Apr. 9, 2016 9:02 am
So, here’s the thing. The scientific literature is awash with studies identifying biological differences as potential biomarkers. The problem is, that you can have a very profound biological difference between two groups of patients, but that difference is profoundly useless as a biomarker. Say what? To illustrate how this paradox arises, think of a well-established biological difference –...  Read More
Feb. 18, 2016 6:13 am
I have had my results for a long time: but I do not yet know how I am to arrive at them. Carl Gauss (1777-1855) Sometimes, when working on a problem, I may intuitively know the answer. But it can take many months before I work out the solution and can show my working. I'd like to think that this is because I'm a genius. But I'm not. The reality is that I often think in...  Read More
Feb. 7, 2016 4:50 am
The other day, I was faced with a complex dataset for analysis. A simplistic analysis presented massive multiplicity problems: we had multiple cytokines, at multiple time points, at multiple doses and multiple treatments. Initial plots of the data suggested there was not much going on. However, a multivariate analysis of variance flagged some real differences. Interpreting those differences...  Read More
Jan. 31, 2016 4:44 am
Ignore outliers at your peril: Outliers are often the most valuable data you have. Outliers often fly in the face of the scientific narrative. While, other studies have reported that identifying data that are inconsistent with current thinking is one of the critical success factors leading to scientific breakthroughs 7 , we observe that many jobbing scientists seek to...  Read More
Jan. 24, 2016 4:09 am
Stories help people make sense of the world. But when someone begins to believe those stories, and accommodate facts into those stories, they may become guilty of narrative bias. Theories help scientists make sense of the world. But when scientists begin to believe those theories, and accommodate facts into those theories, they may become guilty of narrative bias. Fortunately, scientists...  Read More
Jan. 6, 2016 12:31 pm
The Herschel Building in Newcastle University is home to a cluster of exciting, new,innovative spin-out companies at the leading edge of biomedical technology. I popped in there the other day to meet a client. As expected I learned that the building is named after the famous astronomer and composer William Herschel (1738-1822). Herschel is most famous for his discovery of Uranus in 1781. He...  Read More
Dec. 25, 2015 9:51 am
England is mired in history and tradition - "ritual's footsteps ankle deep in stone." One of the upsides of this is that with a little research, a trip to even the smallest and most obscure of villages or towns often yields some interesting historical surprises. Last weekend I found myself visiting the town of Burnopfield. If you've heard of Burnopfield I'd be rather surprised. It is a tiny...  Read More
Dec. 20, 2015 3:39 am
Every scientist knows that small, underpowered, studies are less likely to lead to statistically significant results. The Winner's Curse though is less well known. This refers to the observation that studies demonstrating an effect often provide inflated estimates of that effect. Such inflation is expected when an effect has to pass a certain threshold — such as reaching statistical...  Read More
Dec. 12, 2015 4:51 am
The website 'Shooting Tracker' collates data on mass shootings in the US. Mass shootings are defined as those with four or more victims. The US averages around one such mass shooting a day. I stumbled upon this analysis of mass shootings for the period 2013-2015: https://mpiccirilli.github.io/#plotting-data-on-maps Honestly? I can't tell you how bizarre it is for people living in Europe...  Read More
Dec. 2, 2015 6:21 am
I've been looking at outliers and was reminded of Maier's Law. If the facts do not conform to the theory, they must be disposed of. N.R. Maier, "American Psychologist", March 1960 Thanks to Tim Everitt for pointing me in the direction of this paper.  Read More
Nov. 26, 2015 6:28 am
I met with those clever people at Lazy Grace last week. They reminded me again of the story of Abraham Wald . Abraham Wald was a brilliant statistician forced to flee Nazi persecution of the Jews in Hungary. Wald observed that the data we don't have are often the most revealing. Looking to add armour plates to protect returning bombers during the Second World War, Wald advised that the plates...  Read More
Nov. 24, 2015 5:13 am
Many scientists believe that small experiments, guided by scientific intuition, are simpler and more efficient than design of experiments. This belief is strong and persists even in the face of data demonstrating that it is clearly wrong. The Design of Experiments (DOE) allows scientists to identify those experiments maximizing the amount of information about what is happening in the often...  Read More
Nov. 22, 2015 4:21 am
This week's research meeting was really interesting. One of the problems with Big Data is there is tons of it, most of it is garbage, and usually you don't have the one bit you really need. We were running through the key results from the analysis of what is one of the largest data sets ever collected from patients with this particular disease. The interpretation raged back and forth. After ten...  Read More
Nov. 7, 2015 6:04 am
Some time ago I shared three blog items on "Why Do Scientists Usually Get The Answers They Expect?" Many scientists believe that small experiments, guided by scientific intuition, are simpler and more efficient than Design of Experiments. This belief is strong and persists even in the face of data demonstrating that it is clearly wrong. These have now been written up in the paper ...  Read More
Oct. 31, 2015 6:14 am
Any statement that equates two errors is wronger than wrong when one of the errors is clearly more wrong than the other. Asimov's Axiom As Asimov put it: "When people thought the earth was flat, they were wrong. When people thought the earth was spherical, they were wrong. But if you think that thinking the earth is spherical is just as wrong as thinking the earth is flat,...  Read More
