A New Disquiet About Some Generic Drugs - NYTimes.com

Let me start by saying I'm a fan of generic drugs. They save Americans billions of dollars each year and give us access to wonderful drugs at affordable prices. I've recommended generics in this column many times and use them myself when possible.

But there is a gnawing concern among some doctors and researchers that certain prescription generic drugs may not work as well as their brand-name counterparts. The problem is not pervasive, but it's something consumers should be aware of — especially now that more insurers insist that patients take generic medications when they are available.

Let me also prepare the groundwork for what I hope will be full and frank reader comments, by acknowledging that this issue is controversial.

Joe Graedon, who has been writing about pharmaceuticals for three decades and runs a consumer advocacy Web site, the People's Pharmacy (peoplespharmacy.com), was 100 percent behind generics for many years.

"We were the country's leading generic enthusiasts," he told me recently. But over the last eight or nine years, Mr. Graedon began hearing about "misadventures" from people who read his syndicated newspaper column, also called The People's Pharmacy.

The stories were typically from patients who were switched from a brand name drug to a generic one and had side effects or found that their symptoms returned — or even became worse than before they were medicated. Most recently Mr. Graedon has been hearing complaints on his Web site about generic forms of the antidepressant Wellbutrin XL 300 (known as Budeprion XL 300 in one generic form), the heart medicine Toprol XL (metoprolol succinate) and the antiseizure medicine Keppra (levetiracetam).

"Consumers are told generics are identical to brand name drugs, but that is clearly not always the case," Mr. Graedon said.

Some specialists, particularly cardiologists and neurologists, are concerned about generic formulations of drugs in which a slight variation could have a serious effect on a patient's health. The American Academy of Neurology has a position paper that says, in part, "The A.A.N. opposes generic substitution of anticonvulsant drugs for the treatment of epilepsy without the attending physician's approval."

But insurers tend to argue otherwise. On Thursday, ExpressScripts, which handles drug insurance for big employers, put out a news release announcing results of a study it sponsored that found no difference in hospitalizations or emergency-room visits for people on brand-name epilepsy drugs compared with those taking generics.

The Food and Drug Administration, meanwhile, says it stands behind generic medications and its methods for approving them.

"We have not seen any scientific studies that show generics do not hold up as well as brand name drugs," says Gary J. Buehler, director of the agency's office of generic drugs. "We believe the generic drugs we approve work in everyone."

The American Medical Association concurs. A spokeswoman for the group told me in an e-mail message, "the A.M.A. position is that as a whole generic drugs do work as well as name-brand drugs."

Yet, after hundreds of consumers posted messages about problems with the generic drug Budeprion XL 300 on the People's Pharmacy Web site, Mr. Graedon worked with an independent laboratory, ConsumerLab.com, to test the drug, which in other generic versions is typically known as bupropion.

The lab found that Budeprion XL 300 released the active drug at a different rate than the brand name Wellbutrin XL 300. Mr. Graedon and the lab conjecture that the different dissolution rates might be to blame for the reported side effects and lower effectiveness of Budeprion.

But Mr. Buehler at the F.D.A. explained to me that over the course of 24 hours a patient ends up with the same amount of the drug in the bloodstream, so there should be no reason for a variation in effectiveness. "We remain puzzled," he said.

The maker of Budeprion XL 300, Teva Pharmaceutical Industries, recently announced that it would conduct a clinical trial comparing its product against the original, Wellbutrin XL.

A Teva spokeswoman said in an e-mail message that the company was working with the F.D.A. on a study "specifically designed to answer the questions raised following the recent anecdotal commentary on generic budeprion."

"We believe the study and the resulting data will provide further scientific support for the product's bioequivalence to the innovator drug," she said.

To parse that statement — or at least understand "bioequivalence" — it is worth taking a step back to consider what a generic drug is and how it gets approved.

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http://www.nytimes.com/2009/12/19/health/19patient.html?em=&pagewanted=print

CBC News - Measuring the return from electronic health records is murky math, at best

I recently flew into Charleston, S.C., to see how the Medical University of South Carolina was handling its electronic health record systems. I went Deep South because MUSC has had the Oacis medical record system in place since 1993 ? it was the first hospital system in the world to buy one.

