You might suspect, for example, that the study was sponsored by a drug company and authored by researchers with financial interests tied to those drug companies. You might wonder if these associations could possibly - just possibly - influence not only the results of the study, but how those results are reported. You might also find yourself questioning the objectivity of a study with the title “Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin” (JUPITER).

If you’re asking yourself these questions, you are definitely on the right track. The study was indeed sponsored by a drug company, AstraZeneca. And each author of this study received money in the form of grants, consulting fees and honoraria from pharmaceutical companies - in some cases up to twelve different companies, including AstraZeneca, the study sponsor. Take a look at this list detailing the financial interests of the study authors (now required by the New England Journal of Medicine and other prominent publications):

Now, the fact that these researchers receive money from all of these drug companies doesn’t mean that they are dishonest or that their data are invalid. However, if you think these conflicts of interest do not influence the outcomes of clinical research, then I suggest you read an article I published a few months ago called When It Comes To Drug Claims, Skepticism Is Healthy.

Now that you’ve put on your “Healthy Skeptic” goggles, we can move on and more closely examine the study itself. There are several things you need to be aware of as we discuss it.

First, although the press articles claim that the study looked at statin use in healthy populations, the subjects were people who had normal cholesterol but high CRP levels. CRP, or C-Reactive Protein, is a measure of inflammation in the body. It is now widely accepted even in the mainstream medical community that inflammation is a major risk factor for heart disease. And because inflammation is a sign of an underlying disease process, these patients were not, in fact, “healthy” as claimed.

There is little doubt that statins reduce inflammation, which can help prevent atherosclerosis. It appears that the benefits of statins are mainly due to this characteristic, rather than to their cholesterol-lowering effects. So it’s no surprise that the statins reduced rates of heart disease and mortality in this population that had inflammation going into the study.

I should also mention, however, that the predictive value of CRP for heart disease is highly controversial. Though some studies show a correlation between high CRP levels and heart disease, many others do not. Many physicians feel that CRP is not a useful indicator in clinical practice.

The second thing you need to be aware of is the difference between relative and absolute risk reduction. Relative risk reduction (RRR) measures how much the risk is reduced in the experimental group compared to a control group. Absolute risk reduction (ARR) is just the absolute difference in outcome rates between the control and treatment groups.

To make this more clear, let’s consider an example. Say that 2000 people enter a study for a particular drug and 1000 of them are randomized to placebo. At the end of the study, one person in the drug group died versus two people in the placebo group. The relative risk reduction of the drug group would thus be 50% (0.002 - 0.001/0.002). That sounds really impressive! The headline for this study might read “New drug reduces chance of dying by 50%!”. While technically true, you can see how misleading this can be. Why? Because when most people read that headline, they will interpret it to mean that if they take that drug, their risk of dying will be reduced by 50%, which is not even close to being true.

The absolute risk reduction, on the other hand, is always a much more modest number. Using the same example above, the absolute risk reduction in the drug group would have been a paltry one-tenth of a percent, or 0.1% (0.002 - 0.001). That’s not a very catchy headline, is it? “New drug reduces risk of dying by one-tenth of a percent”. It just doesn’t grab you the same way. But this is actually a more realistic view of what happened in the study and what we could expect to happen in the real world.

In fact, one could just as accurately say that in this hypothetical study, a patient has a 1-in-1000 (0.1%) chance of their life being saved by the drug. Said another way, 1,000 patients would have to be treated with this drug in order to save a single life. This measurement is called the Needed Number to Treat, and is another means for interpreting the results of clinical trials.

With that in mind, let’s examine the data from the JUPITER study. The actual numbers were 198 deaths out of 8901 in the statin group and 247 deaths out of 8901 in the placebo group. The relative risk reduction for total mortality (deaths) in the drug group was 19.8% [(247/8901 - 198/8901) / (247/8901)]. That means that the risk of death for people taking Crestor was 19.8% smaller than those taking placebo.

But what happens when we look at the absolute risk reduction numbers? According to the data, 2.77% (0.02774) of people taking the placebo died after two years versus 2.24% (0.02224) of people taking Crestor. This amounts to a difference of 0.55%, or one-half of one percent.

Here’s a graphical illustration of the difference in mortality between the Crestor and placebo group:

If you’re having trouble making much of a difference, I don’t blame you!

To make this even more clear, let’s use the Needed Number to Treat method of evaluating these results. According to the study data, 182 people would have to be treated with Crestor for two years in order to save a single life.

