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Tuesday, May 8, 2018

Skin in the game: industry funding of science

Of late, I have been the target of lot of Twitterati innuendos about my independence as a scientist. I realise that short of repenting at the feet of whatever God or Goddess of scientific purity that might be nominated by the sacred college of the holy and undivided Twitterati,  I will remain besmirched, sullied and rendered utterly untrustworthy by the high priests of Twitterati scientific morality.

Whether it was Warren Buffet or William Shakespeare who is responsible for the phrase ‘skin in the game’, matters little. It is still understood to represent  an apparent or real vested interest in some topic. In science, such interests must be declared in any oral or written opinion in the context of any scientific endeavour such as the delivery of a lecture, the seeking of publicly funded research grants, the publication of scientific papers or the participation in any advisory committee. To fail to adhere to the principle of  a declaration of interest (DoI) is to fall short of minimal requirements of scientific integrity. A DoI can translate into a Conflict of Interest (CoI) if the situation arises where a scientist offers an opinion in any forum where he or she has an interest in the outcome of the forum’s deliberations. Usually that involves the scientist being excused or recused, whatever the correct term might be. Because there are no written laws or guidelines that cover every eventuality, individual integrity is an absolute expectation in science.

Some scientists and some research institutes adopt the view that their work should not be funded by industry. Rather, they focus all their research on public funding with no industrial ties. In so doing, they become immune to any questioning of the provenance of their wisdom. Other scientists adopt an entirely opposite view and are of the opinion that engagement with industry is an essential societal role to deliver economic growth and increase employment, in effect, to give the funding agency and the tax payer, a return on investment. Neither of these positions is either right or wrong. They simply represent a world view of individuals or institutes and in that regard are no different from other contrasting choices: vegetarianism v. meat eating; democrat v. republican; theism and atheism; tax cuts v. social investment. A constant difficulty for scientists who engage with industry, is that the advocates that populate Twitter, just don’t understand the mechanics of industry involvement in research. So for their benefit, here is a tutorial on joint academic industry funding with apologies for the length.

Two types of industrial funding exist which involve academic researchers. First, there is research commissioned by a single company to solve some particular problem they need investigating. This is far more rare an event than would popularly be believed by the Twitterati.  The main reason why academics don’t like such work is that, often, it is pure contract research and frequently involves research questions that are marginal to their publicly funded strategy. All researchers have such a strategy which maps out a research path they want to pursue. It governs their choice of conferences to attend, journals to read and funding to chase. But, for practical and political reasons, academics often have to undertake this type of contract work for some commercial entity. The last one I was involved in, perhaps only one in the last decade of my working life, was an Irish mushroom company who had used special lighting techniques in the growing of mushrooms to boost the levels of the mushroom Vitamin D2. We found in our human intervention studies that whereas the D2 type was well absorbed, the active component of  blood vitamin D, did not improve; important for the company, not for us, other than a published paper on the results[1]. However, for a publicly funded academic to tell a small local company with a research need to sod off and not be a nuisance will win one no favours in the university and would be frowned upon by state agencies. But, as I say, such industry funding is rare enough and is generally very low in the pecking order of largely publicly funded scientists..

 The second type of industry involvement in research is as a full partner in publicly funded research. Here in Europe, most of that international competitive public funding is from the Commission of the  European Union, through its Directorate General on Research and Innovation. It is probably the largest global funder of multi-centre and multi-disciplinary research programmes, addressing what they regard as ‘grand societal issues”. Thus, my last EU grant was that of Food4me ( which amounted to a €12m investment in research on personalised nutrition ( a current output of 46 peer-reviewed papers). And, as is obligatory under EU funding, the inclusion of industrial partners within the research consortium was 100% mandatory. These companies receive funds just as academic partners do. In Food4Me, our biggest industrial partner was the Dutch electronics giant, Philips, who have an interest in personalised nutrition for their smart kitchen research. The Swiss food giant DSM was involved with a major interest in companion diagnostic tools alongside a small University of Oslo start up, Vitas. We had a global legal firm Heller & Heckman who worked with Swedish academics on the legal and ethical side, we had a Belgian food business consultancy (Biosense looking at business models) and an Irish software  company, Crème Global, who wrote the software code. These companies worked with a group of 14 academic research groups.  Across most individual EU states and definitely here in Ireland, the same rule applies: to get research income, you must  have appropriate industrial partners.

These consortia, small or large, always enter a legally binding agreement over the ownership of new knowledge generated in the grant and the nature of its dissemination and use. This consortium agreement will list every single deliverable envisaged for the project. These deliverables include the publication of scientific papers. No company can dream of gagging research findings that emerge from the work since that would involve a breach of contract under Belgian law. Worse still, it would do massive reputational damage to the company. The scientific world works in small cells and word travels fast.  The research agreement will also allow the industrial partners to licence intellectual property from the consortium as a whole. If they don’t use it, the intellectual property reverts back to the project funder to dispose of, as best suits them.

