The picture that presents itself is shocking. A majority of randomized controlled trials of drugs is funded by the respective companies by now, they adhere to high scientific standards and are published in high-ranking peer-reviewed journals, and they still manage to be deceptive — for instance, being four times more likely to yield favorable results than independently funded studies in one comparison. How?

From the journal article:

The companies seem to get the results they want not by fiddling the results, which would be far too crude and possibly detectable by peer review, but rather by asking the “right” questions—and there are many ways to do this [10]. Some of the methods for achieving favourable results are listed in the Sidebar, but there are many ways to hugely increase the chance of producing favourable results, and there are many hired guns who will think up new ways and stay one jump ahead of peer reviewers.

Then, various publishing strategies are available to ensure maximum exposure of positive results. Companies have resorted to trying to suppress negative studies [11,12], but this is a crude strategy—and one that should rarely be necessary if the company is asking the “right” questions. A much better strategy is to publish positive results more than once, often in supplements to journals, which are highly profitable to the publishers and shown to be of dubious quality [13,14]. Companies will usually conduct multicentre trials, and there is huge scope for publishing different results from different centres at different times in different journals. It’s also possible to combine the results from different centres in multiple combinations.

These strategies have been exposed in the cases of risperidone [15] and odansetron [16], but it’s a huge amount of work to discover how many trials are truly independent and how many are simply the same results being published more than once. And usually it’s impossible to tell from the published studies: it’s necessary to go back to the authors and get data on individual patients.

Here are the „sidebar“ tricks to „ask the right questions“:

• Conduct a trial of your drug against a treatment known to be inferior.
• Trial your drugs against too low a dose of a competitor drug.
• Conduct a trial of your drug against too high a dose of a competitor drug (making your drug seem less toxic).
• Conduct trials that are too small to show differences from competitor drugs.
• Use multiple endpoints in the trial and select for publication those that give favourable results.
• Do multicentre trials and select for publication results from centres that are favourable.
• Conduct subgroup analyses and select for publication those that are favourable.
• Present results that are most likely to impress—for example, reduction in relative rather than absolute risk.

All that makes the work very hard for peer-reviewers, as most of these manipulations will not be visible in the manuscript and, as mentioned, could only be revealed through additional data provided from the authors…

The editors‘ and publishers‘ own financial interest play an important role, too, of course:

Publishers know that pharmaceutical companies will often purchase thousands of dollars‘ worth of reprints, and the profit margin on reprints is likely to be 70%. Editors, too, know that publishing such studies is highly profitable, and editors are increasingly responsible for the budgets of their journals and for producing a profit for the owners. Many owners—including academic societies—depend on profits from their journals. An editor may thus face a frighteningly stark conflict of interest: publish a trial that will bring US$100 000 of profit or meet the end-of-year budget by firing an editor.

The majority of high-ranking articles are by now payed for by the industry:

[…] between two-thirds and three-quarters of the trials published in the major journals—Annals of Internal Medicine, JAMA, Lancet, and New England Journal of Medicine—are funded by the industry [9].

And the interest of the pharmaceutical companies is easily explained:

A large trial published in a major journal has the journal’s stamp of approval (unlike the advertising), will be distributed around the world, and may well receive global media coverage, particularly if promoted simultaneously by press releases from both the journal and the expensive public-relations firm hired by the pharmaceutical company that sponsored the trial. For a drug company, a favourable trial is worth thousands of pages of advertising, which is why a company will sometimes spend upwards of a million dollars on reprints of the trial for worldwide distribution. The doctors receiving the reprints may not read them, but they will be impressed by the name of the journal from which they come. The quality of the journal will bless the quality of the drug.

For how this is realized in practice, I highly recommend the Guardian article, but here is a decisive part about this new industry:

Drug companies exert this hold on knowledge through publication planning agencies, an obscure subsection of the pharmaceutical industry that has ballooned in size in recent years, and is now a key lever in the commercial machinery that gets drugs sold.

The planning companies are paid to implement high-impact publication strategies for specific drugs. They target the most influential academics to act as authors, draft the articles, and ensure that these include clearly-defined branding messages and appear in the most prestigious journals.

[…]

There are now at least 250 different companies engaged in the business of planning clinical publications for the pharmaceutical industry, according to the International Society for Medical Publication Professionals, which said it has over 1000 individual members.

Now, the most interesting aspect of the PLoS article is maybe its recommendations for solving that problem, particularly this radical idea:

Secondly, journals should perhaps stop publishing trials. Instead, the protocols and results should be made available on regulated Web sites. Only such a radical step, I think, will stop journals from being beholden to companies. Instead of publishing trials, journals could concentrate on critically describing them.

That would be pretty interesting work for a researcher! But he or she would still need somebody to pay for that, and it would certainly not be the industry.