Now that may not sound like a large number to you, especially if yours was one of the lives saved. However, when evaluating the viability of any potential treatment three considerations (above and beyond the efficacy of the treatment) must be taken into account: cost, side effects, and alternatives.

Let’s look at cost first. The cost of one patient taking Crestor for one year is approximately $1,300. Therefore, to prevent 49 deaths 8,901 people would have to take Crestor for two years at a cost of $23 million dollars. That is an enormously expensive treatment by any measure.

Second, this particular study did not register significant side effects in the statin group. This is very fishy, though, since nearly every other study on statins to date has shown significant side effects and the approval of Crestor itself was delayed by the FDA due to concern about Crestor side effects.

While all statins are associated with rare instances of rhabdomyolysis, a breakdown of muscle cells, Crestor had shown in studies before its approval that the potentially deadly disease had surfaced in seven people. Crestor’s potential muscle- and liver-damaging side effects become more worrisome and difficult to justify in patients who are essentially healthy.

What’s more, the study only lasted two years. That’s not long enough to adequately establish safety for the drug, especially if people are going to use it “preventatively”, which means they could be taking it for several years and even decades. Statins have caused cancer in every single animal study to date. Since cancer can take up to 25 years to develop after initial exposure to the carcinogen, we simply cannot know at this point that statins won’t also significantly increase the risk of cancer in adults.

Finally, before jumping on the statin bandwagon and recommending that we spend billions of dollars treating healthy people with Crestor, we should consider if there isn’t a less costly and risky way of preventing deaths due to inflammation and heart disease.

Wouldn’t you know it, there sure is!

For the last decade medical research has increasingly demonstrated that heart disease is caused not by high cholesterol levels, but by inflammation and oxidative damage. A full explanation of these mechanisms is beyond the scope of this post, but for more details you can read two previous articles: Cholesterol Doesn’t Cause Heart Disease and How To Increase Your Risk of Heart Disease.

So, if we want to prevent and even treat heart disease, we need to address the causes of inflammation and oxidative damage. Again, there’s not room to go into great detail on this here but in general the primary causes of inflammation and oxidative damage are 1) a diet high in polyunsaturated oil (PUFA) and refined flour and sugar, 2) lack of physical activity, 3) stress and 4) smoking.

We can thus prevent heart disease by avoiding PUFA and refined/processed food, getting adequate exercise, reducing stress and not smoking. These simple dietary and lifestyle changes are likely to produce even better results than a statin, for a fraction of the cost and without any side effects. In fact, the only side effects of this approach are improved physiological and psychological health! For more specific recommendations, read my article Preventing Heart Disease Without Drugs.

Taking a statin to “prevent” inflammation and heart disease is rather like bailing water with a pail to prevent a boat from sinking instead of simply plugging the leak. Unfortunately, our entire health care system is oriented around “bailing water with a pail”, which is to say treating the symptoms of disease, instead of “plugging the leak”, or addressing the causes of disease before it develops. The reason this is the case is because there’s a lot more money to be made from drugs, surgery and other costly interventions than there is from encouraging people to eat well, exercise and reduce stress.

Even if we ignore all of the issues I’ve pointed out above, the best thing we can say about this study is that a small group of unusual patients - those with low LDL-cholesterol AND high C-reactive protein - may slightly decrease their risk for all-cause mortality by taking a drug that costs them almost $1,300 per year and slightly increases their risk for developing diabetes.

That’s the best spin possible given the data from this study. Compare that to the mainstream media headlines, and you’ll have a clear understanding of how financial conflicts of interest are seriously damaging the integrity and value of clinical research.

At least the media wasn’t completely fooled. They did manage to at least include the perspective of sane doctors who questioned the desirability of millions of relatively healthy people taking drugs for the rest of their lives. According to the Wall Street Journal:

From the New York Times:

From Fox News:

If you know of someone who is considering a statin after reading about the JUPITER study, please do them a favor and send them a link to this article first. They should hear both sides of the story before making such a significant decision.

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On June 8th the New York Times published an article underscoring these consequences and illuminating the risks that inevitably come with financial ties between researchers and drug companies.

The article revealed that Dr. Joseph Biederman, a world-renowned child psychiatrist at Harvard, accepted at least $1.6 million in consulting fees from drug makers from 2000 to 2007 but did not disclose any of this income to university officials. By failing to report this income, Dr. Biederman and colleagues may have violated both federal and university research rules designed to prevent conflicts of interest.

