Thursday, March 30, 2006
Professor George Zimmer, a cancer patient who participated in a number of Phase I clinical trials, provided an interesting perspective on drug trial participation:
“Human participants in a protocol differ in two ways from the rats and dogs that preceded them. First, because human participants are not distinguished by breed, they do not have identical or blanket reactions to an experiment…Second, human patients have differing mental and personality characteristics…but the trials cannot compensate for the thoughts and emotions of individual participants. These important facets of the whole person are largely ignored when trial programs are designed” (Daugherty, Siegler, Ratain & Zimmer, 1997, p.892).
“Although Professor Zimmer describes personal experiences encountered during his battle against cancer, his views on how some patients respond to incurable illnesses certainly apply to many other terminal diseases. Zimmer raises serious questions about basic aspects of clinical trials…” (Daugherty, Siegler, Ratain & Zimmer, 1997, p.893).
His essay also highlights the importance of considering the unique particularities that each individual trial participant brings to the trial site. In HIV vaccine trials, for instance, there are unique social consequences of HIV infection that must be considered in the ethical analysis of vaccine trials. “People infected with HIV have experienced stigma, marginalization, and discrimination in many forms. Volunteers participating in HIV vaccine trials may be falsely identified as HIV-positive simply through their association with the trial…Thus, the risk of social and psychological harm for human subjects participating in vaccine research is substantial” (Guenter, Esparza & Macklin, 2000, p.38). And this coupled with the physical risks of participating in drug trial research – risks that have been clearly demonstrated in what appeared to be a test for a simple anti-inflammatory drug.
The ethical complexities involved in clinical human subjects research may be one of the factors that have slow down progression to the final step of randomized, controlled large-scale Phase III efficacy trials, despite the fact that many candidate HIV vaccines have proceeded to the point of testing for safety in human subjects (Phase I and Phase II clinical trials). Other challenges facing these trials are scientific, logistical, political, and economic (Guenter, Esparza & Macklin, 2000).
Meanwhile, few drug trials in South Africa seem to get past Phase I research. Could these challenges be part of what is slowing the trial process down? Or is the red tape of regulatory procedures compromising the medical research industry in this country? Clinical trials are pulling in up to R2-billion a year in South Africa, according to a recent report, but researchers fear the industry may be compromised by the slowness of regulatory authorities to approve, or reject, potential trials.
It is not unknown for multinational drugs companies to test unproven drugs on vulnerable subjects in the developing world. Because of this, South African regulators have to balance competing in a competitive international market with ensuring that trials participants are not exploited. But researchers are concerned that lack of human resources is slowing down the clinical trials registration process, encouraging companies to look elsewhere.
Daugherty, C.K., Siegler, M., Ratain, M.J., & Zimmer, G. (1997). Learning from our patients: One participant’s impact on clinical trial research and informed consent. Annals of Internal Medicine, 126, 892-897.
Guenter, D., Esparza, J., & Macklin, R. (2000). Ethical considerations in international HIV vaccine trials: Summary of a consultative process conducted by the Joint United Nations Programme on HIV/AIDS (UNAIDS). Journal of Medical Ethics, 26, 37-43.
Wednesday, March 29, 2006
It would be unethical to test the suspected viruses in humans, so for now all of the evidence for their effect on people comes from associative data. Previous work done shows that in a randomly tested population, 30 percent of obese people had been exposed to one of the suspected viruses as compared to only five percent of lean people.
Tuesday, March 28, 2006
From military and security issues to human enhancement, artificial intelligence, and more, these papers give readers a peek under the lid of Pandora's box to see what the future might hold.
Sunday, March 26, 2006
Still, it's nice to see that L'Oreal, in conjunction with UNESCO, has launched an open, online forum designed to support and highlight the role in women in science. As reported on the wonderful yet underappreciated news resource SciDev.net, the AGORA forum "will focus on topics such as science education for girls and women, women of science and sustainable development, bioethics and diversity."
Hopefully, this forum will not languish in obscurity like so many UNESCO projects but will become a dynamic community that supports the role of women in science and academia, and that leads even more women to demand greater (and equal) access to education, particularly in developing countries.
Friday, March 24, 2006
In a study of attitudes and beliefs about blood donation in Nigeria, even well-educated donors believed that they could contract HIV or hepatitis from blood donation. Others were afraid of what they believed to be side effects of blood donation, including weight loss, sexual failure, convulsion and sudden death. One study of HIV and blood donation in the KwaZulu-Natal province in South Africa found that “despite very sound knowledge about HIV and high risk factors, significant proportions of respondents apparently fail to make a link between high risk behaviour and lack of suitability for blood donation…A secondary but disturbing finding is repeated indications among a small minority of respondents of a desire to spread HIV if they find themselves to be HIV-positive…”
The power of beliefs – factual and fictitious - around HIV/AIDS is explored by Diane Goldstein, in her book, Once Upon a Virus: AIDS Legends and Vernacular Risk Perception. Goldstein traces “the rich tradition of AIDS legends in relation to current scholarship on belief…Since reports of the first cases of HIV/AIDS in the early 1980s, contemporary, or "urban," legends about origins of the virus, modes of transmission, deliberate infection, withheld treatment, and minority genocide have proliferated…Though fascinating, intriguing, and often frightening, these narratives more than merely entertain. They warn and inform, articulate notions of risk, provide political commentary on public health actions, and offer insight into the relationship between cultural and health truths. As parts of community discourse about the nature of disease, legends provide powerful information about cultural understandings of the virus.”
