How to do science
<a href="http://www.nytimes.com/2002/07/10/health/10HORM.html?ex=1027320154&ei=1&en=72fbdf8f7d93bae2 " target="_blank">Article in the Times.</a>
In summary, we've believed for years and years that post-menopausal women should take hormones to help with everything from symptoms of menopause to heart disease to osteoporosis. Turns out that the trend was started by a guy who wrote a book funded by the pharmaceutical company that sold the hormone, and the confirmation of his ideas was based on inadequate scientific studies.
When they got around to appropriate studies (i.e., with a control group) recently, they met resistance from groups who said they shouldn't use a control group because no women should be denied the benefits of the hormones <img src="graemlins/bugeye.gif" border="0" alt="[Skeptical]" /> .
As the study got underway, they discovered that the women on the hormone therapy were more likely to have cardiovascular disease, not less. So they had to stop the study early.
The only reason they had previously found that women on the hormones were less likely to have heart disease is that they were healthier to begin with - not because the hormones themselves helped them.
How many herbs and "dietary supplements," almost none of which have undergone these types of controlled studies, are causing more problems than benefits?
How many of the groups who think we should "streamline" FDA approval will take the lesson from this?
How many luddites are going to distrust science even more because they'll think that science screwed up, when in fact it's the reverse?
[quote]The new study was different from the rest because it involved thousands of healthy women and had a control group, with half the women taking dummy pills. In addition, it looked for evidence of disease like heart attacks and cancer rather than indirect indicators like cholesterol levels, which can be misleading.
"This is definitive evidence," said Dr. Deborah Grady, who directs the Mount Zion Women's Health Clinical Research Center at the University of California in San Francisco.
The tale of estrogen therapy began in 1966, when an enthusiastic doctor, Robert Wilson, wrote a best-selling book. He called it "Feminine Forever" and flew around the country promoting it, telling women and doctors alike that estrogen, the feminine hormone, could keep women young, healthy and attractive. It was just so natural ? women would be replacing a hormone they had lost at menopause just as diabetics replace the insulin their pancreas fails to make.
"At age 50, there are no ova, no follicles, no theca, no estrogen ? truly a galloping catastrophe," Dr. Wilson wrote in 1972 in The Journal of the American Geriatric Society, referring to the eggs and surrounding tissue. But, he continued, estrogen can save these women. "Breasts and genital organs will not shrivel. Such women will be much more pleasant to live with and will not become dull and unattractive."
Dr. Wilson died in 1981, but his son, Ronald Wilson, said yesterday that Wyeth-Ayerst had paid all the expenses of writing "Feminine Forever" and financed his father's organization, the Wilson Research Foundation, which had offices on Park Avenue in Manhattan.
Mr. Wilson, who lives in Cary, N.C., said the company had also paid his parents to lecture to women's groups on the book. Wyeth said it could not confirm the account because it was so long ago.
By 1975, Wyeth's product, Premarin, had become the fifth leading prescription drug in the United States, said Nadine F. Marks, an associate professor at the University of Wisconsin at Madison, who co-wrote a research paper on hormone therapy. "Even textbooks for gynecologists and obstetricians in the 1960's would explain how a woman's life could be destroyed if she didn't have estrogen in her body," Dr. Marks said.<hr></blockquote>
[quote]There was no doubt that the drugs helped many women through a difficult time when their sleep was disrupted by night sweats and their days by hot flashes.
"There is nothing else out there that addresses the symptoms of menopause," said Dr. Victoria Kusiak, vice president of global medical affairs at Wyeth.
But scientists and doctors were saying something more ? that it could be used for disease prevention.
Many were impressed by evidence from dozens of observational studies in which women who happened to take estrogen were compared to women who did not. The drawback to these studies, however, is that women who decide to take estrogen, studies have shown, tend to be different from those who do not. They are healthier, leaner, less likely to smoke. The question is, does estrogen make women healthy, or do healthy women take estrogen?<hr></blockquote>
[quote]Even as some scientists and advocates for women began arguing that at least there should be a more vigorous test of the estrogen hypothesis, it retained its power.
