Ethical Care Necessitates Synthesizing the Best Available Evidence

Moti Gorin, Chan Kulatunga-Moruzi, Ari R. Joffe & J. Cohn

Pages 73-76 | Publié en ligne : 06 juin 2025 - The American Journal of Bioethics - Volume 25, 2025

https://www.tandfonline.com/doi/full/10.1080/15265161.2025.2497990

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INTRODUCTION: EVIDENCE IS KEY

Findings of systematic evidence reviews critically undermine numerous assertions advanced by Jeffrey Kirby (Citation2025) in “A Multi-Lens Ethics Analysis of Gender-Affirming Care for Youth with Implications for Practice and Policy”, with consequences for his ethical conclusions.

Well conducted systematic reviews of evidence are foundational components of evidence-based medicine. Using standardized protocols designed to minimize bias and ensure reliability, they rigorously evaluate the quality of existing scientific evidence, summarizing

the literature on a particular question [using] explicitly defined and reproducible methods to systematically search, critically appraise, and synthesise primary research information (Cass Citation2024, 54).

Systematic reviews are also the basis for trustworthy clinical guidelines (Block Citation2023) and provide the most reliable information regarding evidence certainty/quality (individual studies are lower quality; expert opinion is lowest [Cass Citation2024; McDeavitt et al. Citation2025]). Overviews of systematic reviews (umbrella reviews), such as Brignardello-Petersen and Wiercioch (Citation2022), rigorously synthesize systematic reviews of studies.

STATE OF THE EVIDENCE

Multiple systematic reviews of the scientific evidence underpinning pediatric medical transition (puberty blockers, hormones, surgery), commissioned by international health authorities and independently conducted by leading researchers in the UK, Europe, and Canada, have all come to the same conclusion: the evidence for benefit is low and very low certainty (Brignardello-Petersen and Wiercioch Citation2022; Cass Citation2024; McDeavitt et al. Citation2025; Miroshnychenko et al., Citation2024, Citation2025a, Citation2025b). Low or very low certainty is a GRADE framework rating corresponding to “limited” or “very little” confidence that the true outcome will match the effect estimate, i.e. “[t]he true effect may be/is likely to be substantially different from the estimate” of the effect, respectively (Miroshnychenko et al. Citation2024, 86). More broadly, “[d]ue to important limitations in the body of evidence, there is great uncertainty about the effects of puberty blockers, cross-sex hormones and surgeries in young people [ages 21 and below] with gender dysphoria” (Brignardello-Petersen and Wiercioch Citation2022, 5). Pediatric gender medicine is “an area of remarkably weak evidence” (Cass Citation2024, 13).

Table 1 summarizes several potential beneficial outcomes assessed by systematic reviews using GRADE or modified GRADE.

Kirby’s ethical analysis omits these significant scientific developments. It relies instead on a small, highly select sample of weak and sometimes outdated studies, most of which were included in the aforementioned systematic reviews (see also Abbruzzese et al. [Citation2023]), to claim “enhanced mental health functioning and wellbeing” (Kriby Citation2025, 63). Nor does Kirby provide evidence in support of his claims regarding other hypothesized benefits (Kirby Citation2025). Moreover, medical interventions do not appear to provide “time to think” [Cass Citation2024, 176]. Pediatric GAC (Gender Affirming Care) presents known or plausible risks to fertility, sexual function, bone mineral density, developing cognitive function, cardiovascular health, and other important health outcomes (Abbruzzese et al., Citation2023; Cass Citation2024; McDeavitt et al. Citation2025). Kirby asserts that “small numbers” of patients detransition (Kirby Citation2025), mentioning a single study with inadequate follow-up time; however, detransition and regret rates are unknown (Brignardello-Petersen and Wiercioch 2022; Cass Citation2024; McDeavitt et al. Citation2025).

The evidence Kirby presents, therefore, is inadequate to support his claim that identified benefits “appear to outweigh the known, mild to moderate, identified burdens of GAC” (Kirby Citation2025, 63). Neither the studies he cites nor the body of evidence more generally support the statement that “the current comparative analysis of the benefits and burdens of GAC for youth supports continued use, of a version of the gender-affirming care model for youth” (Kirby Citation2025, 68).

MISCHARACTERIZATION OF THE DEBATE AS POLITICAL

Finland, Sweden, and the UK have issued updated, more cautious recommendations based upon and explained by robust systematic evidence reviews (Cass Citation2024; Pasternak et al., Citation2019)—not by “a strong/dominant wave of political opposition” (Kirby Citation2025, 66). On the basis of their systematic reviews, Sweden concluded that the “risks of puberty blockers and treatment with hormones ‘currently outweigh the possible benefits’ for minors” (Block Citation2023, 2) and now recommends psychological support as first line treatment, as do Finland and the UK (Block Citation2023; Cass Citation2024).

Strikingly, Kirby makes no mention of these major international developments. He instead claims that parents reluctant to endorse medical transition for their children “may be influenced by the emerging conservative, parental-rights movement” (Kirby Citation2025, 60). Another possibility, left unexplored by Kirby, is that these parents are aware of scientific developments in the field and consequently assess medical intervention as inappropriate for their children, given the unproven benefits and known risks.

