Posts Tagged ‘FDA’

As reported by heartwire, and a savvy reader, Lapeyre here at Cartagena Surgery, the FDA has gone ahead and approved TAVI/ TAVR for patients that are eligible for open surgery.  [We must think alike, as I was drafting this post when I received the reader mail].

Despite the FDA’s previously cited concerns over the excessive stroke rate with the Sapien device (as discussed in the article re-posted below) – the FDA approved the use of this therapy as an alternative to surgery on June 13th.

Now we can sit back and watch as the up selling of this device to the public as news hits the US media and the television advertisements begin.  Soon this device will crowd out surgery as interventionalists cite “patient refused surgery” as the criteria for implantation, no matter what the best interest of the patient really is.  I wonder if they will even disclose the heightened stroke rate when they start implanting this into patients at a much higher rate.  Of the 12 members of the FDA panel, only one member voted against the expansion criteria.

As reported by Shelley Wood in a follow-up Heartwire article , only Dr Valluvan Jeevanandam spoke out against expanding the criteria for use, stating,   “I think this is a very good technology, and it gives us an alternative to AVR surgery, and I’m sure the device will continue to get better,” Jeevanandam, a cardiovascular surgeon, told heartwire after the meeting.

“However, at the current time, compared with standard AVR, this device has a higher stroke rate and a high rate of aortic insufficiency, did not meet the criteria for noninferiority* in males, and has a high incidence of vascular complications.”

These are all issues that need to be very clearly explained to patients as part of the informed-consent process, he stressed. Otherwise, patients who are “enamored at the idea of avoiding a sternotomy” may not fully understand these risks.”  

I fully concur with Dr. Valluvan Jeevanandam except that I might re-phase the term ‘enamored of.’  Actually, I think our so-called peers need to quit coercing patients by intentionally scaring them – in order to bill more procedures out of them.  [Don’t believe it?  Then check out Mark Midei and our overstenting archives.]

I will continue to champion well-established therapies with strong long term data.  I know this will get me labeled as ‘old-fashioned’ (or worse) but as we’ve seen in cardiology – numerous times; easy is not always the best answer..

The is no easy button

Yes, conventional surgery hurts – it’s not glamorous, it’s not pretty.  But it’s (statistically) darn safe these days, and most of the surgeons doing it have done it thousands of times.. Even the bioprosthetic valves have a long durability than previously thought – meaning not everyone has to take warfarin..

We shouldn’t exploit people’s fears of surgery to use quasi-experimental procedures, no matter how “cool” they sound..

* I hope readers remember that ‘noninferiority’ is a lesser standard that superior to, or even EQUAL to..

FDA flags strokes, trial conduct, as TAVI maker seeks expanded role for Sapien – from Heartwire.com (Shelley Wood).

Gaithersburg, MD – A higher risk of stroke and differences in how patients randomized to different procedures were actually treated and evaluated within the PARTNER A trial, which compared transcatheter aortic-valve implantation (TAVI) with surgery, are issues the US Food and Drug Administration (FDA) hopes its expert advisors can help clarify in weighing the pros and cons of expanding approval of the Sapien transcatheter valve (Edwards Lifesciences) [1,2]. Those issues and others are detailed in an FDA briefing document, posted online today, that the agency’s Circulatory System Devices Panel will consider in advance of Wednesday’s meeting.

As previously reported by heartwire, the FDA last year reviewed and subsequently approved the Sapien valve and transfemoral delivery system in patients not suited to open-valve replacement, based primarily on the PARTNER B results. Wednesday’s meeting, drawing heavily on the  PARTNER A results, will help the FDA decide whether to expand approval to high-risk patients who are surgery eligible and whether to approve the transapical approach also tested in PARTNER A.

In briefing documents posted online today, the FDA directed its advisors to pay special attention to a number of issues relating to trial conduct as well as patient outcomes.

In particular, the FDA review cites the “doubling” of neurological events seen in the Sapien-treated patients in the first 30 days postprocedure, with a higher stroke rate seen among transapical as compared with the transfemoral group.

The FDA documents also query “attempt-to-treat” decisions, including the higher number of patients randomized to surgery in whom no treatment was attempted; longer delays to treatment in surgical patients; and the higher number of concomitant operations seen in the surgical aortic-valve-replacement group—all factors that could have influenced adverse-event and survival rates in this group.

FDA is also asking its expert panel to weigh in on whether both the transfemoral and transapical approaches should be approved, given the numerically higher mortality in the transapically treated patients as compared with the transfemorally treated patients in the device arm.

