FDA Issues Warning on CCSVI

[Squeakycat]

The FDA has issued a warning letter to Dr. Mehta blocking his clinical trial because in their opinion (or the pharmaceutical company that put them up to going after him) he will be using a "significant risk device," to do extracranial venous angioplasty of people with Multiple Sclerosis.

A search of the FDA website says that this is only the third warning letter ever issued by the FDA under a program to protect the public from the risks of clinical trials.

This enforcement action basically means that anyone doing CCSVI research will have to go through the same hoops drug and device manufacturers go through to prove in advance of research that their device is not likely to cause harm, something they do because they expect to make a ton of money on their approved device or drug.

If they hadn't classified venous angioplasty as a significant risk device, Dr. Mehta, and others, could have gone forward with their research as long as they noted that the devices (angioplasty balloons) were not specifically approved to treat extracranial veins of people with Multiple Sclerosis to an IRB. But by classifying it as a significant risk device, they force anyone who wants to study CCSVI treatment to get a specific exemption from the FDA, just as manufacturers do when they first start studying a new drug or device.

Their reasoning is buried in what is known as a 483 Form that they may or may not make public at some point. I am going to formally ask for that reasoning, but they don't have to answer me and probably won't.

It seems complete bullshit to say that venous angioplasty of extracranial veins qualifies as a "significant risk device" which they define this way:

(m) Significant risk device means an investigational device that:

(1) Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;
(2) Is purported or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject;
(3) Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or
(4) Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.

http://www.gpo.gov/fdsys/pkg/CFR-2011-t ... 1-vol8.pdf

So far, they have gone after Dr. Mehta. Don't be surprised when the FDA police start knocking on the doors of others doing research on CCSVI.

The neuros and pharma say that they can't support CCSVI without further research and they and their friends are now hell bent on making sure that research never happens.

And the FDA proves once again that they are great at protecting manufacturers from the public regardless of who is in the White House.

[Cece]

Here is the specific violation:

Failure to submit an application to the FDA and obtain IRB and FDA approval prior to allowing subjects to participate in an investigation [21 CFR 812.40 and 21 CFR 812.42]

You failed to submit an IDE application to the FDA and obtain FDA approval before allowing subjects to participate in the (b)(4). The (b)(4) investigated the safety or effectiveness of angioplasty balloon devices for percutaneous transluminal angioplasty in treating extracranial venous obstructive lesions and its influence on the clinical outcomes of Multiple Sclerosis patients. Investigating angioplasty balloon devices within the (b)(4) to determine their safety or effectiveness for this unapproved and uncleared use constitutes a clinical investigation under 21 CFR Part 812. Because the devices studied for this use present a potential for serious risk to the health, safety, or welfare of the subjects, the devices are significant risk devices, as defined in 21 CFR 812.3(m). As a result, you must submit an IDE application to FDA to use the significant risk devices in an investigation. 21 CFR 812.20.

What is an IDE application? Is it difficult to get FDA approval? Are other trials not related to CCSVI which involve angioplasty equally required to do an IDE application and get FDA approval before commencing? This could be nothing more than an oversight on Dr. Mehta's part, for not getting this squared away before the trial began. Dr. Siskin's trial has been underway for just as long. Did he submit an IDE application, and was it approved or denied? We need answers.

Thanks for posting, Squeakycat.
Letters to Dr. Mehta always contain bad news. Remember this one? It was when we first heard of Medicare denying coverage of CCSVI. http://www.thisisms.com/forum/chronic-c ... 70-15.html

[David1949]

Thanks for pointing this out. Our Constitution lays out a federal government that has limited powers. But it has grown far beyond it's Constitutional basis. And now it gets involved in details of our lives that it has no business being involved it. I know this is not a political forum but at this point it becomes political. Obama won't change this. It's happening under his watch. Romney won't change it either. There is only one candidate who is steadfastly committed to the Constitution and that's Ron Paul. If you vote for Romney or Obama then you are voting for more of the same.

Do you want freedom or do you want the government to run your life for you?

