Ben Goldacre believes doctors are only “imagining that we’re practicing evidence-based medicine” because less than half of all clinical studies ever get published.

Goldacre says that there are many reasons why a large portion of clinical data goes unreported, but he has three main arguments.

Get Rid of the Negative

One of the biggest reasons why studies go unreported is because they have negative side effects.  While no company wants to be known for producing a harmful drug, Goldacre says successful trials are much more likely to be reported.

“The best currently available evidence comes from systematic reviews on the problem of missing trial data, which show that about half of all trials conducted and completed for the medicines we use today haven’t gone on to be published, and that trials with positive results are twice as likely to be published as trials with negative results,” said Goldacre.

On top of negative consequences, Goldacre says trials go underreported because there was a fatal error in the procedure.  Companies don’t want to admit that they paid millions of dollars for a new drug only to see it fail because of a controllable error, so they don’t publish the results.  Not publishing the results won’t bring their money back, and future studies could learn from the failed trials.

Loose Reporting Restrictions

The second reason why clinical trials go unpublished is because medical regulations are loosely enforced, and there are loopholes that allow the companies to “legally” refrain from publishing the complete data.

Goldacre said that in 2005, the International Committee of Medical Journal Editors enacted a regulation that required every study to be registered in public before it was published in a journal.

“The idea was if that everybody who’s got a positive result wants to publish it in a journal, then that’s a real carrot that journal editors can use to force people to register their trials,” said Goldacre.

The idea was well-intended, but it was loosely enforced.

“A paper published five years after these regulations came into force looked at every trial published in the top 10 journals in the big five fields of medicine,” said Goldacre.  “Half of them weren’t registered properly, and a quarter of them weren’t registered at all.”

Goldacre says the Food and Drug Administration is also at fault.  In 2007, the FDA enacted a law stating that the results of every clinical trial must be published to ClinicalTrial.gov within one year of completion, yet there was only 22% compliance among drug companies.

“Four out of five trials ignored this law, and yet no fine has ever been levied by the FDA,” said Goldacre. “Even if one had been levied at $10,000 a day, that’s basically a parking ticket to a big drug company making a few billion off one drug.”

The More Eyes, the Better

The final reason clinical trial data goes underreported stems from the idea that regulators want to keep their work to themselves so they can discover the cures on their own.  Goldacre says the public suffers behind this close-minded approach.

“There’s an idea among regulators that it’s okay for them to make decisions behind closed doors and just tell doctors what to do,” said Goldacre.  “I think that doesn’t work anymore because science isn’t about just telling someone the answer. Science is about being clear, open, and transparent about your methods and your results.”

Simply put, the more people that have access to a problem, the greater the chance that it can be solved quicker and more efficiently.

“Problems with Vioxx weren’t spotted by the FDA; they were spotted by an independent cardiologist, he said.  “Problems with Avandia weren’t spotted by regulators; they were spotted by individual academic researchers.”

A Change on the Horizon

Goldacre hopes to change to face of clinical trial reporting by getting pharmaceutical companies to agree to release their data, regardless of the results.  He hopes that awareness of the issue will also lead to patients putting pressure on drug companies.

“I believe very strongly that when patients come to realize the extent to which we’ve failed them by not addressing missing data, they will be, well, disappointed is the most relaxed word I can think of,” said Goldacre.  “I think they’ll be appalled.”

To assist in trial reporting, Goldacre has created the website AllTrials.net.  He has been talking with major pharmaceutical companies and smaller patient groups in hopes of getting their support.  So far over 80 patient groups have agreed to register their studies, and Goldacre even received support from GlaxoSmithKline, one of the largest drug companies in the world.  Goldacre hopes GSK’s support will lead to more companies registering their studies.

“I don’t think GSK will be the only company to sign up,” he said.  “I think we’re going to enter a very interesting era where potentially the market is differentiated by ethical companies who’ve made a commitment to sharing all their trial results, and unethical companies who are still aggressively defending their ability to withhold information from doctors and patients.”

Dr. Silverman comments

The director of my residency program and one of my mentors, Dr. Eric Radin, a pioneer in Orthopaedic surgery and a true clinical scientist, once said that the medical community could learn so much from ‘The Journal of Failed Study’, yet no such publication exists.

Dr. Radin believed so much could be learned from the trials that didn’t work out the way the researchers had intended.  If we took away the stigma of a failure we would open the door to such greater and faster learning.

For a minimum, a section entitled ‘poor design’ would be a source of constant education and cost savings. How much money is wasted because true design is faulty from the get go but we can’t see the confounding variable of importance?

But, with respect to my typical conspiracy suspicions combined with the obvious implications of the article, eliminating the bias of making studies that didn’t give results in a company’s favor be published could save lives.  Company’s truly should open up and expect the meta-analysis to eventually fall in their favor.

