Download Lectures on Biostatistics (1971). Corrected and searchable version of Google books edition
Download review of Lectures on Biostatistics (THES, 1973).
honey
There have been some really excellent books about quackery this year. This isn’t one of them, because
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Nice dedication uh? |
it is about a lot more than quackery It is about the scientific method in general. and in particular about how often it is misunderstood by journalists. Abuse of evidence by the pharmaceutical industry is treated just as harshly as abuse of evidence by homeopaths and you get the low-down on both.
“More importantly, you will also see how a health myth can be created, fostered and maintained by the alternative medicine industry using all the same tricks on you, the public, which big pharma uses on doctors. This is about something much bigger than homeopathy.” (p.28)
Sir Iain Chalmers, a founder of the Cochrane Collaboration , co-author of the best lay text on evidence says: “Bad Science introduces the basic scientific principles to help everyone become a more effective bullshit detector”. And there is no more invaluable skill than being a bullshit detector.
Chalmers says also “Ben Goldacre has succeeded where the ‘public engagement in science’ organisations have so signally failed.” That is exactly right. ‘Public engagement’ has rapidly become bureaucratised, and at its worst, is no better than a branch of the university’s marketing department. This sort of public engagement corrupts as much as it enlightens. Goldacre enlightens, and he also makes you laugh.
In the introduction, Goldacre says
“You cannot reason people out of positions that they didn’t reason themselves into.” (p xii)
It’s a nice point, but the rest of the book makes a magnificent attempt to do just that.
There is quite a lot about medicine, of course, that’s his job, after all. But it isn’t all quackery by a long chalk Quackery is merely a good hook to hang the arguments on about how you distinguish what’s true from what isn’t. That’s partly because quacks make every mistake known to mankind (sometimes through ignorance, sometimes just to boost sales), and partly just because it is a topic that interests people, and with which they are bombarded every day I feel exactly the same. If I were to talk about the statistics of single ion channels, nobody would read it (big mistake -it’s fascinating), but if one can use the case of honey versus cough medicine to explain the analysis of variance, there is a chance that someone might find it interesting.
As much as anything, Goldacre’s book is about C.P. Snow’s two cultures. The chapters on the distortion and trivialisation of science in the media are just terrific.
“My basic hypothesis is this: the people who run the media are humanities graduates with little understanding of science, who wear their ignorance as a badge of honour. Secretly, deep down, perhaps they resent the fact that they have denied themselves access to the most significant developments in the history of Western thought from the past two hundred years.” Chapter 11, p. 207
“.. . . here is the information I would like from a newspaper to help me make decisions about my health, when reporting on a risk: I want to know who you’re talking about (e.g. men in their fifties): I want to know what the baseline risk is (e.g. four men out of a hundred will have a heart attack over ten years); and I want to know what the increase in risk is , as a natural frequency [not as relative risk] (two extra men out of that hundred will have a heart attack over ten years). I also want to know exactly what’s causing that increase in risk -an occasional headache pill or a daily tub full of pain-relieving medication for arthritis. Then I will consider reading your newspapers again, instead of blogs which are written by people who understand research , and which link reliably back to the original academic paper, so that I can double check their précis when I wish. ” (p. 242)
I detect some ambiguity in references to things that aren’t true. Sometimes there is magnanimity. At other times he is a grade one kick-ass ninja. For example
I can very happily view posh cosmetics -and other forms of quackery -as a special, self-administered, voluntary tax on people who don’t understand science properly (p. 26)
Of course nobody wants to ban cosmetics, or even homeopathy. But a lot of bad consequences flow from being over-tolerant of lies if you take it too far (he doesn’t). The lying dilemma and the training dilemma are among them. Some unthinking doctors will refer troublesome patients to a reflexologist. That gets the worried-well out of their surgery but neglects the inevitable consequence that Human Resources box-ticking zombies will then insist on having courses that teach the big toe is connected to the kidney (or whatever) so that reflexologists can have an official qualification in mystical mumbo-jumbo.
Is there anything missing from the book? Well inevitably. There are plenty of villains among the peddlers of nutri-bollocks, and in the media. But there isn’t much about the people who seem to me to be in some ways even worse. What about the black-suited men and women in the Ministry of Health and in some vice-chancellors’ chairs who betray their institutions and betray the public through some unfathomable
mixture of political correctness, scientific ignorance and greed? What about the ludicrous behaviour of quangos like Skills for Health? You have to wait right to the end of the book to hear about universities. But when it comes, it is well worth the wait.
“I’m not surprised that there are people with odd ideas about medicine, or that they sell those ideas. But I am spectacularly, supremely, incandescently unimpressed when a a university starts to offer BSc science courses in them.” (p. 317)
It’s almost worth buying Ben Goldacre’s book for that sentence alone.
