S. Senn

S. Senn: Lauding Lord (Guest Post)

Posted on October 29, 2022 by Mayo

 

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Stephen Senn
Consultant Statistician
Edinburgh, Scotland

A Diet of Terms

A large university is interested in investigating the effects on the students of the diet provided in the university dining halls and any sex difference in these effects. Various types of data are gathered. In particular, the weight of each student at the time of his arrival in September and their weight the following June are recorded.(P304)

This is how Frederic Lord (1912-2000) introduced the paradox (1) that now bears his name. It is justly famous (or notorious). However, the addition of sex as a factor adds nothing to the essence of the paradox and (in my opinion) merely confuses the issue. Furthermore, studying the effect of diet needs some sort of control. Therefore, I shall consider the paradox in the purer form proposed by Wainer and Brown (2), which was subtly modified by Pearl and Mackenzie in The Book of Why (3) (See pp212-217). Continue reading →

Categories: Lord's paradox, S. Senn | 8 Comments

S. Senn: The Many Halls Problem (Guest Post)

Posted on November 2, 2021 by Mayo

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Stephen Senn
Consultant Statistician
Edinburgh, Scotland

 

The Many Halls Problem
It’s not that paradox but another

Generalisation is passing…from the consideration of a restricted set to that of a more comprehensive set containing the restricted one…Generalization may be useful in the solution of problems. George Pólya [1] (P108)

Introduction

In a previous blog  https://www.linkedin.com/pulse/cause-concern-stephen-senn/ I considered Lord’s Paradox[2], applying John Nelder’s calculus of experiments[3, 4]. Lord’s paradox involves two different analyses of the effect of two different diets, one for each of two different student halls, on weight of students. One statistician compares the so-called change scores or gain scores (final weight minus initial weight) and the other compares final weights, adjusting for initial weights using analysis of covariance. Since the mean initial weights vary between halls, the two analyses will come to different conclusions unless the slope of final on initial weights just happens to be one (in practice, it would usually be less). The fact that two apparently reasonable analyses would lead to different conclusions constitutes the paradox. I chose the version of the paradox outlined by Wainer and Brown [5] and also discussed in The Book of Why[6].  I illustrated this by considering two different experiments: one in which, as in the original example, the diet varies between halls and a further example in which it varies within halls. I simulated some data which are available in the appendix to that blog but which can also be downloaded from here http://www.senns.uk/Lords_Paradox_Simulated.xls so that any reader who wishes to try their hand at analysis can have a go. Continue reading →

Categories: Lord's paradox, S. Senn | 7 Comments

Fair shares: sexual justice in patient recruitment in clinical trials

Posted on August 7, 2021 by Mayo

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Stephen Senn
Consultant Statistician
Edinburgh, Scotland

It is hard to argue against the proposition that approaches to clinical research should treat not only men but also women fairly, and of course this applies also to other ways one might subdivide patients. However, agreeing to such a principle is not the same as acting on it and when one comes to consider what in practice one might do, it is far from clear what the principle ought to be. In other words, the more one thinks about implementing such a principle the less obvious it becomes as to what it is.

Three possible rules

Continue reading →

Categories: evidence-based policy, PhilPharma, RCTs, S. Senn | 5 Comments

S. Senn: “Beta testing”: The Pfizer/BioNTech statistical analysis of their Covid-19 vaccine trial (guest post)

Posted on January 17, 2021 by Mayo

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Stephen Senn

Consultant Statistician
Edinburgh, Scotland

The usual warning

Although I have researched on clinical trial design for many years, prior to the COVID-19 epidemic I had had nothing to do with vaccines. The only object of these amateur musings is to amuse amateurs by raising some issues I have pondered and found interesting. Continue reading →

Categories: covid-19, PhilStat/Med, S. Senn | 16 Comments

S. Senn: Testing Times (Guest post)

Posted on October 28, 2020 by Mayo

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Stephen Senn
Consultant Statistician
Edinburgh, Scotland

