Every three minutes

From a Guardian article on a new theory about the aetiology of Alzheimer disease:

It is thought that this year one person every three minutes will develop dementia.

It’s hard to explain statistics in a way that they feel real to people, but is “one person every three minutes” really a useful way to think about a disease that develops gradually over many years, as opposed to, say, muggings? Perhaps they meant to say “one person every three minutes will be diagnosed with dementia”.

Do all babies look alike?

And if not, why don’t they have any privacy rights with regard to their photographs?

Here is the illustration provided by the BBC on its home page for a report on the decision to approve fertility procedures that take genetic material from three different people:

Not a three-parent baby, but they are expected to look similar to this one.
Not a three-person baby, but manufacturers promise they will look similar to this model.

One wonders what purpose this photograph serves. Are there readers who see the headline and think, “Wait, babies, I’ve heard of them. Can’t quite remember what they look like…” In what sense is this an illustration of the article? It’s not even a newborn infant. They might as well have shown a 90-year-old lady, because making three-person babies inevitably leads to the eventual creation of three-person 90-year-olds. It might be even more relevant to show an elderly person, because that’s the goal: the purpose of the procedure is to improve the health and longevity of the humans so conceived.

They could have used their stock photograph of weirdly lighted lab technicians pipetting something into a test tube instead.

I’m wondering, who is this baby who is standing in for a “three-person baby”? I’m used to seeing children have their features blurred out in news photos. But, of course, this one was presumably a “volunteer” model. One baby can stand in for all babies. (As long as it’s white, of course.)

What does an anti-vaccine activist want?

With the swelling of interest in the anti-vaccine movement, inspired by the recent California measles outbreak, I’ve seen a number of opinions published similar to this one from Ian Steadman in the New Statesman

Then there’s also this to think about: if somebody’s distrust of scientific and/or political authority is so great, for whatever reason – maybe they’ve been scared by sensationalist stories in the media, or maybe they sincerely believe the government has no moral right to dictate health choices to citizens – that they’re willing to significantly increase their child’s risk of catching a (possibly fatal) illness, then calling them names and telling them scientists and politicians disagree with them is probably futile. Arguing that “the science is settled” with someone whose stance is predicated on the belief that the standards of proof used by scientists are flawed is definitely futile.

The article is excellent, but I don’t entirely agree with this sentiment. Living in Berkeley and Oxford, I have encountered some vaccine refuseniks, and it’s not clear to me that they have anything as definable as a belief about “the standards of proof used by scientists”. Rather, I think that they have a desperate need to feel special, protected not by mass vaccination — and definitely not by anything as infra dig as “herd immunity” — but by their special virtue, which may be Christian purity or organic health-food purity. Continue reading “What does an anti-vaccine activist want?”

The value of diagnosis

What is diagnosis worth, if there is no treatment? This is a perennial question in medical ethics. I recall a passage in Roy Porter’s history of medicine, The Greatest Benefit to Mankind, referring to the sardonic praise heaped upon the clinic in Vienna (I think it was), where the magisterial diagnoses were always “swiftly confirmed at the autopsy”.

An article in Salon recounts the revelation from autopsy that comedian Robin Williams was suffering from Lewy body dementia at the time of his recent suicide. The article quotes the programming director of the Lewy Body Dementia Association, saying “Though his death is terribly sad, it’s a good opportunity to inform people about this disease and the importance of early diagnosis.” I know this is the sort of thing that someone in her position is required to say, but given that there is no cure, and very little by way of effective treatment, I wonder what “importance of early diagnosis” she is referring to, and what she takes the relevance of this event in particular to be. That early diagnosis allows you to know what’s happening while you’re still fit enough to take your own life?

Association by guilt

Guilt by association — you’re friends with a terrible person so you must also be one — is generally recognised as a pernicious logical fallacy. But what should we call this comment by Israeli Foreign Ministry spokesman Paul Hirschson, explaining why Norwegian trauma surgeon Mads Gilbert has been banned from returning to Gaza after he made critical remarks about the Israeli military activities this past summer? Dr Gilbert, he opined, is

not on the side of decency and peace and he’s got a horrible track record. I wouldn’t be surprised if his acquaintances are among the worst people in the world.

In other words, he’s a terrible person, so I’m sure his friends are too. Is this association by guilt?

False positives, false confidence, and ebola

Designing a screening test is hard. You have a large population, almost all of whom do not have whichever condition you’re searching for. Thus, even with a tiny probability of error, most of the cases you pick up will be incorrect — false positives, in the jargon. So you try to set the bar reasonably high; but set it too high and you’ll miss most of the real cases — false negatives.