Dr. Stefanick said that when the new study was being planned, doctors and researchers said it was unethical because in the most rigorous studies, a group of women would be taking placebos. They would be denied the benefits of the hormones, these critics said.
All along, as hormone therapy grew in popularity, some refused to be convinced. One group, the National Women's Health Network, said it was offended by the message and questioned the data.
The message, said Cynthia Pearson, executive director of the network, "was sexist and ageist." It had a constant refrain, she added. "Stay young. Stay healthy. Stay sexually vital. Be less of a pain to your husband."
"The claims were too good to be true," Ms. Pearson said. "Each time there was anything negative about the drug, a new claim arose to keep it alive."
"The science was accurate but it was extrapolated beyond imagination," Ms. Pearson said. "We started saying: Not proven, not proven, not proven."
In 1990, when Wyeth, the leading maker of estrogen, went before the Food and Drug Administration with a request to label the drug as protective against heart disease, Ms. Pearson was there.
"We stood there and said, Hello? You couldn't approve a drug for healthy men without a randomized clinical trial. Even aspirin had to have a randomized controlled trial with healthy men," she said, alluding to the data that persuaded the F.D.A. to allow aspirin makers to market their product as protective against heart attacks. In a randomized controlled trial, patients are divided at random into groups, with each group taking a different treatment or placebo. They are considered the gold standard of scientific evidence.
The agency's advisory committee recommended that the company be able to market estrogen as protective against heart disease, but the panel was overruled by the agency, which said better data were needed.
In the end, Wyeth began a randomized controlled study that most doctors and researchers assumed would prove estrogen's beneficial effects on the heart. The study, known as HERS, involved women who had already had heart disease, a group in whom effects should be easiest to find.
At the same time, amid lobbying by women's groups and criticism by congresswomen about the lack of attention paid to women's health, Congress appropriated money for a new research initiative at the National Institutes of Health. That led to the latest huge and expensive study of hormone replacement therapy.
The emerging data from both that study, the Women's Health Initiative and HERS are sobering. HERS found that far from protecting women against heart attacks, the combination therapy actually increased their risk in the first few years of taking the drugs.
The Women's Health Initiative includes a group of women who have had hysterectomies and who are taking estrogen alone. That part of the study is continuing because the data have not shown significant risk or significant benefit from the hormone.
The other part of the study, of women taking the hormone combination, was the part that was halted. It found that if 10,000 women take the hormones for one year, eight more will develop invasive breast cancer than a similar group not taking the hormones, seven more will have heart attacks, eight more will have strokes and eight more will have blood clots in their lungs. The benefits are six fewer instances of colorectal cancers and five fewer hip fractures.
There is no one overwhelming danger, said Dr. Claude Lenfant, director of the National Heart, Lung and Blood Institute. "It is a global risk."<hr></blockquote>
In summary, we've believed for years and years that post-menopausal women should take hormones to help with everything from symptoms of menopause to heart disease to osteoporosis. Turns out that the trend was started by a guy who wrote a book funded by the pharmaceutical company that sold the hormone, and the confirmation of his ideas was based on inadequate scientific studies.
When they got around to appropriate studies (i.e., with a control group) recently, they met resistance from groups who said they shouldn't use a control group because no women should be denied the benefits of the hormones <img src="graemlins/bugeye.gif" border="0" alt="[Skeptical]" /> .
As the study got underway, they discovered that the women on the hormone therapy were more likely to have cardiovascular disease, not less. So they had to stop the study early.
The only reason they had previously found that women on the hormones were less likely to have heart disease is that they were healthier to begin with - not because the hormones themselves helped them.
How many herbs and "dietary supplements," almost none of which have undergone these types of controlled studies, are causing more problems than benefits?
How many of the groups who think we should "streamline" FDA approval will take the lesson from this?
How many luddites are going to distrust science even more because they'll think that science screwed up, when in fact it's the reverse?
