An Evidence-Free Critique of the Cass Review

An overview of what the Yale group paper gets wrong

The Cass Review has reset the international debate on pediatric gender medicine. The Final Report, which was the product of 3.5 years work and was supported by 8 systematic reviews and 1 research study, found that the current practices of gender affirming treatment is supported by only low-quality evidence and that the Endocrine Society and WPATH guidelines are not reliable. In the United Kingdom, the Review has already led to significant restrictions on the availability of puberty blockers and cross sex hormones. The new Labour government has endorsed the Review and NHS England has announced plans to implement its recommendations.

So far, the Cass Review has had little impact in North America and the advocates of gender affirming care are determined to keep it that way. The usual suspects have been publishing a stream of poorly argued and misleading critiques of the Review. The critique that is currently receiving the widest exposure is a white paper An Evidence-Based Critique of “The Cass Review” on Gender-affirming Care for Adolescent Gender Dysphoria. The white paper has nine authors led by Meredithe McNamara, a Assistant Professor of Pediatrics at the Yale School of Medicine. Jack Turban and Johanna Olson-Kennedy are among the other authors. The paper is not peer reviewed and is hosted on the Yale Law School website. It will be referred to as the Yale paper and the authors as the Yale group.

Despite its title, the paper offers little in the way of evidence but relies on sheer volume of minor quibbles, irrelevancies, logical fallacies and outright falsehoods to overwhelm its readers. It is an illustration of  Brandolini’s law: “The amount of energy needed to refute bullshit is an order of magnitude bigger than to produce it.”  The Yale paper has multiple errors of fact or logic and questionable citations on every page, but since it is 39 pages long and has 105 footnotes, it will take hundreds of hours of work to produce a detailed response. While that work is being done (and it is ongoing) the Yale group paper can be shared and cited as the last word on the matter.

Nevertheless, there are some overriding errors in the Yale group paper that can be identified now. This article simply highlights some major themes. It does not comment on some of the more complex issues on evidence-based medicine or call out the many errors which should be too obvious to require much comment.

Minimizing the Effect of the Review

The Yale paper begins by trying to minimize the extent to which the Cass Review represents a rejection of the current model of pediatric gender care. They claim, correctly, that the Cass Review does not recommend a ban on gender affirming treatments for minors. However, they ignore the fact that in the English National Health System a legislated ban is unnecessary since the same results can be obtained through administrative policies. The NHS has already issued service specifications which halt new prescriptions of puberty blockers except as part of a research study and restricts the prescriptions of cross-sex hormones to ages 16 and older. While these changes fall short of a total ban, they are a major change from prior practice in England and current practice in North America.

A second way the Yale team tries to underplay the significance of the Cass Review is by claiming that there is substantial agreement between the Cass Review and the Endocrine Society and WPATH guidelines on key issues. They present quotes from each of these documents which suggests that Cass agrees with WPATH and the Endocrine Society that certain youth with gender dysphoria will benefit from medical transition, that there is a need for a “holistic, comprehensive and individualized assessment and treatment plan” and that “treatment of co-occurring mental health conditions is essential.”

Despite some similarities in language, there is a fundamental difference in the understanding of gender dysphoria between the Cass Review and WPATH and the Endocrine Society. The Cass Review’s understanding is illustrated in a graphic from the Interim Report. Cass sees gender dysphoria as a complex phenomenon with many pathways in and many pathways out. WPATH and the Endocrine Society have little to say about the pathways in and are only interested in the medical pathway out.

While the Cass Review does not entirely reject medical transition, it regards it as only one possible pathway that should be resorted for young people only rarely and with great caution. It expresses concern about the risks of regret and the difficulty of determining which patients will actually benefit from medical transition which is largely absent in the WPATH and Endocrine Society guidelines.

