PRODISC STUDY

 

Report your Prodisc ‘Adverse Event’ here (‘begin’ on right)

Search MAUDE here.  Enter ‘PRODISC-L’ as  Brand Name

 

Introduction:  “ProDisc™ was developed by a start-up company known as Spine Solutions Inc. A New York investment firm, Viscogliosi Brothers, helped found Spine Solutions and financed the disc’s development and research. The Viscogliosi Brothers offered the ProDisc clinical investigators substantial investment opportunities in Spine Solutions, as well as consulting contracts that included gifts of company stock and stock options.” NJ AG

 

The Viscogliosi Brothers sold Spine Solutions to Synthes for $175 Million, with another $175 Million to be awarded upon achievement of certain fda approval milestones.  The global market for disc replacement was projected to grow to $3 Billion by 2008. Synthes

 

"It is outrageous that doctors who are testing, and in many cases, recommending the use of certain high-risk medical devices are being compensated with stock in the very companies that make these devices," Attorney General, Anne Milgram.

 

"The investigation revealed that a majority of the physicians who participated in these clinical trials had significant investments in the products — investments that would have been worthless had the product failed to obtain regulatory approval from the FDA. And, the investigation revealed that Synthes, which acquired ProDisc while the clinical trials were underway, failed to disclose these financial conflicts of interest to the FDA.”

 

“Medical device makers have a duty to make certain that clinical trial results are accurate and unbiased, In creating these financial incentives for doctors, Synthes and the rest of the industry have done the exact opposite.”  Attorney General, Anne Milgram.

 

"The process of approval and monitoring of both of these disk replacements by the FDA has occurred under suspicious and secretive circumstances that suggest that this is the work of undue influence by industry. I believe this presents a real danger to the American people in a circumstance of money triumphing over patient care." Dr. Charles Rosen"

 

"But when they stand to profit from FDA approval of the product they are testing, the investigator’s objectivity is called into question." ..."This suggests a dangerous conflict of interest." ... " raise serious questions about the reliability of the study’s data"  Senator Charles Grassley

 

This study collects papers, articles, quotations and concerns regarding the Prodisc™ Artificial Disc Replacement Device manufactured and distributed by Synthes Inc.  The intent here is to pose questions, and provide the sources which instigate these questions, shed light on them, or contradict the conclusions of financially invested parties.  This study is independent, not sponsored by industry, and the authors have no financial investment in any of the companies, products or processes studied.

 

This study is dedicated to Anastasia, Linda and Jamie – all Prodisc patients, in terrible pain, who feel they were deceived.

 

KEY POINTS:

 

1.       The FDA approved an IDE trial for the Prodisc based on E.U. data.  This data was collected by a surgeon who was found to have invested $50,000 in the device.

·         Nowhere, in any medical paper, are patients warned that the surgeons involved in the Prodisc Trials were betting on its success.

2.       Spine Solutions (Prodisc owner) was sold to Synthes for $350 Million, with $175 Million to be awarded upon FDA approval.  Many surgeons stood to gain from this.

·         The New Jersey AG hints that upwards of 15 Million would have been lost by the surgeons, if the Prodisc failed FDA approval.

3.       The FDA IDE trials of the Prodisc-L were compromised as most of the surgeons involved were financially leveraged to the success of the Prodisc over Fusion.

·         Would you want a surgeon performing a Fusion on you, if you knew he was betting are your inferior results?

4.       The V-Bros were investigated for fraudulent financial activities.  The case was dismissed, because the V-Bros had succeeded in providing the specific investors a profit.

·         So, the V-Bros got their $175 Million, and paid off the investors – and this makes the alleged fraud and embezzlement OK?

5.       The FDA trials were not constructed to show superiority of the Prodisc-L over the traditional fusion. 

·         And yet, the surgeons claim superiority of the Prodisc-L over fusion … even though this was forbidden by the FDA.

6.       In the FDA trial reports published by the surgeons: The Prodisc outperform the Fusion, in all metrics – except that the Fusion patients took less narcotics

·         Notably, the surgeons did not have control over how much narcotics the patients took.

7.       The Control Subject’s fusion method employed iliac crest bone harvesting, instead of rhBMP2, to promote osteogenesis, or trabecular bridging bone.

·         Synthes has no reservation in warning patients about Fusions and iliac crest bone harvesting – but do not warn that Prodisc revision could kill them.

8.       The claims of the benefit of the Prodisc-L regarding mitigation of Adjacent Segment Degeneration, have not been proven, according to various papers.

·         Of course, it is made to sound like this is a well known, proven fact.   However, many studies note otherwise, and this is not advertised.

9.       The key claims of the Prodisc-L maintaining motion are questionable, as some studies show positive motion, while others show very limited.

10.    The longevity of a Prodisc-L TDR has not been proven, and reported life-spans are conflicting, from 10 years to life-time.

·         A solid Fusion’s life-span is not a concern.   Recent fusion success rates are above 99%. 

11.    Some Prodisc investors claim the Prodisc-L ‘maintains natural motion’.    Exactly what ‘maintaining’ and ‘natural motion’ are, are conveniently not defined.

·         An independent analysis shows it allows hyper-dynamics, which may harm facet joints.

12.    The Prodisc-L has been implicated as causing a progression of facet arthrosis, which is a leading driver of Prodisc Revision.

·         Upwards of 30% of Prodisc patients are reported as acquiring, or exacerbating facet arthrosis, post Prodisc implantation.

13.    Prodisc-L revision has been noted to be life-threatening and traumatic by 27 sources, including surgeons. 

·         The life threatening danger of the Prodisc-L revision, and ways to mitigate it, are not discussed in any product brochures seen.

14.    Facet arthrosis is not listed as a contraindication on some product brochures, although it is listed as an ‘exclusion’ in the FDA trials.

·         In fact, the FDA Device Labeling does not list facet arthrosis as a contraindication – even though such patients were excluded from the trials.

15.    Three Synthes Executives were indicted for criminal conspiracy in 2010 (2002-2004, Norian XA). 

·         Were those Executives also involved in the Prodisc-L FDA trials?  What about the field sales agents who oversaw patient’s deaths?

16.    The Prodisc-L received ‘Me Too’ FDA status, based on the J&J Charité FDA trials.  However, J&J were denied Preemption in a case claiming the Charité is defective.

·         Not only does the money trail for the Prodisc-L trials go all the way back to the first EU studies review, but even the ‘me-too’ device is suspect!

 

PRODISC DEVICE LABELING: QUESTIONABLE DISCREPANCIES

 

It appears that the contraindication for 'facet arthrosis' has been left off the Prodisc-L device labeling.  Of course, facet arthrosis is a common and natural secondary effect of the pathogenis of DDD, as the disc collapses and the facets take the load.  Given that 97% of fusion patients in a study (pg 11) were found to have facet arthrosis, with 84.5% (82/97) of them being symptomatic, it would clearly be a huge financial blow to the Prodisc-L market potential, if 84% of fusion patients were excluded from Prodisc-L TDA.

