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This policy document is part of a response submitted by the Progress Educational Trust (PET) to the Human Fertilisation and Embryology Authority's Consultation on its 8th Code of Practice and Revised Consent Forms.

Please add any general comments about the guidance in the Code of Practice

It is essential that the processing of applications for licences for PGD for a new condition is accelerated. The amount of time it currently takes the HFEA to approve a licence application is unacceptable, as it causes frustration for clinicians and prolongs distress and anxiety for patients.

The Human Fertilisation and Embryology Act 2008 states that the HFEA cannot authorise PGD to test for a 'gene, chromosome or mitochondrion abnormality' unless it is 'satisfied' that 'there is a significant risk that a person with the abnormality will have or develop a serious physical or mental disability, a serious illness or any other serious medical condition'. Parliament does not, in our interpretation of this wording, appear to be instructing the HFEA that it must define either precisely or in advance which tests may be performed on an embryo. Rather, Parliament appears to be instructing the HFEA only that it should be satisfied that the person deciding which tests may be performed on an embryo is qualified to make that decision, and is operating under the general principle laid down by Parliament - that is, that the condition being tested for must be 'serious'.

The HFEA's proposed changes to its Code of Practice in relation to PGD - particularly the removal of the statement 'the seriousness of the condition should be a matter for discussion between the people seeking treatment and the clinical team' from the existing Code of Practice - appear to remove decisions about the determination of seriousness for which PGD is being sought, from the clinical encounter between clinician and patient, and place these decisions instead with the HFEA. We believe that such a radical shift in the locus of decisionmaking is both unfortunate and unnecessary, and that the HFEA can instead 'satisfy' its statutory obligations regarding PGD by using the following model.

The centre seeking to carry out PGD should appoint its own multidisciplinary team, to form decisions about seriousness on a case-by-case basis, using a set of broad and flexible criteria which may be drawn up by the HFEA and included in its Code of Practice. (The HFEA already has just such a set of criteria, in its existing Code of Practice.) The centre should notify the HFEA, perhaps by a rapid notification system, when it has decided that PGD is warranted.

The HFEA can use its established inspection process to satisfy itself that centres are using its criteria and multidisciplinary team to make decisions about PGD. The HFEA can also draw up and impose appropriate penalties where clinics are found not to have followed this guidance, drawing where necessary upon existing procedures for penalising breaches of the terms of a license, and imposing conditions upon licenses where there is concern.

This would be a better system than in-house decisionmaking at the HFEA, because a local multidisciplinary medical team would have a greater range of experience and expertise in making clinical judgments on a case-by-case basis. It is noteworthy that many clinics already do this, and have a higher incidence of refusing to offer PGD in particular cases - even where they already have a licence for the condition - than the HFEA does in refusing a licence.

Another theme of the HFEA's proposed changes to its Code of Practice in relation to PGD is an apparent attempt to make decisions about PGD less subjective and more objective. This is misguided, because subjectivity is an inevitable part of deciding whether there is - in the words of the statute - a 'significant risk' of a 'serious condition'. It is impossible to establish 'risk' without involving the patients themselves, so as to appreciate the burden that any given condition would have upon them.

Risk has two components - the chance or probability of the condition being screened for occurring, and the extent of damage or burden to the patient. The former is largely a matter of scientific knowledge, empirical recurrence data and clinical diagnostic skills (although even here there is the subjective element of what constitutes too high a chance in light of the burden). The latter has a considerable subjective element, and can only be arrived at by discussion between the patient(s) and their clinician(s).

In other words, genetic counselling is needed to determine the burden and therefore the risk. Assessment of whether a risk is serious or not must necessarily include a subjective component, and resists any objectification.

In contrast with PGD and the HFEA's new Code of Practice, UK abortion law provides a model where a great deal of subjectivity is accommodated. If it is appropriate and lawful for a couple to seek a termination on the grounds of a fetal abnormality, then how can it be inappropriate for them to seek PGD under the same circumstances? Another relevant point of comparison is prenatal diagnosis, which is a medical act with no specific licensing except for GMC registration (although abortion regulation applies with selective termination of pregnancy).

The unavoidable truth is that there is no definitive list of conditions 'serious' enough to warrant PGD, and it would be neither practicable nor desirable to create such a list. Of course, there exists a list of conditions for which the HFEA has granted licenses to practice PGD to date, which is something rather different. And even here, there are potential problems in having this unavoidable list - as the HFEA knows, having decided not to release the list.

Although the HFEA's procedure for licensing PGD is likely to change under the terms of new legislation, it is essential that any 'list' of conditions relating to PGD remains an end product rather than a starting point of the licensing process. Any attempt to draw up a list to be used as a starting point would inevitably fall short of accommodating deserving uses of PGD and future developments in human genetics and assisted reproduction. The list would need perpetual review, to the extent that it would cease to function as a useful starting point for licensing all but immediately.

Still another reason to avoid the drawing up of a list of serious conditions, is the inevitable opprobrium that this would attract from those who have such conditions. They may see the inclusion of their condition on the list as pejorative, implying that they should have been screened out before birth. Conversely, others would take umbrage at the exclusion of their condition from the list, because they believe its debilitating consequences to be insufficiently recognised. It is easy to envisage patient groups actively lobbying or seeking judicial review from both perspectives, in order to have their condition added to or removed from such a list.

There are other ways of prescribing serious conditions, besides a simple list, but these too are problematic. For instance, in one of its presentations at its 26 January 2009 consultative meeting on PGD in London, the HFEA proposed a 'decision tool' for PGD. This tool involved various factors, under the two headings 'Disease facts' and 'Impact/burden', being permutated in order to decide whether PGD for a particular condition should be licensed.

