EU threatens to terminate TETRA Consortium funding for phase 2 trachea transplant trial

Martin Birchall is throat surgeon at the UCL in London and former partner of Paolo Macchiarini in their “pioneering” trachea transplants (see my earlier reporting), where tracheas from dead donors were decellurised and seeded with patient’s own bone marrow cells, all in order to achieve their alleged regeneration. Their first common trachea transplant recipient, operated in 2008 in Barcelona, is presently in a very grave medical condition, yet Birchall still insists that she is “alive and well today”, in this YouTube video from April 2016, where he calls for patients to participate in his clinical trials.

Unfortunately for Birchall and UCL, but possible fortunately for their patients, the funding for his trials seems to be slipping away. The Macchiarini-led  BIOTRACHEA project, funded by EU with €7 Million, was terminated before it reached the clinical stage where patients would become involved (see my detailed report here). University of California Davis threw Birchall out of a $4.4 Million collaboration project on stem cell-driven airway transplants due to “logistical difficulties of intercontinental collaboration”.  Another major Europe-wide project, namely the TETRA Consortium, funded by the EU with €7 Million (see my detailed report here), led by Birchall together with the company Videregen, is now in grave danger as well, as the statement by the EU spokesperson below suggests.

TETRA is supposed to be a clinical phase 2 trial, which was peer reviewed and approved before its predecessor, the INSPIRE phase 1 trial even began recruiting patients. Even more unusually, INSPIRE received its ethical approval only on 3.11.2015, when TETRA was already in place, ready to pay out from 01.01.2016.

Update 7.06.2016: some INSPIRE medical details are published at NHS site. There, it seems its ethics approval was granted by South Central – Oxford A Research Ethics Committee, on January 7th, 2016, when the EU funding for the follow-up trial TETRA already began being paid out.

INSPIRE started already in 2014, with £1.9 Million of funding from the governmental funder Innovate UK. The documentation does not seem ready yet, no recruitment is announced and in fact, it might never happen. As things look now, the four patients INSPIRE was supposed to transplant with regenerated tracheas may never be recruited. Also the INSPIRE trial is led primarily by Birchall and Videregen. The intended upscaling from just four patients in INSPIRE (where just one accidental outlier can create a mirage of a miracle cure) to 5 clinical sites in Europe, 2 manufacturing facilities in London and Munich and potentially hundreds or thousands of transplant recipients with TETRA was tremendously optimistic indeed.

My attempts to obtain any information about the INSPIRE trial were efficiently thwarted by both UCL and the UCL Hospitals (UCLH), where Birchall is associated with, as professor and surgeon. I recurred to the British law of Freedom of Information Act 2000 (FOIA), which mandates that public institutions (which UCL and UCLH are) must share information within 20 working days after request, provided of course this information can legally be shared. What I requested was this: empty consent patient recruitment forms and the information brochures, which contain no personal information whatsoever. Videregen and Birchall refused to share those with me. UCL and especially UCLH acted in all possible elusive ways to avoid addressing this request. This is how my FOIA inquiries were dealt with:

Alex Daybank, spokesperson of UCL, declared in regard to TETRA:

“I am informed that The TETRA project is in the technology transfer phase in preparation for the clinical trial. Clinical documentation has not yet been finalised. When completed, the clinical protocol and associated documentation will be submitted to national Competent Authorities and national ethics committees for approval before the trial is authorised to commence in compliance with Good Clinical Practice in accordance with EU Clinical Trial Directives”.

When I asked about the allegedly ongoing phase 1 trial INSPIRE, Daybank stated:

“Having established that the EUDACT reference for this study is 2015-002108-10, I can confirm that this study is a commercial trial and that UCL is not involved in the overall management of the study. The patient information that you referred to in your request would have been submitted to the JRO [Joint Research Office, -LS] for UCLH approval as they are a trial site. You may wish to note that that JRO is jointly operated by UCL and UCLH and as such staffed by employees from each organisation with separate information systems and email addresses. Having established the facts surrounding this study we have concluded that UCL does not hold this information for the purposes of the FOI Act and therefore we cannot make decisions regarding its potential disclosure”.