Testing Times

Screening for attention

There has been much comment on Twitter and other social media about testing for coronavirus and the relationship between a test being positive and the person tested having been infected. Some primitive form of Bayesian reasoning is often used  to justify concern that an apparent positive may actually be falsely so, with specificity and sensitivity taking the roles of likelihoods and prevalence that of a prior distribution. This way of looking at testing dates back at least to a paper of 1959 by Ledley and Lusted[1]. However, as others[2, 3] have pointed out, there is a trap for the unwary in this, in that it is implicitly assumed that specificity and sensitivity are constant values unaffected by prevalence and it is far from obvious that this should be the case. Continue reading →

Categories: S. Senn, significance tests, Testing Assumptions | 14 Comments

Souvenir From the NISS Stat Debate for Users of Bayes Factors (& P-Values)

Posted on October 24, 2020 by Mayo

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What would I say is the most important takeaway from last week’s NISS “statistics debate” if you’re using (or contemplating using) Bayes factors (BFs)–of the sort Jim Berger recommends–as replacements for P-values? It is that J. Berger only regards the BFs as appropriate when there’s grounds for a high concentration (or spike) of probability on a sharp null hypothesis,            e.g.,H0: θ = θ0.

Thus, it is crucial to distinguish between precise hypotheses that are just stated for convenience and have no special prior believability, and precise hypotheses which do correspond to a concentration of prior belief. (J. Berger and Delampady 1987, p. 330).

Continue reading →

Categories: bayes factors, Berger, P-values, S. Senn | 4 Comments

Stephen Senn: Losing Control (guest post)

Posted on July 20, 2020 by Mayo

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Stephen Senn
Consultant Statistician
Edinburgh

Losing Control

Match points

The idea of local control is fundamental to the design and analysis of experiments and contributes greatly to a design’s efficiency. In clinical trials such control is often accompanied by randomisation and the way that the randomisation is carried out has a close relationship to how the analysis should proceed. For example, if a parallel group trial is carried out in different centres, but randomisation is ‘blocked’ by centre then, logically, centre should be in the model (Senn, S. J. & Lewis, R. J., 2019). On the other hand if all the patients in a given centre are allocated the same treatment at random, as in a so-called cluster randomised trial, then the fundamental unit of inference becomes the centre and patients are regarded as repeated measures on it. In other words, the way in which the allocation has been carried out effects the degree of matching that has been achieved and this, in turn, is related to the analysis that should be employed. A previous blog of mine, To Infinity and Beyond,  discusses the point. Continue reading →

Categories: covid-19, randomization, RCTs, S. Senn | 16 Comments

S. Senn: Randomisation is not about balance, nor about homogeneity but about randomness (Guest Post)

Posted on April 20, 2020 by Mayo

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Stephen Senn
Consultant Statistician
Edinburgh

The intellectual illness of clinical drug evaluation that I have discussed here can be cured, and it will be cured when we restore intellectual primacy to the questions we ask, not the methods by which we answer them. Lewis Sheiner1

Cause for concern

In their recent essay Causal Evidence and Dispositions in Medicine and Public Health2, Elena Rocca and Rani Lill Anjum challenge, ‘the epistemic primacy of randomised controlled trials (RCTs) for establishing causality in medicine and public health’. That an otherwise stimulating essay by two philosophers, experts on causality, which makes many excellent points on the nature of evidence, repeats a common misunderstanding about randomised clinical trials, is grounds enough for me to address this topic again.  Before, however, explaining why I disagree with Rocca and Anjum on RCTs, I want to make clear that I agree with much of what they say. I loathe these pyramids of evidence, beloved by some members of the evidence-based movement, which have RCTs at the apex or possibly occupying a second place just underneath meta-analyses of RCTs. In fact, although I am a great fan of RCTs and (usually) of intention to treat analysis, I am convinced that RCTs alone are not enough. My thinking on this was profoundly affected by Lewis Sheiner’s essay of nearly thirty years ago (from which the quote at the beginning of this blog is taken). Lewis was interested in many aspects of investigating the effects of drugs and would, I am sure, have approved of Rocca and Anjum’s insistence that there are many layers of understanding how and why things work, and that means of investigating them may have to range from basic laboratory experiments to patient narratives via RCTs. Rocca and Anjum’s essay provides a good discussion of the various ‘causal tasks’ that need to be addressed and backs this up with some excellent examples. Continue reading →