The next form of industry-academia engagement involves consultancy work where an academic, with a global reputation in his or her research field, is engaged by a company to help them with technical issues of both a general or specific nature. I will illustrate the issue with two examples. In 2009, I was invited to join Google’s Food Innovation Lab community, specifically to a small group that wanted to explore options in personalised nutrition. I visited their headquarters in Silicon Valley, California about 9 times over a three year period before deciding that their interest in personalised nutrition was quite a long way from where I saw it going. Now, neither I nor my employer, UCD, got any payment from Google: Zippo, Nada. Apparently, I was to serve on this Google think tank because I was privileged to be asked and should be honoured to work for nothing for the richest company in the world! I began calling them Froogle. In contrast, I was invited to join a top level international advisory committee for Nestlé for which I received an honorarium. They wheeled out their different research projects and we tore them apart. For their own good of course. So which is the greater sin? To share my hard won expertise  with the richest company in the world for nothing or with the largest food company running the largest food lab in the world (400 PhDs) for an honorarium?? High priests of the Twitterati School of Scientific Morality, please advise. On my first visit to Google, I tore strips off one group for their sheer naivety in studying the school food programme in Mountain View Ca. That was my job, to speak my mind. In Nestlé, I grew tired of some of their hype about how great they were at food fortification and let them know in no uncertain terms. They re-shaped their interest in public health nutrition, for the better, and maybe my crankiness to senior management was a contributory factor. In neither case would I ever dance to their tune. Nobody tells me what to do!!

Then there is the case of accepting  a task which is not so general in nature but has a very specific purpose and one which neatly fits into one’s research portfolio. Thus I chair an international consortium ) (US, Canada, Denmark, France , UK, Spain), co-funded by Cereal Partners Worldwide (Switzerland) and General Mills (US) on breakfast in human nutrition and for this I receive a consultancy fee. The project will lead to about 6-9 papers, individually peer reviewed and will, for the first time, outline options for an evidence-based approach to defining nutritional standards for breakfast, the meal everyone agrees is of great importance (e.g. WHO. AHA, all dietetic associations, most governments and almost all parents).

Finally, scientists are asked to sit on Boards of non-profit organisations which are industry funded or boards which are state funded. As regards the former, I am an unremunerated  non-executive member of the Board of the European branch of the International Life Sciences Institute (industry funded) and I have just retired as chair of the Board of the state funded Food Safety authority of Ireland, which carries a small remuneration. 

Some scientists make the decision not to accept the honorarium for themselves but rather to pass it on to their university and ultimately to their research students. That doesn’t seem to matter to the high priests of  the Twitterati School of Scientific Morality. Nor did it matter to the British Medical Journal. In 2015, it ‘uncovered’ a network of scientists advising the UK government who had connections with the food industry[2]. In particular, it singled out Professor Susan Jebb from the Oxford School of Public Health, who at the time of the alleged naughty industrial collusion was at the MRC’s (Medical Research Council) Nutrition Lab in Cambridge. Jebb pointed out that all of this work followed the MRC protocol for external funding, that the contribution of industry was made public in the relevant scientific papers, that she personally received no money from industry and that all this pre-dated her taking on the chair of a very important UK advisory committee on strategies to reduce obesity[3]. A phone call from the BMJ would have revealed such but why let the truth get in the way of a good story.  In this business, we get used to the constant harassment on industry funding. Here in Ireland, the law requires all academics to complete an annual Declaration of Interest under the Ethics in Public Office Act 1995[4].

Of late. There is growing interest in seeking declarations of interest which do not involve industry or financial remuneration[5]. Let’s imagine that some appropriate state agency is asked to review the evidence that veganism is perfectly compatible with optimal nutrition in adolescents. Would you be impressed if the chair was a vegan? Would you be happy for someone to be a member of the committee if they had an adolescent child who was a practicing vegan.  And what about someone who has written several popular books which argue some issue or other. Are they capable of being independent thinkers?

Transparency is the key to ensuring honesty and integrity in all aspects of scientific evaluation. And all interests must be made transparent whether they involve industry or anything else that might be seen by the outside world to shape world views.

[1] Effect of supplementation with vitamin D2-enhanced mushrooms on vitamin D status in healthy adults.J Nutr Sci. 2013 Aug 29;2:e29. doi: 10.1017/jns.2013.22. eCollection 2013.
[5] Disclosures in Nutrition Research: Why It Is Different. JAMA. 2018 Feb 13;319(6):547-548. doi: 10.1001/jama.2017.18571. Ioannidis JPA1Trepanowski JF2,3.

