HFEA Licence Committee Meeting 9 January 2014 Finsbury Tower, Bunhill Row, London, EC1Y 8HF

Transcription

1 Minutes Item 7 HFEA Licence Committee Meeting 9 January 2014 Finsbury Tower, Bunhill Row, London, EC1Y 8HF Centre 0101 (CARE Nottingham) - Grade A Incident Report Members of the Committee: Andy Greenfield (lay) (Chair) Bishop Lee Rayfield (lay) Debbie Barber (professional) Committee Secretary: Lauren Crawford Legal Adviser: Sarah Ellson, Field Fisher Waterhouse Observing: Sam Hartley, Head of Governance and Licensing, HFEA Declarations of Interest: members of the Committee declared that they had no conflicts of interest in relation to this item. The following papers were considered by the Committee: Executive Summary Statement by Person Responsible regarding future use of Genesis Genetics Europe Centre s final incident report re IN Centre s additional information re IN03581 Clinical Pathology Accreditation report on de novo misdiagnosis CARE Nottingham s misdiagnosis summary 2 ESHRE PGD Consortium data collection XI: cycles from January to December 2008 with pregnancy follow-up to October 2009 The causes of misdiagnosis and adverse outcomes in PGD, Wilton et al, Hum Rep Vol No 1 pp1 to Minutes of Licence Committee meeting 7 November 2013 (tabled) The Committee also had before it: HFEA Protocol for the Conduct of Licence Committee Meetings and Hearings 8th edition of the HFEA Code of Practice Human Fertilisation and Embryology Act 1990 (as amended) 1 Previously considered on the 7 November As above 3 As above

2 Decision trees for granting and renewing licences and considering requests to vary a licence (including the PGD decision tree); and Guidance for members of Authority and Committees on the handling of conflicts of interest approved by the Authority on 21 January Guidance on periods for which new or renewed licences should be granted Standing Orders and Instrument of Delegation Indicative Sanctions Guidance HFEA Directions Guide to Licensing Compliance and Enforcement Policy Policy on Publication of Authority and Committee Papers Background 1. At the previous meeting of the Licence Committee held on 7 November 2013, the Committee was presented with a suite of papers relating to two incidents reported by CARE Nottingham involving PGD misdiagnoses. The first set related to a case involving PGD of Neurofibromatosis Type 1 and consisted of a completed report of the incident investigation carried out by the executive, CARE Nottingham and Genesis Genetics Europe (GGEu): an action plan drawn up by GGEu: and a written statement provided by the Person Responsible (PR) setting out her role in the oversight of the implementation of corrective actions undertaken by GGEu together with assurances as to why GGEu remain a suitable third party to perform the PGD analysis on behalf of CARE Nottingham. 2. A second initial set of papers was provided to brief the Licence Committee that a further potential PGD misdiagnosis incident had been reported. Very little information was available at the time of presenting the papers to the Licence Committee as the incident had only recently then come to light. This second case involved PGD of sickle cell anaemia. The treatment cycle took place in 2008, resulting in an unsuccessful pregnancy. In 2012 the patient transferred her remaining two frozen embryos to a centre based in London and underwent a frozen embryo transfer. This treatment resulted in a successful pregnancy and live birth. However, following the safe delivery of the baby a heel prick test at birth revealed symptoms of sickle cell anaemia. At the time this incident was reported the baby s diagnosis had not been confirmed but the Consultant Paediatric Haematologist looking after the older sibling saw no reason to consider an alternative diagnosis. 3. The Committee on 7 November 2013 decided to adjourn the item for receipt of further information and asked the additional information should include: a. Final investigation reports for both incidents; b. Further information regarding PGD diagnosis error rates across the sector for comparison; c. Further information about Genesis Genetics Europe including how many other centres use their labs for PGD and whether they have other labs;