On the other hand, if you have a suspicion of the condition in a particular case, it’s much easier. You can set the threshold much lower without being swamped by false positives. What would be really dumb is to use the same threshold from the screening test to judge a case where there are individual grounds for suspicion. But that’s apparently what doctors in Spain did with the nurse who was infected with Ebola. From the Daily Beast:

When Teresa Romero Ramos, the Spanish nurse now afflicted with the deadly Ebola virus first felt feverish on September 30, she reportedly called her family doctor and told him she had been working with Ebola patients just like Thomas Eric Duncan who died today in Dallas. Her fever was low-grade, just 38 degrees Celsius (100 degrees Fahrenheit), far enough below the 38.6-degree Ebola red alert temperature to not cause alarm. Her doctor told her to take two aspirin, keep an eye on her fever and keep in touch.

She was caring for Ebola patients, she developed a fever, but they decided not to treat it like a possible case of Ebola because her fever was 0.6 degrees below the screening threshold for Ebola.

A failure of elementary statistical understanding, and who knows how many lives it will cost.

Percents are hard

Some really bad science reporting from the BBC. They report on a new study finding the incidence of diagnosed coeliac disease increasing (and decreasing incidence of dermatitis herpetiformis, though this doesn’t rate a mention) in the UK. Diagnoses have gone up from 5.2 to 19.1 per 100,000 in about 20 years, which they attribute to increased awareness. Except, they don’t say what that is 100,000 of. You have to go back to the original article to see that it is person-years, and that they are talking about incidence, and not prevalence (in technical parlance); they use the word “rate”, which is pretty ambiguous, and commonly used — particularly in everyday speech — to refer to prevalence. If you read it casually — and, despite being a borderline expert in the subject, I misread it at first myself —  you might think they mean that 19 in 100,000 of the population of Britain suffers from coeliac; that would be about 12,000 people, hardly enough to explain the condition’s cultural prominence (and prominent placement on the BBC website). In fact, they estimate that about 150,000 have diagnosed CD in the UK.

As if aiming maximally to compound the confusion, they quote one of the authors saying

“This [increase] is a diagnostic phenomenon, not an incidence phenomenon. It is exactly what we had anticipated.”

In the article they (appropriately) refer to the rate of diagnosis as incidence, but here they say it’s not about “incidence”.

To make matters worse, they continue with this comment:

Previous studies have suggested around 1% of the population would test positive for the condition – but the data from this study suggests only 0.25% are diagnosed.

I think that normally, if you say “only x% are diagnosed” is meant relative to the number of cases; here it would mean 0.25% of the 1%. But, in fact, they mean to compare the 0.25% of the population who are diagnosed with the 1% who actually suffer from the disease.

Vitamins, homeopathy, and economic austerity

I was thinking about this comment by Paul Krugman, about the hegemonic certainty among European banking elites that genuine solid prosperity will only come through a long period of suffering through budget austerity:

Europe’s Very Serious People — people who believe in austerity regardless of circumstances, and who also say things like this, from the Bundesbank’s Jens Weidmann, declaring that “the money printer is definitely not the way to solve [Europe’s problems]“. This is stated as if it is a self-evident truth — even though any PRE can easily make the case (as Praet does) that the money printer is, in fact, something that can offer a great deal of help in solving Europe’s problems.

It reminded me of a similar but opposite delusion that I have noticed among health cranks promoting vitamins. “Pharmaceuticals” are by nature unnatural, and to be viewed with suspicion, even while few are willing to go full Christian Scientist when their lives are at stake. The presumption is that there are side effects, maybe worse than the disease, and the companies that developed and manufactured the drugs are basically pernicious in their goals and methods. “Vitamins”, on the other hand, even when manufactured by the same pharmaceutical company in the same factory, are presumptively good, even in doses far exceeding anything that has ever been tested clinically, much less found in nature. On the other side of the holistic medicine world — but often the same people — are the homeopaths, who take nonexistent doses of generally poisonous substance, under the plausible theory that once they’ve been diluted down to the point where not a single molecule of the substance is left in the vial, it can’t hurt.

But how could it help? That’s where they get into some mystical physics. But if we accept the efficacy of water memory, or whatever the explanation is supposed to be, then why should we continue to assume that the modified water couldn’t hurt? My presumption is that anything effective enough to help is also effective enough to harm, and it’s all a matter of getting the timing and the dosage right. That’s why there are few really easy questions in medicine. It’s always a matter of tradeoffs. The same with the vitamins. How can they help if they can’t hurt? And how could a large dose of a completely untargeted substance be more likely to help than to hurt? And indeed, every trial I know of that has put large doses of vitamins to the test has found them to be generally harmful.

One of the greatest nuggets of wisdom offered up by a (nonreligious) crackpot was Paracelsus’s famous apothegm:

Alle Ding’ sind Gift, und nichts ohn’ Gift; allein die Dosis macht, daß ein Ding kein Gift ist.
All things are poison, and nothing is without poison; only the dose permits something not to be poisonous.

