Tuesday, February 28, 2012

Appointment with My orthopedic surgeon today to follow up my revision in Nov: tidbits

Couple of things I found of interest:

(1) Teeth cleaning, fillings , antibiotics and the hip? Had an appointment with my dentist prior to seeing the orthopedic surgeon today.  I had not taken antibiotics prior to the visit and the Dentist was not particularly happy about the fact.  After questioning my orthopedic surgeon today, he highly recommended taking antibiotics prior to any dental appointment for the rest of my life, especially if it involves teeth cleaning.  Why?  too much bacteria in the blood after teeth cleaning.  You don't want to risk infection getting to the hip.

(2) Hips lighting up on Pet scans.  I found it interesting that in Pet scans, hypermetabolic activity (something lighting up) may result from either inflammation, infection or cancerous growths.  So I asked the Orthopedic surgeon about the inflammation of the the revised hip.  He told me that the hip will likely remain inflamed for a year post revision.  Gee, how interesting is that?   and we  think we are better in 3 months!

(3) Start up- I asked the surgeon why after 3 months I was having some issues getting going...taking the first few steps as a limp after I had been sitting.  He said this was perfectly normal.  He said they call it "start up."  Your walking gets better after you take the first few steps and the longer you  walk, the less you limp.  All signs of the hip getting better.  He assured me it would stop over time.

I requested another Chromium and cobalt blood test to look at my levels 3 months post op.  He wrote the script.   He requires another post op check at 6 months.  Got an Xray as well.  Hip was in great position.

We discussed at some length, the tumors that have been discovered in the last few months and we have a plan to address the examination (testing) of them.  I will provide some feedback on that once we have it.

Connie

J&J expects insider to restore stability

Published: February 27, 2012 3:00 a.m.

Drew Armstrong and Robert Langreth |

Sunday, February 26, 2012

Document: 2009 E-Mail on Hip Device (just discovered)

Published: February 21, 2012   

New York Times

In August 2009, the Food and Drug Administration notified DePuy Orthopaedics, a Johnson & Johnson subsidiary, through a “non-approvable” letter that it had turned down its application to sell a version of a hip device called the A.S.R. in the United States. On Aug. 21, Pamela Plouhar, vice president for worldwide clinical affairs at DePuy, sent the following e-mail to three company executives — including David Floyd, then DePuy’s president — reporting the F.D.A. action and its implications. The disclosures in the e-mail contrast with statements made in recent years by the company, which continued to market the device in Europe (and a related model in the United States) before announcing a recall in 2010. Here is the text of the e-mail, followed by a statement issued by DePuy on Tuesday in response to questions from The New York Times

2009 Internal E-Mail [from a depuy colleague to internal colleagues around 8/2009]

Sarah, David and Martin,

We have finally received the long awaited letter from FDA regarding the ASR PMA. It is a non-approval letter. A copy of the letter is attached.

The FDA took issue with several aspects of the pooled clinical data and subsequent data analysis and have essential asked us for a new clinical data set and analysis, which are cited for the major cause of the non-approvable classification (the 5 major deficiencies on page 1 and 2). There are also several other deficiencies associated with the clinical data noted in Items 1-3. FDA has also requested additional information related to fatigue testing (item 4), sterilization (item 5 and 6) packaging validation (item 7) Porocoat characterization (Item 8) and HA coating (item 9).

The clinical data deficiencies are the major concern. There are a few issues.
       
1. There have been a significant number of revisions within the ASR group (both in the IDE and in the OUS study) as opposed to very few in the control group.
       
2. The demographics of the control group are significantly different than the ASR group, which seriously complicates the analysis.

3. There are insufficient numbers of subjects in the original IDE cohort to demonstrate non-inferiority and even when the data is pooled with data from OUS, we are unable to demonstrate non-inferiority unless we exclude one site with one site with very poor results which was attributed to failure to use ASR specific instruments. FDA took major issue with this and believes that we have not demonstrated the required non-inferiority.

We are currently evaluating the data that is available to address FDA concerns and recommendation to provide a new data set. One possibility, especially to address issue 2 above is to determine if we can identify a demographically matched data set by pooling data from the ASR data sets and the other IDE control datasets. The team’s concern is that given the revision rate in the ASR group that we will still not be able to demonstrate non-inferiority with additional downside risk. Any need to enroll new ASR cases will significantly delay the PMA submission and approval by years.

We will provide you with a more detailed evaluation in the coming weeks, but we did want you to be aware of the significant risk associated with the FDA approval of this product. This comes at a time when ASR data from national registries (Australia and UK) is being closely scrutinized because of higher revision rates.

Please let me know if you have any comments or questions.

Pam

DePuy Statement on Tuesday

The ASR Hip Resurfacing System was not “rejected” by the U.S. Food and Drug Administration (FDA), nor did the company inappropriately sell it in other countries.
       
In the U.S., the ASR™ XL total hip replacement system was first cleared by the FDA for marketing in 2005 via the 510k process. DePuy filed a submission containing clinical data for pre-market approval (PMA) for the hip resurfacing version of the ASR device with the FDA in July 2007. In August 2009, DePuy received a letter from the FDA stating that based on the data submitted, the FDA was unable to assess safety and effectiveness for the ASR Hip Resurfacing System. The FDA recommended that DePuy provide a new clinical data set to support the potential determination of a reasonable assurance of safety and effectiveness. The letter concluded with the various options available to the company under FDA regulations, including the right to decide not to submit a new dataset and withdraw the application.

At the same time that the company received this FDA letter, market demand for hip resurfacing was declining rapidly. DePuy chose not to move forward with gathering additional data based on the declining demand for hip resurfacing. This was purely a business decision for the U.S. market. The decision not to pursue the ASR Resurfacing PMA application in the U.S. did not impact the use of the ASR Hip System in other countries.

