How Helpful Are New Drugs? Not So Clear

Tyler Cowen links to a paper by Frank Lichtenberg, an economist at Columbia University, that tries to estimate the benefits of drug company innovation by estimating how much new drugs prolong life compared to older drugs. The paper compares people equated in a variety of ways except the “vintage” (date of approval) of the drugs they take. Does taking newer drugs increase life-span? is the question Lichtenberg wants to answer. He concludes they do. He says his findings “suggest that two-thirds of the 0.6-year increase in the life expectancy of elderly Americans during 1996-2003 was due to the increase in drug vintage” — that is, to newer drugs.

An obvious problem is that Lichtenberg has not controlled for health-consciousness. This is a standard epidemiological point. People who adopt Conventional Healthy Behavior X (e.g., eat less fat) are more likely to adopt Conventional Healthy Behavior Y (e.g., find a better doctor) than those who don’t. For example, a study found that people who drink a proper amount of wine eat more vegetables. Another reason for a correlation between conventionally-healthy practices is mild depression. People who are mildly depressed are less likely to do twenty different helpful things (including “eat healthy” and “find a better doctor”) than people who are not mildly depressed. (And mild depression seems to be common.) Perhaps doctors differ. (Lichtenberg concludes there are big differences.) Perhaps better doctors (a) prescribe more recent drugs and (b) do other things that benefit their patients. Lichtenberg does not discuss these possibilities.

A subtle problem with Lichtenberg’s conclusion that we benefit from drug company innovation is that drug-company-like thinking — the notion that health problems should be “solved” with drugs — interferes with a better way of thinking: the notion that to solve a health problem, we should find out what aspects of the environment cause it. I suppose this is why we have Schools of Public Health — because this way of thinking, advocated at schools of public health, is so incompatible with what is said and done at medical schools. Public health thinking has a clear and impressive track record — for example, the disappearance of infectious disease as a major source of death. There are plenty of other examples: the drop in lung cancer after it was discovered that smoking causes lung cancer, the drop in birth defects after it was discovered that folate deficiency causes birth defects. Thinking centered on drugs has done nothing so helpful. Spending enormous amounts of money to develop new drugs shifts resources away from more cost-effective research: about environmental causes and prevention. Someone should ask the directors of the Susan K. Komen Foundation: Why “race for the cure”? Wouldn’t spending the money on prevention research save more lives?

 

Assorted Links

  • Experiments suggest flu shots reduce heart attacks and death. Huge reduction: 50%. The new report (a conference talk, not a paper) is a reanalysis of four earlier experiments. I was surprised to learn that the CDC uses heart attack outbreaks to locate flu outbreaks, implying that the new finding is not a fluke — there really is a strong connection. I already knew heart attacks are more common in the winter, which also supports a connection with flu.
  • Une histoire des haines d’écrivains by Boquel Anne and Kern Etienne. Published 2009. About literary feuds. One of my students was reading a Chinese translation.
  • Correspondences between sounds and tastes.
  • Report on fraudulent Dutch research. “The 108-page report says colleagues who worked with Stapel had not been sufficiently critical. This was not deliberate fraud but ‘academic carelessness’, the report said.” I doubt it. Based on my experience with Chandra, I believe Stapel’s colleagues had doubts but did nothing from some combination of careerism (doing something would have cost too much, for example a lot of time, and gained them nothing), ignorance (not their field), and decency (they saw no great value in ruining someone). I wonder if the report considered these other possible explanations (careerism, ignorance, decency).

Thanks to Tim Beneke.

The Emphasis on Education in China

One of my students grew up and went to high school in Nanjing, population 8 million. Her acceptance to Tsinghua was such a big deal that when her acceptance letter reached the local post office they called to tell her. The post office also alerted journalists. When the letter was delivered to her house, there were about 20 journalists on hand. One of them, from a TV station, asked her to say something to those who failed.

Thirty Years of Breast Cancer Screening May Have Done More Harm Than Good

A recent op-ed in the New York Times by H. Gilbert Welch, a co-author of Overdiagnosis, describes a tragedy of ignorance and overconfidence. The current emphasis on regular mammograms began thirty years ago. They will prevent breast cancer, doctors and health experts told hundreds of millions of women. They will allow early detection of cancers that, if not caught early, would become life-threatening. The campaign was very successful. According to the paper cited by Welch, about 70% of American women report getting such screening.

It is now abundantly clear this was a mistake. If screening worked perfectly — if all of the cancers it detected were dangerous — the rate of late-stage breast cancer should have gone down by the amount that the rate of early-stage breast cancer went up. Over the thirty years of screening, the rate of (detected) early-stage breast cancers among women over 40 doubled, no doubt because of screening. (Over the same period the rate of early-stage breast cancers among women under 40 barely changed.) In spite of all this early detection and treatment, the rate of late-stage breast cancer among women over 40 stayed essentially the same. All that screening (billions of mammograms), all that chemo and surgery and radiation, all that worry and time and misery — and no clear benefit to the women screened and those who paid for the screening, treatment, and so on. Roughly all of the “cancers” detected by screening and then, at great cost, removed, aren’t dangerous, it turns out.