Gillian Bennett (of the Folklore Society, UK) has written an interesting review of the narratives and topics explored in Once Upon a Virus. The first chapter of the book, “Tag, you’ve got AIDS: HIV in folklore and legend” explores some popular jokes, myths and children’s games involving AIDS references. Some of the issues reviewed in the “Bad people and body fluids: Contemporary legend and AIDS discourse” chapter include vernacular concerns about health, emergent meanings, tainted food and contaminated space, and deliberately infecting the other. “Banishing all the spindles from the kingdom” describes the legends of deliberate infection – the dangers of infected needles in cinema seats or of mad dancers who inject others in nightclubs – that “assert that the danger is not in the bedroom at all but ‘out there’ where we are all vulnerable.”
One wonders whether this latest tele-recruiter’s inspired idea of jokingly telling a blood donor she is HIV-positive has the potential to become another narrative of yet another chapter in the AIDS myths and urban legends book.
Thursday, March 23, 2006
Wednesday, March 22, 2006
Tuesday, March 21, 2006
The vast differences between humans and chimpanzees are due more to changes in gene regulation than differences in individual genes themselves, researchers from Yale, the University of Chicago, and the Hall Institute in Parkville, Victoria, Australia, argue in the March 9, 2006, issue of the journal Nature.
The scientists provide powerful new evidence for a 30-year-old theory, proposed in a classic paper from Mary-Claire King and Allan Wilson of Berkeley. That 1975 paper documented the 99-percent similarity of genes from humans and chimps and suggested that altered gene regulation, rather than changes in coding, might explain how so few genetic changes could produce the wide anatomic and behavioral differences between the two.
Using novel gene-array technology to measure the extent of gene expression in thousands of genes simultaneously, this study shows that as humans diverged from their ape ancestors in the last five million years, genes for transcription factors--which control the expression of other genes--were four times as likely to have changed their own expression patterns as the genes they regulate.
Because they influence the activity of many "downstream" genetic targets, small changes in the expression of these regulatory genes can have an enormous impact.
"When we looked at gene expression, we found fairly small changes in 65 million years of the macaque, orangutan, and chimpanzee evolution," said study author Yoav Gilad, PhD, assistant professor of human genetics at the University of Chicago, "followed by rapid change, along the five million years of the human lineage, that was concentrated on these specific groups of genes. This rapid evolution in transcription factors occurred only in humans."
"For 30 years scientists have suspected that gene regulation has played a central role in human evolution," said Kevin White, PhD, associate professor of genetics and ecology and evolution at Yale and senior author of the study. "In addition to lending support to the idea that changes in gene regulation are a key part of our evolutionary history, these new results help to define exactly which regulatory factors may be important, at least in certain tissues. This helps open the door to a functional dissection of the role of gene regulation during the evolution of modern humans."
To measure changes in gene expression from different species, White and Gilad developed the first multi-species gene array. This allowed them to compare the level of expression of more than 1,000 genes between humans, chimps, orangutans and rhesus macaques--representing about 70 million years of evolution. To make the samples comparable, the researchers studied tissue from the liver--one of the most homogeneous sources--from five adult males from each of the four species.
They focused their search on expression levels of two sets of genes, those that remained largely unchanged across all four species, suggesting that there was little room--or need--for improvement, and those that changed most dramatically, usually in the human lineage--an indication of powerful incentives to adapt to a changing environment.
Of the 1,056 genes from all four species, 60 percent had fairly consistent expression levels across all four species. "The expression levels of these genes seem to have remained constant for about 70 million years," the authors wrote, "suggesting that their regulation is under evolutionary constraint."
Many of these genes are involved in basic cellular processes. The authors suggest that altering the regulation of these fundamental and ancient genes may be harmful. In fact, five of the 100 most stable genes have altered expression levels in liver cancer.
When they also looked for human genes with significantly higher or lower expression levels, they found 14 genes with increased expression and five with decreased expression. While only 10 percent of the genes in the total array were transcription factors, 42 percent of those with increased expression in humans were. None of those with lower expression were transcription factors. This pattern, the authors note, is consistent with "directional selection."
Previous studies have found that many of these same genes have also evolved rapidly in humans, accumulating changes in their coding sequence as well as in expression rates. "Together," they add, "these findings raise the possibility that the function and regulation of transcription factors have been substantially modified in the human lineage."
This is a very efficient way to make big changes with very little effort, according to Gilad. By altering transcription factors, the entire regulatory network can change with very few mutations, increasing the impact and minimizing the risk.
"The big question," he said, "is why are humans so different? What sort of changes in the environment or lifestyle would drive such a rapid shift in the expression of genes--in this case in the liver--in humans and in no other primate?"
Part of the answer, he suspects, is rapid alterations in diet, probably related to the acquisition of fire and the emerging preference for cooked food. "No other animal relies on cooked food," he said. "Perhaps something in the cooking process altered the biochemical requirements for maximal access to nutrients as well as the need to process the natural toxins found in plant and animal foods."
This is just the first of a series of similar studies, said Gilad, that will look at changes in gene expression over evolutionary time. The next steps are to look at larger arrays of genes and to focus on other tissue types.