 

1.  The IDE trials explicitly, and strictly, excluded patients with Facet joint degeneration / disease.   However, the device labeling does not list this as a contraindication, but rather as 'has not been determined'.  : p050010c.pdf

 

2.  The FDA Prodisc-L Supplemental Information states:     The following potential adverse events (singly or in combination) which may be expected to occur, but were not observed in the clinical trial, could also result from the implantation of the PRODISC®-L Total Disc Replacement:  -> Facet joint degeneration

 

3.  The FDA Prodisc-L Supplemental Information states:  “Additionally, one PRODISC®-L subject underwent revision because the polyethylene inlay had been inserted backwards; and one PRODISC®-L subject underwent posterior supplemental fixation (fusion) for facet disease at the implanted level”

 

 

 

Many articles have been written regarding the financial ties between Doctors and Big Med.  Various investigations have ensued, indictments and fines levied, and calls for more transparency – some in the form of CIA’s (Corporate Integrity Agreements).  The FDA’s policies have come under scrutiny, and concerns have been raised about surgeons who invested in the devices they were supposedly double-blind, objectively testing.

However, from the ‘lay’ patient’s point of view, whom simply wants to know if a medicine or device will help them, the waters have become exceedingly more murky and dangerous.  She has been told that the FDA does not have any rules against surgeons investing in the devices they test – and even when they are caught red-handed concealing those back-room deals, the trial data is still considered valid.  She no longer trusts the FDA.  She has learned that many, many surgeons commonly receive kick-backs, stock-options and exorbitant fees from what she calls ‘The Pushers’.  She can not trust surgeons.   She learns that the editor of a journal (Spine Journal) was highly compensated by a device maker – and the published data has potentially been skewed.   She can not even trust the journals.   She had learned that the Device Makers (Synthes) have circumvented the FDA trials process, leading to the deaths of several unsuspecting experiment subjects.  Even deaths are hardly of concern.   After learning this, she might turn to the public forums, to try to get the unbiased advice of her peers.  Too late, she learns that the surgeons have cast their long shadows over those sources as well – to the extent that many failure cases have been banned and cleansed from the sites.   

In the end, the only thing she has learned, is that everything she has read is manipulated by the perversion of medicine for personal profit.

 

Hopefully, the following will shed some light on the shadier back-side of this ‘medicine’

 

I.        RECORD TIME TO FDA TRIALS

1.           How did the Prodisc attain FDA clinical trial status in record time?  (EU Data)

2.           Is the E.U. Data valid, unbiased and consistent with other trial data?

3.           Are there other concerns regarding Dr. Bertagnoli’s practice and claims?

4.           Were the authors of the E.U. trials financially motivated?  What were the motivators?

5.           Was Dr. Bertaganoli also and investor with the V-Bros?

6.           Has a Synthes Surgeon Trainer, denied any error with a patient, while many of his peers found her contraindicated?

II.       COMPROMISED FDA TRIALS

7.           Were many of the investigators in the Prodisc FDA trial financially motivated?

8.           Did Synthes reveal to the public that trial data was incomplete?

9.           Has the Prodisc TDR been subjected to standard U.S. FDA clinical trial analysis?

10.         How did the the Charite’, receive FDA approval? (whose FDA approval lead to the Prodisc-L recieving ‘ME TOO’ FDA status)

11.         Is it possible that the Prodisc Vs. Fusion trial experiments were influenced by the investigators?

12.         Why has the FDA not revoked the PMA (Pre-Market Approavable) Letter to Synthes on the Prodisc ...

13.         Has the FDA approved other ADR devices with questionable qualifications?

14.         Is the U.S. FDA capable of keeping up with the globalization of medical experimentation?

15.         Does the FDA require truly scientific data in the evaluation of device performance?

III.           PRODISC DESIGN ISSUES

16.         Do the biomechanics of the Prodisc-L replicate those of the natural spine?

17.         Does the Prodisc design, with it’s Center of Rotation in the center of the Ball, induce abnormal forces on the facets?

18.         The Prodisc inlay sizes are limited to 10mm, 12mm and 15mm in height.  Does this match all physiologies?

19.         Do the Prodisc’s Keels create a risk of Vertical Split Fractures?

20.         Do the biomechanics of the Prodisc-L contribute to A/P shear, such that the Poly core can be dislodged?

IV.          QUESTIONABLE CLAIMS OF PERFORMANCE

21.         Does the Prodisc-L Device restore or maintain natural motion?

22.         Has the Prodisc been proven to mitigate adjacent segment degeneration?

23.         Has Fusion been shown, by at least one unbiased surgeon, to have better outcomes than Prodisc at 6 months?

24.         Is there evidence to contradict the findings of the (financially motivated) Prodisc FDA examiners (aka physicians)?

25.         Has the FDA found the Prodisc to be superior to best-in-class Fusion techniques:

26.         Has any literature and trial review found a clear, scientific basis of superiority of Prodisc over latest fusion (rhBMP) methods?

27.         Given their insider-knowledge on the Fusion vs. Disc Replacement, what do spine surgeons choose?

28.         Have various insurance investigators found the Prodisc trials insufficient, and issued ‘non coverage’ notices?

V.      LIFE-THREATENING ISSUES

29.         Have any trial results suggested that the Prodisc-L induces, or contributes to, facet degeneration?

30.         Is facet degeneration a leading cause of Revision?

31.         Is a late-stage revision of a Prodisc-L at L4/5 potentially life-threatening?

32.         Is the longevity and durability of the Prodisc known to last a lifetime? (ie, will they need a life-threatening revision?)

33.         Have the dangers of the Prodisc TDR been equitably communicated by the manufacturer?

34.         Does the manufacturer of the Prodisc provide a Warranty on the device?

VI.          MARKET MAKERS

35.         Is it possible that U.S. patients who go to Germany for a Prodisc, might be used for training and experimentation?

36.         Does the manufacturer of the Prodisc-L promote the use of patients for hand-on Surgeon training?

37.         Is it possible that a Synthes Consultant surgeon is implanting Prodiscs into 90% of patients, while 7% are indicated?

38.         Has a Synthes Consultant Surgeon been using patients to expand the envelope of selection?

39.         Does the Device Manufacturer illicit false fear, in referring to iliac crest harvesting?

40.         Do public forums inequitably promote the ADR devices, while banning failure cases

41.         Are financially interested spine surgeons involved in the selection of articles posted to journals?

VII.         CRIMINAL INDICTMENTS, LAWSUITES AND SHADY DEALS

42.         Is there a lawsuit regarding the Prodisc / FDA fraud still in court?

43.         Would the Viscogliosi investors have recouped their investments and more, if the Prodisc FDA trials had failed (and $175 Million not awarded)?

44.         Did Venture capitalists recruit surgeons to invest in the Prodisc before the FDA trials, knowing there would be a huge payout?

45.         Are clinical trials being migrated to off-shore sites, which have lax regulations, and little patient protection?