3 Discussion d. Clarity on the status of the patients affected by the incident. 4. The Committee noted that they had now received the additional information that had been requested. 5. The Committee noted the Clinical Pathology Accreditation (CPA) report relating to the incident relating to the Neurofibromatosis Type 1 misdiagnosis. The report confirms the conclusions reached in the original HFEA investigation, that the misdiagnosis of Neurofibromatosis Type 1 was the result of operator error rather than any systemic failure of laboratory procedures or processes. The corrective actions proposed by the laboratory were considered likely to minimise the risk of such failures occurring in the future. 6. The Committee noted that regarding the sickle cell anaemia case, the PR has provided additional information. The information outlines that it will be difficult to ascertain the root cause of this incident because of the elapsed time but explains that the procedures used now are considerably different to those used in The PR has outlined measures that she has implemented to ensure that she is made aware of any trends in misdiagnosis by GGEu so that she is better able to monitor the performance of this third party. 7. The Committee noted that the executive have concluded that there is no benefit from further investigation into the causes of this incident and that the information provided by the PR demonstrates the ongoing suitability of the clinic s third party laboratory. 8. The Committee noted that the executive consider that lessons have been learnt in relation to these incidents and recognises that the PR has engaged effectively with the investigation process and has given due consideration to the safety of their service provided by their third party laboratory. Decision 9. The Committee were satisfied that the necessary corrective actions have been taken by both the centre and the executive in both of these cases and closed these incidents. Signed: Date: 23/01/2014 Andy Greenfield (Chair)

4 Incident Report IN03434 Contents: A. Report by CARE Nottingham Appendices VG-SM.11168_PGD.pdf VG-SM 11168_PGD Report - amended.pdf 3. Final Report from GGEu - Investigation of case G-M misdiagnosis report i.pdf Note: All names have been replaced with a code: P = Patient C = Consultant E = Embryologist G = Genetics scientist N = Nurse / ODP

5 A: CARE Nottingham report Report by: Dr Lucy Jenner, Person Responsible and Lab Manager (CARE) Date of discovery of incident: Date of report: Patient CARE Numbers: and HFEA incident no: IN03434 Misdiagnosis following PGD 1.0 BACKGROUND Couple attended for PGD for Neurofibromatosis. 2.0 Treatment cycle Female partner (P1) underwent controlled ovarian stimulation and had oocyte retrieval (OR) on Embryo biopsy was performed 3 days post OR and 10 embryos were biopsied. Genetic analysis was performed by GGEu. Of the 10 embryos tested, 2 of these returned a result of unaffected/normal, 3 results shown to be affected and 5 had insufficient data on the report for a result to be given. On in conjunction with the embryo development information one of the unaffected embryos was transferred, and one was frozen for future use. Four of the no result embryos were re-biopsied at the blastocyst stage as per routine protocol and frozen pending the results of this re-testing for possible future use. A positive pregnancy test was done on 16/07/13. On the testing lab, GGEu contacted the PR of the centre to inform us that on re-reading the original data from the Day 3 biopsy they had found that the results had been interpreted incorrectly and the results report issued had given incorrect diagnosis for the embryos. Therefore the embryo that was transferred and the embryo that was frozen were affected with the genetic disease, and the 3 embryos that had been discarded were unaffected. 3. Oocyte and embryo movement witness checks Process Egg collection Confirmation of the identity of the egg provider. Patient asked to state her full name and date of birth. Cross checked against the egg provider s records and laboratory data sheet by the person performing the procedure and another appropriate person. Culture dishes used at egg collection are marked with the female patient s full name and CARE number. These are checked at the time of placing the eggs collected into culture Sperm Sample Confirmation of identity of the sperm provider. Patient asked to state his full name and date of birth. Cross-checked against the label on the sperm receptacle Date and time Signatures present E1 (Embryologist) C1 (Medical Director) N2 (HCA) E1 (Embryologist) P2 (partner) N1 (Nurse Practitioner)