Additional authors include Alicia Oshlack, Gordon Smyth and Terence Speed from the Hall Institute in Parkville, Victoria, Australia. The study was supported grants from the Keck Foundation, the Beckman Foundation and the National Human Genome Research Institute to Professor White.
At these rates only the super rich can afford to get sick. Should the rest of us then fold our tents and simply prepare to suffer and or die? As an attorney, I understand clearly that corporations are in the business of making money and that their loyalties lie with their shareholders. But patients are not consumers and life saving or life restoring drugs are not commodities like cars. While many of us require a car in order to get to and from work or even to do our work, the car, as long as it runs and is safe, can be second hand, old, dented, whatever. That does not apply to drugs, especially drugs that can make the difference between life and death, or working or not working, or comfort or pain. It seems to me patently unethical to put the profit motive ahead of the human purpose. But so long as we allow industry to change the language to “consumer” and “product,” then the argument for more patient friendly approaches will fall on dead ears.
Corporations may not have a heart and a soul but as ethicists we must begin to change the vocabulary and dialogue to bring about affordable drugs along with accessible health care.
[Crossposted at Health Advocacyslc.blogspot.com.]
-- Alice Herb
From Technology Review this morning: The treatment begins with an injection of an unremarkable-looking clear fluid. Invisible inside, however, are particles precisely engineered to slip past barriers such as blood vessel walls, latch onto cancer cells, and trick the cells into engulfing them as if they were food. These Trojan particles flag the cells with a fluorescent dye and simultaneously destroy them with a drug.
Developed by University of Michigan physician and researcher James Baker, these multipurpose nanoparticles -- which should be ready for patient trials later this year -- are at the leading edge of a nanotechnology-based medical revolution. Such methodically designed nanoparticles have the potential to transfigure the diagnosis and treatment of not only cancer but virtually any disease.
Eight months ago the Food and Drug Administration (FDA) approved a pocket-watch-sized device billed as "a pacemaker for the brain," the newest cutting-edge treatment for as many as 4 million adults whose severe depression is not relieved by psychotherapy, drugs or even shock treatments.Since then, more than 550 Americans have undergone surgery to have a vagus nerve stimulator (VNS) implanted in their chests to activate parts of their brains. However, the only rigorous clinical trial of the device -- which is approved to treat severe epilepsy -- failed to demonstrate effectiveness in alleviating depression.
What happened to evidence-based medicine?
Monday, March 20, 2006
New evidence unearthed by scientists at the Food and Drug Administration, Duke University and other centers are looking into the possibility that dopamine, which is associated with a host of addictive behaviors, may turn some patients into obsessive pleasure seekers.
In a related matter, AJOB guest bloggers Christina Persaud and Yang Liu, do an excellent post on the ethical issues relating to nootropic and brain enhancement drugs.
Sunday, March 19, 2006
How do the children born of these lists fare? A continuing study of a group of children in England, who were conceived by single women using donor sperm concludes that so far they are healthy and well adjusted. But the long-term questions of how these children will fare or about the different experiences of girls and boys have yet to be answered.
In a related story on CBS' 60 Minutes, an estimated 30,000 children per year are born in this country to mothers who have been artificially inseminated with sperm from an anonymous donor. Most of these children grow up never knowing their biological father — but now, with the help of sperm bank records and the Internet, some of them are finding half-brothers and half-sisters they never knew they had, who were sired by the same anonymous donor, forging family ties they never knew existed and re-defining the family relationships.
The change in policy is being recommended by the American Red Cross, the American Association of Blood Banks and America's Blood Centers, which collect virtually all the blood used for transfusions nationwide.
Saturday, March 18, 2006
Friday, March 17, 2006
Thursday, March 16, 2006
Nonetheless, this report comes after calls for more transparency regarding drug trial results as it is evident that drug companies are neither legally required nor ethically compelled to make all the data publicly available. In fact, according to an article published in the New England Journal of Medicine last year, several major pharmaceutical companies do withhold important details about clinical drug trials. Although a clinical trial registration website exists to monitor and track clinical trial results, it by no means makes it mandatory for drug companies to make public all findings from such trials.
So what went wrong in this London trial? Was it just a fluke, a drug that may have been safe in animals but evoked a negative reaction in humans? Or were the correct procedures not followed, resulting in the human administration of a drug that had not yet been declared safe for testing in humans? Authorities are now looking into the testing procedures: watch this space.
Wednesday, March 15, 2006
The theory, first put forward by researchers at Southampton University, is that the fetus responds to an adverse environment by re-setting its growth plans to prepare for a life in a deprived environment. But if that environment turns out not to be deprived it is not best equipped to survive. Fearing that life outside the womb is going to be as deprived as it is inside, the fetus may, for example, create a level of insulin resistance that allows survival in times of famine through efficient storage of fat in rare times of plenty. But in a postnatal world of constant plenty, that set-up would lead to a greater risk of obesity, diabetes and heart disease. Research shows that babies conceived during the Dutch famine (1944-1945) were more prone to heart disease and obesity.
Most human disease is the result of the interaction of genetic susceptibility and environmental factors. While most research has looked at environmental effects after birth, studies at Southampton University and elsewhere claim that the 266 or so days from conception to birth is the time when much of what will happen during the decades ahead is determined. The mother’s diet, hormonal changes, changes in the placenta, maternal exposure to disease and toxins and the general weight, fitness and lifestyle of the mother are all said to contribute.
