Bioethics: January 2008 Archives

When Drug Trials Go Wrong

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          Today’s Wall Street Journal has an interesting story by Sarah Rubenstein titled “When Drug Trials Go Wrong, Patients Have Little Recourse.” The story recounts the experience of Suzanne Davenport who was the subject in a clinical trial testing drugs for Parkinson’s disease. As a result, she is wheelchair bound and living in a nursing home. The story makes mention of the cases we have filed on behalf of injured human subjects.

         The article notes that the consent form Ms. Davenport signed promised: "If you are injured as a direct result of research procedures, you will receive treatment at no cost." Yet when Ms. Davenport’s family wrote to the researchers requesting that they pay for her treatment, they did not receive a favorable response.

          Too often researchers and their sponsors fail to care for the human subjects in their trials when an adverse event occurs. If they would do so in the first instance, they might avoid the litigation that is sure to follow.

Alan Milstein

On gene therapy and informed consent

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This appeared first at
blog-bioethics.net.

 

By Alan Milstein

January’s issue of Human Gene Therapy offers some intriguing commentary on the issue of informed consent in gene transfer trials. I became aware of the articles when a writer for TheScientist Blog called for my reaction to the Editorial by James Wilson, because I had represented the Gelsinger family after the death of their son in the experiment sponsored by Dr. Wilson and because I currently represent the family of Jolie Mohr, whose recent death renewed the debate over the informed consent process in this field of research.

My initial reaction reported by the caller reflects my surprise that Dr. Wilson would thrust himself into the debate when the informed consent process he used during his trial was so deficient.

In the Editorial, Wilson writes:‘I encourage the professional gene therapy societies and various related foundations to work together in the new year to undertake a critical review of the conduct of our clinical trials... it behooves us to get ahead of this issue and put in place more effective ways to assure that research subjects who courageously give of themselves can do so with a full and unbiased understanding of the risks and benefits of their participation.”

The Issue includes commentaries by Art Caplan and Jeffrey Kahn who both question whether subjects in such trials are ever able to understand the mechanism of gene transfer and the risks associated with this nascent technology. Both call for subject advocates to be included in the process so that the human subject has a representative who can understand the risks and benefits of participation and offer advice on whether participation is in his or her best interest. Kahn questions whether the name of the field itself, splattered through the pages of the informed consent documents, misrepresents gene transfer as a proven therapy when, of course, it is not. Caplan laments: “very little has changed in the past decade in the way informed consent is obtained from perspective subjects.”

Wilson makes no mention of the specific problems in the informed consent process in the Gelsinger experiment but some of the commentators imply they were primarily the inability of an 18 year old subject and his father to understand such complex research. While that certainly was the case, it ignores the failure of Wilson and his team to include in the document the monkey deaths that had occurred in the pre-clinical research, the prior adverse events involving other human subjects in the earlier cohorts, and the extent of the financial stake both Wilson and the University of Pennsylvania had in a successful outcome. These are issues the family could understand without a subject advocate.

What is most troubling is that Wilson has not written an explanation of what really went wrong in the Gelsinger research and what lessons should be learned. Such an article was supposed to be an express condition of the settlement of the claims brought by the government against Wilson and the University of Pennsylvania. At least this was the promise made by the United States Attorney to me and Mr. Gelsinger, a promise as yet still unfulfilled.

"Do No Harm" Means Just That

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An editorial in this week's New England Journal of Medicine considers the role physicians should have in assisting the state in executing prisoners by lethal injection. They write:   "We are concerned that, regardless of its decision in Baze v. Rees, the Court may include language in its opinion that will turn again to the medical profession to legitimize a form of lethal injection that, meeting an appropriate constitutional standard, will not be considered 'cruel and unusual punishment.' On the surface, lethal injection is a deceptively simple procedure, but its practical application has been fraught with numerous technical difficulties. Without the involvement of physicians and other medical professionals with special training in the use of anesthetic drugs and related agents, it is unlikely that lethal injection will ever meet a constitutional standard of decency. But do we as a society want the nation's physicians to do this? We believe not."

The editorial looks ahead to the decision of the United States Supreme Court in Baze v. Rees, in which the Court must decide whether lethal injection in Kentucky constitutes cruel and unusual punishment and is thus unconstitutional. The cocktail used in Kentucky, according to medical experts, frequently results in agonizing and prolonged pain; indeed, it is outlawed for use by veterinarians in putting animals to sleep.

The executing states would love the medical profession to assist executioners in their unseemly business and a few of the Justices seem to welcome such a scenario in their questions posed at the January 7 oral argument in the case. Certainly, anesthesiologists could develop a cocktail and method that would avoid or at least limit the pain suffered by the condemned.

The authors in the NEJM cogently argue against such a practice. If physicians are to honor their oath and “Do No Harm,” they must resist calls to participate in the killing of prisoners, however heinous their crime.

