Dr John Rumbold, Lecturer at NLS https://www.ntu.ac.uk/staff-profiles/law/john-rumbold
The final report of the Cass Review into the provision of care at the UK’s Gender Identity Development Service (GIDS) is a document that will be scrutinised extensively in the coming months. The reaction to the Cass Review will likely also be the subject of much academic scrutiny. The Cass Review limited itself to the provision of treatment for gender-distressed children, rather than any wider considerations about the nature of gender dysphoria and/or trans identities. There is much to discuss about the Cass Review, but this article exclusively concerns evidence-based medicine (EBM).
The analysis of the evidence for the Cass Review was performed by experts in assessment of medical research at the University of York. One of the key findings was a weak evidence base for the interventions offered by GIDS. It would be a mistake to focus purely on the Cass Review, when a number of reviews of gender affirmative care have been conducted in various countries and come to similar conclusions in respect of a weak evidence base.. There is an editorial in the BMJ commenting on the findings of the review and how it corresponds to reviews from other countries.
What is evidence-based medicine?
The practice of medicine is influenced by both an understanding of medical science and clinical experience. One of the fathers of modern medicine, William Osler, famously said
He who studies medicine without books sails an uncharted sea, but he who studies medicine without patients does not go to sea at all.
The reliance on experience and expertise can lead to the use of treatment without a proper scientific basis. There have been many treatments used for decades or longer where the medical consensus was that these treatments were effective – but they were ineffective or even harmful. There are a number of reasons why this is the case, not least of which is groupthink. Many treatments have been used in the past that were not just ineffective but actually harmful.
The EBM movement arose in the 80s and spread around the world over the next two decades. The methodology of EBM includes the use of a hierarchy of evidence. The highest level of individual pieces of evidence is the prospective randomised controlled trial (PRCT). Given that there may be a number of contradictory PRCTs, a key element of EBM is the meta-analysis, where a standard methodology provides a way of concluding the net result of the studies as a whole. Studies will be weighted according to the rigour of their methodology and studies with poor methodology may be excluded from the meta-analysis altogether. This is the highest form of evidence.
Expert consensus is low level evidence. Cass commented on the politics of the various bodies involved in the provision of gender affirmative care and how the mutual recognition of expertise lead to an impression of greater consensus and stronger evidence than was the case. She also comments on the issues that are more specific to the treatment of gender-distressed children, which include pressures from activist groups. These seem to have influenced the adoption of certain practices even though the evidence base was poor.
Why is the evidence base important?
It is reasonable to assume that the providers of gender affirmative care are acting from the best of motives. They are dealing with gender-distressed children and want to relieve their distress. They want to provide patient-centred care and respect patient autonomy. We know that there are certain, well defined and limited, circumstances where it is entirely ethical to provide a treatment even when it has not yet been proven. For example, experimental treatments were used during the Ebola epidemic.
However, the field of oncology demonstrates the importance of properly conducted research in advancing the state of medical science. Hence why even when there is no known treatment for a particular cancer, doctors are keen to enrol patients in formal studies. Patients will benefit from better care, and will also be placed on the experimental drug after the end of the study if it has been proven to work.
There are some additional difficulties in the area of gender affirmative care. It will be impossible to conduct a trial where the subjects and the researchers are unaware whether or not a puberty blocker has been administered for obvious reasons. However, this does not mean that meaningful research cannot be conducted (and it is recognized in the principles of EBM that certain types of research are practicably difficult in certain areas). Contrary to comments made in the Commons debate, it is not the case that 100 studies were rejected.
There are some key questions for the wider medical community from the practice at gender-affirming care across the globe. Why was a particular area of medical practice allowed to develop and practise protocols that had a poor evidence base? What can we do to prevent this in the future?
What if there is no evidence?
It is important that doctors are able to provide personalised care and innovate. There are after all limits on the current scientific evidence, and an individual patient may require treatment tailored to their situation. Evidence-based medicine cannot cover every conceivable eventuality.
One of the major issues with GIDS was the failure to systematically collect data on the patient population and their outcomes. Although observational data is not the strongest form of evidence in the pyramid, it is nonetheless better than having no systematic data at all. It was notable that six out of the seven adult clinics did not cooperate with the Cass Review. It is hard to understand why this would be in anyone’s interests. They have now agreed to release their data.
However, the situation at GIDS was arguably not one of tailored care where doctors were providing a treatment in situations where there were no alternative options. There was adoption of a protocol to be used routinely that was not supported by good evidence, outside of the conduct of a clinical trial. There was frequent administration of puberty blockers as the preferred option for a number of reasons. There was evidence that children were coached about how to obtain puberty blockers from GIDS.
