Designer Babies?

From the AP. Link here.

By MALCOLM RITTER, AP Science Writer Mon May 12, 6:25 PM ET

NEW YORK - News that scientists have for the first time genetically altered a human embryo is drawing fire from some watchdog groups that say it's a step toward creating "designer babies."

But an author of the study says the work was focused on stem cells. He notes that the researchers used an abnormal embryo that could never have developed into a baby anyway.

"None of us wants to make designer babies," said Dr. Zev Rosenwaks, director of the Center for Reproductive Medicine and Infertility at NewYork-Presbyterian/Weill Cornell Medical Center.

The idea of designer babies is that someday, scientists may insert particular genes into embryos to produce babies with desired traits like intelligence or athletic ability. Some people find that notion repugnant, saying it turns children into designed objects, and would create an unequal society where some people are genetically enriched while others would be considered inferior.

The study appears to be the first report of genetically modifying a human embryo. It was presented last fall at a meeting of the American Society for Reproductive Medicine, but didn't draw widespread public attention then. The result was reported over the weekend by The Sunday Times of London, which said British authorities highlighted the work in a recent report.

Rosenwaks and colleagues did the work with an embryo that had extra chromosomes, making it nonviable. Following a standard procedure used in animals, they inserted a gene that acts as a marker that can be easily followed over time. The embryo cells took up the gene, he said.

The goal was to see if a gene introduced into an abnormal embryo could be traced in stem cells that are harvested from the embryo, he said. Such work could help shed light on why abnormal embryos fail to develop, he said.

No stem cells were recovered from the human embryo, said Rosenwaks, noting that abnormal embryos frequently don't develop well enough to produce them.

Marcy Darnovsky, associate executive director of the Center for Genetics and Society, said the Cornell scientists were developing techniques that others might use to make genetically modified people, "and they're doing it without any kind of public debate."

A London-based group called Human Genetics Alert similarly criticized the work.

But Kathy Hudson, director of the Genetics and Public Policy Center in Washington, D.C., said she's not troubled by the work. She said the idea of successfully modifying babies by inserting genes remains a technically daunting challenge.

"We're not even close to having that technology in hand to be able to do it right," she said, and it would be ethically unacceptable to try it when it's unsafe.

A few questions:

1. Does it matter that they used an "abnormal embryo?"

2. While it would certainly be unethical for this group of scientists to use this technology for human modification, aren't others able to do so?

3. If so, should the progress be halted based on the possible malfeasance/malevolence of others?

4. Although the idea of successfully modifying babies is a technically daunting challenge at this time, doesn't that seem to be a planned goal?

5. Is that bad?

6. Couldn't we have a better name than "Designer Babies." Sounds like an LA girls pop band.

No Such Thing as a Free....

.... Medication Sample?

In the Empowered Patient column on CNN's website, Elizabeth Cohen wrote, "In a University of Chicago study published this month, those receiving [medication] samples spent $166 in the six months before they obtained free medicine, $244 when they received the samples, and $212 in the six months after that." Since "free samples aren't always so free when you look at it long-term," Cohen lists five steps to take when a physician offers a sample. These include asking "your doctor how long you'll be taking the drug," finding out "if there's a cheaper alternative" to the drug offered, requesting that "your pharmacist to call your doctor" to "suggest cheaper alternatives," doing "your own price shopping," and keeping in mind that physicians "are often hesitant to change a prescription."

Dr. Adair then goes on to note that his physician "was being nice to me, or he thought he was." "Doctors think they're helping people by giving free samples, but we don't think through the long-term consequences."

