PATHWAYS Trial: Participant Info Sheets Fail HRA Standards

PATHWAYS Trial Participant Information Sheets do not meet HRA standards

Participant Information Sheets (PIS) are a legal requirement to enable those taking part in research to give informed consent or (in the case of children) assent. The Health Research Authority (HRA) has set standards for PIS.

The following list of concerns has been sent to the HRA and the author, who is a parent of a trans identifying child, has kindly allowed us to reproduce their letter to the HRA here.

Summary of concerns

The PATHWAYS PIS fails to meet HRA requirements in several ways. The PIS does not provide a clear or realistic account of the risk/benefit profile of puberty suppression, nor does it offer adequate information about the condition being treated, or the reasons for treatment. The PIS has insufficient information about the likely implications of the trial intervention or about what can realistically be achieved for a child who joins the trial.

The PIS-Y for young people to assent to participation has not been adapted in line with HRA standards to differentiate it from the parental consent PIS. The accompanying Easy Read document falls far short of the HRA recommendations for this kind of information.

As a result, the PIS does not provide parents or children with “good information”, which the HRA emphasises is required “to be able to decide whether to take part in research”.

The importance of accuracy in the PIS cannot be underestimated, particularly in light of the Multi Professional Review Group report on Tavistock GIDS referrals for puberty blockers, which found that “child and parental misconceptions about puberty, puberty blockers and hormones […] were often evident in the child and parental statements” even after the service “had deemed the child appropriate for referral for physical intervention”. The PATHWAYS PIS should have been designed to minimise the risk of these widespread patient/parent misconceptions recurring. 

1. Risk/benefit profile inadequately described

HRA guidance on creating a Participant Information Sheet states that “in order to facilitate fair decision-making, you must state clearly what the risks and benefits of your study realistically are.” The PATHWAYS PIS fails to meet this HRA standard in a number of key areas.

Failure to acknowledge a “critically important” risk

The PIS fails to inform parents that puberty suppression may affect their child’s identity development and thus ignores one of the “critically important unanswered questions” identified by Dr Hilary Cass when she first recommended research into puberty suppression for gender dysphoria in her July 2022 letter to NHSE. 

Dr Cass described the key uncertainties regarding puberty suppression as follows: 
(1) “It is the […] option regarding a ‘pause’ for decision making about which we have the least information […] We therefore have no way of knowing whether, rather than buying time to make a decision, puberty blockers may disrupt that decision-making process.”
(2) “There has been very limited research on the short-, medium- or longer-term impact of puberty-blockers on neurocognitive development.”

It is clear from Dr Cass’s letter that she expected the aforementioned questions to be pivotal in any subsequent research: “In light of these critically important unanswered questions, I would suggest that consideration is given to the rapid establishment of the necessary research infrastructure to prospectively enrol young people being considered for hormone treatment into a formal research programme.” 

However, the PATHWAYS trial is not designed in a way that will offer meaningful insight on either of these questions. Instead (as described in more detail below) the trial proceeds based on the unevidenced hypothesis that puberty blockers might offer “time to think”.

In the PIS, parents are a) misled about what the trial can offer in terms of addressing the key uncertainties about puberty suppression; and b) are not informed about significant risks this intervention poses to their child. On the implication of question (1), the PIS lacks any kind of clear statement equivalent to the final Cass Review acknowledgement that puberty blockers “may change the trajectory of psychosexual and gender identity development”. In terms of question (2), Cass warns that “brain maturation may be temporarily or permanently disrupted by puberty blockers, which could have significant impact on the ability to make complex risk-laden decisions, as well as possible longer-term neuropsychological consequences.” The PIS mention of “concerns that GnRHa might affect brain development and learning” cannot reasonably be interpreted as referring to identity development or complex risk-laden decision-making given the subsequent statement “based on findings from animal studies”. Parents are thus not fully informed of critical risks to their child.

