Both patients and doctors are being manipulated to the tune of billions of dollars.
The information in this blog post may shock you, but it is information that the public needs to be made aware of. The exploitation discussed here centers on the effectiveness of drug trials, and some of the ways big pharmaceutical companies manage to make health claims which are, in many cases, false.
The first thing to examine is how drug efficacy is calculated by pharmaceutical manufacturers. How do they arrive at their numbers in the first place? It’s not actually that complicated although most of us have been led to believe we need a PHD to make sense of their statistics. When a drug actually works, (think of the dramatic benefits of discovering insulin or penicillin), the results are so obvious that statistics or percentages quickly become secondary to the observable benefits. However, the math games begin when a new drug doesn’t work as well as hoped, when its benefits are not so obvious, or when profits may be in jeopardy.
The illusion of percentages
Imagine you were given a choice been two prizes. Prize one is 10% of a mystery amount of money, and prize two is 90% of a mystery amount of money. All things being equal, 90% seems like the better choice. However, there is a catch. What if prize one was 10% of a million dollars, ($100, 000), and prize two was 90% of a hundred dollars ($90)? Does that change your mind about what the better choice is? Of course it does.
What is missing in this scenario is something called an absolute number. Both of the percentage values presented are accurate; 10% of a million is $100, 000 and 90% of one hundred is 90$. But, if we want to know which is the better choice, we need to know something called an absolute value. It is with the absolute value that we determine if a result is significant. Otherwise any number you come up with is only useful (in this case) as a marketing tool. It is completely useless for the purposes of comparing the real benefits of choices. If we don’t know what the real benefits are then who cares about percentages? This factor particularly important when evaluating treatments that could be beneficial but which are associated with risks of significant negative side-effects. Without it, there is no way to assess a risk-benefit ratio.
Remember these words, absolute and relative. Absolute numbers or values are the real/precise numbers. Relative numbers or values are dependent on other numbers. In other words, they are relative to other (absolute) numbers. Percentages are relative. With a percentage in isolation, you do not know a precise number. You only know one half of the available data and it is the one advertiser companies want you to focus on. Ninety percent improved or effective sounds like a significant number. However, until you know the absolute value of what it represents or what it is compared to, it could mean nothing at all (or worse!).
If you walked into a medical clinic and you were given a piece of paper saying that you were facing a 100% increase in your risk of contracting a given disease it would sound really terrifying! That is because it sounds like a guarantee that you will get sick. However, discovering that it is actually just a percentage of a larger number means it could very well be a paper tiger. What if that 100% risk represents an increase from one to two out of a thousand in the general population? Would you still be terrified now that you know the absolute number being compared to?
Let’s step away from medicine for a moment and look into really clear example of stacking the odds … gambling … what if someone told you could increase your odds at winning the lottery by 100%? Pretty good deal right? Whoa, … not so fast …
Canada’s biggest lotto jackpot was won by a group of oil workers in our province of Alberta. This lucky group of 17 took home $54.3 million in October of 2005. Not bad for a day’s purchase. The truly impressive number in this equation was actually the odds of winning: one in 13,983,816. So, if you increased your odds of winning the lottery by 100%, in this case it would mean … drum roll …TWO in 13,983,816!
Not quite worth a lot of risk once you know the absolute numbers, even when the likelihood of winning is increased by a whopping 100%.
It might seem juvenile to put it in the terms above, but prescription drugs and risky surgeries are encouraged this way all the time. The data is accurate, but its value is not being accurately portrayed. This is like 90% of 100 dollars versus 10% of a million; the percentages mean nothing without the full picture.
My favourite example of this kind of trickery was the Lipitor ads that boldly told us that the drug would reduce heart attack risk by 36%. Now that you know that percentages by themselves are useless because they are relative, it leads us to ask what the real numbers are.
Here’s how they got the data they are bragging about:
The 36 percent relative risk reduction figure came from a study published in Drugs called Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial.