[quote]The new study was different from the rest because it involved thousands of healthy women and had a control group, with half the women taking dummy pills. In addition, it looked for evidence of disease like heart attacks and cancer rather than indirect indicators like cholesterol levels, which can be misleading.
"This is definitive evidence," said Dr. Deborah Grady, who directs the Mount Zion Women's Health Clinical Research Center at the University of California in San Francisco.
The tale of estrogen therapy began in 1966, when an enthusiastic doctor, Robert Wilson, wrote a best-selling book. He called it "Feminine Forever" and flew around the country promoting it, telling women and doctors alike that estrogen, the feminine hormone, could keep women young, healthy and attractive. It was just so natural ? women would be replacing a hormone they had lost at menopause just as diabetics replace the insulin their pancreas fails to make.
"At age 50, there are no ova, no follicles, no theca, no estrogen ? truly a galloping catastrophe," Dr. Wilson wrote in 1972 in The Journal of the American Geriatric Society, referring to the eggs and surrounding tissue. But, he continued, estrogen can save these women. "Breasts and genital organs will not shrivel. Such women will be much more pleasant to live with and will not become dull and unattractive."
Dr. Wilson died in 1981, but his son, Ronald Wilson, said yesterday that Wyeth-Ayerst had paid all the expenses of writing "Feminine Forever" and financed his father's organization, the Wilson Research Foundation, which had offices on Park Avenue in Manhattan.
Mr. Wilson, who lives in Cary, N.C., said the company had also paid his parents to lecture to women's groups on the book. Wyeth said it could not confirm the account because it was so long ago.
By 1975, Wyeth's product, Premarin, had become the fifth leading prescription drug in the United States, said Nadine F. Marks, an associate professor at the University of Wisconsin at Madison, who co-wrote a research paper on hormone therapy. "Even textbooks for gynecologists and obstetricians in the 1960's would explain how a woman's life could be destroyed if she didn't have estrogen in her body," Dr. Marks said.<hr></blockquote>
[quote]There was no doubt that the drugs helped many women through a difficult time when their sleep was disrupted by night sweats and their days by hot flashes.
"There is nothing else out there that addresses the symptoms of menopause," said Dr. Victoria Kusiak, vice president of global medical affairs at Wyeth.
But scientists and doctors were saying something more ? that it could be used for disease prevention.
Many were impressed by evidence from dozens of observational studies in which women who happened to take estrogen were compared to women who did not. The drawback to these studies, however, is that women who decide to take estrogen, studies have shown, tend to be different from those who do not. They are healthier, leaner, less likely to smoke. The question is, does estrogen make women healthy, or do healthy women take estrogen?<hr></blockquote>
[quote]Even as some scientists and advocates for women began arguing that at least there should be a more vigorous test of the estrogen hypothesis, it retained its power.
Dr. Stefanick said that when the new study was being planned, doctors and researchers said it was unethical because in the most rigorous studies, a group of women would be taking placebos. They would be denied the benefits of the hormones, these critics said.
All along, as hormone therapy grew in popularity, some refused to be convinced. One group, the National Women's Health Network, said it was offended by the message and questioned the data.
The message, said Cynthia Pearson, executive director of the network, "was sexist and ageist." It had a constant refrain, she added. "Stay young. Stay healthy. Stay sexually vital. Be less of a pain to your husband."
"The claims were too good to be true," Ms. Pearson said. "Each time there was anything negative about the drug, a new claim arose to keep it alive."
"The science was accurate but it was extrapolated beyond imagination," Ms. Pearson said. "We started saying: Not proven, not proven, not proven."
In 1990, when Wyeth, the leading maker of estrogen, went before the Food and Drug Administration with a request to label the drug as protective against heart disease, Ms. Pearson was there.
