Fellow me

Last summer I have applied for a NIHR Research Methods fellowship. Earlier this week the results have come out and they have liked my proposal, which is of course great news. 

The idea of this project is to critically evaluate the stepped wedge design (SWD) in clinical trials. This is a relatively new design, effectively an extension of cross-over design, in which a given intervention is rolled out in clusters that unilaterally switch treatment at different time points. The first time point usually coincides with a baseline measurement where all the clusters are assigned to the control arm. Subsequently, clusters begin to receive the active treatment, but, unlike in a standard cross-over trial, once the intervention is given, it is not removed. The time at which the intervention is started is randomly determined.

This on the one hand typically increases the duration of the study (because several time points are usually needed to reach a fixed level of statistical power); however, on the other hand, the SWD has shown the potential to be more efficient than standard cluster randomised (CR) designs.

But of course, much as for standard cross-over designs, the actual gains depend on specific settings and parameters specifications (eg in terms of the the number of clusters and time points; the clusters size; the level of correlation between measurements in the same cluster and across time). So we'll try and investigate these issues and see under which conditions the SWD works better than other strategies. As part of the proposed outputs of this research, we have indicated that we'll produce a toolbox (in R) to perform sample size calculations and guide the analysis of the actual data.

The Big Bayes theorem theory

While we were eating a forkful of what was supposed to be a frittata, but turned out to be very fluffy mushroom scrambled eggs earlier, we were half watching an episode of The Big Bang Theory. 

Long story short, my eye was caught by Sheldon explaining how he is estimating his life expectancy, clearly using Bayes's theorem (although he didn't refer to it in his speech to Leonard).

Good stuff, Shelly!

Bad teacher(s)

This morning there has been some frenzy on the UK media (eg here or here) after the publication of a pamphlet by David Willetts, a junior minister for University and Science under the infamous coalition government.

The minister's point is that, comparatively to what used to be case in the past (notably in 1963 before changes in policy that led to increase in the number of university students), the proportion of time spent teaching by university lecturers is decreased in favour of the time that they spend otherwise.

Now, of course, this is not necessarily bad or good per se, but the minister says in his paper that "Looking back we will wonder how the higher education system was ever allowed to become so lopsided away from teaching." 

Well, one easy answer is of course to point out that apart from the huge increase in the number of students $-$ it would actually be interesting to have reasonable figures on the time spent teaching per-student, in comparison with pre-1963! $-$ the government(s) have switched the emphasis to research by decreasing the amount of funding available for universities and rewarding private initiative to obtain research money, eg from industry, or simply making the process of funding increasingly competitive!

Again, not necessarily a bad thing, but certainly not something to coolly swipe under the rug...

R2jags & BCEA (& the examples from BMHE)

Recently, Yu-Sung Su and Masanao Yajima, the developers of the R2jags package, have released a new version (the current one is 0.03-11). As far as I understand it, one of the main changes is that since the update, R2jags no longer depends on the R2WinBUGS package (although it "imports" it).

The consequence of this is that you can no longer use the R2WinBUGS functions, such as for example bugs or attach.bugs(), by just loading R2jags. In fact, there's a new function attach.jags() that allows you to attach the object you obtain as a result of the call to the jags function and containing, among other things, the MCMC simulations.

More importantly, if you also use BCEA and try to replicate the examples I describe in BMHE (for example see here, here, here and here) you are in trouble. All the code I have produced was running OK under the previous version of R2jags, but now you do get an error message when you try to attach the JAGS object using the attach.bugs() command.

Fortunately, this is not a huge problem and you actually have two options to solve it: the first one is to add to all those scripts a formal call to R2WinBUGS, eg library(R2WinBUGS). This will make the attach.bugs() command available again and so the rest of the code will run OK.

The second way is to actually use the attach.jags() command directly. In this, you don't need to load R2WinBUGS; however (because, as Sheldon Cooper would say: "what's life without whimsy?"), in this case you have to change the argument to this function, since attach.jags() takes a rjags object, while  attach.bugs() wants a bugs object.

So, for example, assume you have the following code.
library(R2jags)
model <- jags(data,inits,parameters.to.save,
        model.file="some_file.txt", n.chains=2, 
        n.iter, n.burnin, n.thin, DIC=TRUE, 
        working.directory=working.dir, progress.bar="text")
and you want to make the object model (and all the elements contained in it) available to your R session, you can either do
library(R2WinBUGS)
attach.bugs(model$BUGSoutput)
(notice that model is an object in the class rjags, while its element BUGSoutput is in the class bugs), or do
attach.jags(model)
directly.