Further, the clear changes in the patient population did not trigger any investigation of the reasons behind this. The application of the principles of EBM would suggest caution in using the results of one study to justify treatment of a very different group of patients. Consequently, there was only the appearance of evidence-based care. Puberty blockers were being prescribed outside of the parameters of the original Dutch study, and the differences between the Dutch protocol and the practice at GIDS only grew wider with time. It could not be assumed therefore that the same results would be obtained.
What is the solution?
The Cass Review makes a number of recommendations. Naturally, these are specific to the area of the treatment of gender-distressed children and young people. The recommendation most pertinent here is Recommendation 32:
Wider guidance applicable to all NHS services should be developed to support providers and commissioners to ensure that innovation is encouraged but that there is appropriate scrutiny and clinical governance to avoid incremental creep of practice in the absence of evidence.
It can be persuasively argued that all care should be informed by the scientific evidence and that not doing so contravenes medical ethics. Kamran Abbasi states in his editorial in the BMJ:
One emerging criticism of the Cass review is that it set the methodological bar too high for research to be included in its analysis and discarded too many studies on the basis of quality. In fact, the reality is different: studies in gender medicine fall woefully short in terms of methodological rigour; the methodological bar for gender medicine studies was set too low, generating research findings that are therefore hard to interpret. The methodological quality of research matters because a drug efficacy study in humans with an inappropriate or no control group is a potential breach of research ethics. Offering treatments without an adequate understanding of benefits and harms is unethical.
Although we would no longer say that the literal meaning of primum non nocere applies, it is true that all treatment must justified by a balancing of benefits and harms. Where there is insufficient evidence, there is an ethical imperative to obtain that evidence through appropriate research. Recommendations 19-21 address the need for the Regional Centres to conduct research, which would be coordinated by the NHS Provider Collaborative and the Research Oversight Group.
It can be argued that the proper protection of patients requires that the formulation of guidelines conform to the principles of evidence-based medicine. The Care Quality Commission (CQC) has powers to inspect and regulate all providers of health and social care in England (as per the Health and Social Care Act 2008). It also demands that all providers only administer “safe and effective care” as per Regulation 12 of the Health and Social Care Act 2008 (Regulated Activities) Regulations 2014, which would arguably not be the case if treatment protocols conflict with the recommendations of the Cass Review. This would be a mechanism for ensuring that private clinics do not continue to prescribe puberty blockers inappropriately, for example, as the CQC has the power to prosecute providers for breaches of these duties.
The objection to this would be that the advance of medical knowledge might be stifled by preventing innovation. In this case, there was no advance in medical knowledge because of the failure to properly monitor treatment. The opportunity to examine the benefits and harms of puberty blockers in a large number of patients was missed.
A regulatory mechanism to ensure that standard treatment protocols are evidence-based would protect patients. There are a number of ways that this could be achieved. Crucially, these mechanisms must not depend on an assessment just by specialists within the particular field. They require impartial experts in the assessment of medical evidence. The Cass Review was required in order to urgently address a deficit in the evaluation of gender-affirming treatment. Measures should be taken to prevent the need for such retrospective action in future .
This could involve a modest addition to the remit of the CQC, for example. CQC guidance already requires that providers should “consult nationally recognised guidance about delivering safe care and treatment and implement this as appropriate”.
Innovations should only be permitted when subject to oversight that ensures that benefits and harms are studied. Clinicians should be made aware of the need for a more rigorous consent process in these circumstances. Some hospitals do have processes for approval of e.g. innovative surgical procedures, but these are not universal. It does seem remarkable that an experimental treatment can be provided by such a long period of time without proper scrutiny in the age of EBM. Lessons must be learned.
Further Reading
Some pertinent medical history
Gomes, M.D.M. and Haynes, R.B., 2019. William Osler (1849–1919) at the Roots of Evidence-Based Medicine. Canadian Journal of General Internal Medicine, 14(4), pp.23-27.
Tan, S.Y. and Yip, A., 2014. António Egas Moniz (1874–1955): lobotomy pioneer and Nobel laureate. Singapore Medical Journal, 55(4), p.175.
Rigas, B., Feretis, C. and Papavassiliou, E.D., 1999. John Lykoudis: an unappreciated discoverer of the cause and treatment of peptic ulcer disease. The Lancet, 354(9190), pp.1634-1635.
Commentary on the Cass Review
Abbasi, K. The Cass review: an opportunity to unite behind evidence informed care in gender medicine. BMJ 2024;385:q837
Campbell, D., 2024. Ban on children’s puberty blockers to be enforced in private sector in England. Guardian Apr 11th 2024.
More or Less: Behind the Stats (looking at the methods of the Cass Review)
Comments