Regulating mitochondrial donation: seeking expert views. Background document

Transcription

1 Regulating mitochondrial donation: seeking expert views Background document June 2015

2 Contents Introduction 3 What we need from you 3 Licensing mitochondrial donation 4 Licensing the clinic to undertake mitochondrial donation 4 Individual patient approval 5 Questions to consider 6 Best practice guidance and other requirements 7 Mitochondrial donor screening 7 Age limit for mitochondrial donors 7 The 10 family limit 7 Consent and information provision 8 Questions to consider 9 Follow-up studies 10 Question to consider 10 Regulating mitochondrial donation: seeking expert views 2

3 Introduction Researchers are developing medical techniques, known as mitochondrial donation, that could allow mothers to avoid passing on genetically inherited mitochondrial diseases to their children. The most developed techniques, maternal spindle transfer (MST) and pro-nuclear transfer (PNT), involve a patient going through an IVF cycle but with additional steps. In both MST and PNT, nuclear DNA (the vast majority of genes in a cell, which make us who we are) is moved from a patient s egg or embryo containing unhealthy mitochondria to a donor s egg or embryo containing healthy mitochondria. The nuclear DNA has been removed from the donor s egg or embryo before this process takes place. You can find out more about these techniques on our website. In February 2015 Parliament approved regulations to permit MST and PNT to avoid serious mitochondrial disease. The regulations, which come into force on 29 October 2015: modify the definition of permitted egg and permitted embryo in the Human Fertilisation and Embryology Act to allow an egg or embryo created by MST or PNT to be used in treatment set out the process and circumstances that must be met for a clinic to perform MST or PNT, and introduce a different system for providing information to children conceived from mitochondrial donation. Over the last four years, we have looked extensively at public attitudes towards mitochondrial donation and their safety and efficacy (see a summary on our website). Now we are designing a system to regulate and license mitochondrial donation so that clinics wishing to carry out these treatments can apply for permission to do so. What we need from you This document summarises our plans for regulating and licensing mitochondrial donation and asks for your feedback on key areas relating to: the licensing process policy issues, and follow-up studies. Once you ve read about our plans in this document, please complete our online survey by 6 July 2015 to give us your views. We will also be holding a workshop on 23 June 2015 where you can give us your views in person. It s important to point out that we are not asking you to comment on the wider ethical and scientific issues involved, nor the statutory framework. We are asking for your help to finalise the system we will use to regulate and license mitochondrial donation, ready for when the regulations come into force. Regulating mitochondrial donation: seeking expert views 3

4 Licensing mitochondrial donation The licensing process has two stages: the licensing of a clinic to undertake mitochondrial donation, and the authorisation to undertake the treatment in the case of a particular patient (individual patient approval). Our scientific panel recommended that, before the first clinical case of MST or PNT can happen, further experiments should be carried out. 1 Once our board ( the Authority ) is made aware that these essential experiments have been completed, we will convene an expert panel to make an assessment of the safety and efficacy of these techniques. The Authority will receive this panel s report. If it decides that the techniques are safe and effective enough to be used in clinical practice, any clinic wishing to use the technique clinically can apply for a licence and will need to follow the process outlined below. This would only need to be done once, presuming that the techniques are shown to be safe. Licensing the clinic to undertake mitochondrial donation Before any HFEA-licensed clinic can undertake mitochondrial donation for treatment purposes, it will need to apply to us to vary its licence to include the necessary express provision to carry out MST and/or PNT. This will follow the same process as a clinic applying to vary its licence for other purposes (such as the addition of embryo testing) ie, by way of an application to our Licence Committee. As part of this process, the clinic will need to submit to us the necessary evidence to demonstrate the competence of the clinic staff and suitability of its premises and processes with specific reference to PNT and/or MST. All staff either directly involved in mitochondrial donation techniques, or staff involved with patients receiving such treatment, must be suitably qualified, trained and assessed as competent for the tasks they perform. For example, we propose that clinics will need to demonstrate the competence of their clinical embryologists to perform mitochondrial donation techniques, by submitting: information about their experience of performing micro-manipulation on human or animal (eg, mice) eggs or embryos information on their specific experience of carrying out MST and/or PNT in treatment, training or research references to support their experience and knowledge, and any other information that may demonstrate competence. Evidence will also be required of suitable validation of equipment and processes. We propose that the whole process of MST/PNT, including the transfer of embryos to the woman, must be carried out at a clinic specifically licensed to carry out that technique. 1 See Third scientific review of the safety and efficacy of methods to avoid mitochondrial disease through assisted conception: 2014 update. Regulating mitochondrial donation: seeking expert views 4