Le Tour

Today I've given the talk on the model for structural zeros and the related R package BCEs0 for the third time in three weeks (this time it was at the London School of Hygiene and Tropical Medicine).

Le Tour is going quite well, I think $-$ in all three occasions, the talk has been well received. What I think is also interesting is that each time I have received a very different set of questions.

At GSK, people in the audience asked questions on the broader methodology for cost-effectiveness analysis (which they weren't probably very familiar with). In Las Palmas, most questions were about the details of the Bayesian model (for example, the use, or misuse, of the DIC as a measure of model fit and to apply structural sensitivity analysis).

Today, most questions were about the substantial aspects of the economic evaluation. For example, Richard made the interesting point that the model for structural zeros could be turned into a model for "structural ones" in the utility measure $-$ the problem being that sometimes when QALYs are used as the measure of effectiveness, a bunch of patients are associated with a value of 1, which indicates maximum utility. 

This effectively generates a two-component mixture (individuals with utilities in $[0;1)$ and individuals with a utility value of exactly 1). The extension of the hurdle model should be able to do the trick in this case too. This may be a good thing to do for my undergraduate student who will do her project on health economics!

Election night(s)

The 2013 ISBA elections are finally underway! From today (and until November 15th) members will be able to cast their vote for several posts, by simply visiting this webpage.

As I mentioned here, this time around I am one of the candidates, specifically for the section on Biostatistics and Pharmaceutical Statistics (my statement is here $-$ just navigate to the relevant section).

Like any self-respecting candidate, I have already cast my vote $-$ it has always amused me that top politicians are always shown on television casting their vote 21 seconds after the ballot is open. Unfortunately, no TV crew was there to record the operations...

Road trip

Today I had a meeting for one of the projects in which I'm involved. This is a big research grant (in which I have a marginal role, to be honest), with the aim of evaluating some occupational therapy for people with dementia and their carers. 

Nothing special there, you might say; in fact, nothing special there. Except that the meeting was to be held in a far and remote location...

View Larger Map

The main research team are located in a hospital in North East London (well, I suppose that's technically Essex) $-$ a good 32 miles (that's 52 km) from home. So I had a kind-of-nice road trip to get to my meeting, which basically crossed London from one side to the other. Fortunately it wasn't too cold and it hasn't rained, while I was going, so the journey wasn't too bad. Some parts of London are just awesome! 

Self-syndication

This is a piece I've written for The SWITCH project website. SWITCH is a research project addressing issues related to the social market economy in Europe. The topics addressed in the project range from macro financial sustainability conditions to the dynamics of science and innovation. I'm self-syndicating the piece here.

The OECD has just released an interesting working paper comparing the issue of value of pharmaceutical innovations and its impact on pricing. The main, well known argument is that policy on pricing should have impact in the short term (by lowering costs with respect to benefits) as well as in the long term (by encouraging R&D and innovation). The report analyses 12 countries, mostly (but not exclusively) in qualitative terms. One obvious result is that heterogeneity among them is observed, particularly among countries which have guidelines on the use of economic evaluation to drive the process of reimbursement and pricing, and those which do not. 

Of course, even among those formally considering cost-effectiveness considerations there are differences and the evidence is not conclusive as to, for example, which cost-effectiveness threshold should be selected. In particular, this has implications when discussing specific diseases and thus pharmaceutical interventions, such as terminal illnesses (eg cancer). In that respect, there is perhaps an argument to suggest the use of alternative utility functions, which for example include a measure of lower risk aversion on the part of the decision-maker. 

While this aspect is only marginally hinted in the report, the tremendous implications from the technical point of view is clear. Tools such as the expected value of information can be used more extensively to aid in quantifying the value of deferring decisions (on reimbursement or pricing) in order to reduce the uncertainty characterising the evidence presented by the company. This is relevant as, almost invariably, files are based on limited evidence from clinical trials, which may need complementing from post-marketing or observational data. 

Finally (a point missing from the report — although to be fair, this was not their main objective), the all important issue of the underlying assumption that the market is able to adjust instantly to the introduction of new, cost-effective interventions: most of the times, we observe older interventions staying on the market for a longer time. While this can be justified (eg by bringing to bear the uncertainty in the cost-effectiveness profile of the new intervention), it is also likely to produce a loss of optimality. Again, the expected value of information could be used to determine a form of pay back (eg from the companies allowed to remain on the market with a drug which is potentially non cost-effective), which could lead to alternative pricing policies [Baio, G., Russo, P. (2009). A Decision-Theoretic Framework for the Application of Cost-Effectiveness Analysis in Regulatory Processes. Pharmacoeconomics 27(8), 645-655 doi:10.2165/11310250-000000000-00000].

