XMRV testing: The REDLABS, trading as VIP Dx, WPI connection

We were all rocked by the dismissal of Dr Mikovits from the WPI last September. Next she was arrested, and then we heard that the VIPDx tests, costing some $550 a throw, were worthless. Did this mean the whole XMRV story was false? What was the politics behind it all? What connection was there between the WPI, VIPDx, and Lombardi, how was Dr Judy involved, and what was behind the sacking? Were those paid-for tests really a waste of time? This is from an article by ME Advocacy.

XMRV testing: The REDLABS, trading as VIP Dx, WPI connection

Since September 2011, I along with several of my friends, who also have ME, have been left feeling battered by the events surrounding the ME retroviruses. Although other labs had avoided use of the methods from Lombardi et al. for nearly two years, the blood study and testing at VIP Dx, was a promise to patients that science was finally going to take over control of this disease. But on the 3rd October 2011, on reading that Annette Whittemore had closed the WPI research program, everything felt like it had fallen apart. In all honesty the emotion on that day was nothing compared to how I felt on reading that Dr Judy Mikovits had been arrested.

I have tried to gather every bit of information I could find to work out what has been going on. Most of what follows will raise more questions than answers, but here's where I've got to so far. My questions are:

1) Were the tests sold to patients by REDLABS (trading under the name VIP Dx) clinically validated? Where is their analytical and clinical sensitivity data?

2) Why would the NIH invite REDLABS (trading as VIP Dx), an independent company with a vested interest, to take part in the Blood working group (BWG) without seeing their clinical validation data? Has the analytical and clinical sensitivity data been seen by Graham Simmons, Michael Busch or Steven Kleinman of the BWG? Why were the results of the REDLABS team lead by Dr Lombardi not published in the BWG paper? This was the one chance to clinically validate the commercial REDLABS/VIP DX tests in the eyes of the world? Why was this chance not taken, what went wrong?

3) How did the trust set up by the Whittmore’s for their interests in REDLABS (trading as VIP Dx) operate, and how was the money generated by XMRV testing spent by the Whittmore’s?

Note: From now on I will refer to VIP Dx as REDLABS
Note: REDLABS USA Inc is not R.E.D. Laboratories in Belgium. The Belgian lab is not related to this presentation


PART 1: AN XMRV TEST FOR SALE

Lombardi et al. was published on the 8th October 2009 (1). It then took only 20 days for a commercial agreement to be reached between the WPI and REDLABS for XMRV tests to be sold to patients.

Note: this does not say clinically validated

WPI Research Scientist and co-author of the Science paper, Dr Vincent Lombardi, is providing technical assistance and oversight of the VIP Dx testing. In exchange for the non-exclusive license, VIP Dx will pay a royalty to WPI for each test it conducts.

“We structured the licensing contract to be sure that any and all profits that might emerge at VIP Dx from XMRV testing come directly back to WPI to benefit the research program” said Whittemore.

It is important to appreciate that just because research data is published, it does not mean that a test has been clinically validated. This type of validation would require samples from hundreds of healthy volunteers. So is it possible to do this kind of work in 20 days? If the Whittemore Peterson Institute laboratory research data is all that was published, what data was used to grant a licence? And who approved that licence? If the only data available were from Lombardi et al. (2009), then the tests would still need to be clinically validated.

As Annette Whittemore was President of the WPI (the non profit organization)(4), it means that she effectively entered into a licensing agreement with REDLABS, a company wholly controlled by her husband, Harvey Whittemore (5). REDLABS therefore had legal responsibility and liability for selling XMRV tests.

This does not mean that REDLABS and the WPI research laboratory were one in the same. They were completely separate physically and legally. The lead scientist at the WPI research lab, Dr Judy Mikovits, did not work for REDLABS and had no authority over testing or oversight at that clinical laboratory. As the principle investigator, Dr Mikovits would not supervise or monitor any activities taking place there. It was Dr Vincent Lombardi who was given responsibility for overseeing the testing at REDLABS and it was Dr Lombardi who was also instrumental in changing the methods used by REDLABS to methods not used in Lombardi et al. (3).