While WPATH does discuss the need for a diagnosis, it regards it more as something that is needed for insurance and legal requirements than an essential component of care. Jack Turban, one of the members of the Yale group, has made equivocal statements on the need for assessments. In his recent book, he suggests that they are unnecessary. By contrast, the Cass Review emphasizes the need for a thorough diagnostic process that includes a differential diagnosis which considers whether a patient’s distress might be due to causes other than gender dysphoria and therefore that transition may not be appropriate. The interim report of the Cass Review noted that many clinicians have been afraid to formulate a differential diagnosis because of pressure from professional bodies to take a purely affirmative approach.

With co-existing mental health conditions, WPATH and the Endocrine Society are mainly concerned that these conditions be controlled to prepare the patient for hormonal treatments. The Cass Review calls for a genuinely holistic approach in which all of the patient’s mental health and neurodevelopmental conditions are taken into account and treated through an individualized plan which may or may not include medical transition.

Bias and Expertise

The Yale group shows a total lack of understanding of basic principles of evidence-based medicine such as the management of bias and conflicts of interest. They describe their expertise which  they say includes  “86 years of experience in caring for more than 4800 transgender youth and have published 278 peer-reviewed studies, 168 of which are in the field of gender-affirming care.”

They contrast this with the Cass Review saying,

The transparency and expertise of our group starkly contrast with the Review’s authors. Most of the Review’s known contributors have neither research nor clinical experience in transgender healthcare. The Review incorrectly assumes that clinicians who provide and conduct research in transgender healthcare are biased. Expertise is not considered bias in any other realm of science or medicine, and it should not be here.(p. 3)

The experience of the Yale group may not be all that they claim. For example, Leor Sapir reports that in depositions in court cases where she has been an expert witness, Meredithe McNamara has admitted that she does not provide gender-affirming care and has only referred two patients to gender clinics.

However, the more important point is that in evidence-based medicine, direct clinical expertise is considered to be a source of bias. Evidence-based medicine was developed to replace the GOBSAT or Good Old Boys (and girls and non-binaries) Sitting Around a Table model of decision making. Guideline development protocols include conflict of interest rules which screen members for financial and non-financial conflicts of interest. Financial conflicts can arise from receiving financial support from a drug manufacturer whose products are being evaluated or from earning a substantial part of one’s income from a treatment under review. Non-financial conflicts include having published research which is being evaluated or being involved in patient advocacy. A properly constituted guideline development group will consult with subject matter experts (who will almost inevitably have conflicts of interest) but the final recommendations will be approved only by members who are free of conflicts. These will generally be scientific experts with specific expertise in evaluating medical research.

Although the Cass Review was not intended as a formal guideline development group, it reflects this basic principle. Dr. Cass was selected to conduct the review precisely because, although she is an experienced pediatrician, she had not worked on a gender clinic or taken part in the debate over gender-affirming treatments.

Randomized Control Trials

The Yale team claims that the Cass Review insisted that only randomized control trials could provide high quality evidence and argue at length that this type of trial is not feasible in gender medicine. This issue has been raised before and was dealt with by Dr. Cass in a FAQ to the final report. While the Cass Review does describe randomized control trials as the “gold standard” in medical research, it recognized that well designed cohort studies can also provide at least moderate quality evidence.

The problem that the Cass Review and the systematic reviews it commissioned looked at all of the studies on gender affirming care using assessment tools designed for evaluating non-randomized studies and still found that the evidence was low quality. The problem with the evidence base is not just the absence of randomized control trials. All of the existing clinical studies of any kind are poorly designed, inconclusive or both.

The Systematic Reviews

One of the foundations of the Cass Review is the series of systematic reviews which were prepared by a team at the University of York. The Yale group realized that undermining these reviews was essential to discrediting Cass, but they do not have much to go on.

The first objection they raised looked like it had some substance. One of the requirements for a systematic review is that a protocol describing the review methodology be registered in advance. The protocol for the systematic reviews which the York team registered stated that they would use the Mixed Methods Assessment Tool (MMAT) to evaluate studies but the systematic reviews of puberty blockers, cross-sex hormones and social transition actually used a modified version of the Newcastle Ottawa Scale. The Yale group objected that this deviation from the registered protocol was not explained or justified.