Dr. Biederman is one of the most influential researchers in child psychiatry. Although many of his studies are small and often financed by pharmaceutical companies, his work has nevertheless directly contributed to a controversial 40-fold increase from 1994 to 2003 in the diagnosis of pediatric bipolar disorder and a concurrent rise in the use of powerful antipsychotic medicines in children.

We know from my previous post that it has been shown that studies funded by pharmaceutical companies are more likely to show positive results for the drug. We also know that the veracity of clinical trials which are the basis of approval of new drugs by the FDA has been called into question in recent studies because of three major flaws: conflicts of interest on the part of investigators (like Biederman); inappropriate involvement of research sponsors (drug companies) in study design and management; and publication bias in disseminating results (if a study has negative results, the drug company doesn’t publish it).

When a researcher like Dr. Biederman is paid millions by a drug company to study it’s product, we must wonder whether we can expect his work to be objective and accurate. But when that researcher repeatedly lies about the money he received, the integrity of his work should be in serious doubt.

In one revealing example, Dr. Biederman reported no income from Johnson & Johnson for 2001 in a disclosure report filed with Harvard University. When asked to check again, he said he received $3,500. But Johnson & Johnson told Congressional investigators that Mr. Biederman was paid $58,169 in 2001.

The consulting arrangements of Dr. Biederman’s entire research group at Harvard were already controversial because of the researcher’s advocacy of unapproved (”off-label”) uses of psychiatric medicines in children. Dr. Biederman and his colleagues have promoted the aggressive diagnosis and treatment of childhood bipolar disorder with antipsychotic drugs - although these drugs have never been approved for such use. In fact, neuroleptic drugs have not been approved for use in children at all.

As a result of Dr. Biederman’s promotion of both the diagnosis and treatment for childhood bipolar disorder, antipsychotic drug use in children has exploded. Roughly half a million children and teenagers were given at least one prescription for an antipsychotic in 2007, including 20,500 under 6 years of age, according to Medco Health Solutions, a pharmacy benefit manager.

The dramatic increase in antipsychotic prescriptions in children has occurred despite the lack of evidence that these medication improve children’s lives over time. On the contrary, it is well known that children are susceptible to the weight gain and metabolic problems caused by the drugs. Children typically gain twice as much weight in the first six months on atypical neuroleptic drugs (risperidone, olanzapine, etc.) as they should through normal growth, adding an average of 2 to 3 inches to their waistline. This is mostly abdominal fat, which also increases their risk of diabetes and heart disease.

There is also some evidence which suggests that these drugs may cause permanent changes to the structure and function of the brain (Breggin 1997). In other words, they cause brain damage.

The research of Dr. Biederman’s group, which has served as the basis for the rise in bipolar diagnoses and antipsychotic use in children, has been widely criticized by other psychiatrists and researchers.

The studies published by Dr. Biederman’s group were so small and “loosely” designed that they were largely inconclusive. In some studies testing antipsychotic drugs, the group defined improvement as a decline of 30 percent or more on a scale called the Young Mania Rating Scale, which is well below the 50 percent change that most researchers use as the standard.

Controlling for bias in these types of studies is particularly important, given that the scale is subjective and depends on reports from physicians, parents and children.

More broadly, psychiatrists have said that revelations of undisclosed payments from drug makers to leading researchers are especially damaging for psychiatry.

“The price we pay for these kinds of revelations is credibility, and we just can’t afford to lose any more of that in this field,” said Dr. E. Fuller Torrey, executive director of the Stanley Medical Research Institute, which finances psychiatric studies. “In the area of child psychiatry in particular, we know much less than we should, and we desperately need research that is not influenced by industry money.”

I couldn’t have said it better myself.

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Much of what I write may challenge your current beliefs and contradict what you’ve heard about depression and antidepressants. My hope is that today’s post about the influence of the pharmaceutical industry on doctors, researchers and patients will inspire you to re-examine what you’ve been told so far and approach everything you hear in the future with a “healthy skepticism”.

The truth is that all of our beliefs about depression have been tainted, quite intentionally, by the more than $20 billion spent each year by pharmaceutical companies to promote their drugs (an amount greater than the gross domestic product of all but 70 of the world’s richest nations). In 2000, the pharmaceutical industry had a combined lobbying and campaign contribution budget of $200 million - larger than any other industry (Wayne & Peterson, 2001). The industry has 625 registered lobbyists, more than there are members of congress (Wayne & Peterson, 2001). The industry also underwrites about 70% of clinical drug trials in the United States (DeAngelis et al., 2001).