Friday, March 16, 2018

Weight loss: Are calories less important than food patterns?

{For personal reasons, mainly involving the restoration of an 1843 cottage in Dublin’s south coastal village of Blackrock, I have been absent from blogging for a while. I’m back now with renewed vigour to pursue the best of nutrition science and to tackle, mercilessly, nutribabble.}

 One of the latest trends in nutrition is to reduce our focus on nutrients and to sharpen our focus on the role of particular food patterns in promoting health. High up on the list of foods to avoid are processed (or ultra-processed) foods or foods high in fats, refined sugars and salt. A recent paper from Stanford University has been widely cited (not by the authors) as evidence that advice on caloric intake is less important in weight loss than the quality of the diet consumed[1]. In this study which was well designed, with adequate statistical power and ample duration, the authors describe the advice given to subjects (all were obese) thus: “No explicit instructions for energy (kilocalories) restriction were given. Both diet groups were instructed to (1) maximize vegetable intake; (2) minimize intake of added sugars, refined flours, and trans fats; and (3) focus on whole foods that were minimally processed, nutrient dense, and prepared at home whenever possible.” There were two treatment groups: a high-carbohydrate, low-fat diet and the opposite, a high-fat, low-carbohydrate diet. The two groups were given dietary advice to achieve the food pattern outlined above. Both groups lost weight after the 12 moths of intervention to the level of about 5.5 ( lbs) on average.

Here is how the New York Times reported the findings (Anahad O’Connor February 8th, 2018): Anyone who has ever been on a diet knows that the standard prescription for weight loss is to reduce the amount of calories you consume. But a new study, published … in JAMA, may turn that advice on its head. It found that people who cut back on added sugar, refined grains and highly processed foods while concentrating on eating plenty of vegetables and whole foods — without worrying about counting calories or limiting portion sizes — lost significant amounts of weight over the course of a year”. A distinguished Dean from Tufts in Boston was quoted as saying: “The research lends strong support to the notion that diet quality, not quantity, is what helps people lose and manage their weight most easily in the long run. It also suggests that health authorities should shift away from telling the public to obsess over calories and instead encourage Americans to avoid processed foods that are made with refined starches and added sugar, like bagels, white bread, refined flour and sugary snacks and beverages”.  The NYT piece was quoted across the globe by lazy editors to fill column inches with a pretty impressive story. Regrettably, it was a misleading story which opted to hide from its readers one awfully important point.

You see, the JAMA paper gives data on caloric intake at the beginning of the study and also at 3, 6 and 12 months of the intervention. Right throughout the study, irrespective of which of the two diets were being followed, no differences were seen between the two groups in calorie intake. So, for convenience of communication, I’ll give the average values of the two treatments at the different times. At baseline, the average daily caloric intake was 2150. By month 3, it had fallen to 1580. It then rose to 1620 by month 6 and at the 12 month conclusion, it was 1700. Thus, the 12 month figure was all of 450 fewer calories consumed
every day. The average body mass index (BMI; kg/m2) was 33, which means that the two groups were well into the obesity category of body weight. At that body weight and that daily caloric deficit from food alone, weight loss was no miraculous discovery. Which raises now a few questions.

Why were readers of the New York Times (NYT) misled so as to believe that calories don’t matter in weight loss? Is it so obvious to the NYT that the food patterns recommended were somehow so bound to lead to a caloric deficit that it needn’t be mentioned to its readers? Or is it remotely possible that the NYT never really read the paper and thus missed this whopping caloric deficit? I doubt I’ll ever know the answer. But if I was a journalist, I would be inclined to poke a bit further into this paper. We know from the paper that there was considerable variability in weight loss but no data are given. We also are not given any data about the changes that occurred in food intake , particularly to provide supporting data on the target foods (less of the sugary type, more of the complex carbohydrate food, more vegetables etc.). But the big question is why was the average relapse so low? Thus at three months, the mean daily caloric intake was 1580 and by month 12, it had slipped back a bit but only to 1700 kcal per day, a 9-month average regain of just 120 kcal per day. The human body absolutely defends a prevailing weight such that as all dieters know, the maintenance of weight loss requires enormous perseverance. Take your eye off the tiller for one moment and the tidal wave of our obesogenic environment will sweep you back on the rocks. So why not on this diet? I don’t know the answer to that but I do know that the anti-processed food lobby will argue that it is proof that processed food fosters a false appetite and that once that is taken away with a change to minimally processed home prepared foods, appetite regulation returns and low energy intakes are the result. There is however a little fly in the ointment here from another paper which set out to study the link between the intake of ‘ultra-processed foods’ and cancer[2].