Quite apart from the staggering size of the mistake and the long time needed to notice it, screening has been promoted with specious logic.

Proponents have used the most misleading screening statistic there is: survival rates. A recent Komen Foundation campaign typifies the approach: “Early detection saves lives. The five-year survival rate for breast cancer when caught early is 98 percent. When it’s not? It decreases to 23 percent.” Survival rates always go up with early diagnosis: people who get a diagnosis earlier in life will live longer with their diagnosis, even if it doesn’t change their time of death by one iota.

Did those making the 98% vs. 23% argument not understand this?

I applaud Welch’s research, but his op-ed has gaps. A unbiased assessment of breast cancer screening would include not only the (lack of) benefits but also the (full) costs. Treatment for a harmless “cancer” may cause worse health than no treatment. Maybe chemotherapy and radiation and surgery increase other cancers, for example. What about the effect of all those mammograms on overall cancer rate? Welch fails to consider this.

Welch also fails to make the most basic and important point of all. To reduce breast cancer, it would be a good idea to learn what environmental factors cause it. (For example, maybe poor sleep causes breast cancer.) Then it could be actually prevented. Much more cheaply and effectively. Yet the Komen Foundation and the Canadian Breast Cancer Foundation say “race for the cure” instead of trying to improve prevention.

 

Assorted Links

Thanks to Paul Nash, Grace Liu and Anne Weiss.

The Physical Spacing Effect: New Way to Learn Chinese Works Shockingly Well

Two years ago I taped a bunch of Chinese flash cards (Chinese character on one side, English meaning on the other) to my living room wall (shown above). I’ll study them in off moments, I thought. I didn’t. It was embarrassing when guests pointed to a card and said, “What’s that?” But not embarrassing enough.

A few weeks ago, I can’t remember why, I decided to test myself: how many do I know? About 20%. I’ll try to learn more, I thought. I was astonished how fast I learned the rest. It took little time and almost no effort. I didn’t need “study sessions”. I glanced at the array now and then, looked for cards I didn’t know yet, and flipped them to find out the answer. After a few days I knew all of them.

I had been using conventional methods (flash cards studied in ordinary ways, Anki, Skritter) and an unconventional method (treadmill study) to learn this material for years. In spite of spending more than a hundred hours on each method, I had never gotten very far. I might get to 500 characters and backslide due to lack of study. Treadmill walking while studying made studying much more pleasant, but I found I would still prefer to watch TV rather than study Chinese. Maybe part of the problem was too many days skipped. After you skip four days, for example, you have a discouragingly large number of cards to review. Plainly these methods work for others. They didn’t work for me.

After my success with the two-year-old cards, I put up another array (8 x 13). I already knew about 40% of them. I learned the rest in a day or so. Then I put up a 10 x 12 array. I tested myself on them one morning. I knew 30 of them. I studied them during the day for maybe 30 minutes in little pieces throughout the day. The next morning I tested myself again (about 12 hours from the last time I had studied them). Now I knew 105 — I had learned 75 in one day, almost effortlessly. That day I studied for a few minutes. The next morning I tested myself again. Now I knew all but one of them.

I did not notice any facilitation of learning when I studied flash cards while walking around. In that case, unlike this one, (a) they were in roughly the same position relative to my body and (b) had no consistent physical location. I noticed the same facilitation of learning during a Chinese lesson in a cafe. I was having trouble remembering three Chinese words (e.g., the Chinese word that means graduate). I wrote each of them on a piece of paper with the English on one side and the Chinese on the other. I put the three pieces of paper at widely-separated places on the table. I studied them briefly, a few seconds each. That was enough. Five days later I still remember them (having used them a few times since then). This happened in a place (a cafe) with which I wasn’t familiar, unlike my living room. Maybe the general principle will be it is much easier to learn an association if it is in a new place.

It’s very early in my use of this method, but I doubt it’s a fluke. It connects with several things we (= psychology professors) already know. 1. The mnemonic device called the method of loci. You put things you want to learn in different places in a well-remembered landscape (e.g. different places in a building you know well). Usually the method is used to learn lists, such as the digits of pi or the order of cards in a deck. You place different items in the list in different places in the imagined place. Then you “walk” (in your imagination) through the imagined place. The method dates back to ancient Rome. 2. The power of interference. Thousands of experiments have shown that learning X makes it harder to learn similar Y. X and Y might be two lists, for example. The greater the similarity, the bigger the effect. What you learn on Monday makes it harder to learn stuff on Tuesday (proactive interference); what you learn on Tuesday makes it harder to remember what you learned on Monday (retroactive interference). To anyone familiar with these experiments, my discovery has a simple “explanation”: spatial interference. 3. Evolutionary plausibility. The study of printed materials (e.g., books) is so recent it is hard to imagine our brain has evolved to make it easy. In contrast, thousands and millions of years ago we had to learn about things in different places. Learning about food and danger in different places was especially important. When language arrived, the necessary learning (at first, attaching names to objects) is quite similar to my learning because the named objects were in different places. The study of vitamins and to some extent my work (especially the power of morning faces) show how hard it can be to figure out what we need for our brains and bodies to work well. How non-intuitive the answers may be.