Consumer Reports has detailed the marketing strategies used by drug companies, including:

• giving free samples and information to doctors
• advertising in medical journals
• using “ask your doctor” media advertisements aimed directly at the consumer (the U.S. and New Zealand are the only two countries that allow this)
• sponsoring promotional dinner meetings with substantial gifts or even cash provided for attendees
• paying consultants to speak at scientific meetings where it is possible to circumvent FDA guidelines that require disclosure of side effects
• funding only those research projects that have a high likelihood of producing favorable results for a particular drug company’s product
• terminating negative studies before they are ready for publication
• not publishing studies with negative results
• offering to pay journalists to cover their products
• helping to fund patient advocacy and other public interest groups so the consumer group appears to be publicly carrying the banner of a particular drug

How can we possibly rely on information that is so inexorably intertwined with corporate interests? Corporations have very little motivation to share information that could harm sales of their products, as they are required by law to maximize profits for their shareholders. On the contrary, they have much incentive to do everything in their power to suppress such information. Several studies have shown that researchers who produce data that is contrary to the interests of the pharmaceutical industry risk legal, professional, or even personal attack - directly or indirectly financed by the industry. (Bosley, 2002; Healy, 2002; Monbiot, 2002).

As researcher David Antonuccio points out in his excellent article Antidepressants: A Triumph of Marketing over Science?:

Clinical trials are the basis of approval of new drugs by the FDA, but their reliability is seriously in doubt because of three major flaws: conflicts of interest on the part of investigators; inappropriate involvement of research sponsors in their design and management; and publication bias in disseminating their results. (Quick, 2001)

The situation has become so dire that in September of 2001 the editors of 13 leading medical journals published a joint editorial in which they said:

Huh? Wouldn’t you expect researchers to have these rights already? In many cases, they don’t.

The editor of the prestigious New England Journal of Medicine argued in a separate editorial that the editors didn’t go far enough in their rebuke:

The conflicts of interest between researchers and drug companies is bad enough. But what’s even more distressing is that many doctors do not even read the research to learn about the drugs they are prescribing. Jerry Avorn, a Harvard Medical School professor and drug researcher is a leading authority on how physicians are educated about new drugs. He acknowledges that most physicians have only minimal knowledge about drug studies. Instead, Dr. Avorn has this to say about where most physicians get their knowledge about drugs:

There are now over 90,000 pharmaceutical reps walking the halls of medical offices around the U.S. Since there are less than 600,000 office-based doctors in the U.S. today, there is approximately one full-time drug rep for every six physicians. The drug reps bring free food for office staff, free samples for distribution to patients, free pens, free textbooks and other free gifts. They are also sometimes authorized to provide free vacations for physicians who would enjoy spending a weekend with other physicians in places like Hawaii or the Caribbean hearing the latest “research” on the effectiveness of a drug. In 2006, the pharmaceutical industry spent $2 billion on these types of events alone.

Does all of this advertising and promotion actually influence doctors? You bet it does. A government report found that in just one year the most heavily advertised drugs had prescription increases of 25% (U.S. General Accounting Office, 2002). There is even a formula that generally applies to drug advertising: each dollar spent on advertising increases sales by $4.

Even more discouraging than the influence of drug companies on doctors is the influence of patients who’ve been subjected to drug company advertising on doctors! A study published in the Journal of the American Board of Family Practitioners reported that 49% of patient requests for drugs or other requests prompted by “direct-to-consumer” advertising were not clinically appropriate. Yet 7 out of 10 times, physicians gave into the requests. (And that is by their own admission; there is likely a percentage of physicians who do not want to admit they write prescriptions or order tests on the basis of patient requests.)

The influence of advertising on doctors and patients is particularly relevant in the case of antidepressants. By a wide margin the largest amount spent on advertising by drug companies was on antidepressant promotion - a whopping $367 million dollars per week!(U.S. General Accounting Office, 2002) In fact, it appears that DTC advertising may be the single most effective way a drug company can increase the number of people who are diagnosed with depression and then will begin taking antidepressants (Donohue, 2004).

