The Daily Telegraph - Features
The drugs loophole at the heart of the Tavistock scandal
Puberty blockers were originally licensed only to treat rare conditions. Eleanor Steafel investigates how off-label prescriptions made them more widely used
“Shaky foundations”. That’s how Dr Hilary Cass characterised the ground that gender medicine was built on in this country. In a health system where clinicians are typically cautious, where emerging areas are treated carefully and medicines well regulated, the Cass Review into the gender identity clinic at the Tavistock Centre, in London, determined “quite the reverse” had been true when it came to gender care for children.
Of the myriad holes Cass exposed – from the lack of evidence underpinning the guidelines for managing gender dysphoria, to the insufficient studies supporting the use of hormone treatment – perhaps the most striking were her findings on puberty blockers. The use of the drugs (historically prescribed to pause symptoms in very young children experiencing precocious puberty) was informed by a single, Dutch medical study, which, Cass said, suggested puberty blockers “may improve psychological wellbeing for a narrowly defined group of children with gender incongruence”.
“Some practitioners abandoned normal clinical approaches to holistic assessment which has meant this group of young people have been exceptionalised compared to other young people with similarly complex presentations. They deserve very much better.”
Puberty blockers were meant to simply buy children time to think. In fact, Cass showed the vast majority of children who were prescribed them went on to have hormone treatment. Of the 50 papers on the effects of puberty blockers in adolescents that researchers at the University of York identified for the report, only one was deemed high quality.
In the wake of Cass’s findings, published last week, it’s tempting to look forward – to focus on her recommendations and consider what happens next. But to do that, you have to understand how it happened in the first place. For many, the fact it was possible for clinicians to prescribe an underresearched drug freely to children exposes a gaping hole in our drug regulation system.
At the NHS’s Gender Identity Development Service (Gids) clinics, including the Tavistock in London, puberty blockers were prescribed “off-label”. Put simply, if a drug is being used off-label it will have been originally licensed by the Medicines and Healthcare products Regulatory Agency (MHRA) but is now being used in a different way, for a different condition or group of patients or at a different dosage.
It is common practice in paediatrics, as drugs aren’t generally trialled on children. But National Institute for Health and Care Excellence (Nice) guidelines state that healthcare professionals must “[give] information about the treatment and [discuss] the possible benefits and harms so that the person has enough information to decide whether or not to have the treatment. This is called giving informed consent.”
“The key thing the General
Medical Council would say,” says Prof Anthony Cox, an expert in clinical pharmacy and drug safety at the University of Birmingham, “is that you have to be satisfied there is sufficient evidence or experience of using the medicine to demonstrate safety and efficacy. I think that wasn’t met by Tavistock when prescribing puberty blockers.”
How did they get around it? “They’d argue there was evidence,” says Cox. “And that they’d developed a practice over years. But by the late 2010s it was clear that there were concerns about the lack of evidence.” Those concerns, he says, were being shared by whistleblowers: “who raised their voices and were knocked down”.
There may be a loophole in the system that allowed professionals prescribing these drugs to fall back on the fact it had been licensed and used on children before – just for a different purpose. There was a sense of “What’s the problem?”, says Prof Carl Heneghan, director of the Centre for Evidence-Based Medicine at the University of
Oxford. Using off-label drugs is common practice, he says. “That’s the loophole that’s been used here. We need a much more robust, evidence-based approach for how we licence children’s medicines. That’s why we said we need a new regulator that looks into this.”
The fact the drug had already been prescribed to children legitimised its use in young people experiencing gender dysphoria. “That’s the loophole,” says Heneghan. “You say we’re doing it over here, in precocious puberty, and therefore it’s all right to be using it in children for transgender or gender dysphoria.”
It should have been particularly important to interrogate the way the drugs were being prescribed given the “irreversibility” of the intervention, he says. “That should create a more stringent approach to the regulation.”
For Heneghan, the whole system of off-label drug regulation requires examination. The current one “puts the onus on individual doctors to take the responsibility”.
“I think, given what’s happened with gender dysphoria, there needs to be a real look at the situation,” he says. “Certainly, a general practitioner can’t have the evidence and experience to say ‘I can prescribe off-label in children’ where the harms are quite significant and the use is limited. A regulator, if they were in place, might say, ‘This drug, if it’s to be used off-label, can only be prescribed in the context of secondary care where the person is known to A, B and C.’ That would bring in another level of safety that is missing at this moment in time.