My disclaimer;
I had this procedure 13 days ago and so far it has done nothing for me. But I cannot deny that it has helped many people. The people of this country should be free to decide for themselves if they want to try it or not. And the FDA should drop dead.

[Cece]

We know that Dr. Siskin had a meeting with the FDA back in October, 2010. http://www.thisisms.com/forum/chronic-c ... ml#p138408
I think they'd have directed him on what needed to be done, and he'd have done it.

How to submit an IDE application:
http://www.fda.gov/MedicalDevices/Devic ... 046706.htm

A sponsor of a significant risk device study must submit a complete IDE application to FDA. There are no preprinted forms for an IDE application; however, an IDE application must include certain required information. The sponsor must demonstrate in the application that there is reason to believe that the risks to human subjects from the proposed investigation are outweighed by the anticipated benefits to subjects and the importance of the knowledge to be gained, that the investigation is scientifically sound, and that there is reason to believe that the device as proposed for use will be effective.

There are a number of small safety studies showing angioplasty of CCSVI to be safe. There is a long history of angioplasty itself being safe.
There is reason to believe that angioplasty of a blocked blood vessel will be effective in opening the blood vessel.
The only hang-up might be on the anticipated benefits to subjects, and if those fail to outweigh the small risk.

ok, I think this is a nonstory!
In this document, the FDA has presented a long list of examples of nonsignificant risk and significant risk devices. Percutaneous Transluminal Angioplasty Catheters is listed as a significant risk device.
http://www.fda.gov/downloads/regulatory ... 126418.pdf
What this means is that Dr. Mehta and his IRB erred in not submitting an IDE application, but it is nothing discriminatory against CCSVI. Any use of a percutaneous transluminal angioplasty catheter in any trial would require an IDE application to be made. There is no reason to believe the application would not be approved.

[David1949]

And yet this stuff is OK:

"Biogen Idec have released the latest figures for PML cases and deaths following Tysabri infusions for Multiple Sclerosis

As of March 1, 2012, there have been 212 PML cases, of which 122 have been in the European Economic Area (EEA), 80 in the US and 10 in rest of world (ROW). 46 of the 212 patients with PML have died."
http://www.thisisms.com/forum/tysabri-a ... 19506.html

[blossom]

david1949, i agree!

[Donnchadh]

Perhaps this will force the IR's who want to continue treating CCSVI to move their operations out of the USA? To India? Mexico?

Donnchadh

[Cece]

If you check the clincial trials website for Dr. Mehta's study, it says, "This study has been terminated."
http://clinicaltrials.gov/ct2/show/NCT0 ... svi&rank=1
All the other studies are listed as active or recruiting.
http://clinicaltrials.gov/ct2/results?term=ccsvi

I googled fda and ccsvi, and I get mentions that there are three fda approved trials in the US, but I would assume Dr. Mehta's was counted as one of them.

Michael Shannon, a medical doctor with extensive experience designing and running large clinical trials, says that a phase I safety trial, which could take at least 18 months, is “a 100 per cent total waste of time and money.” CCSVI clinical trials are already well underway in the U.S.,” he notes. “The fact the FDA has approved three double-blinded clinical trials at phase II level should convey to anyone who understands the regulatory process that the FDA is satisfied with the general safety of this procedure which is routinely used throughout North America for all kinds of medical conditions requiring arterial or venous intervention.”

www2.macleans.ca/2011/11/30/hurry-up-and-wait-for-a-ccsvi-strategy/

Here's a Dr. Hunter's take on this in four separate tweets. I think he may be a neurologist.

No further CCSVI Research with treatment will occur in US without FDA approval

FDA apparently wants to rule on safety of the procedure

FDA has jurisdiction over experimental use of devices and drugs

US FDA has stopped CCSVI trial in Rochester, NY citing failure to secure FDA approval

http://www.mschristian.org/msc/index.ph ... a-approved

Does this affect what's done at clinics? Is it considered research if a doctor wants to publish on their single-center data, and would that require FDA approval? I would hope not.

