Posts filed under Research (206)

Two useful pieces, worth reading even if you are neither a scientist nor a science journalist.

Ed Yong writes about what he is looking for when he asks scientists for comments on a research paper.

Note that a lot of this boils down to you telling me something interesting that I couldn’t have predicted. That’s why, when people ask me, “Do you have any specific questions?” the answer is often, “No.” What you have to tell me—what springs into your head—is probably going to be far more interesting that anything I’m expecting you to tell me. Hence, any questions I have will be really broad like, “What does this mean?” or “Do you buy it?” or “How does this fit with other stuff?” or “Science me up, nerd.”

Thomas Hayden describes how he reads scientific articles as a journalist

Just after the authors note “more research is needed,” you’ll usually find the one moment of speculation allowed in most papers. That’s where scientists get to suggest not just what their study contributes to the research enterprise, but what deeper implications it might have, or even how it might be applied. This is as close as the paper will come to answering the question, “So what? Why does any of this even matter?” [Note to science reporters: your job is to push the researchers to tell you more about this. Their job is to resist.]

Two hundred and sixty six years ago today, James Lind began what is regarded as the first proper controlled clinical trial

On the 20th May, 1747, I took twelve patients in the scurvy on board the Salisbury at sea. Their cases were as similar as I could have them. They all in general had putrid gums, the spots and lassitude, with weakness of their knees. They lay together in one place, being a proper apartment for the sick in the fore-hold; and had one diet in common to all, viz., water gruel sweetened with sugar in the morning; fresh mutton broth often times for dinner; at other times puddings, boiled biscuit with sugar etc.; and for supper barley, raisins, rice and currants, sago and wine, or the like. Two of these were ordered each a quart of cyder a day. Two others took twenty five gutts of elixir vitriol three times a day upon an empty stomach, using a gargle strongly acidulated with it for their mouths. Two others took two spoonfuls of vinegar three times a day upon an empty stomach, having their gruels and their other food well acidulated with it, as also the gargle for the mouth. Two of the worst patients, with the tendons in the ham rigid (a symptom none the rest had) were put under a course of sea water. Of this they drank half a pint every day and sometimes more or less as it operated by way of gentle physic. Two others had each two oranges and one lemon given them every day. These they eat with greediness at different times upon an empty stomach. They continued but six days under this course, having consumed the quantity that could be spared. The two remaining patients took the bigness of a nutmeg three times a day of an electuray recommended by an hospital surgeon made of garlic, mustard seed, rad. raphan., balsam of Peru and gum myrrh, using for common drink narley water well acidulated with tamarinds, by a decoction of wich, with the addition of cremor tartar, they were gently purged three or four times during the course.

The consequence was that the most sudden and visible good effects were perceived from the use of the oranges and lemons; one of those who had taken them being at the end of six days fit four duty. The spots were not indeed at that time quite off his body, nor his gums sound; but without any other medicine than a gargarism or elixir of vitriol he became quite healthy before we came into Plymouth, which was on the 16th June. The other was the best recovered of any in his condition, and being now deemed pretty well was appointed nurse to the rest of the sick …

Lind knew very little about scurvy apart from the typical progress of the disease, and he had no real idea of how the treatments might work.  That’s a handicap in coming up with ideas for treatment, but not in doing fair tests of whether treatments work.

The trial didn’t have an untreated group: all the patients got one of the treatments recommended by experts.  There’s no need for a controlled trial to have an untreated group — if there is an existing treatment, you want to compare to that treatment; if there is none, you may want to compare immediate vs delayed treatment.

Despite the dramatic success of fruit juice in the trial, it wasn’t adopted as a treatment. That, sadly, can still be the case today.  New drugs or surgical techniques are taken up enthusiastically, but boring interventions like nurse home visits or surgery checklists get less attention. Still, things are much better than they were even twenty years ago. Nearly all of medicine accepts the idea of randomized controlled comparison, and it is spreading to other areas such as development economics.

There are two excellent, free books about clinical trials and health choices: Testing Treatments, from the James Lind Initiative, and Smart Health Choices, from Les Irwig (at Sydney Uni) and coworkers.

Much of clinical trials development is unapologetically technical, but there are important areas where public participation can help:

• The James Lind Alliance asks patients and clinicians to say what questions matter most.  Clinical trials still tend to answer questions that are scientifically interesting or commercially important, not what actually matters most to patients
• The Cochrane Collaboration is attempting to collect and summarise all randomized trials.  The Cochrane Consumers Network is for non-specialist participation — in particular as Consumer Referees to help ensure that summaries of research address the questions that are important to consumers and are presented in language that consumers can understand.
• Ethics Committees that review clinical trials and other human research in New Zealand are required to have non-specialist community members. This is a substantial commitment, but one that is important if ethics committees are to be more than just red tape.
• And if you haven’t yet signed the AllTrials petition, calling for the results of all clinical trials to be published so we can know what treatments work, now would be an excellent time.

From the Wellcome Trust Monitor, a survey examining knowledge and attitudes related to biomedical science in the UK

The survey found a high level of interest in medical research among the public – more than seven in ten adults (75 per cent) and nearly six out of ten of young people (58 per cent). Despite this, understanding of how research is conducted is not deep – and levels of understanding have fallen since 2009. While most adults (67 per cent) and half of all young people (50 per cent) recognise the concept of a controlled experiment in science, most cannot articulate why this process is effective.

Two-thirds of the adults that were questioned trusted medical practitioners and university scientists to give them accurate information about medical research. This fell to just over one in ten (12 per cent) for government departments and ministers. Journalists scored lowest on trustworthiness — only 8 per cent of adults trusted them to give accurate information about medical research, although this was an improvement on the 2009 figure of 4 per cent.

