The Decline and Fall of Science-based Medicine

The philosophy of science-based medicine (SBM) is a response to perceived shortcomings in the practice of evidence-based medicine. EBM is the movement that strives to make medical treatments less dependent on the authority and experience of doctors, and instead put authority in the best available clinical evidence for that treatment.

“EBM is the conscientious, explicit, judicious and reasonable use of modern, best evidence in making decisions about the care of individual patients.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789163/#:~:text=Evidence%20based%20medicine%20(EBM)%20is,the%20best%20available%20research%20information

The central problem with EBM is that gathering evidence is hard and prone to many difficulties such as,

• placebo effects (people report getting better when being treated regardless);
• regression to the mean (illnesses tend to get better regardless);
• publication biases (people tend to publish positive results and hide their negative results in a drawer);
• poor controls (tests need to be fair & compare like-for-like and so need carefully constructed control groups);
• small sample sizes (cheap and quick trials mislead).

… and so on. For example, acupuncture has been subjected to many clinical tests – mostly low quality, small samples, poor controls, but all trials are positive that come out of China. The evidence quality tends to be low, but in aggregate it is uniformly positive.

Should we accept acupuncture as an effective mode of treatment? Advocates of SBM say – not straight away – we need to also take into account the scientific context of the treatment, asking “Is this plausible given what we know about science?”

If a treatment is implausible then we needs lots of strong evidence, and if it is entirely consistent with everything else we know, then we might accept lower forms of evidence in clinical decision making.

As acupuncture is implausible, then we need strong evidence and should reject this weak evidence base. This may appear like a double standard, but humans think like this quite naturally.

For example, if a small child said to you, “There is a big strange dog in the garden!”, what level of evidence would you require to accept this claim? If you looked out of the window and saw the bushes shaking as if a dog was in there, would you believe the child?

I expect you would. It is quite plausible that a dog has gone astray in the neighbourhood. This happens. Your child can correctly identify dogs. The bush shaking is consistent with a large animal being in there.

But what if the child said “There is a tiger in the garden!”. You look out of the window and see the bush shaking. Would you believe the child? Probably not. Yet you are presented with exactly the same level of evidence: a child’s testimony and a shaking bush.

The blog (Science-Based Medicine), started by Steven Novella and David Gorski, has spent years applying these principles to the claims of quacks – especially around cancer care. It meticulously picks apart the claims of alternative medicine and exposes their evidential and scientific shortcomings. It warns us to avoid the superficially plausible, the ideological and the emotionally appealing – even when presented with best intentions.

The SBM blog has come under the spotlight in the last few days after one of its editors (Harriet Hall, @HHSkepDoc) wrote a review of a book by @AbigailShrier called “Irreversible Damage”. The book looks at how teenage girls are being prescribed the drug Lupron in never seen before numbers to stop their developing puberty. These girls are reporting dysphoria about their emerging sex and sexuality and want to ‘transition’ to be ‘boys’.

The book warns that many in the medical profession have a deep unease about the use of Lupron as there is not an evidence base sufficient to support any particular clinical purpose in this cohort of patients. This caused a stink at the blog as it was seen as ‘transphobic’. The trans activist movement acts as if children have a right to Lupron and doctors have a duty to prescribe it. Any deviation from this “affirmation’ is ‘transphobic’. This is not how SBM works.

Harriet Hall’s blog post was taken down (for “review”) and since then, a number of other blogs have been written to condemn Shrier and her book. The first attempts by Novella and Gorski made it clear they had not read the book. The next was by an “expert” who had just graduated in family medicine a few days earlier. The third was by a “non-binary” doctor with they/them pronouns and blue hair who makes a living from prescribing lupron to such kids.

The theme in these blogs was that Lurpon was safe, well tested and reversible, against what Shrier was claiming in her book. One sleuth spotted though that David Gorski had written about Lupron before.

Gorski was writing about notorious autism quacks, Drs Mark and David Geier. This notorious pair thought that lowering testosterone in children with autism might help their quack chelation therapy. This is what Gorski has to say about the effects of Lupron. He does not mince words: it is equivalent to castrating a male child, or inducing menopause in women. Indeed, the drug has been used to ‘treat’ paedophiles and attempt to lower their libido.

Lupron is the trade name for a drug called leuprolide acetate a synthetic analog of a hormone known as gonadotropin releasing hormone (GnRH, a.k.a. LH-RH). After causing an initial stimulation of gonadotropin receptors by binding to them, chronic administration of Lupron inhibits gonadotropin secretion, specifically leutenizing hormone (LH) and follicle stimulating hormone (FSH). The end result is the inhibition of the synthesis of steroid hormones in the testes in men and in the ovaries in women. In men, testosterone and androgen levels fall to castrate levels, and in women estrogens are reduced to postmenopausal levels.

Gorski is very clear that the Geier’s use goes against the manufacturers usage guidelines. He says, “What the Geiers propose goes way beyond “off label” use; it’s strictly experimental.” And notes it is amazing it could be used in trial as there is no plausibility here.

But we’re not talking about adults here. We’re talking about children. Are there any medically accepted uses of Lupron in children? Yes, but only one: Precocious puberty. Precocious puberty is defined as the onset of secondary sexual characteristics before 8 years old in girls and 9 years old in boys. It can be the result of tumors, central nervous system injury, or congenital anomalies. The package insert for Lupron emphasizes that children should not be treated with Lupron unless they meet the following criteria:

– Onset of secondary sexual characteristics before age 8 in females and age 9 in males.