According to a WPI press release on the 14 January 2010 (3), Dr Vincent Lombardi was a WPI employee when he took up the responsibility of overseeing the XMRV testing at REDLABS. He was also said to have no personal financial interests in REDLABS, and that likewise the WPI family had put their interest in REDLABS into trust.

This begs two questions; did Dr Lombardi have any other kind of financial interest or position of power relating to REDLABS and what was the nature of the trust?

Dr Lombardi was in fact a co-founder of REDLABS. What we do not know is whether Dr Lombardi was ever or still is also a part owner of REDLABS.

Given the wording of the announcement (3) it may well be that Dr Lombardi was a trustee for the Whittemore family beneficial interest in REDLABS. This situation would mean that the Whittemores would effectively retain control of their beneficial interests in the trust, with Dr Lombardi was their employee, allowing them to retain control of the money and the way it was spent. Alternatively, the trustee could be a separate company under Whittemore control. The trustee could then approve monies in the Whittemore REDLABS trust account to be spent on any purpose that the Whittemores wanted.

At the very least, if there was no contrary stipulation in the trust, the Whittmores could spend money at WPI for any purpose. In effect it would mean that money accrued via XMRV testing could enter Whittemore owned bank accounts free of any tax liability or any stipulation on how the money could be spent. The wording in the press release also seems to suggest that the trust be set up for the benefit of WPI (not the WPI) and not specifically to be used for research.

Dr Lombardi was said to have "no personal financial interest" in REDLABS, trading as VIP Dx, by an official WPI press release (3). This is a legal description and should not be viewed as normal english. Not having a personal financial interest does not mean he does not have any financial interest in REDLABS/VIP Dx. Likewise, not having a personal financial interest does not mean that he is not a financially interested person (8). These are specific legal definitions.

If Dr Lombardi as an employee was also a trustee of the trust governing the beneficial interests of the Whittemore family in REDLABS, he would then have an organizational financial interest in REDLABS as opposed to a personal financial interest. Meaning that he would be a financially interested person with an organizational financial interest in REDLABS.

So was Dr Lombardi a trustee? Was Dr Lombardi a financially interested person? And what was the legal nature of that financial interest?

The motive for granting a licence to REDLABS can also be said to not have been as a result of “an overwhelming request for a diagnostic test for XMRV” (2), because negotiations between WPI and REDLABS were already underway prior to publication of Lombardi et al. on the 23rd October 2009 (9). Again, this does raise the question of how these methods were clinically validated?

With Dr Lombardi specifically being assigned to REDLABS, we must also ask whether he ever worked in the research lab after the publication of Lombardi et al. (2009) and why would he therefore be suitable to be the principle investigator on the NIH Research Project Grant (RO1) that Dr Mikovits had been originally been awarded? As operations manager of a commercial company he would be assumed to have a financial conflict of interest under NIH guidelines for principle investigators (10) and his professional research laboratory experience would be in question.

As I noted earlier, the initial licence for testing was for use of the methods employed in Lombardi et al. (2009). At some point Dr Lombardi was instrumental in altering the XMRV tests sold by REDLABS (11), but it has not been confirmed that these new methods were given a license or what data was available to validate these tests.

If there was no new data why were the methods used at REDLABS changed? Were the new methods even given a license? If the answer is yes, who approved the license? Were these new methods clinically validated? How were they validated and who approved the validation? It certainly wasn’t Dr Mikovits, because she had no ability to influence activities at REDLABS.

It was not an easy decision for patients to be tested for a retrovirus and most do not have the cash to spare. I think the entire ME community is entitled to answers to all of the outstanding questions regarding the validation, licensing, financial interests and trust arrangements between WPI, REDLABS and Dr Lombardi. Trust documents and the names of all the trustees should also be made publicly available.


[Please note that this article relates to the XMRV tests that were sold by REDLABS (trading as VIP Dx) and that UNEVX is another separate company unrelated to REDLABS, and that R.E.D Laboratories Belgium is not connected with the REDLABS owned by Harvey Whittemore]


PART 2: coming soon...



