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A new drug for pulmonary arterial hypertension (PAH) Letairis has been released. In PAH small arteries in the lungs narrow and the pressure of blood in the vessels increase and the right side of the heart works harder to pump the blood. The result is enlargement and then weakening of the right sided heart muscle. There is also thickening and loss of efficiency of oxygen exchange in the pulmonary blood vessels. Patients become short of breath, tired, have chest pain, dizziness and often have syncopal episodes. About 100,000 people in the United States have pulmonary arterial hypertension.

Letairis is an ERA, or endothelin receptor antagonists. The drug relaxes the vessels, lowers blood pressure and lightens the load on the heart and lungs.

Gilead the manufacturer notes:

“In two randomized, double-blind, 12-week, placebo-controlled Phase III clinical trials (ARIES-1 and ARIES-2) involving a total of 393 patients, treatment with Letairis resulted in a significant improvement in six-minute walk distance. An increase in walk distance was observed after four weeks of treatment with each dose regimen of Letairis, with a dose-response observed after 12 weeks of treatment. In ARIES-1, placebo-adjusted mean and median changes from baseline of 31 meters and 27 meters (p=0.008), respectively, were observed for the 5 mg dose. Placebo-adjusted mean and median changes from baseline of 51 meters and 39 meters (p less than 0.001), respectively, were observed for the 10 mg dose. In ARIES-2, placebo-adjusted mean and median changes from baseline of 59 meters and 45 meters (p less than 0.001), respectively, were observed for the 5 mg dose.” (Emphasis by medicynic)

“The long-term follow-up of the patients who were treated with Letairis in the two pivotal studies and the open-label extension (n=383) shows that 95 percent were still alive at one year and 94 percent were still receiving Letairis monotherapy. These uncontrolled observations do not allow comparison with a group not given Letairis and cannot be used to determine the long-term effect of Letairis.” (Emphasis by medicynic)

“Gilead is committed first and foremost to patients,” said Dr. Martin. “Our hope is that this program will ensure greater access to care for PAH patients with a variety of circumstances, including the often overlooked group of patients who have some form of prescription insurance but have prohibitively high out-of-pocket expenses.”

In the New York Times it was noted:

“Gilead said Letairis, a once-a-day pill, will cost $3,940 a month, about the same as Tracleer, which is also known as bosentan. The company said it was establishing programs to help uninsured or under-insured patients obtain the drug.”

In summary: the drug doesn’t cure the disease. Exercise improvement, depending on the dose is limited to 100 and 200 feet additional distance in a 6 minute walk. There also may be an improvement in survival but the study for this was not conclusive. The price almost $50,000/year.

It’s wonderful there is progress in this disease but the benefit is quite limited and the price exorbitant–not surprising given the Pharmaceutical Industry’s track record. The only question is when such pricing will break the bank.

The push towards high-deductible health insurance offers the industry yet another way to game the system. Consider the analysis of costs of pregnancy care in the Post–High Deductible Plans Cost More for Maternity Care.

“The study found that those enrolled in a traditional health plan for federal employees (with a $500 annual deductible and $20 co-payments for office visits) would likely pay $1,455 out of pocket for care during an uncomplicated pregnancy and delivery. That compared to $3,000 for families in a high-deductible plan for federal employees and $7,000 for a high-deductible plan offered through small businesses.”

The employer’s goal is to cut costs and thus they provide few options often with skimpy coverage and high deductibles. The employee in these situations has limited or no choice and simply must take what he/she is offered. It’s really not buyer beware but rather take it or leave it.

We can do better.

Interesting article in the NY Times 6/12/07 Incentives Limit any Savings in Treating Cancer.

A number of observations were made in the article, many quite accurate and revealing. However the article did not emphasize or give much weight to the tremendous inflation in drug costs over the past 20 years. In the 80’s the average drug cost at most several hundred dollars/dose, in the 90’s the first drug to cost more than $1000/dose (Taxol when under patent if I recollect correctly) was marketed. We now are in the situation where new drugs are costing several thousand dollars/dose with yearly costs approaching $100,000 for a single drug.

In the Times article article it was noted:

“Cancer patients and their families play a role in rising costs, too, because they understandably want doctors to exhaust every possible treatment, even if the doctors might serve their patients better simply by talking and listening to them.” (Medicynical note: Patients are often desperate and somewhat irrational about treatment alternatives. If given a small chance of short term improvement, even 10%, they will opt for the treatment. This, however, is no different today than in the past.)

“In general, oncologists make money by providing chemotherapy, even when it has little chance of success. Oncologists naturally dislike telling cancer patients that they have exhausted all available treatments. Ending chemotherapy, after all, means acknowledging that a patient’s disease has become terminal.” (Medicynical note: As noted above the difficulty is on both sides, patient and doctor. Removing the conflict of interest of physicians will require major changes in the system of reimbursements. We also need to find a way to foster realistic patient expectations and an understanding of the limits of current technology–the media doesn’t help with this as they publicize research results indiscriminately.)