My confusion with the fda list of significant risk devices (found here: http://www.fda.gov/downloads/regulatory ... 126418.pdf ) is that while angioplasty catheters are on the list, it's not a new catheter that's being trialed, it's an already-approved catheter, and it's being used in a location that is already approved for treatment of outflow obstruction if the outflow obstruction is caused by thrombus, for example.

Does anyone know if Dr. Siskin had applied for an IDE exemption, and if it was approved?

[Cece]

http://saskparty.com/index.php?pageid=N ... newsid=293

Premier Brad Wall announced today that Dr. Gary Siskin of the Albany Medical Centre is in the final stages of Food and Drug Administration (FDA) approval for the largest Liberation Therapy clinical trial of its type, and that Saskatchewan Multiple Sclerosis (MS) patients can now apply to volunteer to participate in the trial.

This was news from January. If he was in the final stages, does that mean he went through the process correctly? Or did the FDA change the rules, now requiring an IDE exemption if one was not required before?

[bestadmom]

And what about BNAC @ SUNY Buffalo? They have a treatment trial going on and are the lead researchers for everything ccsvi. They are a research university, publishing constantly, and they could never proceed without all the proper approvals in place.

I think Mehta screwed up, but I also bet the lobbyists have infiltrated the FDA.

[Cece]

http://und.edu/research/research-econom ... /505-b.pdf
More information on significant risk vs nonsignificant. It would not just be Mehta who screwed up, but also his IRB.

If an Investigator or a Sponsor proposes the initiation of a claimed NSR [nonsignificant risk] investigation to an IRB, and if the IRB agrees
that the device study is NSR and approves the study, the investigation may begin at that institution immediately, without submission of an IDE application to FDA.

I forgot about BNAC's treatment trial. That's reassuring too. The thought of lobbyist influence at the FDA is not reassuring.

[Mossmanor]

I believe it was just that Mehta did not have an IRB approval and did not submit the requisite paperwork before proceding. In general, angioplasty balloons are not approved for use in veins, so this is why he would have had to seek IDE exemption. His trial may not have had adequate follow-up to ensure patient safety.

I am in the UBNS/BNAC treatment trial (PREMiSe II). I know they went through a phase I safety trial first (with IRB approval), and once they had evidence that the procedure was safe, they were able to gain IRB approval to move on to the phase II treatment trial.

The procedure (either catheter venography & IVUS alone, or together with venoplasty) was performed in a hospital setting, I was kept overnight and monitored. I had follow up phone calls a few days post procedure and 1, 3, 6 and 12 month follow-up examinations (Doppler US, MRI/MRV/fMRI and CTV/perfusion). So I can assure you patient safety is top priority.

Buffalo is doing it right, Mehta just didn't follow the procedure.

[bestadmom]

Thanks for posting mossmanor!

BNAC is amazing . I was in the first big ccsvi study along with a few other old-time tims members in Sept 2009. BNAC is top notch. I'm on their patient advisory board and very proud of the studies they are doing, the discoveries they keep making and their deedication to us.

[Squeakycat]

ok, I think this is a nonstory!
In this document, the FDA has presented a long list of examples of nonsignificant risk and significant risk devices. Percutaneous Transluminal Angioplasty Catheters is listed as a significant risk device.
http://www.fda.gov/downloads/regulatory ... 126418.pdf
What this means is that Dr. Mehta and his IRB erred in not submitting an IDE application, but it is nothing discriminatory against CCSVI. Any use of a percutaneous transluminal angioplasty catheter in any trial would require an IDE application to be made. There is no reason to believe the application would not be approved.

You may well be right since PTA catheters are classified as a a Significant Risk Device.

The real question comes down to how "non-trivial" the IDE application is, how long it take for the FDA to review it, and how likely they are to approve and an exemption request.

[Cece]

http://www.fda.gov/MedicalDevices/Devic ... 046164.htm

An IDE application is considered approved 30 days after it has been received by FDA, unless FDA otherwise informs the sponsor prior to 30 calendar days from the date of receipt, that the IDE is approved, approved with conditions, or disapproved.

It looks like a quick process. Unless they disapprove.
I think this looked really bad. Dr. Mehta's study terminated! But it is not as bad as it looked.