More on Avastin (bevacizumab) in Breast Cancer– $400,000/patient

Posted on January 26, 2012 | Leave a comment

There has been much written about the rather minor improvement in breast cancer outcomes with Avastin (bevacizumab).  My last post pointed out one theoretical problem with use of this drug in cancer.

In this week’s NEJM there  are two studies, reporting a small beneficial effect with bevacizumab in patients with early HER2-negative breast cancer.  The authors of one study  note:  (other study here)

The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response among patients with HER2-negative early-stage breast cancer. Efficacy was restricted primarily to patients with triple-negative tumors, in whom the pathological complete response is considered to be a reliable predictor of long-term outcome.

In the study 1948 newly diagnosed breast cancer patients were randomized to receive chemotherapy alone or with concomitant bevacizumab before surgery (neoadjuvant treatment).  The results showed that pathological complete response  was 18.4% in patients receiving bevacizumab and 14.9% without it.  A difference of 3.5%, hardly significant.  In patients with triple negative tumors (ER, PR and HER2 negative) the results were more impressive with 27.9% pathologic complete remission without bevacizumab and 39.3%   with it.  There was no difference in the 1262 ER PR positive patients.  (7.8 and 7.7%)

We don’t know at this time whether the improved CR rate in these patients will translate into improved survival and hopefully cures.

Medicynical Note:  What we can determine however is the cost of the intervention.  Consider the 663 patients that were triple negative.  I assume that about half (I don’t have full access to the article), let’s say 330 patients received bevacizumab.  Then lets take the 39.3% complete response rate,11.6% more than those not receiving the drug, and do a rough estimate of cost. 

39.3% of 330 is 129.69 patients achieved complete remission.  11.6% or 38.38 patients was the incremental benefit.  Assuming a cost in the range of $50,000 for a 3-5 month course of treatment, the total cost of treating these 330 patients with the best outcome in the study would be (paying market prices for the drug) in the range of 16 and a half million dollars.  Dividing that by the incremental benefit of 38.38 the cost of the benefit/patient  was $429,911.

Cost is a real problem for a health care non-system that spends 17% of GDP on health care,  almost twice that of other countries.  Can we afford an intervention that costs over $400,000/patient who benefits?  

I have no particular bias against Avastin (bevacizumab) except for the fact that it (and other similar drugs) appears to have very limited efficacy and is so expensive.  If it were a drug costing $5000-10,000 for a course of treatment I’d say give it a try.  At the present cost and level of efficacy it’s hard to find a strong argument for it’s use, except that it must make the manufacturers and their stockholder a great deal of profit.

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Posted in Cancer medicine (Oncology), General Cynicism, Health Economics, Patents

Avastin (bevacizumab), Sutent (sunitinib)– Fundamental Problems in Cancer Treatment

Posted on January 26, 2012 | Leave a comment

There is wide documentation of the relative ineffectiveness of Avastin (bevacizumab) in breast cancer.  The drug simply doesn’t extend the lives of those treated significantly. 

Why?  It ‘s been an open question with the drug company maintaining that the drug costing between $75,000 and $120,000/year for treatments has some effect and that is enough to warrant it’s continued use.  The FDA differed and removed the breast cancer indication, though some insurers for some some reason continue to pay.

There is now an explanation why the drug failed.

Antiangiogenic therapy has been thought to hold significant potential for the treatment of cancer. However, the efficacy of such treatments, especially in breast cancer patients, has been called into question, as recent clinical trials reveal only limited effectiveness of antiangiogenic agents in prolonging patient survival. New research using preclinical models further suggests that antiangiogenic agents actually increase invasive and metastatic properties of breast cancer cells. We demonstrate that by generating intratumoral hypoxia in human breast cancer xenograpfts, the antiangiogenic agents sunitinib and bevacizumab increase the population of cancer stem cells. 

If the finding is confirmed it provides an explanation of the mediocre results in breast and other cancers for this drug.  It raises question about it’s continued use and certainly would argue against using it alone either as a primary treatment or maintenance therapy option.

Medicynical Note:  One hopes this is new information and that the drug company was not previously aware of the increase population of stems cell generated by presumed antiangiogenic caused hypoxia. 

