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CrossFit Health* provides a platform for truth in Science where truth is hard to find (see photo)

*My favorite CrossFit Health posts predate mid-2020. 

In a 2019 post, CrossFit Health discusses the results of a review which indicates "a significant share of treatments, even if they are in widespread use, will be found ineffective when tested in a rigorous clinical trial".

Researchers looked at over 3,000 randomized controlled trials in JAMA and the Lancet (from 2003-2017), and in the New England Journal of Medicine (from 2011 to 2017). Over 13% of these RCTs (396) in fields ranging from cardiovascular disease to obstetrics and gynecology, included reversals of medication, procedure, vitamin/supplement, and device; over half which were later confirmed by systematic review. Read more about the research at CrossFit Health

Why do we place so much faith in the value of a "puny p"? Read more at CrossFit Health.

"A single p-value cannot denote the truth or falsehood of a statement or hypothesis. The widespread use of "statistical significance" (generally interpreted as "p 0.05") as a license for making a claim of a scientific finding (or implied truth) leads to considerable distortion of the scientific process...The p-value tells us nothing about the size of an effect or its scientific, human, or economic significance." -American Statistical Association (ASA)

Scientific misconduct including "p-hacking", methodological issues and confirmed fraud, is highlighted in another CrossFit Health post, summarized by a quote from a journalist writing for Slate:

"If the replication crisis doesn't mean science is broken, what does broken even mean?"

Did you know the importance of reading published studies in their entirety (rather than just the abstract) to understand their implications? A recent review on research published in psychiatry journals (2012-2017) demonstrated a greater than 50% likelihood for abstracts not to reflect accurately on actual results. Read more about it at CrossFit Health.

Does the depressed friend in your life know about John Ioannidis' research on the effectiveness of antidepressants? Read more about it at CrossFit Health. Ioannidis concludes:

"antidepressants are probably indicated only in select patients with major depression, probably preferentially in those who have severe symptoms and have not responded to anything else. For most patients with some depressive symptoms who are currently taking antidepressants, using these drugs would not have been the preferred option, placebo would be practically as good, if not better, and would save toxicities and cost."

What is the strength of recommendations to reduce consumption of red and processed meat? CrossFit Health reports on a 2019 paper assessing the certainty and strength of observed associations with cardiovascular and all-cause mortality.

John Ioannidis, MD, DSc paints a sobering picture of nutritional epidemiology, concluding "the field needs radical reform" in a 2018 paper summarized by CrossFit Health. He reports:

"implausible estimates of benefits or risks associated with diet probably reflect almost exclusively the magnitude of the cumulative biases in this type of research, with extensive residual confounding and selective reporting. Almost all nutritional variables are correlated with one another; thus, if one variable is causally related to health outcomes, many other variables will also yield significant associations in large enough data sets. With more research involving big data, almost all nutritional variables will be associated with almost all outcomes. Moreover, given the complicated associations of eating behaviors and patterns with many time-varying social and behavioral factors that also affect health, no currently available cohort includes sufficient information to address confounding in nutritional associations.

Furthermore, the literature is shaped by investigators who report nonprespecified results that are possible to analyze in very different ways. Consequently, meta-analyses become weighted averages of expert opinions. In an inverse sequence, instead of carefully conducted primary studies informing guidelines, expert-driven guidelines shaped by advocates dictate what primary studies should report."

Have you heard about systematic fraud and data fabrication discovered by English anesthetist John Carlisle throughout thousands of Randomized Controlled Trials? His data detective-work contributed to the high-profile retraction of PREDIMED. Read more about it at CrossFit Health

Do we indeed "commit to paradigms, and then..bend the data to [them]"? Have you heard that "Generations of doctors were taught the faulty lipid hypothesis "because Ancel Keys' rebuttal of his own data was not accepted by the federal government"? Read more about it at CrossFit Health. 