46.         Is the Device Maker, Synthes, under a Corporate Integrity Agreement (CIA) due to Criminal charges?

47.         Has the company Synthes, been indicted for illegal experimentation without disclosure?

48.         Did the same Synthes executives, criminally charged for Norian XR, make it a company policy to obtain 300 to 400 ‘perfect {Prodisc} surgeries’?

VIII.        BLOODY FEEDING FRENZY

49.         How many surgeons and medical device manufacturers are involved in the feeding frenzy?

50.         Whom were the surgeons involved in the FDA Prodisc Trials?

IX.          Et cognoscetis veritatem et veritas liberabit vos!

51.         Did Dr. Charles Rosen’s advocacy for Ethics sink his nomination for Surgeon General?

52.         What, if anything, has the FDA done to implement the demands of the New Jersey AG.

53.         What, if anything, has Synthes done to comply with the terms of the Settlement with the NJ AG?.

54.         Are there other Prodisc Trials in other countries, by surgeons who do not have a vested interest?

55.         Whom is responsible for oversight of physician/company relationships? Who set the rules, laws?

56.         If a patient does thorough research, a complete comparative analysis, what have they learned?

57.         Why does Synthes not list all the FDA trial exclusions as contraindications?

58.         Why are the Prodisc Device Labeling, and Supplemental information conflicting?

X.      III. PRODISC TRIALS CONCERNS:

XI.          FURTHER STUDIES IN PROGRESS

XII.         REFERENCE ARTICLES

 

If you were a spine patient looking for a solution to your Degenerated Disc problem, and you had read that Dr. Bertagnoli had 96% success rates, and the FDA had completed a rigorous clinical trial of the Prodisc-L, and it was reported to be better than Fusion in all respects, would you opt to have Fusion or Prodisc-L?

However, if you had the answers to the following questions, would you lightly choose Prodisc-L?

===========================================================================

I.                    RECORD TIME TO FDA TRIALS

1.       How did the Prodisc attain FDA clinical trial status in record time?  (EU Data)

§  “In order to evaluate and document the long-term clinical safety and preliminary efficacy of the Prodisc-L to justify a U.S. pivotal clinical trial, Spine Solutions conducted a retrospective study of all patients (64) implanted with Prodisc-L.” … "Dr. Raymond Linovitz, San Dieguito Orthopaedics, Encinitas, CA, a spine surgeon was used as an independent evaluator of the radiographic and clinical information."

§  “92.7% of the patients reported they were satisfied or entirely satisfied with the procedure.”

§  “Marnay recently reported a 7-11-year follow-up on 95% of patients still living and found that 75% of them reported good-to-excellent results:”    http://www.medscape.com/viewarticle/558633

o    Note the correlation of Independent Surgeon above, and the list of surgeons investing in the Prodisc:

§  http://www.ethicaldoctor.org/articles/nytimes3.htm

§  Money Invested (In Prodisc) through Viscogliosi Brothers: Raymond J. Linovitz :  $50,000

o    (A retrospective study sponsored by the company that stood to gain $350 Million, with an ‘independent’ Surgeon who invested $50K?)

2.       Is the E.U. Data valid, unbiased and consistent with other trial data?

§  http://www.medscape.com/viewarticle/557712_4 Bertagnoli et al reported 97% success rates for monosegmental disc replacement procedures with ProDisc II.[27] In a recent report, the same authors published a similarly high success rate of 92% to 96% for multisegmental TDR (10× bisegmental, 15× 3-segmental)[26] and also described 4- and 5-level TDR procedures previously.[38] However, carefully selected other studies[8,16,28] as well as prospective randomized control trials could not confirm such high success rates, even for highly selected monosegmental cases.[9,13,17,18]

§  http://www.medscape.com/viewarticle/542479_4 "Bertagnoli and Kumar have described 98.2% good and excellent results with only 1 complication in 108 patients with different indications for TDR.[9] However, the authors did not provide scientific evidence for their conclusion on so-called prime, good, borderline or poor indications for TDR, nor did they describe a statistical basis on how poor indications were evaluated when almost all patients treated showed excellent results."…FDA-supervised investigational protocol studies as well as carefully selected other studies could not confirm such high success rates.[10,15,16,27,29,34]

3.       Are there other concerns regarding Dr. Bertagnoli’s practice and claims?

4.       Were the authors of the E.U. trials financially motivated?  What were the motivators?

BERTAGNOLI, RUDOLF (Germany (Federal Republic of))
MARNAY, THEIRRY (France)
ECKHOF, STEPHAN (Germany (Federal Republic of))
MAGEE, FRANCIS P. (United States)
(73) Owners: (Country) SPINE SOLUTIONS INC. (United States)

 

5.      Was Dr. Bertaganoli also an investor with the V-Bros?

o   “The influence of Rudi Bertagnoli, chief of spine service, Klinikum, St. Elizabeth, and codeveloper of the ProDisc, was everywhere, and his ProDisc work will likely kick-start lumbar arthroplasty throughout the world..”  http://www.vbllc.com/news_008.html

o   'Spinal Partners III Medical Advisory Board' : Lists Dr Bertagnoli and Dr. Anthony Yeung.   http://www.vbllc.com/pdfs/milestones38.pdf

6.       Has a Synthes Surgeon Trainer, denied any error with a patient, while many of his peers found her contraindicated?

 

II.                  COMPROMISED FDA TRIALS

7.       Were many of the investigators in the Prodisc FDA trial financially motivated?

o    According to the landmark paper produced by the trial participants, there are no disclosures to be made.

o   http://www.medscape.com/viewarticle/558633

o   The 23 authors include: Jack Zigler, MD; Rick Delamarter, MD; Jeffrey M. Spivak, MD; Raymond J. Linovitz, MD, FACS; Guy O. Danielson III, MD; Thomas T. Haider, MD; Frank Cammisa, MD; Jim Zuchermann, MD; Richard Balderston, MD; Scott Kitchel, MD; Kevin Foley, MD; Robert Watkins, MD; David Bradford, MD; James Yue, MD; Hansen Yuan, MD; Harry Herkowitz, MD; Doug Geiger, MD; John Bendo, MD; Timothy Peppers, MD; Barton Sachs, MD; Federico Girardi, MD; Michael Kropf, MD; Jeff Goldstein, MD

o   Note:  The Sidebar: Key Points states:

1.       * ProDisc®-L total disc replacement has been shown to be safe and efficacious for the treatment of 1-level degenerative disc disease.

2.       * These data represent class I data.

3.       * ProDisc®-L total disc replacement was found to be superior to circumferential fusion by multiple clinical criteria.

4.       * ROM was maintained within a normal functional range in 94% of ProDisc®-L total disc replacement patients.

