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.

World’s greatest healthcare (TM)

What does it mean when a US politician like Chris Christie tells the Republican National Convention the US has “the world’s greatest healthcare system”? Is it like when kids buy a “World’s Greatest Dad” mug for Father’s Day: An expression of affection for an ill-favoured thing, but mine own?

One of my formative political experiences was the summer during graduate school, when I listened on the radio to broadcasts of the US Senate debating the Clinton healthcare proposals. What struck me above all was how the senators universally (it seemed) invoked the unmatched excellence of American health care. “The envy of the world”, “best health care in the world”. The only difference of opinion was, of course, that opponents of the reform said that tinkering with this paragon of perfection would inevitably be disastrous, while supporters argued for making this blessing available to more people.*

So, the politicians certainly appear to believe it, and to believe that it should have policy implications; or to believe that a significant portion of the public believes it; or to believe that a significant portion of the public will respond favourably to the assertion, even if they suspect it is untrue. Is it cognitive dissonance? We’re America dammit, and being the sort of people we are, we certainly wouldn’t put up with a ramshackle healthcare system.

Continue reading “World’s greatest healthcare (TM)”

Will small hospitals kill you?

Disquisition on medical statistics in The Guardian

A recent front-page article in The Guardian claimed to show that small NHS hospitals are killing people. “Huge disparity in NHS death rates revealed” was one headline. “Patients less likely to die in bigger hospitals“. “Safety in numbers for hospital patients” is another headline. The article makes no secret of its political agenda: “The results strongly suggest that smaller units should close. This presents a major challenge to the health secretary, Andrew Lansley, who has stopped all hospital reorganisation.” Online, Polly Toynbee decries “Hospital populism”, saying “Local hospitals may be loved, but they can kill.” Wow. That’s pretty bad. Here’s the schematic of the story: Smart and selfless experts want to save lives. Dumb public clings to habit (in the form of community hospitals). Evil politicians pander to dumb public, clings to campaign promises. “The health secretary, Andrew Lansley, has now put the project on hold, in line with his election promise to halt hospital closures, to the dismay of experts who believe that lives will continue to be lost.”
Continue reading “Will small hospitals kill you?”

In praise of the National Health Scapegoat

All over the world babies are babies, and birth is birth, but having a baby in Oxford is certainly quite a different experience than having a baby in California. The comparison is mostly favourable to Oxford, in our experience. The prime directive of the NHS (which recently celebrated its 60th anniversary) is borrowed from Douglas Adams: Don’t Panic.

The NHS is a great success by any definition. When you factor in the constitutional niggardliness of the British taxpayers and Her Majesty’s government — leading the UK to spend per capita on healthcare substantially less than half what the US spends, and much less than any major industrialised country except Japan — it seems a veritable miracle of efficient socialism. Whereas health research in the US is dominated by the profit motive, producing marginally improved drugs at breathtakingly higher prices*, the NHS has a brilliant record of pioneering cost-effective healthcare solutions, which may be individually trivial, even slightly absurd, but which together add up to systematic and measurable improvements in public health. (For example, this scheme to prevent complications due to chronic lung disease by providing patients with automated telephone warnings of impending cold snaps. Or something as simple as reducing infections by requiring doctors and nurses to wear short sleeves.) Continue reading “In praise of the National Health Scapegoat”