Saturday September 23, 2006
So where were we? Oh yes. Durham Council is running a highly dubious “trial” of a food supplement that is methodologically crippled, and largely incapable of giving meaningful data, but in the process Durham Council staff are appearing all over the papers and television in news stories to promote a pill called Eye Q made by Equazen, suggesting it is effective at improving concentration and learning in normal children, an assertion that is not supported by published trial data, as we have discussed (although it might be if Durham simply did their trials properly). Meanwhile Equazen say they have 20 unpublished trials which all show a benefit for their omega-3 product, but I would have to sign a non-disclosure agreement to read them. Not very collegiate, especially when this important issue of nutrition and behaviour has been all over the papers, thanks to their efforts.
What would happen if you were a pill-peddling food supplement company, and you simply made claims that omega-3 would improve childrens’ concentration and learning, openly, in your adverts, or on your label? Well. A major competitor for Equazen – St Ivel – didn’t have Madeleine Portwood, Dave Ford, and other employees of Durham Council to appear in the media and make claims about their omega-3 product. Nor did they have the chance to put their publicity details at the bottom of Durham Council’s official press releases promoting their product.
So St Ivel made an almost identical claim for their product openly in an advert, and somebody successfully complained about them to the Advertising Standards Authority. Guess who complained? “The complainants challenged whether more Omega 3, and therefore St. Ivel â€˜Advanceâ€™, enhanced children’s concentration and learning.” This is exactly the claim that Equazen’s friends in the media, and their friends in Durham Council, and indeed Equazen, make safely in “news” stories and press releases, away from the regulators. And yet it was Equazen who complained to the ASA about St Ivel. Press your advantage, I say.
So who are the multi-millionaires behind Equazen? One director is an ex-BBC foreign correspondent with a very large address book full of media contacts. The other is Cathra Kelliher, daughter of David Horrobin, the 1980s pill multi-millionaire, whose own food supplements empire â€“ also built on â€œessential fatty acidsâ€ – was worth Â£550 million at its peak. That’s the nutritionism industry: a noble contrast to big pharmaceutical companies, as people like to believe. Or perhaps not.
In 1984, staff at Horrobin’s US distributors were found guilty in court of misbranding their food supplement as a drug; they were circumventing FDA regulations which prevented them making unfounded claims for their supplement pills in advertising, by engineering media coverage that treated the product as if it had proven medical benefits. In the court case, paperwork was exposed from Horrobin, Equazen pÃ©re, in which he explicitly said things like: “Obviously you could not advertise [evening primrose oil] for these purposes but equally obviously there are ways of getting the information across…” Company memos described elaborate promotional schemes: planting articles on their research in the media, deploying researchers to make claims on their behalf, using radio phone-ins (this was the 1970s), and the like.
Horrobin’s products were always in the news, and it was difficult to get hold of that research data too. In 1989 he published a famous meta-analysis of trials on evening primrose oil in eczema in a dermatology journal, finding that evening primrose oil, his lead product, was effective. His meta-analysis included the two oldest studies, excluded the one large published trial available (which was negative), but included seven small positive studies sponsored by his own company (these were still unavailable at the last review I could find, in 2003).
In 1990, two academics had their review of the data binned by the journal after Horrobin’s lawyers got involved. In 1995 the Department of Health commissioned a meta-analysis from a renowned epidemiologist. This included 10 unpublished studies held by the company which was marketing evening primrose oil. The ensuing scene was only fully described by Professor Hywel Williams a decade later (full quotes and references at badscience.net). The company erupted over a leak, and the Department of Health forced all authors and referees to sign written statements to reassure the company. They were not allowed to publish their report. Alternative therapy, the peoples’ medicine! It has since been shown that evening primrose oil is not effective in eczema, and it has lost its medicines license.
Iâ€™m not saying that Equazen are doing anything illegal, or breaking any regulation, but there is a theme here. Undisclosed research data, and advocacy by proxy in the media, are in fact well trodden paths for the pharmaceutical industry, and the food supplement industry, it seems, are no different. In an environment where it is difficult to make claims for food supplements explicitly in adverts, companies will inevitably be even more imaginative about how to get their message across: but personally, I think Iâ€™d rather see it in the adverts than on the news pages.