Categories: RCTs, S. Senn | 32 Comments

Stephen Senn: Being Just about Adjustment (Guest Post)

Posted on March 16, 2020 by Mayo

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Stephen Senn
Consultant Statistician
Edinburgh

Correcting errors about corrected estimates

Randomised clinical trials are a powerful tool for investigating the effects of treatments. Given appropriate design, conduct and analysis they can deliver good estimates of effects. The key feature is concurrent control. Without concurrent control, randomisation is impossible. Randomisation is necessary, although not sufficient, for effective blinding. It also is an appropriate way to deal with unmeasured predictors, that is to say suspected but unobserved factors that might also affect outcome. It does this by ensuring that, in the absence of any treatment effect, the expected value of variation between and within groups is the same. Furthermore, probabilities regarding the relative variation can be delivered and this is what is necessary for valid inference. Continue reading →

Categories: randomization, S. Senn | 6 Comments

S. Senn: To infinity and beyond: how big are your data, really? (guest post)

Posted on March 9, 2019 by Mayo

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Stephen Senn
Consultant Statistician
Edinburgh

What is this n you boast about?

Failure to understand components of variation is the source of much mischief. It can lead researchers to overlook that they can be rich in data-points but poor in information. The important thing is always to understand what varies in the data you have, and to what extent your design, and the purpose you have in mind, master it. The result of failing to understand this can be that you mistakenly calculate standard errors of your estimates that are too small because you divide the variance by an n that is too big. In fact, the problems can go further than this, since you may even pick up the wrong covariance and hence use inappropriate regression coefficients to adjust your estimates.

I shall illustrate this point using clinical trials in asthma. Continue reading →

Categories: Lord's paradox, S. Senn | 9 Comments

Guest Post: STEPHEN SENN: ‘Fisher’s alternative to the alternative’

Posted on February 18, 2019 by Mayo

“You May Believe You Are a Bayesian But You Are Probably Wrong”

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As part of the week of posts on R.A.Fisher (February 17, 1890 – July 29, 1962), I reblog a guest post by Stephen Senn from 2012, and 2017. See especially the comments from Feb 2017. 

‘Fisher’s alternative to the alternative’

By: Stephen Senn

[2012 marked] the 50th anniversary of RA Fisher’s death. It is a good excuse, I think, to draw attention to an aspect of his philosophy of significance testing. In his extremely interesting essay on Fisher, Jimmie Savage drew attention to a problem in Fisher’s approach to testing. In describing Fisher’s aversion to power functions Savage writes, ‘Fisher says that some tests are more sensitive than others, and I cannot help suspecting that that comes to very much the same thing as thinking about the power function.’ (Savage 1976) (P473).

The modern statistician, however, has an advantage here denied to Savage. Savage’s essay was published posthumously in 1976 and the lecture on which it was based was given in Detroit on 29 December 1971 (P441). At that time Fisher’s scientific correspondence did not form part of his available oeuvre but in 1990 Henry Bennett’s magnificent edition of Fisher’s statistical correspondence (Bennett 1990) was published and this throws light on many aspects of Fisher’s thought including on significance tests. Continue reading →

Categories: Fisher, S. Senn, Statistics | Leave a comment

S. Senn: Personal perils: are numbers needed to treat misleading us as to the scope for personalised medicine? (Guest Post)

Posted on July 11, 2018 by Mayo

Personal perils: are numbers needed to treat misleading us as to the scope for personalised medicine?

A common misinterpretation of Numbers Needed to Treat is causing confusion about the scope for personalised medicine.

Stephen Senn
Consultant Statistician,
Edinburgh

Introduction

Thirty years ago, Laupacis et al1 proposed an intuitively appealing way that physicians could decide how to prioritise health care interventions: they could consider how many patients would need to be switched from an inferior treatment to a superior one in order for one to have an improved outcome. They called this the number needed to be treated. It is now more usually referred to as the number needed to treat (NNT).