The GIDS “Early Intervention Study” (EIS) into puberty blockers (beginning in 2011 and published in 2021) provided clearer information than PATHWAYS in terms of spelling out the risk that puberty suppression could impact gender identity development. The GIDS EIS “Young Person Information Sheet” (personal copy) for study participants stated that “hormone blockers could affect your memory, concentration and the way you feel. They can also affect how you feel about your gender and how likely you are to change your mind about your gender identity.” (emphasis added). No new evidence has emerged since then that would warrant omission of this warning.

Misrepresentation of PBs as “time to think” breaches HRA guidance

The PIS states that “puberty suppressing hormones may provide young people with gender incongruence time to explore their gender identity without worrying about their body starting to change”, but does not emphasise how speculative that hypothesis is. A more accurate representation for parents would reflect the Cass Review finding that “there is no evidence that puberty blockers buy time to think”. As it stands, the PIS uses the kind of language the HRA explicitly warned against in its investigation into the GIDS EIS, which stated that “researchers and clinical staff working in gender identity development should consider carefully the terms that they use in describing treatments e.g. avoid referring to puberty suppression as providing a ‘breathing space’, to avoid risk of misunderstanding.”

Failure to update PIS in line with REC instruction

Information released by the HRA shows that a clear instruction was issued by the REC to update the PATHWAYS trial PIS to reflect the risk that puberty blockers might impact the child’s identity development. The REC minutes for 4 September 2025 record that the committee “asked whether blocking the normal biological process of puberty via the study drug might change the participants views, or prevent further development of their views, on self-identity.” The following sentence reports that the PATHWAYS researchers “stated that the gender services were acutely aware of this.” This paragraph concludes by stating “The Committee requested that the impact of the drug be made clear in the PIS (Action 11b).”

Contrary to this stipulation, the PIS has not been updated to reflect the risk outlined by the REC, i.e. that puberty blockers “might change the participants views, or prevent further development of their views, on self-identity”. (Action 11b does not explicitly list this risk, but the nature of the requested PIS update should be clear from the main text on page 3 of the REC minutes that resulted in Action 11b being created).

In addition, the response to the REC question on this matter raises concern that the PATHWAYS team may not have fully understood the question. This in turn may explain why the PIS was not updated as required. The PATHWAYS response (first paragraph on page 3 of the minutes) to the question about puberty suppression altering a child’s identity trajectory refers to a careful 9-month holistic assessment resulting in only 5% of children being deemed clinically eligible for PBs. But this response is about pre-trial screening and is irrelevant to the question of the child’s subsequent trajectory once on puberty blockers. The PATHWAYS researchers conclude their response by stating that “it would be the national Multi-Disciplinary Team (MDT) that made the decision to refer an individual into the trial only when it was confident that this treatment was appropriate for the individual”. The overall response could be taken as implying that children will only be selected for the trial once their gender identity is stable and secure (as established by 9 months of careful exploration). But in this case, why is the treatment rationale described as offering children “time to explore their gender identity”?

Finally, the PATHWAYS researchers told the REC that “the question itself [i.e. whether puberty suppression might impact the child’s identity development] was one of the ones the trial was designed to answer”. However, this question is not listed in the Protocol either as a primary or secondary research objective, or as one of the exploratory objectives. Without further information from the PATHWAYS team, it is not clear how this trial could contribute information to help answer the question of a potential impact of PBs on identity development. The HRA’s previous comment on the GIDS EIS seems to apply equally to the PATHWAYS trial, “the present study was not designed to investigate the implications on persistence or desistence of offering puberty suppression to a wider range of patients, it was limited to a group that had already demonstrated persistence and were actively requesting puberty blockers.”

Likely progression from PBs to hormones omitted

Despite a well-documented high progression rate from puberty blockers to cross-sex hormones (98% in the GIDS EIS, over 90% across a range of other studies in the 2025 US HHS report), there is no mention of this in the PIS. This gives the misleading impression that PBs are a stand-alone treatment, rather than a likely first step towards lifelong medicalisation. Advocates of puberty suppression acknowledge that “these medications are nearly always part of a staged process that includes other treatments.” The MPRG highlighted as a “recurrent concern” the fact that GIDS staff were “not sharing figures around how many children who start puberty blockers go on to hormone treatment”, citing this as an example of the “inadequacy and on occasions inaccuracy of answers given to children and their families”. As a consequence, the MPRG “often requested further confirmation that […] the 98% expectation of progress to hormone treatment had been adequately discussed and understood”. By omitting crucial information about the child’s likely future trajectory, the PATHWAYS PIS fails to remedy this problem.