The saga of trying to get research data from Horrobin and company is told in various places, including this article from the British Medical Journal:
I should say I think a lot of what Horrobin did was interesting and useful, I am very open to the idea that nutritional interventions can be beneficial, and he was a sharp cookie. It’s just about the data. Some relevant bits from the BMJ article, for non-subscribers to that august journal (it’s actually jolly readable), are here:
“Yet many questions surrounding the story of evening primrose oil for eczema remain unanswered: how was this drug licensed in the first place and why have so few data been available in the public domain for open scientific debate?
“In 1989 Horrobin et al published a meta-analysis in the British Journal of Dermatology of the two earliest studies plus another seven small (14-47 participants) company sponsored studies of evening primrose oil (Epogam, Scotia Pharmaceuticals) for atopic dermatitis.8 They found that atopic dermatitis improvement scores for evening primrose oil were significantly better than placebo, with effects on itch being “particularly striking.” Apart from the fact that the seven company trials included in that study have never since appeared in the public domain, the other concern about that meta-analysis was its exclusion of the one other independent and relatively large study (123 participants) by Bamford et al.9 The company authors of the meta-analysis suggested that active versus placebo treatments became mixed up in the Bamford study, based on an analysis done by the company of fatty acid levels in blood samples taken from study participants.8 After this meta-analysis was published, others thought it odd that Bamford et al never published a response to the company’s serious criticisms of their study.10 In fact Bamford immediately wrote a lengthy and clear explanation of the steps that were in place to avoid such purported contamination, but he was refused an opportunity to defend his study with a published response because the journal decided that Bamford’s response did not add anything to the understanding on the use of evening primrose oil as a supplemental treatment for atopic eczema (J Bamford, written communication 12 Nov 2003). In desperation, Bamford tried to publish his response in other dermatology journals, but without success, so his defence of his original paper (a copy of which is now sitting on my desk) has to this day remained unpublished.
“A year later, two British dermatologists wrote a detailed review article on evening primrose oil and atopic dermatitis. Out of courtesy, they showed a copy of the peer reviewed article to the manufacturers, who intimated their intent to pursue the matter legally further if the authors did not withdraw or modify the article substantially. (J Marsden, written communication, 27 November 2003). The article (now sitting on my desk) was never published despite getting to proof stage.
“More significantly, in 1995 the Department of Health commissioned me and a colleague to conduct an individual patient meta-analysis of 20 studies of oral evening primrose oil supplementation for treatment of atopic dermatitis, which included 10 unpublished studies held by the company (Li Wan Po A, Williams HC. A systematic overview of clinical trials of Epogam in atopic eczema. Department of Health, 1995). Although it was our view that the report produced a relatively clear conclusion, we were never allowed to share the report in the public domain for reasons that are still unclear to me, even though it was funded by public money. Shortly after we submitted our report to the Department of Health, Searle, the company then responsible for marketing evening primrose oil, expressed concern that the contents of the report had been leaked, and the authors and referees were required to sign a written statement to the company (through the Department of Health) to indicate that this was not the case.
“Too little data in the public domain”
“The Health Technology Assessment systematic review published in 2000 provided an opportunity for the company to hand over its unpublished studies for inclusion in that report.5 Although Searle wrote back to tell us that they would be “compiling the data,” no data have been forthcoming to date. We can only hope that it will be compiled in time for the current Cochrane review on GLA supplementation for atopic dermatitis.11 Finally, in the autumn of 2002 the Medicines Control Agency withdrew the marketing authorisations for evening primrose oil following a “review of all the relevant information, including new studies,” although which information and new studies is unclear from the very limited information available on the agency’s website.12
“In fairness to the innovators of evening primrose oil for atopic dermatitis, they evaluated their product more than many other products used in dermatology. Nobody would have been happier than myself if evening primrose oil had produced a clinically worthwhile benefit for eczema sufferers. But the history of its development has been marred by lack of data in the public domain. As we bid goodnight to the evening primrose oil story, perhaps we can awaken to a world where all clinical trial data, derived from people who are good enough to volunteer for such studies, reach the light of day, where they can be openly debated in the public domain.”
(Hywel C Williams, professor of dermatoepidemiology, Nottingham)