Business interests trump patient safety, says EU about trachea transplant trial

The European Union (EU) is firmly determined to see dozens of patients transplanted with “regenerated” tracheas made by the method of Paolo Macchiarini.  Just as soon as one €5.5 Million-funded trial, Biotrachea, was terminated (because the replacement plastic material Macchiarini intended to use was not novel enough), EU gave fresh €7 Million to his former partner and now competitor, the UK throat surgeon Martin Birchall (see my report here). Birchall’s TETRA will be using decellurised cadaveric tracheas, “regenerated” with bone marrow and epithelial cells after the method he developed together with his thorax surgery colleague, Macchiarini. It is a phase II clinical trial, which is rapidly progressing while the Birchall’s corresponding phase I trial, INSPIRE (funded by the public funder Innovate UK), isn’t moving anywhere. In fact, it is about to receive a re-evaluation of its ethics approval on December 2^nd 2016, possibly together with Birchall’s other regenerative trial, RegenVox. There, patients are being recruited to have their voice-box replaced with a lab-made one (using same methodology as with trachea); there is also some evidence that the UCL professor already transplanted 3 patients with plastic and cadaveric larynxes even before he applied to the British MRC for the funding of RegenVox in 2012.

I submitted a Freedom of Information (FOI)  inquiry to the EU, asking for the original research proposal of TETRA. My rationale was to compare its science and methodology to that of INSPIRE, which was decried as unscientific and dangerous by the throat surgery specialists I spoke with. The Director-General of the European Commission, Robert-Jan Smits denied my request on the grounds that it lacks an “overriding public interest”, despite the well-known fact that numerous patients have suffered tremendous damage to their health and even died previously when the very same technology was applied by Birchall and Macchiarini. Instead, the EU Commission declared that financial and business interests of the TETRA consortium participants trump all safety concerns about their human research subjects (the full letter can be read here). This is double as scary, also because I am well aware that among my readers are actual prospective patients of Birchall’s. At the same time, the patient information sheet Birchall is using to recruit patients to INSPIRE is highly misinformative (see my report here). Previously, EU ethics commission even approved a much more outrageous patient consent form for Macchiarini’s trachea transplant trial Biotrachea (see my report here). Bottom line: the patients are being duped by the trials’ own consent forms, while the EU has now officially denied these patients and their kin any right to learn from an independent source like my site about what their doctors intend to do to them.

TETRA is about to become the first phase II clinical trial to take place before phase I was completed or, even this is possible, after phase I trial had been called off. In June 2016, the EU indicated to me to terminate TETRA should INSPIRE performance be unsatisfactory (see my article here). But soon after, on September 8th, the EU spokesperson declared:

“The TETRA consortium is obliged to send a comprehensive report on clinical trial status to the European Commission every six months, in addition to periodic project progress reports. As the TETRA project started on 01 January 2016, one such report has already been received, subjected to close inspection by the European Commission and deemed satisfactory.

Ethics checks will also take place before the start of the planned clinical trial and mid-term. The ethics review is foreseen before the TETRA patient recruitment, which is scheduled to begin in July 2018”.

As it looks, not even Brexit will stop TETRA from happening. I then attempted in vain to find out on which criteria INSPIRE is supposed to be evaluated. All I have been offered was a phone conversation I was not allowed to quote, coupled with a demand not to contact the EU on that matter ever again (described also here). I declined that strange offer from a public institution, and received no further communications since.  Knowing how Macchiarini’s BIotrachea was applauded by EU ethics committee, there can be little doubt that Birchall’s phase II clinical trial TETRA will pass the ethics evaluation with flying colours and start transplanting patients Europe-wide as scheduled. Even if the phase I trial INSPIRE until then fails to even recruit its scheduled four patients (originally it was supposed to be 10) or even should lose its own ethics approval.

The British Health Research Authority originally set the date of the ethics examination of Birchall’s INSPIRE (and possibly RegenVox also) on November 4^th, 2016. This was moved now to December 2^nd, to give the laryngologist time to address the evidence I presented about his past work. In 2008, Birchall and his team apparently regenerated the first trachea transplant with bone marrow and epithelial cells in his veterinary lab, breaking all elementary patient safety rules (see my story Claudia’s Trachea). The British health authorities were not informed about this, the entire documentation has disappeared, as the University of Bristol admitted. The patient Claudia Castillo since then suffered many severe complications because the transplant failed utterly, while Macchiarini and Birchall used the resulting publications in The Lancet to make money and careers.

Another “success” case of theirs was that of a 10 year old boy, also transplanted with a cadaveric tracheal graft. Ciaran Finn Lynch lives since with a permanent stent, his true health state is unknown and is not really good even according to Birchall himself (Hamilton et al 2015). Yet these two alleged breakthrough in the regenerative medicine were used by the UCL surgeon as argument to obtain funding of altogether €13 Million for INSPIRE, RegenVox and TETRA.  They are both repeatedly described as fully successful medical cures in the grant application documents I now release. However, in his publication about the child patient Ciaran Finn Lynch, Birchall wrote:

“The use of a tissue-engineered tracheal transplant is currently a potential treatment of last resort. In the reported case, all conventional therapies had failed and the technique was used on compassionate grounds in an urgent setting”.

But: his phase 1 and II clinical trials INSPIRE, RegenVox and TETRA are explicitly NOT about offering a “last resort” to dying patients. Instead, those outside of any life danger and in stable conditions, are invited to forgo standard therapies for tracheal or laryngeal stenosis (constriction) and instead get a potentially lethal transplant from Birchall, for the sake of science. In fact, in his RegenVox proposal Birchall admits to be using human patients as replacement for animals and even cell culture experiments:

“Critically, we also will focus on developing new approaches to reverse translation that will maximise the knowledge and discovery gain from observing the behaviour of cells, stem cells and biological scaffolds (approximating to extracellular matrix) in vivo in man, the “experimental animal of the 21^st Century”.

