I have always been fascinated by numbers, especially those surrounding chance and probabilities. To be honest I’m not that good at them: many years of following horse racing failed to show any significant profit as a result (although to be fair it didn’t show any significant losses).

Assessing probability is something that we all do in our daily lives. Is it likely to rain? No, so I leave my umbrella behind and lo and behold the 5% chance of rain quoted by the Met Office reminds me again that there’s a world of difference between probability and actuality. In our field of drug safety, we have tried to adopt a numerical basis for assessing the likelihood of any particular event: reading a current data sheet will show how we attempt to add a numerical slant to the probability of events rather than relying on vague terms such as “unlikely”, common”, etc. The reason for this surfacing now is the recent publication of a book by David Spiegelhalter “The Art of Uncertainty: How to Navigate Chance, Ignorance, Risk and Luck”. Spiegelhalter is probably Britain’s best known mathematical statistician. He has a wide popular following through his BBC4 programme Tails You Win: The Science of Chance, and is also well known for his work on the statistical input to public enquiries, most recently that concerning the contaminated blood scandal. His book with Anthony Masters on Covid shed lots of light into what was a heated, polarised and largely unscientific debate. Indeed, he was quoted as saying that when he heard a politician saying they were following the science his heart sank! Spiegelhalter is well versed in the areas of healthcare and drug development. For many years he worked with the Medical Research Council Biostatistics Unit in Cambridge and been a consultant for Glaxo Smith Kline, Novartis and the World Anti-Doping Agency.

So why am I reviewing this new book? Because in my many years in the world of the international pharmaceutical industry I have seen us move from a time when decision making was based on personal opinions (with all their attendant prejudices), through early attempts at formal clinical research to the world we now inhabit of the massive controlled clinical trials and evidence-based medicine. Needless to say, this is greatly to be welcomed. But how many of us really understand the role of risk and chance when we are developing or monitoring medicinal products?

As an example, in his book Spiegelhalter looked at the news reports that burnt toast (and by extension other burnt foods) were carcinogenic. He calculated that you would need to eat vast quantities of burnt toast before we really needed to worry. Similarly, he looked at the media reports about us becoming a nation of couch potatoes and that binge watching TV could kill you by causing a pulmonary embolus: the original report warned of a 2.5 times increase in the risk of pulmonary embolism in those watching five hours of television a day but Spiegelhalter calculated that you would need to watch for 19,000 years to expect to die from an embolism! I think I’ll keep calm and carry on watching. Of course, burnt toast and couch potato binging are relatively unimportant in the overall scheme of things but in many other areas a more rational approach to risk and probability is desirable.

What this very readable book (even for the non-mathematically minded) does is to put a very cogent argument forward for embracing uncertainty and put it into all our thinking: putting uncertainty into our numbers. Think back to the Met. Office forecasts: if it says rain is 50% Likely then the number allows us to add a certain precision to our decision as to whether we might need our umbrella. Spiegelhalter gives a much more serious example. At the time of the Cuban missile crisis there was a plan to invade Cuba and the President’s briefing document stated that the invasion had a “Fair” chance of success. It subsequently turned out that the author of the brief meant this as “not too good”: Kennedy interpreted it as fairly good and authorised the Bay of Pigs action with its well-known consequences. (Just as an aside here I can recommend Max Hastings book Abyss as a most readable history of a time when I and most of the world thought we were on the brink of nuclear catastrophe). Since then several NATO member countries have, like the Met Office, put numerical probabilities into nebulous concept words such as “likely” or “uncommonly” to help in military decision making and , we hope, avert catastrophic misjudgements.

So, for all with an interest in the statistics of risk, chance and uncertainty this is an excellent primer and should certainly be of interest to all of us in the world of drug development and safety monitoring.

The Art of Uncertainty Penguin books 1994

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Finally, regular readers of my musing will know that I always look for news of re-purposed drugs, particularly vitamins, given the vast quantity of money spent with little hard evidence. This has been particularly notable with Vitamin D. However, I saw recently a report of a randomised placebo-controlled study from China suggesting that Vitamin K supplementation significantly reduced the frequency, intensity, and duration of nocturnal leg cramps in older adults. When I look back at the plethora of treatments that have been championed for this common and distressing condition it encourages me that people will still consider researching alternatives.