Just months after Korean science’s shooting star Hwang Woo-suk fell from grace after confessing that most of his research was actually fabricated, the international science community is shaken by another scandal surrounding one of the leading figures in cloning research.
Ian Wilmut, the English researcher who started the current frenzy about cloning when he stunned the world with Dolly, a cloned sheep, in 1996, admitted before an employment tribunal at the University of Edinburgh that he did not conduct the experiment after all. Now several parties are trying to take credit for the scientific breakthrough.
Professor Wilmut of Roslin Institute admitted this week that he only played a supporting role in Dolly’s creation, and that most of the credit should instead go to his colleague Keith Campell, who co-authored a paper about Dolly in the prestigious Nature magazine in 1997.
The Verichip is being aggressively marketed by its manufacturer, which is targeting Washington to be the first metropolitan area with multiple hospitals equipped to read the device. Some doctors are welcoming the technology as an exciting innovation that will speed care and prevent errors. But the concept alarms privacy advocates. They worry the devices could make it easier for unauthorized snoops to invade medical records. They also fear that the technology marks a dangerous step toward an Orwellian future in which people will be monitored using the chips or will be required to have them inserted for surveillance.
Tuesday, March 14, 2006
Developed in partnership with the Center for Women Policy Studies, a Washington, D.C.-based
think tank, the goal of the bioethics seminar is to prepare women state legislators to take leadership positions on emerging bioethics issues in health and biotechnology. The planning meeting convenes March 21st, and it will include leaders from the fields of bioethics, medicine, law, and women’s reproductive and human rights.
“We are starting at a state legislative level because that’s where many of these complicated bioethical issues tend to emerge,” said Kathryn M. Hinsch, founder of the WBP. “We firmly believe that women’s voices need to be heard, as women are uniquely affected by issues in biotechnology and healthcare. Women carry babies, live longer than men, and are the predominant caretakers for children, the sick, disabled and elderly people. By providing women legislative leaders the support they need to champion these issues, we can help ensure that the entire spectrum of human experience is represented on these critical issues.”
In a 1993 paper, Dr. Haig first predicted that many complications of pregnancy would turn out to be produced by this conflict. One of the most common complications is pre-eclampsia, in which women experience dangerously high blood pressure late in pregnancy. For decades scientists have puzzled over pre-eclampsia, which occurs in about 6 percent of pregnancies.Dr. Haig proposed that pre-eclampsia was just an extreme form of a strategy used by fetuses, somehow raising the blood pressure of their mothers so as to drive more blood into the relatively low-pressure placenta.
Dr. Haig says that people seem to think that he must have a political agenda, but he explains that he's not talking at all about conscious behaviors -- he's just interested in these mechanisms and why they evolved.
Right now, there are 105,000 ventilators, and even during a regular flu season, about 100,000 are in use. In a worst-case human pandemic, according to the national preparedness plan issued by President Bush in November, the country would need as many as 742,500.
To some experts, the ventilator shortage is the most glaring example of the country's lack of readiness for a pandemic.
"This is a life-or-death issue, and it reflects everything else that's wrong about our pandemic planning," said Dr. Irwin Redlener, director of the National Center for Disaster Preparedness at Columbia University. "The government puts out a 400-page plan, but we don't have any ventilators and there isn't much chance we're going to get them."In a pinch, ambu bags can be used (which I found 12 of on EBay), but they would be be insufficient for a pandemic.
The article, "The Art of Pimping" was published in the Journal of the American Medical Association in 1998 and then the website Neonatology on the Web, picked up the article in 2005: it suggests (tongue-in-cheek) that every 'newly appointed attending must teach himself how to pimp.'
The question is does grilling medical students with questions make them into better doctors? How do we, as patients, benefit from such a bizarre practice?
Monday, March 13, 2006
The ban forbids abortions in all circumstances, including rapes and familial copulation or, in other words, incest. The only exception is in the case where a woman’s life is in danger, which is yet to be clearly defined. Steinem says this legislation was passed without giving South Dakotans the chance to vote on the issue.
While the new law passed by twelve votes in the state Senate (23-12), Steinem believes the government is trying to gain control over a woman’s reproductive freedom. She also took a stab at the media for their inaccurate and minimal coverage of the legislation and the Bush administration’s policies on birth control and abortion.
Read more at seattlepi.com
"This is not like 'Star Trek' science," said Rabbi Brander, a dean at Yeshiva, which has the largest Orthodox rabbinical seminary in the country. "This is stuff that comes up every day. And if the rabbi doesn't understand reproductive technology he can't answer the questions effectively. If he doesn't know the Jewish law he can't answer them, either."
The story quotes Adrienne Asch, who notes (here and in a number of thought-provoking journal articles) that there is a moral difference between abortion for general reasons that apply to the pregnant woman (her life plans, her health, etc.) and reasons specific to that particular fetus. On her view, women have the right to choose whether and when to give birth--but they ought not have the right to choose to abort on the basis of fetal characteristics. One argument against prenatal testing is that it's the beginning of a slippery slope--today it's Down syndrome, in some places it's (already) sex, tomorrow it might be intelligence or height or some other characteristic. Basing abortion decisions on a single characteristic is, Asch and her coauthors claim, confusing the part with the whole--seeing only that characteristic and nothing else. They also note that, in many cases, parents may be basing their decisions on an inaccurate or incomplete understanding of what it's really like to raise a disabled child. Moreover, they say, entering parenthood isn't like (and shouldn't be like) shopping: we should take what we get.