TRUSTWORTHY GUIDELINES

Kirby’s recommendations rely upon what he calls “standard-of-care guidelines” (Kirby Citation2025, 66), and he characterizes the World Professional Association for Transgender Health (WPATH), the Endocrine Society, and two other organizations deferring to or part of WPATH as “acknowledged, credible agencies/organizations that develop and revise GAC practice guidelines” (Kirby Citation2025, 63). However, in a formal assessment (Cass Citation2024), WPATH and Endocrine Society guidelines were not recommended for use, while the Finnish and Swedish guidelines, based upon proper evidence synthesis, were. Trustworthy guidelines are based upon systematic reviews of evidence and must “link the strength of the recommendations to the quality of the evidence” (Block Citation2023, 2). In contrast, WPATH’s adolescent guidelines inaccurately claim that a systematic review of outcomes in adolescents was “not possible” (although some were already in hand, see for example, Brignardello-Petersen and Wiercioch [Citation2022]), while those of the Endocrine Society make strong recommendations on the basis of low and very low quality evidence with no justification (Block Citation2023). Moreover, it has now come to light that WPATH had commissioned systematic reviews, but interfered with their publication (Cheung et al., Citation2025).

“MISINFORMATION” RELATED TO HEALTH RESEARCH

Kirby also discusses “the misunderstanding of, and/or the intentional promotion of mis/disinformation about, the nature and types of research that can and should inform gender-affirming care for youth” (Kirby Citation2025, 65). He implies those concerned about the limited evidence demand randomized controlled trials (RCTs). This is untrue and mischaracterizes the requirements of evidence-based medicine (Cass Citation2024; Cheung et al., Citation2025; McDeavitt et al. Citation2025). Kirby, then, inexplicably claims: “Ironically, Dr. Cass’s conclusion that, for the majority, a medical pathway is not the best way to manage the gender-related distress of youth at the present time is not grounded by existing research” (Kirby Citation2025, 66). In fact, the Cass Review recommendations are based upon its synthesis of commissioned qualitative research, seven commissioned (peer-reviewed) systematic reviews, four other systematic reviews, and engagement with all groups of stakeholders, including patients and parents (Cass Citation2024). The Cass Review is the most comprehensive and rigorous synthesis of the evidence base for pediatric GAC to date. Kirby’s criticisms of the Cass Review appear to be relying upon a non-peer reviewed Yale Law School website essay containing numerous inaccuracies and unsupported claims, already addressed in peer-reviewed critiques (Cheung et al. Citation2025; McDeavitt et al. Citation2025). We also note the Cass Review statement is not as strong as Kirby reports, but rather: “For the majority of young people, a medical pathway may not be the best way….” (Cass Citation2024, 30, italics added).

Notably, despite his criticisms, several of Kirby’s own recommendations already are incorporated into the Cass Review. For instance, Kirby recommends (Kirby Citation2025, 67–68):

public health care policy should be meaningfully informed by the outcomes of a dynamic process of deliberative engagement by legitimate stakeholders (including those who are directly affected by the policy, i.e., in this case TDGY and their parents), topic-domain experts, relevant, non-politicized health organizations and relevant resource persons including, as appropriate, health law and health-care-ethics participants.

The Cass Review addressed this goal with commissioned qualitative research and meetings with >1,000 stakeholders (Cass Citation2024).

Also, Kirby states “like/similar individuals and groups of people should be treated alike/similarly unless a relevant difference can be demonstrated between/among them that warrants different treatment” (Kirby Citation2025, 64). Dr. Cass concurs: “Firstly, you [the young people] must have the same standards of care as everyone else in the NHS, and that means basing treatments on good evidence” (Cass Citation2024, 14).

CONCLUSION

An updated and accurate picture of the state of the underlying scientific evidence and the relevant clinical guidelines undermines Kirby’s ethical claims in support of pediatric GAC. First, it is not true that evidence supports a favorable risk/benefit ratio for the use of hormonal or surgical interventions to treat pediatric gender dysphoria. Therefore, the offering and provision of these interventions to adolescents for these purposes is inconsistent with clinicians’ duties of nonmaleficence and beneficence. Second, while Kirby certainly is correct that clinicians have a duty to respect patient autonomy, this does not entail a duty to offer interventions that lack a positive risk/benefit ratio. On the contrary, clinicians have a duty to abstain from providing treatments whose anticipated benefits are not proportionate to their anticipated harms. Finally, while it is an injustice to withhold beneficial, evidence-based treatments from vulnerable patients, it also is an injustice to offer and provide to vulnerable patients interventions where risks outweigh benefits, especially when alternative therapy is available. Kirby and the authors of the Finnish, Swedish and UK recommendations all aim to alleviate the suffering of vulnerable youth and improve their health. However, only the latter three, prioritizing “[s]tandard evidence-based psychological and psychopharmacological treatment” (Cass Citation2024, 31) propose an approach that is grounded in the best available evidence and hence consistent with best medical practice.