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AUTH/2984/10/17 - Health Professional v Astellas UK

Case number:AUTH/2984/10/17
Case ref:Health Professional v Astellas UK
Description:Provision of funding linked to use of Advagraf and failure to provide comprehensive, accurate information
No breach:No breaches Clauses 2, 9.1 and 18.5.
Breach:Breaches Clauses 2, 9.1 and 18.5. Public reprimand, Report to ABPI Board
Appeal:Appeal by complainant
Status:Breach ruled, case report pending
Review:Published in the November 2018 Review
Received:13/10/2017
Completed:04/09/2018
Case Summary:

A hospital doctor alleged that Astellas Pharmaceuticals Limited had inappropriately awarded research funding (in region of £250,000) in 2009 in association with the use of Advagraf (tacrolimus) which was indicated for use in kidney and liver transplant patients to prevent rejection.  The complainant alleged that the funding was made available to a senior clinician for him/her to study the efficacy of a newly adopted immunosuppressive protocol at the renal transplant unit of a named hospital.  According to the complainant, the protocol adopted in 2009 was abandoned by 2012 because of poor outcomes.  The protocol was used for patients who received a renal transplant from a living donor and included the use of Advagraf (de novo), azathioprine and prednisolone.
 
The complainant acknowledged that a long time had elapsed since the event, but the details had only come to his/her attention recently.  The complainant was concerned that there was a link between the adoption of the protocol and the provision of funding.  The complainant also stated that funding, or part thereof, was withdrawn when the outcome was not as expected. 
 
The detailed response from Astellas UK appears below.
 
The Panel noted that in May 2009 the Astellas Investigator Driven Study Evaluation Committee (IDSEC) had 'approved in principle' a request for £250,000 to fund two studies but wanted a number of questions answered.  Each study was to use Advagraf and was due to start in January 2010.  Astellas UK submitted that neither study went ahead and no funds were made available by Astellas UK at the time.  In 2010 a request for £50,000 for a special purpose fund to support ongoing clinical research from one of the two health professionals who previously asked for the study funding was agreed.  According to Astellas UK the payment was made as a medical and educational good and service (MEGS) on 21 December 2010.  The relevant Code was the 2008 edition.  Following the agreement to donate £50,000, the hospital wrote, confirming that the '… £50,000 grant would permit implementation of a new clinical protocol using Advagraf in de novo live related kidney transplantation and to support ongoing clinical research in the area of renal transplantation.  The funding would allow the team to employ bank nursing staff/statistical support to extract and analyse fundamental data'.  There was no mention in a memorandum of agreement between Astellas UK and the hospital (signed in June 2010) about the clinical protocol but it mentioned that the funding was to support continuing clinical research in the area of transplantation at the hospital to facilitate employment of bank nursing staff statistical support to extract and analyse the data.
 
Astellas UK had not provided the protocol.  The complainant stated it was used from 2009 to 2012 and alleged that following its adoption, Astellas UK agreed to fund a study. 
 
It was not clear when or why Astellas UK decided not to fund the two studies following the request in April 2009.  As no payment had been made there was no evidence of inappropriate funding for research in this regard.  The Panel therefore ruled no breach of the 2008 Code including Clause 2.  The complainant appealed these rulings.
 
In October 2010 Astellas UK paid £50,000 to the named hospital's special purpose fund.  The Panel considered that this payment came within the complainant's general allegation about funding following the adoption of the immunosuppressive protocol.  The Panel was concerned about the hospital's description of how the money was to be used which was sent to Astellas UK prior to the payment being made; this was not mentioned in the original request or the signed contract.  There was no information before the Panel demonstrating that funding had been withdrawn when the outcome was not as expected as alleged.
 
The Panel noted with concern the complainant's allegation that the clinical protocol to use Advagraf de novo was abandoned by 2012 because of poor outcomes.  No copy of the protocol was provided.  There were no details about when or how it was agreed.  The complainant referred to its adoption in 2009 which was before Astellas UK made the payment of £50,000 in 2010.  The Panel noted that in his/her letter of 6 October 2010 a senior person at the hospital with a fundraising role referred to using the £50,000 for implementation of the protocol.  The Panel noted that the initial request for the £50,000 funding stated 'As per our recent conversations about clinical research and medical education in the …'.  The Panel had no knowledge of the content of these conversations.
 
Although the Panel was concerned about the circumstances, particularly the impression given, it did not consider that the complainant had shown, on the balance of probabilities, that the funding was inappropriately linked to the use of Astellas UK's product.  The Panel therefore ruled on balance no breach of the Code including Clause 2.
 
On appeal the complainant alleged that the exchange of correspondence between Astellas UK, the requesting health professional and the hospital fundraiser indicated extensive undisclosed discussions.  There was no indication of patient or wider NHS benefit in the request.
 
The complainant alleged that Astellas UK agreeing to fund two investigator driven clinical studies (IDS) in May-June 2009, had certainly influenced the subsequent adoption of Advagraf in the hospital protocol in September 2009.  The change was proposed by the same applicants of the IDS and MEGS.
 
The Appeal Board noted that the complainant, bore the burden of proof.  There was no evidence that funding had been provided for either of the two IDS.  The Appeal Board therefore upheld the Panel's ruling of no breach of the 2008 Code including Clause 2 of the 2008 Code.  The appeal on these points was unsuccessful.
 
The Appeal Board noted that according to the complainant in September 2009 the immunosuppressive clinical protocol at the named hospital was changed to Advagraf (de novo), azathioprine and prednisolone; the first patient was enrolled in November 2009.  The Appeal Board noted, with concern, the complainant's submission that the hospital's clinical protocol was abandoned in 2012 due to high rejection rates, which the complainant submitted had been the subject of internal discussion within the hospital.  The Appeal Board noted that the hospital's clinical protocol was the same as that proposed with regard to the second study in the IDSEC application and used Advagraf de novo.
 
The Appeal Board noted Astellas' submission that multiple factors might be involved in the rejection rates and also that there was no evidence to suggest that the provision of the subsequent MEGS to the hospital was linked, directly or indirectly to the hospital changing its immunosuppressant protocol.  The Appeal Board considered that since the submission of the application for funding for the studies, there was evidence of ongoing interaction and dialogue between the hospital and certain key individuals at Astellas UK related to provision of funds to the hospital. 
 
The Appeal Board noted the dates of key events.
 
The Appeal Board also noted the largely illegible document provided by Astellas which appeared to be headed 2009, the format of which appeared to be closely similar to the 2010 memorandum agreement for the £50,000 MEGS payment between Astellas UK and the hospital.  It was partially signed.  The second signature clause for the health professional bore an indecipherable signature and date.  The first signature clause, unsigned, was for a specific Astellas UK member of staff from the medical department.  In the Appeal Board's view this document showed that, on the balance of probabilities, at the very least, there was some dialogue between the key individuals at both the hospital and Astellas UK about the provision of funds, via the MEGS route resulting in the partially signed document.
 
The Appeal Board noted that on 11 May 2010 one of the health professionals who had applied for the study funding to the IDSEC in 2009 wrote to a member of Astellas UK's medical department (first employee) referring to recent conversations about '…clinical research…' to ask for £50,000 for the [special purpose fund] to support ongoing clinical research to facilitate employment of bank nursing staff/statistical support to extract and analyse the necessary data from the hospital's database.  The Appeal Board noted that at that time, given Astellas UK's previous and ongoing interactions at the hospital, including the involvement of the first employee, on the balance of probabilities, Astellas UK would have known about the hospital's clinical protocol and the switch to use Advagraf in combination.  A memorandum of agreement between Astellas UK and the hospital dated 27 May 2010 was signed by the applicant on 4 June and by Astellas UK on 14 June.  The document mentioned that the grant was to support 'your continuing clinical research in the area of transplantation at [named hospital]', and that it was to facilitate employment of bank nursing staff/statistical support to extract and analyse the necessary data from the department's database.  There was no mention in the memorandum of agreement about the hospital's clinical protocol.  Following the agreement to donate £50,000, a hospital fundraiser wrote on 6 October 2010 confirming that the '… £50,000 grant would be used as part of the ongoing clinical research; it would '… permit implementation of a new clinical protocol using Advagraf in Denovo live related kidney transplantation and to support ongoing clinical research in the area of renal transplantation.  The funding shall allow the team to employ bank nursing staff/statistical support to extract and analyse fundamental data'.  The first employee responded to the applicant with a letter dated 14 October 2010 headed 'Re: Funding to support your continuing clinical research in the area of transplantation at … [hospital]' and enclosed a cheque for £50,000.
 
The Appeal Board noted Astellas' submission that the director at the hospital was mistaken that the clinical protocol was new.  The Appeal Board was concerned about the description in the letter of how the money was to be used noting that it was received by Astellas UK before the payment was made; 'the implementation of a new clinical protocol' was not mentioned in the original request or the signed agreement.  In the Appeal Board's view, the letter from the hospital made it clear that the hospital considered that the payment was linked to its use of Advagraf.  The Appeal Board noted that the memorandum of agreement stated that 'You agree to use the Support for the purposes described in this letter only and you will return the Support to the Company if it is not used for these purposes'.  Yet despite the reply stating that '… £50,000 grant would permit implementation of a new clinical protocol using Advagraf …' there was no information before the Appeal Board to demonstrate that Astellas UK had taken any action or followed up how the funding was subsequently used. 
 
The Appeal Board noted from Astellas UK at the appeal, that the relevant standard operating procedure at Astellas UK at that time would have allowed the grant on the basis that it was for patient benefit and that it would have been approved by a grants committee, yet there was no record of this.  In this regard the Appeal Board noted that the 2008 Code required MEGS to be documented and kept on record.  Whilst noting the passage of time the Appeal Board was concerned about other missing core documentation such as records of contacts made by certain Astellas staff with the key health professionals and material submitted to IDSEC.  The Appeal Board considered that whilst this had happened several years ago, by the standards required at that time, the documentation was poor.  The Appeal Board queried Astellas UK's decision to award the grant given the company's recent interactions with the hospital regarding the IDSEC applications and the clinical switch to using Advagraf and the fact that MEGS were required to be non-promotional and must not constitute an inducement to prescribe, supply, administer, recommend, buy or sell a medicine.
 
The Appeal Board noted its comments above.  The Appeal Board noted the common themes between the second study, the 2009-2012 hospital protocol and that the study funding requested was to help support a renal research fellow and research nurse – which echoed the reference in the MEGS application for support for a nurse/statistical support to extract and analyse data.  The Appeal Board noted the ongoing dialogue about funding outlined above and the failure to keep proper records and that the hospital linked the provision of the funds to Advagraf.  The Appeal Board considered that the cumulative effect was that on the balance of probabilities, the payment did not satisfy the requirements for MEGS and was inappropriately linked to the use of Advagraf.  The Appeal Board ruled breaches of the Code including a failure to maintain high standards.  The Appeal Board considered that the circumstances were such that Astellas UK had brought discredit upon, and reduced confidence in, the industry.  A breach of Clause 2 of the 2008 Code was ruled.  The appeal on these points was successful.
 
During the re-audits in April 2018 in relation to other cases concerning Astellas UK and Astellas Europe (Cases AUTH/2780/7/15, AUTH/2883/10/16 and Cases AUTH/2939/2/17 and AUTH/2940/2/17) when those carrying out the re-audits followed up on the Appeal Board's concerns in Case AUTH/2984/10/17, a timeline (dated November 2010) was supplied which included details relevant to Case AUTH/2984/10/17 which had not been supplied previously.  On receipt of further information from Astellas UK, the original Panel was reconvened to consider the matter.
 
The detailed response from Astellas UK is given below and included a report from external counsel which was asked by Astellas to conduct an investigation.
 
The Panel noted that its concerns were broader than outlined in the scope of the external counsel report requisitioned by Astellas including whether the apparent failure to provide a complete response reflected a cultural approach to compliance and the Code, noting that the failure to provide complete and accurate information had previously been an issue in Case AUTH/2780/7/15.
 
Numerous documents were requested by the PMCPA and these were supplied by Astellas UK with its response to the detailed questions.  The Panel did not understand why these documents were not supplied with the company's responses to the complaint and appeal.
 
The Panel had a number of very serious concerns about the responses from Astellas and its approach to ensuring that comprehensive details were provided for both the Panel and the Appeal Board.
 
The Panel was extremely concerned about the company's responses.  It appeared that the investigation into the complaint was inadequate.  Astellas staff knew there was a timeline but Astellas UK appeared not to attempt to locate the November 2010 timeline nor was it provided in response to the complaint.  Further, the Astellas UK timeline which was provided for the appeal was inconsistent with the November 2010 timeline.  Astellas had not commented on the accuracy or otherwise of the November 2010 timeline.
 
The Astellas timeline provided in response to the appeal stated that Astellas closed the study application as not progressed in January 2010 as no revised proposal was submitted by the hospital and the written request for a grant was received on 11 May 2010.
 
The position regarding the separation of the discussion of the funding of the studies and the provision of a MEGS was not as clearly delineated as implied by the Astellas timeline provided for the appeal.  It also appeared that there was more information about the de novo study than that supplied by Astellas UK in response to the complaint including that the de novo study had been approved by IDSEC on 27 November 2009 and the UK brand team decided not to support this IDS.  It was not clear why such a decision was left to a brand team.  It also implied that the possible funding of the study was a commercial/marketing decision rather than a medical one.  The UK brand team would know about the change of treatment protocol in the hospital and it could be argued that there was no additional benefit to the company in funding the de novo study when it considered the matter in November 2009. 
 
The Panel was concerned that Astellas had detailed information about the de novo study including the IDSEC submission but these had not been supplied in response to the complaint or appeal.  This was inexplicable.  It was of further concern that in response to a request for clarification from the PMCPA, Astellas submitted that material not provided previously was found as a result of the external counsel investigation.  That was not so in relation to the de novo study.  Details were set out in the company's response to the complaint and appeal and yet no source material was provided at that stage.
 
It was of concern that the request letter from the hospital dated 11 May 2010 provided by Astellas in its response of 7 November 2017 was different to that previously supplied by Astellas as it did not include the wording:
 
          'to implement our new clinical protocol using Advagraf in de novo live donor kidney transplantation and'
 
The letter provided in November 2017 included details of the salary etc for the statistical support.  One possible explanation for the differences was that on receiving the letter from the hospital someone at Astellas asked the hospital to amend its request.  There was no evidence in that regard.  Nonetheless, the original letter from the hospital was highly relevant.
 
The Panel was extremely concerned to note that Astellas' response of 26 January 2018, in relation to the appeal, specifically stated that there was no reference to using the grant to implement this protocol in the original request or the signed contract for the grant.  Astellas also submitted, as part of its response to the appeal, that there was a misunderstanding or misstatement by a hospital fundraiser in the letter of 6 October 2010 who had referred to a 'new' protocol.
 
The external counsel report stated that discussions around the studies closed in January 2011.  This was inconsistent with information provided for the appeal that another member of Astellas UK's medical department (second employee) visited the hospital in January 2010 to confirm in person that the two studies would not go ahead as IDSEC had not received a response.  The November 2010 timeline clearly indicated discussions up until October 2010 in relation to the switch study.  The external counsel report stated that on 22 December 2010 two named members of the medical department (the second employee and the first employee's line manager) met one of the health professionals to inform him/her that the switch study would not be progressed and to present the MEGS cheque (now made out to the correct payee).  The Astellas timeline referred to this cheque as 'grant cheque issued by Astellas' on 21 December 2010.
 
The Panel was concerned about the impression given by this meeting when the health professionals from the hospital were both informed that the study would not be progressed and presented with the cheque for £50,000.  The Panel noted an email from the second employee dated 22 December 2010 to a number of Astellas staff including senior leaders, the first employee and members of the UK brand team to report on the meeting (a copy of the November 2010 timeline was attached to the email).  The email mentioned that 'we did of course soften the blow by delivering a £50k cheque today under the MEGS agreement which was for separate work and [the named health professional] seemed grateful for that'.  At that meeting the company agreed to cover the cost of an expert who had prepared the study protocol, research ethics preparation and attended project planning meetings.  A copy of an invoice for £2,500 was provided.  This was the first mention of an additional and relevant payment in relation to the activities at issue, albeit to a third party.  It underlined the importance of doing a broad indepth investigation at the outset.
 
It appeared that Astellas had not made any reasonable effort to look at the issues in the broadest sense to understand the relationship between various Astellas UK staff and the hospital. 
 
The Panel noted the submission from Astellas regarding the timing of events and acknowledged that the time period around an audit/re-audit would be particularly demanding for any pharmaceutical company.  Astellas was advised by the PMCPA case preparation manager that a complaint had been received and the response time was extended by the case preparation manager beyond the 10 working days, Astellas did not ask for an extension of time at either stage.
 
In the Panel's view, there was less overlap with the October 2017 re-audits than that implied by Astellas.  The correspondence from the PMCPA referred to the possibility of requesting an extension and indeed the case preparation manager had decided herself to provide one at the outset, in the absence of any such request from Astellas.  The Panel considered that stating that Astellas UK was in the middle of a major and important re-audit did not give a fair impression about the demands on the company resulting from the re-audits when responding to the complaint and the complainant's appeal.
 
The Panel noted that effective self-regulation relied upon the submission of accurate responses to the PMCPA.  There was an expectation that companies comprehensively investigated all the circumstances surrounding complaints.  Failure to do so and failure to provide an accurate, comprehensive response were serious matters.  The PMCPA was extremely concerned about the additional information which only came to light as a result of an interview at the April 2018 re-audits.  The Appeal Board had also commented on the limited documentation provided.  It appeared that the company either did not recognise the importance and relevance of key information and decided not to follow up key information or decided to ignore this information.  It was clear that the investigation team had not obtained all the relevant information from staff.  The Panel was concerned about the statement in the external counsel report that information from interviewees did not always appear to have been read in full and incorporated into the responses and that there was a lack of follow-up of potentially relevant issues.  Overall, in the Panel's view, the compilation of the response had been reckless; there appeared to be a complete absence of care and attention and due diligence.
 
The Panel noted Astellas' submission that overall this additional information would not have altered the company's submissions to the Panel and the Appeal Board but that Astellas accepted that there might have been a fuller response.
 
The Panel was extremely concerned about the inadequate investigation which led to incomplete and misleading responses.  The missing information was relevant to rulings.  The Panel had previously ruled, on balance, no breach of the Code in relation to the £50,000 MEGS payment.  It was extremely concerning that the final outcome of this case would have been different if the complainant, a busy NHS health professional, had not appealed.  Effective self-regulation should not rely on the fact that a health professional appealed a ruling to trigger a process which ultimately led to more complete disclosure.  Nor should effective self-regulation be reliant upon the coincidental timing of the re-audits which fortuitously gave the opportunity for the PMCPA to follow-up on the Appeal Board's concerns about documentation.
 
The Panel considered that Astellas UK's behaviour in investigating this matter in October 2017 was unacceptable and was completely inconsistent with the recent and numerous commitments made elsewhere to upholding the highest standards.  Astellas Europe and Astellas UK had been audited 5 times since December 2015.  It was beyond belief that Astellas UK would not follow its standard operating procedure (SOP) given all the training and emphasis in the company to doing that.  In previous cases Astellas had been found seriously wanting in taking appropriate action when responding to the PMCPA.  The current suspension of Astellas UK from membership of the ABPI would end on 24 June 2018 and the ABPI Board decided on 5 June there was no need for it to consider expelling Astellas UK from membership.  In reviewing the report of the April 2018 re-audits, neither the Appeal Board nor the ABPI Board took into account the matters raised following the appeal in Case AUTH/2984/10/17 as these were still to be considered by the PMCPA.  The report of the April 2018 re-audits included a brief summary of the position. 
 
Taking all the circumstances into account, including Astellas UK's acknowledgement that it had failed to follow its processes, the PMCPA decided to report Astellas UK to the Appeal Board under Paragraph 8.2 of the Constitution and Procedure.  Given the seriousness of the Panel's concerns and the other cases, the Panel considered that the report to the Appeal Board should be heard at its meeting on 20 June 2018.
 
The detailed comments from Astellas UK on the report from the Panel appear below.
 
The Appeal Board noted that Astellas UK was currently suspended from membership of the ABPI until 24 June 2018, having been suspended for the maximum 2 year period.  At its meeting on 5 June 2018 in relation to Cases AUTH/2780/7/15, AUTH/2883/10/16 and Cases AUTH/2939/2/17 and AUTH/2940/2/17, the ABPI Board decided, on the evidence before it at that time which included the report of the April 2018 re-audits and a summary framework agreed by the Appeal Board, that there was no need to consider expelling Astellas.  In reaching its decision, the ABPI Board noted that Astellas UK was still to respond in relation to the matters raised in Case AUTH/2984/10/17.  Further re-audits were required by the Appeal Board to be carried out in March 2019 (Cases AUTH/2780/7/15, AUTH/2883/10/16 and Cases AUTH/2939/2/17 and AUTH/2940/2/17).
 
The Appeal Board considered the report in Case AUTH/2984/10/17 on 20 June.  It noted that the report concerned Astellas UK's recent failure to properly investigate an historic matter including its failure to disclose all relevant documentation to the Panel and Appeal Board, and the company's current approach to compliance.  The Appeal Board's role was to consider whether the circumstances warranted the imposition of further sanctions under Paragraphs 11.3 and 12.1 of the Constitution and Procedure.
 
The Appeal Board noted that Astellas UK had accepted all the rulings of breaches of the Code including Clause 2.  The Appeal Board also noted Astellas UK's apology that its responses were not as complete as they should have been.  It also noted Astellas UK's view that there were apparent failings in the process of requesting, providing and reviewing information.  The company stated it had identified amendments to its processes to address these.  The Appeal Board also noted Astellas submissions regarding its responses to the Panel and appeal including Astellas' view that its position in the appeal response would have remained the same in that there was no evidence to indicate that funding was offered or provided as an inducement for the hospital to place Advagraf on its immunosuppressant protocol. 
 
The Appeal Board noted the very detailed consideration of the Panel including its comments on material not previously provided and its view that, overall, the compilation of the company's responses had been reckless; there appeared to be a complete absence of care and attention and due diligence.  The Appeal Board also noted that the Astellas representatives referred to aspects of Astellas' investigation as 'too casual', 'cavalier' and stated that the mistakes made were being addressed.  The company representatives stated that there was not an institutional failing with respect to compliance in Case AUTH/2984/10/17, a phrase previously used by the PMCPA to describe Astellas' compliance status.
 
The Appeal Board noted the historical nature of the matters at issue and accepted that retrieving some materials might not have been straightforward.  The Appeal Board noted the company's submission in this regard.  Nonetheless, the Appeal Board did not consider that the matter at issue in Case AUTH/2984/10/17 was as complex as implied by the company.  In the Appeal Board's view, notwithstanding the historical nature of the matters at issue, adopting basic principles of good governance and compliance practice, common sense and a positive cultural approach to transparency and disclosure should have facilitated more accurate responses and complete disclosure.  That such an approach, apparently and on the evidence before the Appeal Board, was not consciously adopted at the outset was, in the Appeal Board's view, and given Astellas' recent compliance history, both inexplicable and inexcusable.
 
The Appeal Board was deeply concerned about the lack of rigour which Astellas had applied in conducting its investigation.
 
In the Appeal Board's view, the failures of the investigation team were startling and included an apparent failure, at the outset, to proactively seek information, bearing in mind the broad scope of the case preparation manager's request; primarily, using informal modes of communication (verbal and text messages) to seek critical information; an acknowledged failure to read all information including critical and relevant information provided by staff and an acknowledged failure to properly interrogate material and staff and adopt a policy of full disclosure.
 
The Appeal Board noted that despite Astellas knowingly deviating from its complaints SOP the company had made no record of this including any written agreed deviations.
 
The Appeal Board noted the Panel's assessment of the additional information and paperwork including the two different versions of the important letter from the hospital dated 11 May 2010 requesting the MEGS and the emails dated 9 and 10 December 2009 between the first and second employees, that the payment of the MEGS was now clearly linked to the change in the hospital treatment protocol to use Astellas' medicine in a manner consistent with the de novo study which had previously been rejected by Astellas' own IDSEC due to patient safety concerns current at that time.  The Appeal Board noted that one version of the letter from the health professional at the hospital to Astellas dated 11 May 2010 linked the MEGS payment to the implementation of '… our new clinical protocol using Advagraf in de novo live donor kidney transplantation' and was highly relevant and had not been previously disclosed.  The Appeal Board noted the company's explanation at the consideration of the report that, on receipt, the first employee asked the health professional to submit an amended version.  This amended version of the 11 May 2010 letter had originally been provided to one of the investigators on 31 October 2017 as part of the investigation and disclosed to the PMCPA as part of its response to the complaint.  The original 11 May 2010 letter linking the MEGS to the hospital treatment protocol was subsequently provided by the first employee to the investigator but it was unclear whether that attachment to an email dated 3 November 2017 had ever been opened and if so whether its significance had been realised.  The Appeal Board considered that the original letter dated 11 May 2010 was highly relevant and provided compelling evidence that at the very least from the hospital's perspective the MEGS was linked to the product. 
 
According to the November 2010 timeline, a newly designed de novo study was reviewed and approved by IDSEC on 27 November 2009 although the UK brand team subsequently decided not to support it.
 
The Appeal Board noted that according to the complainant in Case AUTH/2984/10/17, the hospital treatment protocol was ceased when higher than average rates of rejection were being recorded.  Astellas had submitted in that case that multiple factors might be involved in the rejection rates.  The Appeal Board noted that the historic patient safety issue was not the subject of the complaint in Case AUTH/2984/10/17 and therefore had not been considered or ruled upon as a discrete issue but rather arose as a coincidental matter during the consideration of that case.  The Appeal Board noted its relevant comments above in the Appeal Board ruling.  At the consideration of the report the company representatives explained that they had contacted the hospital after the appeal in Case AUTH/2984/10/17 because of the need to be transparent given the seriousness of the information re patient safety which came to light at the appeal.  The Appeal Board noted that some of the newly disclosed material was relevant to the historic patient safety issues.  The Appeal Board further noted that previous cases had raised patient safety issues (Case AUTH/2883/10/16 and Cases AUTH/2939/2/17 and AUTH/2940/2/17).  It was of serious concern that a current investigation into a complaint that revealed an historic patient safety issue was so poor.
 
The Appeal Board considered that this case warranted the imposition of further sanctions and considered that it would be artificial to consider the proportionality of such sanctions without due regard to previous cases and 5 audits and re-audits over the past 3 years.
 
The Appeal Board noted that Astellas UK had apologised for its failings in this case and it stated that it was due to undertake measures to ensure that such failings did not reoccur.  Nonetheless, the Appeal Board considered that it was fundamental for effective self-regulation for companies to provide accurate information to the Panel and the Appeal Board and for failing to do so it publicly reprimanded Astellas UK in accordance with Paragraph 11.3 of the Constitution and Procedure.
 
The Appeal Board noted that when it considered the report of the April 2018 re-audits at its meeting on 17 May 2018 it had decided that on the information before it, and noting that Astellas UK was still to respond in relation to the matters raised in Case AUTH/2984/10/17, that sufficient progress had been made by the companies such that the Appeal Board did not consider that it warranted a recommendation for the expulsion of Astellas UK from membership of the ABPI.  Whilst noting that the expulsion of a member company was entirely a matter for the ABPI Board, the Appeal Board considered that had this report in Case AUTH/2984/10/17 been before it when it considered the report of the April 2018 re-audits including the summary framework, it would have considered that insufficient progress had been made on certain parameters and the Appeal Board would have recommended that the ABPI Board expel Astellas from membership of the ABPI.  The Appeal Board had previously expressed the view that if a company was expelled from membership from the ABPI for issues relevant to patient safety then the period of expulsion should be for 5 years.
 
The Appeal Board considered that this case raised very serious matters including the historic issues relating to patient safety.  In addition, given the level of scrutiny the companies were already under in relation to compliance, the Appeal Board was very concerned about the issues as set out above.  Consequently, taking all the circumstances into account, the Appeal Board decided that in accordance with Paragraph 12.1 of the Constitution and Procedure, Astellas UK should be reported to the ABPI Board.  Whilst noting the ABPI Board's role and responsibilities in determining any expulsion, the Appeal Board recommended that Astellas should be expelled from membership of the ABPI for a minimum of 5 years.
 
The Appeal Board noted that the case raised issues other than the conduct of Astellas.  It noted Astellas' statement that following the appeal in March 2018 it had written to the hospital about patient safety issues and considered that the case report, when available, should be provided to the hospital trust at issue as well as the Care Quality Commission, the independent regulator of health and social care in England, with a covering letter.  The Appeal Board requested that it be provided with a draft of the covering letters for comment.  The Appeal Board noted that the MHRA would receive a copy of the case report in any event.
 
The detailed comments from Astellas UK on the report from the Appeal Board appears below.  The company submitted extensive comments including criticism of the Appeal Board's approach and consideration particularly that there was a lack of due process and unfair and prejudicial treatment of Astellas UK.
 
The ABPI Board noted the report from the Appeal Board and Astellas UK's comments.
 
When the ABPI Board had last considered matters relating to Astellas in June 2018 (Cases AUTH/2780/7/15, AUTH/2883/10/16 and Cases AUTH/2939/2/17 and AUTH/2940/2/17), it had been clear that the company would need to ensure that there was an ongoing commitment to sustained culture change throughout the organisation.  Previous audits had shown that the compliance culture was improving, so it was disappointing that the company had been reported to the ABPI Board once more.
 
The view of the Appeal Board was clear.  In addition to the report to the ABPI Board in Case AUTH/2984/10/17 and the recommendation that Astellas UK be expelled from membership of the ABPI for five years, the Appeal Board decided that Astellas UK should be publicly reprimanded.
 
However, the ABPI Board remained clear in its view that compliance was an ongoing journey that required continual self-adjustment and improvement.  The ABPI Board had confidence that a named senior leader at Astellas UK would be able to lead the company forward on this journey.
 
The ABPI Board considered the reputation of the industry to be of utmost importance, and therefore carefully considered all of the information before it.  The ABPI Board concluded that although Astellas had made mistakes, in its view there was no malintent from the company to conceal.  The ABPI Board noted the company's submission that measures had now been taken to address the issues arising from this case.  The ABPI Board noted Astellas UK's submission that at no point were any patient safety issues caused by the conduct of Astellas and that the use of Advagraf within the protocol was in line with the SPC for the time the hospital protocol was in force.  The ABPI Board further noted that patient safety was not the subject of the complaint.
 
The ABPI Board was already due to see the reports of the PMCPA's 2019 re-audits of Astellas UK and Astellas Europe as a result of its consideration of re-audits in other cases.  The failures identified in this case should be considered as a part of those re-audits.  The Board would look closely at the report of the re-audits to ensure that it remained satisfied with the position of the companies.

 
Taking everything into account, the ABPI Board decided that no further action should be taken in relation to this report from the Appeal Board.