Another question worth considering, mentioned only briefly in this article, is whether there already exists a pro-abortion bias in the medical community in cases where genetic abnormalities are identified through prenatal tests. If this bias does exist--and my sense is that it does, at least in the minds of some physicians--are women really free to choose?
Friday, March 10, 2006
The authors explain that if military men in gas masks invade people’s homes and communities the reaction will be panic and mass hysteria. In order for such a government response to run smoothly McGee and Caplan suggest educational classes and town meetings where officials explain what will need to be done if Avian Flu spreads widely to humans.
Read more: Arthur Caplan and Glenn McGee on Bioethics at timesunion.com
Thursday, March 09, 2006
The National Center for Men has prepared a lawsuit -- nicknamed Roe v. Wade for Men -- to be filed Thursday in U.S. District Court in Michigan on behalf of a 25-year-old computer programmer ordered to pay child support for his ex-girlfriend's daughter.
The suit addresses the issue of male reproductive rights, contending that lack of such rights violates the U.S. Constitution's equal protection clause.
The gist of the argument: If a pregnant woman can choose among abortion, adoption or raising a child, a man involved in an unintended pregnancy should have the choice of declining the financial responsibilities of fatherhood. The activists involved hope to spark discussion even if they lose.
Concerned feminist representatives have joined together on this common ground, outraged by the casual attitude of the biotech industry towards the female body. Like-minded leaders and groups from around the world are invited to join a list which already includes representation from the USA Europe and Asia.
(hat tip to Jennifer Lahl)
(Photo: Duncan Andrew, The Witness)
I have a question I’d like answered: Do you get female gnomes? There seems to be some confusion around this point, as the Cambridge Advanced Learner’s English Dictionary defines a gnome as a very small old man with a long beard and pointed hat. But other accounts and many garden gnome displays lend testimony to the fact that there are indeed both male and female gnomes.
Which brings me to the issue I want to raise, my point(ed hat) of contention, as it were. Having been alerted to the issue of garden gnome liberation by a cutting-edge journalistic piece appearing in our local newspaper this week, I did some investigation into the phenomenon. And what I found was alarmingly reflective of the discrimination perpetuated against women in (real) society.
As reported in The Witness this week, “garden gnome liberation is a worldwide phenomenon…a political movement dedicated to liberating gnomes from the gardens in which they are shackled…removing gnomes from gardens and either taking them out to the woods to release them or smashing them to set their spirits free.” A (g)noble cause, and one taken up in earnest by liberation movements around the world – like the Free the Gnomes group in the United States.
But if one looks more closely at the reports and photographic testimonies of the struggle for gnome civil liberties and rescue attempts around the world, one notices that the gnomes that are liberated all share one common characteristic: they are all male gnomes. What about the female gnomes? Could these liberation fronts be operating on the assumption that women are more contented to stay ‘shackled’ in floral domesticity, while men have the biological need and moral right to be set free, to run wild?
Wednesday, March 08, 2006
heart attacks might be a risk for coffee drinkers with a common genetic trait that makes caffeine linger in their bodies. In a study published in the Journal of the American Medical Association, researchers found that individuals with a certain genetic profile that were "slow metabolizers" of caffeine -- slow-metabolizers, those who drank two or more cups of coffee daily were at least 36 percent more likely to have a nonfatal heart attack than those who drank little or no coffee.
How do you know if you're a slow metabolizer or fast metabolizer? Currently, there's no easy way to know if you're a fast or slow caffeine metabolizer. Staying awake all night if you drink coffee in the afternoon doesn't mean you're a slow metabolizer -- there is a genetic test that could answer the question is used in research, but is not commercially available at this time.
So, in the meanwhile, I'll guess I'll take my chances and enjoy my morning java ritual.
The AMA is trying to call attention to underage drinking among women because their bodies process alcohol differently and put them at greater risk for health problems -- Sizable numbers reported getting sick from drinking, and blacking out and engaging in unprotected sex or sex with more than one partner, activities that increase their risks for sexually transmitted diseases and unwanted pregnancies. The AMA said the findings highlight the need for alternative spring break activities.
Tuesday, March 07, 2006
Traditional notions of personhood usually require humanity, but if we're still evolving then perhaps we should be considering evolving notions of personhood. Which brings us to another interesting question: should be trying to control our evolution (and, in fact, haven't we already have by so many improvements in medical technology and health care, at least in this country) or should we be letting nature takes its course?
Dana Reeve, best known for her tireless efforts in supporting her late husband, Christopher Reeve, and their support of stem cell research to find a cure for paralysis, died yesterday of lung cancer.
She served as chairwoman of the Christopher Reeve Foundation and founded the Christopher and Dana Reeve Paralysis Resource Center.
Kathy Lewis, president and CEO of the foundation, said "Dana will always be remembered for her passion, strength and ceaseless courage that became her hallmark... Along with her husband, Christopher, she faced adversity with grace and determination, bringing hope to millions around the world."