“There needs to be a tightening of the regulations to prevent this happening again.” Meanwhile the MHRA, he says, “should say it is our responsibility to keep children safe and ultimately we will take the can for when it goes wrong”.
The MHRA is clear it has not licensed any medicines for treating gender dysphoria. Dr Alison Cave, its chief safety officer, says: “Clinicians, under their professional responsibility, may decide to prescribe a medicine ‘off-label’. This is a matter of clinical practice and is not regulated by the MHRA.” Patient safety, she adds, is their top priority.
Dr Sallie Baxendale, a professor of clinical neuropsychology at UCL, says that, though doctors have a right to prescribe off-label, puberty blockers “escaped out into the wild”. “Now they’re bringing it right the way back to ‘OK, if you want to use this drug, it’s got to be part of research. If it’s going to be part of research it will have to go through an ethics committee, so you will have to present to the ethics committee the reasons why you want to use it, why you think it’s going to work, who you’re going to give it to, why you’re going to give it to them.’ All of that will have to be set out and that’s going to be a challenge on the back of Cass.”
Baxendale points to the dysfunctional prescription process at Gids, as laid out in Time to Think by Hannah Barnes. “She described how psychologists, who do not have prescribing rights, were making recommendations for the drugs. Endocrinologists were then prescribing them on the recommendation of psychologists.
“Barnes reports that it became a process where no one really took responsibility for the treatment. The psychologists were not responsible because they weren’t actually prescribing. The endocrinologists were only going on what the psychologists said. That’s why Cass insists on a medically led service now, as part of a multidisciplinary team.
“It’s extraordinary that such a model developed with an experimental, off-label treatment.”
Ashley Grossman, a consultant endocrinologist and professor of endocrinology at Oxford, says if he was prescribing a drug off-label he would first run it past a multidisciplinary group or a pharmacology committee in his hospital and “get other people’s views”. “Almost certainly that didn’t happen at all [at Gids] and that was the problem,” he says. “I think people came from a viewpoint that any child that says ‘I’m in the wrong sex’ had to be believed automatically and had to transition.
“It was an affirmation of a change without any counselling, any discussion, any consideration of other possibilities. It was a mindset that was pointed in one direction and one direction alone.”
The result, he says, was children “being treated with essentially a completely new and experimental drug – experimental in the sense that it had never been used in this situation.” Campaigners have long insisted that puberty blockers are “just one possible part of a young person’s gender journey”.
Grossman points out that people who raised doubts about the drugs “were shut down”. “On social media, a lot of us who were concerned were frightened to put our heads above the parapet because of the trolling and nastiness that went around.”
“A custom of practice, and perhaps ideology led clinicians at Gids to believe they were doing the right thing,” says Cox. “I don’t think they had the evidence to say it was safe and effective.” Any structures that may have hindered the use of a controversial drug weren’t present at Gids, he says. “If your whole organisation has a sort of groupthink going on, then the normal mechanisms you might have in place within an NHS trust to oversee such things like prescribing would start to fail.”
It didn’t help that the Tavistock was seen as an expert hub. “If you’re considered to be a national centre of excellence in whatever condition you’re dealing with there is a certain expectation that there would be a level of professionalism that would mean that you wouldn’t get this sort of behaviour,” says Cox. “You would have thought a national centre would be the type of place that would be on top of the evidence.”
He wonders if there should be a “review of professional bodies” but warns against overcorrecting. “It’s dangerous to start tying the hands of clinicians too much because you will end up having a perverse outcome in that you will cause harm to patients by creating a system where you can’t actually use medicines that there is evidence for.” What’s clear, he says, is that in the case of puberty blockers, it was too “simplistic” a defence to argue that off-label prescribing was common practice in paediatrics.
“Off-label drugs [should be] used with due regard to safety and efficacy,” says Cox. “And if that isn’t happening there’s a failure. And if you’ve got people telling you there’s a potential issue and you’re not taking that seriously, and you develop a groupthink that ‘We are right’ and have an almost ideological stance towards the use of a drug, then I think you’ve gone down a really dangerous dead end.”
Many hope that dead end has come to its conclusion with Cass – that the loophole will be closed.
Maria Caulfield, the health minister, says: “There are no circumstances where a child under the age of 18 should be prescribed puberty blockers off-label for gender dysphoria under the recommendations of the Cass Review. We are working to implement all of Dr Cass’s recommendations, including closing any loopholes to prevent these treatments from being given to children.”
‘Off-label puberty blockers escaped out into the wild. No one took the blame’