REFERENCES

1) Lombardi et al. 2009. Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome. Science. http://www.sciencemag.org/content/326/5952/585
2) Frankie Vigil, R&R Partners for Whittemore Peterson Institute, 28 October 2009. http://www.wpinstitute.org/news/docs/WPI Release Diagnostic Test.pdf
3) Frankie Vigil, R&R Partners for Whittemore Peterson Institute, 14 January 2010 http://wpinstitute.org/news/docs/WPI_pressrel_011410.pdf
4) Annette Whittemore profile, WPI President. http://www.wpinstitute.org/about/about_execboard.html
5) Harvey Whittemore, REDLABS USA INC. http://nvsos.gov/sosentitysearch/CorpDetails.aspx?lx8nvq=3HqeF%2fFCg2b8fQKoGUKjpg%3d%3d
6) HIPAASpace NPI form: 1356473177 REDLABS USA INC http://www.hipaaspace.com/Medical_B..._Provider_Identifier/Codes/NPI_1356473177.pdf
7) Vincent C. Lombardi profile, WPI. http://www.wpinstitute.org/research/research_profiles.html
02x1: Financial Disclosure Issues Concerning Trustees, Executors, and Administrators. http://www.oge.gov/DisplayTemplates/ModelSub.aspx?id=1293
8) Lombardi et al., 2009. http://www.sciencemag.org/content/326/5952/585.full.pdf
NIH. Financial Conflict of Interest. http://grants.nih.gov/grants/policy/coi/tutorial/fcoi.pdf
9) Statement of Vincent Lombardi, Phd, Clinical Lab Director, VIP Dx, 14 October 2011. http://niceguidelines.blogspot.co.uk/2011/10/statement-by-vincent-lombardi.html
10) Dr Mikovits, 4 October 2011. http://news.sciencemag.org/scienceinsider/2011/10/xmrv-researcher-fired.html
11) Statement of Vincent Lombardi, Phd, Clinical Lab Director, VIP Dx, 14 October 2011. http://niceguidelines.blogspot.co.uk/2011/10/statement-by-vincent-lombardi.html
12) Dr Mikovits, 4 October 2011. http://news.sciencemag.org/scienceinsider/2011/10/xmrv-researcher-fired.html

I gave the link to ME Advocacy, where you will find the article. This is not connected to HMRV Advocacy.

I have not heard of any replies from VIP Dx, apart from the quote and link referenced (11), which is a screenshot of the statement on the VIP Dx website.

Re: ME Advocacy. Seemingly overly concerned with excusing Dr Mikovits from any implication of responsibility, this ‘analysis’ is confused and confusing, and fails to reference all the relevant material that is now in the public domain, notably the legal depositions in proceedings between Whittemore/Seeno.

The focus on clinical validation is something of a non sequitur. Certainly the tests offered by VIPdx were without validation, but Clinical Validation could never have been achieved given that there was no body of independent study that supported the existence, in human blood, of the clinical entity that the tests purported to identify. Whether or not the test protocol used in the research published in Lombardi et al 2009 was capable of accurately identifying its claimed target (XMRV), the issue is rendered irrelevant because there was (as of 2010), nor has there been since, any independent validation of the presence of XMRV in human blood.

If no research group could confirm the findings of Lombardi et al 2009, there was simply no basis on which a clinically valid test could be established. This was pointed out by numbers of observers at the time. Validation requires some exterior or alternative reference, no such reference had ever been established for the WPI research, so validation has never been possible. The use of the term clinically validated in Lombardi’s statement of 14the October 2011 is certainly misleading.

Mikovits statement: “I've asked them for the better part of 2 years to show me that what we got in Lombardi et al. is the same thing they're selling to patients.” is equally a non sequitur – if there was nothing capable of validation in the original work, then any commercial test derived from that work would lack verification by independent reference; neither the testing used in the research nor the VIPdx test could have any value in terms of producing validated data – because there has been no validation. (yes the circularity is as nuts as it sounds)

Another irrelevance is the question of how Lombardi may have tweaked the testing regime to provide a commercially viable test. The research level testing was unvalidated by independent study, therefore it was irrelevant what was done in the tweaking. That ‘tweaking’ was necessary is unsurprising, the small number of tests carried out in a research phase are not developed with cost effectiveness in mind, finessing protocols used in research is almost always required in order to make mass testing feasible.