This is another area where the PATHWAYS PIS does not reflect the HRA’s own previous advice in relation to the GIDS EIS, which made clear that puberty suppression should be described as the first step on a medical pathway involving progression to cross-sex hormones: “it would have reduced confusion if the purpose of the treatment had been described as being offered specifically to children demonstrating a strong and persistent gender identity dysphoria at an early stage in puberty, such that the suppression of puberty would allow subsequent cross-sex hormone treatment without the need to surgically reverse or otherwise mask the unwanted physical effects of puberty in the birth gender.”

Uncertain evidence base for hormones omitted

There is no mention in the PIS of how weak the evidence base is for cross-sex hormones at 16-18, which is the likely next stage for trial participants. This uncertain evidence is why the Cass Review recommended “extreme caution” when considering cross-sex hormones from age 16, and the need for “a clear clinical rationale for providing hormones at this stage rather than waiting until an individual reaches 18” in order to “keep options open during this important developmental window”. In the year following the closure of the GIDS service, not a single patient aged 16-18 was deemed appropriate for cross-sex hormones. The PB trial is likely to fundamentally change that situation, yet parents are not warned about the lack of safety and efficacy data for cross-sex hormones, or of the Cass Review conclusion that “even after masculinising/feminising hormones, dysphoria may still persist”. The failure to provide this information obscures understanding of what will happen “after the research study”, which the HRA lists as a key component in a PIS.

Risks of developmental ‘limbo’ omitted

The PIS does not spell out the consequences of suspending a child’s natural development such that they are out of sync with their peers in terms of physical, psychosocial and sexual development. The Cass Review found that “there are no good studies on the psychological, psychosexual and developmental impact of this period of divergence from peers”. The Review also warns that “if a young person is already on puberty blockers they will need to make the decision to consent to masculinising/feminising hormones at a point when their psychosexual development has been paused, and possibly with little experience of their biological puberty”. The PIS fails to explain to parents that puberty suppression will put their child in an artificial developmental ‘limbo’ with an unknown potential risk of iatrogenic harm.

Speculative benefits are overstated 

The PIS states “doctors have thought [puberty suppression] might help young people to focus more on things that improve their quality of life, like their interests, school, friendships and relationships. However, there is currently limited evidence to show whether these outcomes are consistently achieved when young people take GnRHa.” By including the word “consistently”, the PIS inaccurately implies that these outcomes are achieved, just not all the time.

Unrealistic representation of fertility preservation prospects

The PIS briefly mentions fertility, including the child being “referred to a fertility specialist to discuss storing eggs or sperm”. This does not accurately reflect the profound challenges and uncertainties of attempting fertility preservation at such a young age. For girls, there is no mention that egg preservation alone is not the only consideration if they proceed on a medical pathway (e.g. that could impact pregnancy itself). Parents need to understand that fertility preservation for children of this age who do not have a life-threatening condition is unprecedented.

Insufficient clarity around sexual dysfunction risk

The PIS briefly mentions a risk to “sexual development and function”, but does not adequately explain in non-technical language what this might mean so that a parent can understand the potential implications for their child’s future ability to participate in healthy sexual relationships and to experience orgasm. Parents are thus not fully informed about the nature of the risk they are consenting to on behalf of their child. This must be spelled out more clearly, particularly given the high progression rate from PBs to cross-sex hormones. The specific risk associated with early puberty suppression (e.g. at Tanner Stage 2) followed by cross-sex hormones must also be addressed explicitly so that parents can understand the pros and cons of the timing of the intervention.

