Tag Archives: Director’s Choice – From the Journals

Bayesian Analysis of Clinical Trial Results: Coming of Age

I have long argued for greater use of Bayesian interpretation of clinical trial results – I suggested this approach with respect to trials of treatment for rare diseases back in 1994.[1] This approach is now advocated in a recent report in JAMA.[2] The approach advocated is the use of a neutral, an enthusiastic, and a sceptical prior. The authors also outline an approach to be used when the data is not compatible with the prior; in such a scenario they advocate a ‘data wins’ rule. I would wish to ensure that the trial was of impeccable design with complete follow up before accepting such an approach. For instance, I would allow my sceptical prior to dominate positive results from a potentially biased trial of homeopathy.

— Richard Lilford, CLAHRC WM Director


  1. Lilford RJ, Thornton JG, Braunholtz D. Clinical Trials and Rare Diseases – a Way Out of a Conundrum. BMJ. 1995; 311: 1621-5.
  2. Quintana M, Viele K, Lewis RJ. Bayesian Analysis: Using Prior Information to Interpret the Results of Clinical Trials. JAMA. 2017; 318(16): 1605-6.

Is it Possible to Teach Empathy?

News blog readers will know that I am fascinated by the question of whether it is possible to teach people to be kinder, more patient-centered, and to show more empathy. A recent meta-analysis of RCTs sheds important light on the critical issue of empathy training.[1] Unlike previous systematic reviews, this study included only experimental studies. Overall, 19 studies met the inclusion criteria for the meta-analysis.

One important issue concerns how the endpoint was measured. In 11 of the 19 included studies the outcome was an objective measure, while in the remainder the outcome was self-reported.

Overall, educational interventions produced a positive benefit that was statistically significant. When the authors made an adjustment for possible publication bias, the effect size was only slightly reduced, remaining highly significant statistically.

I expected to find that the effect size was greater for the self-reported outcomes than for objective outcomes. In fact, the effect size was larger and more highly significant for the objective measures of effect.

Some people classify empathy training in two forms: cognitive and effective, to cover the intellectual and emotional aspects of empathy. Others have questioned this dichotomy, arguing that the emotional and the cognitive parts have to interact to produce empathetic behaviour. As it turned out, all studies included a cognitive component.

This is a very interesting and important study. My main problem with the study is that they do not give a breakdown according to whether the objective measure was self-reported or objective. Also, the results do not tell us how enduring the effects were. I have argued before that one of the main criteria of good communication and compassionate care is the desire to achieve these projectors. The most important thing to instil is a deep-seated desire to do a better job. It would seem that training has a part to play in achieving this objective. However, sustained exposure to excellent role models is also critically important and a crucial part of the education of health professionals.

— Richard Lilford, CLAHRC WM Director


  1. Teding van Berkhout E & Malouff JM. The Efficacy of Empathy Training: A Meta-analysis of Randomized Controlled Trials. J Counsel Psychol. 2016; 63(1): 32-41.

Importance of Cohort Rather Than Cross-Sectional Studies to Determine the Heritability of Conditions

In a recent News Blog we showed how longitudinal studies could improve on cross-sectional epidemiological studies using alcohol-induced effects on lexical cognition, as our example.[1]

Cross-sectional twin studies may also under-estimate inheritability of disorders, such as Autism Spectrum Disorder (ASD), because the control twin may be in a ‘yet to be diagnosed’ state. An interesting article in JAMA shows that the inheritability of ASD is much higher if the correct (longitudinal) method is used.[2] All studies agree that familial environment has hardly any effect on the probability of ASD.

— Richard Lilford, CLAHRC WM Director


  1. Lilford RJ. Alcohol and its Effects. NIHR CLAHRC West Midlands News Blog. 18 August 2017.
  2. Sandin S, Lichtenstein P, Kuja-Halkola R, Hultman C, Larsson H, Reichenberg A. The Heritability of Autism Spectrum Disorder. JAMA. 2017; 318(12): 1182-4.