General questions the FDA panel will be answering Wednesday include those related to the issues above, as well as to different outcomes seen in men and women, the importance of paravalvular regurgitation seen in patients treated with TAVI, valve durability, the required anticoagulation/antiplatelet regimen, and obtaining true informed consent.

Voting questions center on whether the evidence is sufficient to demonstrate safety and efficacy and whether the benefits of the new device outweigh the risks.

Industry analysts reading the tea leaves in the FDA’s review see the agency’s briefing document as largely promising, with Wells Fargo’s Larry Biegelsen predicting a “tough day, but positive panel outcome” and JP Morgan’s Michael Weinstein stating that the FDA synopsis contained “no major surprises; positive outcome expected.”

In other cardiology news, 

New guidelines recommend the discontinuation of prasugrel a full seven days before surgery to prevent catastrophic bleeding complications. (The cynical side of me expects to see a bigger push by the industry to use prasugrel now that clopidogrel is generic.)  Expect to see a couple more “Ask your doctor” ads..


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Several new headlines concerning a recent executive order by President Obama in an attempt to alleviate the escalating drug shortages that have been plaguing the country.

Reuters wire story :

‘FDA Commissioner Margaret Hamburg said the latest order would not be able to
prevent all future drug shortages. “But we can make a really meaningful
difference by expanding our net of early warnings,” she told reporters.

FDA officials have been investigating the problem but have had trouble
identifying a root cause and coming up with a solution.’

As we’ve mentioned on several previous posts – Here, Here and Here  – one of the real reasons for the drug shortages are a lack of profitability by the manufacturers.  Once a drug becomes generic – it becomes less profitable, and more likely to become a target for shortfalls and ‘grey market’ price gouging.  It doesn’t matter if millions of people are taking life-saving cardiac medications – once they fall under the walmart/ CVS/ Kmart / discount retailer $4.00 price plan  – you can predict a future shortage.   Even cancer drugs play into this.   As we’ve seen time and time again – critical, life-saving ‘cardiac arrest’ drugs are not exempt from this problem.

CNN coverage :

“As the number of shortages has grown, prices have skyrocketed in certain instances.

The White House cited an August Premier health care alliance report estimating that the “typical gray market vendor” jacks up prices by 650% on average.

“At the extreme,” the White House statement noted, “a drug used to treat high blood pressure that was normally priced at $25.90 was being sold at $1,200 due to a drug shortage.”

Now, if only the government would step in and take things one step farther – and actually punish/ hold companies accountable for creating intentional drug shortages – then we’d be talking… proponents of ‘free market’ economics might scream about authoritarian tactics – unless of course, it’s their chemotherapy, or life-saving medications that are unavailable…

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Here’s the latest news on TAVI in the United States – and the status of the procedure, which is currently undergoing further evaluation by the FDA.

Here are some highlights from the article:

“In July, the FDA’s  Circulatory System Device Panel favored TAVI approval in the U.S. The  panel voted on three items, including: safety, effectiveness and whether  the benefits outweigh the risks. If the FDA accepts panel  recommendations, TAVI procedures would be available to U.S. patients.

However, CMS noted that it is aware of the high stroke and death rates associated with TAVI, and said that it remains concerned about adverse events that may occur, particularly when the procedure is performed by less experienced operators. Rates of stroke and death at 30 days were 6.7 percent and 5 percent, respectively, for those who received TAVI. At one year, these rates were 10.6 percent and 30.7 percent, CMS reported.”

As readers know; here at Cartagena Surgery – we’ve advised caution for the time being – until we have more long-term outcome data on transcatheter aortic valves.

However, after much consideration, and discussion with other people both in and outside the field of cardiac surgery – I have decided that I will begin interviewing and bringing more information about the procedure and providers performing this procedure in the USA.  Ultimately, while I may personally, (and professionally) feel that the TAVI procedure has not undergoing sufficient rigorous testing for my patients – I do not want to withhold information from them.

So, I have started writing and contacting providers to obtain more information about the physicians and medical centers performing this procedure. I will discuss these providers further in future posts.

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I am getting ready to head out on an extended road trip this morning, but before hitting the highway, I wanted to post of some headlines for discussion.  As you know, in the past, I have advised caution to people regarding some of the newest medical devices (such as the new aortic valve therapies and carotid stents.)  One of the reasons I am always initially cautious about new devices is the current approval process.  Unlike the process for many consumer goods such as cosmetics, medications and food products – medical devices do not always undergo rigorous testing.

