Chapter 10: Article 1
If you recall back the very beginning of our journey together, you'll remember I introduced you to Ben Goldacre. He gave a Ted Talk 8 years ago that should have been broadcast in whole on the nightly news, GLOBALLY, but it wasn't. The title of his talk, What doctors don't know about the drugs they prescribe, is something we need to really reflect on. We put our trust, and our lives into the hands of doctors. We value their education, their intellect, their ability to weigh and evaluate the science. Scientific research guides every decision they make. So what if doctors don't know, simply because the evidence base of scientific research is lacking, or worse, what if it's purposefully biased? Dr. Goldacre explained (emphasis mine):
...publication bias. That's the technical term for the phenomenon where unflattering data gets lost, gets unpublished, is left missing in action...
...this problem of negative results that go missing in action is still very prevalent. In fact it's so prevalent that it cuts to the core of evidence-based medicine. So this is a drug called reboxetine, and this is a drug that I myself have prescribed. It's an antidepressant. And I'm a very nerdy doctor, so I read all of the studies that I could on this drug. I read the one study that was published that showed that reboxetine was better than placebo, and I read the other three studies that were published that showed that reboxetine was just as good as any other antidepressant, and because this patient hadn't done well on those other antidepressants, I thought, well, reboxetine is just as good. It's one to try. But it turned out that I was misled. In fact, seven trials were conducted comparing reboxetine against a dummy placebo sugar pill. One of them was positive and that was published, but six of them were negative and they were left unpublished. Three trials were published comparing reboxetine against other antidepressants in which reboxetine was just as good, and they were published, but three times as many patients' worth of data was collected which showed that reboxetine was worse than those other treatments, and those trials were not published. I felt misled.
...This is a cancer at the core of evidence-based medicine. If I flipped a coin 100 times but then withheld the results from you from half of those tosses, I could make it look as if I had a coin that always came up heads...this is exactly what we blindly tolerate in the whole of evidence-based medicine. And to me, this is research misconduct.
Dr Marcia Angell, the former Editor-In-Chief of the New England Journal of medicine gave a lecture titled, The Truth About the Drug Companies (link Here). Below are a few summary points of the deficiencies that she described:
clinical trials, which are sponsored by the industry are usually designed by industry to optimize the potential of favourable conclusions for the drug
clinical trials test drugs in young, healthy people, because they are less likely to experience side effects
clinical trials provide important information, but that data is not a true representation of all potential side effects. Angell describes how once a drug is licensed for use in the general population, people of varying health conditions, people with different exposures to various medications, all are given the drug, not just the young and healthy. Because of that, the drug side effects increase and can include much more serious reactions than was observed during the clinical trial.
Angell explained an aspect of testing that allows for inferior drugs to flood the market. She stated:
[Drug] Approval depends on the company demonstrating in clinical trials that their new drug is reasonably safe and effective. But compared with what? They don't have to compare their new drugs with existing drugs to treat the same condition. They merely have to compare their new drug with a sugar pill, with a placebo. So the drug merely has to be better than nothing. Nothing is what the sugar pill is. This is a very low standard. People usually think that FDA approval means that a drug offers something better, that it wouldn't come on the market unless it offers something better. But for all we know, every drug that comes on the market to treat a particular condition, is worse than the one before. We have no way of knowing, is it better? Is it worse? Is it much the same? All we know is that it's likely to be more effective than a placebo.
But what happens if the drug is never compared to a placebo, not even originally?
The FDA subtly acknowledges within their Code of Federal Regulations that their testing format for vaccines is inferior to that for drugs. The Code of Federal Regulations 21 CFR 201.57 states (emphasis mine):
Any statements comparing the safety or effectiveness of the drug with other agents for the same indication must, except for biological products [vaccines], be supported by substantial evidence derived from adequate and well-controlled studies as defined in 314.126(b)...For biological products, such statements must be supported by substantial evidence.
The omission in that regulation is revealing. Though pharmaceutical drugs need "substantial evidence" demonstrated through "adequate and well-controlled studies,"vaccines aren't held to that same standard. Vaccine studies do NOT have to meet the standard of "adequate and well controlled."
The purpose of a vaccine is to alter the immune system. The immune system determines a person's level of health for the rest of their life. And despite that important fact, the long term health of these vaccine trial participants has NEVER been measured, evaluated and compared against a group that received a placebo.