Medical device registration requirements are defined by a country’s legislation. The legislation specifies the data required for the submission and approval process. DePuy properly complied with the regulatory process for each separate country where the ASR Hip System was available. At the time of the PMA submission in the U.S., the ASR Resurfacing System had already been approved for marketing by regulatory authorities in other countries. For example, in Europe, the ASR™ XL Acetabular System and DePuy ASR™ Hip Resurfacing System met the requirements of the Directives specified by the European Union for all medical devices and received CE mark approval.
DePuy markets a product, and this was done for the ASR Hip System.

xxxx

[From connie:  so it would appear that the issue that many of the investigators/researchers and collaborators  in England who were working on this hip were not told of the FDA's denial for approval for the resurfacing in the States.  Depuy's position is  that they were not legally required to disseminate information from one countrie's regulatory system to another.  I think the issue in England is they should have been told and they weren't regardless of what they were legally bound to do.]

Related posts:

 Hip Maker Discussed Failures

J&J hip recall: Internal emails detail FDA's non-approval letter

Hip Implant U.S. Rejected Was Sold Overseas

Saturday, February 25, 2012

Hip Maker Discussed Failures

The e-mail at issue was written in August 2009 by a vice president of a Johnson & Johnson subsidiary, DePuy Orthopaedics, just days after the F.D.A. confidentially notified the device maker that it would not approve one version of the hip for sale in this country. In the e-mail, the executive, Pamela Plouhar, explained the reasons for the agency’s decision to three other top executives, including DePuy’s president at the time, David Floyd.
       
Ms. Plouhar reported that the device had not met F.D.A. approval standards and that a major concern was its high rate of early failure, or “revision,” during clinical trials. She also cautioned that providing the F.D.A. with more data might not change its stance and that it might take years to conduct new studies of the hip, known as the ASR, or articular surface replacement.

“The team’s concern is that given the revision rate in the ASR group that we will still not be able to demonstrate non-inferiority, with additional downside risk,” Ms. Plouhar wrote.
       
To win approval, a novel medical device like the DePuy hip must be shown to be reasonably safe and effective. One way to prove that is to show that it is at least as effective as, or not inferior to, a traditional hip implant.

In her e-mail, Ms. Plouhar said there had been “a significant number of revisions in the ASR group” compared with “very few in the control group.”

Many artificial hips last 15 years or more before they wear out and need to be replaced. But by 2008, data from orthopedic databases overseas showed that the ASR was failing at high rates in patients after just a few years. The device also sheds metallic debris as it wears, particles that have damaged tissue in some patients or caused crippling injuries.

A DePuy spokeswoman, Mindy Tinsley, declined to respond to specific questions about the e-mail. In a statement, she said that the e-mail was “simply a notification to senior management about the F.D.A. feedback as the company appropriately continued to study data” about the implant so that it could make responsible decisions on the behalf of patients.

Last week, Andrew Ekdahl, the current president of DePuy, said in a statement issued in response to an earlier article in The New York Times that any implication that the F.D.A. had determined there were safety issues with the device was “simply untrue.”

In her 2009 e-mail, Ms. Plouhar referred to complaints about early failures of the ASR from doctors and regulators abroad. Regulators in Australia were then pressuring DePuy to withdraw the artificial hip from the market there or face having it forced off.

“This comes at a time when ASR data from national registries (Australia and UK) is being closely scrutinized because of higher revision rates,” she wrote.

DePuy does not appear to have violated any laws by not publicly releasing the F.D.A. ruling, which was contained in a so-called nonapprovable letter. The F.D.A., as a matter of policy, does not release such decisions, saying that they may contain confidential business information.

But DePuy’s decision not to publicize the agency’s findings to doctors, patients and others while continuing to market the device may undercut its defense in the 5,000 related lawsuits pending against it and could also tarnish its reputation.

Throughout the episode, DePuy blamed orthopedic surgeons for the model’s failures, saying that doctors were not positioning a component properly. But the clinical findings rejected by the F.D.A. came from A.S.R. studies run by surgeons hand-picked by DePuy, including some who had developed the implant and received royalties or consulting fees in connection with it. 

 The e-mail containing Ms. Plouhar’s report about the F.D.A. decision is among thousands of company documents released to lawyers suing the company under a court-ordered seal.
It is not known how many patients received the implant in the year between the F.D.A. decision and the recall. But during the device’s eight years on the market, it was used in an estimated 93,000 people, about one-third of them in the United States.

The version of the device rejected by the F.D.A. was developed by DePuy for use in a hip replacement procedure called resurfacing, which is a bone-sparing alternative to standard surgery. The company started selling the implant abroad around 2003 but because resurfacing was a new procedure, the F.D.A. required DePuy to run clinical trials before selling the device in the United States.

However, while those studies were under way, DePuy used a regulatory loophole in 2005 to start marketing a version of the implant in the United States for use in standard hip replacement surgery. Both versions of the device used the same critical component, a solid metal cup that replaced a patient’s hip socket. Experts say the component was flawed in design. In the wake of the F.D.A.’s 2009 decision to reject the resurfacing version of the device, DePuy executives wrote in internal e-mails that the device’s fate appeared sealed.
       
“Can’t imagine we would go any further in the U.S.,” one executive wrote.

In September 2009, just weeks after the F.D.A. decision, other documents indicate that top DePuy executives decided to phase out the device. The company announced the move that November.
Company executives said then that the move reflected declining sales of the implant, rather than safety issues. In his statement last week, Mr. Ekdahl, the company’s president, reiterated that position.
“This was purely a business decision,” Mr. Ekdahl stated.    

I will publish the Depuy letter as I found it interesting.
         