5.       * There were no major complications in either group in this study.

o   Note, in the ‘Discussion’ section, the authors list many benefits and superior facets of Prodisc TDA over Fusion.  However, they state “Finally, narcotics use decreased by over 50% in successful patients.”   This statement does not differentiate between Prodisc and Fusion patients.  Whereas, it is reported in the FDA report:  “Of patients achieving overall success at 24 months, only 31% of control and 39% of investigational patients remained on narcotics.”   It would appear to the lay reader, that the authors have taken this data point, twisted it to represent a positive, and covered up a negative for the Prodisc.  Given such ‘statistics’, this begs the question of how much influence the surgeons had over other statistical data gathering, analysis and presentation.

o    According to a NY Times article, Financial Ties are Cited as Issue in Spine Study, which apparently references information obtained from discovery in a lawsuit against one of the investigators, at least 10 of the above surgeons held significant financial interest in the device’s maker, Spine Solutions, through funds operated by the Viscogliosi Brothers.

o   Richard A Balderston:     $250,000                              Raymond J. Linovitz:       $50,000

o   Frank P. Cammisa Jr.:     $250,000                              Jeffrey M. Spivak:            $50,000

o   Guy O. Danielson III:       $200,000                              Jack E. Zigler:                      $25,000

o   James F. Zucherman:     $165,000                              Kevin Foley:                       $20,000

o   Thomas J. Errico:              $100,000                              Timothy A. Peppers        $20,000

o   Note: Thomas J. Errico’s involvement is unclear, as he is not listed as an author.  However, the paper notes 38 surgeons and 17 sites involved.

o    According to a May 2011 Press Release

o   The New Jersey Board of Medical Examiners reprimanded Thomas Errico, Jeffrey Goldstein and Richard Balderston for not disclosing to their research institutions their financial interests in clinical studies of Synthes' ProDisc spinal device in which they participated. Errico and Goldstein also were ordered to pay civil fines.

o   "The undisclosed conflicts of interest on the part of these doctors undercut public trust in the medical profession," New Jersey Attorney General Paula Dow said in a statement

o    Senator Charles Grassley called the case a matter of Fraud to the consumer - which it certainly is.

o   http://www.nj.gov/oag/newsreleases09/050509-FDA-letter.pdf
"The investigation revealed that a majority of the physicians who participated in these clinical trials had significant investments in the products — investments that would have been worthless had the product failed to obtain regulatory approval from the FDA. And, the investigation revealed that Synthes, which acquired ProDisc while the clinical trials were underway, failed to disclose these financial conflicts of interest to the FDA."

o   http://www.healthreformwatch.com/tag/prodisc/
"Notably, the state pursued the case as a matter of consumer fraud. The premise being that the failure to fully disclose such conflicts constituted such for both human trial subjects and the purchasing public."

o    ProDisc was developed by Spine Solutions Inc. with financing from a New York investment firm that offered the ProDisc clinical investigators investment opportunities in Spine Solutions and consulting contracts that included gifts of company stock and stock options. When Synthes bought Spine Solutions in 2003, it failed to fully disclose these conflicts of interest to FDA, which signed off on Synthes's applications for premarket approval of ProDisc despite “plainly inadequate” financial conflict disclosures.” NJ Attorney General,  www.policymed.com article

o    "As things stand, the public often has no knowledge that a ‘clinically tested and recommended' medical device was evaluated and endorsed by people with a financial stake in seeing it sell,  This is simply wrong and it must stop."  - NJ Attorney General, Anne Milgram, 05/05/2009

8.       Did Synthes reveal to the public that trial data was incomplete?

o   http://blue.regence.com/trgmedpol/surgery/sur127.html

·         There is only one randomized, controlled trial of sufficient duration to begin to measure long-term health outcomes. (17) Five-year outcomes were reported on a subset of the original 375 patient cohort in the two-year CHARITE IDE trial. Of the initial 14 investigational sites, six sites declined participation in the five-year continuation study, and an additional eight patients were excluded from analysis. Of the remaining 233 patients, the five-year assessment included only 57% (n=133), or 30% of the original study population. Given the limitations of the original IDE trial and the 43% to 70% loss to follow-up, the results from the five-year follow-up cannot be interpreted.  The remaining published randomized trials of TDR in the lumbar spine do not permit conclusions regarding long-term health outcomes. (12-16) Data from these studies are unreliable due to the following design flaws which undermine the validity of the results:

1.       The maximum study duration was limited to two years. All of the authors of articles related to the FDA trials for the CHARITE and ProDisc-L discs specifically noted that two years follow-up does not allow conclusions about the impact of TDR on adjacent-level DDD compared with fusion.

2.       In the pivotal trial for the ProDisc-L, conclusions are not possible due to missing data. Eleven percent of fusion patients and 7.5% of ProDisc-L patients were excluded from the results. No intent-to-treat analysis was provided.

9.       Has the Prodisc TDR been subjected to standard U.S. FDA clinical trial analysis?

o    According to an article:  http://www.ethicaldoctor.org/articles/thestreetbacklash.htm 

§  In early 2005, when Synthes submitted the Prodisc study to the F.D.A. as part of the company’s application for approval, it used results for 162 patients who had received the device and 80 who had spinal fusion surgery.

§  The results did not include 50 Prodisc patients who were considered 'training cases' - surgeries performed to let doctors learn how to implant the devices. Such training is fairly common in device trials.

§  An additional 21 patients, about 10 percent of those studied, were also excluded from the reported results.

§  A Medicare official, Dr. Steve Phurrough, said 10 percent was unusually high. While it is impossible to tell what the outcome of the study would have been otherwise, Dr. Phurrough said, 'it gives us pause.' The agency decided last August not to cover the disk for most Medicare patients.

§  { 50 + 21 = 71 patients excluded.  71/162 = 43.8%.  The FDA Trials reported 63.5% overall success for the 162 Prodisc patients. Thus, 59 of the 162 Prodisc patients were ‘failures’.  Allowing for possible failure on the 71 excluded patients, then the total possible failures would be 59 + 71 = 130.   The total Prodisc patient cohort was potentially 162 + 71 = 233.   The overall Prodisc success rate would then be: (233-130)/233 = 44%. The Fusion patients, which did not have any mysterious exclusions, had an FDA success rate of 45.1%. }

§  {Opinion:  Counting the 71 exclusions as failures, the Prodisc total potential cohort would have a 44% success rate, while the Fusion control patients had a 45.1% success rate.}

 

10. How did the the Charite’, receive FDA approval? (whose FDA approval lead to the Prodisc-L recieving ‘ME TOO’ FDA status)

o    {Note, the Prodisc-L TDR received FDA IDE trial status based on the "ME TOO" rule, where the pioneering device was the Charite’ from J&J}

o    The Charite’ was compared to the BAK fusion.  "The stand-alone BAK is a failed operation; it hasn't been done in years," Rosen says. "So they picked the worst possible operation to compare these things to." Dr. Charles Rosen ( interview )

o    An FDA transcript shows that the agency's own statistician portrayed the study as "strongly biased" in favor of Charite."

o    "It should be noted that the rate of adverse events was higher in the training subjects group compared to the randomized subjects in the study," Serhio del Castillo, one of the FDA's lead reviewers for the disc, said during the hearing process. "However, please note that the training subjects were not included in the assessment of safety." … “Whenever a significant percentage is excluded, for any reason, it leaves a reviewer skeptical of the data analysis."