Und wer wurde noch nicht beim Anblick verlockender Beeren auf einer Wanderung von wohlmeinenden Freunden vor dem Fuchsbandwurm gewarnt? Zu Unrecht. Zwar ist die Infektion mit dem Fuchsbandwurm wirklich gefährlich. Aber es gab 2008 nur 26 Fälle in Deutschland. Und die haben sehr wahrscheinlich nichts mit Beeren zu tun:

Der Molekularbiologe Klaus Brehm sagt: »Es ist für keinen einzigen Patienten erwiesen, dass er sich so angesteckt hat.« Und Andreas Hensel vom Bundesinstitut für Risikobewertung sagt, die Warnungen würden von der »Risiko-Industrie« hervorgebracht. Tatsächlich geht die Hauptgefahr einer Infektion von Haustieren aus, die eine befallene Maus oder Ratte gefressen haben.

Die EFSA, meint darum Sarah Häuser, Chemieexpertin der Umweltorganisation BUND, sei „regelrecht unterwandert“. Die im September noch einmal bestätigte Entscheidung der Behörde zur Unbedenklichkeit von BPA zeige „deutlich, dass die interessierte Industrie dort mehr Gehör findet als unabhängige Forscher.“ Diesen Eindruck bestätigt auch Andreas Gies, Fachmann für Umweltchemikalien beim Umweltbundesamt (UBA). Die EFSA stütze sich fast ausschließlich auf Studien, die von der Industrie bezahlt seien und „die Finanzierung bestimmt das Ergebnis“, klagt Gies.

Die Argumentation der EFSA treibt laut dem Toxikologen Gilbert Schönfelder von der Berliner Charité wilde Blüten:

Im Tierversuch sei nachgewiesen, dass BPA die Fruchtbarkeit mindern und das Erbgut verändern könne. Darum sei es „nicht akzeptabel“, dass die EFSA-Experten mehr als 80 Studien über BPA-Funde im menschlichen Blut aus der Bewertung ausschließen und so die tatsächliche Belastung im Alltag unterschätzen, klagt er. Zur Begründung heißt es in den EFSA-Gutachten, die Messungen seien ungenau und mit den bekannten Aufnahmepfaden nicht erklärbar – nach Meinung von Schönfelder eine unhaltbare Argumentation. „Wenn die Daten der Hypothese widersprechen, dann muss die Hypothese zurückgewiesen werden, nicht die Daten“, forderten er und vier weitere Toxikologen.

Nachdem insgesamt die Hinweise sehr stark sind, dass die Geldgeber einen großen Einfluss auf die Ergebnisse von wissenschaftlichen Untersuchungen haben, wüsste ich wirklich gerne, wie der zustande kommt. Ich bin jemand, der grundsätzlich ungern böse Absicht unterstellt. Aber wenn es daran nicht liegt, müsste das nicht heißen, dass die wissenschaftliche Methodik so schwach ist, dass sehr subtile Vorannahmen und Motive der Forschenden derart durchschlagen können? Keine schöne Vorstellung.

Judging from a NYTimes book review of „Disconnect“ by Devra Davis, though, the German radiation paranoia might turn out to be quite sensible. To put it cautiously: It is at least scientifically plausible that cell phone usage (i.e. holding it to your head while speaking) is linked to brain cancer:

Over all, there has not been a general increase in its incidence since cellphones arrived. But the average masks an increase in brain cancer in the 20-to-29 age group and a drop for the older population.

“Most cancers have multiple causes,” she says, but she points to laboratory research that suggests mechanisms by which low-energy radiation could damage cells in ways that could possibly lead to cancer.

And as with other historical (smoking) and contemporary (plastic bottles) issues of the kind, it is very plausible that the industry (and also industry-sponsored research) are trying to tell us everything is alright:

He [Henry Lai, a research professor in the bioengineering department at the University of Washington] maintains a database that holds 400 scientific papers on possible biological effects of radiation from wireless communication. He found that 28 percent of studies with cellphone industry funding showed some sort of effect, while 67 percent of studies without such funding did so. “That’s not trivial,” he said.

I’m really curious how this topic will be seen 50 years from now. In the meantime — there are a lot of other reasons to not use cell phones too much, anyway!

Let’s start with the nutritional facts, hopefully old news for most people:

Agriculture Department data show that cheese is a major reason the average American diet contains too much saturated fat.

Saturated fats are link to a range of health problems, especially heart and cardiovascular diseases.

The industry’s problem started with a public effort to eat more healthy, in a way:

Urged on by government warnings about saturated fat, Americans have been moving toward low-fat milk for decades, leaving a surplus of whole milk and milk fat. Yet the government, through Dairy Management, is engaged in an effort to find ways to get dairy back into Americans’ diets, primarily through cheese.