Friday, February 24, 2012

At J&J, The Weldon Legacy Is Marred By Scandals...J&J Chef Announces Retirement




After two years of scandal and controversy, Johnson & Johnson took a step that a vocal number of critics had been seeking months ago. The health care giant announced that ceo Bill Weldon would retire in April, although he will remain chairman for an unspecified period of time, and that he will be replaced by Alex Gorsky, one of two succession candidates who currently oversees the medical device and diagnostics business.

The move capped a fractious episode for the maker of such venerable products as Band-Aids and Johnson’s Baby Shampoo. Since January 2010, the health care giant has recalled tens of millions of products, mostly over-the-counter items such as Tylenol, Benadryl and Motrin, but also syringes, hip replacements, contact lenses and prescription drugs, due to manufacturing problems that seemed to permeate every corporate nook and cranny. Oh yes, there were shortages of Tampon and certain shampoos, too.

By now, the fallout is well known. The quality control gaffes led to a consent decree with the FDA; highly publicized congressional hearings; various government investigations; hundreds of job losses; the closure of a key plant; a reorganization of the McNeil Consumer Healthcare unit; eroded consumer confidence; numerous lawsuits, and hundreds of millions of dollars in lost sales. Consequently, J&J dropped to 7th place on the annual Corporate Reputation poll from Harris Interactive, its lowest-ever ranking.

Wall Street, however, has been more patient with Weldon. Rather than clamor for his head, investors have taken the long view and decided that J&J remains greater than the sum of its parts, especially since the health care giant has benefited from acquisitions that occurred on his watch, such as the Tibotec unit that sells HIV meds. Over the past year, in fact, J&J stock has increased roughly 18 percent, despite the recall debacle.

Still, the Weldon legacy may well reflect scandals. And yes, there was more than one. Consider the drumbeat of news about the safety of hip replacements sold by its DePuy unit. A recent report indicated marketing continued in Europe and other countries even after the FDA rejected the product for the US. Another revealed that a J&J executive wrote in a company e-mail that the FDA rejected the device after reviewing company studies showing significant premature failures, which contradicted public statements.

There has also been a string of legal setbacks surrounding the marketing of the Risperdal antipsychotic. J&J has reportedly reached a tentative deal to pay up to $1 billion to settle a federal probe that would resolve civil charges, and also agreed to a misdemeanor charge over the same issues. Last month, though, J&J marched into a Texas courtroom to defend a lawsuit brought by state officials, who charged the company orchestrated a controversial program that was designed to boost prescriptions in the public sector nationwide. But J&J quickly settled for $158 million after just one week of scathing and unflattering testimony (see here).

All of these problems figured prominently in a widely publicized, but ultimately unsuccessful shareholder derivative lawsuit, which a special board committee, not surprisingly, argued was meritless - its own investigation found no red flags or indications of systemic failure that were overlooked by the board or the J&J executive team. And the committee maintained there was no evidence Weldon engaged in or had knowledge of any wrongdoing. A federal judge dismissed the suit last fall (read here and here).

By then, J&J stock had been ascending, as investors decided the myriad problems were largely baked into the stock. This has offered Weldon needed support, of course, since increasing shareholder value is one of the few positive developments that he can point to during this stretch. But for long-term investors, the last two years were not quite as stellar as the more recent gains in J&J shares might suggest.

Consider this: in early January 2010, when the recall mess began, J&J stock traded just north of $60. Right now, shares go for $65, an 8 percent gain. Meanwhile, the Dow rose from 10,583 to 12,938 during the same period, a 22.2 percent increase. Granted, an 8 percent rise is not shabby and this does not include dividends. Nonetheless, one is tempted to wonder if J&J stock would have performed even better had the health care giant not experienced so many setbacks for so long across so many of its businesses.

In other words, the Weldon reign, which began a decade ago, will marked by the proverbial ‘what if?’ What if worldwide staffing in healthcare compliance and quality and control had not been so dramatically reduced several years ago? What if the restructuring of the McNeil unit, which involved absorbing the Pfizer consumer business and a subsequent hiring freeze, had been handled differently? These were failings conceded by J&J special committee in defending against the shareholder lawsuit.

Like a smart acquisition – such as Cougar Biotechnology, which yielded the Zytiga prostate cancer med – these mistakes also occurred on the Weldon watch. And while some other drug or device may one day reach the market thanks to a well-crafted deal, the scramble to regain shelf space and market share will challenge McNeil for some time to come. Similarly, restoring corporate reputation, which J&J has held out for decades as a valuable, if intangible asset, will also take hard work. And this is not the kind of work that an outgoing ceo should want to leave for others to clean up.

Thursday, February 23, 2012

Granulomas Redux...What are they again?

As you know, I have been addressing the granuloma question in some detail.   Had lots of questions so I thought it might be appropriate to address in more detail.  From the perspective of the hip, a granuloma may come into play as a reaction to the high levels of toxic metals in the body.  A small portion of the hip population is reported to have these ( less than 1%) but  most of the time, no one would know they are present unless they are discovered by accident through some unrelated radiology procedures or scan.  Honestly, I question that low incidence of these granulomas.

1.  Granulomas remain enigmatic. 

·         While they  have been studied extensively, much is unknown about them.  They are also hard to define.   Defining a granuloma is difficult.  In the orthopedic community, one might call a granuloma a pseudotumor of which there are hundreds of articles written on the occurrence of these with hip artheroplasty (both initial and revised procedures.)

2.  What are granulomas and what is their purpose?

·         A granuloma,

o   In its simplest form is an inflammation characterized by the presence of lymphocytes (white blood cell ), monocytes (Monocytes are a type of white blood cell) and plasma cells .  It is is a medical term for a tiny collection of immune cells known as macrophages. The role of a macrophage is to phagocytose (engulf and then digest) cellular debris and pathogens.  Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate it.....like perhaps metals.

o   In a complex form can be defined as a collection of mature mononuclear phagocytes which may or may not be accompanied by necrosis.