More broadly, how can it be that our pharmaceutical industry sells drugs (sometimes even effective drugs) at twice the median and average income of citizens.  This is not a sustainable model either for business or for health care.

There’s obviously something wrong with our drug development system; drug patents: our non-system of health care; and our payment schemes.  If we ultimately want to reform health care these issues need to be addressed.

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Posted in Cancer medicine (Oncology), General Cynicism, Health Economics, Patents

High Deductible Plan: Changes Behavior, Delays Care

Posted on January 24, 2012 | Leave a comment

Nice review of an article in the Journal of General Internal Medicine at the Incidental Economist.  The article documents delays in care by people with chronic illness and high deductible coverage. 

It was pointed out:

  that people aren’t very good at discriminating between necessary and unnecessary care. This is fine if you’re healthy, when pretty much all care is unnecessary. If you’re sick, though, then across the board care cuts can be bad.

And they found:

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More than a quarter of adults had delayed or went without care because of cost. Adults were specifically more likely to delay or forego acute care visits, chronic care visits, checkups, and tests.

There were similar findings for care in children whose families had this type coverage.  The delays were particularly noted in those below 400% of the poverty line. 

Medicynical Note:  I’ve previously expressed reservations regarding high deductible insurance  and Health Savings Accounts.    

For those at or below the median wage, high out of pocket expenses influence whether or not to seek care—a form of implicit financial rationing.  In this setting the least knowledgeable, most emotionally involved get to decide whether or not to go for expensive interventions  for which they will have to pay. 

This might work if our costs were affordable, but they’re not.

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Posted in General Cynicism, Health Economics

Lung Cancer Treatment: Joe Paterno, a Teaching Moment

Posted on January 22, 2012 | Leave a comment

At age 85 a person’s life balance is quite fragile.  Medical problems that at a younger age have no effect on the quality or quantity of life can at age 85 have major consequences.  Flu may lead to pneumonia; a simple fall may break a bone and lead to complications; cancer treatments may have life threatening consequences.

At one time aggressively treating a person over age 80 with chemotherapy, much less chemotherapy combined with radiation, would have been unthinkable.  With medical “progress,” however, we believe that we can aggressively treat everyone, including the aged.

This was todays headline:  Joe Paterno, Penn State’s legendary football coach, dies:

Former Penn State head coach Joe Paterno, his body ravaged by chemotherapy and radiation treatments for lung cancer, died early Sunday morning at Mount Nittany Medical Center in State College.

Medicynical Note:  I don’t know how the advantages and disadvantages of treatment were spun to Mr. Paterno by his doctors. 

I can infer from the approach, chemo and radiation, that the disease was nonresectable (not amenable to surgery).  That is, it was either locally advanced or metastatic.  It is a fact that virtually all such patients (young and old) will have  limited benefit from aggressive treatment, and not be cured, regardless of age.  The results of studies in stage 3 and 4 lung cancer range  from  no survival benefit to a  few month’s longer life (median benefit).   Meanwhile many of these patients will have significant side effects, often debilitating and life threatening. 

Regarding those over age 80 and the benefits of lung cancer treatment,  see here:

The > or =80 age group was less likely to be subjected to surgery or chemotherapy, and had inferior outcomes when compared with the 70-79 age group and the <70 age group. Survival improvement was not observed in the > or =80 age group.

Regarding elderly patients with lung cancer: (note the difference between the elderly (age 70-79 and those over age 80)

Evidence supports that elderly patients with good PS and limited comorbidity may benefit from combination chemotherapy. Age alone should not dictate treatment-related decisions in patients with advanced NSCLC. Elderly patients with a good PS enjoy longer survival and a better quality of life when treated with chemotherapy compared with supportive care alone. Caution should be exercised when extrapolating data for elderly patients (aged 70–79 years) to patients aged 80 years or older because only a very small number of patients aged 80 years or older have been enrolled on clinical trials, and the benefit in this group is uncertain. (Medicynical emphasis)

Mr. Paterno’s treatment decision was, I’m sure, his own choice, influenced by his physicians as well as his personal beliefs.  His poor outcome is within the range of expected results for this terrible disease. 

Addendum:  Mr. Paterno is reported to have been diagnosed with small cell cancer of the lung with metastasis at diagnosis.  As with non-small cell lung cancer there is little data indicating a significant benefit for patients over age 80 from aggressive treatment.