She is survived by her father, Dr. Charles Morosini; sisters Deborah Morosini and Adrienne Morosini Heilman; two stepchildren, Matthew and Alexandra; and her son.
Monday, March 06, 2006
As we posted before,
Significantly, what antiabortion legislation requires of women is quite different from what child-support legislation requires of delinquent fathers. To be sure, such fathers must pay child support, but they are never forced to what lawyers call “specific performance.” They aren’t required by law to change diapers, give baths, prepare and serve meals, help with homework, or take their children to soccer practice. All unwilling fathers have to do is pay up every month. Specific performance, in fact, is seen as a form of servitude that may lawfully be required only of conscripts when there is a clear and present danger to the state. It may not be imposed even on convicted felons. If a drunk driver smashes into your house, he might have to go to prison or (under certain victim compensation laws) pay for damages, but he doesn’t have to repair your brickwork or replace your broken door with his own hands. If your architect breaks her contract with you by failing to produce the agreed-upon blueprints, the court can impose a fine, but it can’t make her sit down at her drafting table and do the promised work.
And that, when all is said and done, is the difference the
Way to go, Hilde!
US Representative Maurice D. Hinchey (Democrat- New York), "said while the agency insisted that it demanded that drug makers prove their medication safe, those demands 'continue to be blatantly ignored by the pharmaceutical industry.'"
In reply, Dr John Jenkins, director of the FDA Office of New Drugs, "emphasized that only 5 percent of promised drug trials were officially considered 'delayed.' In many cases, trials have been pending for more than a decdade but are not considered delayed because the agency never insisted on a specific timeline for them."
Fellow blogger Roy Poses has a good comment on this story:
I agree that potentially beneficial drugs should be put on the market as soon as possible with the least red-tape. Randomized controlled trials that have adequate statistical power to determine if a drug has benefits when compared to a placebo may not have enough power to determine all its important adverse effects. Thus it may make sense, when a drug offers important benefits beyond any treatment currently available, to allow it on the market without complete safety information, and then to require post-marketing studies, with more statistical power (but perhaps also with more methodologic biases) to assess its adverse effects. But patients and physicians need to know about the all important possible hazards of potentially beneficial medicines to make optimal decisions about whether to use them. So it is crucial that these post-marketing studies get done as quickly as possible.
I don't understand why the FDA has been mandating these studies, but not mandating any deadlines for their completion. Patients and physicians are ill-served by delays (whether officialy defined or not) in accomplishing these studies.
If pharmaceutical companies really want to increase their trustworthiness to patients and physicians, they ought to consider completing all pending post-marketing studies expeditiously. And in my humble opinion, the FDA needs to hold pharmaceutical companies accountable for their failure to complete such studies in reasonable amounts of time.
Date: 06-14-04 22:37
We - Nancy M.P. King and Ken Kipnis - have been doing research on the ethics of waived-consent clinical studies now permitted under 21 CFR Part 50. Such a study is underway: a well-publicized multi-center trial, sponsored by Northfield Laboratories and testing a hemoglobin-based oxygen carrier (PolyHeme) on trauma victims. One of us - NK - had noticed a possibly serious problem that seemed to have been missed, and Robert Orr, a physician evaluating the PolyHeme protocol at the University of Vermont, contacted KK about the same issue. This posting is a request for comments and information that might throw light on the concerns we set out below.
The Northfield protocol provides that trial subjects - trauma patients in hemorrhagic shock who are being treated by EMTs - randomly receive either saline solution or PolyHeme. Enrollment occurs in the field under the waived-consent exception, before arrival at the emergency department. The research subject/trauma patient is likely to be in a medically exigent circumstance and incapable of consent, either because of the injuries or because of the gravity of the situation and the complexity of the consent process. Apart from slowing blood loss and replacing fluids, hemorrhagic shock is not satisfactorily treatable in the field.
Once at the hospital, efforts are to be made to secure consent for continued participation either from the patient/subject or a legally authorized representative. However if formal withdrawal from the study does not occur, participation continues by default during a 12-hour period in the hospital. Patients/subjects in the control group receive standard treatment: saline and blood as needed. However patients/subjects in the experimental group continue to receive PolyHeme instead of blood for oxygen delivery: up to six units of PolyHeme for up to 12 hours, at which point their participation in the trial ends.
The study can be divided into two phases. The first (PolyHeme vs. saline) occurs in the field. The second phase (PolyHeme vs. blood) occurs for up to 12 hours after hospital admission.
We believe it is a serious problem that the special circumstances that justify waiver of consent in the field cease to obtain shortly after admission to the hospital. After they arrive, the patients/research subjects can be typed and transfused, complying with a standard of practice not available to EMTs. Provided that certain other conditions are satisfied, we accept that the use of an investigational product like PolyHeme, instead of saline, can be justified when blood is unavailable (as in an ambulance) and the medically exigent patient/subject cannot consent. But this same investigational procedure becomes deeply problematic if the optimal treatment - blood transfusion - is available but being experimentally withheld without consent.
We believe that, at a minimum, it is obligatory to separate the field trial (PolyHeme vs. saline) and the clinical trial (PolyHeme vs. blood). We think it is an ongoing mistake to be piggy-backing the latter onto the former, with its much weaker consent requirements.