·         One of the basic functions of the granuloma is to rid the host of unwanted substances…like metals or a million other things.  The introduction of a foreign substance into the host evokes acute inflammation.  Leukocytes engulf the invader and attempt to destroy it.  When their attempt is successful, the inflammation resides.  If not, the invader comes to lie within mononuclear phagocytes.  The continued presence of the invader, especially in a particulate form and in high concentration may stimulate mononuclear phagocytes to mature, coalesce and divide.  A mature granuloma results.  If the intruder and its components are particularly stimulatory or if delayed sensitivity develops, the macrophages mature even further to epitheloid cells.  The resultant epitheliod granuloma persists until the foreign intruder is destroyed.  Then the lesions slowly resolve as the mononuclears die, revert to less mature forms or wander off.

3.  The tempo at which granulmatous inflammation develops can vary considerably and depends upon the inciting agent and the state of the host.  The lesions can grow in as few of as 3 days.  The further development into epiteliod lesions require 22 days.  The accumulation and number of epitheloid cells are accelerated in hosts displaying strong delayed hypersensitivity to the evoking agent.

4. High turnover granulomas induced by relatively toxic substances  proliferate briskly.  The natural history of high-turnover granulomas is to develop into low turnover lesions as the inciting agent is degraded.  The granuloma itself persists until the inciting agent is destroyed.  The constituent macrophages could have several possible ends:  division, emigration or death.

5. One certain property needed for the granuloma development is the persistence of the evoking agent.  Granulomas persist only so long as does the inciting agent.  Some hypersensitivity-mediated granulomas require the agent to be in particulate form.  A high local concentration of a given agent is more likely to evoke a granuloma. 

5.  In summary:  Agents which evoke granulomas are likely to be persistent, particulate substances that are capable of producing modest maturation of macrophages.  Under appropriate circumstance, mature granulomas can evolve into epitheloid lesions, a change representing intensification of maturation.  The two processes are similar metabolically and morphologically and both are reversible after removal of the stimulant.  The presence of the granuloma does signify that a foreign substance has resisted destruction by the acute inflammatory response and is being sequestered and destroyed by mature elements of the mononuclear phagocyte system.  This is the body’s primary defense mechanism to foreign substances that are not welcome.

Delayed hypersensitivity can however greatly augment and accelerate the development of mature granulomas.
6.  Necrosis accompanies many granulomas.  In many cases the development of the delayed hypersensitivity to the intruder produces necrosis.  Factors other than hypersensitivity produce necrosis. 


 Prior posts that covered this topic:
Seeking information.......Granulomas, histiocytosis, type IV immune response.... (part 1 of x in this series)

So what is the cause of these pseudotumors after the second revision? (part 2 of x in this series)

Granulomas, necrotic pseudotumors post revision.....what is the story on this? (part 3 of x)

Background on Type IV Immune response (part 4 of x)

Background on Type IV Immune response (part 5 of x)

Background on Type IV Immune response (part 6 of x)

Connie's status with her investigation into tumor type growths (7 of x)

Granuloma journal articles provided to my medical Team related to the hip (8 of 8)

hope this post helps!

Wednesday, February 22, 2012

J&J hip recall: Internal emails detail FDA's non-approval letter

February 22, 2012 by MassDevice staff

Uncovered internal emails from Johnson & Johnson subsidiary DePuy Orthopaedics highlight the company's decisions to abandon a PMA bid for the now-defunct ASR hip resurfacing implants amid "a significant number of revisions" during clinical trials.

A newly uncovered Johnson & Johnson (NYSE:JNJ) email may pose problems for the health care giant in the ongoing lawsuits over defunct hip implants made by subsidiary DePuy Orthopaedics.
DePuy has insisted that the recalled ASR metal-on-metal hip resurfacing implants had failed due to improper positioning during surgery, but those arguments may lose some of their luster in light of an internal email from 2009 in which a company employee notes "a significant number of revisions" associated with the device in clinical trials.

See this post for the NY times article:  http://www.mydepuyhiprecall.com/2012/02/hip-implant-us-rejected-was-sold.html

The email, written by DePuy executive Pam Plouhar, outlines the FDA's decision not to grant pre-market approval to the ASR implant and notes the higher of corrective surgeries required by patients who received the device compared to a control group, according to a report by the New York Times

While the FDA non-approval letter remains confidential, Plouhar explains in her email that "the FDA took issue with several aspects of the pooled clinical data," especially concerned that "there have been a significant number of revisions within the ASR group (both in the IDE and in the OUS study) as opposed to very few in the control group."

"The team's concern is that given the revision rate in the ASR group that we will still not be able to demonstrate non-inferiority with additional downside risk," Plouhar added. "This comes at a time when ASR data from national registries (Australia and UK) is being closely scrutinized because of higher revision rates."

At the time, Australian regulators were urging DePuy to withdraw the devices from the market or be forced off, according to the Times.

J&J withdrew its PMA application shortly thereafter, a decision which the company has publicly said was driven by lackluster sales and a softening market.

"At the same time that the company received this FDA letter, market demand for hip resurfacing was declining rapidly," DePuy said in a statement released this week. "DePuy chose not to move forward with gathering additional data based on the declining demand for hip resurfacing. This was purely a business decision for the U.S. market."

The ASR implants had already been on the market overseas since 2003, and continued to sell in the European Union and other countries for another year after the abandoned FDA bid.