No mention of detransition or regret as potential harms

The PIS makes no mention of the risk that a child might in future feel differently about their gender identity or that they may regret the medical steps taken at such a young age. Parents of a distressed young adolescent need to be made aware of the Cass Review finding that “whilst some young people may feel an urgency to transition, young adults looking back at their younger selves would often advise slowing down.” Parents also need help to understand child development and the fluidity of identity during this phase of life: “the Review heard accounts from young adults and parents about young people who felt certain about a binary gender identity in teenage years and then became more fluid in young adulthood or reverted to their birth-registered gender”. This vitally important conclusion by the Cass Review — that children’s long-term feelings about their identity are unpredictable — is omitted from the PIS. A lack of reliable data on the prevalence of identity change, detransition or regret does not justify omitting these outcomes from the PIS, the unknowns are just as important.

Risks of post-trial continuation of PBs are not explained

For participants who complete the 2-year PB trial and are not yet 16, cross-sex hormones are not a treatment option and there is a possibility that the child will be approved to continue on puberty blockers. The PIS covers this on pages 9-10 in the section “What happens when my child’s treatment in the trial ends?”. This section does not reflect the magnitude of the risk the child could potentially be exposed to during this extended treatment-outside-the-trial period. Parents need clear information that consenting to their child’s participation in the trial may result in extended exposure to PBs beyond the trial period itself, resulting in a possible suppression of puberty for 5 years or more (e.g. for an 11 year old approved for trial participation who continues on PBs until the age of 16). This prolonged exposure to what is currently a banned substance may compound the cognitive, bone health and other unknown risks that apply during the 2-year trial period, but this is not explained in the PIS.

Potential treatment side effects are minimised

The PIS tells parents that “most side effects are mild and go away when treatment stops”. Although this statement is made in relation to the use of GnRHa for indications such as precocious puberty, it could easily be misinterpreted as being applicable in the context of the trial too. The Multi Professional Review Group emphasised the importance of “correcting parents when they quoted use in [gender dysphoria] to be the same as licensed use in precocious puberty”, which they found to be a common misconception. The PIS should spell out that the impact of puberty blockers is likely to be quite different for trial participants. For instance, the impact of GnRHa on patients in mid-late puberty may be particularly profound as a recent study found “side effects, especially hot flushes, abdominal discomfort, and emotional disturbances, were significantly more common in the Tanner 4/5 group.” At the very least, the claim of “mild” side effects is potentially misleading. Given the timing of puberty suppression for trial participants during a period that is crucial for bone health and cognitive development, claims about the duration of any side effects should also be avoided. 

2. Inadequate portrayal of the condition being treated 

HRA guidance on creating a Participant Information Sheet states that it must “provide clear information on the essential elements of the study, such as […] the condition or treatment under study”. The PATHWAYS PIS does not meet that standard, particularly in light of the Cass Review findings that prompted this research and the MPRG report that found widespread “grave misunderstandings of the nature of gender dysphoria” among parents of children referred for hormonal interventions.

Inadequate information about “gender incongruence”

The PIS indicates that the condition being treated is “gender incongruence”, which it describes as being “when a person’s gender identity does not match their sex registered at birth.” Gender identity is not defined in the PIS, nor is there any acknowledgement that this is a subjective and contested concept. This term does not meet the HRA requirement to use “non-technical terms that a lay person will easily understand”. The PIS fails to point out that the term gender identity is not used in the ICD-11 diagnosis of gender incongruence. Parents are thus given a definition of gender incongruence that is different to the official clinical description, using a technical or specialist term (gender identity) that is undefined.

Subjective and uncertain nature of the diagnosis not acknowledged

The PIS fails to explain that a diagnosis of “gender incongruence” (or “gender dysphoria” as previously used) lacks predictive power. The Cass Review found that “although a diagnosis of gender dysphoria has been seen as necessary for initiating medical treatment, it is not reliably predictive of whether that young person will have longstanding gender incongruence in the future, or whether medical intervention will be the best option for them.” This is echoed in the MPRG report, which found that “the DSM-5 diagnostic criteria for gender dysphoria has [sic] a low threshold based on overlapping criteria, and is likely to create false positives”. The PIS gives parents a false sense of confidence in the clinical diagnosis and its significance for their child by failing to mention diagnostic uncertainty.