I could go on, but I think you get the point. As consumers and patients we simply cannot rely on profit-driven drug companies to give us accurate information about their products. And unfortunately, because of the massive conflicts of interest that exist between researchers, physicians and the pharmaceutical industry - we cannot necessarily rely on our doctors or even scientific studies to show us the way.

Luckily for us, there are still studies being done by independent researchers and those brave enough to risk the ire of the drug companies that we can turn to for honest, unbiased data. Unsurprisingly, these studies often have very different results than those sponsored by the industry. Thanks to the Freedom of Information Act, some researchers have even been able to access the studies done by the drug companies that they never published (obviously the ones that were least favorable to their drugs).

When these independent and unpublished studies are analyzed, a very different picture of depression and the efficacy of antidepressants begins to emerge.

Contrary to popular belief:

You might be shocked by some of these statements. Though I was already very skeptical about antidepressants before beginning this research, I myself have been blown away by the complete lack of evidence supporting the theory that depression is a biological disease and the very strong evidence that antidepressants are no more effective than placebo.

I’ll be writing in more detail about several of the points to come in the coming weeks, so please stay tuned!

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The numbers were gathered last year by Medco Health Solutions Inc., which manages prescription benefits for about one in five Americans.

The data indicates that 51 percent of American children and adults were taking one or more prescription drugs for a chronic condition, up from 47 percent in 2001. The use of drugs to treat health problems was seen in all demographic groups:

• Almost two-thirds of women 20 and older
• One in four children and teenagers
• 52 percent of adult men
• Three-quarters of people 65 or older

28 percent of women and 22 percent of men over 65 take five or more medicines regularly.

Exactly what medications are people taking? In 2006, the top five drugs by sales were Lipitor, Nexium, Prevacid, Advair Diskus and Singulair. Lipitor lowers cholesterol, Nexium & Prevacid lower stomach acid, and Advair Diskus and Singulair address asthma and allergies respectively.

The drugs on this list reveal much about the weakness of the mainstream medical model. Cholesterol and stomach acid are both normal, protective substances in the body. Cholesterol is no more the cause of heart disease than stomach acid is the cause of GERD or ulcers. But one of the fundamental flaws of western medicine is its tendency to treat the symptom or effect rather than the cause. Unfortunately for patients, doing so can actually make things worse, not better.

Cholesterol plays many essential roles in the body, and and lowering it arbitrarily not only doesn’t prevent heart disease, but can actually increase the risk of dying from a heart attack in elderly people. Likewise, stomach acid is crucial in protecting us from the pathogens we might otherwise ingest with food. Stomach acid is also required for protein digestion. It is well-established in the scientific literature that the primary cause of ulcers is a bacterium called h. pylori - not stomach acid. And there is also evidence suggesting that GERD (gastro-esophageal reflux disease) is caused by low - not high - stomach acid.

But I digress.

The scariest part of this study is the surge in children’s use of medicines to treat weight-related problems and other illnesses previously considered adult problems. Medco estimates about 1.2 million American children now are taking pills for Type 2 diabetes, sleeping troubles and gastrointestinal problems such as heartburn.

The majority of these conditions - diabetes, sleeping troubles and gastrointestinal issues - can be treated by simple diet and lifestyle changes. These changes have none of the adverse effects and risks of drugs, and their benefits extend far beyond the potential therapeutic action of the medications.

Medication has improved and even saved the lives of many in this country and around the world. Yet there’s a difference between drugs that are “medically necessary” and drugs that are prescribed in lieu of other less harmful and risky - but more labor intensive - interventions such as diet and exercise.

But as Dr. Robert Epstein, cheif medical officer at Franklin Lakes, N.J.-based Medco said, ‘We’ve become a couch potato culture (and) it’s a lot easier to pop a pill” than to exercise regularly or diet.

I couldn’t have said it better myself.

One reason for the increase in medication use is the pharmaceutical industry’s “relentless advertising”. Since that is unlikely to change anytime soon, experts say the proportion of Americans on chronic medications can only multiply.

“Unless we do things to change the way we’re managing health in this country … things will get worse instead of getting better,” predicted Daniel Jones, a heart specialist and dean of the University of Mississippi’s medical school.

Luckily, we don’t have to wait around for that to happen. As individuals we can take responsibility for our own health care using diet, exercise and lifestyle changes. We can choose to use “alternative” modalities such as acupuncture and homeopathy to keep us healthy. And we can take action to reduce stress and promote emotional and psychological well-being.

Recommended Links

• Americans Taking Prescription Drugs in Greater Numbers

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