Soon after withdrawing the PMA application, DePuy announced plans to phase out the ASR implants amid declining sales. About a year later, in August 2010, the company issued a global recall of the ASR resurfacing implants, as well as a related ASR cup, due to a high rate of revision surgeries required to correct or remove defective implants.

The devices have been used on about 93,000 patients worldwide, according to DePuy, which is currently mired in a multi-district lawsuit under an Ohio federal court.

Tuesday, February 21, 2012

New House Bill to Change Medical Device Approvals Process

(exerpts from Rottenstein web site)

Future Models Wouldn’t ‘Repeat Same Flaw’ under the Bill

On February 2, 2012, Bloomberg‘s Web site reported that House Democrat Edward Markey (MA) sponsored a bill that would prevent medical device manufacturers from claiming their new products are “substantially equivalent” to existing, approved problematic devices. Specifically, the bill came about not because of the DePuy hip recall but because of a 1999 recall of vaginal mesh manufactured by Boston Scientific. Despite the numerous injuries Boston Scientific’s mesh caused women, subsequent manufacturers still used it to help their newer meshes through the 510(k) process. As a result, many women were injured.

If passed into law, the bill would permit the FDA to deny 510(k) premarket approval if the manufacturer of the preexisting device(s) had recalled their product or if the FDA was in the process of deciding to remove it. Manufacturers would also have to demonstrate how their new devices differed from troubled ones, and importantly, they would have to report to Congress if any devices in their current products’ “device lineages” had been recalled.

When asked to comment on the bill, Representative Markey said, “If an automobile is recalled for a major safety problem, we wouldn’t allow future models to repeat this same flaw, and the same should be true for the medical devices used in our bodies.” “The bill ensures that devices do not mimic the mistakes made by other products.”

Monday, February 20, 2012

Why I Won't Invest In J&J

Forbes
David Vinjamuri, Contributor  (2/16/12)

Four years ago, I would have said that Johnson & Johnson was one of the best companies in the world. As a former J&J marketer (for almost half of the 90′s) and a second generation J&J alum (my dad worked in finance for J&J in the 60′s), I was proud of the ethical standards of the company. No longer. The shock first hit me in 2010 when my infant son’s fever spiked above 104 degrees and our pediatrician warned me not to use infant Tylenol if I happened to find it on the shelves.
J&J has issued more than twenty-five recalls since 2009 and the problems aren’t slowing down. Yesterday, The New York Times reported that the cloud surrounding the marketing of an artificial hip by the DePuy division of Johnson & Johnson is growing:
The health care products giant Johnson & Johnson continued to market an artificial hip in Europe and elsewhere overseas after the Food and Drug Administration rejected its sale in the United States based on a review of company safety studies.
During that period, the company also continued to sell in this country a related model, which earlier went on the market using a regulatory loophole that did not require a similar safety review.
The market hasn’t quite caught on. Johnson & Johnson’s share price is up 12% over the past three years (although the S&P has done much better .) The public trusts J&J, too: this week the Harris Poll ranked Johnson & Johnson as the 7th most reputable brand in the world. That’s down from #2 last year, but it doesn’t sound like a company that has been plagued by recalls and ethical lapses for three years.
But brands are durable and Johnson & Johnson has one of the strongest. Business schools around the world still teach the 1982 Tylenol Tampering incident as a model ethics case. Fortune named former CEO Jim Burke one of the “greatest CEOs of all time” for his handling of the crisis. In 1982, Johnson & Johnson pulled Tylenol off the shelves in just seven days after the death of twelve-year-old Mary Kellerman was followed by a string of six more deaths in Chicagoland. This wasn’t a typical passive recall, either. Johnson & Johnson sent headquarters personnel into the field to help get the product off shelves and ran a massive media campaign to promote awareness.
If this sounds like a no-brainer, it wasn’t. The deaths were all local and the company had already ruled out a manufacturing problem at the time of the recall. Business pundits predicted that J&J was putting Tylenol permanently out of business. But because of the design of the Tylenol product at the time (a capsule), Johnson & Johnson couldn’t prevent a copycat from tampering with the pain reliever.
So you’d think the company would know exactly what to do if anything ever happened to Tylenol again, right?
Just over a quarter of a century later, Johnson & Johnson was faced with more complaints about Tylenol, but took a very different course. Complaints of an odd smell and nausea or stomach upset from Tylenol caplets surfaced as early as 2008, but McNeil – a J&J company – took no public actions for more than a year as Reed Abelson reported for The New York Times:
McNeil did not alert the F.D.A. until September 2009 and then didn’t start a substantial recall until December 2009 — during an F.D.A. inspection of the plant, according to F.D.A. documents.
In January 2010, the agency sent a warning letter to Peter Luther, the president of McNeil, complaining that the company’s initial investigation “was unjustifiably delayed and terminated prematurely.” It said that even though consumers had also complained about a moldy smell in Rolaids and Extra-Strength Tylenol, the company had not widened its investigation to include those products.
At the Johnson & Johnson I knew, a revelation of this magnitude would have rocked the company to its core and set things aright. But that’s not what happened. Since 2009, Johnson and Johnson has issued more than 25 different recalls on products as diverse as Motrin, Rolaids, DePuy artificial hips and Aveeno baby lotion. Instead of taking responsibility, Johnson & Johnson CEO William Weldon ducked for cover. When Congress asked him to testify, he instead had back surgery and sent Colleen Goggins in his place. Ms. Goggins, who headed the consumer group, was retired from the company the following spring. But Topamax, Risperdal, Blake Silicon Drains, DePuy artificial hips and numerous other products recalled came from areas not under Goggin’s supervision. (FULL DISCLOSURE: I worked for Colleen Goggins at Johnson & Johnson in the 1990’s).
Johnson & Johnson can fairly say a number of things in its defense. The manufacturing issues with products from McNeil have been hard to trace and may relate to a pallet supplier. There is no discernible connection between many of the other recalls and it is often the case that when a company’s actions reflect negatively on the supervision of the FDA that company is subsequently held to a higher standard. There have been lots and lots of statements by senior J&J management attesting to the company’s intentions to put things right.
I raised the issue of the recalls on a group for J&J alumni on LinkedIn and there were a variety of opinions but one thing kept resurfacing, a theme which I also heard from friends still at Johnson & Johnson: the company culture has changed. The LinkedIn group is private, so I can’t attribute it here, but here is a similar comment from an anonymous forum. The post is titled “The Credo is Dead”:
JNJ used to be a great place to work. Now, the higher level management is full of mediocre, self-serving yes-men. It’s really sad how the company has changed.
To be clear, this is just one comment from an anonymous source in a forum where disgruntled or laid-off employees come to grouse. And even on that thread there are some who defend J&J. But when I listen to people who once loved the company I can’t help but come away with a feeling that something has changed.
So I am sad to say that as a parent and an ex-employee, I no longer trust the company or its brands. And as an investor, I won’t be putting my money in Johnson & Johnson.

