Think very carefully the next time your physician prescribes you a pill or offers you a bit of medical advice. Medical-research studies should not be trusted.
Science is part and parcel humility. Scientists do not seek to impose their needs and wants on Nature, but instead humbly interrogate Nature and take seriously what they find. We are aware that revered scientists have been wrong. We understand human imperfection. We insist on independent and — to the extent possible — quantitative verification of proposed tenets of belief. Carl Sagan The Demon-Haunted World: Science as a Candle in the Dark
Carl Sagan would agree that modern science has taken a terrible turn. Corporate influence, conflict of interest, ego, and greed have corrupted the science of science if you will. The results are bad scientific practices, a dearth of independent research, misinformation, and studies designed to produce favourable results. And not for the health of the individual. Big Pharma is arguably more concerned with competition than consumer protection.
“It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines,” stated Dr. Marcia Angell, the former editor of the prestigious The New England Journal of Medicine. “I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor,” she wrote in a 2009 piece titled Drug Companies & Doctors: A Story of Corruption
Years later, Richard Horton, editor of The Lancet echoed this sentiment: “…Something has gone fundamentally wrong with one of our greatest human creations…The case against science is straightforward: much of the scientific literature, perhaps half, may simply be untrue. Afflicted by studies with small sample sizes, tiny effects, invalid exploratory analyses, and flagrant conflicts of interest, together with an obsession for pursuing fashionable trends of dubious importance, science has taken a turn towards darkness.”
Clinical Trials: High Rate Of Wrongness
Prescription drug intake is at all-time high. In 2014, 4.3 billion prescriptions were filled by Americans – that’s approximately three prescriptions per person. All those drugs cost consumers $374 billion, according to a Consumer Safety report. It’s hard to believe that despite all that pill popping, one in every two people today suffer from a chronic illness, according to a recent study.
Each successful new drug costs, on average, roughly $800 million to develop and, depending on many variables, this number can reach $1.5 billion. To get approved by the FDA, a drug has to undergo several clinical trials to prove its value and benefits to patients. Consider that according to Consumer Reports, their parameters do not adequately assess safety. The studies oftentimes are too small, too short, and/or too unrealistic.
Meanwhile, looking back on past decades, the majority of drug trials were originally administered and funded by the National Institute of Health (NIH). Today, however, researchers from John Hopkins University found that “the drug and device industry now funds six times more clinical trials than the federal government.”
“What this means is that drug manufacturers and private investors are funding more clinical trials that they have a personal stake in,” explains Caitlin Hoff, Health & Safety Investigator for ConsumerSafety. “This bias has led to trial data being skewed, tests being ill-preformed, or key findings being left out of reports.”
Take for instance a study authored by Reshma Jagsi, M.D., D.Phil., assistant professor of radiation oncology at the U-M Medical School, that found that nearly one-third of cancer research published in high-impact journals disclosed a conflict of interest.
“… We as a society may wish to rethink how we want our research efforts to be funded and directed,” says Jagsi.“It has been very hard to secure research funding, especially in recent years, so it’s been only natural for researchers to turn to industry. If we wish to minimize the potential for bias, we need to increase other sources of support.”
These shortcomings point to hidden or misleading studies for all sorts of conditions, including depression, Alzheimer’s disease, type 2 diabetes, and menopausal symptoms, according to researchers at the Institute for Quality and Efficiency in Health Care (IQWiG) in Germany.
“You can’t say this is an isolated problem,” said Beate Wieseler, deputy head of IQWiG’s Drug Assessment Department. “It’s widespread, and it affects drug companies, universities and regulatory authorities.”
Furthermore, it’s recognized that medical journals or pharmaceutical companies that sponsor research tend to report only on “positive” results while the negative ones have that prove more harmful than helpful remain buried in the FDA archives. This practice greatly biases the medical literature, medical education, and treatment decisions.
“In view of this control and the conflicts of interest that permeate the enterprise, it is not surprising that industry-sponsored trials published in medical journals consistently favor sponsors’ drugs-largely because negative results are not published, positive results are repeatedly published in slightly different forms, and a positive spin is put on even negative results, adds Angell.
A review of 74 clinical trials of antidepressants, for example, found that 37 of 38 positive studies were published. But of the 36 negative studies, 33 were either not published or published in a form that conveyed a positive outcome.
Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies).
The missing or skewed studies, writes LiveScience, helped create the impression that 94 percent of antidepressant trials had produced positive results, according to an analysis, published in the New England Journal of Medicine. In reality, all the studies together showed just 51-percent positive results.
“We know that not all studies that investigate drugs are published,” says Wieseler. “The published literature tends to overestimate benefits and underestimate harms …”
Selective publishing can prevent the rapid spread of beneficial treatments or interventions, but more commonly it means that bad news and failure of medical interventions go unpublished. Keep in mind that most medical journals as well receive half or more of their income from pharmaceutical company advertising and reprint orders, and dozens of others [journals] are owned by companies like Wolters Kluwer, a medical publisher that also provides marketing services to the pharmaceutical industry.
The German researchers looked beyond just antidepressants and found reporting bias in 40 instances involving about 50 different pharmaceutical drugs, surgical procedures, diagnostic tools and preventive interventions.
To add insult to injury, consider another study published in the Journal of the American Medical Association in 2005 found that one-third of all medical studies turn out to be wrong. False findings may be the majority or even the vast majority of published research claims.
And how about the research that suggests that science is facing a “reproducibility crisis” where more than two-thirds of researchers have tried and failed to reproduce another scientist’s experiments, according to an article in the BBC.
From his lab at the University of Virginia’s Centre for Open Science, immunologist Dr Tim Errington runs The Reproducibility Project, which attempted to repeat the findings reported in five landmark cancer studies. After meticulous research involving painstaking attention to detail over several years (the project was launched in 2011), the team was able to confirm only two of the original studies’ findings.
“It’s worrying because replication is supposed to be a hallmark of scientific integrity,” says Dr Errington.
While science is not perfect, it is supposed to be self-correcting.
In 2010, John Ioannidis, a professor of epidemiology at the University of Ioannina School of Medicine in Greece, also found that nearly half of published articles in scientific journals contained findings that were false, in the sense that independent researchers couldn’t replicate them.
And according to a 2016 survey published in the journal Nature, more than 70 percent of researchers have tried and failed to reproduce another scientist’s experiments. (Although 52 percent of those surveyed agree that there is a significant ‘crisis’ of reproducibility, less than 31 percent think that failure to reproduce published results means that the result is probably wrong, and most say that they still trust the published literature).
Ioannidis discovered that the range of errors being committed was astonishing: “from what questions researchers posed, to how they set up the studies, to which patients they recruited for the studies, to which measurements they took, to how they analyzed the data, to how they presented their results, to how particular studies came to be published in medical journals,” according to an article in The Atlantic titled Lies, Damned Lies, and Medical Science.
He told The Atlantic that “Even when the evidence shows that a particular research idea is wrong, if you have thousands of scientists who have invested their careers in it, they’ll continue to publish papers on it,” he says. “It’s like an epidemic, in the sense that they’re infected with these wrong ideas, and they’re spreading it to other researchers through journals.”
Marketing “Medicine” To The Media And Masses
Turns out pharmaceutical companies put more money into marketing than research and development.
In his book Health Tips, Myths and Tricks: A Physician’s Advice Morton Tavel, MD., Clinical Professor Emeritus of Medicine, Indiana University School of Medicine went over 13 years (from 2003-2015) of financial reports for 12 major pharmaceutical companies. While Pfizer, which reported more than $67 billion in revenue in 2011, spent $9 billion on research and development, they spent over $19 billion on marketing.
According to IMS Health, a pharmaceutical intelligence company which tracks drug sales and marketing, drug makers spent $4.3 billion to reach consumers and $6.6 billion on promotions aimed at both patients and physicians.
Must be working. Prescription drug spending in the United States increased from $40 billion in 1990 to $234 billion in 2008, and now accounts for about 10 percent of healthcare expenditures.
Twenty percent of folks get sucked into TV ads or other forms of advertising, and 59 percent of those said their doctor agreed to write a prescription for that product, according to ConsumerReports.org.
So drug studies make newspaper headlines, what does that do?
As LiveScience puts it, “The media is known to distort key aspects of medical studies, twisting findings by virtue of ignorance, blowing obscure, unpublished “breakthroughs” out of proportion, and frequently failing to disclose industry funding even when the researchers do mention it.”