The MPRG found widespread misconceptions about the underlying diagnosis among parents whose children were being referred for endocrine treatments by GIDS: “many [parents] betrayed grave misunderstandings of the nature of gender dysphoria and the outcome of physical treatments.” The PATHWAYS PIS does not contain adequate information to ensure such misconceptions are avoided in future.

No mention of diagnostic overshadowing

The PIS states that “puberty can be a difficult time for children and young people with gender incongruence, as the physical changes they experience may not align with their gender identity.” This is a speculative statement based firstly on the idea that children have an inner “gender identity” and secondly that this “identity” can somehow be misaligned from their body. Without a definition of gender identity or an explanation of its relationship to the body, this is conjecture. Many parents will be unaware that this description of the child’s experience lacks objective evidence. The PIS also fails to highlight the myriad reasons why “puberty can be a difficult time for children and young people”. Parents are not warned how easily symptoms of distress can be misinterpreted.

Omission of peer and socio-cultural influences (including online content)

The social component of the child’s experience is never mentioned in the PIS. Parents are thus given no understanding of the Cass Review observation that “all experiences of health and illness are understood through the norms and beliefs of an individual’s trusted social group. Thus, it is more likely that bodily discomfort, mental distress or perceived differences from peers may be interpreted through this cultural lens.” 

Failure to address possible impact of social transition on the child

Parents are not warned that decisions they have taken previously, e.g. to refer to their child by a different name or pronouns, could have impacted the child’s identity development and the urge to pursue a medicalised pathway.

The Cass Review found that “it is possible that social transition in childhood may change the trajectory of gender identity development for children with early gender incongruence” and that, although a causal connection cannot be proven, “those who had socially transitioned at an earlier age and/or prior to being seen in clinic were more likely to proceed to a medical pathway.” Despite these concerns the Review also noted that “in the UK and internationally, it is now the norm for many children and young people to present to gender clinics having undergone full or partial social transition.” 

The MPRG report found that children “living in stealth” (i.e. who have socially transitioned to live as the opposite sex and whose friends, teachers etc. may not be aware of this decision) often displayed a “fear of ‘being found out’”. The MPRG observed that “living in stealth appears to increase a child’s level of stress and anxiety with resultant behaviour and mental health problems, including social withdrawal, with children becoming increasingly isolated”. The Cass Review reports that this in turn can drive “a sense of urgency to access puberty blockers”. The MPRG also warned that previously in GIDS there was “inconsistent evidence of the individual impact of social transition being explore [sic] with children and their families”, and the implication is clearly that this should be remedied given the MPRG “concern” about “parents having already adopted an affirmative approach”.

The PIS should make clear the potential link between social transition and “a sense of urgency to access puberty blockers” to help ensure parents do not misinterpret their child’s distress and their expressed desire to pursue a medical pathway.

No information about adolescent brain development

The PIS does not inform parents about the reality of adolescent brain development and the fact that this continues into adulthood. As the Cass Review describes, “the ‘future orientated’ prefrontal cortex matures later, with development continuing into an individual’s 20s, and […] is concerned with executive functions such as complex decision making, rational judgement, inhibition of impulsivity, planning and prioritisation”. Without a developmentally informed understanding of their child’s capabilities, parents cannot consent to a treatment that may be influenced by early adolescent neurological changes e.g. “changes in the limbic area, which is ‘present-orientated’ and concerned with risk taking and sensation seeking, begin with puberty; this part of the brain becomes super sensitised, drives emotional volatility, pleasure and novelty seeking, and also makes adolescents more sensitive to social rejection, as well as vulnerable to addiction and a range of mental health problems.” (Cass 6.37)

No mention of natural resolution of distress

The PIS does not mention the possibility that a child’s distress or discomfort about their natal sex might resolve naturally without medical intervention. The PIS fails to inform parents about historic data showing that cross-sex identity commonly resolves during puberty (see point 2.6 of the Cass Review), or that many of these children grow up to understand themselves as same-sex attracted. Other children may simply mature sufficiently to appreciate that non-conformity with sociocultural gender norms is not what makes someone male or female, or they may reach an understanding that the distress previously interpreted as a sign of “gender incongruence” was in fact caused by other issues. By beginning the PIS with a description that suggests candidates for puberty suppression have a “gender identity does not match their sex”, the implication is that these children have an inherent problem that will not resolve of its own accord. 

