Unreported Side Effects of Powerful Drugs (part 3)

A comment on the previous post in this series — thanks, Vesna! — led me to a horrifying story about what happened to someone whose doctor prescribed statins (an expensive and nearly worthless class of drugs) because his cholesterol numbers were bad. (My friend and collaborator Norman Temple has written about the true value of statins.) The doctor did not warn him of the dangers, which were great. When his troubles began, he should have simply stopped the drug. What actually happened was that his doctor prescribed another dangerous drug. And his troubles got worse. Shades of Jane Brody!

I know a similar story. The elderly mother of a friend of mine was taken to the emergency room of a hospital because she had some sort of attack. It was the third such attack in a year. Her children were concerned. She was not of sound mind. Heroic measures to help her? Or a peaceful death? They chose a peaceful death. She was moved to a hospice. By mistake, her six prescriptions failed to be transferred. A clerical error. So she wasn’t able to take her usual drugs. She soon got better! Within a week or two she returned home. The drugs her doctor had prescribed had been killing her. Nobody had noticed.

First do no harm is a scary motto because it shows that those who take it seriously — supposedly the entire medical profession — aren’t thinking clearly, as I’ve heard Robin Hanson point out. It’s like English teachers having a motto with a word spelled wrong. And the consequences of doctors not thinking clearly — not doing something as obvious as stopping dangerous drugs when the patient gets worse — can be terrible. My suggested replacement motto: Learn something from everyone who comes to you for help.

This is closely related to self-experimentation, of course, which is all about figuring out for oneself what effect something has. I got a lot more interested in self-experimentation when it showed me that an acne drug I’d been prescribed was worthless.

Part 1.

How Should We Fight Infections?

In the latest New Yorke r, an article by Jerome Groopman is about the emergence of even-more-antibiotic-resistant bacteria.

I asked him what we should do to combat these new superbugs. “Nobody has the answer right now,” he said. “The fact of the matter is that we have found all the easy targets” for drug development. He went on, “So the only other thing we can do is continue to work on antibiotic stewardship.”

All the easy targets, huh? Here’s an easy target that hasn’t been exploited: Why are colds more common in the winter? Many diseases are more common in the winter. I believe it’s because sleep is worse in the winter. While you are asleep is when your body does its best job of fighting off infection. When I vastly improved my sleep — by standing much more, and by getting more morning light — I vastly reduced the number of easy-to-notice colds that I got. I still got cold infections, I think, but they merely caused me to sleep more than usual for a few days.

Several years ago I noticed an introductory epidemiology course in the UC Berkeley School of Public Health was taught by someone I knew. I called him. “Is your course going to cover what makes our ability to fight off infection go up or down?” I asked. No, he said. That is the usual answer. The question of why colds are more common in the winter is not part of the traditional study of epidemiology.

The connections between sleep and fighting off infection are so strong I’m pretty sure I’m right about this (that colds are more common in the winter because sleep is worse). Why, then, haven’t sleep researchers looked into this? Strangely enough, they may not have thought of it; I haven’t come across this idea in any book about sleep I’ve read. (If you’ve seen it somewhere, please let me know!) Justifications of sleep research tend to revolve around car accidents, which are often caused by too little sleep.

More. My point is not that poorer sleep causes more colds in the winter; it’s that it’s an easy target. Suppose you think the colds/winter connection is caused by less Vitamin D in the winter. An experiment in which one group gets Vitamin D supplements in the winter and another group doesn’t is easy to do, given the great health implications.

My Humor Research


[Rosie Shuster] did have one quality she could privately lord over her classmates: her father was a comedian. . . A life in comedy meant that Frank Shuster nodded, rather than laughed, at jokes that worked.

From American Nerd: The Story of My People by Benjamin Nugent, pp. 62-3. When I was in college I came up with a theory: Laughter is caused by sudden pleasure. Obviously we enjoy jokes, and jokes have punchlines. People laugh in lots of situations not involving humor and as far as I can tell they always involve sudden pleasure — unexpectedly seeing an old friend, for example.