The speculations by ME Advocacy on the financial relationships behind Redlabs, borders upon the bizarre. The fact that Press Releases put out by WPI were wrong, poorly worded and/or obfuscatory isn’t evidence of the financial arrangements that actually applied. What is clear that from 2005 Redlabs was owned by the Wingfield Nevada Group, which by 2010 was in the sole control of members of the Seeno family (for details: http://cfsmirror.blogspot.co.uk/2012/01/good-science-cant-happen-in-bad.html ). The Whittemores may have misrepresented their interests in the Redlabs business, but to the effect of overstatement (they had in fact no transferable beneficial interest as was claimed) rather than obscuring actual financial benefit.

ME Advocacy’s assertion that R.E.D Labs(Belgium) is/was unrelated to Redlabs/VIPdx is misleading, not only do the two entities have a shared foundational basis, but R.E.D Labs(Belgium) entered into a similar licencing arrangement with WPI as did VIPdx. (for details: http://cfsmirror.blogspot.co.uk/2012/05/profit-and-loss.html ). The WPI annual statements to the IRS (Form 990) make it clear that whatever the dubious quality of the VIPdx tests, the licencing procedure was financially beneficial to the WPI and the ‘at cost’ claim made by the WPI for the WPI/VIPdx licencing agreement where VIPdx took no profit, seems based on fact. Ironically it was such practices that probably earned Harvey Whittemore the wrath of the owners of the company, who by 2010, the Seeno family.
Nonee of the actors in this saga can be said to have come out with their reputations fully intact. Arrogance, intransigence, naivety and bombasticity appear to have been the overriding influences – venality does not appear to have played a significant role.

IVI

Regarding the ownership of REDLABS, this document clearly shows it's Harvey all the way http://nvsos.gov/sosentitysearch/CorpDetails.aspx?lx8nvq=3HqeF%2fFCg2b8fQKoGUKjpg%3d%3d

Are you saying that Harvey Whittemore has a financial interest in R.E.D. Laboratories in Belgium? Or that they have a financial interest in REDLABS Nevada? Who the WPI licensed their test to is irrelevant to the questions raised.

How is that a non-sequitur? Mikovits is making no claims for either Lombardi or VIP Dx (REDLABS) here. She was asking, from 2009, what test was being sold to patients.

A lot of us, me included, were heavily involved in raising funds for the WPI in the spring and summer of 2011. A lot of us bought tests from VIP Dx (REDLABS), thinking it was the same as was used in the Lombardi paper. I don't think it's bizarre at all to look into the financing.

I’m afraid that document doesn’t mean what you think it means. There is no information on shareholder ownership, merely a listing of the officers of the company and the technical share issue status. If you click the hyper link at the bottom of the NVOS entry page, and then go to the bottom of the new page – you will see that the business only came into existence in 2004. If you then go to http://www.rgj.com/assets/pdf/J7184397127.PDF you will see that RED labs became 50% owned by the Seenos in 2004, and in 2005 this shared ownership was rolled up into the Wingfield Group. Subsequently Whittmore ceded full ownership to members of the Seeno family.

What WAS the (relevant) question again ? R.E.D. Laboratories Belgium was directly involved in marketing of the useless VIPdx tests – how is that irrelevant to the issue of patients being mis-sold a product/service ? The foundational (pre 2004) Redlabs (US – not a Nevada listing) did indeed have a directorial level (as well as a philosophical – see http://cfsmirror.blogspot.co.uk/2012/05/profit-and-loss.html ) connection via Charles Taylor Herst. Post 2004 all ownership in Redlabs (Nevada) would appear to have been exercised via Wingfield.

It didn’t matter whether it (the test) was “the same thing they're selling to patients” or not; without external validation (via what in science is understood as replication) of the Lombardi et al 2009 paper, there could never be a validated test. If no one else can find what one research group has found – the normal assumption in the practice of science is that the finding is flawed, i.e it is incapable of validation.
Lombardi et al did find something of scientific significance, which has been subsequently validated - that commonly used laboratory reagents have become routinely, though erratically, contaminated with a novel mouse derived RV. Sadly the original researchers failed to recognise the importance of their findings.