3. Unrealistic description of the trial’s scientific value

The HRA says that “deciding to take part in a research study can be a big decision and people need good information to be able to make that decision”. This decision requires an accurate account of why this particular research is required rather than obtaining the information in a different way. The PIS falls short of this in two key areas. 

Availability of data for past PB patients not mentioned

An unknown but significant number of children (estimates range from over 1000 up to 2000) underwent puberty suppression at the now closed GIDS service. Follow-up data for this patient cohort is theoretically available, but access was obstructed by the adult gender services. This is vital information for parents who are considering whether or not to consent to their child’s participation in the PATHWAYS trial. Some parents may conclude that obtaining historic outcome data (via the data linkage study) should take precedence over a new experiment involving their child. The PIS tells parents that the evidence for PBs is uncertain, but does not inform them of this existing potential source of information on patient outcomes, including rates of hospital episodes, fertility treatments, deaths, medication prescribing, surgeries, physical health and mental health information for past puberty blocker patients.

Unrealistic portrayal of what the trial is capable of achieving

The PIS tells parents that this trial will “[find] out how [puberty suppression] affects [children’s] quality of life, mental and physical health and how they feel about their bodies and their gender”. Data will be collected to “see if these get better, stay the same or get worse – we won’t know until we complete the study”. There is no acknowledgement in the PIS of the very serious limitations of the trial design, in which differences between the delayed and immediate-treatment control group are likely to be confounded by placebo effects. As a result, the trial is unlikely to offer reliable insights into quality of life or mental health following puberty suppression. The statement “we won’t know until we complete the study” gives the false impression that definitive information will be achieved by the end of the trial. Parents are thus consenting to their child’s participation in research of debatable value under the false impression that this trial will produce robust findings.

4. Lack of clarity about biological and legal reality

The HRA states that the PIS should include information on “what will happen to participants during and after the research study” (emphasis added). The PIS fails to offer parents an accurate understanding of what can realistically be achieved in the event of their child proceeding with medical transition following puberty suppression (the overwhelmingly likely outcome according to previous research findings and the HRA’s own account). The language used in the PIS does not meet the HRA requirement to “avoid potentially misunderstood words […] or phrases or words with dual or nuanced meanings” (e.g. “gender” which can be interpreted as meaning “biological sex”, or “sociocultural norms associated with the sex classes”, or as a short form for “gender identity”). 

Unclear language around sex and gender

The PIS does not at any point state that it is not possible to change sex. In fact, it gives parents the opposite impression. The term “sex registered at birth” is used, which could be taken to imply that sex is an administrative characteristic, rather than an objective and unchangeable material reality. In one place, the term “sex assigned at birth” is used, which implies an even more arbitrary quality to what is a non-arbitrary personal characteristic. The misleading idea that sex is a mutable characteristic is reinforced by the statements about pregnancy tests and contraception being required “if your child was female sex at birth” and “if your child was female at birth”. Parents are thus fundamentally misled about their child’s reality.

The online questionnaires that will be completed by trial participants are described as asking “how they feel about their gender and body”. This implies that the child has a “gender”, but no definition or explanation is provided. Similarly, the consideration of what to do in terms of treatment at the end of the 2-year trial period is described in terms of the child’s “experience of their gender and body”. Again, no explanation is provided as to what “gender” means in this context. 

Legal context for decision-making not mentioned

The PIS makes no mention of the UK legal context, which is that even an adult in possession of a Gender Recognition Certificate is regarded as male or female in line with their biological sex under the terms of the Equality Act 2010. This is vital contextual information for parents to appreciate the legal reality for their child (see 2025 Supreme Court ruling in For Women Scotland Ltd v The Scottish Ministers). 