Which is only to say, as this passage implies, there should be a limited number of joke categories and they should be far from mysterious. I once wrote a bunch of jokes from the TV show Cheers on cards and sorted them into categories. Later I classified six months of New Yorker cartoons and Spy accepted it. It was my first submission and I was thrilled.

More. Mike Kenny put it better than me. That I was able to get my research published in a magazine I adored was “ a fusing of the intellectual with the practical.” I was going to say it was a practical application of pure research.

Research Assistant Needed in Cognitive Science Lab

Saul Sternberg, whom I interviewed about research design and research strategy,is looking for a research assistant:

A full-time research assistantship is available in Saul Sternberg’s laboratory at the University of Pennsylvania in Philadelphia. Â Applicants should be college graduates with computer programming skills and an interest in the study of human behavior. Current research topics include (1) interaction of brain and biomechanics in the control of timed actions (as in music performance), and (2) how visual information is encoded, transformed, and retrieved within the first two or three seconds after it is displayed. Details.

Saul is a member of the National Academy of Sciences and has won the American Psychological Association’s award for Distinguished Scientific Contribution.

He and I have written four papers together, three about Ranjit Chandra’s research and one about reaction time and mental models. In the Acknowledgments section of The Shangri-La Diet, I wrote, “I have learned more experimental psychology from Saul Sternberg, a research scientist at Bell Labs and a professor at the University of Pennsylvania, than from anyone else.”

The Bechdel Test and Denise Richards

I loved Alison Bechdel’s Fun Home. It was one of the best books I read in 2007. So I was pleased to learn of the Bechdel Test, which can be applied to TV and movies:

To pass it your movie [or TV show] must have the following:

1) there are at least two named female characters, who

2) talk to each other about

3) something other than a man.

Few movies or TV shows pass it, said Jennifer Kesler.

I came across this test after spending a pleasant morning analyzing data while listening to the first six episodes of Denise Richards: It’s Complicated which I found on YouTube. (Such as part 1 of Episode 1.) The show consisted mainly of two named female characters — Denise and sister, Denise and friend, Denise and daughter — talking to each other about something other than a man.

I was surprised how much I liked it. When Denise and her dad (who lives with her) interview people to be her assistant, it was amusing (Denise has about 20 pets; one applicant said she didn’t like pets); when she gets mad at an entertainment journalist, it was forgivable; when she enters her nephew’s room to find him and his friends looking at a Playboy with her on the cover, it was unforgettable. The entertainment journalist wants to know why she is doing the reality show. “My [recently dead] mom wanted me to do it,” Denise says. The journalist can barely keep from laughing. “A deathbed wish?” she says. Denise got upset, so let me answer: The better you know almost anyone, the more you like them.

How to avoid demonization.

More. Gillian Flynn, one of Entertainment Weekly‘s TV reviewers, hated the show — gave it a D. Could reviewers be overly negative because they are forced to watch?

More about Unreported Side Effects of Powerful Drugs

A few days ago I blogged about how Tim Lundeen, via careful and repeated measurement — let’s call it self-experimentation — uncovered a serious and previously-unreported side effect of a drug he was taking. Tim’s example illustrates an important use of self-experimentation: discovering unreported side effects, which I believe are common.

By coincidence today I came across a talk about the very subject of unmentioned side effects: Alison Bass speaking about her new book, Side Effects: A Prosecutor, a Whistleblower, and a Bestselling Antidepressant on Trial. Near the end, Bass said,

It’s not the just the antidepressants, it’s not just the antipsychotics. This is happening with a lot of other drugs. With Vioxx, with Vytorin, an anti-cholesterol drug, with Propries [?] and Marimet [?], anti-anemia drugs. Where again and again the drug companies know that there are more severe side effects and they’re not letting the public know about that. It just keeps happening, unfortunately.

