Editor's Notes:

Samuel Johnson is reputed to have observed that hell is paved with good intentions. The corollary to this should be "particularly the good intentions of activists." In this article, the Washington Post relates how AIDS activists have scuttled foreign trials of the AIDS drug tenofovir, which could—eventually—turn out to be the first successful drug prophylactic against the disease.

In the name of "protecting" prostitutes in poor nations from "Western imperialism" (by the Bill and Melinda Gates Foundation, those imperialists extraordinaire) activists have slowed efforts to find a treatment that could provide those same prostitutes with real protection.

On a Sunday afternoon in November, Yunang Soma stood shoulder-to-shoulder with other prostitutes on a makeshift stage in a park and shouted to the crowd: "The U.S. says it wants to help poor people, but it is killing the poor people!"

Soma was protesting a trial of the drug tenofovir, which scientists think may one day serve as an effective "chemical vaccine" against the human immunodeficiency virus, which causes AIDS. Unlike true vaccines, which give a person lasting immunity to a disease but have proved difficult to develop for HIV, tenofovir is a daily pill. Scientists hope it will protect against infection for a few hours or maybe even days. The trial, funded by the Bill & Melinda Gates Foundation, was designed to see if it can stop people from becoming infected with HIV even if the virus enters their bodies.

But researchers have run into a highly organized opposition that they say was engineered by foreign activists. The demonstrators have succeeded in shutting down the trial in Cambodia, but the protests continue there. Soma and her colleagues are intent on halting all trials of tenofovir, worldwide...

Fabrice Pilorge, 39, of the Paris branch of the AIDS group Act Up, which advised the protesters, said he never intended to have the trial halted. He said he only wanted to get better benefits for the participants. "What we did is going to slow research," he acknowledged. "As an activist, we always want the research to be fast."

Perhaps the activists ought to have thought this one through a bit more. Unfortunately, righteous indignation and anti–corporate ideology seems to have overwhelmed their common sense.

Another quotation comes to mind in this case, this time from Juvenal: Quis custodiet ipsos custodes? Translation: Who guards the guardians?

Read the whole article.

Editor's Notes:

This is a very interesting article on off–label drug use that is probably unduly alarming on the effects of off–label prescribing. Still, it is well worth reading for a window into the enormous complexity that doctors must grapple with in their attempts to help patients.

Every day in medical offices around the country, physicians hand patients prescriptions for drugs to treat conditions for which the medicines haven't been approved. Once a drug is approved by the Food and Drug Administration (FDA), a doctor can, with rare exceptions, legally prescribe it "off label": for use as he or she sees fit.

That's a primary reason people with depression or attention-deficit disorder are prescribed drugs approved to treat seizures, acne patients are given prescriptions for antibiotics, and insomniacs are advised to take a schizophrenia drug. And it's why tens of millions of post–menopausal women for years were told to take estrogen, a drug approved to treat osteoporosis, as a way of staving off heart disease, improving their mood and memory, and smoothing wrinkles.

Off–label use of drugs may be axiomatic in medicine, but a new study published in the Archives of Internal Medicine finds that the practice is frequently grounded more in anecdote than in hard science.

Using data from a national survey of 3,500 office-based physicians, researchers found that 21 percent of the 725 million prescriptions written in 2001 were for off–label uses. Seventy–three percent of these prescriptions lacked strong scientific justification, such as a clinical trial, and were based on observational studies, case reports or no discernable evidence. And without solid evidence of safety and effectiveness, the researchers maintain, consumers run the risk of taking ineffective, expensive and potentially dangerous drugs...

Many patients and some physicians, he said, think that if the FDA has approved a drug, it is safe and effective for multiple conditions, which is not the case. FDA approval is narrowly focused on a specific condition or ailment—such as heart disease—and for use in a specific population, such as adults or women. In other cases, Stafford said, doctors may not tell patients they are giving them an off–label drug.

The article implies that what we really need is "rational drug use", i.e. treatment based on the "gold standard" for clinical evidence, the double blind placebo–controlled clinical trials often used for FDA approval.

The problem is that human complexity frustrates the attempt to determine how a given chemical will interact with an individual patient's particular genetic background and disease history. Even the best clinical trials tend to restrict enrollment to a very narrow class of patients for a very specific indication at a given dosage. Thus FDA approval, by its very nature, may tell us little about the full utility (or risks) of a drug at the time of its release.

This is neither the fault of the agency nor the industry. It is simply the state of our technology at the present time. Like it or not, the "real world" is where much of our knowledge about drugs will be gained.

For instance, even after a massive government-sponsored effort to study hormone replacement therapy in women, researchers and doctors are still debating the findings.

Advocating for the "rational" use of drugs may be fine in theory, but bad in practice. Until better diagnostic tests are available that can truly personalize routine medical decisions (and these are probably a long way off), physicians will be forced to use trial and error prescribing to help patients when known remedies fail.

