Norms, Values, and Science

In 2000 Vioxx promised arthritis sufferers a way to ease pain with less trauma to the stomach than naproxen, an older and cheaper drug in such products as Aleve. Merck, the respected drug giant that created Vioxx, funded the VIGOR study, headed by Claire Bombardier, Director of Rheumatology at the University of Toronto, and this study was published by the prestigious New England Journal of Medicine in November 2000 (Claire Bombardier, et al. “Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients with Rheumatoid Arthritis,” NEJM Volume 343:1520-1528.) The study revealed that Vioxx users had four times the rate of heart attacks as naproxen users. The higher risk came about, the study explained, because naproxen protected the heart, not because Vioxx hurt it. But the authors have been accused of withholding evidence about the drug's heart risks by editors of the New England Journal of Medicine. It was found that three heart attacks out of a total of 20 were omitted from the data just two days before the article was published. Were they included, the study would have revealed an even higher risk of heart attacks among Vioxx users. Merck stopped selling Vioxx last year because another study found that patients taking the drug for more than 18 months doubled their risk of heart attacks and strokes. Since then more than 7,000 people have sued Merck, blaming Vioxx for injuries or deaths. Recently, Dr. Gregory D. Curfman, Executive Editor of the NEJM, said that he should have been more aggressive in challenging the research when it was first submitted for publication. An editorial by Gregory D. Curfman, Stephen Morrissey, and Jeffrey M. Drazen, the editors of NEJM, appears in print in the today's issue of NEJM.

This incident is the latest to raise troubling questions about selective disclosure of data in industry sponsored clinical trials. To be sure, there will always be risks and contraindications with any medication, but health care regulators, providers, and patients can't assess those risks if they aren't given all the information. (See the latest regulatory contibution, note this registry is voluntary.) Important questions that emerge in this case are ones that Jerry Avorn asks us to think of as “pharmacoepistemological”. Epistemological questions are those that involve the nature and the scope of knowledge, truth, and justification of claims. Thus pharmacoepistemological questions have to do with how it is that we-- regulators, patients, and providers-- know that a drug is effective and safe enough to use. How do we --regulators, patients, and providers--get drug information and how can we determine if the information is trustworthy? It is the norm that the most trustworthy sources are scientific articles written in prestigious peer-reviewed journals by experts in the field who work at accredited institutions of higher learning. But in this procedure there is the assumption that people who submit the manuscripts will be telling the truth and not fudging data.

The fraudulent data announcing the creation of human embryonic stem cell lines that were submitted to and published by the world respected journal Science again reminds us that we get to know about empirical data as they are presented to us by trustworthy sources. But all along the chain of transmission of data, from lab investigator to department chair to external funding agency to the editorial board of the journal, we find human beings. And human beings have interests. Bias and interest are not the same thing. Bias can occur because of some interest or other that is contrary to the interest of the truthful and full transmission of data. The problem is not that there are values and interests inherent in the scientific project. This in itself does not make science “subjective." The values of truth telling and full disclosure are essential to good science. Thus, it is the kinds of values and human interests that affect the process that invite scrutiny. We have to ask what values are being advocated and whose interests are being served.

The Bioethics-meets-Jerry-Springer debacle (otherwise known as the Korean Stem Cell Fiasco)

I have been watching in horrified silence and disbelief as the entire story of Hwang Woo Suk and the deceptions surrounding his research and so-called 'findings' has unfolded. The story has all the elements a bad Jerry Springer episode: lies, deceit, betrayal -- the only that is missing is someone ripping off their clothing. And just when you think things can't get much worse, another layer of untruthfulness is revealed; colleague and fellow blogger Glenn McGee is right: it's like peeling an onion -- and it's enough to make you cry. Hundreds of blogs are following the story -- and not surprisingly, opponents of stem cell research are feeling righteous indignation and justification. The consequences of this Hwang's actions will be felt for a long time to come: public faith has been lost and future stem cell research will face heightened scrutiny. The best thing that can come from this fiasco is facing up to what we must learn from this painful lesson -- the importance of teaching and enforcing truthfulness and transparency in research.