The York team has now registered an update to their protocol which explains the reasons for the change. The review protocol was registered to cover a series of questions which became the basis of nine published reviews. The team selected MMAT as a catch-all for the different types of studies they expected to examine. However, after they began to look at the actual studies, they concluded that it would be preferable to use an assessment tool which was best suited to the kind of studies they would be examining for each review question. They selected the Newcastle Ottawa Scale for three of the reviews because it was specifically designed for evaluating the kind of non-random studies that make up most of the evidence base for pediatric gender medicine. (Take note that far from disregarding any studies that were not randomized control trials, the review team selected an assessment tool adapted to non-random studies.)

The Yale group raises other technical concerns about the review methodology which will have to be dealt with in detail by someone with expertise in evidence-based medicine. However, the key question is whether any of these concerns are sufficient to invalidate the findings of the systematic reviews. This seems unlikely as there have been six other systematic reviews of pediatric gender affirming care which have used different methodologies but reached the same conclusion as the York reviews: the evidence supporting gender affirming care for children and young people is low certainty.

Evidence in Pediatric Care

Since it is hard to make a case that the evidence for pediatric gender medicine is anything but low quality, the Yale group has a fallback position of arguing that this does not matter because making treatment decisions on the basis of low-quality evidence is common practice in pediatric medicine. However, none of the examples they give are comparable to gender affirming treatments.

A number of examples are drawn from decisions that have to be made in a neonatal intensive care unit. These involve situations where all of the alternatives are only supported by low certainty evidence but the consequence of failing to treat will be death. Further, the intended result of treatment is a healthy baby. This is one of the exceptional situations where  strong recommendations based on low certainty evidence may be justified.

By contrast, gender affirming care treats psychological conditions which, in past, often resolved during the normal process of maturation in puberty. Puberty blockers and cross-sex hormones have serious side effects and even in a best-case scenario, a patient who proceeds with medical transition will be dependent on artificial hormones for life.

A second example the refer to is the use of weight loss drugs weight loss drugs to treat childhood obesity. This is another area where the evidence is low certainty. However, unlike gender dysphoria, obesity has an objective diagnostic test and can lead worsened health and shortened life expectancy if untreated. Also unlike the WPATH and Endocrine Society guidelines, the AAP guideline on childhood obesity acknowledges the limits of the evidence base makes cautious recommendations. It says that doctors “may offer” children ages 8 to 11 weight loss drugs “as an adjunct to health behaviour and lifestyle treatment.”

They also make a comparison to reproductive healthcare but fail to realized that reproductive healthcare for adolescents does not include treatments which lead to permanent sterility, which will result from the combination of puberty blockers and cross-sex hormones.

Long Run Data

Some of the criticisms that the Yale group makes are really concessions to their critics. For example, the Cass Review expresses concern the lack of long-term studies which follow children from the start of puberty suppression to adulthood to determine whether they grow into healthy and happy adults. The 2014 Amsterdam clinic study is still the only study which does this and it only followed up one-year post-surgery and has other significant problems. The Yale Group describes this concern with long-term data “outsized” and “vague: and makes the astonishing statement, “Further, the Review expects an abundance of long-term data on treatments that have only been more readily available for gender-affirming purposes over the past 8-10 years.”

This statement contradicts assurances offered by advocates of gender affirming care that the medications in question have been around for decades. Jack Turban says this in his recent book (at p. 136) and Meredithe McNamara makes a similar statement in one of her expert reports. If pressed, they would no doubt claim that the use “for decades” relates to precocious puberty. They Yale group can’t have it both ways. If there is limited long term data on a treatment you cannot confidently assert that it is effective.

One Treatment or Two?

The Yale group makes what is really another concession to critics of gender affirming care when it objects that the Cass Review and its associated systematic reviews evaluated puberty blockers and cross-sex hormones as separate treatments. The Yale group says that “puberty pausing medications themselves are not gender-affirming: they simply aim to pause the anatomical and physiological changes associated with puberty.”