5 Individual patient approval Before a clinic licensed to do MST and/or PNT is permitted to carry out the treatment for a specific patient, it will need to apply to our Statutory Approvals Committee (SAC) for approval. If granted, approval can only be given for the treatment to be applied to the particular patient, in the circumstances described in the regulations. The regulations prescribe the circumstances in which either MST or PNT can be applied to an egg or embryo. Step one of the approval is the assessment of whether there is a particular risk of the egg or embryo having a mitochondrial abnormality caused by mitochondrial DNA. The biology of mitochondrial disease means that for any woman carrying mutant mitochondrial DNA (mtdna), even if only a few molecules of affected mtdna are present, there is almost a 100% risk that her eggs will have mitochondrial abnormalities caused by mitochondrial DNA. We therefore propose that the presence of a mutation in the female patient s mtdna alone is sufficient to satisfy the test for particular risk. The second step is the assessment of whether there is a significant risk that a child with those abnormalities will have, or develop, a serious mitochondrial disease. In order for us to assess significant risk, we propose asking clinics to submit evidence on the scientific literature, family history and patient history. Clinicians will be able to submit other evidence that in their view may be relevant to the assessment of significant risk. When making an assessment of seriousness we propose that this should be made, where possible, based on the most severe symptoms that could be expected for a particular case. To support an application, a clinic will need to submit patient-specific information on: the patient s mutant mtdna load and mutation threshold the patient s medical history the patient s family medical history of the mtdna mutation or disease scientific literature relevant to the mtdna mutation or disease, and any additional information which the clinician may consider is relevant to the application. Regulating mitochondrial donation: seeking expert views 5

6 Questions to consider We ve set out what we propose to do. Now we want to hear your views about some specific issues on the individual patient approval process. 1. Before a clinic can be licensed to carry out PNT and/or MST they must be able to demonstrate they have the necessary skills and competency. Do you think the proposed approach for assessing the competency of a clinical embryologist is appropriate? Do you have any suggestions for alternative or additional evidence that could demonstrate the competency of a clinical embryologist intending to perform one or both of these techniques? 2. Before a clinic licensed to do MST and/or PNT is permitted to carry out the treatment for a specific patient, the patient s case must satisfy criteria outlined in the regulations. a) MST and/or PNT can only be carried out for a specific patient where there is a particular risk of the egg or embryo having a mitochondrial abnormality caused by mitochondrial DNA. Do you think the proposed approach for assessing the particular risk by reference to the presence of mutant mitochondria is appropriate? Please provide details of any other relevant measures, evidence, or criteria that could be used to determine the presence of a particular risk (please refer to p5 of this document). b) Does this proposed process take into account all aspects relevant to the risk, and seriousness, of the disease and mitochondria disease biology? Please provide details of any other relevant information that could support an application for a particular patient. Regulating mitochondrial donation: seeking expert views 6

7 Best practice guidance and other requirements We propose making a number of changes to our guidance and requirements to cover the use of mitochondrial donation in clinical treatment. We would like to hear your views on: mitochondrial donor screening age limit for mitochondrial donors the 10 family limit consent and information provision. Mitochondrial donor screening Mitochondrial donors will provide their eggs in the same way as egg donors for treatment (the same will apply to men who provide sperm used in the PNT process). As their eggs will be processed and used to create embryos, the risk of infectious diseases being transmitted is likely to be the same. Therefore, most of the same requirements for laboratory tests and storage set out in licence condition T52 in relation to sperm and egg donors will apply to mitochondrial donors, except for genetic screening (for autosomal recessive genes known to be prevalent, according to international scientific evidence, in the donor s ethnic background). It will also be relevant to assess mitochondrial donors medical history and the risk of transmitting inherited conditions known to be present in the family, which could possibly be inherited by mitochondrial DNA. Age limit for mitochondrial donors Age will be an important consideration when selecting mitochondrial donors as the mitochondrial DNA has a very high mutation rate resulting in numerous new mutations over a person s lifetime, and potentially resulting in decreased mitochondrial function. The age of the donor may also affect the number of viable eggs that are collected. We are proposing that the guidelines on the age limit for egg donors should apply to mitochondrial donors. Professional guidelines state that eggs should not be taken from donors aged 36 or over. We propose to advise clinics to observe this age limit unless there are exceptional reasons. The 10 family limit The family limit refers to the number of families a single donor can help to create. The current limit is based on the perceived social and psychological interests of donors and donor-conceived people in maintaining a relatively small number of siblings/children. It is also there to minimise the possibility of two children from the same donor having a relationship with each other without knowing they are genetically related. We propose that the 10 family limit should also apply to women donating their mitochondria. In the case of a woman who donates eggs for treatment and mitochondrial donation, she can only donate to a total of 10 families across both types of donation. You could argue that the reasons for setting the limit at 10 (as outlined above) do not apply in the same way to children born from mitochondrial donation. However, we think that the Regulating mitochondrial donation: seeking expert views 7