This study from France used a cohort recruited through the Internet and who had their diet analysed through digital interaction using a multiple pass 24-hour recall. In all, 104,980 subjects were eligible to participate and did so over the period  2009-1017. The study was about cancer and that will not feature in this blog. Rather, we will focus on the weight of these subjects expressed as BMI (kg/m2). The population was divided into quartiles according to the contribution (weight by weight) of ultra-processed foods to overall food intake. The respective contributions (% w/w) of ultra- processed foods to the diets of the French subjects were thus: Q1 = 9; Q2 = 14 ; Q3 = 20 and Q4 = 32. And across this spectrum of ultra-processed food intake, BMI remained constant to the first decimal point at 23.8 kg/m2. The literature abounds in studies linking ultra-processed foods to obesity. Mais apparemment, pas en France. (But apparently, not in France).

So returning to the Stanford study, we have no differences in weight loss between those on a low fat-high carbohydrate diet as opposed those on a high fat-low carbohydrate diet over a 12 month period. They showed precisely the same caloric deficit over that period so one concludes that it simply doesn’t matter what advice one is given for a reduction in fat or in carbohydrate, the bottom line is that if that advice leads to a calorie deficit, then weight loss will accrue, irrespective of what the NYT might say. Quite how there was so little mean relapse in this study is as yet unexplained but as mentioned above, the anti-processed food advocates will argue that the abandonment of such foods returns people to a diet where appetite control in returns. The fly in the ointment of the French paper will never be raised.

Fine up to a point. However,  a previous NIH funded study, the “Pounds Lost Study” with weight loss programmes varying in fat and carbohydrate and reaching a similar conclusion to the Stanford study, showed a steady weight loss to 12 months with a significant weight loss relapse thereafter[3]. My calculation of the data presented in the tables of the Stanford study is that the average resting metabolic rate might be about 1,450 kcal per day which might not seem a million miles from the reported energy intake at 12 months, 1,700 kcal. However, the former is calculated based on weight stability but with dieting, this will fall by about 15%[4] to 1,230 kcal/d. Either these people will continue to lose weight or that deficit will drive a weight regain process. All the available science would show a slow relenting return to original bodyweight in a large proportion of the population. Maybe the Stanford study will show that better investment in food choice and tutoring on home cooking might help. Here’s hoping it does.

This Stanford study is very well designed, well executed and fairly reported. More data on food intake (% consumers and consumer only intake) would have been welcome but there’s only so much one can do for modern journals with page restrictions and charges. It adds significantly to the data on the relative role of the main energy macronutrients (carbohydrate & fat) and it is consistency with existing data. Regrettably, it will be long cited out of context as the study which showed that its diet quality that counts, not calories.

[1] Christopher D. Gardner, PhD; John F. Trepanowski, PhD; Liana C. Del Gobbo, PhD; Michelle E. Hauser, MD;
Joseph Rigdon, PhD; John P. A. Ioannidis, MD, DSc; Manisha Desai, PhD; Abby C. King, PhD . Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion  The DIETFITS Randomized Clinical Trial. JAMA. 2018;319(7):667-679. doi:10.1001/jama.2018.0245

[2] Thibault Fiolet, Bernard Srour, Laury Sellem,  Emmanuelle Kesse-Guyot, Benjamin Allès, Caroline
Méjean,Mélanie Deschasaux, Philippine Fassier, Paule Latino-Martel,Marie Beslay, Serge Hercberg,, Céline Lavalette, Carlos A Monteiro, Chantal Julia, Mathilde Touvier; Consumption of ultra-processed foods and cancer risk: results from NutriNet-Santé prospective cohort; BMJ 2018;360:k322 | doi: 10.1136/bmj.k322

[3] Frank M. Sacks, M.D., George A. Bray, M.D., Vincent J. Carey, Ph.D., Steven R. Smith, M.D., Donna H. Ryan, M.D., Stephen D. Anton, Ph.D., Katherine McManus, M.S., R.D., Catherine M. Champagne, Ph.D., Louise M. Bishop, M.S., R.D., Nancy Laranjo, B.A., Meryl S. Leboff, M.D., Jennifer C. Rood, Ph.D., Lilian de Jonge, Ph.D., Frank L. Greenway, M.D., Catherine M. Loria, Ph.D., Eva Obarzanek, Ph.D., and Donald A. Williamson, Ph.D.
Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates; N Engl J Med 2009;360:859-73
[4] Erin Fothergill, Juen Guo, Lilian Howard, Jennifer C. Kerns, Nicolas D. Knuth, Robert Brychta, Kong Y. Chen, Monica C. Skarulis, Mary Walter, Peter J. Walter, Kevin D. Hal; Persistent metabolic adaptation 6 years after “The Biggest Loser” competition; Obesity (2016) 24, 1612-1619. doi:10.1002/oby.21538