Sunday, February 19, 2012

Hip Implant U.S. Rejected Was Sold Overseas

By BARRY MEIER  NEW YORK TIMES

Published: February 14, 2012
The health care products giant Johnson & Johnson continued to market an artificial hip in Europe and elsewhere overseas after the Food and Drug Administration rejected its sale in the United States based on a review of company safety studies
During that period, the company also continued to sell in this country a related model, which earlier went on the market using a regulatory loophole that did not require a similar safety review.
It is not known how many people overseas received the replacement hip after the agency decided in 2009 not to approve it, nor the number who received the closely linked implant sold in this country. During some eight years on the market, the two implants were used in about 93,000 patients worldwide, about one-third of them in the United States. Both models were based on the same component, an all-metal hip socket cup that experts say was faulty in design.
The DePuy orthopedic division of Johnson & Johnson, citing declining sales, began phasing out both models of the device — formally known as an articular surface replacement device, which DePuy marketed under the name ASR — in November 2009 and formally recalled them in August 2010 amid reports in databases of orthopedic patients abroad showing they were failing prematurely at high rates.
But in a confidential letter, the F.D.A. told Johnson & Johnson in August 2009 that company studies and clinical data submitted to gain approval in the United States to sell the model available overseas were inadequate to determine the implant’s safety and effectiveness, according to a summary of the letter reviewed by The New York Times.
The agency also told the company it would need added clinical data to pursue the application, a process that would probably have taken a year or more. DePuy’s receipt of the notice came as regulators and surgeons abroad as well as doctors in this country were raising serious questions about growing failures of both models of the implant.
A spokeswoman for DePuy confirmed that the company had received the agency’s so-called nonapproval letter. But the spokeswoman, Mindy Tinsley, declined to release the letter or to respond to questions about when, or if, DePuy disclosed the ruling to doctors, patients, investors or regulators abroad.
A principal researcher on the clinical studies submitted by the company to the F.D.A. said he was not informed of the agency’s decision. Also, a review of publicly available information indicates that the company did not discuss the agency’s nonapproval letter in financial reports or in presentations to analysts while the device remained on the market.
There is no suggestion that Johnson & Johnson broke the law. Regulatory standards in other countries, like those in Europe, for approving the sale of medical devices are typically lower than here. A spokeswoman for a British regulatory agency, the Medicines and Healthcare Products Regulatory Agency, said that companies like Johnson & Johnson were not required to notify it when the F.D.A. refused to approve a product that was used in patients there.
However, the F.D.A.’s rejection may further deepen the company’s legal and financial problems surrounding the ASR. Last month, the company took a special $3 billion charge, much of it related to anticipated legal and medical expenses associated with the recall. An estimated 5,000 lawsuits involving the device are pending, including some from patients crippled by tiny particles of metallic debris shed by the implants.
William Vodra, a lawyer who specializes in F.D.A. regulation, said that, in general, drug and medical device makers typically disclose nonapproval letters if they might have a material impact on a company’s finances. Mr. Vodra added that apart from that financial calculation, there was no hard-and-fast rule about making such rulings public.
Mr. Vodra said that if a company decided to withhold a nonapproval letter that contained important safety information about a device used by doctors, it could face damage to its brand. “They have to think long and hard of the reputational impact,” he said.
The handling of the ASR highlights how the F.D.A., by keeping its approval process confidential, may affect the health and safety of patients. An agency spokesman, Morgan Liscinsky, declined to disclose the letter on the ASR, saying the agency had a policy of not releasing such notices because they might contain confidential business information.
The version of the ASR rejected by the agency was developed by DePuy for use in a hip replacement procedure called resurfacing, which is a bone-sparing alternative to standard surgery. DePuy started selling the implant abroad around 2003. But because resurfacing was a new procedure, the agency required the company to run clinical trials before selling the device here.
In 2005, while those studies were under way, DePuy used a less rigorous regulatory pathway to win F.D.A. clearance to sell a version of the ASR based on the same metal hip cup for use in traditional joint replacement surgery. Because that version resembled hip implants already on the market, the agency was authorized to clear it for sale without clinical testing.
It was apparently within weeks of getting the F.D.A. letter in August 2009 that DePuy executives began a strategy to slowly phase out ASR sales while shifting surgeons to other company implants.
Three months after the letter, in November 2009, the company publicly announced its decision to phase out the ASR, attributing the move to declining sales. The company also said then that it had withdrawn its F.D.A. application for the resurfacing version of the device.
In a statement, Ms. Tinsley, the DePuy spokeswoman, said the company “weighed the additional data that would be required for approval against the declining market demand for hip resurfacing.”
It is not known precisely what the agency’s letter stated nor is it clear how, or if, the agency’s concerns about the resurfacing version of the hip implant applied to the model used in this country in standard replacement surgeries. The agency can reject approving a device for various reasons, including cases where it is seeking only small amount of added data.
Copies of the letter that might have been provided to lawyers involved in litigation against Johnson & Johnson have been sealed by the court. But the summary of the letter to DePuy suggests that it was long and detailed — 13 pages in all.
Before the recall, DePuy long defended the articular surface replacement device, saying that any failures associated with it reflected failures by surgeons to properly implant the hip cup. The surgeons who performed the study of the resurfacing version of the device that was rejected by the F.D.A. were handpicked by DePuy and included the model’s designers.
Dr. Antoni Nargol, an orthopedic surgeon in England who worked on the study that DePuy submitted to the F.D.A. and later became a critic of the device, said in a telephone interview that the company had never informed him that its application for approval in the United States had been rejected.
In March 2010, The Times disclosed that F.D.A. records showed that the agency had received 300 complaints about the ASR, virtually all of them involving patients who had to undergo replacement operation just a few years after getting the device. That number has since reached into the thousands.
DePuy continued to insist then that it was safe, but in August 2010, after data in a British registry of orthopedic patients showed high failure rates for the ASR, the company recalled both versions of the device.