Consider that it is inevitable that some hospitalized patients/research subjects on PolyHeme will die during the critical 12-hour interval when blood is available but being withheld. We expect that plaintiffs' attorneys will scrutinize these deaths in efforts to ground claims of liability. Putting the point most dramatically, these people will have died while being denied an available, standard medical treatment (blood transfusions) following unconsented-to enrollment in a research study. Despite the good results obtained in earlier trials, the use of PolyHeme is still an investigational procedure that can only be substituted for established practices with consent (except under circumstances that plainly do not obtain in the hospital setting).
We are aware of the risks associated with the use of allogeneic blood and appreciate that the availability of a safer oxygen carrier will be a medical advancement. But even though blood is less than ideal, it doesn't follow that it is "unsatisfactory" under the Federal Regs. If it did follow, the waiver could be applied whenever an investigator was sufficiently impressed by an experimental treatment that promised superiority to a less-than-perfect standard treatment. Hemorrhagic shock can be treated in the hospital using blood, though this standard intervention may not be as safe and effective as PolyHeme may someday be definitively shown to be. Of course there is a need for further clinical research comparing PolyHeme and blood, but only with the consent of the research subjects.
We have puzzled over the 12-hour clinical phase of the trial. Emergency departments participating in the Northfield study will typically receive patients/subjects less than one hour post-trauma. But the study is designed to mimic a 12-hour period without access to blood. Unlike remote areas and ships (which do not seem to be participating in this study), 12-hour delays are not common problems in the communities where the studies will be done. So why include this troubling feature? We believe it reflects the circumstances of combat-wounded soldiers when evacuation to field hospitals is impossible. The military could plainly benefit from this new technology, once it is approved. If military applications are the reason for the clinical phase of the study, than the additional risks imposed upon hospitalized civilian trauma victims are intended to benefit, neither the patients/subjects nor those subsequently injured in their communities but rather, soldiers fighting overseas. While both of us endorse the obligation to provide the highest-quality care to injured American troops, we think that duty cannot justify departures from ethical principles governing research on non-consenting civilian human subjects.
These reservations have already been communicated to Northfield but there has been no reply. Both of us are intent on keeping our minds open and that is why we post this message now. We welcome comments and suggestions that can throw light on the concerns we have raised above.
Kenneth Kipnis, Ph.D. (University of Hawaii)
Nancy M.P. King, J.D. (University of North Carolina)
A special issue on the Northfield trial will be forthcoming in AJOB with two pieces by King, Kipnis, and Nelson; they also published an article in the March issue of IRB, on problems that have emerged involving oversight of the PolyHeme study: "Trials and Errors: Barriers to Oversight of Research Conducted un ther Emergency Research Consent Waiver."
Sunday, March 05, 2006
A UK report claims that since 1994, 18,000 stem cell patents, two-third in the US, have been issued. This is described as a “patent thicket problem” and seriously slows the pace of innovative research and it promises costly therapies since companies want to recover money spent at the development level. Goozner wonders whether all grant recipients could agree to donate exclusive license to a common patent pool supervised by a new non-profit organization set up for that purpose. Patent pools have worked in other technologies, like open source software. Patent pools could also work in biomedicine.
While the article concerns developing new therapeutics in the advanced industrial world, it is applicable to developing drugs for neglected diseases.
Friday, March 03, 2006
Last year, about 80 bills in 20 states sought to cut noncitizens' access to health care or other services, or to require benefit agencies to tell the authorities about applicants with immigration violations. Arizona voters approved such a requirement in 2004 with Proposition 200. Virginia has barred adults without proof of citizenship or lawful presence from state and local benefits. Maryland's governor excluded lawful immigrant children and pregnant women from a state medical program for which they had been eligible.
Mean-spirited and short-sighted is the phrase that comes to mind.
Not Indians, apparently: An article in Wired by Jennifer Kahn called A Nation of Guinea Pigs, describe how drug companies are conducting clinical trials in South Asia, using tens of thousands of poor Indians as "guinea pigs."
Fellow blogger Chris MacDonald does a nice job of outlining the ethical issues:
- Drug companies pay hospitals and doctors to enroll patients in drug trials. The potential for conflict of interest is clear: hospitals and doctors, far from wealthy themselves, may succumb to financial temptations to enroll patients inappropriately. Of course (and with a few important differences) the same worry applies here in North America.
- Most of the people being enrolled in trials are poor, illiterate, and culturally deferential to doctors. Their ability to give free and informed consent is questionable.
- Most of the drugs being tested are drugs that are irrelevant to the health needs of a nation like India; they're mostly medicines (like blood-pressure drugs) aimed at the North American & European markets.
Kahn points out that the path of medical progress is strewn with cases of questionable ethics, desperate practices, and misguided experimentalism, if not outright exploitation. And since patients with the fewest options are invariably the ones most likely to try (or be forcibly volunteered for) risky new treatments, be it an artificial heart, an unproven pill, or a radical lobotomy, they're also the ones who bear the brunt of medicine's experimental nature. In this light, outsourcing trials to a country where decent medical care is scarce, and medication scarcer, is just the globalization of an old equation. Can this really be justified?