This book is a romp through the folly, greed and above all the ignorance of much in our society. It’s deeply educational. And it makes you laugh. What more could you want?
This afternoon I went to the Coliseum to see a revival of Jonathan Miller’s 1986 production of the Mikado. It was beautifully staged. The well-known patter song of Ko-Ko, the Lord High Executioner of Japan, begged for a version that deals with anti-science (original here). The serious post will come later. Meanwhile here’s some late night rhyming.
Ko-Ko
As some day it may happen that a victim must be found,
I’ve got a little list — I’ve got a little list
Of society offenders who might well be underground,
And who never would be missed — who never would be missed!
There’s the pestilential bureaucrats who want to send you on a course —
The HR folks who treat you not as human but as mere resource
Skills specialists who think that education just means training
And all ex-scientists who used to work, but now are only feigning
They’d none of ’em be missed — they’d none of ’em be missed!
Chorus.
He’s got ’em on the list — he’s got ’em on the list;
And they’ll none of ’em be missed — they’ll none of ’em be missed.
Ko-Ko
And that deluded nuisance, whom no one understands
The homeopathist – I’ve got her on the list!
All Reiki folks, pill hucksters and layers on of hands
They’d none of ’em be missed — they’d none of ’em be missed.
And herbalists and Princes who like to talk to trees
Those phony nutritionists who’ll treat you for large fees
And that singular anomaly, the acupuncturist —
I don’t think they’d be missed — I’m sure they’d not be missed!
Chorus.
You may put ’em on the list — you may put ’em on the list;
And they’ll none of ’em be missed — they’ll none of ’em be missed!
Ko-Ko
There’s the vision statement writer, and others of that sort
And the crystal therapist — I’ve got him on the list!
And the people who think long words are a substitute for thought
They never would be missed — they never would be missed!
Then those whose knight starvation makes them crave the honours list
So all below must suffer in case their chance is missed
And those who think that science can be judged by its citations
And so kill creativity by funding only applications
But it really doesn’t matter whom you put upon the list,
For they’d none of ’em be missed — they’d none of ’em be missed!
Chorus
You may put ’em on the list — you may put ’em on the list;
And they’ll none of ’em be missed — they’ll none of ’em be missed!
Postscript
I replaced two lines after my pedantic sister pointed out their imperfect rhyme and scansion. Personally I’m with Charles Babbage.
Here is letter that Babbage is said to have written to Tennyson after reading “The vision of sin”.
In your otherwise beautiful poem there is a verse that reads:
“Every moment dies a man
Every moment one is born”It must be manifest that, were this true, the population of the world would be at a standstill. In truth the rate of birth is slightly in excess of that of death. I would suggest that in the next edition of your poem you have it read:
“Every moment dies a man
Every moment 1 1/16 is born”Strictly speaking this is not correct. The actual figure is a decimal so long that I cannot get it in the line, but I believe that 1 1/16 will be sufficiently accurate for poetry.
I am etc,
(The Mathematical Gazette, 1927, p270)
The press releases (STOP PRESS)
Uhuh, here we go again.
All over the media we see headlines like “Honey ‘beats cough medicine’ “.
Take for example, the Daily Telegraph, where Ben Farmer writes “Honey is better at treating children’s coughs than an ingredient used in many over-the-counter medicines, according to new research”.
That is NOT what the research found This is what the research paper itself says (DM refers to the standard ‘cough suppressant’ dextromethorphan, which is already known to be ineffective).
| “honey was significantly superior to no treatment for cough frequency’ DM was not better than no treatment for any outcome. Comparison of honey with DM revealed no significant differences.” |
See it? No detectable difference between honey and standard cough medicine.
Everyone in the media misinterpreted what the paper said, but at least one blogger is already on to it, with Today’s “duh” study is a honey”.
At first sight, the results seem contradictory, No difference between honey and DM, No difference between DM and ‘no treatment’. So how can honey be better than ‘no treatment’?
The study was by Ian M. Paul, MD, MSc; Jessica Beiler, MPH; Amyee McMonagle, RN; Michele L. Shaffer, PhD; Laura Duda, MD; Cheston M. Berlin Jr, MD, published in Archives of Pediatrics & Adolescent Medicine 2007, 161, 1140 – 1146.
What was done
The design of this trial was pretty good apart from one thing Three things were compared (a) buckwheat honey, (b) a standard ‘cough suppressant’, dextromethorphan in a honey-flavoured syrup that was designed to be similar to the honey (DM for short), and (c) no treatment whatsoever.