Saturday, February 18, 2012

Interesting finding on a new Pseudotumor study just published

I was pretty surprised at this observation.  There are literally hundreds of articles on pseudotumors and .......look at the conclusion of this study from last month....Why am I surprised?  Why would I think there is nothing more concrete on these things...?

J Bone Joint Surg Am. 2012 Jan 4;94(1):86-93.

Pseudotumors associated with total hip arthroplasty.



Source


Hip and Knee Reconstruction, The McMinn Centre, 25 Highfield Road, Edgbaston, Birmingham, B15 3DP, UK.

Abstract

Pseudotumors are a rare but important complication occurring with all types of hip replacements.The true prevalence of pseudotumors is debated.Potential causes of pseudotumors may include foreign-body reaction, hypersensitivity, and wear debris.The conduct of clinical trials on the incidence, causes, and treatments of pseudotumors has been inadequate as few investigators have used a randomized controlled design to compare various implant types

Thursday, February 16, 2012

What is a pseudotumor and what is the occurance of them in post hip patients?

Pseudotumors are a rare but important complication occurring with all types of hip replacements.The true prevalence of pseudotumors is debated.Potential causes of pseudotumors may include foreign-body reaction, hypersensitivity, and wear debris.The conduct of clinical trials on the incidence, causes, and treatments of pseudotumors has been inadequate as few investigators have used a randomized controlled design to compare various implant types
another definition>
Pseudotumors are sterile inflammatory lesions found in the soft tissues surrounding metal-on-metal (MOM) and metal-on-polyethylene hip arthroplasties. In patients with MOM hip arthroplasties, pseudotumors are thought to represent an adverse reaction to metal wear debris. However, the pathogenesis of these lesions remains unclear.

Another tidbit

A recent study conducted in Canada on the occurrences of pseudotumors showed that the incidences less than .1%.
I like this description below written by  by Patricia Walter :

Patients and prospective patients are always concerned about the complications that could occur after a hip resurfacing surgery. The typical problems include femur neck fractures, dislocations, loose acetabular cups, improperly positioned acetabular cups, high metal ions, infections, pseudotumors, ALVAL and metalosis.

There has been a lot of discussion among patients on discussion groups about the high metal ion issue and pseudotumors. I am not a doctor or medically trained. I am a Patient Advocate, Hip Resurfacing Patient and Mechanical Engineer. I had the opportunity to attend the Second Annual U.S. Comprehensive Course on Total Hip Resurfacing Arthroplasty October 24–25, 2008 Los Angeles, CA. I listened to discussions about the metal ion issues and pseudotumors. I am going to explain what I learned in simple, non-medical terms since that is all I can do.
As an observer, I learned that the high metal ion issue has occurred in a small number of cases as a post op problem after a hip resurfacing. One of the most likely reasons, according to the experienced surgeons and presenters at the course, was the incorrect placement of the acetabular cup which resulted in additional wear on the bearing surface between the acetabular cup and the femur cap component. The hip resurfacing device is really a metal bearing made of High Carbon Cobalt-Chromium alloys. A bearing is designed to equally spread out the load over the load bearing components. If the components are not aligned properly, then only part of the bearing is loaded resulting in much more wear in that area possibly causing a high metal ion level. It was also explained that women seem to have more problems with high metal ions than men. Perhaps, this is due to the fact that most women use smaller sized hip resurfacing devices which causes more loading on the bearing surfaces than the men's larger sized devices.

When there is an abnormally high metal ion release from misplaced components, it seems to cause the surrounding tissue and bone to react adversely. The surrounding tissue and bone tends to become abnormal. Some doctors call the tissue reaction pseudotumors, AVAL (aseptic lymphocyte dominated vasculitis associated lesion), & others call it metalosis. Whatever name given to the abnormal reaction, it is not good to have this happening around the hip device since it could become loose, pain could result and possibly more severe medical reactions could happen. 
[From connie: While the idea of the occurrence of a pseudotumor or AVAL or whatever you want to call the adverse reaction, the idea of the component installation causing the problem is questioned now.  I just read a study showing that it is likely a patient sensitivity issue to the metal not a badly placed implant.]













Wednesday, February 15, 2012

What tests can you do post revision to ensure that everything is ok?

Question:
Can you please advise what type of tests/scans should be done in post depuy hip revision replacements?
We have undergone a revision a few months ago and the doctors have only done the heavy metals blood checks. We want to do more in depth x-ray scan and so forth to ensure all is okay. But the doctor is not sure and of course we are not sure how to go about it.