The Controversial Virgin Territory

"It's the ultimate gift for the man who has everything." This is what Ms. Yarborough, a 40 year old medical assistant felt about her recent 17th anniversary gift - a surgery to reattach her hymen, making her appear a virgin again - to her husband. This controversial medical procedure, hymenoplasty, originally intended to protect females in the Middle East and Latin America, is gaining popularity in the U.S. for cosmetic reasons. “Last year, 9.2 million cosmetic procedures were performed in the U.S., 24% more than in 2000, according to the American Society of Plastic Surgeons.” The booming popularity of this procedure seems to reflect a wider trend of cosmetic surgery’s increased visibility and society’s increased acceptance of it. Visibility is achieved by various means-hymenoplasty adverts can be seen in magazines, local newspapers, online, and even on billboards. Troy Robbin Hailparn, an obstetrician and gynecologist, advertises vaginal cosmetic surgery on 23 billboards around San Antonio. EdwardJacobson, a Greenwich, Conn., OB-GYN, offers international patients vaginal-makeover “packages” that include airfare, limousine travel and hotel accommodation. "Revirgination" can cost over $5,000, but at Ridgewood Health and Beauty Center, a spa and cosmetic-surgery center in the New York City borough of Queens it costs as little as $1,800. The center's owner, Cuban-born Esmeralda Vanegas, has given away hymenoplasties on a Spanish-language radio station. Ms. Vanegas isn't a doctor and doesn't perform the procedure, but rather leases space to five plastic surgeons.

However, not everyone is excited by such prospects. Many religious groups that value abstinence until marriage say hymen repair is a deception. Devout Roman Catholics consider sex before marriage sinful and equate female virginity with near divinity. Hymen replacement is "misleading and misguided," says Kathleen Raviele, a gynecologist and vice president of the Catholic Medical Association in Needham, Mass. "The best thing is to remain chaste until marriage and then have that genuine experience on your wedding night."

For many Muslims, sexual purity, especially for women, is a way of maintaining the family’s sanctity. But Islamic law also prohibits lying and frivolous cosmetic surgery, says Uzma Mazhar, a St. Louis psychotherapist known for her Web site, CrescentLife.com, which provides Islamic perspectives on Western issues. "What people forget is that Islam teaches us to be honest and fair,"Ms. Mazhar says. "A family should think about this before they present a woman as a virgin when she's not."

Other criticisms of hymenoplasty include questions of the procedures legitimacy and safety. The ethics committee of the American College of Obstetricians and Gynecologists, concerned about the marketing of revirgination, has not taken a formal position on the matter, but has expressed concern over the lack of information in the medical literature regarding the procedure, a fact that may mean performers of the procedure are improperly trained. Marco Pelosi II, an obstetrician and gynecologist in Bayonne, N.J. had this to say about hymenoplasty: "no one used to talk about it, but that's changing," "Really, it's not like a heart transplant-it’s a very simple procedure."On the contrary, Thomas G. Stovall, a recent president of the Society of Gynecologic Surgeons, says "hymen repair is a totally bogus procedure." In general, he says, surgery marketed to improve one's sex life rarely works. As for hymen replacement, "most importantly, it doesn't make you a virgin again."

Despite this fact, women are enticed by the ability to tighten their vaginal walls and even redesign the look of their private parts; participating women often indicate that such measures were meant to boost their own confidence levels or please their partners. A 51-year-old patient-a Manhattan attorney and mother of three-had her hymen reattached her hymen and her vaginal walls tightened in 2003. "I thought it would add that extra sparkle to our marriage," says the woman. However, a 26-year-old Latin American woman who lives in New York's Queens who had a hymen repair in 2001 says it took almost two months for her to feel comfortable again. It took even longer for her to enjoy sex. Despite her discomfort, the married mother of two says she’s still glad she had the surgery. She says her husband wanted to experience intercourse with a virgin, explaining that "if a woman isn't a virgin when she gets married, a man can always put her down for that."