Related source:  MedPage Today

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Not what the Doctor Ordered

The case study of Dr. Pepper is fascinating.  In 2001, Dr. Pepper sat in third-place in the soda industry, but their position was anything but comfortable.  See, Dr. Pepper was forced to defend its product on two fronts.  On one side, marketers were trying to catch Coca-Cola and Pepsi, while the other side was trying to fend off cheaper alternatives.  Marketers decided the best way to battle both fronts was to create spinoffs of their original and diet Dr. Pepper flavors.

“If we are to re-establish Dr Pepper back to its historic growth rates, we have to add more excitement,” the company’s president, Jack Kilduff, said.

Dr. Pepper executives thought they had bottled that excitement when the released “Red Fusion”, the first spin off in the 115-year history of the company.  Alas, Red Fusion was a colossal failure, as Dr. Pepper enthusiasts described the drink as “Disgusting”, “Gagging”, and “Never again”.

Bring in the Nerds

Cadbury Schweppes, the parent company of Dr. Pepper, was extremely disappointed by the sales of Red Fusion, but they knew there was a market for Dr. Pepper spinoffs.  That’s when they turned to Dr. Howard Moskowitz, who specialized in “optimizing” different types of foods.

“I’ve optimized pizzas. I’ve optimized salad dressings and pickles,” Moskowitz said in an interview.  ”In this field, I’m a game change.”

Moskowitz believes there is an exact science to the food and beverage industry.  The perfect chip or soda will appeal to the consumer in many ways, but it always offers one similar component; it keeps the consumer coming back for more.

The method to his madness is rather simple.  Moskowitz runs focus groups that ask people to rate a product on a variety of different factors to find their “bliss point”.  Some of the factors include crunchiness, texture, shape, size, density, and taste, as well as questions about the consumer’s likelihood to buy the product.  Once the data is in the computer, the only thing left is to optimize a product from the consumer demands.

“The mathematical model maps out the ingredients to the sensory perceptions these ingredients create,” he said.  “So I can just dial a new product. This is the engineering approach.”

Moskowitz first started optimizing foods when he worked for the U.S. Army.  The army had contracted Moskowitz because they found that soldiers were not getting enough nutrition from their rations, but it wasn’t because the food itself lacked nutrition.  The problem was soldiers were throwing away half full rations because the food didn’t appeal to them.  Through his research, Moskowitz found that in order to strike a perfect formula, a food needed to be alluring enough to eat, but not feature an overriding or distinct flavor that tells the brain to stop.

Putting the Formula to Work

Cadbury Schweppes wanted Moskowitz to create a new product featuring cherry and vanilla flavors.  Moskowitz formed nearly 4,000 tasting groups to try several different variations of the cherry and vanilla concoctions.

With the help of his data, Moskowitz compiled a 135-page report that detailed each and every opinion a tester had about the new products.  Nestled in the report on page 83 were the exact measurements for creating the best spinoff.

The biggest change with the new spinoff was the amount of Dr. Pepper syrup the company added.  In Red Fusion, 2 milliliters of syrup were used, but the perfect recipe suggested only 1.69 milliliters were necessary.  Not only did Dr. Pepper create a better tasting product, but they also saved millions by not wasting syrup.

The product that came out was known as Cherry Vanilla Dr. Pepper, and is still selling strong on shelves today.

Dr. Silverman comments

Dr. Moskowitz’s took a very rational approach to determine what was most pleasing to the average human. He calls it the “bliss point”.  By asking people how they felt when they tasted different formulations of Dr. Pepper, not whether it tasted good or better than another, he was able to pinpoint an ideal recipe.

Dr. Jonah Leherer, a neuroscientist and frequent contributor to the New York Times, has studied the emotional response of sensation, in particular that of taste.  The neurochemical effects of certain substances on the brain can be measured and become predictable.

It’s not the taste that keeps people coming back for more, (if that were true, cigarettes would taste good); it’s the emotional response to ingesting that particular substance.

Dr. Pepper cherry vanilla is good, and I know that firsthand because the marketing companies have convinced me to try their soda, even though I know of the harmful effects. Does it make me feel duped? Rather, it has been more of an “A Ha!” moment. It has given me pause and made me promise myself to pay attention to my emotional response more than my stomach. Now the phrase, “CAVEAT EMPTOR” (let the buyer beware) gets even more meaningful.

This article is powerful, because we can no longer claim blissful ignorance. The companies that make these products are led by their bottom line. The best way to sell soda is to wrap up a bottle full of “pleasant emotional experience”, then give it to the marketers to get the people to try it through psychological pressures, like commercial advertising. It’s government-sanctioned, taxable, legal substance dealing.

In Parts 2 and 3 of The Science of Food, we’ll look at how Lunchables and Fritos grew to immense popularity, and the health risks associated with our favorite snack foods.

Related source:  NY Times

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