The optimal therapeutic approach in older patients remains unclear. A population analysis showed that increasing age was associated with a decreased performance status and increased comorbidity.  Older patients were less likely to be treated with combined chemoradiation therapy, more intensive chemotherapy, and PCI. Older patients were also less likely to respond to therapy and had poorer survival outcomes. Whether this was a result of age and its associated comorbidities or suboptimal treatment delivery remains uncertain.

And:

Among patients with limited disease, the proportion receiving chemoradiation increased from 35% to almost 60% for those aged 60–69, from 28% to 48% in age group 70–74, from 17% to 33% in age group 75–79, but remained <10% for those aged 80+. Among patients with extensive disease, the proportion receiving chemotherapy (CT) decreased from 81% of patients aged 60–64 to 23% of those aged 85+, without substantial changes over time. Survival has only improved for patients <80 years.

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Posted in Cancer medicine (Oncology), Ethics, General Cynicism

GDP increase from Health Spending: Decreased Discretionary Spending the Result

Posted on January 21, 2012 | Leave a comment

It’s reported that consumer spending has increased since the 1960’s  from 61% to  71% of the the gross domestic product.  However, most of the increment is health care costs. 

Medical payments now account for about 16 percent of total consumer spending, more than food and clothing combined, which make up about 11 percent, or housing, which accounts for about 15 percent. The rising cost of health care means it will consume an even bigger share of the world’s largest economy as the population ages, according to economists like Jay Feldman.

“At the consumer level, it may squeeze out other discretionary spending,” Feldman, an economist at Credit Suisse in New York, said in an e-mail. “At the government level, rising Medicare and Medicaid spending will inevitably put pressure on other government spending priorities. At the business level, it could curtail investment, or more likely, suppress wages.”

Capture

Medicynical Note:  Increased discretionary consumer spending as a proportion of GDP (over the last 50 years in the U.S.) is an oxymoron.

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Posted in General Cynicism, Health Economics

Health Spending Growth: Regressing or on Hiatus

Posted on January 20, 2012 | Leave a comment

Uwe Reinhardt has some thoughts on the “moderation” of health spending.  He notes:

First, depending on the beginning and end points one chooses for calculation, the average percentage points by which the annual growth in health spending has exceeded the average annual growth in G.D.P. over the chosen period – a difference known among health policy analysts simply as “excess cost growth” – can vary quite a bit. One really needs charts like these to study the phenomenon, not point-to-point averages.

Second, the annual growth in real health spending per capita appears to have fluctuated around a long-run trend that has declined ever so gently over the longer period (see the blue line in Chart 3). That trend reflects in part that the annual growth in real G.D.P. per capita has also fluctuated around a gently declining trend line. As is shown in Chart 4, the trend line around which excess growth fluctuates is virtually flat.

The graphs show a huge yearly difference in the rate of increase in health care spending.  Read the article to view them.

Medicynical Note:  What’s missing from the article is a comparison of the increase in costs of health care with increases (or lack thereof) in income over the same period.  GDP increments miss entirely the huge disparities in wealth that have evolved in the past 30 years and the resulting poverty, decreases in real income, and decreases in the ability to pay for anything, including health care. 

The dilemma of U.S. health care is seems obvious.  Our costs have exceeded our individual and collective ability to pay.  How to resolve the disparity is the issue.

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Posted in General Cynicism, Health Economics

Two Ruined Lives: Boy 15 shoots sister

Posted on January 17, 2012 | Leave a comment

A sad but uniquely American happening: 

The teen likely killed his sister sometime after 8 a.m., when his parents left to go grocery shopping in Fort Smith, about 40 miles away, Boen said. The boy turned himself in at the sheriff’s department about an hour and a half later.

And:

Guns were confiscated from the family’s home and vehicle, the sheriff said. Authorities were trying to determine which weapon was used in the shooting.

Medicynical Note:  More than two lives ruined.  If you must have guns, please keep them locked up.

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Posted in Uncategorized

Great Moments in Medicine: Outpatient shocked by $45 billion dollar hospital bill

Posted on January 17, 2012 | Leave a comment

Mad Magazine famously pointed out the inflation in medical costs in the late 60’s with a parody on ads by Parke Davis (By Ken Freas). 