Such attitudes irk feminists, who say hymen repair is a manifestation of bigger social pressures that keep women subservient to men. "It comes with a whole set of norms of a macho culture," says Silvana Paternostro, Colombian-born author of "In the Land of God and Man: Confronting Our Sexual Culture." Some feminists liken hymenoplasty to female genital mutilation, a procedure that often forces women to endure genitalia alterations that Western women now pay for.

Read more: “U.S. Women Seek A Second First Time Hymen Surgery Is on the Rise And Drawing Criticism", AMY CHOZICK, THE WALL STREET JOURNAL; December 15, 2005

The Medicare drug "benefit"--benefits whom, again?

So there, I said it. This morning's story on NPR nicely illustrates two important points about the new Medicare drug benefit, which has been touted by its supporters as an improvement for elderly Americans.

Point number one: It's going to be a disaster. The people it's supposedly helping are being asked to choose from a bewildering number of plans, which can differ in cost by thousands of dollars, depending on a given person's (current!!) medications. The NPR story features an interview with a woman who does this for a living--and it takes her about an hour and a half to figure out what is the best choice for a particular person. Oh, and the tools people are supposed to use for this? The Internet. . . and while many of us know tech-savvy elders, it's simply irresponsible for the Internet to be positioned as the primary resource here. There are toll-free numbers set up for assistance, to be sure, but reports indicate that it's hard to get through to a live person. And we're not even talking yet about the actual implementation of this behemoth. Why did we do this, again? Oh, yeah--so that pharmas would have an opportunity to maximize profits. What part of "safety net" don't we understand?

Point number two: Given the inadequate support being provided for elders, guess who is supposed to leap in to fill the gap? The "adult children" of these folks, that's the plan. Let's be honest, folks: that's daughters and daughters-in-law. Just one more example of uabsolutely essential work (unpaid, "caring-centered," time-consuming, and invisible) that ends up on women's plates by fiat and assumption. Externalized costs, anyone?

More controversy on embryonic stem cell research

Embryonic stem cell research might now be more potentially viable for the UK Stem Cell Bank, which learned that samples from 150 random human embryos, far fewer than previously thought, might be able to generate materials beneficial for two thirds of the population. Embryonic stem cells can mature into various types of tissue that can potentially be used to replace “diseased or damaged tissue in conditions such as diabetes and neurodegenerative disorders.” A University of Cambridge team studying such potentialities has explained that the tissues generated from a mere ten samples of specific genetic makeup could theoretically support a UK bank. Researcher Professor Roger Pederson points out that a selective process as described would require “additional regulatory review.”

Displeased opponents say "false hope" is being raised among "desperate patients". Disregarding such criticisms, many scientists welcome stem cell research from spare IVF embryos as offering the possibility of a more cost-effective and practical alternative to therapeutic cloning. The scientific team calculated that cells from 150 random embryos would be enough to provide the best possible match for 13% of recipients, a favourable level of match for 65%, and some use for as many as 85%. Surprisingly, just 10 types of specifically selected genetic material would be enough to provide a favourable level of match for 78% of recipients.

At present the UK bank contains stem cells suitable only for research. Professor Pedersen told the BBC News website that “this research tells us is that the number of lines needed to achieve a significant clinical value is in the practical realm.” Professor Pederson also said that researchers were already working from spare IVF embryos. Dr Glyn Stacey, director of the UK Stem Cell Bank, acknowledged the importance of recent findings, but admitted researchers were still “a long way away in terms of establishing the basic cell culture methods” and do not know “whether all stem cell lines will give the full range of tissues." The charity Life argues that research had shown adult stem cells preferable to embryonic stem cells fro the purposes of treating disease. Spokesman Matthew O'Gorman said: "The UK stem cell debate is obscured by hype which only serves to raise false hope among desperate patients. “Embryonic stem cell research involves destructive experiments on tiny human beings, which is why it has been outlawed in the majority of countries worldwide.” Read more:

A Pill for Alcoholism?