Just as it would be foolish to think the problem is limited to mental-health drugs, it would be foolish to think the problem is limited to side effects, that drug company researchers do everything right except fail to report side effects. Tim’s example shows how hard it is to learn about unreported side effects — so it is only realistic to think that there are other big problems with drug company research we don’t know about. Bass mentioned one I didn’t know about. A company did a clinical trial of Paxil. The goal was to see if the drug helped with Measures of Depression A and B. Turns out it didn’t: no effect. So the company changed the measures! They shifted to reporting different measures that the drug did seem to improve. Creating the hypothesis to be tested after the data supposedly supporting that hypothesis had already been collected. Without making this clear. (Which I presciently mentioned here, in response to an interesting comment by Andrew Gelman.) And if you think that drug companies do research like this — in ways that seriously damage people’s lives — but everyone else, such as academia, is really good, that is as realistic as thinking the problem with drug company research is restricted to side effects. Self-experimentation has all sorts of limitations, yes, but (a) you know what they are and (b) it is cheap enough so that you can gather more data to deal with the problems. Drug company research and lots of other research is too expensive to fail — or even be honest about shortcomings.

This is an aspect of scientific method that scientists rarely discuss: the effect of cost on honesty. Is there an economic term (a Veblen good, perhaps?) for things whose quality goes down as their cost goes up?

Interview with Bruce Gray, Web-Savvy Sculptor (part 3)

ROBERTS What mistakes have you made with regard to the web?

GRAY I remember years ago I went to a company that was one of those web search enhancement companies and you were supposed to pay them a monthly fee and they would beef up your meta tags and stuff like this, and give you some advice on how to do the stuff, just tweaking out your website to make it more optimized. I was looking at some of the stuff they do, and one of the things was putting in these pages, your background pages, all kinds of meta tags, like keywords in white on a white background–that was kind of technique–a lot of people still use that, but it’s very highly frowned upon in the search engine world and if they catch people doing that kind of thing, they can definitely drop you down on your rankings status there and when I read that, I was like, ’Wow, this is the company I’m paying to do this for me and they’re doing something that the search engines don’t like you to do,’ so I dropped them. I want to be legitimate. I don’t want anybody to have any reason to take away any of my rankings status there.

ROBERTS Are there other artists who have gone into the web more than you? You’re by far the farthest in of anyone I’ve met.

GRAY I don’t know anybody else who has remotely the kind of website detail and depth that I do. I just try to put up, literally, almost every piece I’ve made that I can at least get a photo of. My website is way more in-depth and detailed than any other artist I know, by far.

ROBERTS Yes, that was my impression.

GRAY That helps, obviously.

ROBERTS Yes. Has anyone from the art world come and interviewed you about your web strategy?

GRAY I’ve definitely been asked about it quite a few times, actually. There was a book that came out years ago about selling art without galleries–I got interviewed about that kind of thing. Actually, almost anytime that I get asked about my sales, I start talking about the web and everybody gets very interested in how I’m doing it.

ROBERTS Has there been articles focused on that particular topic–you and the web?

GRAY No.

ROBERTS What else have you learned besides don’t go with that optimization company?

GRAY That you basically just have to keep up with it, keep it fresh, don’t make it too complex. I can’t tell you how many times, you know, I’m pretty web savvy, and I go to websites all the time that you get on to them and they’re so slow loading and when they do finally load, it’s like playing that game Myst to even try to find the buttons to go to anything. It’s almost more of a showcase for the web designer more than it is for the company that they’re trying to represent and I think that’s a huge mistake, because people just get too lost in that, and I think that’s a mistake that’s extremely commonplace.

ROBERTS You mean to have some kind of Flash animation, or something?