I went there to check out the system because all the hospitals in Montreal, along with Sunnybrook Hospital in Toronto and the Children's Hospital of Eastern Ontario in Ottawa (not to mention almost the entire state of South Australia) either have or are about to use an Oacis system supplied by Canada's Telus Health Solutions.

I especially wanted to see the effectiveness of an EHR system after it had been used for 16 years in a locale that has a million patient visits a year.

At first glance, everything seemed somewhere between coolisimo and highly efficient.

Larry Afrin, who is both a hematologist and director of information technology for MUSC's Office of Graduate Medical Education, demonstrated how he could comb through 16 years' worth of medical records and uncover a previously unforeseen negative interaction between a standard antibiotic and the suppressed immune system of patients undergoing chemotherapy.

He then showed me, with a couple of keystrokes, how you can retrieve an electronic version of a chest X-ray, or indeed any image, at will. And finally, he gleefully described how the moment Oacis was put in place he had torn up stacks and stacks of the three-by-five-inch cards on which he previously wrote all his patients' medical particulars to refer to when visiting their bedsides.

Following the money

With these successes in mind, I began asking people at MUSC a very different kind of question. Had the purchase of electronic health records saved or made money for the hospital?

I asked first because cost-saving is the lure many EHR vendors claim or imply when selling their products.

Novarad Corp. of Utah, for example, crows on its website about one of its products: "Because it takes care of all of your information and imaging needs, you'll start saving tons of money before you even plug it in." It then directs purchasers towards an online return-on-investment calculator to figure out their future savings.

Companies are not alone in seeing the EHR systems turning into operational gold for hospitals and clinics.

Canada Health Infoway, the federally funded agency partnering with provinces and territories to create a cross-country electronic health record system, commissioned a private consulting firm to monetize the values of computerized health imaging ? what is known as PACS, or picture archiving and communication systems.

Their estimate [http://www2.infoway-inforoute.ca/documents/chi%20diagnostic%20imaging%20report_engreport.pdf]: It could save our medical system up to $1 billion a year in existing or projected expenses.

Another study CHI quotes says EHRs could save the country as a whole $6 billion to $7 billion. In the U.S., Rand Corp. estimated in 2005 [http://content.healthaffairs.org/cgi/content/full/24/5/1103] that a digitized American medical system could save that country $81 billion annually.

But what is happening on the ground in South Carolina is a lot less convincing.

After 16 years of experience with electronic health records, and after spending $23 million a year on its clinical computer systems, MUSC still doesn't know if it is saving or making money.

"We have some studies underway to document ROI ? that is, the return on our investment ? but at this stage we feel we can't say it has been positive," says Frank Clark, chief information officer for the MUSC.

What about all those money-saving claims from companies?

"Vapourware," Clark says in his soft southern accent.

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http://www.cbc.ca/health/story/2009/12/03/f-electronic-health-records-strauss.html

Mammogram Math - NYTimes.com

In his inaugural address, Barack Obama promised to restore science to its "rightful place." This has partly occurred, as evidenced by this month's release of 13 new human embryonic stem-cell lines. The recent brouhaha over the guidelines put forth by the government task force on breast-cancer screening, however, illustrates how tricky it can be to deliver on this promise. One big reason is that people may not like or even understand what scientists say, especially when what they say is complex, counterintuitive or ambiguous.

As we now know, the panel of scientists advised that routine screening for asymptomatic women in their 40s was not warranted and that mammograms for women 50 or over should be given biennially rather than annually. The response was furious. Fortunately, both the panel's concerns and the public's reaction to its recommendations may be better understood by delving into the murky area between mathematics and psychology.

Much of our discomfort with the panel's findings stems from a basic intuition: since earlier and more frequent screening increases the likelihood of detecting a possibly fatal cancer, it is always desirable. But is this really so? Consider the technique mathematicians call a reductio ad absurdum, taking a statement to an extreme in order to refute it. Applying it to the contention that more screening is always better leads us to note that if screening catches the breast cancers of some asymptomatic women in their 40s, then it would also catch those of some asymptomatic women in their 30s. But why stop there? Why not monthly mammograms beginning at age 15?

The answer, of course, is that they would cause more harm than good. Alas, it's not easy to weigh the dangers of breast cancer against the cumulative effects of radiation from dozens of mammograms, the invasiveness of biopsies (some of them minor operations) and the aggressive and debilitating treatment of slow-growing tumors that would never prove fatal.