This research was a subcategory from a larger study that looked at 20,000 subjects with high blood pressure as well as three other cardiovascular risk factors. The study participants were randomized into two groups. Each group took one or the other of two blood pressure lowering medications. From within the larger group, around 10,000 subjects were selected who also had cholesterol levels at or below 250 mg/dl (6.5 mmol/l). In addition to the blood pressure medications, half of this group got 10 mg of Lipitor (atorvastatin) per day while the other half got a placebo along with their blood pressure medication. Note: high blood pressure is itself a major factor in the risk of a heart attack. Further note that the results of this work can only be applied to people who already have high blood pressure and two other risk factors for heart disease. If you don’t have those risks, the drug has no benefit. Most prescribing doctors forget or don’t mention that part of the study.
In the Lipitor/placebo arm of this research, the endpoint for an individual’s participation was defined as a non-fatal heart attack or death from heart disease.
After around 3 ½ years, this section of the project was discontinued because there were a noteworthy number of either heart attacks of deaths from heart disease in the placebo group. As a result, the researchers felt it was unethical to prolong the study.
When the data were assessed, it turned out that the group taking Lipitor experienced a 36 percent decrease in relative risk for heart disease. Thus, the outpouring of advertisements for Lipitor ensued.
These results sound awesome, but they are not actually that impressive. 36% is the relative risk reduction. Look at the graph from the study, the vertical axis tells you that the absolute percentage difference is a drop from 3.0% to 1.9%. That’s only a difference of 1.1%!! According to Liptor’s own webpage at the FDA absolute reduction is only 1.2%!!
Dr. Michael Eades MD has an excellent way of illustrating this difference with the following image:
The side effects from statin drugs include: muscle pain & muscle wasting, liver damage, rashes, elevated blood sugar/type 2 diabetes, as well as nerve damage. Considering that these drugs are 98.8% ineffective, what the heck are we taking them for?
This is why you always, always want to know the absolute risk before you make a decision on anything based on relative risk. Because absolute risk numbers are usually pretty low in drug studies, the pharmaceutical industry typically uses them \to sell their medicines. When someone tells you to take a drug, ask about the absolute risk associated with its research.
According to a review published in the Expert Review of Clinical Pharmacology, other studies of statins show similarly unremarkable results. In absolute terms, statin users had between 1.2 and 1.5 percent fewer cardiovascular complications than those taking placebo. The authors believe that for statins, “…their modest benefits are more than offset by their adverse effects.” Statin drugs have over 300 listed side-effects with the FDA, which include heart failure and the progression of heart disease. Yes, you read that correctly; this is a heart medication approved by various international health agencies which actually promotes heart disease. That sure is an amazing business model. It involves creating a solution, which is really exacerbating a problem, so you need to keep buying more of the supposed solution, which is actually making the problem even worse. The potential for profit is amazing!
In March of 2015, Okuyama and colleagues at Nagoya City University published a report called Statin Drugs Stimulate Atherosclerosis and Heart Failure: pharmacological mechanisms. In this report they explain the biochemical basis for their claim that statins may contribute to clogged arteries and heart muscle failure. The researchers in question cite several mechanisms by which statin drugs promote heart disease. They close by saying that, “…the epidemic of heart failure and atherosclerosis that plagues the modern world may paradoxically be aggravated by the pervasive use of statin drugs.” My! Oh My! It sure is a good thing that statins decrease heart attack rates by 33% (relative) on paper or this entire category of very profitable drugs would be totally useless. The impact on Big Pharma would be catastrophic. (Please note the sarcasm here!)
Primary prevention vs. secondary prevention
If that wasn’t shocking enough, there’s more! If we want to get to the real efficacy rates behind these magical prescription drugs, we also need to understand primary vs. secondary prevention. Primary prevention aims to prevent disease or injury before it occurs at all, while secondary prevention aims to reduce the impact of a disease or injury that has already occurred. There are huge differences between these two groups, as well as their relationship to risk benefit ratios.