Americans now eat an average of 33 pounds of cheese a year, nearly triple the 1970 rate. Cheese has become the largest source of saturated fat; an ounce of many cheeses contains as much saturated fat as a glass of whole milk.

It would be a waste to throw that fat away, too, wouldn’t it? If you wanna have fat-free milk, why not go for tasty milk alternatives like soy, rice or oat milk? Just a brief vegan intermezzo.

Now the really interesting and shocking part is the relation between pro-cheese campaigns and health-food campaigns:

Dairy Management runs the largest of 18 Agriculture Department programs that market beef, pork, potatoes and other commodities. Their budgets are largely paid by levies imposed on farmers, but Dairy Management, which reported expenditures of $136 million last year, also received $5.3 million that year from the Agriculture Department to promote dairy sales overseas.

By comparison, the department’s Center for Nutrition Policy and Promotion, which promotes healthy diets, has a total budget of $6.5 million.

So the total spending ratio is about 20 to 1, and the government spends about the same amount of money on promoting cheese alone (there 17 more similar programs) as it does on eating healthy. Somehow I have the feeling that small-government proponents in the Republican party would still worry more about the healthy food part, labeling it a government intrusion into American’s kitchens.

The story falls into complete absurdity when science enters the field, and the double credibility of scientific and government backing promote what turns out as something closer to lies than mistakes:

“Great news for dieters,” Dairy Management said in an advertisement in People magazine in 2005. “Clinical studies show that people on a reduced-calorie diet who consume three servings of milk, cheese or yogurt each day can lose significantly more weight and more body fat than those who just cut calories.”

With milk consumption in decline, Dairy Management had hit on a fresh marketing strategy with its weight-loss campaign.

When the campaign began in 2003, a Dairy Management official said it was inspired by newly relaxed federal rules on health claims and the ensuing “rapid growth of ‘better for you’ products.”

True, there had been a study backing that claim at the time. But evidence was soon mounting it was false. And was suppressed and ignored:

One such study was conducted by Jean Harvey-Berino, chairwoman of the Department of Nutrition and Food Sciences at the University of Vermont. “I think they felt they had a lot riding on it,” she said of the weight loss claim, “and felt it was a cash cow if it worked out.”

“I’m a big promoter of dairy,” she added, noting that her research was also paid for by Dairy Management.

But by 2004, her study had found no evidence of weight loss. She said Dairy Management took the news poorly, threatening to audit her work. She said she was astonished when the organization pressed on with its ad campaign.

“I thought they were crazy, and that eventually somebody would catch up with them,” she said.

Her study was published in 2005, and at scientific meetings she heard from other researchers who also failed to confirm Dr. Zemel’s work, including Dr. Jack A. Yanovski, an obesity unit chief at the National Institutes of Health.

But in late 2006, Dairy Management was still citing the weight-loss claim in urging the Agriculture Department not to cut the amount of cheese in federal food assistance programs. “The available data provide strong support for a beneficial effect of increased dairy foods on body weight and body composition,” two organization officials wrote, making no mention of Dr. Harvey-Berino’s findings.

Having dismissed the weight-loss claim in 2005, the federal nutrition advisory committee this summer again found the underlying science “not convincing.”

This specific campaign has been halted, but the general direction has not changed:

Meanwhile, Dairy Management, which allotted $12.4 million for nutrition research in 2008, has moved on to finance studies on promising opportunities, including the promotion of chocolate milk as a sports recovery drink and the use of cheese to entice children into eating healthy foods like string beans.

At the same time the organization works with corporations to increase the usage of cheese, and boasts with its successes:

And unlike with its advertising campaigns, Dairy Management and the Agriculture Department could point to specific results with these projects. The “Summer of Cheese” promotion it developed with Pizza Hut in 2002 generated the use of 102 million additional pounds of cheese, the department reported to Congress.

Sad for health. Sad for animals. Sad for science. Sad for democracy.

Ein NYTimes Op-Ed vom März beschäftigt sich mit Antibiotika-resistenten Bakterienstämmen. Zum einen ist das mal wieder eine Gesundheitsbedrohung, die all die gehypten Erreger in den Schatten stellt — z.B. sterben anscheinend jährlich 18.000 Amerikaner an MRSA, mehr als an AIDS.

Zur Entstehung des Problems tragen Ärzte bei, die zu leichtfertig Antibiotika verschreiben. Aber vor allem die Massentierhaltung:

A study by the Union of Concerned Scientists found that in the United States, 70 percent of antibiotics are used to feed healthy livestock, with 14 percent more used to treat sick livestock. Only about 16 percent are used to treat humans and their pets, the study found.