Within fifteen years, NNTs were so well established that the then editor of the British Medical Journal, Richard Smith could write:  ‘Anybody familiar with the notion of “number needed to treat” (NNT) knows that it’s usually necessary to treat many patients in order for one to benefit’2. Fifteen years further on, bringing us up to date,  Wikipedia makes a similar point ‘The NNT is the average number of patients who need to be treated to prevent one additional bad outcome (e.g. the number of patients that need to be treated for one of them to benefit compared with a control in a clinical trial).’3

This common interpretation is false, as I have pointed out previously in two blogs on this site: Responder Despondency and  Painful Dichotomies. Nevertheless, it seems to me the point is worth making again and the thirty-year anniversary of NNTs provides a good excuse. Continue reading →

Categories: personalized medicine, PhilStat/Med, S. Senn | 7 Comments

Guest Blog: STEPHEN SENN: ‘Fisher’s alternative to the alternative’

Posted on February 18, 2018 by Mayo

“You May Believe You Are a Bayesian But You Are Probably Wrong”

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As part of the week of recognizing R.A.Fisher (February 17, 1890 – July 29, 1962), I reblog a guest post by Stephen Senn from 2012/2017.  The comments from 2017 lead to a troubling issue that I will bring up in the comments today.

‘Fisher’s alternative to the alternative’

By: Stephen Senn

[2012 marked] the 50th anniversary of RA Fisher’s death. It is a good excuse, I think, to draw attention to an aspect of his philosophy of significance testing. In his extremely interesting essay on Fisher, Jimmie Savage drew attention to a problem in Fisher’s approach to testing. In describing Fisher’s aversion to power functions Savage writes, ‘Fisher says that some tests are more sensitive than others, and I cannot help suspecting that that comes to very much the same thing as thinking about the power function.’ (Savage 1976) (P473).

The modern statistician, however, has an advantage here denied to Savage. Savage’s essay was published posthumously in 1976 and the lecture on which it was based was given in Detroit on 29 December 1971 (P441). At that time Fisher’s scientific correspondence did not form part of his available oeuvre but in 1990 Henry Bennett’s magnificent edition of Fisher’s statistical correspondence (Bennett 1990) was published and this throws light on many aspects of Fisher’s thought including on significance tests. Continue reading →

Categories: Fisher, S. Senn, Statistics | 1 Comment

S. Senn: Evidence Based or Person-centred? A Statistical debate (Guest Post)

Posted on January 30, 2018 by Mayo

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Stephen Senn
Head of  Competence Center
for Methodology and Statistics (CCMS)
Luxembourg Institute of Health
Twitter @stephensenn

Evidence Based or Person-centred? A statistical debate

It was hearing Stephen Mumford and Rani Lill Anjum (RLA) in January 2017 speaking at the Epistemology of Causal Inference in Pharmacology conference in Munich organised by Jürgen Landes, Barbara Osmani and Roland Poellinger, that inspired me to buy their book, Causation A Very Short Introduction[1]. Although I do not agree with all that is said in it and also could not pretend to understand all it says, I can recommend it highly as an interesting introduction to issues in causality, some of which will be familiar to statisticians but some not at all.

Since I have a long-standing interest in researching into ways of delivering personalised medicine, I was interested to see a reference on Twitter to a piece by RLA, Evidence based or person centered? An ontological debate, in which she claims that the choice between evidence based or person-centred medicine is ultimately ontological[2]. I don’t dispute that thinking about health care delivery in ontological terms might be interesting. However, I do dispute that there is any meaningful choice between evidence based medicine (EBM) and person centred healthcare (PCH). To suggest so is to commit a category mistake by suggesting that means are alternatives to ends.

In fact, EBM will be essential to delivering effective PCH, as I shall now explain. Continue reading →

Categories: personalized medicine, RCTs, S. Senn | 7 Comments

Frequentstein’s Bride: What’s wrong with using (1 – β)/α as a measure of evidence against the null?

Posted on May 23, 2017 by Mayo

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ONE YEAR AGO: …and growing more relevant all the time. Rather than leak any of my new book*, I reblog some earlier posts, even if they’re a bit scruffy. This was first blogged here (with a slightly different title). It’s married to posts on “the P-values overstate the evidence against the null fallacy”, such as this, and is wedded to this one on “How to Tell What’s True About Power if You’re Practicing within the Frequentist Tribe”. 

