The Elephant-Sized Flaw in Large Clinical Trials

Imagine you’re like me and have a genetic variation in your D2 Dopamine receptor code which makes some aspects of “executive functioning” difficult. (I was always the last one to finish my lab work in Chemistry, Biochemistry, and General Physics — though I got the highest final score in Physics Lab, so I’m not claiming to be stupid.)

Anyway, you’ve got this D2 challenge in your brain, you do some reading and discover that organic velvet bean powder has L-dopa that might help you with things like working faster through cookbook recipes.

You buy some velvet bean powder, try it and, wow, you’re not only more efficient, your mood improves.

You should feel ecstatic, right?

But no, you’re vaguely suspicious because you’re a medical doctor. Professors and attendings have warned you that anecdotal evidence is worthless, and the placebo effect is ready and waiting to make a fool of you. 

To avoid embarrassment, you decide you need a double-blinded, prospective clinical trial with a large number of test subjects and proper randomization. Anything less would be rubbish.

Fortunately, this is not a problem. You’re also a multi-billionaire who can fund a complete drug trial.

Of course, you didn’t get rich by ignoring opportunity. You plan to make money with these velvet beans. 

Knowing that your problem starts with genetic D2 variation, common sense tells you to study a few thousand people who have the same genetic makeup.

But what about your target buyer? A businessperson looks there first.

From that perspective, you want the FDA approval to apply to as many people as possible so you can hand out genetically modified velvet bean pills to the broader public and make more money.

You therefore choose the typical mainstream experimental design: Thousands of unselected participants taken in randomly and then randomized and blinded into trial and control groups. You’ll also blind the people administering the bean pills and placebos so no one can fault your study.

Ten years and 1.2 billion dollars later, the trial ends and the stats come back from the math geeks, those rare professionals who honestly understands statistics and can manipulate them dishonestly.

Despite their efforts, they bring you bad news. There is no statistical evidence that your patented velvet bean extract improves executive functioning or mood.

Rats!

You go home and glare at your dog, then apologize with an organic carrot.

If you publish the paper, the entire world of mainstream MD’s, those smart women and men who don’t read the scientific literature or think for themselves because they’re too busy and frightened of lawsuits – those dedicated, exhausted people will hear from their educators, the drug reps, that velvet beans are rubbish. “This is just another example of the functional medicine quacks peddling snake oil.”

But you take organic velvet bean powder every day, it’s made a real difference. In the kitchen now, you’re turning out Molten Lava Cakes faster than the famous TV chefs. You feel more grounded and calm, too.

What should you do?

It’s obvious, isn’t it? Common sense tells you to go back and do a clinical trial using people with the D2 receptor issue, testing the organic velvet bean powder that works for you, not the GMO stuff your lab cooked up for megabucks.

Unfortunately, this common-sense approach rarely if ever happens in the real world. Negative studies like this are routinely published, and the mainstream fails to see the elephant-sized flaw in their assumptions: the human population is vastly more diverse than previously known at the genetic and biochemical level.

Genetic diversity is relevant to every branch of medicine because single nucleotide polymorphisms (genetic SNPs), like the one that affects my D2 receptors, create a huge diversity in disease susceptibility at the root-cause level, as well as a myriad of diversity in personal strengths and weaknesses within every system of the body.

From the central nervous system to the skin, genetic SNPs are the rule, not the exception. And science has hardly begun to uncover them all or understand their complex interplay across systems.

I have another common genetic SNP that reduces my ability to “detoxify” caffeine by about 60%.

With this knowledge, I’ve lowered my caffeine intake from several double mochas a day (at the VA Med Center years ago), to two cups of green tea per day. This reversed an unbearable sensation of vascular congestion in my legs. (n=1)

I also have a SNP that makes me inefficient at converting beta-carotene to vitamin A, a few SNPs that increase my need of several B vitamins for adequate methylation to keep my homocysteine levels down, and numerous others that I won’t bore you with. But despite all my SNPs, I’m still quite healthy for a 63-year-old man.

The thing is, genetic SNPs are so common, you yourself almost certainly have at least one, more likely a handful. So it’s irrational for researchers to lump you into a huge unselected “normal” population when they’re testing something. And it’s misinformed and lazy for MD’s, however busy they are, to ignore your SNPs and follow cookbook-official protocols when treating you. They need to read more broadly and act with integrity even if it costs them.

Genetic diversity is why functional medicine, imperfect as it is, will become central to mainstream medical care someday. The establishment will change the name from functional medicine to something they haven’t already disparaged.

Currently, they say functional medicine is not evidence-based. In some ways that’s true.

But when it comes to reversing chronic disease rather than just controlling its progression, functional medicine is more evidence-based than mainstream medicine because it uses personal genetic data that the mainstream ignores.

Moreover, it understands the elephant-sized flaw in the mainstream’s large clinical debunking trials. 

Morrill Talmage Moorehead, MD

Photo by Rafael on Unsplash


If War Generals were MD’s

It’s midnight. Your squad sits in a valley with hills on all sides. Fifty hills. The ground beneath your boots vibrates with enemy tanks rumbling beyond the blind horizon.

Wouldn’t it be wonderful if they attacked from one direction? They’ve done it before.

But they could just as easily attack from fifty directions, the way you would.

You’ve seen war up close. You place a priority on winning.

But the Generals back in DC are MD’s now. Their “evidence based medicine” extends to every problem humanity faces, even war.

Today they’ve set up a test. Your orders are to defend whatever comes over the big hill to the north, ignoring attacks from other directions.

If your troops lose, the Generals will have ruled out the hill to the North.