From Connie:

The only published protocol for monitoring purposes I know of right now is  the blood test for Cr and Co levels.

I presume this question arose as a result of my recent findings of the tumors.  A couple of comments:

(1) I don't know if these "tumors" are a result of the hip but we are examining the prospects of that.
(2)  If they are tumors, they can be benign or malignant.  I am hoping for the latter due to the results of the Pet scan.
(3) I identified these tumors incidental to an alternate exam that had absolutely nothing to do with the hip
(4) The test we used was a CT scan.  I was being followed annually for the last 5 years for something unrelated to the hip. We know that one year ago, no tumors were apparent anywhere.  When the scan was run this time, a multitude of tumors/enlarged lymph nodes appeared in the chest and pelvic cavity.
(5) I am looking into what tests can be used to eliminate the hip as being either causative or contributory to any of these tumors.
(6) 99.9% of the physicians, including but not limited to orthopedic surgeons will not  know anything about the nature of the tests that should be performed if faced with these growths insofar as the hip is concerned.  That is my personal experience.  We are seeking outside consults to guide this process.
(7) Most of the oncology physicians are interested in one thing and one thing only:
  • Is the growth cancerous?
  • What treatment should be instituted, should they be cancer to, get rid of the tumor.
(8) Given that oncologists often times do not know the origin of the cancer, understanding the cause appears to be off the radar of interest.  This has been my experience.  Sadly, cause does not inform treatment in cancer.  Only the nature of the cancer informs treatment.
(9) I don't know what they might do if the tumors are not cancerous.

I understand from the literature that the type of growth I am referring to (granulomas) are not typical ( much less than  than 1% of the patient population.)  I think it is  unlikely that you will get approval from any insurance company to run a CT scan for the propose of looking for growths when you are asymptomatic. I wouldn't do it myself because radiation is a risk in and of itself.  We were monitoring a few very small nodules in one organ which seemed to have doubled in size in one year.  This then precipitated the need for the CT scan and even then, I was leery of getting any more CT scans due to the radiation.  The pet scan of course, exposes you to higher radiation yet.  Tests involving radiation are not ones I would personally request unless there is a particular presenting symptom or growth to require those tests.

This whole testing area is net new area in my mind related to possible hip related issues.  I will get to the bottom of the testing and will let you know what I find.  My question may differ from yours though.  I have growths that require diagnosis.  I am not sure what you would look for otherwise given the incidence of occurrence  of these are  low.


previous posts

Connie's status with her investigation into tumor type growths (7 of x)

Granuloma journal articles provided to my medical Team related to the hip (8 of x)

Reminder:  I am not a doctor.  I am not trained medically.  I have no particular insight into this other than what I have read in the medical  journal articles.

Tuesday, February 14, 2012

Granuloma journal articles provided to my medical Team related to the hip (8 of 8)

Necrotic granulomatous pseudotumours in bilateral resurfacing hip arthoplasties: evidence for a type IV immune response

Lymphocyte proliferation responses in patients with pseudotumors following metal-on-metal hip resurfacing arthroplasty

Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty

Nanotoxicology of metal wear particles in total joint arthroplasty: a review of current concepts

Histological features of pseudotumor-like tissues from metal-on-metal hips

Heterotopic excessive wear granuloma mistaken for an aneurysm of the external iliac artery

Pelvic pseudotumor: an unusual presentation of an extra-articular granuloma in a well-fixed total hip arthroplasty

Pseudotumour in the bladder as a complication of total hip replacement: ultrasonography, CT and MR findings

Examination of granuloma of revised cemented or cementless total hip arthroplasties using inductively coupled plasma atomic emission spectrometry (ICP-OES)].

Hip arthroplasty with mass-like pelvic granulomatous disease: PET imaging.

Exaggerated pigmented granulomatous reaction to the artificial joint implant mimics metastatic melanoma Suture granuloma mimicking infection following total hip arthroplasty. A report of three cases.

Wear debris from total hip arthroplasty presenting as an intrapelvic mass.


Aggressive granulomatous lesion presenting as tumor in cementless long stem total hip arthroplasty.

Aggressive granulomatous lesions after hip arthroplasty.

Metallosis of the skin mimicking malignant skin tumour.
Hidden intrapelvic granulomatous lesions associated with total hip arthroplasty: a report of two cases.

Aggressive granulomatosis causing a painful hip arthroplasty. Findings on bone and Ga-67 imaging.

Systemic granulomatous reaction in hip prosthesis. Apropos of 2 anatomoclinical cases].
Granulomatous reaction in total hip arthroplasty.

Aggressive granulomatous lesions associated with hip arthroplasty. Immunopathological studies.

Necrotic and inflammatory changes in metal-on-metal resurfacing hip arthroplasties.

Necrotic granulomatous pseudotumours in bilateral resurfacing hip arthoplasties: evidence for a type IV immune response.



Sinus histiocytosis of pelvic lymph nodes after hip replacement. A histiocytic proliferation induced by cobalt-chromium and titanium
Chromium-induced lymph node histiocytic proliferation after hip replacement. A case report.
 
Lymphadenopathy associated with total joint prostheses. A report of two cases and a review of the literature.
Changes seen in lymph nodes draining the sites of large joint prostheses.
Prior posts on this subject:

Seeking information.......Granulomas, histiocytosis, type IV immune response.... (part 1 of x in this series)

So what is the cause of these pseudotumors after the second revision? (part 2 of x in this series)

Granulomas, necrotic pseudotumors post revision.....what is the story on this? (part 3 of x)

Background on Type IV Immune response (part 4 of x)

Background on Type IV Immune response (part 5 of x)

Background on Type IV Immune response (part 6 of x)