In a November 2012 dated letter of support for RegenVox, issued by the UCL business spin-off UCLB, the university proudly declares:

“UCLB is delighted to be part of the excellent team assembled for this project. Prof Birchall was part of the team involved in the very first Laryngeal implant procedure using a polymer based organ scaffold (engineered at UCL) which was populated by autologous stem cells. Two subsequent procedures were successfully performed using a donor hollow organ seeded with stem cells for compassionate use”.

What? So far, Birchall never ever mentioned anywhere having transplanted 3 patients with plastic or cadaveric larynxes. Did he hide them because the outcome was nothing to be proud of? Or did UCLB willfully misrepresent Birchall’s trachea transplant recipients as fictional laryngeal transplant cases? Birchall’s recipient of the plastic trachea, Keziah Shorten, was originally tricked by Macchiarini to agree to a cadaveric trachea transplant which disastrously failed. Keziah was dying of the complications and received a palliative replacement trachea transplant made out of plastic in London, which most likely finished her off. Is this the case UCLB was so immensely proud of?

All this human experimenting is according to the EU Commission none of public’s business. These are the three reasons why my FOI inquiry about the TETRA research proposal was denied yesterday (full letter here):

“Article 4(2), first indent, of Regulation 1049/2001 provides that the “institutions shall refuse access to a document where disclosure would undermine the protection of […] commercial interests of a natural or legal person, including intellectual property”.

The document requested is the proposal which was submitted by the coordinator of the TETRA project. It contains a detailed description of works and studies to be undertaken under the project, as well as a description of specific project activities, milestones and the corresponding timetable of the planned implementation. The project proposal also includes the technical and budget details of the planned project and solutions to be employed during its realisation. Therefore, such information has to be considered as inside and unique knowledge of the applicants.

The public disclosure of such information might undermine the commercial interests of the applicants, as it would give other potential grant applicants in ongoing or future calls the possibility to copy from that application and use it to support their own application. It might also give the competitors of the grant beneficiary an unfair commercial advantage, as the former would be able to use this information in their favour by anticipating the grant beneficiary’s strategies and weaknesses”.

Basically, transplanting potentially lethal cadaveric trachea is a tough and competitive business, much valued by the EU. Other doctors might be keen to steal this exclusive technology to experiment on their own patients, willy-nilly. Who knows, dispatching unsuspecting and relatively healthy patients with rotting cadaveric organ implants might became a world-wide export hit, for the benefit of EU economy! I.e., unless Macchiarini corners the market first, operating from Russia. EU is therefore perfectly right to be watchful when protecting the financial interests of Birchall and his commercial partner, the company Videregen.

And then of course there are privacy concerns. Who exactly is the recipient of the EU research funding and what their work emails and office phone numbers might be, is top secret, as the EU Commission Director-General  Smits declares:

“The document requested contains personal data, namely the name, surname, email address, phone number, and fax number of staff members of the participants to the project TETRA. This information clearly constitutes personal data in the meaning of Article 2(a) of Regulation (EC) 45/2001.

According to Article 8(b) of Regulation (EC) 45/2001, personal data shall only be transferred to a recipient in the EU/EEA if the recipient establishes the necessity of having the data transferred and if there is no reason to assume that the data subject’s legitimate interests might be prejudiced. Those two conditions are cumulative. In the present case, you have not put forward any arguments to substantiate a need to obtain these personal data. Furthermore, it cannot be assumed that such disclosure would not prejudice the legitimate rights of the persons concerned”.

This is completely bizarre. Even in the notoriously privacy concerned Germany, the recipients of public funding are always listed on the website of the central funding agency DFG, like here. Smits obviously misrepresents the case for privacy, also because even the TETRA Consortium itself proudly lists every single one of its lead members on their own website. To protect the names of the people who publicly boldly advertise for TETRA, Smits finally kills my FOI inquiry by declaring:

“The exception laid down in Article 4(2) of Regulation (EC) 1049/2001 {protection of commercial interests) applies unless there is an overriding public interest in disclosure of the document requested. Such an interest must, firstly, be a public interest and, secondly, outweigh the harm caused by disclosure. We have found no elements in this instance which could indicate the existence of an overriding public interest in the sense of Regulation (EC) 1049/2001 that would outweigh the need to protect the interests identified in the present letter.

The exception provided for in Article 4(1)(b) of Regulation (EC) 1049/2001 (protection of privacy and the integrity of the individual) is an absolute exception which cannot be balanced by an overriding public interest”.

However, another EU institution quickly pointed out that Smits’ arguments are actually invalid:

I issued an appeal, as advised by Ask the EU. Meanwhile here is the documentation for RegenVox and INSPIRE I obtained from elsewhere.

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Update 21.12.2016. The EU Commission Secretary General Alexander Italianer now denied my FOI inquiry in a final decision (full letter here), making clear that the commercial interests of Videregen et al are too important. He also declared the absence of “overriding public interests” because no patients have been operated yet, and when they will be, it will happen with their informed consent and under the oversight of proper authorities. Knowing how EU’s predecessor trial Biotrachea passed ethics approval with flying colours and what kind of patient consent form was prepared, this is a somewhat peculiar viewpoint. One can only hope that TETRA eventually stumbles over a perceived lack of novelty, like Biotrachea did.