In spring 2025, NHS England may launch its much-anticipated “Pathways” trial into puberty blockers, a £10.7 million endeavour led by King’s College London and backed by the National Institute for Health and Care Research. This follows the Cass Review’s damning verdict on the thin evidence behind these drugs—gonadotropin-releasing hormone agonists used to pause puberty in children with gender dysphoria—and a subsequent halt to their routine use in March 2024. With recruitment set to begin via England’s new regional gender services, the study promises answers where Cass found none.
Yet, as The Quackometer has long cautioned, clinical trials can be fertile ground for misleading scientific distortion of the truth, and even fraud, if not designed with care. The potential for an unethical trial is huge.
Full study details are not yet available. So , here is what to look out for as warning signs that this trial will just add more ideological noise or true insight.
How might this trial might falter? And what you should watch for to ensure it yields truth, not illusion and more harm to children.
A Selective Cohort
The trial’s success hinges on who takes part. If it enrols only the healthiest or least complex cases—perhaps younger children with milder dysphoria—it risks painting an misleading sunny picture. Excluding those with mental health challenges or other vulnerabilities, could mask harms flagged by Dr. Hilary Cass. A robust design must reflect the full spectrum of gender clinic referrals, not a curated subset. The protocol, still unpublished, will reveal much.
Watch out for the inclusion criteria for the trial and check the cohort matches the intended treatment group.
Controls in Question
Without a proper control group, any benefits could be misattributed to blockers rather than time, therapy, or natural resilience. A trial lacking a good comparison group, randomisation or a placebo arm—admittedly tricky with drugs that halt puberty—might lean on weak comparators, like minimal support, to inflate results. Ideally, it should pit blockers against the psychosocial care NHS England now champions. Anything less invites doubt. We will not know what is the best way to treat these kids.
Watch out for unsuitable control and comparison groups that do not allow for a fair test that can inform clinical decisions.
Scale and Scope
Small trials often miss rare but serious side effects—fertility risks or cognitive impacts, say—while amplifying chance successes. With eight hubs planned by 2026, the study has the reach to recruit widely, but a skimpy sample would undermine its weight. Numbers matter; a cohort in the hundreds, not dozens, is the minimum for credibility. Given we can anticipate blockers will prevent critical development, the trial needs to show how it is ethical to recruit such a large cohort and answer a genuinely critical clinical question.
Watch out for dodgy ethics in recruitment where there is not clear equipoise in the chosen cohort.
Time Horizons
Two years of follow-up sounds thorough, yet blockers’ effects unfold over decades—bone density loss or regret may only emerge later. The Cass Review urged long-term scrutiny, and a six-year study could deliver if it tracks participants beyond the initial phase. A truncated timeline, though, risks capturing fleeting gains while dodging deeper harms.
Watch out for the trial capturing the initial honeymoon “euphoria” of being treated while missing the actual impact of these drugs.
Outcome Ambiguity
Trials can falter by chasing many vague goals—“reduced distress” or “improved well-being”—then cherry-picking what shines. Pre-registering specific, measurable endpoints on a platform like ClinicalTrials.gov, and reporting all results, even the null ones, is non-negotiable. Selective reporting plagued past gender medicine studies; this one must break that mould. Cass reported that the clinical intent of using blockers was inconsistent. That cannot be allowed to happen in this trial.
Watch out for vague, ambiguous outcomes without a clear clinical intent and justification.
Statistical Sleight of Hand
Data can be massaged—outliers discarded, analyses tweaked—until a positive spins out. Transparency in statistical methods, set before a single child enrols, is the antidote. Independent oversight, not just the trial team’s word, will signal rigour.
Watch out for oversight and published protocols being published before the first child is treated.
Blinding Challenges
Blockers’ effects are hard to mask, risking bias in subjective outcomes like mood. Clinicians or families aware of treatment status might skew assessments. A blinded design, perhaps with sham procedures, is a tall order but worth pursuing. Absent that, expect questions over reliability.
Watch out for blinding problems being ignored. There is no way this can be avoided. Expect rigorous efforts to minimise reporting bias.
Hiding Harms
Adverse events—think osteoporosis or brain changes—could be downplayed as “unrelated” or buried in footnotes. Full disclosure of every scan, test, and dropout reason, published raw, is essential. The Tavistock era taught us opacity breeds mistrust.
Watch out for a clear statement on how the trial intends to handle drop-outs and adverse events.
Outside Influence
With the whole “affirmative care” model at stake, and so many people vested in its success, conflicts of interest loom. Pharmaceutical firms, though less dominant here than in private markets, could nudge the narrative. The trial’s leaders at King’s and South London and Maudsley must declare ties; independence is non-negotiable.
Watch out for activists interference and those who are deeply vested being involved.
A Movable Framework
No public protocol yet leaves room for post-hoc fiddling—shifting endpoints or treatments after peeking at data. Ethical approval hangs in the balance, and critics like Keira Bell stand ready to challenge a loose design. A locked, transparent blueprint, released soon, is the only way forward.
Watch out for ways to ensure public pressure on NHS England and the Health Secretary for this trial to be ethical is strongly felt.
The Stakes
This trial aims to resolve a contentious question—do blockers help more than they harm?—yet its very premise raises doubts. The Quackometer contends that an ethical study is near-impossible when the treatment rests on ideological notions like the “trans child” and “gender identity,” rather than a clear clinical foundation. The Cass Review laid bare a field steeped in ideology over evidence, and Pathways risks perpetuating this mindset.
If it proceeds, it must be held to the highest standard—broad recruitment, robust controls, extended timelines, and untainted data—to limit the potential damage to children. Yet, given the murky waters it navigates, such rigour seems unlikely.
A piercing spotlight, unrelenting and public, is the least these vulnerable participants deserve.
“The Quackometer contends that an ethical study is near-impossible when the treatment rests on ideological notions like the “trans child” and “gender identity,” rather than a clear clinical foundation.”
How common is it for a study to be carried out by the NHS when the underlying reasoning is as shaky as this? Is there any similar instance?