Alan Milstein

           

med mar.jpgThe California Supreme Court has held that employers may terminate employees who test positive for marijuana use even if such use is prescribed by a physician to treat chronic pain. The Court held in
Ross v. RagingWire:

 "We conclude that the lower courts were correct:  Nothing in the text or history of the Compassionate Use Act suggests the voters intended the measure to address the respective rights and duties of employers and employees.  Under California law, an employer may require preemployment    drug tests and take illegal drug use into consideration in making employment decisions.  We thus affirm."

Ross had been terminated after his preemployment drug test revealed the presence of THC, though he had given the drug testing company and his employer a certification from his doctor that the marijuana was used to treat chronic back pain. California is one of thirteen enlightened states with a Compassionate Use Act which permits marijuana use for medical reasons. Some medical historians note that marijuana or cannabis has been used for medicinal purposes for over 4000 years and, prior to the introduction of aspirin in the mid- nineteenth century, was widely used to relieve pain.

Despite the clear views of the people of California in approving such legislation, the majority reasoned that the Act did not “eliminate marijuana’s potential for abuse or an employer’s legitimate interest in whether an employee uses the drug.” 

The dissent recognized that the  majority “disrespects the will of California’s voters” in failing to protect an employee’s off-duty use of marijuana where a doctor had recommended it. Termination of such an employee, according to the dissent, would be a violation of the California Fair Employment and Housing Act unless the employer could demonstrate that the off-duty use would impair the employer’s operations. The employer offered no such defense in this case.

Alan Milstein

 

Borrowed Brains May Lead to Damages

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brain.jpg  A Yiddish Proverb claims "Borrowed brains have no value." Maybe. But not when it comes to litigation.  

          When 30 year old Mark Albrecht drowned after an epileptic seizure, the state ordered an autopsy by the local coroner. After the procedure, the body was returned to the family for burial. What was not returned was Albrecht’s brain which had been removed by the coroner and later cremated and discarded as medical waste.

            The family filed a class action lawsuit against all of Ohio’s coroners. At issue is whether the next of kin have a protected right in the organs of their loved ones or at least the right to be notified after the organs are removed with the opportunity to claim them when the state no longer needs them. The federal court certified the issue to the Ohio Supreme Court which just heard oral argument in the matter. The briefs can be accessed on line as can the oral argument.

            Both sides claim an adverse result will lead to an avalanche of further trouble. The coroners claim a plaintiff’s win here would greatly restrict the right of the state to conduct autopsies, an argument with little merit. The plaintiffs, on the other hand, claim scientists would view a decision favorable to the defense as an invitation to harvest organs obtained in autopsy for use in medical research.

            The bottom line is that it would seem to ask little of the coroners if they had to give notice to the interested families of the autopsy procedures and the right to obtain the removed body parts after the autopsy is completed.

Alan Milstein

Informed Consent in Gene Transfer Trials

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Here is an article in TheScientist Blog which includes my reaction to the Editorial by James Wilson in the January issue of Human Gene Therapy.

Alan Milstein

Logo Parentis

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pharma_logos.gifIf you have ever thought it odd that your physican wrote your prescription on a pen inscribed with the very logo of the company whose drug he or she was prescribing, you are not alone. Now, the
Minnesota Star Tribune reports, SMDC Health System of Duluth has banned all drug-logo freebies at its four hospitals and 17 clinics in Minnesota and Wisconsin. Said Dr, Kenneth Irons, Chief of Community Clinics:"We're part of a leading trend that's trying to get away from the pharmaceutical companies essentially controlling what's prescribed in this country. This shows people we're not in the pharmaceutical companies' back pockets."

In response, SMDC employees turned in 18,700 items, including Nexavar pens, Combivir note pads, Vioxx mouse pads, Advair and Levitra clipboards, a disembodied stuffed nose from Allegra that exclaims, "That's snot funny," clocks, mugs, surgical caps, calculators, tape dispensers, and a stress-relieving squeeze toy made to look like a red blood cell.

            Not surprisingly, BigPharma is not pleased that its sales representatives have to cease such back-door direct to patient marketing techniques. “This is the first time I've ever heard of a systematic round-up of pens," said Ken Johnson, senior vice president of Washington, D.C.-based Pharmaceutical Research and Manufacturers of America. "Clearly there's a marketing backlash we've seen in a number of states. But this is a bit draconian."

          Not according to Dr. Sidney Wolfe, director of health research for Public Citizen, a nonprofit consumer advocacy group in Washington: "A hundred thousand a year is nickels and dimes compared to the savings patients will experience when they aren't prescribed the most expensive drugs inappropriately. All this stuff that's handed out is really influence peddling. It's legalized bribery."