A Debt of Gratitude

For a while now I have been working closely with the African Population and Health Research Center (APHRC), which is based in Nairobi, Kenya. Last week’s issue of the Lancet carried an article on the APHRC, where they paid tribute to the outgoing director Alex Ezeh.[1] Alex had the wisdom to identify the enormous challenge posed by the rapidly expanding slums in African cities. He and his colleagues have produced ground-breaking work on health dynamics in urban slums. He was my inspiration, and I followed where he led. Together we compiled a Lancet Series summarising the state of the literature regarding the health of people living in the slums and proposing models to inform future research and policy making.[2] [3] These studies were recently summarised in the African version of ‘The Conversation’.[4] Our work has resulted in the award of a NIHR unit to study the provision of healthcare in slums in Africa and Asia. We have also secured funds from the Rockefeller foundation to run a Bellagio conference on statistical aspects of slum health. Currently, we are pursuing research into water and sanitation in slums, as this is one of the biggest problems leading to diarrhoea, stunting and death, especially in children under the age of five.

I have an enormous debt of gratitude to APHRC in general and Alex Ezeh in particular. I look forward to my ongoing association with Alex and to working very closely with his outstanding successor, Catherine Kyobutungi, who was also profiled in last week’s Lancet.[5]

— Richard Lilford, CLAHRC WM Director


    1. Green A. The African Population and Health Research Center. Lancet. 2017; 390: 1940.
    2. Ezeh A, Oyebode O, Satterthwaite D, et al. The history, geography, and sociology of slums and the health problems of people who live in slums. Lancet. 2017; 389: 547-58.
    3. Lilford RJ, Oyebode O, Satterthwaite D, et al. Improving the Health and Welfare of People Living in Slums. Lancet .2017; 389: 559-70.
    4. Ezeh A, Sewankambo N, Plot P. Why the Path to Longer and Healthier Lives for all Africans is in Reach. The Conversation. 13 September 2017.
    5. Berman P. Catherine Kyobutungi: leading African health research capacity. Lancet. 2017; 390: 1942.


Breastfeeding and SIDS

Over the years many studies have shown an association between breastfeeding and decreased risk of sudden infant death syndrome (SIDS), with a previous meta-analysis showing an adjusted odds ratio of 0.55 (95% CI 0.44-0.69), which increased to 0.27 (95% CI 0.24-0.31) with exclusive breastfeeding.[1] However, it has been difficult to identify just how long breastfeeding needs to continue to realise this benefit. This is because duration of breastfeeding has not been correlated with reduction in risk. As a follow-up to their original meta-analysis, Thompson and colleagues worked in cooperation with the authors of the included studies to obtain individual-level data.[2] They were able to glean information on duration of breastfeeding so that the association between duration and effect could be examined. In total 9,104 infants were analysed from eight case-control studies. Although analysis showed some protection against SIDS associated with any breastfeeding up to 2 months, this was not statistically significant after controlling for potential confounders. When confounders were controlled for, analysis found that any breastfeeding for at least 2 months, compared to no breastfeeding, had an adjusted odds ratio (aOR) of 0.60 (95% CI 0.44-0.82), while it was a similar aOR of 0.61 (95% CI 0.42-0.87) for exclusive breastfeeding. The aOR for any amount of breastfeeding compared to none improved with increased duration – an aOR of 0.40 (95% CI 0.26-0.63) with 4-6 months breastfeeding, and 0.36 (95% CI 0.22-0.61) with at least 6 months breastfeeding. A similar improvement was seen with at least 4 months of exclusive breastfeeding (aOR 0.46, 95% CI 0.29-0.74).

In order to lower the incidence of SIDS it is important that new mothers are encouraged to breastfeed and to continue for at least 2 months, even if they are unable to do so exclusively, as any amount of breastfeeding seems to confer more protection than none.