The is also a history of widespread and rapid adoption of many of these devices, sometimes followed by numerous device recalls from the manufacturers, and the FDA.  Sometimes these recalls are relatively minor, but sometimes they aren’t.  Recent recalls have included surgical prosthetics, implantable mesh and other implanted items.

Now a new report suggests that the reason for all of the recalls, and the high incidence of faulty equipment is a poor initial review process.  The authors suggest a complete overhaul of the entire evaluation and approval process for patient safety.  (The actual report can be downloaded free here.)

Experts say medical device review system flawed

Special interests and medical lobbyists attempt to discredit report (before it’s even published)

All of this makes it bewildering, and frightening for patients out there, facing surgery. Some of the things we need to consider during all of this is:

1.  what are the options (for my condition):

Do I need surgery right now?  (or is this an elective procedure).  Depending on what surgery / condition a person has – the answers may differ widely.  In a previously untreatable condition, or a condition with very limited options (such as heart failure requiring transplantation) – new devices such as the heartmate II may be the best option for patients that would otherwise die waiting for a transplant.  Other patients – needing valve replacement, or carotid stents (two topics covered here) may opt to use the older, well-proven surgical therapies instead of the newest technologies.

This also ties into our next question.

2.  What other devices/ options are available?  Do I have alternatives to [this new treatment].  (ie. What have they used in the past)   How well did these older treatments work?  Am I a good candidate for this?

In the previous example, of a patient being considered for a heartmate ventricular assist device – there are few alternatives available.  Heart transplants are not also available, and many patients are not eligible for transplantation.  In that example, the new generation devices are essential and life-saving.  These patients may not otherwise survive long enough to worry about long-term complications.

However, for many patients, the patient’s medical condition itself may be a treatment limiting factor.  Sometimes the older treatments were effective, and proven but patients may be poor candidates for that treatment due to frail overall condition, multiple co-morbidities or other medical conditions.  This is often the rational for providing patients with experimental treatment therapies.

However, one of the things I do caution patients is – do your research, and ask heart – don’t make assumptions**.  This is important, particularly when talking about catheter based interventions – for heart valves, carotid disease, aneurysm repair.

When these new therapies first came out (stenting)- we all assumed that it would be safer for elderly patients and the medically fragile.  But, instead the research has yielded quite a few surprises. 

One of the biggest surprises was in the treatment of abdominal aortic aneurysms (AAA).  The research actually proved that open surgery was safer than we thought it was, and that people who we initially thought were poor surgical candidates, actually did quite well with open surgery.  EVAR (endovascular aortic repair with stent grafts) has been a wonderful development in the treatment of vascular disease, but not for the reasons we initially anticipated.  Elective treatment of aneurysms with stent grafts is still problematic at times – with endoleaks, and less durability over time than expected.  Patients receiving stent grafts end up needing a lot more follow-up than people who have open surgery.  But in  the emergent treatment of AAA rupture (which carries a 50% mortality for open surgery), EVAR has been wildly successful.

Research into the outcomes of both carotid stenting and TAVI have yielded similar results – regarding the overall safety of the procedures that these devices were invented to replace.  Carotid endartarectomy and traditional aortic valve replacement have turned out to be safer in sicker/ and older patients than we would have ever imagined.  If it hadn’t been for studies comparing surgery to the new procedures in these populations, we would have never known this.

This isn’t to say that we should avoid new technology or stop innovating or advancing medicine.  But we need to ensure that the process doesn’t endanger our patients while doing so.  Part of this is ensuring that new devices are well researched/ studied and tested before being used on a wide scale among our patients – to prevent avoidable injury or possible death.  Patients and providers place our trust in the FDA and other government agencies in ensuring that manufacturers provide safe products – so shouldn’t those government procedures actually work?  The FDA is the same organization that prevented General Mills (Cheerios) from making exaggerated claims about cholesterol lowering properties of their cereals (and rightly so, in my opinion).  Shouldn’t they do the same to protect the public from potentially unsafe therapies?

** You may not be as high-risk as you might think, and the new therapy may not be as safe as you assume.**

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This report comes out of Sri Lanka   “Patients die as Cardiac surgery unit stays closed,” but the implications hit close to home for anyone that has been following the news reports of critical drug shortages.  While many Americans take comfort in the fact that these stories of patient deaths come from other countries “over there” this is merely an exercise of blissful ignorance.

Drug shortages have plagued the United States for several years – its just that usually patients don’t notice them.  An on-going propofol (yes – the drug Michael Jackson used) shortage has made surgical anesthesia more difficult for the last several months as doctors scramble to find replacement medications.

