The Grey Literature – Page 11 – The Grey Literature

Rethinking Research Ethics: The Case of Postmarketing Trials

Good news!

Toward the end of the year in which I was working on my thesis, my supervisor had me write up a shorter version of my thesis for an attempt at publication. This was no small feat—imagine trying to compress a 90-page master’s thesis into 2 pages!

After my RA-ship ended, my supervisor, Jonathan Kimmelman, and Alex John London took the paper, made some substantial edits, and submitted it to a couple journals. The paper was accepted, and as of this week, it was published in Science.

Needless to say, I’m thrilled. :D

The Carlisle-Desroches Quidditch Hoop Construction Manual

I discovered last week that the Carlisle-Desroches Quidditch Hoop Construction Manual was incorporated into the latest version of the IQA rulebook! Hooray!

We never received any official notice from the IQA—we found out about this when one of my teammates noticed a reference to the design on the IQA site. Anyway, we’re honoured, and this has inspired us to put some more work into it. Also, one of the members of the McGill Quidditch team has asked us to re-think the bases for the hoops this summer.

Hence, we plan to build, test and release the Mark II Carlisle-Desroches Quidditch Hoop over the course of the summer. The new design which will be the same as the original, but with an alternate base that’s probably made of PVC rather than the current bucket-o-concrete. For the record, I like the bucket-o-concrete, but some have raised concerns about safety. They’re afraid that people will hit their heads.

Chord progression for “Mad Man with a Box”

For those who are interested in such things, the chord progression (well the interesting part of it anyway) for “Mad Man with a Box” (one of the themes from season 5–6 of Doctor Who) is as follows.

Key area: d-

i-V43/V-viiº-i64-III6 (or I6/iii—it’s a pivot chord to the relative major, F+, the key in which the remaining chords will be written)-IV-I64-V7/vi-vi

I resolved it to a vi chord, but often it’s left unresolved.

If you wanted to keep it all in the key area of d minor, you could write it more simply like this:

i-V43/V-viiº-i64-I6/iii-IV/iii-I64/iii-V7-i

Game theory and medical research

I recently learned what exactly a Nash equilibrium is, and like any obnoxious academic with a new idea, I’m really excited about it. Hence, I will apply what I’ve learned in Game Theory so far to the field of medical research ethics.

First, some definitions: A Nash equilibrium is a set of strategies that the players in a formalised game adopt such that the utility that each player receives for her chosen strategy is the greatest, given the choices of strategies of all the other players in the game.

This could be formalised as follows:

A Nash equilibrium exists when u_i (a_i, a_-i) ≥ u_i (a_i′, a_-i) for all a_i′ and all i, where:

u_i is a function whose range is utility values for player i and whose domain is an ordered n-tuple of strategies taken by all the players in the game

a_i is the chosen strategy of player i

a_-i is the set of chosen strategies for all the other players, and

a_i′ is some alternate strategy that player i might adopt.

What’s interesting about Nash equilibria is that given a particular formalised game, other non-Nash sets of strategies are “unstable”—that is, if a player finds out that given the strategy choices of the other players, she could have made a better decision, she will change her strategy accordingly.

The famous Prisoner’s Dilemma (look it up if you haven’t heard of it) is a great example of a Nash equilibrium where the outcome for each of the players is not optimal, even though they are in equilibrium.

What’s interesting to me about things like this is how it can be applied to medical research, if we make certain simplifying assumptions. Let’s imagine that medical research is like a two-player game. The players are the pharmaceutical industry on the one hand and some other participant in human research on the other.

In the tables below, Big Pharma has two strategies open to it—developing a “seeding” study or developing a “quality” study. The other participant (who could be a research subject or a physician-investigator or a journal that publishes medical research papers) also has two strategies available—participating in the study developed by Big Pharma, or not participating.

If the other stakeholder in the research project doesn’t participate, neither Big Pharma nor the participant receive any benefit. The utility outcomes for Big Pharma and the other stakeholder are 0, 0, respectively.

If the other stakeholder participates and the study is a high-quality study that provides socially valuable medical information, Big Pharma and the other stakeholder receive utilities of 1, 1, respectively.

But, if it turns out that the pharmaceutical company has produced a “seeding” study—one that is designed for narrow ends, namely those of being a marketing tool to get physicians used to prescribing a drug that has already received licensure—the pharmaceutical company receives a utility of 2 and the other stakeholder receives a utility of -1. That is to say, Big Pharma gets a big payout, because hundreds of doctors are now prescribing the drug, but the other stakeholder incurs a net harm in some way. (If she is a study participant, he may feel used or cheated. If she is a doctor, it may be a source of professional embarrassment. If it is a journal that published a “seeding” study, that journal will lose some of its reputation, etc.)