— Peter Chilton, Research Fellow


  1. Hauck FR, Thompson JM, Tanabe KO, Moon RY, Vennemann MM. Breastfeeding and reduced risk of sudden infant death syndrome: a meta-analysis. Pediatrics. 2011; 128(1): 103–10
  2. Thompson JMD, Tanabe K, Moon RY, Mitchell EA, McGarvey C, Tappin D, Blair PS, Hauck FR. Duration of Breastfeeding and Risk of SIDS: An Individual Participant Data Meta-analysis. Pediatrics. 2017: e20171324.

A Very Interesting Paper Using Mendelian Randomisation to Determine the Effect of Extra Years of Education on Heart Disease

It turns out that there are a number of genes, all associated with aspects of neurodevelopment, that predict how many years a person will spend in formal education.[1] It is already very well established that more years of education are associated with large reductions in coronary heart disease (CHD) (mediated by behaviour such as lower calorie intake, less smoking, more exercise).[2] So the authors of a recent well-written and most interesting BMJ paper did the obvious thing.[3] [4] They related the (random) presence or absence of educational propensity genes to CHD. Bingo, they measured a large effect (the genes that predispose to larger durations of formal education associate with reduced CHD). Now, the thing with Mendelian randomisation is that the genotype must not be linked to the outcome (CHD in this case), other than through the putative explanatory variable (duration of education in this case). The authors are aware that it is quite possible that education genes are linked to the outcome (CHD), net of (any) effect on education. To deal with this possibility they perform sensitivity analyses. They examine the association of genetic variates associated with education and the behaviours that lead to CHD. If the effects on education and on CHD behaviours are similar across the genetic variates this suggests that the effect on CHD is through education and not through another variable. And so it was. They also looked to see whether genetic variants already known to be associated with CHD (genes for high cholesterol, etc.) were also associated with education. If the genes associated with education do not associate with these other risk factors, then that favours a cause and effect explanation. There was no association. However, such an association would only be expected if there was a ‘massive’ effect of ‘education genes’ that bypassed education.

This all falls short of proof. Since the educational genes lead to education through mental processes, it is reasonable to suppose that almost all genetic variates that affect education also affect behaviour. Thus, they would affect CHD, even if there was no extra education. The authors say that their conclusion is strongly supported by identical twin studies where one twin stayed longer in education than the other, but this too ignores the fact that these twins are different, for all that their inherited genotype is the same, and so these differences could be the cause of both increased education and decrease in the behaviours that lead to heart disease.

One more point ­– even if years of education really are causative, this might well apply only to people genetically predisposed to more education and may not apply among those not so predisposed – there may be an interaction between the genes that predisposes to education and response to that education. After all, why would one persist in the classroom if you were not predisposed to benefit from the experience? People not predisposed would find being coerced to do so most unpalatable, and such an approach could even have a perverse effect. This is an excellent article and is beautifully presented. But I am a little more sceptical than the authors. I would like to see a debate on the issues.

— Richard Lilford, CLAHRC WM Director


  1. Okbay A, Beauchamp JP, Fontana MA, et al. Genome-wide association study identifies 74 loci associated with educational attainment. Nature. 2016; 533(7604): 539–42.
  2. Veronesi G, Ferrario MM, Kuulasmaa K, et al. Educational class inequalities in the incidence of coronary heart disease in EuropeHeart. 201635895865.
  3. Tillmann T, Vaucher J, Okbay A, et al. Education and coronary heart disease: Mendelian randomisation study. BMJ. 2017; 358: j3542.
  4. Richards JB & Evans DM. Back to School to Protect Against Coronary Heart Disease? BMJ. 2017; 358: j3849.