The delusion of the austerians is to believe that monetary expansion — “the money printer”, encouraging inflation — obviously can’t help the economy, it can only hurt. Now, there are serious arguments that purport to show that monetary policy has no effect at all on the “real economy”. My nonspecialist impression is that these arguments have been mostly seen off by behavioural economics, but it’s a plausible idea, in principle. Intuitively, it seems strange that something as ethereal as changing the numbers on the central bank’s balance sheet will be effective in mobilising idle labour.

But if you think that inflation and deficit spending are efficacious, it is implausible to suppose that they can only be harmful. I have respect for the conservative mindset that says, tinkering with a complicated structure is more likely to kill than to cure, but it’s not as though this is just some crackpot idea that some radicals just made up last Tuesday. Smart people have been thinking for quite a while about how to structure and dose fiscal stimulus. They might be wrong, but they’re not likely to be obviously wrong.

For the same reason that it can’t be self-evident that megadoses of vitamins couldn’t hurt.

Avastin didn’t fail the clinical trial. The clinical trial failed Avastin.

Writing in the NY Times, management professor Clifton Leaf quotes (apparently with approval) comments that ought to win the GlaxoSmithKline Prize for Self-Serving Distortions by a Pharmaceutical Company. Referring to the prominent recent failure of Genentech’s cancer drug Avastin to prolong the lives of patients with glioblastoma multiforme, Leaf writes

Doctors had no more clarity after the trial about how to treat brain cancer patients than they had before. Some patients did do better on the drug, and indeed, doctors and patients insist that some who take Avastin significantly beat the average. But the trial was unable to discover these “responders” along the way, much less examine what might have accounted for the difference. (Dr. Gilbert is working to figure that out now.)

Indeed, even after some 400 completed clinical trials in various cancers, it’s not clear why Avastin works (or doesn’t work) in any single patient. “Despite looking at hundreds of potential predictive biomarkers, we do not currently have a way to predict who is most likely to respond to Avastin and who is not,” says a spokesperson for Genentech, a division of the Swiss pharmaceutical giant Roche, which makes the drug.

This is, in technical terms, a load of crap, and it’s exactly the sort of crap that double-blind randomised clinical trials are supposed to rescue us from. People are generally prone to see patterns in random outcomes; physicians are probably worse than the average person, because their training and their culture biases them toward action over inaction.

It’s bizarre, the breezy self-confidence with which Leaf (and the Genentech spokesman) can point to a trial where the treatment group did worse than the placebo group — median survival of 15.7 months vs. 16.1 months — and conclude that the drug is helping some people, we just can’t tell which they are. If there are “responders”, who do better with Avastin than they would have otherwise, then there must also be a subgroup of patients who were harmed by the treatment. (If the “responders” are a very small subset, or the benefits are very small, they could just be lost in the statistical noise, but of course that’s true for any test. You can only say the average effect is likely in a certain range, not that it is definitely zero.)

It’s not impossible that there are some measurable criteria that would isolate a subgroup of patients who would benefit from Avastin, and separate them from another subgroup that would be harmed by it. But I don’t think there is anything but wishful thinking driving insistence that there must be something there, just because doctors have the impression that some patients are being helped. The history of medicine is littered with treatments that physicians were absolutely sure were effective, because they’d seen them work, but that were demonstrated to be useless (or worse) when tested with an appropriate study design. (See portacaval shunt.)

The system of clinical trials that we have is predicated on the presumption that most treatments we try just won’t work, so we want strong positive evidence that they do. This is all the more true when cognitive biases and financial self interest are pushing people to see benefits that are simply not there.

Benjamin Franklin’s advice on vaccination

I’ve never seen Franklin brought into the discussion of parents’ refusal to vaccinate their children. This passage from his autobiography made a deep impression on me:

In 1736 I lost one of my sons, a fine boy of four years old, by the small-pox, taken in the common way. I long regretted bitterly, and still regret that I had not given it to him by inoculation. This I mention for the sake of parents who omit that operation, on the supposition that they should never forgive themselves if a child died under it; my example showing that the regret may be the same either way, and that, therefore, the safer should be chosen.

More comments on Andrew Wakefield and the MMR-autism hoax here.

I once was at a parents’ meeting in Oxford where a homeopath had been invited to speak. I was genuinely nonplussed that she was raving against vaccines. Aren’t vaccines the one great success of the homeopathic world-view? Giving a tiny dose of the disease-causing agent to cure (or prevent) the disease. Her answer was incomprehensible to me, but seemed to suggest that the very fact that there was a measurable physiologic effect showed that they weren’t any good (from a homeopathic perspective). And the fact that pharmaceutical firms made the vaccines was all you needed to know about their chthonic nature.

I fled the meeting in revulsion when the homeopath started prating about homeopathic cures for tetanus.