5. Failure to meet HRA ‘Easy Read’ standards

The Participant Information Sheets are complemented by an “Easy Read” document designed as a “plain language study description” for anyone “who would like to find out more about PATHWAYS TRIAL and what taking part in the study involves”. This document does not come close to meeting the HRA’s recommended standards on producing this type of documentation (i.e. guidance from DHSC “aimed at people who commission or produce Easy Read information”). Two brief examples are given below as an illustration of the Easy Read document’s shortcomings:

1. Recommendation: “Make sure words and sentences are easy to understand. Avoid jargon or complicated words as much as possible”.
   The PATHWAYS Easy Read document begins with the sentence “PATHWAYS TRIAL is a research study that will explore how puberty suppressing hormones (medicines that pause puberty) impact the physical, social, and emotional wellbeing of young people with gender incongruence.” At a minimum, the words “puberty” and “gender incongruence” should be defined, but many of the other words used here are not Easy Read compatible (and the guidance specifically states to “use hyphens for words such as well-being”). The Easy Read document later states that “gender incongruence is when someone’s gender doesn’t match the sex they were registered at birth”: the term “gender” is undefined, and the complex notion of “sex registered at birth” is used in place of the simpler and more accurate “sex”. Later, the term “gender identity” is used once but never defined or referred to again, despite it being integral to the claim about what puberty blockers may offer (i.e. the opportunity to “explore […] gender identity”).
2. Recommendation: “Each sentence to be as short as possible. More than 15 words is harder to read.” 
   This target is rarely met in the PATHWAYS Easy Read document. Many sentences are well over double that length and are crammed with complex vocabulary (the opening sentence quoted above is 30 words long and is far from unusual).

6. Unrealistic promise in relation to patient safeguarding

The HRA states that “potential participants should also be told at the outset if it is possible that they might be withdrawn from the study because of information that comes to light that relates specifically to them and their health.” The PIS states that following puberty suppression “some people may feel more anxious or low in mood, so we will check in with your child regularly about how they are feeling” but also assures parents that “your child’s treatment will not be stopped if you or your child tell us about their difficult feelings or experiences.” This is not a guarantee that researchers are in a position to offer. Concerns about patient safety and well-being could arise from the information provided to researchers during the course of the trial. There may be a need to pass on information if the patient is at risk, and appropriate patient safeguarding may require reconsideration of the intervention, irrespective of the beliefs or wishes of the patient and/or their parent. 

7. Information in PIS-Y fails to meet HRA standards

The HRA guidance on creating a Participant Information Sheet for a child or young person offering assentstates “when seeking assent, an information sheet for children and young people should be much shorter and simpler than a PIS designed for obtaining consent” (emphasis added). The PATHWAYS parent (consent PIS) and young person (assent PIS-Y) information sheets are almost identical in length (26 pages) and content. The main wording differences involve superficial rephrasing, such as changing “you and your child” in the parent version to “you” in the young person sheet. The PIS-Y is thus neither shorter nor simpler than the PIS for parents.

Complex topics, such as fertility, are not addressed in an age-appropriate manner in the PIS-Y. Phrasing such as “possible options you have for your fertility for the future” is not as clear, for example, as the “Young Person Information Sheet” created for the GIDS EIS (personal copy), which stated in simple terms that “hormone blockers could affect your ability to have a baby”. There is no mention that taking testosterone, for many girls the likely sequel to taking puberty blockers, will adversely affect ability to “have a baby”, as at least 50% develop uterine atrophy. The passing mention of an impact on “sexual development and function” in the PIS-Y fails to use age-appropriate language or to explain the possible implications of the treatment for the young person’s future healthy relationships in a way that prospective trial participants (aged approximately 11-15) could understand.

8. Outdated reference to one of the trial drugs

PIS should remove “Goserelin” in line with the trial Protocol

Both parent and child versions of the PIS need to be updated in line with the latest trial Protocol to remove mention of Goserelin as a possible alternative for puberty suppression. The main drug will be Triptorelin, but previous versions of the Protocol listed both Leuprorelin and Goserelin as possible alternatives. The latter has now been removed as a treatment option. 

Reference documents

Abbreviations

PBs: refers to “puberty blockers”. Also referred to in the PIS as “puberty suppressing hormones” or “gonadotropin releasing hormone analogues (GnRHa)”.