NPR reported this weekend that the University of Virginia is conducting a study on a new drug to help alcoholics who are trying to quit drinking. The drug called topiramate (Topamax®) has shown some remarkable successes, but has not yet been approved by the FDA to treat alcoholics. To date, three medications--disulfiram (Antabuse®), naltrexone (Trexan®), and acamprosate (Campral®)--have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of alcohol dependence, but barely 20% of people who need them, use them. Recently, however, there has been research supporting a more central role for medications in the treatment of alcohol-seeking behavior. This behavior appears to be related neurobiologically to dopamine and other neurotransmitters that can alter dopamine function. Topiramate was originally synthesized as a potential anti-diabetic agent and was found to be similar to anticonvulsants. It used for example in the treatment of adult migraine headache. It is a GABA-receptor agonist (GABA is the predominant inhibitory neurotransmitter) and a glutamate antagonist (glutamate is a predominant excitatory neurotransmitter). In a chronic alcoholic state, GABA is decreased while glutamate and dopamine are increased. Work done in 2003 by Dr. Bankole Johnson and his team at the University of Texas at San Antonio have shown that topiramate blocks the glutamate receptors and increases the GABA effect; this combined effect produced a decrease in heavy drinking days and alcohol craving (a person can have one drink and not crave the second third, fourth, fifth, etc.) with an increase in non-drinking days.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) claims that almost 18 million people in the USA abuse or are addicted to alcohol. According to BusinessWeek, this abuse and addiction costs the USA around $185 billion a year in medical services, lost wages, and law enforcement resources. The NIAAA also claims that alcohol affects women differently than men. “Women become more impaired than men do after drinking the same amount of alcohol, even when differences in body weight are taken into account. This is because women's bodies have less water than men's bodies. Because alcohol mixes with body water, a given amount of alcohol becomes more highly concentrated in a woman's body than in a man's. In other words, it would be like dropping the same amount of alcohol into a much smaller pail of water. That is why the recommended drinking limit for women is lower than for men… In addition, chronic alcohol abuse takes a heavier physical toll on women than on men. Alcohol dependence and related medical problems, such as brain, heart, and liver damage, progress more rapidly in women than in men.” For information on alcoholism science go here.

Women's Bioethics Blog Nominated for 2005 Medical Weblog Award

Medgadget is hosting their Second Annual Medical Weblog Awards and this very Women's Bioethics Blog is a nominee. The awards are designed to honor the very best in the medical blogosphere, as decided by the readers. The categories are: Best Medical Weblog; Best New Medical Weblog (established in 2005); Best Literary Medical Weblog; Best Clinical Sciences Weblog; Best Health Policies/Ethics Weblog; and, Best Medical Technologies/Informatics Weblog. Nominations will be accepted until Friday, December 30, 2005. Polls will be open from Tuesday, January 3, 2006 and will close at midnight on Sunday, January 15, 2005 (PST).
Awards will be announced on Wednesday, January 25, 2006. Check it out and vote.
http://www.medgadget.com/archives/2005/11/the_2005_medica.html

Frozen eggs, anyone?

Interesting Slate article and blog.bioethics.net post about how a young economist at the University of Virginia found that a woman in her 20s will increase her lifetime earnings by 10 percent if she delays the birth of her first child by a year. Part of that is because she'll earn higher wages—about 3 percent higher—for the rest of her life; the rest is because she'll work longer hours. For college-educated women, the effects are even bigger. For professional women, the effects are bigger yet—for these women, the wage hike is not 3 percent, but 4.7 percent.

Do you throw--make that think--like a girl?

In this story on NPR's Science Friday broadcast yesterday, Ira Flatow and his guests talk about claims regarding gender differences in cognitive abilities. This is a panel held in conjunction with the American Psychological Association's Science Leadership Conference in Washington, DC, in a forum with DC high school students.

Nora Newcombe, a professor of psychology, says that while there is evidence of differences, there's no evidence of one sex being smarter than the other (overall). In general, women are better at writing, at memory tasks, some fine motor tasks, and speech. Men tend to be better at spatial imagery,. In general, women tend to do better with "book learning" type tasks, and men do better with "fluid tasks," meaning extracurricular learning and novel problem-solving.