The exact weight the panel gave to these considerations is unclear, but one factor that was clearly relevant was the problem of frequent false positives when testing for a relatively rare condition. A little vignette with made-up numbers may shed some light. Assume there is a screening test for a certain cancer that is 95 percent accurate; that is, if someone has the cancer, the test will be positive 95 percent of the time. Let's also assume that if someone doesn't have the cancer, the test will be positive just 1 percent of the time. Assume further that 0.5 percent — one out of 200 people — actually have this type of cancer. Now imagine that you've taken the test and that your doctor somberly intones that you've tested positive. Does this mean you're likely to have the cancer? Surprisingly, the answer is no.

To see why, let's suppose 100,000 screenings for this cancer are conducted. Of these, how many are positive? On average, 500 of these 100,000 people (0.5 percent of 100,000) will have cancer, and so, since 95 percent of these 500 people will test positive, we will have, on average, 475 positive tests (.95 x 500). Of the 99,500 people without cancer, 1 percent will test positive for a total of 995 false-positive tests (.01 x 99,500 = 995). Thus of the total of 1,470 positive tests (995 + 475 = 1,470), most of them (995) will be false positives, and so the probability of having this cancer given that you tested positive for it is only 475/1,470, or about 32 percent! This is to be contrasted with the probability that you will test positive given that you have the cancer, which by assumption is 95 percent.

The arithmetic may be trivial, but the answer is decidedly counterintuitive and hence easy to reject or ignore. Most people don't naturally think probabilistically, nor do they respond appropriately to very large or very small numbers. For many, the only probability values they know are "50-50" and "one in a million." Whatever the probabilities associated with a medical test, the fact remains that there will commonly be a high percentage of false positives when screening for rare conditions. Moreover, these false positives will receive further treatments, a good percentage of which will have harmful consequences. This is especially likely with repeated testing over decades.

Another concern is measurement. Since we calculate the length of survival from the time of diagnosis, ever more sensitive screening starts the clock ticking sooner. As a result, survival times can appear to be longer even if the earlier diagnosis has no real effect on survival.

Cognitive biases also make it difficult to see the competing desiderata the panel was charged with balancing. One such bias is the availability heuristic, the tendency to estimate the frequency of a phenomenon by how easily it comes to mind. People can much more readily picture a friend dying of cancer than they can call up images of anonymous people suffering from the consequences of testing. Another bias is the anchoring effect, the tendency to be overly influenced by any initially proposed number. People quickly become anchored to such a number, whether it makes sense or not ("we use only 10 percent of our brains"), and they're reluctant to abandon it. If accustomed to an annual mammography, they're likely for that reason alone to resist biennial (or even semiannual) ones.

Whatever the role of these biases, the bottom line is that the new recommendations are evidence-based. This doesn't mean other right-thinking people would necessarily come to the same judgments. To oppose the recommendations, however, requires facts and argument, not invective.

John Allen Paulos, professor of mathematics at Temple University, is the author most recently of "Irreligion."

http://www.nytimes.com/2009/12/13/magazine/13Fob-wwln-t.html?ref=magazine

Children on Medicaid Found More Likely to Get Antipsychotics - NYTimes.com

New federally financed drug research reveals a stark disparity: children covered by Medicaid are given powerful antipsychotic medicines at a rate four times higher than children whose parents have private insurance. And the Medicaid children are more likely to receive the drugs for less severe conditions than their middle-class counterparts, the data shows.

Those findings, by a team from Rutgers and Columbia, are almost certain to add fuel to a long-running debate. Do too many children from poor families receive powerful psychiatric drugs not because they actually need them — but because it is deemed the most efficient and cost-effective way to control problems that may be handled much differently for middle-class children?

The questions go beyond the psychological impact on Medicaid children, serious as that may be. Antipsychotic drugs can also have severe physical side effects, causing drastic weight gain and metabolic changes resulting in lifelong physical problems.

On Tuesday, a pediatric advisory committee to the Food and Drug Administration met to discuss the health risks for all children who take antipsychotics. The panel will consider recommending new label warnings for the drugs, which are now used by an estimated 300,000 people under age 18 in this country, counting both Medicaid patients and those with private insurance.