The (third) runway bride

I think I should disclaim the conflict of interest in this one (since Marta is one of the authors of the paper), but it was really, really cool to see her study on the impact on health of noise pollution close to airports in the newspapers today (for example here or here)! 

I thought that the Daily Mail would be also all over the news, while, interestingly, there's nothing on their homepage (although they do mention the article here).

I think the choice of pictures to accompany the articles is also quite interesting: The Guardian chose a rather romantic picture of an airplane taking off from Heathrow at dawn (or sunset $-$ I couldn't quite tell), while both the BBC and the Daily Mail had pictures of airplanes extremely close to properties or the ground (well, they were landing, after all...).

The original paper is linked here.

Happy birthday

Sylvia Richardson (who's now the head of the MRC Biostatistics Unit in Cambridge, and part of our RDD project) asks me to advertise the MRC Biostatistic Unit's Centenary Conference, which will be held in Queens' College Cambridge on March 26th 2014. 

More info are at this webpage, and here is a flyer $-$ the deadline for submission of contributed papers and posters is 28th October.

Video killed the radio stars

Francisco tells me that they have uploaded my talk (which I gave last week in ULPGC). I haven't seen it all, but the bit I did see is not too bad, I thought... Check it out!

 

Nice & weird people in the Canary island (oh: I went there for work too!)

The past one has been a very interesting week, which I've spent visiting the University of Las Palmas, in the Canary Island. Since it was the last week on maternity leave for Marta, we all went. I knew the weather would be good, but we didn't expect it to be so nice $-$ like proper summer weather!

We were really lucky to start with, as while we were driving to the airport last Saturday, I accidentally got the wrong turn before entering the motorway and by doing that, we were able to see a massive queue ahead. So we decided to ask our phone to drive us to the airport through the Surrey back roads. We got a bit scared because the navigator kept telling us to turn into small roads that looked nothing like going to the airport, but in the end we actually got there on time (unlike 15 people who actually missed the flight).

Of all the family, XY has enjoyed the week the most. He has spent most of the time eating, walking around and being chatted up by the nice, friendly people in the streets of Las Palmas. At first he was a bit puzzled by people speaking in Spanish (I guess it sounded close enough to Italian, but not quite Italian, so it freaked him out a bit). But then he got used to it and started waiving at people when they were stopping us in the streets to say that he was so "precioso", or "lindo", or "guapo".

Speaking of which, I found it amazing how we could relatively easily get by with our Spanitalian. In fact, I did study a bit Spanish, which was helpful, but for most things we could speak to people without resorting to hand-waiving or English (of course that's not ground-breaking news $-$ but it was nice).

Which brings me to the actual reason of the trip, which was a week of meeting with Miguel Negrín and Francisco Vázquez Polo. We mainly talked about some work in health economics, specifically related to the application of utility functions different from the standard net benefit (which is defined as $ke - c$, where $e,c$ are the variables of clinical effectiveness and cost, respectively, and $k$ is a willingness-to-pay parameter, used to rescale the benefits and put them on a monetary scale). In the beginning I wasn't quite convinced about their argument, but then we got to talk and, while I'm still not 100% sure of all the implications, I think this is an interesting problem and definitely worth investigating. So we'll try and work on this together, which is a good outcome of the visit $-$ and I'll post about this, once we (I) have clearer ideas/material. I also gave a seminar on the structural zero model, expanding on the talk I gave at GSK a few days back. I think this is really interesting and I seem to get useful comments, which I'll definitely use in my revision of the paper.

The last day we rented a car and decided to tour the island of Gran Canaria. We'd never been there before, so we didn't really know much, but Miguel and Francisco made a couple of suggestions. While we were walking around in Maspalomas, a weird Italian lady stopped us and started to blab. She looked interested in us, but in fact asked us how old we were 3 times in the space of 5 minutes and told us pretty much the same things about 20 times. As it turned out, she was working for a holiday resort (apparently they have taken some sand from Bahamas and brought it there before building the resort $-$ I am still annoyed with myself that I didn't turned around and left as she actually said that, as if it was some amazing thing which was supposed to make me want to divorce Marta and marry her instead). Anyway, she wanted us to get some sort of scratch'n'win ticket. We weren't really interested but she started scratching a couple and apparently we won either an iPad, a free one-week holiday (in one of their "amazing resorts"), or €500 in cash. To get the prize we "only" had to go and see the resort with the Bahamas beach, which we could only do by going with a cab that she had to call (and there was no other way, "because those are the rules"). We went back to the car and actually visited the nice little town of Teror (not very big and not very much to do, but still quite nice and much less hot!).