Food for thought for physicians and patients. But, let's look into this one. The primary study is in April's Medical Care--and an article by Dr. G. Caleb Alexander. For those interested, the link is here. (A pleasant surprise was noted, by the way, seeing one of my colleagues as co-author, Dr. J. Zhang, right here in Richmond.) I was pleased to see that the study included an analysis to try to differentiate the possible confounding variable of samples being due to increased health demand. (i.e. a sicker patient needs a more expensive medication). This is a difficult variable, and was dealt with fairly logically; although the authors do note that there can still be confounding data skewing to explain the cost difference. They also do note some possible selection bias. I think this is perhaps likely in explaining the difference in sample usage being lower in those with less income, on Medicaid, etc. Commonly, lower income patients and Medicaid recipients are in facilities, insurance structures, or community-based programs which do not encourage samples. For example, one living in a group home, or in a community health center, which is not designed to process samples, and prefers (or demands) prescriptions only.
All-in-all, a this represents a fairly well designed study, that does not portend to be anything beyond a starting point for consideration and further research (naturally!). Of course, there will be media-savvy (or hungry) types that will immediately use this data for the purpose of bad-mouthing the insurance companies and perhaps demanding that doctors further distance themselves from this evil industry by no longer accepting samples: In an posting in 2005, Dr David Pisetsky at Duke University (jointandbone.org forum editor) presents the perils of seeing drug reps and accepting free samples. He suggests that it may be time to "pull up the welcome mat, close the door to my office, and put up a 'No Solicitors' sign."

"Does free mean free?" the headlines read. Well, of course it does--(unless the doc is charging in the parking lot or selling samples to the local pharmacy, in which case may a warm HMO await them in hell). No study will ever show a positive cost analysis of identical prescriptions being given vs. samples (e.g. a sample given of Lipitor vs. a prescription).

I am curious though to the possible rationale for studies like this. Is to promote the usage of generic medications? Perhaps more restrictive formularies? Or, is this a not-so-indirect attack on the pharmaceutical industry, or health care providers? (I didn't know we were just "often hesitant to change prescriptions!")

So, what can we learn from this study? First, that there is a possibility that when medication samples are given to patients, there is a possibility of being a greater long-term cost to those patients (or their insurance companies). Second, that the current studies do not provide sufficient data to condemn the practice of giving samples by physicians. and Third, it would make logical sense for patients and physicians to dialogue regarding samples, and treatment options, and that certainly should help not only the patient's decision-making, but maybe their wallet as well.

Bursting Boomers

From a recent news article from the APA:

NBC Nightly News (4/14) reported that "there's a new warning that this nation's medical care system for seniors is nowhere near ready to deal with the 78 million Baby Boomers who are about to begin turning 65," according to a study by the federal Institute of Medicine (IOM), which is part of the National Academy of Sciences.

The 242-page publication states that "[h]ealthcare institutions must rapidly increase training in geriatric care to ward off an 'impending crisis,'" the Wall Street Journal adds. In fact, the report characterizes "the U.S. healthcare workforce [as] 'too small and woefully unprepared' for the growing elderly population," and portrays "a stark picture of increased demand for healthcare workers -- unmet by a stagnant, or even dwindling, supply of those trained to treat the elderly." According to John W. Rowe, chairman of the committee which compiled the data, and former chairman and chief executive of Aetna, Inc., "This could be seen as evidence that our society places little value on the expertise needed to care for vulnerable, frail, older Americans."

The study found that currently, there are insufficient "specialists in geriatric medicine," training is inadequate, and the few "specialists that do exist are underpaid," the AP reports. In fact, the investigators charge that "Medicare may even hinder seniors from getting the best care, because of its low reimbursement rates, a focus on treating short-term health problems rather than managing chronic conditions, and lack of coverage for preventive services or for healthcare providers' time spent collaborating with a patient's other providers."

The data also indicate that since "one out of five Americans will be 65 or older" by 2030, "Medicare, Medicaid, and other health plans will need to pay higher rates for the services of geriatric specialists and direct-care workers to attract more health professionals to geriatric careers".

A crisis looms on the horizon. Are we preparing? Sadly, the answer seems, no. Less doctors are accepting Medicare, due to declining reimbursements. Nursing and Continuing Care Facilities are not likely to keep up with the need of the populations, especially for the lower income groups.

Physicians themselves do not appear well prepared for this burgeoning population. Geriatric patients require more time, due to a higher level of complexity from multiple medical concerns, a greater variability in responses and side effects from treatment, and difficulty with communication. Greater time needs to be spent collaborating with families and coordinating with other physicians. If the numbers noted above are correct, it's time to start preparing....