Oct. 27, 2015 9:07 am
I've been reading a great little book by Siddhartha Mukherjee on The Laws of Medicine: Field Notes from an Uncertain Science [1]. There are just Three Laws. We covered the First Law in The Laws of Medicine: The First Law The Second Law states: 'Normals' teach us rules; 'outliers' teach us laws. The argument is that most data, most patients, most experience provide rules of...  Read More
Oct. 25, 2015 5:14 am
I’ve been reading a great little book by Siddhartha Mukherjee on The Laws of Medicine: Field Notes from an Uncertain Science [1]. There are just Three Laws. The first law may be poorly formulated, but states: A strong intuition is much more powerful than a weak test. While intuition is attractive, beguiling, and often wholly or completely wrong [2] – the thrust of the argument is...  Read More
Oct. 21, 2015 12:11 pm
Six months ago I was doing some calculations and came up with a crazy result. I thought, “That can’t be right.” I let it slide. I left it alone for a few weeks. But that crazy result bugged me. I went back to it. And played with it some more. No matter what I did, I couldn’t make it go away. I began to entertain a radical idea “Maybe it was right?” That meant a problem thought to be...  Read More
Oct. 17, 2015 8:20 am
I was reading Simon Singh "The Simpsons and their Mathematical Secrets" where I discovered the story of Grace Hopper and the development of COBOL. Hopper spent most of her career in the US Navy eventually reaching the rank of Rear Admiral. She also has a destroyer - the USS Hopper - named after he. I think this is quite cool. Reading around I learned that as a young girl her scientific...  Read More
Oct. 13, 2015 7:51 am
The recent interview with Medicine Maker caught me in a candid and expansive mood saying what I really think about pharmaceutical research and development. In particular I was outspoken in describing how closing the door on faltering projects then opens the door to prospective future gains. Now read on... --- Admitting defeat in pharma R&D and terminating a failing project is a hard...  Read More
Oct. 9, 2015 5:44 am
I've worked with some pretty sharp people in my time, but few as sharp as Prof Stephen Senn. He cuts to the nub of any issue with consummate ease. And his razor sharp wit permits him to demolish shoddy thinking to the music of belly laughing audiences. I don't know how he does it, but he appears to have an encyclopaedic recall of all things and an original viewpoint on everything. And if I...  Read More
Oct. 4, 2015 5:15 am
The first time a scientist is called upon to present a piece of scientific data can be rather daunting. You might hope that lab meetings provide a caring and supportive environments for the new scientist. It doesn't always work out like that. It can be a crucible. Anyone and everyone seems to hold strong views about your data. And everyone appears to be competing to tear your research apart....  Read More
Sep. 29, 2015 7:35 am
I've not been blogging for a while and someone asked what was going on! Well, the thing is, I made an amazing discovery. So amazing, that it has consumed me for the last six months. How is it amazing? I discovered a way of doing something that I thought impossible. In fact, only last year, I foolishly wrote a paper stating that this thing was 'unknown and unknowable'. Don't get me wrong; I...  Read More
Sep. 29, 2015 6:06 am
Already it’s been a busy week. I was reminded again of the 90-90 Rule of project management. The first 90% of the task takes 10% of the time, and the last 10% takes the other 90%.  Read More
May 3, 2015 4:37 am
There is a graveyard in London called Bunhill Fields. Now a public park, it was used as a burial ground from 1665 until 1854. It contains the graves of many notable people, including John Bunyan (d. 1688), author of The Pilgrim's Progress Daniel Defoe (d. 1731), author of Robinson Crusoe William Blake (d. 1827), artist and poet Bunhill Fields also includes the tombs of two famous...  Read More
Apr. 22, 2015 8:13 am
Recently, David Trafimow, Editor of the Journal of Basic and Applied Social Psychology announced that traditional hypothesis testing would be banned from that journal. The flawed rationale was that probability, or p-values, are "logically invalid". In a previous Editorial setting out his position, he cites his earlier paper outlining his thinking[1]. Ignoring the hysteria following the...  Read More
Apr. 6, 2015 3:23 am
I heard a sculptor talking about artistic ideas. She described how her students would come to her and talk excitedly about their ideas. Rather than argue, or point out potential problems, she would set them to work on the idea. Ninety percent of the ideas never came to pass. The ideas were often brilliant. Turning them into a palpable reality was impossible. Clay can be an unforgiving...  Read More
Mar. 29, 2015 1:07 pm
The Wimbledon Effect is used to describe a successful organization that resists the need to change until it is too late for change to be effective. It is named after the English All Tennis Association tournament of the same name. Wimbledon became a victim of its own success in the 1990s after failing to respond to changes in the professional tennis game. One of the key problems was the...  Read More
Mar. 28, 2015 4:03 am
I watched Monica Lewinsky's recent TED 2015 talk and it got me thinking about the internet and the use and abuse of Comments. There are a few places on the internet where Comments are used, for the most part, with respect. Comments in the BestThinking pages, for example, are usually inoffensive. Sometimes you get comments from "passionate people" (British-speak for "loonies"). And...  Read More
Mar. 19, 2015 3:18 am
Everyone has heard of the placebo effect: the expectation of a positive treatment effect can have a positive treatment effect even if the "treatment" is a sham treatment or inert drug treatment. The nocebo effect is the opposite effect. Where negative expectations can have a negative effect on treatment outcomes. List the possible adverse effects of a drug, and sure enough a significant...  Read More
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