KATE WILLIAM - How The Science Gets ‘Settled’ on Vaccines

Scores of people actually think the science is 'settled' on vaccines...and that's not by accident. Here's how the drug industry shapes your beliefs.

Almost 75% of U.S. clinical trials in medicine are now funded by the pharmaceutical industry.

A Phase III clinical trial may enrol 1000 – 5000 people over many years, and cost hundreds of millions of dollars to complete. Average cost per trial participant is around $36,000. That’s a lot of incentive to make it worth your while!

Analysis shows that trials funded by the industry are 5x more likely to recommend the experimental drug as treatment of choice, REGARDLESS of whether the results justify it, or not.

There a number of ways clinical trials can be manipulated to give the results you want – or the appearance of the results you want…

First, you choose the people who are most likely to give the results you want. If you are looking at the safety of a vaccine, you enrol those who are least likely to have adverse reactions, and exclude those with a history of seizures, recent fevers or illness, or any blood clotting disorder. (In the real world, these very people people are often urged to get the vaccine.)

Other methods used to increase the legitimacy (or sales) of your product include:
i) Seeding trials: Where a drug company induces a doctor to prescribe a certain drug to their patients, in order to gain feedback on the product. These are usually scientifically meaningless, have no clear end-points, but they are large-scale so represent considerable sales for the company. The doctor usually gets paid to enter patients in the trial.

ii) Switching trials: This is a variant of the seeding trial. Doctors are recruited to switch their patients from their usual treatment, to a new treatment. Again, the drug companies know that this will often lead to long-term customers.
iii) post-marketing surveillance: This is yet another variant of the seeding and switching trials, although with more scientific justification, as they are often published, and can provide important data on adverse effects. Again, doctors are paid substantial sums, and the patients may believe they are getting new and ‘better’ treatments.

iv) Dosage: The dose can be manipulated in order to give the desired results. For example, a competitor drug may be given at less-than-optimal dosage, to make the studied drug look more effective. Or the competitor drug may be given at higher-than-optimal dosages, to make the studied drug look safer.

v) Economic evaluations: These can be easy to manipulate, because they are too complex for the average journal editor or reader to fully understand.

Now, when you get the favourable ‘results’, you have to let the world know all about it! A major randomised trial with favourable results, published in a prestigious journal, is a major win for a drug company, and an essential step in creating a ‘blockbuster’ product.

A 2010 review of six major medical journals found that studies funded by industry are cited more often than those funded by other sources – more than twice as often in some journals.
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So, if the industry-funded studies are more likely to recommend the drug in question (regardless of actual results), and then those same studies are used as a foundation for other research, being cited far more often than independent studies…can you see how the drug industry is able to build up an impression of their products being ‘rigorously tested’ and ‘highly effective’?

The industry has figured out another way to keep their products in the editorial pages – it’s called ‘ghost-writing’. The drug company pays a writer to create an article containing ‘key marketing messages’, which is then sent to a doctor, who agrees to have his/her name attributed to the work in exchange for payment, before it is submitted to medical publications.

Studies suggest that anywhere from 8% to 75% of journal articles may be ghost-written.

Clearly, this might appeal to some doctors who want the prestige of being a published author, quite apart from the financial incentive. The pharmaceutical company has final control over the paper, and if a doctor is not compliant enough, they simply get no further projects.

In many cases, if not all, the ghost-writer and the honorary author have not even viewed the raw data, they have merely been supplied with a summary from the sponsor company. The honorary author is usually chosen because of their credentials, and their ability to influence other prescribers.

Of course, the desired effect of all this published data is threefold: a) it gives the appearance that the drug is thoroughly researched and widely accepted, b) which boosts doctor and patient confidence, c) while simultaneously providing an edge over rival products.

But…peer review!

At the heart of the scientific process is the concept known as peer review – where an author’s work is subjected to the scrutiny of other experts in the same field, before being published. The public perception is that the peer review process acts like a stop-gap that upholds the integrity of the scientific process, and filters out errors or fraud, but does it really?

The British Medical Journal decided to test for themselves how reliable the peer-review process is, by inserting major errors into papers before sending to reviewers. Some reviewers didn’t pick up any of the errors, while most picked up only about a quarter. Nobody picked up all the errors.