Politcally Incorrect Musings #1

Having a chat with the 11 year old son yesterday; he was trying to recall the name of the amusement park in Pittsburgh. I told him Kennywood Park- and he said, "oh, yeah... I thought it was Kennedywood."
This is not a bad idea. We have Dollywood, a Hard Rock Park, and even a proposed Ben & Jerry's Theme Park. Why not the family of Camelot? I humbly submit a few suggestions:

Kennedywood Park: Attractions:

The Chappaquiddick Water Adventure
Michael's Ski-N-Slide Thrill Coaster
The Joe Kennedy Boat Ride and Refreshment Stand
Rose's Fun House
The Patrick Kennedy Bumper Cars
Sirhan Sirhan's Shooting Gallery
Maria Shriver Presents: "The Gropinator:4D Experience"
The JFK Jr. "L'il Captains' Plane Ride"

And for relaxing afterwards:

The William Kennedy Smith Bar and Beach Walk
and The Grassy Knoll Picnic Area

The heart of the matter

Yesterday, a country-wide attack occurred by the medical establishment against the makers of Zetia and Vytorin. These are two newer (and more expensive) cholesterol lowering medications.
A sample news article appears here, in the New York Times.
A brief analysis of the article in The New England Journal of Medicine, (article here) notes that there is failure to separate statistically between the new medications (specifically ezetimibe- found in both Zetia and Vytorin) and the older cholersterol lowering medications, known as statins (simvastatin, specifically, for this study). The ENHANCE study measured the lowereing of LDL ("bad" cholesterol) and the thickness of the intima-media of the femoral and carotid arteries (a way of noting how much plaque is building up in the actual arteries). The latter is designed to measure the amount of atherosclerosis, and thus if the drugs are likely to prevent heart disease. On LDL lowering performance, ezetimibe has shown consistent significance at lowering LDL's better than statins; this was also seen in the ENHANCE study. However, no statistical difference was noted in the intima-media thickness (IMT).
So we again have a study that fails to separate (See previous posts on statistics and separation). This evidince is a bit more solid insofar that the drug makers themselves are sponsoring this study, and that there is an upward trend in thickness noted in the data of the newer drugs. Clearly there would be difficulty in declaring any improvement regarding heart disease from the newer medications, as none to date can be shown, and from the IMT results. But let's note just a few points:

1. The older medication showed no difference in IMT either, yet these medications have been shown to reduce heart disease.
2. Ezetimibe does show consistently and significantly lower levels of cholesterol
3. Long term outcome studies on heart disease have not been finished with the newer medicinces.

However, such points do not stop the mainstream media from finding all to willing physicians to get on the TV, radio, and news to declare the absolute failure of these newer products.
I woke up yesterday to hearing a cardiologist on a morning TV program saying "You can prescribe these medications; they just don't work." A similar statement is noted in the NYT article, where Dr. Krumholz recommends going back to statins, because "they work." Well, perhaps.... but not any better than the newer medication if we are to believe the results of the ENHANCE study.

What the ENHANCE study shows, is that we do not understand the mechanisms and correlations between cholesterol and heart disease, and that we need to wait to consider outcome data, before any declaration of what does and doesn't work in prevention of heart disease. In the meanwhile, the newer medications should be considered as part of the ongoing armament to lowering cholesterol. The recommendations for treatment of Familial Hypercholesterolemia have never been to use the newer medications first, so continuing to follow these guidelines and start with more traditional treatment is currently prudent.

Yes, newer is not always better- but remember that statins were the new, expensive drugs once too.