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Parody sadly has become reality:  Outpatient shocked by $45 billion bill.

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Posted in General Cynicism, Health Economics

Malaria: Artemisinin, Antimalarial with a political agenda

Posted on January 17, 2012 | Leave a comment

Fascinating story of the development of artemisinin, a antimalarial developed in China during the Vietnam era. 

Artemisinin’s discovery is being talked about as a candidate for a Nobel Prize in Medicine. Millions of American taxpayer dollars are spent on it for Africa every year.

But few people realize that in one of the paradoxes of history, the drug was discovered thanks to Mao Zedong, who was acting to help the North Vietnamese in their jungle war against the Americans. Or that it languished for 30 years thanks to China’s isolation and the indifference of Western donors, health agencies and drug companies.

Medicynical Note:  Perversely, the delay in development and distribution prevented it’s wide use, and perhaps the development of resistance.  It remains an effective agent.

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Posted in Health Economics, Patents, World Health

Product Line! Bottom Line! The New Paradigm for Medicine—Sleep Apnea

Posted on January 16, 2012 | Leave a comment

In the past 30 years the diagnosis of sleep apnea has gone from being an oddity to a mainline healthcare business.  Testing and prescribing has become a niche that provides lucrative revenue to specialized businesses.   As noted here:

It’s a condition shown to increase the risk of several serious illnesses, including heart disease, stroke and dementia. Critics, however, worry that overnight tests to diagnose apnea, particularly those done in sleep labs, may be over-prescribed, at great cost to the health care system.

Testing can be a lucrative business, and labs have popped up in free-standing clinics and hospitals across the country. Over the past decade, the number of accredited sleep labs that test for the disorder has quadrupled, according to the American Academy of Sleep Medicine.

At the same time, insurer spending on the procedure has skyrocketed. Medicare payments for sleep testing increased from $62 million in 2001 to $235 million in 2009, according to the Office of the Inspector General.

And:

It’s no secret that the sleep business can be lucrative for physicians. A website for Aviisha, a sleep testing company, has a special page for physicians showing a picture of a doctor with a stack of money in his lab coat pocket. And in February, the American Academy of Sleep Medicine is offering a seminar on the “business of sleep medicine for physicians” at a golf resort in Arizona.

Insurers are catching on and limiting the expensive on site testing encouraging  more use of home testing. 

What’s most interesting about this expenditure is that while there is extensive data showing a short-term improvement in symptoms with treatment there is no long term outcome data documenting effectiveness.  As noted in this presentation by Henry Glick of the University of Pennsylvania from the American Thoracic Society in 2010:

Given the large number of studies, why hasn’t the
question been satisfactorily answered?

  • Shares with health problems such as obesity the fact that while it “makes sense” that treatment should avoid outcomes such as heart attacks and stroke, but no trial has ever demonstrated that treatment actually avoids these outcomes (Medicynical Emphasis)

Medicynical Note:  As noted in a 1999 article on the costs of sleep apnea,

We conclude that patients with undiagnosed sleep apnea had considerably higher medical costs than age and sex matched individuals and that the severity of sleep-disordered breathing was associated with the magnitude of medical costs. Using available data on the prevalence of undiagnosed moderate to severe sleep apnea in middle-aged adults, we estimate that untreated sleep apnea may cause $3.4 billion (probably ten times that amount today) in additional medical costs in the U.S.  Whether medical cost savings occur with treatment of sleep apnea remains to be determined.

Confusing any study of outcomes is the fact that of those treated with CPAP  machines (continues positive pressure) only a minority, perhaps a small minority, continue to use them.

I conclude then, that there is a problem called sleep apnea, caused to a great extent by obesity.   We know, also, that an expensive diagnosis and treatment industry has evolved to manage this problem.  Sleep apnea diagnosis has become a product line for many companies.   There is evidence that  treatments,  some surgical and permanent and others temporary with use of oral appliances and/or machines may (CPAP) improve some symptoms.  But there is no evidence, at this time, that these treatments prevent long term complications (cardiovascular or pulmonary) and death.   For all we know, people treated may have exactly the same outcome as those not treated.

This raising the question of what is a cost effective approach for this problem?  Is our current approach  the most medically effective or do we need to rethink the whole thing?

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