The median age of the children who completed the study was 5.2 years (range, 2.2 – 16.9 years). They all had coughs attributed to upper respiratory tract infection. Thirty-five patients received honey, 33 received DM, and 37 received no treatment.The good thing is that the treatments were allocated randomly to the children, and that the person doing the assessment didn’t know which treatment each child had received. The children didn’t know whether they were getting honey or DM either, but they DID know when they got ‘no treatment’. The trial was carried out over two days. On day one nobody got a treatment, but they filled in a survey that asked, for example, “How frequent was your child’s coughing last night”. The parent had to tick one of seven boxes, from ‘not at all’ (score zero) to ‘extremely’ (score 6). They were then given the treatment allocated to them in a brown paper bag, so the person who gave it didn’t know which it was. The patients then went home and on the next day the same survey was completed by the same parent, over the telephone.
What happened?
First look at the raw data. Here is Figure 2 from the original paper.
The charts show the results for 5 different measures of the severity of cough, and the last chart (F) shows the aggregate score for all the criteria.
The first thing to notice is that there are no error bars on these charts. In my area, at least, no journal would accept a chart like this with no indication of scatter. There is a snag, though. Each patient acts as his/her own control, and that would not be reflected properly if errors bars were calculated for the numbers plotted in Fig. 2. It would therefore have been better to have a chart in which the difference in score between day 1 and day 2 was calculated from each patient, and the size of these differences plotted, with a standard deviation of the mean to indicate the amount of scatter in the observations. I have asked Dr Paul to send me a version that indicates the scatter of the numbers in this way (but I don’t think it will come).
The second thing to notice is that there is there is quite a big difference between the score on the first day (pale columns) and on the second day (dark columns), even in the no treatment group .
Thirdly, the pale columns are all much the same. On the first day the average score was about 4 (“a lot”) though on the second day, even with no treatment, the score fell quite a lot, to something between 2 (“a little”) and 3 (“somewhat”). This is a bit baffling because no treatment was given on either day. Presumably it results from the different settings in which the survey was given, or because the kids were getting better anyway.
Fourthly, insofar as the pale columns (baseline values) are all much the same, the thing you need to concentrate on is the difference, on each chart, between the height of the dark bars, for honey, DM and no treatment. These differences are pretty small, but on all the charts, the honey score is slightly smaller than the DM score, and the DM score is slightly smaller than the ‘no treatment’ score. What are we to make of that?
Here beginneth the statistical lesson.
Because the differences are small, and the scatter is quite big, we have to ask whether the differences are just random fluctuations rather than a result of any real difference between the treatments. That means we need statistics. Here is how the statistical argument works. Put roughly, we ask “how probable is it that the observations could arise by chance”. More precisely, the question is this. If there were no difference between the treatments, what is the probability that we would observe by chance a difference as big as, or bigger than, that seen in the experiment? (You need the subjunctive mood to explain statistics -pity it’s vanishing.)
Above each chart in the Figure we see P < 0.001. This means that there is less than a one in 1000 chance of the results arising by chance. More precisely, if all three treatments (honey, DM and no treatment) were actually identical, it is very unlikely that we’d see these results. The reasonable conclusion is, therefore, that all three treatments are not identical. The problem with this argument is that it tells you nothing about where the differences lie, so it is of no help whatsoever to a patient who is trying to decide what to do about a cough. The other problem is that it includes the ‘no treatment’ group, which was not blind. Both the children and parents were well aware that no treatment was given.
The most helpful comparison is really the properly-blinded comparison between honey and DM. And when this was looked at the result was no significant differences. In other words the small differences between the heights of the dark columns for honey and DM could perfectly well have arisen by chance if honey and DM were identical in their properties.
There isn’t any reason at all to think that honey is better than the standard (but ineffective) cough medicine.
The direct comparison between DM and ‘no treatment’ also shows no significant difference. Yet there are signs of a real difference between ‘no treatment’ and honey, though only for the cough frequency, not the other four measures. The aggregate measure (F in the figure) gave P = 0.04 for the comparison, so the authors are running a risk of 1 in 25 of being wrong in claiming a real effect. Although some people seem to regard a value of P = 0.05 as indicating a real effect, the fact that you’ll make a fool of yourself 1 time in 20 by claiming a real effect when none exists has never seemed to me to be good enough odds to stake one’s reputation on.
The ‘no treatment’ group certainly has some interest, but the fact that it was not blind means that the fact that honey was marginally better than ‘no treatment’ could perfectly well mean that taking honey has a better placebo effect that doing nothing at all. It provides no evidence at all that honey has any genuine therapeutic effect. If it had, one would then have to find out if the therapeutic effect was specific to buckwheat honey, or whether any old honey would do. It could be argued that even if the effect were real rather than placebo, the size of the effect is too small to make all that effort worthwhile.