After the loss, they will select another hill for study with another garrison of expendable troops. You won’t be among them. And you won’t be looking down from Heaven. Now that western science owns DC, there is no Heaven. Namaste.

“One hill at a time” is the motto of “Evidence Based Warfare.”

Though BS scouts have crawled up the hills on their bellies to find enemy troops ascending each of the fifty discovered hills, basic science must be ignored until war deaths can be analyzed and published. It’s the only way to be sure: First, do no harm.

War drums bang in your ears. Enemy tanks leap over the hills.

Your squadron fires North with deadly weapons. Nothing stands against them…

To the North.

But your flanks are exposed. Casualties mount.

Against better judgment you call D.C.

“They’re coming over all fifty, Sir. It’s a multi-pronged, attack.”

“You woke me up for this?”

“General, Sir, I’m sorry, but I’ve got an idea. Listen, I know this is a little late, but if you give the order to defend our flanks, I think we could still…”

The General laughs like a sadistic resident enjoying the pimping of a medical student. “You don’t seem to understand experimental design, Captain. Your job is to isolate one variable. If you go off willy-nilly defending multiple hills, we can’t generate meaningful statistics. Scientific chaos. Evidence Based Warfare demands a blinded, randomized study with one and only one variable at a time. That’s why progress has to be slow.”

It’s the only way to be sure, a voice says in your head.

“But Sir, we are blinded. Totally blinded down here. And honestly, some of my kids aren’t ready to die. Shelly’s barely eighteen.”

Silence.

“Sir, I know we’re going to die, I can accept that. But can’t we go down with a fight this time?”

Silence.

“Just this once? Hello?”

“Do you want the words, ‘Snake Oil Soldier’ carved into your gravestone, Captain? There’s one scientific way. You know it. You know you know it.”

“Yes, but couldn’t we just think outside the…

“What is it we’re doing here, Captain? Come on now, you know the drill. Say it with me…”

“Evidence Based Warfare.”

“Good. And what’s your motto, soldier?”

“One hill at a time, Sir…” Your last words on Earth.

I wrote this to illustrate the blind spot in so-called “Evidence Based Medicine,” the inappropriately named paradigm of emotional superiority currently pushed in western medicine as the only way to weed out bad science.

If you’re familiar with Dale Bredesen’s breakthrough work on Alzheimer’s Disease, then you know that this lethal disease can’t be approached with the same methods and assumptions that have worked against simple diseases with a single cause.

Alzheimer’s is a multifactorial killer with dozens of separate biochemical points of failure coming together to cause what is wrongly considered a single disease – simply because of its appearance under a light microscope.

Aerobic exercise and carbohydrate restriction are two of the many components of Bredesen’s protocol, a multifactorial therapy that is unequivocally working in the fight against dementia.

Ironically, some MD’s are calling for a slower approach with double-blinded studies and monotherapeutic (one-pill) experimental trials.

Someone needs to ask these critics how to doubly blind a study that involves exercise, fasting, eliminating all simple carbohydrates, doing yoga, meditation, eating more vegetables, limiting meat intake, using an electric tooth flosser and an electric tooth-brush in addition to taking multiple non-prescription pills and prescription hormonal replacement therapy.

Let’s see… one group exercises, the control group doesn’t, one group does yoga, the controls don’t, (etc.) and somehow neither group knows if they’re the therapeutic group or the “placebo” group? And also the doctors in charge of the experiment can’t know who’s doing what.

It’s an impossible requirement, and the critics know it if they’ve actually read Bredesen’s peer-reviewed articles.

The critics don’t seem to be interested in evidence-based medicine at all. Their agenda appears to be creating a roadblock to effective treatment of Alzheimer’s, along with every other multifactorial disease.

Meanwhile Alzheimer’s patients are suffering and dying in hell’s worst agony.

The rigid absurdity of the critics makes me wonder if they’re not funded by drug companies or maybe the sugar industry.

Drug companies are not objective in this fight. Monotherapy has always meant economic survival to them. A multi-therapeutic approach involving mostly over-the-counter pills and lifestyle changes is likely seen as threatening to their tradition of educating and motivating doctors to sell their products.

Drug reps are the prominent educators of busy MD’s in the US. And our MD’s are busier and more chronically exhausted than most people would ever imagine.

My short story is intended to clarify the weakness of the current experimental design paradigm that cannot accommodate multifactoral diseases like Alzheimer’s in an efficient, reasonable way.

The truly scientific and compassionate way to approach complex disease is to save dying patients as efficiently as possible by applying basic science knowledge in multifactoral human studies, despite the technical “shortcomings” of such studies. We must not let cranky perfectionists stop medical breakthroughs the way they’re trying to shout down Dale Bredesen’s monumental accomplishments.

Why let the “perfect” be the enemy of the good? Perfectionism isn’t perfect. It’s flawed like everything else on Earth.

I hope medical practitioners and their patients will allow “Reality Based Medicine” to dominate the 21st century rather than the straightjacket of yesterday’s simplistic experimental designs that targeted one disease caused by one organism, treated with one antibiotic. That mindset worked for a while with simple problems, but it’s the wrong approach to modern complex diseases like Alzheimer’s.

Medical science needs to defend all fifty hills at the same time or patients will continue to die unnecessarily.

If you know someone, a relative or friend who has Alzheimer’s disease or just early memory problems, please click here, I’m begging you. Learn about Dale Bredesen’s unprecedented work, then send an email to the person you have in mind, sharing Bredesen’s links.

I’m telling you, this is important. Do it for the sheer joy of helping someone who needs you!

Do not put it off, please.

Run! Go! Get to da Chappa!!!

With warmest regards,

Morrill Talmage Moorehead, MD

http://www.storiform.com