Meanwhile, a group of Medicaid medical directors from 16 states, under a project they call Too Many, Too Much, Too Young, has been experimenting with ways to reduce prescriptions of antipsychotic drugs among Medicaid children.

They plan to publish a report early next year.

The Rutgers-Columbia study will also be published early next year, in the peer-reviewed journal Health Affairs. But the findings have already been posted on the Web, setting off discussion among experts who treat and study troubled young people.

Some experts say they are stunned by the disparity in prescribing patterns. But others say it reinforces previous indications, and their own experience, that children with diagnoses of mental or emotional problems in low-income families are more likely to be given drugs than receive family counseling or psychotherapy.

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http://www.nytimes.com/2009/12/12/health/12medicaid.html?hpw=&pagewanted=print

Menopause, as Brought to You by the Drug Companies - NYTimes.com

MILLIONS of American women in the 1990s were told they could help their bodies ward off major illness by taking menopausal hormone drugs. Some medical associations said so. Many gynecologists and physicians said so. Respected medical journals said so, too.

Along the way, television commercials positioned hormone drugs as treatments for more than hot flashes and night sweats — just two of the better-known symptoms of menopause, which is technically defined as commencing one year after a woman's last menstrual cycle.

One commercial about estrogen loss by the drug maker Wyeth featured a character named Dr. Heartman in a white coat discussing research into connections between menopause and heart disease, Alzheimer's disease and blindness.

"When considering menopause, consider the entire body of evidence," Dr. Heartman said. "Speak to your doctor about what you can do to help protect your health during and after menopause."

Connie Barton, then a medical office assistant in Peoria, Ill., was one woman who responded to such messages. She says she took Prempro, a hormone drug made by Wyeth, from 1997, when she was 53, until 2002, when she received a diagnosis of breast cancer. As part of her cancer treatment, she had a mastectomy to remove her left breast.

Now Ms. Barton, who said in an interview that she used Prempro in part because her doctor told her it could help prevent heart disease and dementia, is one of more than 13,000 people who have sued Wyeth over the last seven years, claiming in courts across the country that its menopause drugs caused breast cancer and other problems.

The suits also assert, based on recently unsealed court documents, that Wyeth oversold the benefits of menopausal hormones and failed to properly warn of the risks.

In October, a jury in a Pennsylvania state court awarded Ms. Barton $75 million in punitive damages from Wyeth on top of compensatory damages of $3.75 million.

The drug giant Pfizer, which absorbed Wyeth and its hormone drugs in a merger this year, says that Prempro is a safe, federally approved drug that did not cause Ms. Barton's breast cancer. Chris Loder, a Pfizer spokesman, says Wyeth acted responsibly by including a clear warning about a breast cancer risk on Prempro labels and by updating the warning as new evidence emerged.

Mr. Loder also notes that Pfizer plans to appeal every product-liability case on menopausal drugs it loses, including Ms. Barton's.

While Wyeth has faced periodic complaints about its blockbuster menopause drugs, the latest lawsuits have turned the company's menopausal hormone franchise into the kind of case study dissected at Ivy League business schools. Lawyers have made some documents public in the suits, and The New York Times and the nonprofit Public Library of Science filed successful motions to unseal thousands of documents in July.

To be sure, even some doctors who think hormone therapy has risks say it is the most effective treatment for symptoms directly associated with menopause.

The documents that have surfaced in the Wyeth cases offer a rare glimpse inside the file cabinets and hard drives of a major drug company. And the cases demonstrate the importance of litigation in detailing exactly how drug makers operate their businesses, says Dr. Jerome L. Avorn, a professor of medicine at Harvard Medical School who has written about the subject in The Journal of the American Medical Association.

"The information coming out in litigation helps us understand how a belief in a 'protective benefit' of estrogens on the heart was able to spread like wildfire through the medical community," says Dr. Avorn, who is not involved in the Wyeth litigation.

"Thousands of doctors prescribed the drugs for millions of women on that basis," he says, adding that studies later contradicted the belief. "It will be very interesting to see whether the courts are able to connect the dots and make it clear whether this was a kind of medical ventriloquism on Wyeth's part."

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http://www.nytimes.com/2009/12/13/business/13drug.html?_r=1&th=&emc=th&pagewanted=print