We appreciate that this proposed tool was a well-intentioned attempt, on the part of the HFEA, to go beyond the notion of a crude list and to capture the contingency of decisions about PGD. But an uncharitable view of such a tool would liken the consequences of using it to making a patient seeking PGD go through the sort of impersonal assessment that is used by banks to determine their customers' credit rating.

Sensible and consistent regulation of PGD will only be achieved by giving due recognition to the elements that make up 'significant risk' of a 'serious medical condition', in the context of inherited and partly genetic conditions. It has to be remembered that the purpose of PGD is to exclude the family risk of a genetic disorder in the embryo, where the couple are at 'significant risk' - typically a 25% or 50% chance - of transmitting the 'serious medical condition'.

By definition, in Mendelian disorders there is a one-to-one relationship between not having the family mutation and not having the disease caused by that mutation. Where the disease is rare, excluding the family risk via PGD effectively excludes the disease. Where the disease is common (for example breast cancer), only the 'excess' family risk can be excluded via PGD and there remains a possibility that the disease may occur. This 'exclusion benefit' to the patient exists, even if the Mendelian condition shows variable penetrance (that is, not all mutation carriers manifest the disease) or variable expression (that is, only a proportion manifest the 'serious' complication - for example, 20% of those with the condition have mental retardation).

In summary, PGD for Mendelian disorders presents relatively few difficulties, for two reasons. First, prospective parents can have DNA mutation testing to establish their high chance (50% or 25%) of transmitting the mutation(s) to their offspring. Second, exclusion of the family disease (for rare disorders) or the excess family risk (for common diseases such as breast cancer) is possible, by demonstrating the absence of the family mutation(s) in the embryo.

Unfortunately neither of these two factors applies to common, complex (non-Mendelian) disorders at the present time, and probably never will for the vast majority of such disorders. Excluding transmission of a known susceptibility gene (DNA variant) may not significantly reduce the chance of the common disease occurring. The family history of the condition may be due to an (as yet unknown) rare DNA variant.

In other situations, a common disease may arise from many different DNA variants acting in consort, but the chance of the same high 'dose' of variants being transmitted to the prospective child might be small. As research continues on genetic susceptibility, this small probability might become predictable, but there will always be wide confidence limits for such predictions of common disease.

One possible scenario is that a few common susceptibility DNA variants/mutations do indeed contribute greatly to the risk of a common disease. This seems to be the case for the contribution of various filaggrin gene mutations to eczema and atopic (allergic) asthma.

Filaggrin is nature's moisturiser, and the one in ten northern Europeans carrying a single mutation have only 50% of filaggrin in their skin (the one in four hundred with a double dose have no filaggrin). A study of the two commonest filaggrin mutations in the Avon Longitudinal Study of Parents and Childhood - a general population birth cohort - showed that 6% of the study participants carried a mutation, and this increased their risk of eczema and/or atopic asthma threefold. There is also an increased risk of peanut allergy.

The 'population attributable risk' for eczema/atopic asthma, from just these two mutations, was 15%. In other words, as explained by Henderson et al in their paper The Burden of Disease Associated with Filaggrin Mutations: A Population-Based, Longitudinal Birth Cohort Study, these two mutations account for the 15% of the prevalence in the population.

What are the implications of this for PGD? If a child had severe eczema including life-threatening peanut allergy, and was found to be carrying two filaggrin mutations, it may well be that for the child's family, excluding all or at least two filaggrin mutations in a future embryo would not only considerably reduce the chance of eczema recurring, but would provide sufficient reassurance to the couple to try for another child (a sibling for their first child). In these circumstances, there would be good reasons to practice what might be crudely summarised as 'PGD for eczema', even though superficially eczema does not appear to be a 'serious' condition.

In addition to these clinical nuances, there is a broader political reason for keeping the emphasis in the HFEA Code of Practice on subjective rather than objective decisionmaking about PGD. The recent trend in government policy leans towards greater involvement of stakeholders, including patients and clinicians, in healthcare. In light of this, Parliament is unlikely to have intended to deliberately diminish patient and clinician choice and input into the decisionmaking process.

10.4 of the HFEA's proposed new Code of Practice refers to 'the experience of the people seeking treatment' as a factor that should be taken into account when considering whether PGD is appropriate,, with the word ' experience' replacing the word 'view' in the equivalent section of the existing Code of Practice. This helps neither the clinician nor the patient, and threatens to compromise their their input into the decisionmaking process.

The most likely inference, from use of the word 'experience' or its synonyms in this section of the Code of Practice, is that a patient needs to have undergone a distressing experience before PGD can be practiced - for example, terminations on the grounds of fetal abnormality, miscarriages caused as a result of the genetic defect, a certain number of family members who are afflicted, or successful completion of a workshop. Confusingly, a contrary interpretation could also be placed upon the word 'experience' - a patient could be characterised as so distressed by a previous experience, that they lack the perspective necessary to make a proper decision. Either interpretation represents an unacceptably dim view of the patient's capacity to make decisions in light of their past.

The use of the word 'experience' in place of 'view' also appears to place the clinician under an obligation to probe their patients' personal situation in a more rigorous way, without any corresponding guidance as to how the patients' personal situation is to be evaluated. There is no evidence to suggest that existing relationships between patients and clinicians are insufficient for arriving at sensible decisions about PGD, and there is certainly no evidence to suggest that existing relationships between patients and clinicians should be modified in the way that encouraging consideration of patient 'experience' would appear to suggest.