GRAY Yes, they have just too much crap. It’s too complex–you can’t even find the buttons, the navigation’s almost impossible. To even find how to make contact, or even get to the next page, you have to mouse all over the images and try to find what is the button, and these are gigantic companies and stuff. I’m just always amazed that they do things like that. And the other reality is that you’ve go to think who is looking at your website and who’s your market. In my world–in the art market world–my clientele tend to be older and very wealthy, 50s to 80s, mostly retired or with very hefty bank accounts, and the one thing that they don’t know is computers. Most of these people are not that computer savvy and if they get to your webpage and they can’t navigate around, or if they get to your webpage and it says, ’You’re going to have to download the latest version of Flash,’ and this, that, and the other thing, they’re going to be like, ’Oh, well the hell with that. What the hell is a download? What’s Flash?’ Seriously, I mean I have very smart people that just don’t have any reason to be that web or even computer savvy. They completed most of their career before everybody really go into computers that heavily, so they just don’t know them that well. So you have to make it–at least make the navigation–pretty simple, and no major drama to at least get to the home page. The fancy Flash opening thing in my opinion is just only a showcase for the Flash or the web designer.

ROBERTS I would imagine artists like yourself don’t have a lot of Flash on their pages.

GRAY Well, a lot of them do.

ROBERTS Really?

GRAY I’m all for doing that kind of thing, too, but if I wanted to do that, I would have it as the secondary page. Have the home page where you can have the two buttons, because that’s what a lot of people do. Go to the HTML version or go to the Flash version. At least if you separate it off on your home page, then people at least have the option before they get stuck in this window of a ten minute download.

ROBERTS What are your hopes–do you have other things you’re hoping for out of your webpage, your web presence, that you haven’t gotten yet? Or is it working pretty well?

GRAY Well, it’s been working pretty well. I just basically want it to continue to grow and get better. And it gradually is. Every year I do some new things and it adds a little bit more–new museums and things linking in–the more of that kind of stuff, the better.

ROBERTS When you say you do new things, you mean you add links or you add whole concepts or categories?

GRAY I mean I add the links any time that I’m on television or any books, magazines, weblogs or anything–all of that stuff. I link to them and they link to me, and it’s just another notch in the credibility factor.

ROBERTS I see, so it’s an ongoing process of trying to increase linkage and so forth.

GRAY Right. But that is the most important credibility factor in the web search engine world these days–good qualified links coming in to your site. Links that go out don’t mean anything; you can have six million of them and they don’t care.

ROBERTS Yes, I see what you mean. Is there anything about you and the web we haven’t asked about?

GRAY The one other thing that I think I should mention is that there is other ways of enhancing your web experience aside from just your own webpage and that’s things that are free, like My Space or LinkedIn for instance, are classic examples. They are very searchable in Google and they rank the information on these sites quite highly, so it’s good to have supplemental ways of people seeing your work other than just your own website. One of the reasons for that, and one of the reasons I kind of got into trying to go around and hook up with these other art websites is because of things like: Years ago, Yahoo! decided that they weren’t going to even list my home page anymore unless I paid them, so when they start doing things like that, you know, my website wouldn’t even be listed but all the other websites that mention me or link to me, those are all listed. I still get the listing on Yahoo! but not directly. I think that my website is listed now, but it’s down on the third page or so of listings for ’Bruce Gray sculptor.’

ROBERTS So if I search Yahoo! for ’Bruce Gray sculptor,’ I get your home page on the third page of listings–is that what you’re saying?

GRAY Something like that, yes. You’ll see a whole bunch of other stuff first, let’s put it that way. And that’s not that way on Google. That’s why everybody uses Google now. If the other search engine’s going to make a lot of the cool stuff have to pay to be on there, then obviously they’re not going to have anywhere near the level of listings that Google does, so what’s the point of even bothering with it?

ROBERTS Yes, I see what you mean.

GRAY That’s why they’re not doing so well.

ROBERTS Yes, the act of desperation. I think that covers it well. Thank you very much for your time.

The whole interview.

Benfotiamine and Self-Experimentation: Surprising Results

Tim Lundeen, whose fish oil/arithmetic results impressed me, recently tried taking benfotiamine (a fat-soluble version of thiamine) to reduce damage caused by high blood sugar. Things did not go as he expected:

I bought 100mg capsules from Life Extension Foundation, and starting taking 1 per day in the morning with breakfast. Over the course of 3-4 weeks, the two small dead spots on the bottoms of my big toes started to feel normal, and I didn’t notice them anymore when I went walking. My energy and general mood were good, and my fasting blood sugar readings were basically unchanged, staying in the 85-95 range. Scores on my daily math speed test were good, possibly slightly better than before.