	Participate	Not
“Seeding” study	2, -1	0, 0 *
“Quality” study	1, 1	0, 0
Table 1. Asterisk (*) indicates Nash equilibrium.

So if we go through each set of strategies that the players in this game can take, we find that the one with the asterisk is the only one that is a Nash equilibrium. This is because if you are Big Pharma in this game, given that the other stakeholder has chosen not to participate, you are indifferent between strategies, and if you are the other stakeholder, given that Big Pharma has chosen to develop a “seeding” study, your best choice is to not participate.

It’s interesting to note that this setup is analogous to markets for financial products and other “confidence goods,” where the buyer has a really hard time telling the difference between high and low quality products.

But what if no one caught on that the study was a “seeding” study? Let’s imagine that Big Pharma got away with running a seeding study and no one ever figured out that that’s what it was. We would end up with a game that can be represented as follows:

	Participate	Not
“Seeding” study	2, 1 *	0, 0
“Quality” study	1, 1	0, 0
Table 2. Asterisk (*) indicates Nash equilibrium.

Here, the equilibrium has shifted. This explains why pharmaceutical companies try to develop “seeding” studies, and why they try to hide it.

So the question becomes, how can we set up the “rules of the game” of medical research in order to shift the equilibrium such that other stakeholders will participate and the pharmaceutical company will develop quality studies?

Or to put it another way, if we assume that the utility for non-participation for all players is 0, and that both the pharmaceutical company and the other stakeholder should both come away from a quality study having received some utility, what value for x will put the Nash equilibrium where the asterisk is in the table below?

	Participate	Not
“Seeding” study	x, -1	0, 0
“Quality” study	1, 1 *	0, 0
Table 3. Asterisk (*) indicates Nash equilibrium.

The value of x must be less than 1 in order for the Nash equilibrium to fall where the pharmaceutical company develops a “quality” study and the other stakeholder participates. This is because if x = 1, Big Pharma will be indifferent between its strategies, given the choice of the other player, and if x > 1, as we saw in Table 1, the equilibrium will shift to where Big Pharma produces a “seeding” study and the other stakeholder declines to participate.

So in real life, how do we make x to be less than 1? There has to be some sort of sanction or penalty for pharmaceutical companies for producing seeding studies that makes their expected utility less than that of a quality study. This can be done by either putting a tax on seeding studies or by making regulations against seeding studies outright.

Game theory course

So the Online Game Theory course that I was talking about started, and it’s just as good as I thought it would be! As of when I’m posting this, you have forty-five minutes left to register, if you want to join me.

I took an actual university course for credit in Decisions Analysis when I was an undergrad, which was one of the best educational experiences of my life. Decisions Analysis is the science of making rational decisions under conditions of uncertainty. The way that the profs for the online Game Theory course describe Game Theory is that it is the science of describing the actions of idealised actors within a particular system, given certain simplifying assumptions. Decision Theory, they say, is like a subset of Game Theory—it is like Game Theory where there’s only one player. This is very exciting to me.

I have already learned how to formalise a number of things that I investigated during the course of my thesis. Further, I now know what the actual definition of a Nash equilibrium is. It’s a concept that I had a sort of fuzzy handle on before, but now I think I could express it formally using proper notation and apply the concept to ideas like the medical research enterprise or smartphone application development systems.

I’ll keep you updated with regard to some of the more interesting results that I find. :)

Free online game theory course

So a few months ago I signed up for a free online course in Game Theory, taught by two professors at Stanford. I like Stanford. Ever since I discovered the Stanford Encyclopaedia of Philosophy as an undergrad (the one website that philosophy profs will allow you to cite in your papers), I had a profound respect for this institution’s free online offerings.

The course isn’t for credit at all—there’s just video lectures, and “quizzes” integrated into the videos. I guess I’m sort of interested in it because it relates to my thesis subject. Ever since I wrote my thesis on it, I find the whole idea of collaborative enterprises fascinating, and I would love to be able to more rigorously analyse what regulations would make a complex system with multiple stakeholders work best.