Sometimes, the shortages are merely a nuisance – when certain drugs are limited to specific forms or dosages in availability, or closely-related drugs are suitable substitutes.  But sometimes, more frequently, in the last few years – these shortages have become more critical, with life-saving drugs such as chemotherapy.  The implications of these shortages are devastating – cancer patients with no drugs to arrest their disease, but somehow less dramatic, and thus less noteworthy than the Sri Lanka story above.

Vaccines, essential in stamping out endemic diseases have been in shortfall for over a decade.  Anesthesia agents – essential for surgical procedures, along with emergency medications (for cardiac arrest, acute coronary syndromes and other acute conditions) have become scarce – and affect almost every hospital in the nation.  The medscape article re-posted below talks about the delays in care, but no one seems to have calculated the toll this is taking on our patients.  However, two recent reports have brought more attention to this issue.

How many patients died, like in Sri Lanka because they didn’t receive the life-saving drugs they needed?  How many patients suffered because their surgeries were cancelled or delayed due to medication shortfalls?  How many patients sickened because the appropriate antibiotics were not available?

More disturbingly, these shortages aren’t just nationwide – or limited to so-called ‘third world nations’. Canada, and the United Kingdom have reported several shortages as well.  Surprisingly, in many of the places I’ve visited in Latin America – the concept is almost unheard of.

While US politicians make the appropriate noises over the latest round of shortages – congress has done essentially nothing to remedy this problem, despite (or because of) close ties to pharmaceutical lobbies.

Many of these critical shortages occur when companies simply decide to stop making these medications. How can Americans pay such exorbitant prices for brand name drugs only to have companies abandon the medications once they become affordable?  Yet, these very companies are protected by congressional laws prohibiting importation of generic substitutes.  (Lawmakers passed these regulations several years ago after drug companies starting complaining about the large numbers of Americans/ American companies going to Canada for their medications.  They claimed it was done for ‘patient safety’ but no proof was ever provided.  In fact, the largest/ most widespread tainted drugs incident to ever hit American shores – came by legitimate means – ie. the devastating heparin scandal.**)  [looking for references for these statements – read it but can’t recall where.  cartagena surgery].

Currently, these lobbies are placing the blame on the FDA for stringent regulations after the tainted heparin that killed patients of patients a few years ago – but that’s a secondary cause, used to divert attention from profit margins.  Unfortunately, it’s a cry taken up by several corporate bloggers.  It’s not question of patient safety compromises versus drug availability.  It’s greed, pure and unadulterated.

In a day and age, where a dollar increase in gas prices brings a national outcry, and a presidential response – where’s Obama now?  Why in this era of Enron, Lehman brothers, Madoff scandals and unparalleled corporate avarice are pharmaceutical giants going unchecked?

So, in the end it’s only a matter of time before American drug shortages, bring similar headlines to those in that far off nation.

Oncologists facing critical drug shortages – calls for federal oversight

Critical shortages in Oregon

** the official number of deaths from tainted heparin in the US is 81 -200, but most nephrologists/ pharmacists I’ve spoke with think this number is way, way too low – but that deaths were masked by patients’ underlying conditions.

**** just to clarify for readers, the new proposed legislature does nothing to alleviate shortages – they just want the manufacturers to warn the FDA about them.

Article re-post from Medscape (12 July 2011)

Drug Shortages Often Delay Care at Hospitals

Robert Lowes

July 12, 2011 — Prescription drug shortages always or frequently delay patient care at 20% of the nation’s hospitals, and at 11%, patients often receive a less-effective medication, according to a new survey by the American Hospital Association.

Virtually every hospital (99.5%) reported experiencing a shortage of at least 1 drug in the last 6 months. For 44% of hospitals, 21 drugs or more were in short supply.

The number of drugs in shortage nearly tripled from 61 in 2005 to 178 in 2010, according to the US Food and Drug Administration (FDA). Those numbers do not include vaccines, immune globulin products, and other biologics, or products made from blood, tissue, or other biological materials, the agency states.

Reasons given for the scarcities are many: a lack of raw materials, increased demand for some agents, barriers posed by FDA regulations, the use of slim “just-in-time” inventories, and manufacturers declining to make low-profit generics, to name a few. Some of the most critical shortages involve cancer drugs, and more than half of the hospitals surveyed (66%) reported a shortage of these drugs.

Other therapeutic areas with high levels of drug shortages are surgery/anesthesia (95%), emergency medicine (91%), cardiology (90%), gastroenterology/nutrition (89%), pain management (88%), and infectious diseases (83%).

Less than half of the hospitals reported shortages for drugs in neurology (41%), endocrinology (40%), obstetrics/gynecology (39%), allergy (28%), psychiatry (25%), or other (34%).