– The clinical diagnosis must be confirmed by a pubertal response to GnRH (adequate secretion of LH in response to a challenge with injected GnRH) and bone age advanced at least one year beyond chronological age.

– Baseline evaluation has to include: Height and weight measurements; sex steroid levels; adrenal steroid level to rule out congenital adrenal hyperplasia; beta-chorionic gonadotropin (beta-HCG) to rule out a beta-HCG-secreting tumor; pelvic and adrenal ultrasound to rule out a steroid-secreting tumor; and a CT of the head to rule out an intracranial tumor.

Also, precocious puberty is a rare condition.

The idea that chemical castration can help cure autism is an extraordinary claim – and so that required extraordinary evidence. As Gorski says,

Once again, if you’re going to propose doing something as radical as shutting down steroid hormone synthesis in children, you’d better have damned good evidence to justify it, and the Geiers don’t.”

So the big question is, why does Gorski refuse to embark on a similar analysis and condemnation when another group of doctors decide to use lupron in an off-label way without an evidence base for the required benefits and associated risks?

Why are the Geiers condemned unconditionally, but gender doctors given a free pass? The common reasoning among gender activists is that use of Lupron on children is not new. So shut up. But as Gorski himself says,

“Are there any medically accepted uses of Lupron in children? Yes, but only one: Precocious puberty.”

As any advocate of EBM will tell you, evidence used on one cohort of patients to achieve a particular clinical outcome, cannot simply be transferred to another cohort. And most definitely cannot be transferred for a different clinical purpose with different clinical outcomes. In precocious puberty, the children will be much younger and still undergo a typical puberty. Lupron is used to delay onset. Using the same drug on teenage girls to stop puberty means that child may never undergo anything like a typical puberty and will almost certainly go on to cross-sex hormones. That has significant implications for child development in bones, brain and reproductive function.

“Once again, if you’re going to propose doing something as radical as shutting down steroid hormone synthesis in children, you’d better have damned good evidence to justify it, …”

The question is, do gender doctors have that damned good evidence?

What is the clinical justification for using Lupron on these children who are distressed about their emerging sex and sexuality? What outcome is desired? How can you tell if you have succeeded? What risks are there?

There are no good answers to any of these questions.

We lack the systematic and formal appraisal of the evidence base here in the literature. One alarm bell was raised by a blog for the BMJ Evidence Based Medicine journal that concluded that at best this was ‘experimental’ with little knowledge of risks.

The development of these interventions should, therefore, occur in the context of research, and treatments for under 18 gender dysphoric children and adolescents remain largely experimental. There are a large number of unanswered questions that include the age at start, reversibility; adverse events, long term effects on mental health, quality of life, bone mineral density, osteoporosis in later life and cognition. We wonder whether off label use is appropriate and justified for drugs such as spironolactone which can cause substantial harms and even death. We are also ignorant of the long-term safety profiles of the different GAH regimens. The current evidence base does not support informed decision making and safe practice in children.

https://blogs.bmj.com/bmjebmspotlight/2019/02/25/gender-affirming-hormone-in-children-and-adolescents-evidence-review/

A more thorough appraisal was conduced by the UK’s National Institute of Health and Care Excellence (NICE). As part of a government review, they concluded the evidence base was, “assessed as very low certainty.” In a comment from the Society for Evidence-Based Gender Medicine, they say the NICE report makes “sobering reading”,

In SEGM’s view, the “low confidence in the balance of risks and benefits” of hormonal interventions calls for extreme caution when working with gender-dysphoric youth, who are in the midst of a developmentally-appropriate phase of identity exploration and consolidation. While there may be short-term psychological benefits associated with the administration of hormonal interventions to youth, they must be weighed against the long-term risks to bone health, fertility, and other as yet-unknown risks of life-long hormonal supplementation.

https://segm.org/NICE_gender_medicine_systematic_review_finds_poor_quality_evidence

There is not the evidence to suggest that the use of puberty blockers reduces the psychological distress of gender dysphoria (indeed, it appears to ‘lock it in’) and we do not know the impact on brain, bone and reproductive health, although what evidence there is, is not good.

So why are the editors at the influential blog, Science-Based Medicine steadfastly refusing to engage with the contradiction? Why is David Gorski using a blocking tool on twitter to block anyone who broaches the subject (and all those who ‘like’ such challenges)?

There are several possible explanations. The subject is very charged and very political. Criticising “gender affirming care” including these blockers will get you complained about to employers, condemned, called transphobic, cancelled. Are they afraid?

Or are the editors now vested in the concepts of gender ideology where use of puberty blockers and cross-sex hormones is not a clinical use at all – but a *destiny* for “trans children” to live their *authentic life*? A completely ideological and pseudoscientific view.

We may never know as the blog posts on the web site are bluffing out the false view that this is a settled question. People who raise this are blocked. This is the antithesis of science-based medicine. No clinical question should be off-limits. No evaluation of risks should be brushed aside. No acceptance of a treatment can be made without it being in the context of science, evidence and medical ethics.

However this now unfolds, this is becoming a very damaging event for, not just the SBM blog, but for the very fight that it is right to insist medicine happens within a rational and scientific framework, where free discussion of evidence and its meaning can take place.