A couple more things
It is already well known, from several good studies, that DM is useless, no better than placebo. This inconvenient fact has not yet reached many places that it should have (not even mentioned on wikipedia for example), but the American Academy of Pediatrics says
“Numerous prescription and nonprescription medications are currently available for suppression of cough, a common symptom in children. Because adverse effects and overdosage associated with the administration of cough and cold preparations in children have been reported, education of patients and parents about the lack of proven antitussive effects and the potential risks of these products is needed.”
The discussion in the paper by Paul et al, seems surprisingly upbeat about honey, in the light of their own findings. I’m surprised that they use the term ‘demulcent’ which I had thought to have died out, like the word ‘tonic’, on the grounds that it had no defined meaning
It is because meaningless terms and useless medicines die out eventually that medicine makes progress. The problem with alternative medicine is that nothing dies out: on the contrary they keep adding myths.
And finally
Always look at the end of the paper. On this one we see that the study was paid for by the National Honey Board. Dr Paul assures me that the funding source had no say in the design or analysis, which is as it should be.
Financial Disclosure: Dr Paul has been a consultant to the Consumer Healthcare Products Association and McNeil Consumer Healthcare.
Funding/Support: This work was supported by an unrestricted research grant from the National Honey Board, an industry-funded agency of the US Department of Agriculture.
So what is the practical outcome?
My conclusion from all this is simple. If you have got a cough, tough luck. There isn’t really anything available, conventional or alternative, that does much good. You’ll just have to wait for it to get better. But if you want to take something that tastes nice, why not honey? It almost certainly won’t do any good but it tastes good and it’s safer than the standard cough medicine.
The sponsor’s interpretation
It seems that the sponsor of the work is happy with the misinterpretation.
Charlotte Jordan a project manager of research at the National Honey Board, believes the finding confirms what your grandmother told you.
“This is a really exciting finding,” she said. “For a long time it’s been folklore medicine to use honey when you have a cough or a cold, but it’s exciting to have a scientific study to back that up.”
Just one problem, That is NOT what the paper says.
How did all this mis-reporting happen?
One reason is misleading press releases. Universities and Academic journals now engage in shameless PR, spin and hype. They prostitute good science.
Download press releases from Penn State, JAMA and Press Association [pdf file]
Here is the highly misleading bit of hype that came from the Press Office of the Pennsylvania State University. The headline is “Honey a better option for childhood cough than OTCs” (OTC means over-the-counter medicines that contain DM). That contradicts directly the paper which says “Comparison of honey with DM revealed no significant differences”.
Likewise the statement in the Penn State release “Honey did a better job reducing the severity, frequency and bothersome nature of nighttime cough from upper respiratory infection than DM or no treatment” is equally incompatible with “Comparison of honey with DM revealed no significant differences”. Its only possible justification is from the 3 way comparison by analysis of variance and that does not tell us what we need to know.
To make matters worse, the media office is not to blame this time. Ms Manlove told me tonight that the press release had been approved by Dr Paul himself.
| Contact: Megan W. Manlove Penn State Honey a better option for childhood cough than OTCs A new study by a Penn State College of Medicine research team found that honey may offer parents an effective and safe alternative than over the counter children’s cough medicines. The study found that a small dose of buckwheat honey given before bedtime provided better relief of nighttime cough and sleep difficulty in children than no treatment or dextromethorphan (DM), a cough suppressant found in many over-the-counter cold medications. Honey did a better job reducing the severity, frequency and bothersome nature of nighttime cough from upper respiratory infection than DM or no treatment. Honey also showed a positive effect on the sleep quality of both the coughing child and the child’s parents. DM was not significantly better at alleviating symptoms than no treatment. . . . |
All that Candice Yakel, of the Office for Research Protections at Penn State had ro say in the matter was
“Our investigators stand by the conclusions of the study as reported in the Archives of Pediatric and Adolescent Medicine and as characterized in our press release of December 3, 2007.”
And here is the equally misleading bit of hype issued by the Journal of the American Medical Association (Ms Manlove tells me that this was also approved bt Dr Paul).
| JAMA and Archives Journals Study suggests honey may help relieve children’s cough, improve sleep during colds
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The Press Association release was equally bad, and probably the one used by many of the reporters as a basis for stories in the media. The opening statement is totally wrong.
| 1 HEALTH Honey Embargoed to 2100 Monday December 3 HONEY BEST FOR KIDDIES’ COUGHS SAY RESEARCHERS By John von Radowitz, PA Science Correspondent Natural honey is a better remedy for children’s coughs than expensive over-the-counter medicines, researchers said today. A dose of buckwheat honey before bedtime easily outperformed a cough suppressant widely used in commercial treatments, a US study found. . . . |
Follow-up
There is a review of over-the-counter cough medicines in the BMJ (2002) [free full text]. It concludes “Recommendation of over the counter cough medicines to patients is not justified by current evidence”.