Chance News 58

Quotations

Berkeley law professor Kevin Quinn is working on a "statistical time machine" to compare Supreme Court justices' positions across historical time periods. He emailed Carl Bialik ("Statistical Time Travel Helps Answer What-Ifs", The Wall Street Journal, November 12, 2009) the following quotation:

The famous statistician George Box once wrote that "all models are wrong, but some are useful."

Submitted by Margaret Cibes

Everyone believes in the normal law, the experimenters because they imagine that it is a mathematical theorem, and the mathematicians because they think it is an experimental fact.

Henri Poincare

Submitted by Steve Simon

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Forsooths

In a Wall Street Journal article, "These Hobbyists Add to Calculators, Multiplying Their Fun", November 17, 2009, Dionne Searcey reports:

After two months of trying to crack the code - a process that involved factoring two huge prime numbers - Mr. Moody says he succeeded in July.

Submitted by Margaret Cibes

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The value of negative data

Little Benefit Seen, So Far, in Electronic Patient Records, Steve Lohr, The New York Times, November 15, 2009.

Study Raises Questions About Cholesterol Drug’s Benefit, Natasha Singer, The New York Times, November 15, 2009.

Seeking a Shorter Path to New Drugs, Steve Lohr, The New York Times, November 15, 2009.

Negative data, data that disproves a commonly held belief about the superiority of a particular medical treatment, is especially valuable from an economic perspective, but doesn't get the respect it deserves.

Providing high tech electronic health records should lead to better care, but apparently it doesn't.

The nation is set to begin an ambitious program, backed by $19 billion in government incentives, to accelerate the adoption of computerized patient records in doctors’ offices and hospitals, replacing ink and paper. There is wide agreement that the conversion will bring better care and lower costs, saving the American health care system up to $100 billion a year by some estimates. But a new study comparing 3,000 hospitals at various stages in the adoption of computerized health records has found little difference in the cost and quality of care.

Previous studies had used a selected subset of health care practices.

The study is an unusual effort to measure the impact of electronic health records nationally. Most of the evidence for gains from the technology, Dr. Jha said, has come from looking at an elite group of large, high-performing health providers that have spent years adapting their practices to the technology. The group usually includes Kaiser Permanente, the Mayo Clinic, the Cleveland Clinic and Intermountain Healthcare, among others.

In another study, an expensive cholesterol lowering drug was found to perform less well than a simple inexpensive alternative.

For patients taking a statin to control high cholesterol, adding an old standby drug, niacin, was superior in reducing buildup in the carotid artery to adding Zetia, a newer drug that reduces bad cholesterol, according to a new study. The results of the study, published in The New England Journal of Medicine, were presented here Sunday night at an annual meeting of the American Heart Association.

The study was small (208 patients) and used a surrogate outcome, arterial wall thickness. The findings pitted raising good cholesterol against lowering bad cholesterol, and found that raising good cholesterol was better.

Over the course of the 14-month study, the bad cholesterol of the patients on Zetia decreased by 19.2 percent, but the patients’ arterial wall thickness stayed the same, the study said. In the niacin group, good cholesterol increased by 18.4 percent and the carotid wall thickness decreased.

But the use of arterial wall thickness also led to criticism by Dr. Peter S. Kim, the president of Merck Research Laboratories who said that

a drug’s ability to improve artery-wall thickness has not been proved to automatically correlate with a reduction in heart attacks.

The efficacy of Zetia has also been established on the basis of a surrogate outcome, reduction in levels of bad cholesterol.

Zetia, he said, lowers bad cholesterol and lowering bad cholesterol is a known good. The study results “should be compared to the overwhelming body of evidence that lowering LDL cholesterol is an important thing to do to improve cardiovascular health,” Dr. Kim said.

Others, however, felt that this study showed problems with a heavily marketed drug.

Some cardiologists here hailed the study as an indication that the popularity of Zetia and Vytorin, which had combined sales last year of about $4.6 billion, has far outstripped their evidence of a concrete benefit on heart health.

The final article noted the huge expense associated with drug development. Why does it cost $800 million to bring the average drug to market?

Most of the cost in drug development is the price of failure, said Mervyn Turner, the chief strategy officer at the drug giant Merck. This linear, trial-and-error method is no longer a sustainable model for big pharmaceutical companies. “We invest far too long in bad ideas,” Dr. Turner said in a phone interview. “It is really important to stop that at an earlier stage in the cycle.”

One of the suggestions to reduce drug development cost is to publicize early failures.

One idea is for drug makers to share information about compounds they have tried and shelved, for reasons like toxicity or inefficacy. Although many companies have committed to publishing the results of clinical trials, whether or not they succeed, drug makers don’t typically publish information about projects that fail at an earlier stage. A result is that companies waste many millions going down experimental paths that their competitors have already found to be dead ends.

Submitted by Steve Simon

Questions

1. Some people are trying to put a "spin" on the positive effects of electronic medical records at leading health care institutions and the lack of effect in a nationwide survey, as indicating that the electronic medical record works, but it takes time and effort. Do you agree or disagree?

2. Zetia was approved by the FDA on the basis of a surrogate outcome, reduction in bad cholesterol, rather than in an outcome like decreased mortality or reduction in the number of heart attacks. Should the FDA require a new drug to show effectiveness on a direct measure instead of a surrogate measure?

3. What are the barriers to drug companies sharing information about early failures in the drug development process?

Art for the birds

“A bird’s eye view of art”, Science News, June 30, 2009

According to this very brief article, Japanese Professor Shigeru Watanabe has published a study in Springer’s Animal Cognition, which concludes:

Pigeons could be art critics yet, ... like humans, pigeons can be trained to tell the difference between "good" and "bad" paintings.

Curious readers without access to this journal might be interested in an earlier, full-text online, Watanabe paper, “Pigeons’ Discrimination of Paintings by Monet and Picasso” (Journal of the Experimental Analysis of Behavior, March 1995).

Abstract: Pigeons successfully learned to discriminate color slides of paintings by Monet and Picasso. Following this training, they discriminated novel paintings by Monet and Picasso that had never been presented during the discrimination training. Furthermore, they showed generalization from Monet's to Cezanne's and Renoir's paintings or from Picasso's to Braque's and Matisse's paintings. These results suggest that pigeons' behavior can be controlled by complex visual stimuli in ways that suggest categorization. Upside-down images of Monet's paintings disrupted the discrimination, whereas inverted images of Picasso's did not. This result may indicate that the pigeons' behavior was controlled by objects depicted in impressionists'paintings but was not controlled by objects in cubists' paintings.

This paper describes in great detail (methodology, statistical test results) several controlled experiments on “eight experimentally naïve pigeons."

Submitted by Margaret Cibes