That means that researchers NEVER established a baseline of safety initially. If a baseline of safety was never established, then comparing one drug to another forevermore determines nothing on that front (remember vaccines ARE compared against each other). In that case, Angell's words still ring true, "for all we know, every drug that comes on the market to treat a particular condition, is worse than the one before. We have no way of knowing"...
In Angell's lecture she goes on to state:
When a drug is approved the data on effectiveness are usually pretty reasonably good....the data on safety are less good, because it takes a larger population and a more typical population to see signals of danger.
Dr. Richard Horton, the Editor-In-Chief of the Lancet published an article about the poor quality of research filling the medical journals, he stated:
...much of the scientific literature, perhaps half, may simply be untrue.
...The apparent endemicity of bad research behaviour is alarming. In their quest for telling a compelling story, scientists too often sculpt data to fit their preferred theory of the world. Or they retrofit hypotheses to fit their data.
...Part of the problem is that no-one is incentivised to be right. Instead, scientists are incentivised to be productive and innovative.
Further to that, Cochrane has explained that favourable vaccine conclusions are often reached, even when the data within the study doesn’t actually support the final conclusions drawn. To quote Cochrane (Link Here):
Conclusions favourable to the use of influenza vaccines were associated with a higher risk of bias. In these studies, the authors made claims and drew conclusions that were unsupported by the data they presented. In addition, industry-funded studies are more likely to have favourable conclusions, to be published in significantly higher-impact factor journals and to have higher citation rates than non-industry-funded studies. This difference is not explained by either their size or methodological quality
A British Medical Journal (BMJ) article evaluated the body of evidence for influenza vaccination, and concluded (emphasis mine):
What is already known on this topic:
Study sponsorship [by pharmaceutical industry] is associated with optimistic results
Influenza vaccination continues to be recommended globally, despite growing doubts about the validity of the scientific evidence underpinning policy recommendations
What this study adds:
Evidence is of poor quality, and studies with conclusions in favour of vaccines are of significantly lower methodological quality
Influenza vaccines studies sponsored by industry are published in journals with higher impact factors and are cited more but are of similar size and quality to the others
In 2014, Radio Canada International (RCI) interviewed Dr. Lexchin on the topic, in the interview he states:
Dr. Lexchin: First of all, since the drug companies are paying for these trials, they are the ones that own the data. Now they have to turn the data over to Health Canada in order to get the drug on the market, but they don't have to show the data to anybody else. And there may be things that Health Canada will have missed. But Health Canada also regards this as proprietary data and won't release it to anybody without the drug company's agreeing....
Interviewer: There was a movement by some universities to make sure that if they are doing cooperative research with big companies, such as pharmaceutical companies, that this concept of proprietary not apply to the universities. In other words, if a trial goes badly, that the university can in fact release that information, because I believe you've pointed out that sometimes...when the drug doesn't perform well, the pharmaceutical company will not report that. So it's not generally known that the drug is not working as its supposed to.
Dr. Lexchin: Well, since a number of scandals in the 90s and 2000s, there's certainly been a push by universities to make sure that their researchers, when they sign an agreement to do a trial for the drug company, that that agreement has a clause in it that says that people can publish no matter what the findings are. So that's a good thing. But what's been happening lately is that more and more of the research is moving out of the universities and into the communities. So drug companies will engage in community pediatricians or community gastroenterolgosits for their research, and at that level you don't have these kinds of safeguards around publication of research.
Our doctors can only serve us well if the scientific research that they refer to is of the highest quality. Doctors around the world are very clearly speaking out about the financial influence from the pharmaceutical industry which has compromised the quality of the published scientific research.
CONTINUE to the next article in this series: Ch10: Part 2
Dr. Ben Goldacre - TedMED Talk Here
Dr. Richard Horton - Half of the scientific literature is untrue Here
Lecture by Dr. Marcia Angell - The Truth About the Drug Companies Here
FDA Regulations - Vaccine testing need not be adequate and well controlled Here
Cochrane Review - favourable research is often pharma biased Here
BMJ paper - research that is favourable towards the vaccine is often of poorer methodological quality Here
Dr. Lexchin - those who fund the research create the evidence Here