Unfortunately, I started to gain weight, gaining about 10 pounds over the 10 weeks I took benfotiamine, without any other major changes to my regimen.

Weight gain was not a known side effect. For example, a 2005 study in which 20 patients received the drug for three weeks reported: “No side effects attributable to benfotiamine were observed.” This is on a web page that is trying to sell benfotiamine but there’s nothing unusual about the situation. Studies of drug efficacy are almost always done by drug companies that want to sell the tested drug. What is the term for such a side-effects reporting system? The fox guarding the hen house, perhaps?

It isn’t easy to measure side effects in conventional studies of treatment vs placebo. If you measure the rates of 100 possible side effects, and use a 5% level of significance, one or two true positives will go unnoticed against a background of five or so false positives. So a drug company can paradoxically assure that they will find nothing by casting a very wide net. And there is a larger and more subtle problem that statistics such as the mean do not work well for detecting a large change among a small fraction of the sample. If soft drinks cause 2% of children to become hyperactive and leave the other 98% unchanged, looking at mean hyperactivity scores is a poor way to detect this. A good way to detect such changes is to make many measurements per child. Many did-a-drug-harm-my-chlld? cases come down to parents versus experts. The experts are armed with a a study showing no damage. But this study will inevitably have the weaknesses I’ve just mentioned — especially, use of means and few measurements per subject. The parents, on the other hand, will have used, informally, the more sensitive measurement method.

For these reasons, I suspect drug side effects are woefully underreported. Here is the story of a child with a neurodegenerative disease that might have been caused by “the Gardasil vaccine (or perhaps some other vaccine with key similarities, such as an aluminum adjuvant).” Her parents are trying to find other children with similar symptoms.

Interview with Bruce Gray, Web-Savvy Sculptor (part 2)

Bruce Gray is a Los Angeles sculptor with an impressive website.

ROBERTS Do you know how art galleries have been affected by the web?

GRAY They definitely don’t like it.

ROBERTS How can you tell?

GRAY I’ve heard them complain about it. They have complained about it a lot. Some galleries won’t even represent you if you have a website. Â They also don’t like you to list your prices, because they will usually be asking for twice the money.

ROBERTS Yeah.

GRAY But that’s up to the individual gallery, and it depends how bad they want you. The ones that have the very tight rules on that are usually the galleries that are really hard to get into anyway. But let’s face it, if it’s Gagosian or someone who could triple my prices and turn me into an overnight sensation, then hey, I’ll take the freaking website down, but until that happens, I need something to keep the bills paid and the web is definitely doing it. Like I’ve told all my artist friends, every single artist in the world should have a website.

ROBERTS Yeah, and what will the world be like?

GRAY Another great thing is that it’s a portfolio that you have with you wherever you go. It’s very easy to show people my work at their homes, or even through my iPhone. I keep 300 dpi images up there too on a hidden page. So say I’m out of town, and I get a call that someone needs a large image for a magazine article, I can just give them that link and I don’t even have to send them anything.

ROBERTS Does this mean that people will be able to buy art at lower prices because the middle man is cut out?

GRAY It does, absolutely.

ROBERTS Are there any signs of this actually happening? You’re bringing people in to the art market because the prices are lower.

GRAY Of the artists I know, that’s basically what people have been telling me. Obviously when you’re going directly to an artist’s studio, it’s kind of the same thing as buying through the internet. You’re cutting out any gallery or dealers in most cases, unless people have signed on for one of those deals where you’re supposed to give your dealer a percentage even if you make your own direct sales, which I just don’t understand why anybody would sign on for that, but I do know people who have that, and they generally get some kind of stipend or something, but I don’t know. It doesn’t look like a good deal to me.

ROBERTS It sounds like there should be new customers in the art world, and I wonder if there are any signs of that.