The Herald has a completely over-the-top presentation of what might be an important issue. The headline is “Hospital choice key to kids’ survival”, and the story starts off

Where ambulances take badly injured children first seems to affect their chances, paediatric surgeons say.

Starship children’s hospital surgeons have found that sending badly injured children to the wrong hospital may be contributing to a child death rate from injuries that is twice the rate of Australia’s.

The data:

Six (7 per cent) of the 88 children who went first to Middlemore died, but so did one (8 per cent) of the 12 who went directly to Starship.

That is, to the extent the data tell us anything, the evidence is against the headline.  Of course, the uncertainties are huge: a 95% confidence interval for the relative odds of dying after being sent to Middlemore goes from a 40-fold decrease to a 12-fold increase.  There’s basically no information in the survival data.

So, how much of the two-fold higher rate of death in NZ compared to Australia could reasonably be explained by suboptimal hospital choice? One of the surgeons involved in the study says

… overseas research showed that a good trauma protocol system could cut the death rate for injured adults by 20 to 30 per cent, but there was no good data for children.

That is, hardly any of the difference between NZ and Australia — especially as this specific hospital-choice issue only applies to one sector of one city in New Zealand, with less than 10% of the national population.

On the other hand, we see

The head of Starship’s emergency department, Dr Mike Shepherd, said the major factors contributing to New Zealand’s high fatal injury rate for children lay outside the hospital system in policies such as driver blood-alcohol limits, graduated driver licensing, and laws requiring children’s booster seats and swimming pool fences.

That sounds plausible, but if it’s the whole story you would expect high levels of non-fatal as well as fatal injuries. The overall rate of hospitalisations for injuries in children 0-14 years is almost identical in NZ (1395 per 100 000 per year, p29) and Australia (‘about’ 1500 per 100 000 per year, page v).

Headline:  Study: Dark chocolate calms you down

Lead:

Eating dark chocolate can calm you down according to a new study.

Number of people actually given dark chocolate in the study: 0  (more…)

Dan Kahan, a researcher in the Cultural Cognition project at Yale Law School, has an interesting post on “the science communication problem”

The motivation behind this research has been to understand the science communication problem. The “science communication problem” (as I use this phrase) refers to the failure of valid, compelling, widely available science to quiet public controversy over risk and other policy relevant facts to which it directly speaks. The climate change debate is a conspicuous example, but there are many others

A long piece in the Washington Post: by Ezra Klein, recommended by Atul Gawande

Brenner puts it more vividly. “There is a bias in medicine against talking to people and for cutting, scanning and chopping into them. If this was a pill or or a machine with these results it would be front-page news in the Wall Street Journal. If we could get these results for your grandmother, you’d say, ‘Of course I want that.’ But then you’d say, what are the risks? Does she need to have chemotherapy? Does she need to be put in a scanner? Is it a surgery? And you’d say, no, you just have to have a nurse come visit her every week.”

From the Stephen Wolfram blog, lots of analysis of Facebook friend data with well-designed graphs.  For example, this graph shows how the mean age of your `friends’ is related to your age.

Those under 40 have Facebook friends of about the same age, but after than the age distribution levels off and becomes much more variable.

The New York Times has a story about finding interactions between common medications using internet search histories.  The research, published in the Journal of the American Medical Informatics Association, looks at search histories containing searches for two medication names and also for possible symptoms.  For example, their primary success was finding that people who searched for information on paroxetine (an antidepressant) and pravastatin (a cholesterol-lowering drug) were more likely to search for information on a set of symptoms that can be caused by high blood sugar.  These two drugs are now known to interact to cause high blood sugar in some people, although this wasn’t known at the time the internet searches took place.

This approach is promising, but like so many approaches to safety of medications it is limited by the huge number of possibilities.  The researchers knew where to look: they knew which drugs to examine and which symptoms to follow. With the thousands of different medications, leading to millions of possible interacting pairs and dozens or hundreds of sets of symptoms it becomes much harder to know what’s going on.

Drug safety is hard.

Statistical decision theory is about making decisions in the presence of uncertainty. We can’t know everything, but we still need to make choices.  In decision theory we assume that the world isn’t out to get us — if cigarette smoke is toxic, it is so regardless of whether or not we study it, and whether or not we’re trying to stamp it out. Murphy’s Law is true, but only as an engineering design principle, not a fact about the malevolence of Nature.

Game theory is the evil twin of decision theory — it’s about making choices in the presence of competition, when the other players aren’t precisely out to get you, but they are out to do the best for themselves.  There are a few examples of game theory in medical statistics: how do you set up regulations so that making effective drugs is more profitable than making ineffective ones? how do you use new antibiotics, given that resistance will inevitably develop? Typically, though, game theory works best in ecology, where natural selection ensures that organisms behave as if they were trying to maximise their numbers of descendants given the behaviour of other organisms.

A UCLA professor teaching a course in behavioural ecology decided to try to make his students really appreciate the problems of cooperation and competition that arise in game theory:

A week before the test, I told my class that the Game Theory exam would be insanely hard—far harder than any that had established my rep as a hard prof.  But as recompense, for this one time only, students could cheat. They could bring and use anything or anyone they liked, including animal behavior experts. (Richard Dawkins in town? Bring him!) They could surf the Web. They could talk to each other or call friends who’d taken the course before. They could offer me bribes. (I wouldn’t take them, but neither would I report it to the Dean.) Only violations of state or federal criminal law such as kidnapping my dog, blackmail, or threats of violence were out of bounds.