…….”With the new limits on cancer drug profits, some cancer doctors are searching for new income – like performing chemotherapy more often or installing multimillion-dollar imaging machines where they profit when their patients receive diagnostic scans.” (Medicynical view: This is not the whole story. For many years Medicare underpaid support services in physician’s offices. They covered, for example, only a small part of the cost of providing infusion services. Part of the deal Medicare made with physicians when they changed the reimbursement system for drugs was to allow increased reimbursement for necessary support services. I’m uncertain whether some or all of the increase in “physician procedures” noted in the article is this adjustment in Medicare reimbursements. It should be noted also that while we take steps to limit excess profits for the physician there is no similar voiced concern or limit on profits for drug companies–they charge whatever they wish.)

“Today, the drugs range from relatively inexpensive treatments like Taxol, a breast cancer drug that costs about $150 a dose, to a new wave of biotechnology therapies like Avastin, a drug for colon and lung cancer that can cost as much as $8,800 a dose.” (Medicynical note: It would have been refreshing if the author had given emphasis to the inflation in drug costs and the drug industry’s outrageous abuse of patents. Patents give drug companies a government sanctioned monopoly. The quid pro quo of this privilege should be responsible pricing. In reality, drug pricing has little relation to the cost of development; it’s simply whatever the company thinks people or insurers will pay. If the medication is for a serious illness, such as cancer, the sky’s the limit and it’s pay us what we want or die. The major part of cost inflation in cancer care appears to be from patent abuse and price gouging by the drug companies. This added to significant overutilization and/or gaming of the system by physicians leaves us with out of control expenses.)

Our health care non-system needs to address cost inflation, and conflicts of interest as well as provider and administrative inefficiency. I’m hoping to see some awareness of this issue in the up-coming presidential campaign, but as a good medicynic, am not expecting much.

Value is not in the vocabulary of health care.

When the President talks about markets in health care he seems to mean that price. features and ultimately the value to the individual should determine purchases. That’s not a bad idea when buying a car, television or almost any consumer item. In those areas the item is discretionary and the purchaser does not perceive his/her life to be at risk. There are multiple virtually equivalent options. Pricing is more or less standardized–we all start from the same sticker price. The special features of each option are generic and apply to all those who purchase the item. Time is not critical to the decision process. Finally, understandable information regarding the benefits of each option is available, some from impartial sources.

In health care the consumer believes his/her well-being, ability to live without disability, and even life may be at stake when purchasing services or products. Options may be severely limited. Pricing and quality information (outcomes) is not easily available or understandable. Each patient’s case has variables that make the situation specific to the case and not generic. Hospitals seemingly charge each customer differently with as much as a 100% markup for an individual payer. Time is a factor and delay often unacceptable–delay may mean death. Finally, in most instances a consumer would have difficulty making a rational choice without guidance from his/her professional–who may be biased.

Abstract 6350 from the recent American Society of Clinical Oncology (ASCO):

Source of Funding, conflict of Interest (COI), and the interpretation of cancer clinical trials

This study looked at the interpretation of clinical trials results by investigators with conflicts of interest (i.e. they were one way or another financially linked to a drug company sponsor). The conclusion of the researchers was that “COI (medicynic note–conflict of interest) is associated with highly positive conclusions that use superlatives to promote the experimental arm.”

Combine these findings with other studies that show that conflicts of interest between practicing physicians and drug companies influence a physician’s choice of drugs and you have a picture of an industry fatally compromised at each level by financial interests. Where is the patient’s interest? That appears to be secondary.

It should be noted, with some irony, that it’s impossible to find the declarations of financial conflicts of the authors of abstracts for the 2007 ASCO meeting.

It’s not surprising to a medicynic that for drug companies profits come before patient safety or for that matter integrity.

This from USA today via Yahoo.

From the ASCO Meetings:

Randomized, double-blind multicentre phase III study of bevacizumab in combination with cisplatin and gemcitabine in chemotherapy-naive patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC): BO17704

In this study chemotherapy was compared with two dose levels of bevacizumab (Avastin), an anti-angiogenic agent, in lung cancer patients. Using chemotherapy alone (cisplatin and gemcitabine) progression free survival was 6.1 months. This compared with 6.7 months survival in the group who also received the lower dose of bevacizumab and 6.5 months in the group on the higher dose.

The results were reported to show a statistically significant “improvement” in survival. What is not reported is that the pricing of Avastin (bevacizumab) can be as high as $100,000/year.

There appears to be little or no cost sensitivity, or for matter cost awareness, in medical practice and research. This is one of the most important problems to be confronted as we move towards a national health system. Spending more than most people’s yearly salary or the cost of an automobile to achieve a few months additional survival does not seem reasonable.

What’s wrong with our system is that it’s not a system.

The news that a study found that Vitamin D decreased cancer risk by as much as 60% was impressive and widely touted as a proven means of preventing cancer.