Making billions by using a dangerous unproven drug for prevention
Originally, statin drugs were prescribed only for secondary prevention. They were used in the prevention of a second heart attack or stroke if a patient had already suffered one and had clear signs of heart disease. In other words, clear and present risks justified risks. But, this was not a good way to expand markets and make more money. To help promote the use of these drugs to otherwise healthy people, AstraZeneca, the maker of the cholesterol lowering drug Crestor, funded the JUPITER study, which was published in the New England Journal of Medicine in 2008. This should already be sending up huge red flags, since the authors of the study stand to make billions of dollars based on its results. In fact, regarding conflicts of interest in this article, the Institute of Science in Society voiced their concerns that:
“The lead author is a co-holder of the patent for the hsCRP test used, which became the standard method of measurement at $50.00/test. Nine of the 14 authors had significant financial ties to AstraZeneca, whose investigators also collected, controlled, and managed the raw data and monitored the collection sites. It is well established from other drug company sponsored studies that bias can creep in, such as the preponderance in the placebo group of patients with a family history of heart disease or metabolic syndrome, both of which significantly increase risk.”
In other words the deck was stacked in advance of the study. The placebo group (representing the general population) had a higher proportion of subjects likely to develop heart problems. They would have done more poorly that the test group even if medications were not being administered. Even the smallest results in the test group would appear much more significant than they really were.
The JUPITER study boasted that statin drugs could lower the risk of heart attack by 54 percent, the risk of stroke by 48 percent, the risk of needing angioplasty or bypass surgery by 46 percent, and the risk of death from all causes by 20 percent. But remember they are using relative statistical numbers to boost their results. If you look at absolute risk, statin drugs benefit just 1 percent of the population. This means that out of 100 people treated with the drugs, one person will have one less heart attack.
According to Dr. David M. Diamond, a professor of psychology, molecular pharmacology and physiology at the University of South Florida, “In the Jupiter trial, the public and healthcare workers were informed of a 54 percent reduction in heart attacks, when the actual effect in reduction of coronary events was less than 1 percentage point…”
Is this all beginning to sound familiar? Have you noticed that it all adds up to billions in profits?
According to a May 29th 2013 article in the very pro-business Forbes magazine:
“Statin drugs, already the most-prescribed drug category, saw their use climb 17% to more than 214 million monthly prescriptions annually, according to data provided by IMS Health, a consulting firm that can track drug prescriptions at the pharmacy level.” The article continues and uses the manipulated risk information mentioned above to push the drug even more. It uses statements like “These drugs have been shown, with quite a lot of evidence, to reduce the risk of heart attacks and deaths in a wide range of patients. Those taking statins have about a 20% lower risk of a heart attack.” These statements are a far cry from the 1 percent improvement (absolute) cited by Dr Diamond and by the Institute of Science in Society. However, it is probably worth mentioning that Forbes’ interest is in profit not efficacy.
According to an article in The Telegraph, (Statins: the drug firm’s goldmine) Pfizer’s Lipitor was the world’s top-selling medicine last year, according to IMS, raking in sales of $13.3 billion. Take a deep breath before you read the following … people spent 13.3 billion dollars for a drug that is likely to do nothing, and is even more likely to cause significant side-effects like cancer, erectile dysfunction and muscle wasting. Worst of all, many of these prescriptions, tests and appointments are paid for with tax/insurance dollars, meaning that every single one of us was being robbed that year by Pfizer.
Chemotherapy: The 2% Gamble
A paper entitled Contribution of Cytotoxic Chemotherapy to 5-year Survival in Adult Malignancies, published in 2004 in the Australian Journal of Clinical Oncology, analyzed the accuracy of the actual benefit claimed by chemotherapies in the treatment of adults with the most common forms of cancer. The mainstream media completely ignored the findings of this extremely important paper. It was a meta-analysis. A meta-analysis is a statistical technique for combining the findings from independent studies. It is the form of research most often used when assessing the clinical effectiveness of healthcare interventions. It does this by combining data from multiple randomized control trials. This is a gold standard method for determining the absolute effectiveness of a given medical treatment. Let’s see what they found out regarding the true effectiveness of chemotherapy.