Take for instance, a recent article in BuzzFeed that makes it seem that hemp oil is only shown to have benefits with epilepsy. But the reality is that is simply because Big Pharma and the FDA are about to bring a synthetic CBD to market for epilepsy. There are in fact several studies that show the broad-ranging benefits of CBD on our health. Did the reporter know? Or even bother to research?
Meanwhile, journal editors deserve their fair share of criticism too, adds Horton.
“We aid and abet the worst behaviours. Our acquiescence to the impact factor fuels an unhealthy competition to win a place in a select few journals. Our love of ‘significance’ pollutes the literature with many a statistical fairy-tale.”
Alas, most scientific institutions and journals lack the resources to investigate misconduct properly, let alone ferret out errors in data acquisition and analysis. And consider that “to get funding a.nd tenured positions, and often merely to stay afloat, researchers have to get their work published in well-regarded journals, where rejection rates can climb above 90 percent,” writes The Atlantic’s David H. Fredman in Lies, Damned Lies, and Medical Science.
So while money and beliefs skewer things, so do ambitions, peer review journals that vie to publish the most exciting breakthroughs, journalists that want to nab flashy headlines, and universities that measure success in grants won and papers published.
Modern Science: Consequences Of Negligence
Unfortunately for patients, these factors add up and the repercussions are severe.
Some FDA-approved drugs explains Hoff, have caused serious and/or fatal side effects that were undisclosed to FDA officials, healthcare professionals, and the patients themselves.
In fact, more than half of all prescription drugs cause adverse effects—some serious or fatal—that aren’t detected until after the FDA approves them, sometimes many years later, according to ConsumerReports.org. For instance, Vioxx, Zelnorm, and Baycol were among the widely prescribed drugs found to be safe and effective in large randomized controlled trials before the drugs were yanked from the market as unsafe or not so effective, or both.
Such delayed detection contributes to the high number of drug-related injuries in the U.S. In 2008 alone, the FDA received more than 100,000 reports of serious injuries related to adverse drug events, an increase of about 25 percent over the previous year, according to the Institute for Safe Medication Practices.
Take for example the case of the anticoagulant Xarelto (a Johnson & Johnson/Bayer creation). Xarelto was initially praised for its advancements in blood thinning technology; patients required less monitoring and could take the drug thinner without a restrictive diet. However, Xarelto has no antidote. Because of this, thousands of people have experienced adverse side-effects like severe bleeding and death while taking the drug. In fact, over 20,000 Xarelto lawsuits have been filed against Johnson & Johnson and Bayer.
Hoff adds how cases like these really showcase the true power of the drug industry. “Xarelto is still on the market regardless of potentially flawed research data and the harm that it has done to patients. And many drug manufacturers continue to participate in similar dishonest practices to make money.”
While independent research is minimal, the Trump administration is also making cuts to many federal science agencies, For instance, the White House’s proposal cuts the EPA’s budget to $6.1 billion in 2019, its lowest level since the early 1990s and about 25% below the 2017 mark of $8.1 billion),
“Scientists at EPA are treated as irrelevant now because they are no longer part of the decision-making process,” Betsy Southerland, former Director of EPA’s Office of Science and Technology recently stated. “All environmental decisions come out of Administrator Pruitt’s private meetings with industry and agribusiness.”
Interestingly, however, Trump will issue $3.3 billion for the FDA, an increase of more than $460 million from 2017. The agency’s budget would rise to $5.8 billion when user fees paid by companies who submit drugs or devices to the FDA for review are added in.
In 2013, the pharmaceutical industry paid the FDA about $712 million for prescription drug user fees to “help” the FDA in the process of approving drugs for the sale and distribution in the US.
Currently, there is a push with the current administration states Hoff for a faster drug approval process.
“Minus years of research and development and the actual clinical trials, the FDA’s current drug approval rate is at about 10 months,” says Hoff. If our current administration aims to quicken this process, many worry that less time and care will go into the approval process and more harmful drugs will enter the market,” says Hoff.
Remember, doctors are trained to prescribe drugs. But chances are they have no inkling on the validity of the studies that made these drugs household names in the first place.
“Science is a noble endeavor, but it’s also a low-yield endeavor,” says Ioannidis. “I’m not sure that more than a very small percentage of medical research is ever likely to lead to major improvements in clinical outcomes and quality of life. We should be very comfortable with that fact.”