To examine the effect of the drug shortages on hospitals, the American Hospital Association sent its survey to the chief executive officers of all community hospitals in June 2011. Responses from 820 institutions were included in the analysis. In all, 82% reported delays in patient care as a result of scarce drugs, but 62% said it happens only rarely. Three percent of hospitals said shortages often result in adverse events for patients compared with 32% that said such outcomes are uncommon. Roughly 3 in 4 hospitals are rationing or restricting the use of drugs in short supply, and 92% are incurring higher drug costs to cope with the crisis.

One big peeve among hospital executives is getting blindsided by a drug shortage: 77% said they never or rarely receive an advance warning from the FDA, manufacturers, or middlemen. Such complaints prompted 2 US senators to introduce legislation in February that would require manufacturers to give the FDA early notice of any incident that might lead to a dearth of a particular product. As a result, pharmacists and healthcare providers would have a head start to work around the problem. The bill is now before the Senate Committee on Health, Education, Labor, and Pensions.

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Now all of my long-term readers should be able to spot the flaws in the logic here. One study, funded by a drug company with results that are at odds with just about every other study ever published – and that’s the one the FDA uses to approve/ expand the indications for stenting? Guess it’s just another ‘easy’ solution to sell to patients / primary care providers who don’t have the time and resources to review the literature themselves.  No surprise, since I am guessing that cardiologists will be placing the majority of these stents..

From HeartWire:
FDA approves expanded indication for carotid stenting
May 6, 2011 | Susan Jeffrey

Adapted from Medscape Medical News—a professional news service of WebMD
Silver Spring, MD – The US Food and Drug Administration announced today it approved an expanded indication for the RX Acculink carotid stent system (Abbott Vascular, Santa Clara, CA) to include patients at standard surgical risk for carotid endarterectomy [1].

Previously, the RX Acculink stent, used in conjunction with Abbott’s Accunet or Emboshield embolic-protection devices, was approved for use only in patients requiring carotid revascularization who were at high surgical risk. These high-risk patients were also required to have a reference vessel diameter ranging from 4.0 mm to 9.0 mm at the target lesion and be symptomatic with a stenosis of the common or internal carotid artery of >50%.

The stent was also previously approved in high-risk patients without neurological symptoms but with a stenosis of the common or internal carotid artery >80%.

In January, the FDA’s Circulatory System Devices Panel voted 7 to 3 in favor of this expanded indication for the system, saying the benefits of carotid stenting in patients at standard risk for adverse events from endarterectomy outweighed the risks. wait – are you sure about that?? because most of the data shows that surgical risk is actually well under 1% – and that’s looking at VA studies involving tens of thousands of patients, with multi-year follow-up..

The panel also voted 6 to 4, with one abstention, in support of the safety of carotid stenting in standard-risk surgical patients and 8 to 2, again with one abstention, in a vote that asked about the effectiveness of therapy in this expanded patient population.

“Expanded access to RX Acculink means patients and their healthcare providers have another option for treating clogged neck arteries,” Christy Foreman, director of the Office of Device Evaluation in the FDA’s Center for Devices and Radiological Health, said in a statement.

The FDA based its approval on the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), a 10-year study of 2502 symptomatic and asymptomatic patients at 119 clinical sites in the US and Canada, funded by the National Institute of Neurological Disorders and Stroke with supplemental funding by Abbott.

Patients were treated and followed for at least one year. Results of that study, published in the New England Journal of Medicine, showed that patients treated with stenting had a similar combined rate of death, stroke, and MIs those who underwent surgery [2].

Those who underwent surgery, however, had fewer strokes, and those who had stenting had fewer MIs over follow-up. There was also an effect of age, where older patients had fewer events with surgery, while younger patients had slightly fewer events with stenting. Wait a minute – older patients – surgery is actually safer.. but remember, that’s the excuse we received from the beginning – ‘stents are for the frail old people’.. define ‘slightly fewer’ – does that mean ‘not statistically significant’ because that’s what it sounds like. [cartagena surgery]

The FDA advisory panel emphasized the need for additional long-term follow-up information and the importance of the stent’s use in conjunction with an embolic-protection device.

As a condition of the approval, Abbott is required to conduct a postapproval study that will follow new patients treated with the stent system for at least three years to confirm the results identified in CREST.

The postapproval study will also evaluate how patients age 80 years and older respond to treatment, whether treatment success is affected by operator experience, and whether symptomatic and asymptomatic patients have different outcomes.

“The study is consistent with recommendations made by the expert advisory panel,” the FDA statement notes

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