"We stood there and said, Hello? You couldn't approve a drug for healthy men without a randomized clinical trial. Even aspirin had to have a randomized controlled trial with healthy men," she said, alluding to the data that persuaded the F.D.A. to allow aspirin makers to market their product as protective against heart attacks. In a randomized controlled trial, patients are divided at random into groups, with each group taking a different treatment or placebo. They are considered the gold standard of scientific evidence.
The agency's advisory committee recommended that the company be able to market estrogen as protective against heart disease, but the panel was overruled by the agency, which said better data were needed.
In the end, Wyeth began a randomized controlled study that most doctors and researchers assumed would prove estrogen's beneficial effects on the heart. The study, known as HERS, involved women who had already had heart disease, a group in whom effects should be easiest to find.
At the same time, amid lobbying by women's groups and criticism by congresswomen about the lack of attention paid to women's health, Congress appropriated money for a new research initiative at the National Institutes of Health. That led to the latest huge and expensive study of hormone replacement therapy.
The emerging data from both that study, the Women's Health Initiative and HERS are sobering. HERS found that far from protecting women against heart attacks, the combination therapy actually increased their risk in the first few years of taking the drugs.
The Women's Health Initiative includes a group of women who have had hysterectomies and who are taking estrogen alone. That part of the study is continuing because the data have not shown significant risk or significant benefit from the hormone.
The other part of the study, of women taking the hormone combination, was the part that was halted. It found that if 10,000 women take the hormones for one year, eight more will develop invasive breast cancer than a similar group not taking the hormones, seven more will have heart attacks, eight more will have strokes and eight more will have blood clots in their lungs. The benefits are six fewer instances of colorectal cancers and five fewer hip fractures.
There is no one overwhelming danger, said Dr. Claude Lenfant, director of the National Heart, Lung and Blood Institute. "It is a global risk."<hr></blockquote>
Comments
<strong><a href="http://www.nytimes.com/2002/07/10/health/10HORM.html?ex=1027320154&ei=1&en=72fbdf8f7d93bae2 " target="_blank">Article in the Times.</a>
In summary, we've believed for years and years that post-menopausal women should take hormones to help with everything from symptoms of menopause to heart disease to osteoporosis. Turns out that the trend was started by a guy who wrote a book funded by the pharmaceutical company that sold the hormone, and the confirmation of his ideas was based on inadequate scientific studies.
When they got around to appropriate studies (i.e., with a control group) recently, they met resistance from groups who said they shouldn't use a control group because no women should be denied the benefits of the hormones <img src="graemlins/bugeye.gif" border="0" alt="[Skeptical]" /> .
As the study got underway, they discovered that the women on the hormone therapy were more likely to have cardiovascular disease, not less. So they had to stop the study early.
The only reason they had previously found that women on the hormones were less likely to have heart disease is that they were healthier to begin with - not because the hormones themselves helped them.
How many herbs and "dietary supplements," almost none of which have undergone these types of controlled studies, are causing more problems than benefits?
How many of the groups who think we should "streamline" FDA approval will take the lesson from this?
How many luddites are going to distrust science even more because they'll think that science screwed up, when in fact it's the reverse?
</strong><hr></blockquote>
Clinical studies like this are very hard to do in a scientifical way, there is many biais that could change the results. These kind of studies has been done more than hundred of times, it's more a controversy than a scandal.
We have to wait to make conclusions.
<strong>
Clinical studies like this are very hard to do in a scientifical way, there is many biais that could change the results. These kind of studies has been done more than hundred of times, it's more a controversy than a scandal.
We have to wait to make conclusions.</strong><hr></blockquote>Yes, they are expensive. And it's worth it. Those kinds of studies should provide the sole basis for our use of drugs and therapies.
And who are among the richest companies in the world? The pharmaceutical companies. They can afford to fund them.
<strong>That's why they shouldn't be involved in them at all,because they have a self interest in the outcome...</strong><hr></blockquote>
The self interest is what causes them to do the study in the first place. Without that who would bother?
[quote]<strong>There is a lot of corruption in the medical field because of large pharmaceuticals and chemical companies. </strong><hr></blockquote>
Are you implying that they're falsifying the data?