The best short term solution to this problem is to improve postmarket drug monitoring through routine analysis of drug and patient databases used by large insurers and health care systems–not to call for larger and longer clinical trials, which may not tell us what we really need to know about drug treatments.

Editor's Notes:

While we're all waiting for the next generation of personalized medicines, the best way to catch a glimpse of your own health future is to look carefully at your family history. This approach is also helping cancer researchers use new technologies to better understand the genetic roots of different cancers and help design treatments to fight them.

Scientists hope that by studying the DNA of patients in families where members across several generations get a particular cancer, they can home in on the genetic variations that make these families susceptible.

This is critical because it turns out that the same genes are often involved when people in the general population get cancer. So the genes yield new insights into how cancer works, and for developing drugs. In just the past six months, for instance, the Food and Drug Administration approved two new kidney-cancer drugs that were developed in part using genetic information from cancer-prone families.

Sutent from Pfizer Inc. and Nexavar from Bayer AG's Bayer Pharmaceuticals and Onyx Pharmaceuticals both target proteins linked with a gene that was discovered by studying families who get a rare type of kidney cancer. In other recent studies, researchers have found intriguing clues to the causes of prostate cancer, and are narrowing down the possible genetic roots of colon cancer...

One reason families with inherited cancers are so valuable to research is that they make it much easier to home in on the problematic genes. To find culprit genes in a vast population of patients with varying genetic makeups can be almost impossible. When the people getting the disease are all related, it is often easier for researchers to detect relevant genetic patterns.

"In families, there are more needles and less haystack to search for the cause of the cancer," says Sanford Markowitz, an investigator at the Howard Hughes Medical Institute and professor at the Ireland Cancer Center and the Case Western Reserve University School of Medicine in Cleveland, who heads the familial-colon-cancer study in which Ms. Bowen is participating.

Editor's Notes:

One of the tipping points in the debate over welfare reform was the growing public consensus that welfare recipients had a responsibility to work in return for their benefits. A similar approach is now being applied in some state Medicaid programs, where policymakers are stipulating that poor Medicaid recipients "sign contracts" to abide by good health guidelines in return for certain types of health care coverage.

While some critics fear that this approach will lead to a decline in health benefits for the poor, this seems unlikely. No politician wants to be accused of denying healthcare to poor families. What it may do, however, is push poor recipients to use health care resources more conscientiously and become more proactive about staying in good health. While this is still a developing policy tool, it is one that should be studied carefully.

West Virginia's Medicaid families could face a reduction in benefits if they refuse to sign contracts promising to show up for doctors' appointments and use the emergency room only for emergencies. Kentucky, meanwhile, is putting new limits on prescriptions and visits to therapists.

They're the first two states to take advantage of a new law that makes it easier to mix and match which residents get which benefits under Medicaid, the state–federal program that provides health insurance coverage to about 55 million low–income people.

In years past, when states provided a health benefit for their Medicaid beneficiaries, they had to do so for all of participants in their state. The concept, called comparability, guaranteed comprehensive health insurance coverage for the poorest of the poor. If one person got prescription drug coverage, for example, all participants were entitled to it. Now, comparability is out. Flexibility is in.

Comparability guaranteed that states didn't discriminate against a segment of needy people based on their health conditions, or where they live, said Judith Solomon, a senior fellow at the Center on Budget and Policy Priorities, a liberal think tank.

"At the end of the day, I see this leading to people not getting things they need," Solomon said.

But governors saw the comparability requirements as a straight jacket, forcing them to drop people off the Medicaid rolls completely when trying to slow the program's explosive costs. The governors view the changes approved by Congress as a way to scale back coverage for some rather than dropping people into the ranks of the uninsured.

Editor's Notes:

The media is rife with speculation as to whether or not the new Medicare prescription drug benefit will wind up hurting or helping the Republicans come November. Knight–Ridder takes a wait and see approach:

The program's flaws and shortcomings were exposed early and often in the first few months after its January launch. However, recent news of lower–than–expected drug costs, patient satisfaction and a seemingly successful enrollment drive have given the program a new bounce that could help Republicans fend off future Democratic attacks.

The cost of the drug benefit has declined from a projected $737 billion over 10 years to $675 billion. Beneficiary premiums are averaging $25 a month, down from $37 in last July's budget estimates. And the projected net cost to taxpayers for 2006 will be $30.5 billion, 20 percent less than an earlier estimate of $38.1 billion. In addition to increased competition, Medicare officials credit lower–than–expected drug costs and dampened enrollment for the declines.

But a split decision isn't exactly what Republicans were hoping for when the groundbreaking legislation became law in 2004. The largest expansion in Medicare's history was supposed to be a political knockout.

"There's no question the Republicans thought the passage of (the drug benefit) was their best opportunity in years to neutralize the advantage with senior voters that Democrats have traditionally had on health, and it hasn't worked out that way at all," said Drew Altman, the president of the Kaiser Family Foundation.