GRAY The thing about galleries that you can’t escape is they are going to promote you, at least locally, better than you can yourself. And they give you a certain credibility factor. Obviously someone who’s been around as long as I have, I have enough credits on my biography where people know that I’m legitimate, so I don’t really need to go out there and beg to get in a bunch of shows just to beef up on the lines on my biography. To get in a cool or interesting show, that’s still a good thing to do for anybody and I still do that when I get asked, but I just don’t have to do it as much.

ROBERTS How is the traffic to your website changed over the years?

GRAY It’s pretty damned good. It varies a bit, but it gets a lot of traffic–thousands and thousands of people looking at it every day.

ROBERTSÂ Thousands of distinct visitors per day?

GRAY Yeah. It has been for a long time. Not everybody buys stuff, but a lot of times people, when they purchase art, it’s a decision that can take years to make. They may see something and like it, but it actually takes them several years to commit to buying it. I’ve had that happen a whole bunch of times. People say, ’I really want that, and I’m getting that some day,’ and you’re like, ’Oh yeah, yeah, I’ve heard that,’ and five years later they come back and say, ’Hey, I’m getting that!’ It does happen.

ROBERTS Have you measured a visitors per dollar or hits per dollar–have you ever computed that index? If you make $10,000 and it requires a million hits?

GRAY I’ve never really figured that out.

ROBERTS I wonder how that ratio would change over the years.

GRAYÂ Well, I take all the web statistics with a grain of salt because I don’t think any of them are super accurate. If you go to the several different groups that watch that kind of stuff, they’re all going to give you a different statistic–whether it’s how many sites link into your site, or anything else. If I look online for that kind of information, how many people link to my site, every different page that will give you any of that kind of reference will have a completely different number. You have to just use it like a scale, you just kind of go, ’Okay well it’s going up at least.’

ROBERTS And it might be going up because of robots.

GRAY Robots just basically spider your information and go and update new stuff; that doesn’t really represent hits the way that an individual coming in will.

ROBERTS How does the number of visitors to your site compare now to a year ago?

GRAY I figured it’s just gradually getting better and better. Every year I have a lot more information on there, which attracts new people in, say, maybe a TV show that I had something on–that might attract in a little bit, or like I had some stuff on this Gene Simmons show a couple of years ago and I just noticed recently that they’re using one of my photos from the stills from that on this Gene Simmons site, so all of a sudden I’m getting a bunch of hits in now from that. Each little thing that you add, each little accomplishment, or book appearance or gallery show–all that stuff adds in another layer of keywords and things that people may be searching for. That’s all kind of a weird world how that works, too, because for example–Gene Simmons again–he’s obviously a very famous rock star guy and if you look up his name, I’m not going to get a gazillion hits because I have Gene Simmons’ name on my website, because when you’re talking about someone who is super-famous, if their name is on your site–as a collector for whatever reason–there’s so much other material about them already, that you are so way down in the bottom of the relevancy that if you get one or two hits a week because of their name, that would be about average. Trying to kind of beef up your website by putting in a lot of names like that wouldn’t really do anything.

Part 1.

Slow Weed


Guthrie said that the quasi-legal status of smaller growing arrangements, combined with consumers’ preference for potent, high-maintenance weed, has shifted the balance of the pot business away from large-scale farms. “There’s a lot more people doing little scenes,” he said. The welter of laws pertaining to medical marijuana in California has offered careful operators like Guthrie the best of both worlds: prosecution for growing and selling has become much less likely, while federal busts and seizures keep prices high.

Too bad David Samuels, the author of this well-reported article, doesn’t use the term artisanal marijuana. Artisanal cheesemakers, etc., might learn something helpful from this. For example, maybe it helps that raw milk is slightly illegal. After he wrote Fast Food Nation, Eric Schlosser wrote about underground economies. Maybe he’ll eventually write Slow Food Nation.

A friend of mine spent a year growing pot in her California basement in response to the economic trends described in Samuel’s article. She stopped when her business partner became too unreliable.