The Rush Towards a Paperless Health Service: Stop the Music

I have written repeatedly on the harms that bringing IT into the consultation room can bring. I carried out a trial of computerised data entry during consultations showing that it undermined the clinician/patient relationship – this was over three decades ago.[1] This finding has been replicated many times since, with vivid accounts in Bob Wachter’s outstanding book.[2] It turns out that having to use IT during consultations is one of the main causes of ‘burn-out’ among doctors in the USA. A recent NIHR Programme study, in which CLAHRC WM collaborated, showed that IT is likely undermining patient safety in some aspects of practice (diagnosis; personalised care), even as it improves it in others (prescribing error).[3] Meanwhile, Fawdry has repeatedly argued [4] that the problems in integrating computers across institutions arise not because the IT systems themselves are ‘incompatible’ or because we do not have common ‘ontologies’, but because the underlying medical logic does not synchronise when you slap two systems together. Data in records can be shared (lab results, x-rays, etc.), but that is different to sharing records. So, do not force the pace – let a paperless system evolve. Apply the CLAHRC WM test; never implement an IT system module until you have examined how it affects the pattern of clinician/patient interactions in real world settings. We are sleep-walking into a digital future and completely ignoring the cautionary evidence that is becoming stronger by the year. Remember, nothing in health care – and I really do mean nothing – is as important as the relationships between clinician and patient.

— Richard Lilford, CLAHRC WM Director


  1. Brownbridge G, Lilford RJ, Tindale-Biscoe S. Use of a computer to take booking histories in a hospital antenatal clinic. Acceptability to midwives and patients and effects on the midwife-patient interaction. Med Care. 1988; 26(5): 474-87.
  2. Wachter R. The Digital Doctor: Hope, Hype, and Harm at the Dawn of Medicine’s Computer Age. New York, NY: McGraw-Hill Education. 2015.
  3. Lilford RJ. Introducing Hospital IT Systems – Two Cautionary Tales. NIHR CLAHRC West Midlands News Blog. 4 August 2017.
  4. Fawdry R. Paperless records are not in the best interest of every patient. BMJ. 2013; 346: f2064.

“Why Can’t a Man Be More Like a Woman” – Revisited

In a previous News Blog [1] I reorganised Henry Higgins’s famous line from ‘My Fair Lady’ in response to a paper in JAMA based on MediCare records showing that SMRs (standardised mortality rates) following acute medical admissions were slightly lower when the admitting physician was a woman rather than a man.[2] So what about surgery then? Same pattern I am afraid blokes! Slightly lower adjusted odds ratio (0.96) for harm.[3] True? Probably, since women outperform men on many tasks requiring a combination of care and cognition, as per the above News Blog. But results of this sort may be ephemeral – gender based predilections are notoriously labile as different selection and cultural effects play out in society. For example, the proportion of women studying and excelling in STEM (Science, Technology, Engineering and Mathematics) subjects has been rising steadily.[4] The proportion of women who become boxers or get incarcerated is also rising.[5][6] It seems that women and men are becoming more like each other! But will they ever become the same as each other? The effect of gender on surgical outcomes has been heavily debated and was the topic of the Editor in Chief’s editorial,[7] yet this point about change in the attributes of men vs. women over time was not discussed.

— Richard Lilford, CLAHRC WM Director


  1. Lilford RJ. Are Female Doctors Better Than Male Doctors? NIHR CLAHRC West Midlands News Blog. 13 January 2017.
  2. Tsugawa Y, Jena AB, Figueroa JF, et al. Comparison of Hospital Mortality and Readmission Rates for Medicare Patients Treated by Male vs Female Physicians. JAMA Intern Med. 2017; 177(2): 206-13.
  3. Wallis CJD, Ravi B, Coburn N, et al. Comparison of postoperative outcomes among patients treated by male and female surgeons: a population based matched cohort study. BMJ. 2017; 359: j4366.
  4. WISE. Women in Science, Technology, Engineering and Mathematics: The Talent Pipeline from Classroom to Boardroom. UK Statistics 2014. Bradford: WISE; July 2015.
  5. Sport England. Record Number of Women Get Active. 8 December 2016.
  6. Swavola E, Riley K, Subramanian R. Overlooked: Women and Jails in an Era of Reform. New York, NY: Vera: Injustice of Justice. August 2016.
  7. Marx C. Improving patient outcomes after surgery. BMJ. 2017; 359: j4580.

Is it Safe for One Surgeon to Oversee Two Operations Concurrently?