It was surprising to learn that UCL was not involved in the INSPIRE trial, since the Videregen announcement claimed something completely different, and made no reference to UCLH at all. To which UCL’s spokesperson Daybank replied:

“You’re quite right there is no mention of UCLH in that press statement, however, as I understand it UCLH subsequently became involved as a trial site. I’m also informed that the patient information documents were submitted by Cell Therapy Catapult.

There is a UCL Clinical Investigator but they have not managed submission of these documents to the JRO”.

So surely UCLH would share the INSPIRE/TETRA information with me, especially under FOIA? Fat chance.

Despite receiving from the EU €670,000 of TETRA funding, UCLH through their spokesperson Theodora Brocke-Afful pretended never to have heard of TETRA (or even INSPIRE):

“We would not be able to help with your enquiry at this stage, the reason is we would not hold this information as your FOI request has come through the acute hospitals University College London hospitals (uclh). You need to contact University College London(UCL) for the information”.

Brocke-Afful then proved her true talent for misunderstanding my FOIA requests in a way which can only be admired.

On April 23^rd, I requested by email the information about the INSPIRE trial from UCLH. However, my inquiry was officially received only on May 11^th, which gave UCLH more time to find a solution. Which was simply to pretend I never asked about INSPIRE in the first place, just about TETRA. All I got from UCLH on May 31^st was:

“TETRA trial Consent form and Patient information sheet are not available as the project has not yet reached that stage”.

I tried repeatedly to point to all my previous emails (which were duly received and even replied to), but to no avail.

This was surely not the first time Birchall’s UCL and UCLH took his side, which may be explained by the amount of funding he is able to recruit. Even if “regenerated” trachea transplants are a hot potato now, nobody said anything about using exactly same approach, but with the larynx! As I reported before, Birchall is currently recruiting patients for his RegenVox trial, where they will be transplanted with a decellurised donor larynx, seeded with patients’ own bone marrow cells. The trial is funded with £3 Million by the British MRC, and was supposed to begin already in 2013. It is not clear however how far it progressed.

Even an institutional investigation, which dealt with the evidence the Belgian thorax surgeon Pierre Delaere presented against Birchall and Macchiarini (who used to operate at UCL) found: “no prima facie evidence that any research misconduct had taken place” (details and exclusive documents here).

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In an email to me today, the EU has announced to watch the progress of INSPIRE very closely. The official statement by the European Commission spokesperson below contains a direct implication that TETRA might never take place:

“The European Commission is extremely vigilant in making sure that all EU-funded projects adhere to the highest ethical standards and comply with all regulatory requirements. For each EU-funded project, including in-patient work/clinical trials, the European Commission Grant Agreement explicitly stipulates that work may not start prior to receiving all relevant ethical and regulatory approvals. Disregard of this may lead to immediate suspension or termination of the project in question. In line with this, an ethics review will be carried out before the TETRA trial can begin, and the project ethics adviser will follow and report to the European Commission at every stage of the trial to ensure the safety of patients throughout the project duration.

INSPIRE has been reviewed and approved by the competent authority and national ethics committee in the UK. As substantial preparatory work is needed any ethics approval can take place, the approval documentation is often only available at a later stage in the procedure. All the relevant ethical issues of TETRA were assessed during the proposal’s evaluation; since clinical work may never start before all ethics and regulatory approvals have actually been granted, those are not mandatory at the time of peer review.

Because of strict criteria, only four patients have been identified for inclusion in the INSPIRE trial; the actual recruitment and the first patient review are planned to take place in the coming months. So TETRA trial has not started. If the planned number of patients cannot be recruited or if the outcome of the INSPIRE trial is unsuccessful, the TETRA trial will not take place”.