In their “Comment: A Simple Alternative to p-values,” (on the ASA P-value document), Benjamin and Berger (2016) recommend researchers report a pre-data Rejection Ratio:

It is the probability of rejection when the alternative hypothesis is true, divided by the probability of rejection when the null hypothesis is true, i.e., the ratio of the power of the experiment to the Type I error of the experiment. The rejection ratio has a straightforward interpretation as quantifying the strength of evidence about the alternative hypothesis relative to the null hypothesis conveyed by the experimental result being statistically significant. (Benjamin and Berger 2016, p. 1)

Continue reading →

Categories: Bayesian/frequentist, fallacy of rejection, J. Berger, power, S. Senn | 17 Comments

S. Senn: “Automatic for the people? Not quite” (Guest post)

Posted on April 23, 2017 by Mayo

Stephen Senn

Stephen Senn
Head of  Competence Center for Methodology and Statistics (CCMS)
Luxembourg Institute of Health
Twitter @stephensenn

Automatic for the people? Not quite

What caught my eye was the estimable (in its non-statistical meaning) Richard Lehman tweeting about the equally estimable John Ioannidis. For those who don’t know them, the former is a veteran blogger who keeps a very cool and shrewd eye on the latest medical ‘breakthroughs’ and the latter a serial iconoclast of idols of scientific method. This is what Lehman wrote

Ioannidis hits 8 on the Richter scale: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173184 … Bayes factors consistently quantify strength of evidence, p is valueless.

Since Ioannidis works at Stanford, which is located in the San Francisco Bay Area, he has every right to be interested in earthquakes but on looking up the paper in question, a faint tremor is the best that I can afford it. I shall now try and explain why, but before I do, it is only fair that I acknowledge the very generous, prompt and extensive help I have been given to understand the paper[1] in question by its two authors Don van Ravenzwaaij and Ioannidis himself. Continue reading →

Categories: Bayesian/frequentist, Error Statistics, S. Senn | 18 Comments

Guest Blog: STEPHEN SENN: ‘Fisher’s alternative to the alternative’

Posted on February 22, 2017 by Mayo

“You May Believe You Are a Bayesian But You Are Probably Wrong”

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As part of the week of recognizing R.A.Fisher (February 17, 1890 – July 29, 1962), I reblog a guest post by Stephen Senn from 2012.  (I will comment in the comments.)

‘Fisher’s alternative to the alternative’

By: Stephen Senn

[2012 marked] the 50th anniversary of RA Fisher’s death. It is a good excuse, I think, to draw attention to an aspect of his philosophy of significance testing. In his extremely interesting essay on Fisher, Jimmie Savage drew attention to a problem in Fisher’s approach to testing. In describing Fisher’s aversion to power functions Savage writes, ‘Fisher says that some tests are more sensitive than others, and I cannot help suspecting that that comes to very much the same thing as thinking about the power function.’ (Savage 1976) (P473).

The modern statistician, however, has an advantage here denied to Savage. Savage’s essay was published posthumously in 1976 and the lecture on which it was based was given in Detroit on 29 December 1971 (P441). At that time Fisher’s scientific correspondence did not form part of his available oeuvre but in 1990 Henry Bennett’s magnificent edition of Fisher’s statistical correspondence (Bennett 1990) was published and this throws light on many aspects of Fisher’s thought including on significance tests. Continue reading →

Categories: Fisher, S. Senn, Statistics | 13 Comments

Hocus pocus! Adopt a magician’s stance, if you want to reveal statistical sleights of hand

Posted on February 7, 2017 by Mayo

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Here’s the follow-up post to the one I reblogged on Feb 3 (please read that one first). When they sought to subject Uri Geller to the scrutiny of scientists, magicians had to be brought in because only they were sufficiently trained to spot the subtle sleight of hand shifts by which the magician tricks by misdirection. We, too, have to be magicians to discern the subtle misdirections and shifts of meaning in the discussions of statistical significance tests (and other methods)—even by the same statistical guide. We needn’t suppose anything deliberately devious is going on at all! Often, the statistical guidebook reflects shifts of meaning that grow out of one or another critical argument. These days, they trickle down quickly to statistical guidebooks, thanks to popular articles on the “statistics crisis in science”. The danger is that their own guidebooks contain inconsistencies. To adopt the magician’s stance is to be on the lookout for standard sleights of hand. There aren’t that many.[0]