o    Brent Blumenstein -- a voting member of the FDA advisory panel -- specifically complained about omitted patients during the Charite hearing. "The sponsor's definition of the ITT (intent-to-treat) population ... is incorrect because it deletes randomized patients," Blumenstein said. "To modify the definition of ITT or analysis by arm by deleting patients is tantamount to saying someone is only partly dead."

o    "Any prudent person, who does not have a financial conflict or industry tie, would reasonably conclude that their safety and effectiveness has not been proven by the FDA," {regarding J&J Charite’} "These artificial disc replacements should be recalled by the FDA to protect the American public." " Dr. Charles Rosen,

o    http://www.ethicaldoctor.org/articles/thestreetbacklash.htm 

o    Some doctors decry J&J's new metal disc, known as the Charite, which has been implanted in the spines of several thousand patients. It was approved by regulators after a trial involving only 304 patients--and  only 36% of them fared well enough to get off narcotic painkillers.

o    http://www.forbes.com/forbes/2006/1127/094_print.html 

o    Judge Susan Garsh ruled against DePuy's claim that the company should be protected from the legal action since the FDA approved the device, a legal defense known as preemption.  "there is evidence to support the device does not perform in the manner which DePuy represented to the FDA that it must perform."  

o    http://www.hbsslaw.com/cases-and-investigations/DePuy_lawsuit.htm 

o    Lawsuits against the J&J Charite:

o    Pete Flowers, 200 clients, claims Charite is defective and that J&J improperly marketed the device and did not adequately warn of the disc's dangers.

1.       http://www.foote-meyers.com/articles/DePuy.html  

o    Pulaski and Middleman law,  Houston, Texas  350 patients

1.       http://www.pulaskilawfirm.com/charite_attorney.aspx 

o    Hagens Berman Sobol Shapiro, 100 clients

1.       http://www.hbsslaw.com/DePuy_Investigation.htm

11.   Is it possible that the Prodisc Vs. Fusion trial experiments were influenced by the investigators?

o   The surgeons had access to both the Prodisc and Fusion patients. 

§  Has ANYONE checked the fusion patient results against other (pro-fusion) trial data - of the exact same fusion system? (No)

§  The clinically significant margin of error was 12.5% for the given cohort of 216 (144 Prodisc subjects and 72 fusion), based on Blackwelder methodology (Zigler et al  2007).  If one were to exclude the patients who were treated by financially leveraged surgeons, (lets say half, or 108), then the variance goes way up!   The trial is essentially invalidated.

o   Four Obvious ways the surgeons could influence the trials:

1.       Selection of patients:  If surgeons were involved, they could easily cherry-pick the best candidates for Prodisc, given the obvious higher restrictions on Prodisc.  Naturally, the more problems a patient has (ie, other levels going bad), the less likely they are to be optimal outcomes.  In fact, Dr. Hochshuler (TBI), tried to recruit Anastasia for the Charite trials in 2005.  He was complimentary over about slender figure ... noting how she would be a perfect candidate.  Clearly, the surgeons were involved in the patient selection … at least for the Charite FDA trials.

      • The randomization was held by the sponsor and disclosed to the site only after individual patient enrollment.
      • In: Results of the Prospective, Randomized, Multicenter FDA IDE Study, Zigler et. al. 2007.

2.       Performance:  Surgeons could have easily performed less well, slower, with less fervor, on the Fusion patients.  At least half of the equation can be skewed.

3.       Patient steering:  Surgeons could influence patients, by letting the Fusion patients know their fellow Prodisc recipients were all on doing great.  Fusion patients would be biased negatively.

4.       Post-surgery data collection:  Patricia Kennedy "I'm filling out a questionnaire and saying that my pain level is an '8' on a scale of one to 10," with 10 being the worst, Kennedy says. "And my doctor is writing down that I have 'mild pain.' I don't think so."   Hope Slips for Disc Implants

(Clearly, the surgeons were involved in the back-end data collection as well.  Ergo - all surgeons could do the same.)

o   FDA Trial reports 45.1% success for Circumferential fusion patients, 63.5% success for Prodisc-L
          This includes a Fusion Status success rate of 97.1% - which is significantly below current reports on fusion success rates.

o   FDA Trial reports, Table 3 Adverse Events,  Events generally ‘iatrogenic’  (recall, financially leveraged surgeons benefited from these adverse events)

1.       Dural Tear:  Fusion 2,  Prodisc 0

2.       Clinically signification blood loss:  Fusion 2,  Prodisc 0

o   Would YOU, if you needed a Fusion/Prodisc, volunteer for the Fusion side of it?  Would you be biased?

o   The fact that most of the surgeons involved in the FDA trials were financially invested SHOULD disqualify any data which can be manipulated by the surgeons. Unless, of course, we live in a corrupt back-water lawless country where money rules.

12.   Why has the FDA not revoked the PMA (Pre-Market Approavable) Letter to Synthes on the Prodisc ...

o   …  if they and the Fed know for a fact that half of the surgeons were financially invested in a positive outcome?

13. Has the FDA approved other ADR devices with questionable qualifications?

o   Charles Rosen, founding director of the University of California-Irvine Spine Center, officially asked the FDA to withdraw the discs from the market months ago. He first aired his concerns about the Charite in an article published by TheStreet.com back in early May. He noted that the Charite had been tested against a failed operation, that it still had weak results and that it required life-threatening revisions in the case of failures -- and, ultimately, he questioned why the device had ever won approval in the first place.

o   Hope Slips for Disc Implants, 12/22/2005

14.  Is the U.S. FDA capable of keeping up with the globalization of medical experimentation?

o   This story reveals the manner in which the FDA is gravely underfunded, understaffed, and disempowered by globalization:

o   http://www.vanityfair.com/politics/features/2011/01/deadly-medicine-201101?currentPage=all 

1.       A loop-hole in FDA regulations allows that if a study conducted in the USA finds no benefits, trials from abroad can be used in their stead.  These off-shore sites are quaintly called ‘Rescue Countries’.

2.       Trials of the the drug Ketek were approved, even while serious adverse reaction reports rolled in.  4000 children were exposed.

3.       Under pressure from Congress, the FDA asked the trial be stopped.  A year later, the FDA finally slapped a ban on the drug – only one day before a Congressional hearing.

4.       “In one study, the agency failed to document the financial interests of applicants in 31 percent of applications for new-drug approval. Even when the agency or the company knew of a potential conflict of interest, neither acted to guard against bias in the test results.”

5.       The FDA has “no mandatory public record of the results of drug trials conducted in foreign countries. Nor is there any mandatory public oversight of ongoing trials. If one company were to test an experimental drug that killed more patients than it helped, and kept the results secret, another company might unknowingly repeat the same experiment years later, with the same results.”