The course was supposed to start in “late February 2012,” so I waited until today—I was going to send the professors an email, since February 29th is about as late in February as you can get. So I opened up the site for the course to find a contact email address, and found the following message:

Regarding the start-date of the Game Theory Online course: The University is still finalizing policies to cover its new online courses, and so there has been some delay in the launching of the courses. We anticipate being able to launch the course soon, and will keep you informed of any news on the starting date. Matt and Yoav

I’ll let you know if anything interesting comes of this. Let me know if you sign up for the course yourself. :)

How to break Endnote X5, Visual Basic and Microsoft Word

As many of you know, my old computer Fermat recently died. After a respectful period of mourning, I got a new one. Its name is “Gödel.” (I name my computers after mathematicians, in alphabetical order, starting at E. My first computer was named “Euler,” my second was “Fermat,” and so this one had to be “Gödel.”)

This week, when I opened up Microsoft Word to work on an assignment, I noticed something funny—the Endnote toolbar was missing. Endnote is the reference manager software that I use on pretty much all my school assignments.

I had this problem before, when I first installed Word on Fermat. The problem was that I installed Word after I installed Endnote. I thought it was the same problem, so I reinstalled Endnote. This didn’t help.

So I tried Googling the problem. I tried using the Endnote “customizer,” but that didn’t work. I tried repairing the disc permissions. Eventually, I called Thomson-Reuters technical support who had me go through all the steps I already found on the internet, and eventually told me that I had to re-install Word.

So, I did a full uninstall of Word and a complete reinstall, which was more difficult than expected, because my computer no longer has an optical drive.

I reinstalled Word and Endnote, but to no avail. My reference manager was still unavailable.

I called Microsoft technical support, who had me do all sorts of things—making new users on my computer, shift-restarting, repairing disc permissions again. This was also fruitless, except that they were able to identify that it was a problem with Visual Basic, which is necessary for Endnote-Word integration apparently.

They told me that my installation of Word was corrupted somehow, since Visual Basic was not able to access the folder for Visual Basic macros. They thought it might have something to do with my anti-virus software, and told me to reinstall with my anti-virus turned off.

I did this, but it didn’t help at all.

So I tried thinking about what was different between Gödel and Fermat: Fermat was running Mac OS X 10.6, and Gödel was running 10.7, but that was the only thing I could think of, until I realised that I had named my hard disc “Gödel”—including the two little dots over the O. I renamed the hard disc to “Godel,” and started Word.

Endnote worked immediately.

So the moral of the story is, if you want to break Visual Basic in your installation of Microsoft Word, just put a non-standard character in your hard disc’s name.

Weird thing to find in my readings for “Health and Physical Assessment”

My textbook for “Health and Physical Assessment” is called Physical Examination and Health Assessment (first Canadian edition) by Carolyn Jarvis. I’ve only done two readings from it, and it’s mostly what I expect. Largely, it’s written in a very scientific tone. It’s a textbook about anatomy, some common forms of illness, and techniques on how to assess a patient.

What’s surprising is something I found right in the middle of chapter 18, (thorax and lungs). The author uses an emotive, almost poetic voice to describe the baby’s first breath:

Breath is life. When the newborn inhales the first breath, the lusty cry that follows reassures anxious parents that their baby is all right.

(Jarvis, C. Physical Examination and Health Assessment. First Canadian Edition. p. 442)

The chapter continues immediately afterward in its characteristic, professional manner for the rest of the chapter, as if nothing happened. I read it, and had to go back to make sure that I didn’t imagine it. I don’t even know what they’re trying to get at with the whole “breath is life” thing. It’s almost philosophical, but then there’s no content there.

Just weird, that’s all.

My computer is messed up

Meet my computer, Fermat. Fermat is an old computer. I bought it in 2006, and it’s been through a lot. I’ve started to notice a number of funny things that it does. I like to think of them as quirks of old age, rather than as bugs.

For example, I noticed recently that the green light that normally indicates when the camera is on sometimes turns on even when the camera is off. In fact, it will stay on even though I restart the computer in an effort to turn it off. See attached photo.

It’s kind of creepy, like Fermat is watching me, even though I tell it not to.

Antibiotics and antivirals

More and more often these days, I come across articles about new anti-viral drugs that look really promising. Further, I’m sure we’ve all read or heard about the phenomenon of antibiotic resistance—strains of bacteria who acquire the ability to survive treatment with antibiotics which would otherwise kill the bacteria and cure the patient.

Since the discovery of antibiotics, bacterial infections have been relatively easy to treat, whereas viral infections have been something that can’t be treated directly. The treatment for a bacterial infection is penicillin, but the treatment for the common cold is bed-rest.

What I find interesting about these developments is that we may be entering an age where this is reversed: Bacterial infections may become difficult or impossible to treat directly, while viral infections can be simply and easily cured with drugs.