They on to say that the decision to review puberty blockers and cross sex hormones separately is “deeply problematic because most patients who receive puberty-pausing medications progress to gender-affirming hormone therapy.”

One of the reasons that the Cass Review evaluated puberty blockers and cross-sex hormones separately is because that is how they have been presented in the affirming care model. In the Bell v. Tavistock case the lawyers for the Tavistock clinic argued that puberty blockers and cross sex hormones should be considered as separate treatments for the purposes of informed consent. Puberty blockers were presented as a “pause button” for a diagnostic phase which would provide time to reflect before making the decision to proceed with transition.

Critics of the affirming model have argued that because it has been found that almost all patients given puberty blockers proceed to cross-sex hormones, they should be regarded as a single treatment. Since the combined effects of puberty blockers and cross-sex hormones are clearly established to have irreversible effects, including sterility, it is necessary to consider whether pre-pubescent children in fact have the capacity of consent to these consequences.

Exponential Growth

The Yale group takes issue with the use of the term exponential in the Cass Review to describe the increase in referrals to gender clinics. In fact, the WPATH SOC 8 uses exactly the same language in Chapter 6 where it refers to “the exponential growth in adolescent referral rates.”  Furthermore, the claim by the Cass Review that there was an exponential increase in referrals over 5 years is correct in a strict mathematical sense. Exponential growth means growth that is proportional to the size of the population. The compounding effect means that what starts out as a very small increase, in absolute terms, can turn into a very large increase short time. The data used in the Cass Review shows that referrals to the Tavistock pediatric gender clinic increased from 51 in 2009 to 1,766 in 2016. This represents exponential growth at a factor of 1.66 per year.

A Concluding Self-Own

The final section of the Yale paper contains a major, unforced blunder. It claims that the relationship between the Cass Review and the systematic review team at York University did not follow all of the protocols for a formal clinical guideline development process. The relevancy of this criticism is questionable since the Cass Review was not set up to develop clinical guidelines.

While, the main argument is weak, the Yale group makes their case worse by holding up a systematic review of gender affirming hormones, conducted by Johns Hopkins University at the request of WPATH (Baker et al 2021)  as an example of a proper relation between systematic reviews and guideline development. However, internal WPATH e-mail disclosed under subpoena in the case of Boe v. Marshall show that the relationship between Johns Hopkins team was totally improper. WPATH demanded a high degree of control over the conduct and publication of the systematic reviews. The Johns Hopkins team initially resisted; , but finally agreed to a publication policy which gave WPATH the right to approve all published reviews. The Baker review was the only review published under this new policy. One other review had been published before the policy was implemented. The Johns Hopkins team registered research protocols for 10 other reviews which have never been published. Unlike the Cass Review, WPATH SOC8 does claim to be an evidence-based clinical guideline. All of the York University reviews were published in peer reviewed journals on the same day the Cass Review was released.

It is hard to see why the Yale group, who certainly have one eye on litigation, would include statements that provide fodder for a withering cross-examination. Kellan Baker, who is the lead author of the published review, is a member of the Yale group so they must have been aware of the actual relationship between WPATH and the Johns Hopkins team. By the time the paper was published the WPATH e-mail story had become public. On June 24 and 25 the story had been reported in Twitter/X thread from Leor Sapir, a Substack post from Jesse Singal and was even covered by the New York Times. The Yale group did not publish their document until July 1, 2024 so they had nearly a week to reconsider their position but did nothing.

It may be that the Yale group was so immersed in their ideological bubble that they either totally missed the story or failed to realize how damaging it was to their case. The whole Yale paper seems to be a holdover from only a few years ago when virtually the entire mainstream media was in thrall to gender ideology and trans activists could say almost anything they wanted without fear of contradiction. Those days are over and they are not coming back. The Yale paper did appear to have some influence on the council of the British Medical Association, which recently adopted a resolution critical of the Cass Review. However, the resolution was met with immediate pushback from over 900 doctors who signed a letter opposing the resolution.