems a more serious transgression. Universities are afforded wide discretion in their governance, particularly their right of self-examination. In return, they are expected to hold fast to the highest standards to ensure that their members’ conclusions are objectively based upon the evidence. In research, failure to abide by these standards is known as scientific misconduct, a dangerous poison that affects the progress of science world-wide and the trust that the public has in the advice and guidance scientists provide to society. Columbia University, of course, unambiguously promotes and supports the highest standards of research integrity.
In light of the known facts, this study should never have been performed as conceived, irrespective of its potential gains in knowledge. However, even though a safer dose-escalation study design might have been approved by the IRB and seen as safe by patients, it might not have been completed in time for the commercially important FDA meeting in June 2002.
With respect to the oversight of clinical trials and the value of external watchdogs in general, a number of weaknesses clearly need correcting. The OHRP is the primary organization that oversees organizations’ compliance to the federal government’s regulations regarding the treatment of human subjects. While its regulations and guideline documents are largely comprehensive, they do not provide sufficient guidance to redress compliance failures. In addition, my research strongly suggests the importance of outside perspectives in the anticipation, prevention, diagnosis and correction of failure.(19) Beyond this, internally voiced ethical and safety concerns, such as those in this case, need an independent, outside ear. At Columbia, alarms were raised in sufficient time for swift intervention to have prevented further harm. Unfortunately, no action was taken for seven months, by which time the study had ended.
In spite of the societal benefits of external review, however, we cannot expect institutions like Columbia to voluntarily accept greater outside scrutiny. Organizations, like individuals, are programmed to keep secrets, especially those known as "dark secrets" that are deeply embarrassing or potentially threatening to achieving their immediate goals. While all organizations – like people – occasionally make mistakes, their instinct is to cover them up and punish those who would reveal the inconvenient truths. Although cover-ups often bring harm to the organization as well to its patients, customers, employees and the larger society, institutions nevertheless impose codes of silence and punish their whistleblowers. Unfortunately, in the mental calculus of some leaders, taking the risks of a cover-up appears worth it if such a gamble provides a chance of escaping loss completely, or even coming out a little ahead. That seems to be the case here. Perhaps the biggest remaining question, therefore, is whether Columbia’s trustees will let those responsible get away with it.