Photo source: http://www.sights-and-culture.com/India-country/India-village1.jpg
Thursday, March 02, 2006
The return of the Olympics has renewed questions about the use of drugs and medical science to enhance athletic performance. In the last Winter Olympics in Salt Lake City, the Nordic skiing and cross country skiing teams were beset with doping scandals. The biennial outbreak of doping tests, charges, lies and expulsions leads naturally to the question about the ethics of using drugs to improve performance. While improved technology has given us the ability to detect the subtle, stealthy drugs, the same technology is also allowing for the development of subtler, stealthier drugs. Caplan argues that most of these performance-enhancing drugs are dangerous, risky and unsafe to use and using them to cheat is wrong from a normative point of view.
Caplan contends that, at the end of the day, integrity, as much as technology, will keep the Olympics drug-free. But, if “your countrymen only see gold medals as making the competition worthwhile, and if you yourself are competing with one eye on the opposition and the other on your endorsement contract, then integrity is in trouble.” If fame, honor, and money go only to those who cross the finish line first, then no matter what, the athletes will cheat. Public opinion, as in you and I, are as much responsible for doping in Olympics as unethical athletes and coaches.
But recent events raise the question: does the tolerance towards the gay community reflected in South Africa’s legislation on gay marriage extend to the daily, lived experiences of gay men and women? Tolerance, acceptance, and personal freedom are themes far removed from the events that have made headlines this year regarding gays and lesbians.
First, there was the South African National Blood Service’s (SANBS) decision to exclude all sexually active homosexual men from donating blood, following a statement asking gay people not to donate blood if they have had sex (safe or not) in the past five years, which sparked outrage among the gay community. While the SANBS stuck by its decision, claiming that “international medical reports indicate that men who have sex with men show increased risk of infection with HIV and other blood infections,” members of gay activist and human rights groups argued that the SANBS’s position was not based on local HIV statistics and contributed to the stigmatization and marginalization of the gay community.
If the comments of some African leaders are anything to go by, being gay and black invites more palpable discrimination. Zimbabwe’s president, Robert Mugabe, for example, “called homosexuals ‘worse than pigs and dogs’ and a Namibian minister urged a group of police constables to ‘eliminate’ gays and lesbians from the country.” Even within the borders of South Africa’s democracy and liberal constitution, black, gay individuals face discrimination, prejudice and ostracism daily. And, more than occasionally, violence.
Being black, gay, and female apparently makes you a target for even more savage acts of homophobic hatred: early last month, a 19-year-old lesbian from the Khayelitsha township was clubbed, kicked and beaten to death by a mob of young men. And the slow reaction to her murder amongst the media and police has not been met with much surprise by township gay men and lesbians, who face verbal and physical abuse, rape and intimidation on a daily basis, and for whom “police inertia over hate crime is par for the course” (Marianne Thamm, “Not just another murder” in print edition of Mail&Guardian, Feb 24 – March 2).
Here is another problem generated by a patriarchal belief system, it seems. According to Dawn Betteridge, director of the Triangle Project, “…adopting the clothing and behaviour typical of a ‘butch lesbian’ or the ‘effeminate male,’ is perceived as a threat to masculine dominance…Lesbians who mimic men are seen to be challenging male superiority. Rape and violence against lesbians is common…men who perpetrate such crimes see rape as curative and as an attempt to show women their place in society.”
“Corrective rape, where men try to ‘cure’ a lesbian by forcing her to have sex, still happens, according to gay activists.” Nineteen year-old Zoliswa Nkonyana did not receive this cure. Instead, she, and her lesbian ‘threat’ to masculinity, were simply eliminated. Perhaps the legal team for members of the mob who beat her to death will argue in their defense that, for these youths, ‘prevention’ seemed better than cure...
Wednesday, March 01, 2006
So query, at a time when policymakers have made reducing unintended pregnancies a national priority, and there is such a huge push to restrict access to abortions, why this schizophrenic approach? As Sarah Brown, director of the nonpartisan National Campaign to Prevent Teen Pregnancy, said "The most powerful and least divisive way to decrease abortion is to reduce unintended pregnancy... "If we can make progress reducing unintended pregnancy, we can make enormous progress reducing abortion."
"At every stop I am reminded that whether it is the environment, energy policy, science education or public health, the American public expects our government to make the best decisions based on the best available evidence...
Time and again in my travels I am asked, "What happened to derail Plan B?" I have to answer honestly that I don't know. The manufacturer agreed to take the "controversial" issue of young teens' access to emergency contraception off the table in 2004; now we are talking only about adult access to safe and effective contraception. Over 98 percent of adult women have used some form of contraception. So what is the objection?
Perhaps it is that posed by a small but vocal political minority that insists on labeling emergency contraception as abortion, or at least confusing the two. One of the main questions I hear is, "Does this pill cause an abortion?" In fact, the only connection this pill has with abortion is that it has the potential to prevent the need for one. Emergency contraceptive pills work exactly the same way as other birth control pills, and they do not interfere with or harm an existing pregnancy. Emergency contraception is simply a higher dose of daily birth control pills; it is not RU-486, the "abortion pill." Indeed, emergency contraception has been used as a method to prevent unintended pregnancies for decades by women who had physicians advise them on how many pills in their regular pill pack to take. So people who are comfortable with oral contraceptives as methods of contraception should be just as comfortable with emergency contraception."
It is a disturbing commentary that such a small but vocal group has such pervasive influence that it can effectively cause well-educated individual to ignore scientific evidence... how does one combat this?