Looking at the sale XMRV tests is important – because it allows valuable lessons to be learned about the exploitation and vulnerability of desperate patients. What I wrote regarding MEAdvocay, was that their “speculations ……on the financial relationships behind Redlabs, borders upon the bizarre”. I’m afraid I can’t see where any of those speculations make any sense or how they are related to any of the known positions of the Whittemore family, the WPI or Dr Lombardi. Such speculations only serve to obscure the naked fact regarding the VIPdx tests – which is that such tests were never, and could never have been fit for purpose. The fitness of tests is something that patients should always consider and purchasing outside regulated processes needs to be done with caution if people are not to get ripped off and provided with misinformation and caused unnecessary and inappropriate worry.

IVI

Give me the info. I'm happy to worry for myself, and judge for myself. I disagree with most of what you say, IVI, as you know. Perhaps we can agree to differ in our opinions, and I will continue to present information that I see as important, including the next part of this story, as it arises.

So no problems with cognitive function, lack of technical skill in bioinformatics or specialist medical knowledge ?

This raises a further interesting question which MEAdvocacy ignores – VIPdx required (at least it claimed this was the case) that all tests had to be ordered by a physician, and the ordering physician was solely responsible for providing interpretation to the patient, of any test results. In the UK the ordering of tests by a medical professional is strictly regulated, such that the VIPdx tests could never have been deemed medically appropriate by dint of the lack of any clinical validation. So did VIPdx accept orders for tests without a physician being involved ? Or did UK doctors act outside their professional limitations, and what interpretation did such doctors give on the tests ordered in their name ?

Differing on opinion is one thing, differing on establishable facts is something else, MEAdvocacy has produced a misleading article based on perverse interpretation and ignorance or avoidance of material information. One may have the opinion that the moon is made of green cheese, but that doesn’t obviate knowledge of moon rock.

IVI

so anybody get any compensation for testing paid for at redlabs wpi in last 2 years? or was it valid? i had cfs profiles as well as xmrv, do we know if any of it means anything?

How is any medical test judged to have validity ? In the US there are two standards - firstly there is Laboratory Registration (CLIA) which simply means thaat the Lab in question has been judged of quality in terms of delivering under Government contract (Medicaid/Medicare) secondly there is FDA approval of named tests CLIA and FDA approval are separate processes, so ideally what one would be looking for is an FDA approved test provided by a CLIA registered Lab. Anything else is caveat emptor, excepting that there may well exist a contractual responsibility between the ordering physician and the patient. In the UK this relationship is unequivocal - the physician is solely professionally responsible for only ordering tests which are of assurred quality and of definitive benefit to the patient. VIPdx were absolutely clear that tests could only be ordered by a physician - and failure of the tests would be a matter of contract between the ordering physician and VIPdx -and/or a professional matter between physician and patient.

IVI

interesting, well the doc who ordered mine was a mainstream guy who had opened up his mind, but seems like since then its shut way down, wpi behavior didnt help our cause by any means

Laboratories are subject to medical malpractice claims for the developed of laboratory developed tests, which are considered to be a medical service. Doctors only act as a messenger in the contractual agreement which is between the patient and laboratory.

A US based company selling a test abroad would be liable along with its directors. A doctor in the US or another country including the UK would be entitled to trust that these tests are clinically validated, which is not matter of interpretation. This is established by the laboratory selling the test. Testing for research purposes does not come under CLIA regulations.

Firestormm, there are doctors in the UK organising private bloods for PWME (and many other diseases) and sending the bloods abroad for all manner of unproven tests.

It happens in every single group I belong to for diseases or conditions that don't have good results in the NHS. On one particular group (not ME related) some of the members are doctors working in the NHS. Yet they make the decision (with their private doctors) to have experimental tests abroad. They even make the decision to buy and use experimental drugs.

The divide is between the people with money and the people without money.

Harley St is full of doctors doing this and there are private laboratories with a range of private tests that are often sent abroad.

How many of these tests do you think are validated in any way?

http://www.tdlpathology.com/test-information/a-z-test-list/numbers

It's a different world out there to the NHS. I hear what you are saying. The only point I am trying to make is that in the UK for private patients the same practise is common for many diseases and conditions.

I agree entirely, its always been about money, they will look at everything and everywhere if you pay them enough.