In a separate CrossFit Health series Dr. Timothy Noakes reveals that the science behind the lipid hypothesis has been anything but neutral and free of intellectual bias:

• Ancel Keys' Cholesterol Con, Part 1
• Ancel Keys' Cholesterol Con, Part 2
• Ancel Keys' Cholesterol Con, Part 3
• Ancel Keys' Cholesterol Con, Part 4
• Ancel Keys' Cholesterol Con, Part 5
• Ancel Keys' Cholesterol Con, Part 6

The very lucrative statin industry was spawned out of a notion that lowering cholesterol saves lives. Whether benefits of statin treatment outweigh risks for primary prevention in healthy, asymptomatic people is difficult to ascertain due to regulatory agencies worldwide refusing to share the trial data which supposedly supports their recommendations. There is no informed consent without access to this data. Maryanne Damasi, Ph.D. summarizes the scope of the problem in a CrossFit Health post:

"The U.S. Food and Drug Administration (FDA) is sitting on the largest trove of clinical trial data in the world and will not share the data (including CSRs) with the public or independent researchers because it is considered commercially confidential under the Trade Secrets Act (18 U.S.C 1905). Those who have successfully obtained CSRs usually have taken legal action against the FDA.
...Instead of finding a central archive at the [European Medicines Agency] EMA, we discovered each nation had its own drug regulator. We ended up approaching all 32 countries in the European Union and the European Economic Area to find out which statins they licensed and whether they still held the clinical trial data.
...Our research has highlighted a major problem. There is no easily accessible archive containing information about the licensing of statins nor a central location for holding the trial data. The transparency of this trial data is vital to making informed decisions about medicines and potentially answering important clinical questions."

CrossFit Health summarized the results of a 2019 review which showed the majority of the research evidence (28 randomized controlled trials dating back to 1965) fails to support the hypothesis that a reduction in saturated fat consumption improves cardiovascular outcomes or overall mortality. 

Dr. Timothy Noakes wrote a series on evidence that insulin resistance syndrome (IRS) is the key driver of most of the chronic medical conditions of modern civilization. The science is still anything but settled.

• It's the Insulin Resistance, Stupid: Part 1
• It's the Insulin Resistance, Stupid: Part 2
• It's the Insulin Resistance, Stupid: Part 3
• It's the Insulin Resistance, Stupid: Part 4
• It's the Insulin Resistance, Stupid: Part 5
• It's the Insulin Resistance, Stupid: Part 6
• It's the Insulin Resistance, Stupid: Part 7
• It's the Insulin Resistance, Stupid: Part 8
• It's the Insulin Resistance, Stupid: Part 9
• It's the Insulin Resistance, Stupid: Part 10
• It's the Insulin Resistance, Stupid: Part 11

"the reality is that science is never settled, and skeptics will always play a crucial role in driving scientific progress." - Dr. Timothy Noakes

There is a critical discussion we need to be having on the quality of current published research, scientific objectivity, and the degree to which we can trust modern medical science. If you currently have confidence in modern medical science, understand that "Scientific research has been plagued by conflicts of interest, data dredging, and bias, leading some researchers to assert that approximately 90% of published research relied upon by doctors is flawed". Read more about this problem at CrossFit Health.

I was honored to publish a guest post many years ago from Dr. Malcolm Kendrick highlighting all that can go wrong with our current standard of care model. I'm republishing it here:

Independent regulation needed for Big Pharma

2 Feb 2016

More stark proof that our pharmaceutical industry needs strict and independent regulation. Another case where raw data is reanalyzed YEARS after publishing (14 years), and a pharmaceutical agency is found GUILTY of illegally promoting drugs for treatment of children (they claimed had "remarkable efficacy and safety") despite the fact in the original raw data: "there were clinically significant increases in harms, including suicidal ideation and behavior and other serious adverse events".

RCFN is honored to host this guest post by Dr. Malcolm Kendrick:

Study 329 – where the hell is the outrage?

by Dr. Malcolm Kendrick

To quote from the BMJ 'No correction, no retraction, no apology, no comment…'

Study 329 was started in 1994 by Smith Kline Beecham, which shortly become part of the larger conglomerate Glaxo Smith Kline (GSK). Study 329 looked at the use of paroxetine, an anti-depressant, in adolescents with depression.