6 (marked with the sperm provider s full name, date of birth and CARE number and the full name, date of birth and CARE number of the woman to be treated.) The identifying information provided by the sperm provider is also cross checked against the sperm provider s records. Following sample production the sperm provider signs to confirm that the sample is his. Sperm preparation The sperm provider s full name, date of birth and CARE number and the full name date of birth and CARE number of the woman to be treated are marked on all the sperm tubes at the time the sperm is transferred to them E7 (Embryologist) This information is cross checked by the person performing the procedure and another appropriate person, to the sperm provider s documentation and the documentation of the woman to be treated and information on the original sperm receptacle. Preparation for ICSI (hyaluronidase) The labelling on the culture dish, the hyaluronidase dish and the new culture dish for after stripping are cross-checked against each other and the laboratory documentation. ICSI The labelling on the tube containing the sperm and all dishes containing eggs are checked against the egg provider s documentation to check that the sperm and eggs should be mixed/sperm should be injected into eggs. These checks are made for: 1. Sperm added to ICSI dish 2. Eggs added to ICSI dish Eggs placed into new culture dish after ICSI Dish Change on Day 1 of culture The labelling on the culture dish and the new culture dish are cross-checked against each other and the laboratory documentation. Embryo Biopsy The labelling on the culture dish, the biopsy dish and the new culture dish after biopsy including checking the number of the embryo against the number scratched on the bottom of the dish. Also, the number on the bottom of the biopsy dish is checked against the number on the lid of the PCR tube. Each embryo or cell movement is individually and signed for on the biopsy sheet Embryo Transfer Confirmation of the identity of the patient. Patient asked to state her full name and date of birth. Cross checked against the patient s records and laboratory data sheet by the person performing the procedure and another appropriate person. The identifying information on the laboratory records and the patient s records is cross checked against the patient s records and the information on the dish containing the embryos by the clinician and embryologist performing the 1137 and and 1416 E1 (Embryologist) E1 (Embryologist) E3 (Embryologist) 29/06/13 E4 (Senior Embryologist) 01/07/ E2 (Deputy Lab Manager) E4 (Senior Embryologist) 03/07/ C2 (Consultant) N4 (ODP) C2 (Consultant) E3 (Embryologist)

7 procedure and another appropriate person. The numbers on the culture dish relating to the embryos are cross-checked against the embryo number marked for embryo transfer according to the PGD results sheet. Embryo #8 Embryo cryopreservation/disposal / research / confirmatory diagnosis Embryo freezing The labels on the culture dish are checked against the paperwork and the labels on the freezing dishes as well as the labels on the vitrification straw. The straw is also labelled with the embryo number and this is checked against the numbers on the culture dish and the PGD results sheet. Disposal The labelling on the culture dishes is cross-checked against the laboratory documentation. All items are accounted for by 2 embryologists prior to disposal to check the number of oocytes, 2PN items and 1PN/3PN items. 03/07/ /07/ E3 (Embryologist) E4 (Senior Embryologist) E6 (Deputy Lab Manager) E3 (Embryologist) E3 (Embryologist) 4.0 Embryology Results 4.1 As at 3 rd July 2013 Embryo Number Day 3 clv check biopsy Day 5 Day 6 PGD results/ comment Fate of embryo 1 7c2 2 cells taken EB poor HFB23 Insufficient data Re-bx and F set 2 7c3 2 cells taken HEB HEB poor No DNA signals D poor 3 8c2 Intact HEB FHB32 Affected D Nucleus clear 4 8c3 2 cells taken VEB FHB23 Insufficient data Re-bx and F set 5 7c2 Cell lysed EB poor FHB22 Insufficient data Re-bx and F Nucleus clear set 6 6c2 2 cells taken HEB HEB Affected D 7 10c2 HFB23 - Unaffected F 8 8c2 HFB22 - Unaffected T 9 8c1 HFB22 - No DNA signals Re-bx and F 10 7c2 Cell lysed but clear nucleus HEB deg Affected D Embryo 8 selected for transfer and Embryo 7 for freezing on the basis of PGD results, morphology and developmental status.

8 4.2. Embryology Results as at 17 th July 2013 Following information that the diagnosis given on these first set of results was incorrect, the embryo status is now known to be different to that shown above. The table below shows the actual diagnostic results alongside the embryo information. Embryo Number Day 5 Day 6 PGD results from second read of data and Re-biopsy results Fate of embryo 1 EB poor HFB23 Insufficient data set Affected Re-bx and F 2 HEB poor HEB poor No DNA signals D 3 HEB FHB32 Unaffected D 4 VEB FHB23 Insufficient data set Affected Re-bx and F 5 EB poor FHB22 Insufficient data set Affected Re-bx and F 6 HEB HEB Unaffected D 7 HFB23 - Affected F 8 HFB22 - Affected T 9 HFB22 - No DNA signals Re-bx and F 10 HEB deg Unaffected D 5.0 CONCLUSIONS 5.1. The correct embryos were transferred with respect to the numbering in the dishes and the PGD results The embryo transferred and the embryo frozen are actually affected with the single gene disorder The 3 embryos that were unaffected by the disease were numbers 3, 6 and 10 which have been disposed of at the conclusion of the cycle 5.4. Of the 4 embryos that were re-biopsied and frozen, 3 are affected as a result of the testing, and 1 remained inconclusive The patient has an affected pregnancy and 4 affected embryos in storage; she has no remaining unaffected embryos from this cycle. Update 11/12/13 the patient is aware of the changed status of the frozen embryos. 6.0 PATIENT CARE The patient was contacted on 17 th July to invite her to attend a meeting with Miss Ragunath at CARE so that this news could be given to her and her partner. They attended on Friday 19 th July at 10am and were seen by Dr Ragunath (Medical Director) and Mary Smedley (Nurse Manager and PGD nurse). MR and MS discussed with her the options for the pregnancy going forward including immediate termination, waiting for pre-natal diagnosis. The patient has opted to wait for the 8 week scan and take decisions form there. The couple have arranged to see

9 their regional genetic counselor to discuss the possible effects on the baby should she opt to continue with the pregnancy. The couple were asked to come to Nottingham on Friday the 19 th. Mary and I met with them in the Counselling room and I went on to explain the unfortunate turn of events. Understandably the couple were distraught and after the initial shock of the news I then proceeded to discuss with P1 the options available to her. I went through each clinical scenario in turn, and encouraged her to meet with her geneticist, which she arranged to do on the same day. The couple were clearly not in a position emotionally to come to any decision and went home with a view to making a decision after having met with the geneticist. I later spoke to Dr Sue Huston geneticist who had originally seen and counselled P1. I explained in some detail regarding the misdiagnosis and my conversation with P1 and P2. I have now arranged for P1 to return to the unit for a pregnancy scan which has been brought forward a week in order to discuss the couples options at this stage. M Ragunath, Medical Director, CARE Nottingham. Update 11/12/13 The patient has an ongoing singleton pregnancy EDD She has seen a Geneticist and fully understands the implication of continuing with the pregnancy. She has requested a copy of the incident report which has been provided in the same anonymized format as that provided to the HFEA on GGEu A full investigation has been carried out and the report provided to both the PR of the centre and direct to the HFEA. GGEu have provided the PR with evidence of completion of all the identified preventive and corrective action. 8.0 GGEu and their accrediting body - the CPA The CPA carried out an inspection of GGEu to investigate this incident. GGEu have provided the report from this visit to CARE and to the HFEA. The conclusion of this report was that the lab had carried out a thourough investigation, that the actions identifired and implemented would ensure the furture safety of the diagnosis carried out, and that the lab should retain accreditation although the timing of the next visit is to be brought forward to 12 months from the date of that inspection. Documents provided to CARE and HFEA by GGEu: Investigation of case G-M misdiagnosis report pdf GGEU remedial and corrective actions - IN03434.pdf 3084-CPA Report_on_Misdiagnosis final draft.pdf GGEu preventive action to avoid misdiagnosis and adverse outcomes in PGD.doc 8.0 Final Conclusion The thorough investigation carried out by GGEu, the implementation of the actions identified and the sharing of the findings and conclusions with CARE, the HFEA and the CPA all serve to strengthen our confidence in GGEu as the provider of our genetic diagnostic service.

10 CARE are satisfied that the safety of future patients is not compromised by the continued use of GGEu as a genetic diagnostic laboratory for the treatment of PGD patients. Given the complexity of the science and of the cases for which treatment can be offered it is recognised that GGEu offer a service that is responsive, forward thinking and quality-managed.