6.       In 2008 the F.D.A. inspected just 1.9 percent of trial sites inside the United States to ensure that they were complying with basic standards.  It visited only 45 of the 6,485 locations of trials conducted outside the USA. (0.69 %)

7.       The FDA failed to pull Avandia, even after estimating that it caused 83,000 heart attacks, and it was banned by other countries.

8.       In 2009 the Government Accountability Office conducted a sting operation, winning approval for a clinical trial involving human subjects; the institutional review board failed to discover (if it even tried) that it was dealing with “a bogus company with falsified credentials” and a fake medical device. This was in Los Angeles.

o   "I think that we have already all pretty much agreed that two years is probably not a safe length of time to follow these patients," said Maureen Finnegan, a voting member of the {FDA} advisory panel with financial ties to the industry.  http://www.ethicaldoctor.org/articles/thestreetbacklash.htm

15. Does the FDA require truly scientific data in the evaluation of device performance?

o   CFR 860.7(c)(2) identifies the following sources of valid scientific evidence:

1.       well-controlled investigations

2.       partially controlled studies

3.       studies and objective trials without matched controls

4.       well documented case histories conducted by qualified experts reports of significant human experience with a marketed device from which it can be fairly and responsibly be determined by qualified experts that there is reasonable assurance of the safety and effectiveness of a device under its

o   One might ask, if a study participant is financially invested in a device under investigation, is it not reasonable to assume that ‘partially controlled’, ‘without controls’ and cherry-picked ‘case histories’ might be unfairly biased?

III.                PRODISC DESIGN ISSUES

16.   Do the biomechanics of the Prodisc-L replicate those of the natural spine?

o    NOTE, WITH BALL-AND-SOCKET, THE FACETS ARE FORCED INTO A HORIZONTAL SHEAR, WHICH IS NOT SEEN IN NORMAL DISC BIOMECHANICS

o   

o    Ref:  Huang et al.  The Implications of Constraint in Lumbar Total Disc Replacement,  Journal of Spinal Disorders and Techniques, Vol 16, No. 4, pp 412-417.

(Would you be concerned that the prodisc exceeds by 2x or more, natural kinematics, in all dimensions?

 

1.      Does the Prodisc design, with it’s Center of Rotation in the center of the Ball, induce abnormal forces on the facets?

o   According to the expert opinion of Dr. Andre’ van Ooij,

·         “In our patient group, we saw numerous patients with very severe arthrosis of the facet joints years after the disc replacement. They had developed this arthrosis with grossly subsided prostheses; but also when there was a perfect position of the prosthesis in the intervertebral space, this arthrosis could be present. It seems very unlikely that the Charite´ or other models of disc prosthesis mimic the normal intervertebral movement pattern so closely that normal facet joint movements and loading are possible. Even Lemaire et al24 had some concerns in this matter. The center of rotation for flexion-extension movements in physiologically normal-functioning segments is positioned posteriorly in the disc space.12 With the Charite´ and also the Prodisc prosthesis, this center is centrally or slightly anteriorly positioned, depending on the accuracy of insertion. It is logical to assume that normal intervertebral motion is not possible with such a prosthesis.”

·         van Ooij A, Oner FC, Verbout AJ. Complications of artificial disc replacement: A report of 27 patients with the SB Charite disc. J Spinal Disord Tech. 2003;16(4):369-383.

o   If the natural disc has a COR in the posterior-center of the disc, then the arc of rotation at the facets is proportional to the distance from the facets to the COR.  The Prodisc, with its COR in the center of the lower vertebra, has an arc of rotation proportional to this much larger distance

·         Consequences_of_Prodisc_hyperdynamics_in_a_collapsed_disc_space_with_secondary_facet_arthrosis.htm

·         FACET_MECHANICS  Proves A/P translation of Prodisc in Flexion/Extension image overlays

  Prodisc_ARC_2x.jpg

BLUE:  Normal Center of Rotation

RED:  Prodisc Forced Unnatural Center of Rotation (2X ARC at Facets)

2.       The Prodisc inlay sizes are limited to 10mm, 12mm and 15mm in height.  Does this match all physiologies?

(Assuming you are a petite woman - would you want a device which is 11mm tall, stuck into your 8mm disc space?)

 

3.      Do the Prodisc’s Keels create a risk of Vertical Split Fractures?

o   Vertical Split Fracture of the Vertebral Body Following Total Disc Replacement Using ProDisc: Report of Two Cases

o   Journal of Spinal Disorders & Techniques: October 2005 - Volume 18 - Issue 5 - pp 465-469

o   "The keel design of the ProDisc has the disadvantage that it can cause a vertebral body fracture in some patients."

 

4.      Do the biomechanics of the Prodisc-L contribute to A/P shear, such that the Poly core can be dislodged?

o   “We postulate that in our patient, the wedge shape of the implant with a contribution solely from the superior component (11° of lordosis) may have been responsible for increased shear forces across the segment, resulting in stress fractures of the pedicles and subsequent dislocation of the polyethylene inlay.   … The manufacturers are currently investigating a new version of the prosthesis with the lordosis also included into the inferior plate, which is not yet available presently.”

·         Bilateral Pedicle Fractures Following Anterior Dislocation of the Polyethylene Inlay of a ProDisc® Artificial Disc Replacement A Case Report of an Unusual Complication Philip Mathew, MRCS,* Mark Blackman, FRCS,* Sridhar Redla, MD, FRCR,† and Ahmed A. Hussein, FRCS*

    

I.                    QUESTIONABLE CLAIMS OF PERFORMANCE

5.      Does the Prodisc-L Device restore or maintain natural motion?

o   ProDisc II implant failed to restore normal segmental rotational motion in the sagittal plane, especially at L4-L5 and L5-S1. In the majority of cases, it amounted to less than 45% of the normal range.

·         http://www.ncbi.nlm.nih.gov/pubmed/16816770  Leivseth G, Braaten S, Frobin W, Brinckmann P.

·         Faculty of Medicine, Institute of Neuromedicine, Norwegian University of Science and Technology, Department of Physical Medicine and Rehabilitation, St. Olav's University Hospital, Trondheim, Norway.