Study: Vitamin D Reduces Cancer Risk

Vitamin D found to combat cancer

Sweeping cancer edict: take vitamin D daily

Unfortunately the actual numbers from the study (from AP article) that was published in the American Journal of Clinical Nutrition (not available on the web without payment) are much less impressive:

The researchers at Creighton University in Omaha focused on 1,179 seemingly healthy women with an average age of 67. The women were divided into three groups: 446 got calcium and vitamin D3 supplements, a similar number got calcium alone, and 288 took dummy pills.

The research team gave 1,000 daily international units of vitamin D, more than current guidelines calling for 200 to 600 units depending on a person’s age.

The researchers intended to check mainly for the effects of calcium on bone health. Their interest in cancer risk was secondary.

But the lower cancer risk stood out. Only 13 women, or 3 percent, developed cancer over four years of calcium and vitamin D supplements. With calcium alone, 17 women, or 4 percent, got cancer. With dummy pills, cancer appeared in 20 women, or 7 percent.

That shows a 60 percent lower cancer risk over four years in the group taking both supplements, compared to patients taking placebos. And when the first-year cancers were excluded – the ones mostly likely present before the study began – the findings were stronger still: a 77 percent lower risk for the combo group.

A study with 1179 people divided into three groups is very small. The numbers of cancers in the groups 13 vs 17 vs 20 are interesting particularly because of the different group sizes but in my view not conclusive. The occurrence of cancer in 7% of the placebo group over the 4 years of the study seems higher than the population at large and may indicate a problem with patient selection, rather than a protective effect from the vitamin D.

More work needs to be done before people run out and start taking doses of Vitamin D and calcium because as with all biologically active treatments there are risks–high blood levels of calcium and kidney stones come to mind immediately.

Threats about the non-approval of a drug. Nobody’s bothered with me but as noted previously Provenge has at best marginal activity.

Bill Clinton’s legacy will ultimately rest on his work on HIV, not what he did during his presidency but afterward. His mobilization of generic drug manufacturers to provide inexpensive medications for AIDS treatment programs is remarkable because it works closely with the UN AIDS programs around the world and the individual countries with AIDS problems.

President Bush’s finest hour may also be recognized sometime in the future as his provision of funding to AIDS programs. His AIDS legacy however will have to overcome the program’s built-in subsidy to the patent pharmaceutical industry–the program will only allow use of drugs that are U.S. FDA approved–and it’s questionable limited educational message that emphasizes abstinence and having one partner.

Uganda has been the poster child for the Bush program, claiming a success for an abstinence based educational program. But there are questions about what happened there

“Pro-abstinence-only organizations are increasingly using Uganda as an example to indicate the success of their methods. But this is inappropriate, since the multiplicity of prevention methods used in Uganda mean that the decline in HIV prevalence was certainly not due to abstinence-only messages. Uganda’s success was based not only on encouraging abstinence until marriage but also on encouraging fidelity thereafter and condom use. It involved pragmatic discussion of risky sexual behaviors, strong governmental leadership, and condom distribution. The open and frank discussion of the sexual means of HIV transmission that took place is certainly not a feature of the pro-abstinence-only agenda.”

“Those in charge of America’s PEPFAR initiative accept that the ABC approach in Uganda involved more than only abstinence, but a large cut of the money is still being channeled through Christian organisations. The plans drawn up by some of these faith-based groups tend to be ideological rather than evidence-based and can neglect the other important aspects of HIV prevention. Promoting sexual abstinence until marriage without looking at these other issues is a recipe for failure, and Uganda’s example cannot be allowed to be misused in this way.”

“Unfortunately, there is no easy solution to an HIV epidemic. Uganda may have decreased its HIV prevalence but there have been many deaths in the country, and will be many more yet. There is no simple way to reducing the number of new infections – a number of different interventions are required. Foremost among these are a balanced ABC approach, committed political leadership, a willingness to discuss openly the ways in which HIV transmission can be prevented, and a vigorous response from communities across the country.”

Uganda’s decreased HIV prevalence however, may not represent a success of prevention. The decrease in disease that was reported over the past 15 years appears to have been due more to mortality and out migration than a great success of the ABC prevention method. In 2006 and increase in prevalence in Uganda was noted.

Faith based groups have control over the U.S. program’s message and their bias is affecting the objectivity of analysis and the educational message. It is not a little ironic that these same groups in the 80’s and 90’s essentially abandoned those with HIV and did not become involved with treatment or prevention until recently. Letting their bias against condom use subvert the educational message of the U.S. program is yet another AIDS tragedy–as Uganda may be finding today.

In addition to a more enlightened educational message, one would hope that the Bush program would become more efficient and make use of the least expensive generics for HIV so as to maximize the number of people treated. WHO has a means of certifying the medications which should be more than adequate for this purpose. The use of our FDA approval is simply a sop and subsidy to the patent pharmaceutical industry and blocks utilization of effective inexpensive medications from elsewhere.

Meanwhile, the U.S. hasn’t solved the problem of delivering appropriate treatment to patients here at home.