In a previous News Blog I advocated a ‘Taylorised’ (i.e. assembly plant) type of approach to bariatric surgery,[1] where a small number of (expensive) surgeons and anaesthetists would oversee a workforce of (less expensive) physician’s assistants / auxiliary medical personnel – figure reproduced below for your convenience. The argument was that bariatric surgery was the only really effective treatment for obesity resulting in greatly improved long-term outcomes, yet surgical resources, as currently deployed, could not meet the demand. No News Blog reader wrote in to ask “but is it safe to operate in this way?” A recent study, based on over half-a-million operations suggest that the answer is “yes it is” – complications were no greater when bariatric operations were concurrent than when they were done strictly in series.[2] CLAHRC WM News Blog reader Tim Jones has recently visited an eye hospital in Hyderabad, India, where a Taylorised approach is taken to cataract surgery with massive efficiency gains and complication rates even lower than those in the UK. I have written before saying that medicine cannot and should not be Taylorised.[3] Real medicine lies in diagnosing, explaining and consoling. But procedures are ripe for massive efficiency gains.

An Operations Director oversees a Surgeon and two Anaesthetists who oversee six technicians operating on six patients

— Richard Lilford, CLAHRC WM Director


  1. Lilford RJ. Bariatric Surgery – Improve Five-Year Outcomes. NIHR CLAHRC West Midlands News Blog. 23 June 2017.
  2. Liu JB, Ban KA, Berian JR, et al. Concurrent bariatric operations and association with perioperative outcomes: registry based cohort study. BMJ. 2017; 358: j4244.
  3. Lilford RJ. The Future of Medicine. NIHR CLAHRC West Midlands News Blog.23 October 2015.

Deforestation and Diarrhoea

Contaminated water can lead to numerous diseases, including diarrhoea, a leading cause of child mortality. In a previous News Blog we discussed the importance of water contamination, and the many methods by which it can occur.[1] One such route is contaminated surface water, which has been linked to outbreaks of diarrhoea in previous studies.[2] A major factor affecting the quality of surface water is the ‘watershed condition’ – the natural land cover provided by the ecosystem, such as forests and wetlands. This ecosystem filters pollutants and pathogens from surface water supplies, and can stabilise soil, and minimise erosion and sediment loading.

Herrera and colleagues conducted an observational database study of almost 300,000 children aged under 5 from 35 countries, looking at their health, socioeconomic factors (such as mother’s education, household wealth, access to improved sanitation and water sources), climate (temperature and precipitation) and watershed condition.[3] Watershed condition was measured by estimating the percentage of water that was affected by people and livestock or tree cover upstream from the household.

They found that high tree cover upstream of the child’s household was associated with a lower probability of diarrhoea (odds ratio less than 1, but not specified). This was significant only for rural households, however, not urban. In rural communities it is estimated that only 33% of households obtain their water from piped sources (compared to 79% in urban areas), and 93% of people who use surface water as their main water source live in rural areas.

The authors used a model to estimate that increasing tree cover upstream by 30% would have a similar effect to improving sanitation (an estimated 4% reduction in probability of diarrhoea from baseline). It would, however, not have as great an impact as improving the water source (7% reduction), wealth (12% reduction) or education of the households (13% reduction). It seems that, under certain conditions, conservation strategies that ensure that tree cover is high could serve as effective investments in public health.

— Peter Chilton, Research Fellow


  1. Lilford RJ. A Secondary Sanitary Revolution? What About the First One? NIHR CLAHRC West Midlands News Blog. September 1, 2017.
  2. Bessong, P., Odiyo, J., Musekene, J. & Tessema, A. Spatial distribution of diarrhoea and microbial quality of domestic water during an outbreak of diarrhoea in the Tshikuwi community in Venda, South Africa. J Health Popul Nutr 2009; 27: 652-9.
  3. Herrera D, Ellis A, Fisher B, et al. Upstream watershed condition predicts rural children’s health across 35 developing countries. Nature Comm 2017; 8: 811.