So how did a program with such strong initial public support turn into a possible election-year albatross?

The answers are as complex the drug benefit itself. And if the first five months are a sign of what's to come, special–interest groups, lawmakers and concerned seniors will continue to seek changes that GOP lawmakers will likely oppose.

Realistically, political arguments over the benefit may generate more heat than light. The press surrounding implementation of the benefit has been so relentlessly negative that beneficiaries have been pleasantly surprised by its actual performance. Indeed, opinion surveys thus far have found seniors who signed up for the benefit are saving money and are broadly satisfied with its performance.

Come November, however, other issues—Iraq, the economy, and energy prices—will occupy most voters' attention. For better or worse, Medicare Part D will likely amount to just so much background noise.

Having said that, the real battle over Medicare reform is still at least a year or two away, and that conflict will turn on whether or not seniors have become comfortable with the private management of the drug benefit and are willing to embrace more market driven reforms. In the interim, Democrats will do their best to strip the market elements out of Part D—i.e., adding drug price controls and setting a uniform national formulary. Advocates of market driven Medicare reforms are going to have to roll up their sleeves and start planning the next phase of reform.

To paraphrase John Paul Jones, when it comes to Medicare we have not yet begun to fight.

Editor's Notes:

Our public debate regarding the utility of prescription drugs is often schizophrenic. Take, for example, this article, which points out that caps on patient prescription drug spending often costs insurers more in overall health care spending because of "costly complications" that could've been prevented by appropriate drug treatment.

Placing caps on prescription drug benefits might not actually save insurers money because patients don't take needed medications and often suffer costly complications, according to a study of Medicare beneficiaries published today in the New England Journal of Medicine.

The study of 157,000 Kaiser Permanente members in Northern California in 2003 compared Medicare recipients who had a $1,000 annual limit on their medications with those who had no such limitations. Researchers found that patients with caps spent 31 percent less on their drugs but had more emergency–room visits and hospitalizations.

The Kaiser study found that patients with limited drug benefits did not take their prescribed medications as frequently as people who had drug coverage without caps. Drugs studied included antidiabetic, hypertension and cholesterol–lowering medications.

"Drug coverage makes a big difference and has a substantial impact on patient health," said Dr. John Hsu of Kaiser's Division of Research, lead investigator and author of the report. The study was funded by the Agency for Healthcare Research and Quality, the National Institute on Aging and the Alfred P. Sloan Foundation.

Fair enough so far. But the article concludes by quoting a health care expert who endorses the idea of controlling health care costs "by allowing Medicare to negotiate drug prices and promote the use of generic medications."

Ironically, after presenting data on the cost–effectiveness of prescription drugs, the article goes on to quote an expert who argues that Medicare ought to "negotiate" drug prices directly with manufacturers.

First of all, the government's market leverage and incentives tend towards price controls and other non–price restrictions on drug use—like mandating the use of generics and restricting access to new medicines. In any event, this would amount to a de facto cap on access to many medicines.

A more rational response would be to pay a premium for treatments—prescriptions drugs or anything else—that reduced illness and total health care costs, instead of limiting spending across the board. Pay for performance would help lower drug spending without punishing the very companies driving medical innovation.

Ultimately, shifting to an outcomes–based payment system would benefit the most efficient health care providers and improve patient care. That won't happen, however, until we end our irrational fixation with controlling line item costs.

Editor's Notes:

The Globe reports that the FDA reached an important milestone last week when it approved the first so-called biogeneric drug. It is hoped that, like traditional generics, copies of biotech drugs whose patents have expired will offer patients and providers cheap alternatives for life–saving medicines.

The Food and Drug Administration yesterday approved a generic human growth hormone, a breakthrough that allows its maker to sell its first copy of a biotechnology product in the United States.

The FDA, however, stopped short of resolving how it will approve more complex generic biotechnology products.

Omnitrope, made by a unit of the Swiss drug maker Novartis AG , will treat children and adults with growth disorders. The FDA determined it is so similar to branded products already on sale that the agency could use its extensive knowledge of those drugs to approve Omnitrope.

"This is a promising step in the right direction," said Senator Orrin G. Hatch, Republican of Utah. He said the decision provides "tangible hope" that other generic biological drugs—treatments produced in living cells—can be brought to market...

Despite this milestone, much work still has to be done before the FDA has an official approval process for biogenerics. The debate is proceeding slowly because of conflicting arguments over what data should be required to prove that biogenerics are really equivalent to the original products.

Still, this is ultimately a manufacturing question that the FDA should be able to surmount once the underlying technical questions have been resolved. While biotech companies are leery of generic competition, it is in their best interests to work with biogeneric companies to establish a reliable and fair process for biogeneric approvals. Until then, the lack of such a process will only hurt the industry as consumer resentment mounts over the rising cost of biotech treatments.

In short, it is important to strike the right balance between innovation and pricing, and the biotech industry should be proactive about finding that balance.