Stem cell agency in California hassles court to dismiss lawsuits

Eager to progress with its stem cell project, the newly implemented California Institute of Regenerative Medicine pleaded with a judge to dismiss lawsuits that have impeded it from borrowing $3 billion to be used to fund research grants. Newly created by Proposition 71, the stem cell institute has been hindered by two lawsuits that have challenged its constitutionality and intimidated potential leaders. Filed by politically conservative groups, these lawsuits have delayed the agency’s work, according to deputy attorney general Tamar Pachter. For example, rising interest rates since the agency was first prepared to borrow have cost the state an estimated $15 million. The lawsuits question the authority and intentions of the agency’s managers, many of whom, they allege, are not state officials but employees with individual agendas. The agendas of the filers of such lawsuits have been questioned as well. One of the filers, the People's Advocate and the National Tax Limitation Foundation, which opposes abortion and the “right-to-die,” has admitted its disapproval of stem cell research, but claims its motivations are moral, not religious. The group maintains that only state officials should be able to dole out public funds.

The second lawsuit was filed by a newly created nonprofit called the California Family Bioethics Council, self-described as a “stem cell research watchdog group.” Bioethics lawyer David Llewellyn claims that the selection process, whereby elected officials and college administrators select members of the institute's Independent Citizens Oversight Committee, creates a “conflict of interest.” Human embryonic stem cells are created in the first days after conception and give rise to all the organs and tissues in the human body. Scientists hope to someday use stem cells to replacement diseased tissue. Such prospects anger many social conservatives, including President Bush, because embryos are destroyed during research. President Bush’s 2001 restriction on the use of federal money to fund stem cell work has kept the field infantile, according to scientists.

The pending litigation discourages potential leaders, fearful of the potential futility of their investments. The agency has been kept afloat and has opened a permanent headquarters thanks to a $5 million charitable donation from sound pioneer Ray Dolby and a $3 million loan from the state. Even though it has little money, the agency in September awarded 16 grants totaling $39.7 million to universities and nonprofit medical organizations in California. Rulings on the lawsuits are expected at a later date.

IVF-->slight increase in risk of birth defects

According to a new study from the University of Iowa, babies conceived through in vitro fertilization (IVF) have a slightly increased risk of major birth defects (eg, heart or muscle and skeletal defects) compared with babies made the old-fashioned way. The increase is slight--a risk of 6.2% for babies conceived through IVF, versus 4.4% for naturally conceived infants--but may be worth considering. It is not known whether the increase in risk is the result of IVF, or the result of some other factor; other characteristics of women/couples seeking IVF could account for the rise. In addition, the study addresses only congenital defects--not problems that might arise later in life. Here's the link to the abstract in PubMed.

Women's Health and Intimate Partner Violence against Women

While violence against women is recognized as a major health and economic problem, as well as a human rights issue, a lack of comparable and reliable data on root causes and magnitude has hindered public policy makers. In 1997, in order to collect such data, WHO initiated a study, the initial results of which were published last week as the “WHO Multi-country Study on Women's Health and Domestic Violence against Women”. This report is based on interviews with 24, 000 women in Bangladesh, Brazil, Ethiopia, Japan, Namibia, Peru, Samoa, Serbia and Montenegro, Thailand, and Tanzania by carefully trained interviewers. (Countries in North America and Europe were not included as they had been the subject of previous studies.) It says the percentage of women reporting having been physically or sexually assaulted, or both, in their lifetime ranges from 15% in Japan to 71% in rural Ethiopia. Alarm was expressed at this figure in regard to the spread of HIV and Aids. (See also this article.) It was discovered that violence was more prevalent in poorer countries and that women who lived there were more likely to think the violence was justified. Researcher Lori Heise said it was not clear what was behind the differences between richer and poorer countries, but many of the areas with higher rates were more rural, traditional communities where the problem had remained largely hidden: up to half of the women surveyed had never spoken of their situation to anyone. This report shows that research and policy on women’s health, and indeed promotion of women’s health, including psychological and reproductive health, must consider intimate partner sexual and physical violence against women.