These results suggest a new mnemonic device: Stand in front of an empty wall and imagine on the wall the associations you want to learn, each association in a different place like flashcards. This is a fast way of putting each association in a different place.

 

 

 

No More Antixoxidants

This fascinating blog post by Josh Mittledorf points out that antioxidants, once believed to reduce aging by reducing oxidative damage, have turned out to have the opposite effect. By reducing a hormetic effect, they make things worse. I’m a friend of Bruce Ames, one of main proponents of the free radical theory of aging. I’ve heard him talk about it a dozen times. The turning point — the beginning of the realization that this might be wrong — was this 1994 study, which found that beta-carotene, a potent antioxidant, increased mortality. Bruce did not have a good explanation for the counter-theoretical result. However, Mittledorf doesn’t mention an important fact which doesn’t fit his picture. Selenium, a potent antioxidant, also powerfully reduces cancer. Don’t stop taking selenium.

I also like this theoretical paper by Mittledorf about why aging evolved (turning off certain genes reduces aging) and how its evolution — not easily explained by conventional evolutionary ideas — is part of a range of phenomena that the conventional ideas cannot explain. One reason, maybe the main reason, that aging is adaptive is very Jane Jacobsian: it makes the community more flexible. Less likely to repeat old ways of doing things.

Thanks to Ashish Mukarji.

 

 

How I Read

In a review of a book by Alice Munro, Charles McGrath, who edited her at The New Yorker, wrote:

Many of these stories are told in Munro’s now familiar and much remarked on style, in which chronology is upended and the narrative is apt to begin at the end and end in the middle. She has said that she personally prefers to read stories that way, dipping in at random instead of following along sequentially,

That’s what I do. Most books I find are improved if I start in the middle and hop around. Doing so adds difficulty and mystery, which otherwise they are deficient in. Same reason I usually like reality shows more than scripted shows, scripted shows lack that attractive raw edge. Spy magazine had an article about writing guidelines for a woman’s magazine. The guidelines said start in the middle: Talk about someone (“he” this, “he” that) before identifying them.

A few great writers (Vladimir Nabokov, Jane Jacobs, Tolstoy) I don’t do this with. Some true crime (The Stranger Beside Me by Ann Rule) I don’t do it with. But most books benefit.

 

Flaxseed Lowers Blood Pressure

A new study found that ground flaxseed powerfully lowers blood pressure:

A patient population with peripheral artery disease (PAD) was selected as ideal to benefit from dietary flaxseed. . . . Patients received 30g of milled flaxseed (or placebo) each day over 6 months. [I eat 50 g/day — Seth] . . . No significant adverse events were associated with flaxseed ingestion. . . . SBP in the placebo group increased by ~3 mmHg and DBP remained the same over the experimental period. However, SBP levels were ~10 mmHg lower (P<0.04) and DBP was ~8 mmHg lower (P<0.004) in the flax group compared to placebo. In the flaxseed group, patients with a SBP <140 mmHg at baseline did not receive an anti-hypertensive effect but patients who entered the trial with a SBP > 140 mmHg at baseline obtained a sustained and significant 15 and 7 mmHg reduction in SBP and DBP, respectively, during the six months. . . . one of the most potent anti-hypertensive effects ever observed by a dietary intervention.

This supports my belief that we can improve our overall health by trying to improve our brains (which are more sensitive than the rest of the body). I have blogged about flaxseed oil many times. I became interested in it when I noticed it improved my balance. Balance measurements showed that the optimal dose (2-4 T/day) was higher than flaxseed oil manufacturers suggested. Then I and others noticed that taking this amount of flaxseed oil produced big improvements in gum health. Tyler Cowen, for example, no longer needed gum surgery. Go home, said the surgeon.

Thanks to Grace Liu.

Taobao’s Double Eleven: World’s Biggest eHoliday

Do the heads of eBay and Amazon know about the Chinese shopping site Taobao (like eBay without auctions)? If so, why don’t they imitate it? Maybe they can’t match its bigger selection (e.g., food, detergent) and better prices, but they could imitate the better seller feedback and instant communication (chat boxes) with sellers.

In my theory of human evolution I propose that we have ceremonies, rituals, and festivals (and associated holidays) because they caused trading that would otherwise not have taken place. Ceremonies and so forth increased the demand for certain goods — gifts and high-end clothes, for example. These goods are important economically far out of proportion to their volume or monetary value or daily use because they increase innovation. They help the most skilled artisans– the ones most likely to innovate — make a living.

The leaders of Taobao understand this function of festivals/holiday and have put it to use: They have created new festivals/holidays. The biggest is Double Eleven (November 11), which started five years ago. On Double Eleven, a large fraction of taobao merchants have discounts, big (50%) and small (5%). Sales have grown each year and this year reached about $3 billion, according to one site. According to a Chinese friend, the sales were about $10 billion. CyberMonday (about $1 billion in 2011) is far behind

I have never read about this function of ceremonies, festivals, etc., in any economics book or paper. Double Eleven shows their economic force. This neglect is an example of what I consider the biggest problem with modern economics: lack of attention to and lack of understanding of innovation.