6.       Has the Prodisc been proven to mitigate adjacent segment degeneration?

7.       Has Fusion been shown, by at least one unbiased surgeon, to have better outcomes than Prodisc at 6 months?

o    Delamarter, one of the top spine surgeons in the USA, released a study in 2003, which indicates:

o   Fusion patients did better than Prodisc, after 6 months

o   

o    http://spinesupport.org/papers/2003_delamarter.pdf

8.       Is there evidence to contradict the findings of the (financially motivated) Prodisc FDA examiners (aka physicians)?

o    An analysis of papers by the Congress of Neurological Surgeons, notes that while the Prodisc investigators suggest Prodisc patients fared better, “Others have found that Prodisc and fusion patients reach the same levels of improvement in ODI and VAS ratings after 1 year, but that the arthroplasty patients arrive at those endpoints faster than fusion patients (4).”

o    Trial Results: Narcotic Use. Before surgery, narcotic usage was 76% in the control group and 84% in the investigational group. Of patients achieving overall success at 24 months, only 31% of control and 39% of investigational patients remained on narcotics. In patients not achieving overall success, narcotic usage remained relatively unchanged (76% control and 79% investigational).

o    { Interpretation:  In the category that Surgeons could not influence – narcotic use – the Fusion/Control patients ended up better off}

9.       Has the FDA found the Prodisc to be superior to best-in-class Fusion techniques:

o   BCBS Review:  For a noninferiority comparison, the investigational treatment where the results are not inferior to another treatment is generally considered acceptable if there are other obvious advantages. For the lumbar artificial disc, the advantages are not obvious. Although the disc has been in use in Europe for over 10 years, the design promise of spinal mobility leading to improved outcomes over fusion remains unproven. The ProDisc®-L noninferiority trial has as a comparator 360 degree circumferential fusion. However, it is not clear that a trial designed to demonstrate noninferiority is valid given that the effectiveness of circumferential fusion in degenerative disc disease is not well-established in comparison to conservative treatment. The choice of a clinically relevant difference is crucial in noninferiority and equivalence trials (Gotzche, 2006) however; there is no justification for the noninferiority margin in the ProDisc®-L trial. Knowledge of the effectiveness of circumferential fusion is lacking.

o   Results report of the Prodisc Trials, J. Spine. 2007;32:1155-1162.

·         All results were statistically better for the patients receiving the ProDisc-L than for the patients who had fusion with the exception of the SF-36 and the question regarding whether the patient would undergo the same surgery.”

·         {What the hell does that mean!?  Everything that the Doctor’s measured was better for the Prodisc - but the patients opinions were …. Ummm, confused?}

·         {Recall, this whole trial is suspect given that most investigators were financially invested in acquiring this positive report}

 

10.   Has any literature and trial review found a clear, scientific basis of superiority of Prodisc over latest fusion (rhBMP) methods?

o   CIGNA Coverage Statement

o   Freeman and Davenport (2006), conducted a systematic review of the current evidence for total disc replacement using the Charité or ProDisc devices. Their search produced two randomized trials, two systematic reviews, seven prospective cohort studies, eleven retrospective cohort studies and eight case series. The level of evidence that was assigned to these studies was in accordance with the Center for Evidence Based Medicine, Oxford, UK. The authors concluded that the longterm benefits of TDR in preventing adjacent disc degeneration is unknown; the role of two- or multi-level TDR remains unproven; the role of arthroplasty adjacent to a TDR is unproven; the complications of TDR may not be known for many years; and well-designed prospective RCTs are needed.

o   Patient Outcomes

o   "In December of 2001 Doctors at the New Hampshire Spine Institute reported on a series of 22 patients who had undergone spinal fusion using rhBMP-2 through a laparoscopic approach. The results were reported in the journal Spine 2001; 26:2751-2756. The research was done as part of a larger multicenter study sanctioned by the FDA. The average hospital stay was only 1 day, shorter than for any other reported fusion procedure. Of the 21 patients who completed the study; all of them reported improvement in back pain, leg pain, and function. They all achieved a solid fusion by 6 months and all of them were able to return back to work. This was the first study on spinal fusion that demonstrated a 100% success rate for both clinical and radiographic outcome."  http://www.spineuniverse.com/displayarticle.php/article1708.html 

o   { it is not a secret that rhBMP2 has lead to a dramatic improvement in Fusion success rates. }

 

11.   Given their insider-knowledge on the Fusion vs. Disc Replacement, what do spine surgeons choose?

o   At a recent meeting of the American Orthopaedic Association, surgeons were asked what treatment they would prefer for themselves if they had unrelenting low back pain from a single degenerative disc. 

o   Of the 133 surgeons surveyed(1), only 7 percent stated that they would choose disc replacement. So what would the surgeon's choose? About 47 percent said they would choose spinal fusion and close to 47 percent would choose chronic pain management.

o   Why wouldn't these surgeons elect to have disc replacement? Well, 59 percent felt unsure about the long-term durability of the implants, 30 percent expressed concern that discs will be over-used, and 9 percent worried about the surgical complications.

o   http://www.centerforspinecare.com/approach/dynamicstabilization.html

12.   Have various insurance investigators found the Prodisc trials insufficient, and issued ‘non coverage’ notices?

o    http://www.healthpointcapital.com/research/2007/05/29/on_the_cms_lumbar_disc_non_coverage_proposal/

o    http://blue.regence.com/trgmedpol/surgery/sur127.html
In the pivotal trial for the ProDisc-L, conclusions are not possible due to missing data. Eleven percent of fusion patients and 7.5% of ProDisc-L patients were excluded from the results. No intent-to-treat analysis was provided

II.                  LIFE-THREATENING ISSUES

13.   Have any trial results suggested that the Prodisc-L induces, or contributes to, facet degeneration?

§  Shim et al (2007):  Degradation of disc degeneration was found at the adjacent level above the index surgical site in 19.4% of the Charité implants and 28.6% of the ProDisc implants. The authors did not find this difference to be statistically significant. They concluded that, while the clinical outcomes were fairly good, the facet joint of the index level and the disc at the adjacent level showed an aggravation of the degenerative process in a significant number of patients, regardless of the device used.

14.   Is facet degeneration a leading cause of Revision?

o   Van Ooij and colleagues report that one of 27 patients studied had a spontaneous arthrodesis at the level of the ADR, and 11 had facet arthrosis at either this or another level (40.7% of failure cases).

1.       J Spinal Disord Tech. 2003 Aug;16(4):369-83, van Ooij A, Oner FC, Verbout AJ. Department of Orthopaedic Surgery, University Hospital Maastricht, Maastricht, the Netherlands

15.   Is a late-stage revision of a Prodisc-L at L4/5 potentially life-threatening?

o    “Removal of an infected or dislocated TDR is a life-threatening procedure, and several deaths have already occurred in the United States. Any reoperation places the great vessels at risk.” [5] http://www.aaos.org/news/bulletin/sep07/cover2.asp

o    “Removal of the prosthesis is dangerous, and posterior fusion without removing the prosthesis will give suboptimal results.” [1]

o    "Dr. Kurtz, who has consulted for Medtronic and other medical-device makers, says many younger patients who are getting artificial disks may need a life-threatening operation to remove a worn disk in 10 years or less."  http://www.ethicalspinesurgeon.com/articles/WSJRosen.htm

o     “…Lumber artificial disc replacement will be subjected to a much steeper learning curve, the short and long-term outcomes may be marginal, and the revision for failed implants will be difficult and at times life-threatening” [3]

o     ‘Revision of Lumbar Total Disc Arthroplasty and Other Anterior Instrumentation, March 2008’ “ ...careful preoperative and intraoperative planning may minimize the life-threatening risks posed by reoperation”.  [4]

o    "…Revision surgery for a failed disc arthroplasty is life threatening. Dealing with the scarring around the great vessels is the main challenge...”  “Removal of the implant is a life-threatening surgery because of the extensive scarring of the great vessels..” [6]