So far, the evidence suggests that the peer review process is ‘slow, expensive, ineffective, something of a lottery, prone to bias and abuse, and hopeless at spotting errors and fraud – but of course, the average internet troll doesn’t know that, yet!

The New England Journal of Medicine has long been ‘the journal to beat’, yet two former editors-in-chief left their role in the top job, and went on to publish books exposing the excessive influence of the drug industry.

Meta-Analysis
A meta-analysis looks at data from multiple studies, and is used as part of systematic review. Naturally, these are useful and important in the interpretation of data (and highly influential).

A systematic review of vaccine meta-analyses, found that the methodological quality of all 121 meta-analyses included in the review (100%), were unsatisfactory, and likely biased.

These are the same meta-analyses that are used to guide government policies and legislation, WHO guidelines, doctors opinion…

The Role of Media
In order to further spread the good news of your product, you also need to make some news headlines, via press releases. The media are usually fairly compliant – they want a catchy headline, and…after all, drug companies do help to fund their jobs, via billions of dollars in advertising revenue.

A review of health news and current affair items on free-to-air TV in Sydney, Australia, estimated that up to 42% may have ‘been triggered by press releases and other forms of publicity.

Advertising and press releases are not the only way the pharmaceutical industry can influence the media. Another avenue is through a situation known as an interlocking directorate. This occurs when the director of one company sits on the board of directors of another company.

Many of the major news corporations have directors who also sit on director boards for pharmaceutical companies – and these cosy relationships have been shown to effect how health news is portrayed.

According to research, ‘the media can play an important role in influencing both the demand and supply of medical treatments, REGARDLESS of evidence of effectiveness.
Media coverage can increase uptake of the seasonal influenza vaccine, especially if reported in a headline, that includes words such as ‘vaccine shortage’ [25]. (Creates a sense of urgency.)

The so-called ‘swine flu pandemic’, which turned out to be more panic than pandemic, featured experts and academics making media appearances, promoting the use of retroviral drugs. It was later found that those who promoted retroviral drugs, were 8 times more likely to have links to industry – via research grants, honorarium payments, advisory roles, employment, board membership, speaker’s fees, etc – than those who did not comment on their use.

Getting Your Product Approved
Of course, all your journal articles and press releases are kind of pointless if you can’t get your drug through the regulatory process. In the US, UK, Australia and Canada, the regulatory agencies are all funded by industry, rather than by government.

Congressional investigations and reports have made damning conclusions on both the CDC and FDA: "The Committee’s investigation has determined that conflict of interest rules employed by the FDA and CDC have been weak, enforcement has been lax, and committee members with substantial ties to the pharmaceutical companies have been given waivers to participate in committee meetings”.

If that’s not enough, you also have the ‘revolving door’ between government and industry – former employees now hired by drug companies to liaise with their former work-mates in the regulatory system. Studies suggest that more than half of former assessors at the FDA move on to positions within the pharmaceutical industry – obviously their ‘inside knowledge’ is extremely valuable to the drug companies.

Occasionally, the door swings in the opposite direction – pharma employees moving into government jobs. The current secretary of the Department of Health and Human Services (HHS), Alex Azar was formerly a pharmaceutical lobbyist, and president of the US division of pharmaceutical giant Eli Lilly and Co. In case you are not American, like myself, the HHS department guides the nation’s healthcare programs and policies, so…fairly influential.

Regulatory agents are not only funded by industry, but they also rely on industry to conduct the trials, provide the safety data, and notify them of any issues that may arise post-licensure. What could possibly go wrong?

The agencies themselves do not conduct clinical trials.

The Fate of Failed Clinical Trials
Now, what happens if, despite your best efforts, the clinical trials still didn’t give the results you wanted? You can still salvage your reputation by:
a) Just cut the trial short – to save money, or
b) Simply decide not to publish unfavourable trial results, even though doing so is considered to be scientific malpractice.

Research shows that less than half of government-funded clinical trial results are published in peer-reviewed medical journals within 30 months of trial completion.

One pharmaceutical company managed to suppress trial results for seven years, when they revealed that the drug in question was no more effective than cheaper generic formulations.

That, my friends, is a tiny glimpse into how science gets ‘settled’.

Any questions?

References for all the above (and more) can be found on my website - link here.