Following this study paroxetine was promoted and marketed heavily by GSK as demonstrating, in the words of GKS marketing materials: 'REMARKABLE Efficacy and safety'. Over two million prescriptions were then written for children and adolescents in the US.

However, in 2002 the FDA considered study 329 to be a 'failed trial.' In 2003 the UK recommended that paroxetine should not be used in children and adolescents with depression because it increased the risk of self-harm and potentially suicidal behaviour.

In 2004 the FDA placed a black box warning on all antidepressants in adolescents and children stating that they increased the risk of suicidal thinking and suicidal behaviour in these groups. In 2012 GSK finally agreed to pay £2Bn for fraudulently promoting paroxetine.

But the story does not end here. A group of researchers, who had been heavily critical of this trial, finally managed to get hold of the raw data and carried out a re-analysis under the restoring invisible and abandoned trials (RIAT) initiative. Yes, this saga has been a long one.

The reanalysis was recently published in the BMJ with sadly predictable results. The primary conclusion was that:

'Neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was increase in harms in both groups.'

This is in stark contrast to the original trial results. When it was first published it appeared to demonstrate very clearly that paroxetine was both safe and effective in adolescents with depression. According to GSK it demonstrated '.remarkable efficacy and safety' However, using exactly the same trial data, reanalysed by independent researchers, we now find that paroxetine was both useless and damaging.

So, what has been the consequences for those involved in the initial trial and the writing up thereof? For those who read the BMJ, you will know that I am now quoting verbatim here:

• Despite subsequent FDA and MHRA warning about increased risks of suicidal thinking and behaviour and GSK receiving a record fine, partly for illegal off-label promotion of the drug, the original report has not been retracted or even had a correction
• Academic and professional institutions have failed to publically address the many allegations of wrongdoing
• None of the named authors had intervened to correct the record. An internal enquiry by the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) concluded that no further action was necessary
• Brown University remains silent over its involvement in the study. It refuses even to confirm or deny whether any investigation took place1

I will add to this that a co-author of study 329, Karen Wagner, named eight times in the 2011 US Department of Justice complaint against GSK, is currently the president elect of the American Academy of Child and Adolescent Psychiatry – whose journal, the JAACAP, is where the original study was published.

Taking stock. What do we have? A study was done, and published, demonstrating that paroxetine was safe and effective. The trial data were heavily promoted, resulting in millions of children and adolescents being prescribed paroxetine.

The reality is that this drug was completely ineffective and increased the risk of suicide (amongst other things). This has all been known for many years. The latest re-analysis simply confirms everyone's worst fears.

So surely someone, somewhere, got punished? No they did not. Not only that, but the original published study has not even been retracted. It still sits in the medical database. A young and innocent researcher could come across it, and reference it, and use data from it to support a grant application for a study to use antidepressants in children.

If this were not all completely and absolutely one hundred per-cent fact, you might think we have a possible plot line for a dystopian novel here. A story of terrible corruption where large corporations can distort data through one hundred and eighty degrees, and get away with a fine. A world where bent researchers promote research that results in more children committing suicide, and then move on positions of greater power and authority – with no censure from anyone. To become presidents of major medical societies, for example.

Frankly I don't think I would dare to write a novel with a plot so completely outrageous. Surely someone, somewhere, would be punished for this behaviour. Surely the paper would be retracted. Surely a co-author of such a study would not be in line for a prestigious position. Surely the public would rise up in outrage.

In truth, it seems, nothing is going to happen at all. I must dig out 1984 and read it again, just to depress myself even further.

1: BMJ 2015;351:h4629

Dr. Kendrick gave RCFN permission to reprint his article above, which first appeared on his website

Many failed studies never see the light of day giving medical professionals a skewed idea of drug efficacy (and here's the transcript for that TED talk by Dr. Ben Goldacre) .

When I first advertised Dr. Kendrick's post on RCFN: