Birchall’s trachea transplant trial at UCL suspended by health authorities

The British laryngologist and UCL professor Martin Birchall is in trouble now, despite all his constant attempts to turn claims into facts and declare the “stem cell”-based cadaveric trachea transplant technology (which he initially developed together with Paolo Macchiarini) a full success. Birchall’s own little trachea transplant trial INSPIRE (see background here), where the method was about to be applied once again, and on four patients outside of any life-threatening conditions, has been now suspended indefinitely by the NHS Health Research Authority and its South Central – Oxford A Research Ethics Committee (REC), as I report exclusively below. Meanwhile, the Information Commissioner’s Office (ICO) is investigating Birchall’s employer UCL Hospital for providing me with inappropriate and misleading information about that trial under Freedom of Information Act (see email here). Also, the Human Tissue Authority (HTA) is investigating a suspected loss of laboratory documentation at the veterinary department of Bristol University, where their former professor, his Bristol colleagues and Macchiarini’s student Philipp Jungebluth generated in 2008 a trachea transplant for Macchiarini’s patient Claudia Castillo in Barcelona (for background, see my report here).

On the plus side, Birchall’s larynx transplant trial, RegenVox, is unaffected by the decision of the Oxford REC and can apparently continue to try and recruit patients (see parts of original funding proposal here, here, here and here). Also his other trachea transplant trial, the huge pan-European phase 2 follow-up TETRA is being prepared at full speed, and may start transplanting entire cohorts of patients with cadaveric trachea already in 2018, without its phase 1 predecessor INSPIRE ever moving anywhere (draft proposal for INSPIRE here). The European Union has now once again denied me access to what kind of British and German-made cadaveric trachea transplants TETRA participants intend to implant in UK, Italy and Poland (full letter here, see previous denial here), citing that:

“it is the patients themselves and their families, the treating doctors, the ethics committees and the competent national authorities who have to agree altogether on the participation in any early (experimental) clinical trial”.

The EU Commission Secretary General Alexander Italianer further declared that while the scientific and ethical will be sufficiently covered by the appropriate authorities, the public must never be made aware of the details of these tracheal transplants, because:

“there is a real and non-hypothetical risk that public access to the requested document would undermine the commercial interests, including intellectual property, of the grant applicant”.

Meanwhile, Birchall is busy with fixing the scientific literature, in his own way. He corrected a paper (Birchall et al, 2011) to acknowledge re-use of two figures from his previous paper (Birchall & Macchiarini, 2008) and to quietly remove Macchiarini’s then-affiliation as guest professor at UCL. There were also even more subtle tweaking activities taking place. A paper Birchall co-authored with the former UCL nanotechnology professor Alexander Seifalian (Crowley et al 2014) declared the Barcelona patient Claudia Castillo as fully cured and “leading a normal life”, which of course was far from the truth. The recipient of a Seifalian-made plastic trachea, Andemariam Beyene, was according to authors “doing very well and has returned to a normal life”. But when the paper was submitted, Beyene already endured several operative treatments to try and save his life while suffocating on the infected, clogged and detaching plastic trachea. When the paper celebrating his good health was published in January 2014, the patient was already dead. In a recent Bogan et al 2016 paper, Birchall described the child patient whom he operated in London together with the pediatric surgeon Martin Elliott and Macchiarini (who implanted the cadaveric trachea without any use of bioreactor, by simply sprinkling it with bone marrow cells and growth factors during the transplantation):

“At 6 months post-op, the airway was patent and stable, balloon dilation was still needed, but at 18 months post-surgery the child was healthy and fit with no signs of complication [Elliott et al., 2012]”.

For some reason however, Birchall preferred to quote that 2-year follow-up study, but not his 4-year follow up paper (Hamilton et al 2015) where the transplant’s performance and the patient’s situation were described as much less rosy. His partner Elliott proclaimed in his recent lecture at Gresham College that Macchiarini-made trachea as having “excellent cilial function”, the child patient as having “a good quality of life“, and Macchiarini’s “underlying hypotheses” as “right” despite everything. In a November 2011 lecture, Birchall declared this same patient (who lives with a permanent stent in his airways), as well as Castillo and even the disastrous operations on Keziah Shorten (who first received from Macchiarini a cadaveric trachea, which failed completely and then from Birchall and Macchiarini a palliative plastic one, which failed as well) as successes:

In our post-truth times, repeating a false claim often enough eventually turns it into a fact. Most recently, Birchall managed to convince a Guardian journalist that his 2008 trachea regeneration (namely, “to prepare the cells in a veterinary laboratory” in Bristol) was fully approved by HTA. In fact, back then HTA was only contacted on the phone and in the process quite misinformed about Birchall’s true intentions, namely to tissue-engineer a ready-to-transplant trachea in his veterinary lab. This is what Matthew Silk, HTA’s Head of Communications told me (highlights mine):

“The HTA’s remit at the time included the storage, labelling, processing and traceability requirements (in accordance with the recently introduced Human Tissue (Quality and Safety for Human Application) Regulations 2007), as noted in our statement, the clinical application of the cells themselves did not fall under the HTA’s purview. It was, and on review is, also our understanding that the trachea itself was never in Bristol – that only the processing (and storage) of the cells themselves took place on the premises”.

On behalf of HTA, Silk forwarded me this statement (original here):

Human Tissue Authority Statement on Cell Processing at Bristol University in 2008

In April 2008 the University of Bristol – although not Martin Birchall himself, but the Designated Individual responsible for another HTA licence at the University – approached the Human Tissue Authority (HTA) for advice about work being undertaken relating to cell cultures being prepared for a tissue-engineered airway. At that time this was a new area of work, and the regulations which were relevant to the cell processing – the Human Tissue (Quality and Safety for Human Application) Regulations 2007 – had only recently been implemented. HTA records contain references to a number of telephone conversations between staff at Bristol and the HTA about the work being undertaken, but detailed records of those conversations were not documented, and therefore are not available. We know that staff at Bristol told the HTA this was a potentially life-saving treatment for a very sick patient, though specific details on what the HTA was told about the patient’s condition are not documented. Consequently, we took a proportionate approach which allowed the processing to continue whilst the licensing arrangements were discussed. The HTA explained to the University of Bristol at an early stage that our view was that a licence was required.

During those discussions it became clear that the processing of the cells was almost complete, and that Bristol was about to release them. The HTA wrote to Martin Birchall in June 2008 confirming that a licence would be required should any future work of this nature take place; however, once the cells were sent to the clinic in Barcelona, a licence application was not sought and no further licensable activity was undertaken or planned. This letter can be found on our website here, and explains the decision taken by HTA at the time.

The HTA subsequently received assurances from those involved at Bristol (including a letter from Martin Birchall) that the storage, labelling, processing and traceability requirements of the Human Tissue (Quality and Safety for Human Application) Regulations 2007 (the Regulations) had been met – and confirmation that all licensable activities had ceased.

The Regulations impose a set of standards which must be met to ensure that the premises, facilities, and equipment are fit for purpose, and whilst it would be unusual for work to take place under an HTA licence in what is usually a veterinary laboratory, this is not prohibited. The Standards which the HTA now require establishments undertaking this sort work to meet can be found here.

The HTA has been informed by a third party that they suspect traceability records have not been retained from this procedure in 2008, and the HTA is currently looking into this to establish whether any regulatory action is required.

Stephen Tebbutt, Head of Corporate Governance at NHS Health Research Authority, announced to me in regard to the suspension of the trachea transplant trial INSPIRE by the Oxford Research Ethics Committee (REC):

“A date is not set for a further review with any changes to study design requiring approval by the REC as part of a substantial amendment. The review of the ethical opinion is the responsibility of the REC however independent expert opinions can be sought if the REC requires”.

This is the letter Tebbutt also provided me with (full original here), slightly shortened:

Review of REC opinion

Study title: A Phase I open-label study to assess the safety, tolerability and potential efficacy of a novel tracheal replacement consisting of a tissue engineered de-celluarised tracheal scaffold with seeded autologous mesenchymal stem cells in subjects with severe tracheal stenosis or malacia

REC reference: 15/SC/0629

The South Central – Oxford A REC discussed your concerns with regard to the above study at its November and December meetings.

4th November 2016

The REC considered your blog https://forbetterscience.wordpress.com/2016/08/25/how-ucl-throat-surgeon-martin-birchall-misleads-patients-and-tricks-public-funders/ and a response from Professor Birchall alongside the minutes from the REC meeting where the study was original considered plus the REC application and supporting documents. The REC agreed it was satisfied that the issue you had raised had been addressed by the CI [Chief Investigator, LS] and the decision of the REC remained.

The Committee however noted the further concerns regarding consent procedures you had raised in a subsequent blog and agreed it appropriate to allow the CI to respond to your concerns and for further consideration to take place at the following meeting. In the meantime the REC agreed that, whilst the approval for the study remained, if a participant is to be recruited before the next meeting the CI would need to liaise with the REC Chair before recruitment took place.

2nd December 2016

The Chair informed the Committee that you had raised further concerns in your blog https://forbetterscience.wordpress.com/2016/11/02/claudias-trachea/ however due to the information being received close to the date of the meeting a response from the research team had not been possible. The Chair however advised the Committee that, having spoken with the CI, the decision had been to taken to place the study on hold to allow the research team to work with other regulators, researchers and patients to ensure the final study design is as responsible as possible. Professor Birchall had also advised that they would engage with further PPI [Patient and Public Involvement, -LS] work, including focus groups as appropriate to allow deeper patient involvement in the final trial design and work to develop fair consent and would present to the committee when ready. Therefore I can confirm the study remains on hold at present and subsequent consideration will be required by the REC at a later date.

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Update 9.11.2017. One year after the above article was published, I learned that also the larynx transplant trial RegenVox has been suspended. Quote from a Freedom of Information reply issued by the Medical Health products Regulatory Agency (MHRA) in October 2017, which was forwarded to me:

“Regarding the trial approval, we can clarify that the RegenVox trial has been on temporary halt since March 2017 and that no patients have been treated to date within the trial. The sponsor will need to provide a submission to the MHRA (and ethics committee if appropriate) in the form of a substantial amendment for assessment and authorisation before any restart can be allowed.”