I don’t know Jim Frost, but he gives statistical guidance at the minitab blog. The purpose of my previous post is to point out that Frost uses the probability of a Type I error in two incompatible ways in his posts on significance tests. I assumed he’d want to clear this up, but so far he has not. His response to a comment I made on his blog is this: Continue reading →

Categories: frequentist/Bayesian, P-values, reforming the reformers, S. Senn, Statistics | 39 Comments

Frequentstein: What’s wrong with (1 – β)/α as a measure of evidence against the null? (ii)

Posted on May 22, 2016 by Mayo

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In their “Comment: A Simple Alternative to p-values,” (on the ASA P-value document), Benjamin and Berger (2016) recommend researchers report a pre-data Rejection Ratio:

It is the probability of rejection when the alternative hypothesis is true, divided by the probability of rejection when the null hypothesis is true, i.e., the ratio of the power of the experiment to the Type I error of the experiment. The rejection ratio has a straightforward interpretation as quantifying the strength of evidence about the alternative hypothesis relative to the null hypothesis conveyed by the experimental result being statistically significant. (Benjamin and Berger 2016, p. 1)

The recommendation is much more fully fleshed out in a 2016 paper by Bayarri, Benjamin, Berger, and Sellke (BBBS 2016): Rejection Odds and Rejection Ratios: A Proposal for Statistical Practice in Testing Hypotheses. Their recommendation is:

…that researchers should report the ‘pre-experimental rejection ratio’ when presenting their experimental design and researchers should report the ‘post-experimental rejection ratio’ (or Bayes factor) when presenting their experimental results. (BBBS 2016, p. 3)….

The (pre-experimental) ‘rejection ratio’ Rpre , the ratio of statistical power to significance threshold (i.e., the ratio of the probability of rejecting under H1 and H0 respectively), is shown to capture the strength of evidence in the experiment for H1 over H0. (ibid., p. 2)

But in fact it does no such thing! [See my post from the FUSION conference here.] J. Berger, and his co-authors, will tell you the rejection ratio (and a variety of other measures created over the years) are entirely frequentist because they are created out of frequentist error statistical measures. But a creation built on frequentist measures doesn’t mean the resulting animal captures frequentist error statistical reasoning. It might be a kind of Frequentstein monster! [1] Continue reading →

Categories: J. Berger, power, reforming the reformers, S. Senn, Statistical power, Statistics | 36 Comments

Excerpts from S. Senn’s Letter on “Replication, p-values and Evidence”

Posted on May 12, 2016 by Mayo

old blogspot typewriter

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I first blogged this letter here. Below the references are some more recent blog links of relevance to this issue. 

 Dear Reader:  I am typing in some excerpts from a letter Stephen Senn shared with me in relation to my April 28, 2012 blogpost.  It is a letter to the editor of Statistics in Medicine  in response to S. Goodman. It contains several important points that get to the issues we’ve been discussing. You can read the full letter here. Sincerely, D. G. Mayo

 STATISTICS IN MEDICINE, LETTER TO THE EDITOR

From: Stephen Senn*

Some years ago, in the pages of this journal, Goodman gave an interesting analysis of ‘replication probabilities’ of p-values. Specifically, he considered the possibility that a given experiment had produced a p-value that indicated ‘significance’ or near significance (he considered the range p=0.10 to 0.001) and then calculated the probability that a study with equal power would produce a significant result at the conventional level of significance of 0.05. He showed, for example, that given an uninformative prior, and (subsequently) a resulting p-value that was exactly 0.05 from the first experiment, the probability of significance in the second experiment was 50 per cent. A more general form of this result is as follows. If the first trial yields p=α then the probability that a second trial will be significant at significance level α (and in the same direction as the first trial) is 0.5. Continue reading →

Categories: 4 years ago!, reproducibility, S. Senn, Statistics | Tags: , , , | 3 Comments

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