Alan Milstein

Clinical Trial Results Too Often Delayed: Part II

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nejm.jpgAn article published today in the
New England Journal of Medicine confirms what we have described as a serious problem in the manner in which the FDA allows drug companies to control the release of data in clinical trials. The authors conducted a meta-analysis of clinical trials evaluating the effectiveness of antidepressants. They found that the companies published 97% of the studies in which positive results were found but only 12% of studies in which the findings were negative.

While the drug companies must report the results of all their clinical trials to the FDA, the agency at present is prohibited from publishing the results on its own.

This system has to be changed. Not only do human subjects and patients have the right to review all material information about the drugs or therapies they have been prescribed, but physicians also have the need to review material information before they suggest a particular drug or treatment. While BigPharma may have a monetary interest in keeping negative information about their products from the public, the interest in public health is what the FDA is obligated to protect.

Alan Milstein

 

Clinical Trial Results Too Often Delayed

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This first appeared at Blog.Bioethics.Net.

 

Zetia situation demonstrates need for a more open clinical trial process

By Alan C. Milstein

The news about Zetia and Vytorin once again raises a major problem in the way the FDA allows drug companies to control the information about the clinical trials they conduct, often to the detriment to public health. Apparently, Merck and Schering-Plough had completed the trial which has just hit the media back in April of 2006. While analyzing the results of the 720 human subjects might have taken some time, the data hardly could have been as complex as the two companies claimed in explaining the continued delay in reporting the information which will undoubtedly cost them sales of their drugs.

Meanwhile, there was little reduction in the direct advertising the companies did for the products. We still repeatedly had to witness the actors pretending to be med students on rounds discussing the advantages of Zetia with their mentor and the cute morphing of Aunt Meg and hard-boiled eggs in the Vytorin commercials.

Merck, of course, faced similar criticism about delaying the release of clinical trial data about Vioxx. And all the major players in BigPharma faced tough questioning from Congress over their failure to report the results of clinical trials they conducted which revealed that SSRIs increased the likelihood of suicide and suicide ideation in adolescents while showing no efficacy in the treatment of childhood depression. A long-delayed Black Box warning was the result

This is not a new problem. A few years back, I was investigating the systemic and institutional failures which caused the death of 18 year old Jesse Gelsinger. The Recombinant DNA Activities Committee had previously rejected a call for a Gene Therapy Information Network which would house the adverse events of all gene therapy trials so other investigators and human subjects would have access to the information. A prior trial at a different institution had yielded results which might have predicted Gelsinger’s reaction to the adenovirus but had been marked proprietary by the research team. In an off the record conversation, Phil Noguchi, FDA Director of Cellular and Gene Therapy and a member of the RAC, told Jesse’s father and me that had the network been approved Jesse would not have been killed. A sobering thought, to say the least.

While that network is now in place, more needs to be done to make the clinical trial enterprise in this country transparent and to eliminate the ability of pharmaceutical companies to withhold or delay the results of their clinical trials. The companies will cry that millions are at stake. But those are of lives not just dollars.

Alan C. Milstein is a nationally recognized litigator in the areas of insurance law, products liability, bioethics and clinical trials litigation.

Guinea-pigging Up Close and Personal

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guinea pigs.jpgCarl Ellioitt of the University of Minnesota Center for Bioethics has just published an insightful article in the New Yorker about Phase 1 research: “
Guinea-pigging: Healthy human subjects for drug-safety trials are in demand. But is it a living?” The article describes the nasty side of Phase 1 research in which largely the poor, the needy, and sometimes the peculiar rent their bodies to private research factories occasionally at great personal risk.

Professor Elliott mentions my work at the firm and includes a quote: “This is not something you or I do. This is something the poor do so the rich can get better drugs.”

One of the great myths of human research is that the subjects are motivated by an altruistic belief in the greater good. As the article points out, the truth is that most subjects in Phase 1 research are motivated by the same thing that motivates many of the researchers: money. This recognition doesn’t have to mean that the system is corrupt and needs to be halted, and the article does not advocate for such a position. Medicine and science could not advance without the availability of such human subjects.  What it does mean is that more oversight is needed to make sure such research is conducted safely and that the researchers understand their ethical and legal obligations.

A similar reality check is necessary in Phase 2 and 3 therapeutic research. Altruism rarely is the motivating factor for participation. What the subjects usually want is just to get well and they agree to participate because they think the research is in their best therapeutic interest. Again this does not mean the research enterprise is corrupt or unethical. But it does require more oversight on the part of the FDA and OHRP to make sure both researchers and research subjects understand their roles in the search for new cures and medical advances.

Alan Milstein

About this Archive

This page is a archive of entries in the Bioethics category from January 2008.

Bioethics: December 2007 is the previous archive.

Bioethics: February 2008 is the next archive.

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