Real Science, and RIP Mr. Cope

Just perusing the news today, and I noticed an article out of the Pittsburgh Post Gazette (hardly a right wing rag). This represents a good example of what a scientific study should look like: Blinded, randomized, peer reviewed.
The link is here.
The article shows a study which shows, shockingly(!), that antidepressants can work- and sometimes when one doesn't (I guess the placebo didn't do so hot either), then another one might. It encourages patience, and a well thought out game plan when deciding on type and rationale in treatment.
On a sadder note for my fellow Steelers fans, Myron Cope- voice of the Steelers and inventor of the famed "Terrible Towel," has passed away today. "Yoi!, and double Yoi!"- Hope they have a nice Hot Pastrami (with fries in it, of course) where you are now, pal.
Cope was also an ardent supporter of national and local autism societies, as his own son Danny is autistic. All proceeds from the Terrible Towels went, and will continue to go, to the Allegheny Valley School- a facility that provides community and residential training and programs for children and adults with mental retardation.

Prozac Attack, Take 58

Today's news offers a study from Professor Irving Kirsh, Psychologist in the field of placebo effect. Prof. Kirsh, et al. have done a meta-analysis on 47 clinical trials for depression and have determined that the effect of the most popular medications (always referred to as "drugs" in such studies) for depression provide no benefit, except in severe cases. Of course, much of the media has been reporting with "unbiased" reports, with headlines such as "Antidepressant may not work" "Do we need antidepressants. and "Antidepressants no better than placebos." Even Fox (fair and balanced) fails to disclose some very basic facts regarding this article- the original which can be found here.

Some of those facts are:

1. This article, (published by the way on an open access journal-a sort of wikipedia for scientists) is a meta-analysis. It is a reconstruction of statistics determined after the fact. Given that one can choose the statistical analysis afterwards can allow one to manipulate the data.

2. There is a selection bias regarding studies chosen for the meta-analysis. Per Glaxo Smith Kline's representative, only studies that were submitted prior to approval, rather than a comprehensive (or at least randomly selected comprehensive) set of studies.

3. As we learn in statistics, failure to prove separation (the null hypothesis) does not prove equality. Many things are involved in a study, such as sample size, completion rates, and statistical methods. It is as if I take two animals, a cat and a dog, and try to prove that they are different based on certain criteria (e.g. type of hair, teeth, claws, number of legs, and weight). If I do this with one hundred cats and dogs, I can prove a difference. If I do it with two, I cannot. This failure to separate statistically does not allow me to state that cat=dog!

4. There is a likely bias of the conductor of the study. Prof. Kirsch has been singing this placebo song for years, and is not just limited to antidepressants. He also has written similar opinions regarding Asthma, and Irritable Bowel Syndrome. So what's his angle? Research money? Perhaps. Personal Bias? Attention? I do not know. He is a supporter of cognitive behavioral therapy, in lieu of medication. Furthermore, he espouses the usage of a certain medication for treatment of depression: can you guess which one? How about Placebo! Dr. Kirsch notes in an interview to NPR that regarding the effect of placebos:
"For years and years and years it has been treated as just noise, as trash. Now we're finding out that it's not just trash, it's really treasure. It's something to be mined, something to be understood, something to be made use of."
NPR- CLICK HERE
Fascinating. I'm not sure how he's going to sell that idea to the FDA: Hey! Don't use a drug that might not work, use one that we know won't work.

5. The UK may have a financial agenda. The nationalized system recently has done this with Alzheimer's medications (the NICE study declaring them to be not cost effective). Perhaps we are seeing the UK starting to put up barriers to obtaining treatment for depression.

Well. Any doc worth his salt will tell you that we are quite aware of the "placebo effect." I used to be quite annoyed and amused with a neurologist in my residency days who used to declare that a person was not having a particular neurological condition just because it improved when he gave a shot of saline to the patient. He would smile and state, "must be one of yours." So of course, we should understand that a "placebo effect" can do some interesting things- that is the amazing part of the mind.

I do not fault Prof. Kirsch his opinion or his data. I do not fault the news media for reporting. They both have their rights. I just strongly disagree with the findings as horribly biased, and the reporting as merely sensationalistic. It is, in short, bad science.

The choice for antidepressant treatment should be made after consultation with a qualified health professional. I do not recommend merely "just trying" any medication, psychotropic or otherwise. It would be a shame, though, if doctors or patients allowed such bad science to bias their decision to offer or consider these medications.