8 number of offspring from one donor should be kept low to reduce the risk of one of those donors later being found to have a transmissible disease or condition. It is our current understanding that limiting the amount of families a mitochondrial donor can donate to to 10 is unlikely to have much impact, as very few egg donors go through enough egg donation cycles to donate to this number of families. Consent and information provision Our Code of Practice (guidance note 4) sets out the information that should be provided to patients before consent is obtained (eg, information about the clinic s waiting times, potential risks, likely outcomes etc). We propose that before clinics obtain consent they should provide patients with information about the potential risks of mitochondrial donation, the importance of follow-up studies and encouraging openness with any resulting children. Guidance note 11 in our Code of Practice sets out the information that should be provided to prospective sperm, egg and embryos donors before their consents or samples are taken (eg, information about the screening that will be done and why it is necessary). We propose that good practice regarding sperm and egg donation should apply equally to mitochondria donation. Best practice around information provision regarding unsuspected heritable conditions in donors should also apply to mitochondria donors. This would mean that if a clinic learns, through the birth of an affected child, that a mitochondria donor carries a previously unsuspected mitochondrial disease, then the donor should be notified (if they have indicated that they wish to be notified). Regulating mitochondrial donation: seeking expert views 8

9 Questions to consider We ve set out what we propose to do. Now we want to hear your views about some specific policy issues. 3. Mitochondrial donors will be providing their eggs in the same way as women donating eggs for fertility treatment. What should women donating their mitochondria be screened for? 4. Age may be an important consideration when selecting mitochondrial donors. Professional guidelines state that eggs for fertility treatment should not be taken from donors aged 36 or over. Do you think the proposed approach to apply the same age limit for women donating their mitochondria is appropriate? 5. The family limit refers to the number of families a single donor can help to create. Sperm and egg donors can donate to create a maximum number of 10 families. Do you think the proposed approach to apply the same 10 family limit to women donating their mitochondria is appropriate? Please provide reasons for your answer. 6. We set out the information that should be provided to fertility patients before consent to treatment is obtained. Before patients give their consent to treatment involving mitochondria donation, what information should clinics provide? 7. We set out the information that should be provided to prospective sperm, egg and embryo donors before their consent to donation is obtained. Before women give their consent to donating their mitochondria, what information should clinics provide? Regulating mitochondrial donation: seeking expert views 9

10 Follow-up studies Many experts have recommended that families using mitochondrial donation should be encouraged to take part in long-term follow-up studies in order to monitor any possible effects on children born and future generations. We propose that clinics should have in place a documented process for monitoring children born following mitochondrial donation, where patients have consented to follow up. The clinic should submit this information to us upon application to vary its licence to allow PNT and/or MST. This process should cover what links the clinic has with research groups or mitochondrial disease specialists, what follow up will involve (eg, the method and frequency of contact) and what information the clinic will provide to their patients about follow up. We propose introducing guidance that clinics should encourage their patients to take part in follow-up studies, whilst also acknowledging the rights of patients and their children not to participate in such studies. We also propose requiring clinics performing mitochondrial donation to submit any changes to this process to us on an annual basis. This should be submitted alongside an annual report setting out the clinic s progress on patient uptake of follow-up studies and (non-patient specific) information on the outcomes. If a clinic becomes aware that a child born following mitochondrial donation has been born with a mitochondrial disease, birth defect, or genetic abnormality (which may have been caused by MST or PNT), we will regard this as an adverse incident and the clinic is required by law to report this is to us. Question to consider We ve set out what we propose to do. Now we want to hear your views about follow-up studies. 8. Many experts recommend that families using mitochondrial donation techniques should be encouraged to take part in long-term follow-up studies to monitor any possible effects on children born and future generations. We propose that clinics must submit their process for following-up children to us. Do you think this approach is appropriate? What do you think this process should cover? Regulating mitochondrial donation: seeking expert views 10