Die resistenten Erreger an Tieren stehen in regem Gentausch mit für Menschen gefährlichen Mikroben. Es wäre natürlich möglich, mindestens der präventiven Verwendung von Antibiotika in der Tierhaltung politisch einen Riegel vorzuschieben. Ein entsprechender Vorstoß in Amerika ist aber an den Lobbyisten gescheitert, und nicht mal die Obama-Regierung traut sich ran.

Zum Abschluss kann ich mir ein weiteres Zitat nicht verkneifen, weil es so schön weltuntergangsmäßig klingt:

“We are seeing infections caused by Acinetobacter and special bacteria called KPC Klebsiella that are literally resistant to every antibiotic that is F.D.A. approved,” Dr. Spellberg said. “These are untreatable infections. This is the first time since 1936, the year that sulfa hit the market in the U.S., that we have had this problem.”

The Infectious Diseases Society of America, an organization of doctors and scientists, has been bellowing alarms. It fears that we could slip back to a world in which we’re defenseless against bacterial diseases.

Da geht sie hin, die Illusion von einer sicheren Welt.

Das erstaunliche Ergebnis ist jedenfalls, dass Patienten, die glaubten, mit 75% Wahrscheinlichkeit das aktive Medikament zu erhalten, sich deutlich (und auch was die bei Parkinson recht gut bekannten neurochemischen Veränderungen angeht) von den anderen Gruppen abhoben, insbesondere auch von der Gruppe, die davon ausgingen, dass sie mit Sicherheit das aktive Medikament erhalten würden.

Bezüglich des Verschreibens von Placebos wäre das ein klares Argument dafür — es würde allen Verschreibungen vom Arzt eine zusätzliche „rein psychische“ Wirkung geben, wenn wir uns nicht mehr ganz sicher wären, dass das Medikament „echt“ ist!

Dennoch bin ich insgesamt eher gegen eine derartige Psychologisierung des Allgemeinarztes. Ich finde, es entspricht nicht einem modernen Verständnis von psychologischen Interventionen, wenn derart mit Täuschung gearbeitet wird. Im Gegensatz dazu ziehe ich aus meiner Prüfungslektüre zu systemischer Therapie und Beratung die Vermutung, dass sich ein ähnlicher Effekt auch mit einer sehr kurzen Psychotherapie erreichen ließe. Ich denke, dass ein großer Teil dieses Placeboeffekts bei ungewisser, aber hoffnungsvoller Erwartung durch eine veränderte Aufmerksamkeit zustande kommt, die sich mehr auf die Beobachtung dessen richtet, was sich vielleicht verbessert oder verändert hat. Und das gehört zum Standardinventar systemischer Techniken, mit denen Probleme „verflüssigt“ werden. Übrigens gibt es in dieser Therapierichtung auch schon viel Erfahrung gerade mit chronischen Krankheiten mit starker biologischer Mitverursachung (z.B. Asthma oder Diabetes bei Kindern).

Und im Gegensatz zur wunderheilerartigen Placebointervention wird dabei gleichzeitig die Selbstbestimmung und Autonomie der Patienten/Klienten gestärkt, und ihr Vertrauen in ihre eigenen Problemlösefertigkeiten. Und — ich möchte eine potenzielle Einschränkung meiner Neutralität in dieser Frage nicht verschweigen — mir geht nicht so schnell die Arbeit aus…

Jetzt tritt dazu vielleicht noch Vitamin D, wie die NYTimes berichtet — und zwar unabhängig von der Ernährungsweise:

Most people in the modern world have lifestyles that prevent them from acquiring the levels of vitamin D that evolution intended us to have. The sun’s ultraviolet-B rays absorbed through the skin are the body’s main source of this nutrient. Early humans evolved near the equator, where sun exposure is intense year round, and minimally clothed people spent most of the day outdoors.

In Nahrungsmitteln ist das Vitamin anscheinend praktisch nicht zu finden. Und ein Mangel wird mit Krebs, Kardiovaskulären Erkrankungen und Diabetes in Verbindung gebracht:

Such low levels could account for the high incidence of several chronic diseases in this country, Dr. Holick maintains. For example, he said, in the Northeast, where sun exposure is reduced and vitamin D levels consequently are lower, cancer rates are higher than in the South. Likewise, rates of high blood pressure, heart disease, and prostate cancer are higher among dark-skinned Americans than among whites.

The rising incidence of Type 1 diabetes may be due, in part, to the current practice of protecting the young from sun exposure. When newborn infants in Finland were given 2,000 international units a day, Type 1 diabetes fell by 88 percent, Dr. Holick said.

Beruhigend, dass das Vitamin in meinen Veganer-Tabletten auch schon drin ist. Und zeigt mal wieder, wie schön etwas sein kann, das in unserer Welt selten geworden ist: Sich für wichtige Entscheidungen auf einen Experten zu verlassen, und nicht über alles selbst Bescheid wissen zu müssen.