This carefully detailed Australian study was based on an analysis of results from all of the randomized, controlled clinical trials (RCTs) performed in Australia and the US which reported a statistically significant increase in 5-year survival due to the use of chemotherapy in adult malignancies. Survival data was obtained from the Australian cancer registries and the US National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) registry. The research covered the period of January 1990 until January 2004.
In those cases in which the data were uncertain, the authors intentionally erred on the side of over-estimating the assistance of chemotherapy. Despite this statistical benefit of the doubt, the study determined that overall chemotherapy still contributed to a mere 2 percent improved survival in cancer patients (when compared to the absolute total number of subjects).
Yet despite the mounting evidence of chemotherapy’s lack of effectiveness in prolonging survival, oncologists continue to present chemotherapy as a rational and promising approach to cancer treatment.
One of the papers examined in the meta-analysis referenced above was from 1998. In this clinical trial, out of a total of 10,661 women who were newly diagnosed with breast cancer, 4,638 women were assessed as eligible for chemotherapy. Of these 4,638 women, only 164 (3.5 percent) actually gained some survival benefit from chemotherapy. As the authors point out, even the use of newer chemotherapy regimens for breast cancer, including the taxanes and anthracyclines, may only raise survival by an estimated additional one percent. However, this minor benefit is achieved at the expense of an increased risk of cardiac toxicity and nerve damage.
Woah … those are some pretty heavy statements! What credentials do the authors of this paper have in order to make these types of judgements? Well, all three of the paper’s authors are oncologists. Lead author & Associate Professor Graeme Morgan is a radiation oncologist at Royal North Shore Hospital in Sydney; Professor Robyn Ward is a medical oncologist at University of New South Wales/St. Vincent’s Hospital. The third author, Dr. Michael Barton, is a radiation oncologist and a member of the Collaboration for Cancer Outcomes Research and Evaluation, Liverpool Health Service, Sydney. It should also be noted that Prof. Ward is also a member of the Therapeutic Goods Authority of the Australian Federal Department of Health and Aging. This is the official body that advises the Australian government on the suitability and efficacy of drugs to be listed on the national Pharmaceutical Benefits Schedule (PBS). It is roughly the equivalent of the US Food and Drug Administration. These men are hardly lightweights in the field of cancer research.
Given education about statistics painting this form of treatment as achieving only a two percent improvement in survival rates, would the general public opt for chemotherapy as a rational approach to cancer treatment? Shouldn’t we at least be given accurate information so as to make decisions which are rational and fact based?
A Third Method of Manipulation: Selective Publication
The third, and in many respects most un-nerving, way that drug data is manipulated to inflate benefits is the selective publishing of studies to show a majority of positive results. If the results are not positive, or if they show significant side-effects that should be kept quiet, they are simply not published!
Consider the following findings. Researchers reported the findings of a meta-analysis in the New England Journal of Medicine. They conducted an analytical look at all the work done on antidepressants, both published and unpublished.
To begin with, the unpublished studies were very difficult to find. The researchers needed to search the FDA databases, call other researchers and hunt down hidden data under the Freedom of Information Act. What they eventually found was stunning.
After examining 74 studies relating to 12 drugs and involving over 12,000 people, they found that 37 of 38 trials with positive results were published. That is very nearly all of them. Only 14 of the 36 negative studies were published or in other words, less than 40%. Those negative findings which did get published were, in the words of the investigators, “…published in a way that conveyed a positive outcome.”
That leaves no question. The results were twisted to show the drugs to be more effective than they actually were!
As a closing comment, if we could describe the behaviours of the pharmaceutical industry in one word it would be “shameless!!” We are being sold a lie to the tune of billions of dollars a year, much of it coming out of everyone’s pockets in the form of insurance premiums and taxes. Though this article talks specifically about cholesterol, chemotherapy agents, and antidepressant medications, it is clear that these practices are also common in the dealings of the drug industry at large.
Feeling cheated? You should be …