o    “Revision surgery with explantation of a lumbar TDR carries great risk to the major anterior vessels and is a potentially life-threatening procedure…" [7]

o    The article highlights “the difficulties and risks associated with the use of a repeat anterior approach for the revision of a ProDisc that has failed at the L4-5 level.” [8]

o    “…Five consecutive cases of prosthetic inter-vertebral disc displacement with severe vascular complications on revisional surgery are described. The objective of this case report is to warn spinal surgeons that major vascular complications are likely with anterior displacement of inter-vertebral discs…” [9]

o    “While initial complication rate were found to be low the mobility of the motion segment was not always retained, removal of the device was not always possible…”;  “..removal of such dislocated artificial discs is life threatening…” [10]

o    “Meanwhile, Andre van Ooij, a Danish surgeon who has tracked hundreds of the operations in Europe later offered evidence about the implant's drawbacks… “All of these patients have really terrible leg and back pain," said van Ooij. And "revision is dangerous and sometimes impossible” [11]

o    "Although some patients who have undergone spinal fusion surgeries need revision surgeries, they are generally less problematic than those after artificial disc surgery…..and the [artificial disc revision] surgery can be life-threatening due to the potential for blood loss and other complications" [12]

o    “The longevity of artificial discs is yet known… Revision disc replacement surgery will be a life-threatening operation.” [13]

o     “Most importantly, Peloza [John H. Peloza, M.D Texas] stressed…..revision surgery to remove the implant will be potentially life-threatening in every case," he explained. "And at present, there is no consistently successful strategy to deal with a failed implant." [14]

 

 

 

16.   Is the longevity and durability of the Prodisc known to last a lifetime? (ie, will they need a life-threatening revision?)

17.   Have the dangers of the Prodisc TDR been equitably communicated by the manufacturer?

o    Synthes Patient’s Brochure:  As with any surgery, there are some possible complications that can occur when you have total disc replacement surgery with the Prodisc-L implant” …

§  Need for additional surgery which could include removal of the Prodisc-L implant.

o    Prodisc's retroperitoneal implantation makes repeat anterior access Revision life-threatening.  Prodisc's retroperitoneal implantation makes repeat anterior access Revision life-threatening, especially at L4/L5 due to fibrous entrapment of the large iliac veins.  This danger is not revealed in Synthes' Prodisc Patient’s Brochure, However, revision tools are made available to surgeons.

o    Synthes report:  036.000.432.pdf "An indicated instrument set is available for any revisions to the Prodisc-L. Please contact your Synthes representative."

 

18. Does the manufacturer of the Prodisc provide a Warranty on the device?

o   Yes but only to the original purchaser of the device, e.g., the surgeon or hospital.

III.                MARKET MAKERS

19.   Is it possible that U.S. patients who go to Germany for a Prodisc, might be used for training and experimentation?

20.   Does the manufacturer of the Prodisc-L promote the use of patients for hand-on Surgeon training?

o    http://www.synthes.com/html/uploads/tx_synthevent/Overview_and_Information_Spine_Arthroplasty_courses_02.pdf

o    “One to two surgeries will be performed during the course. You can view the procedure via live transmission with excellent endoscopic imaging. Alternatively, participants will be invited to scrub in and assist the operating surgeon.”

21.   Is it possible that a Synthes Consultant surgeon is implanting Prodiscs into 90% of patients, while 7% are indicated?

o   Bertagnoli states to the Venture capitalists, Viscogliosi Brothers:

22.   Has a Synthes Consultant Surgeon been using patients to expand the envelope of selection?

23.   Does the Device Manufacturer illicit false fear, in referring to iliac crest harvesting?

o   In some brochures, Synthes suggests that patients may have to suffer from iliac crest (hip bone) harvesting ... which is not (in my knowledge) done in the trial fusions.  If it is, then it is certainly not the state of the art.
http://products.synthes.com/prod_support/Product%20Support%20Materials/Patient%20Guides/SPINE/SPPGProDiscL-J6356C.pdf

o   “The traditional method of treatment has been spinal fusion.  In spinal fusion surgery, the unhealthy disc is removed, the bones are fixed in position with implants, and bone graft is placed in the area.  In most cases, the bone graft is obtained from the patient’s hip bone through a separate incision.”

o   “A United States clinical trial established that patients receiving the Prodisc-L Total Disc Replacement achieved pain relief equal to spinal fusion while maintaining some motion in their spine in many cases.  It is believed that maintaining motion may allow your spine to remain healthier longer, but this has not been proven.”

o   “The Prodisc-L Total Disc Replacement surgery does not require a bone graft.  This means you may avoid the pain and healing time associated with the second incision that might be needed if you were to have a fusion procedure which required bone to be taken from your hip.”

o   (How many, if any, of the Fusion Control subjects were subjected to iliac crest bone harvesting?)

24.   Do public forums inequitably promote the ADR devices, while banning failure cases

o   “Industry and its consultants cultivate a public mind set for selling that which is propagated by direct patient advertising, media announcements touting medical breakthroughs, and vast use of the internet to plant information on searches and in chat rooms that are covertly sponsored by industry.

1.       http://aging.senate.gov/events/hr188cr.pdf

o   Prodisc failure cases regularly get banned from public spine-patient forums,

o   A petition with about 12 signees, objects to this practice - many of them banned from the forums, for their honesty and questions

o   Public forums are a major venue of promotion of international medical tourism, for example, ADR support . org, which is run by Richard Longland, aka  ‘Harrison’

o   Harrison is the Admin/Owner/Moderator of ADR support . org . 

1.       "Does this work also help Dr. Rosen gain other employment opportunities, e.g. as an expert witness?" (post)

2.       "I've read that docs like Rosen make some decent money testifying on spine-related cases." (post)

3.       "Dr. Rosen should be more careful about what he says and how his reputation may be tested with such statements!"  (post)

4.       "The Newsday article throws some salt on the wounds with the infamous Dr. Rosen (a paid Medtronic consultant)"  (post)

{ It is unlikely that Dr. Charles Rosen is a paid Medtronic consultant, since he heads up Ethical Spine Surgeons, which opposes such conflicts }

o   A full analysis of ADR Support dot org’s bias for preferred Devices and Surgeons has been compiled.  After it was posted to a yahoo site, Harrison asked the Yahoo admins to shut down the site – which they did according to their policy, that if anyone complains of ‘copyright infringement’, whether valid or not, the site goes down.  Thus, minor excerpts are presented here:

1.       “The overwhelming majority of Charite’ and ProDisc patients fare exceedingly well after surgery;” [2] (post)

2.       "The mud rakers behind almost ALL of these cases are Medtronic consultants;(Peloza, Kurtz, et al)." [5] (post)

{ Mr. Richard Longland is accussing Dr. Peloza of being a mud raker … which is rather insulting }

2.       “I am off to SAS tomorrow, which is in Berlin, Deutschland this year. I will be attending presentations, asking many questions and will be meeting with Dr.(s) Blumenthal and Bertagnoli while there.”  Richard Longland, October 2004  (post)

3.       “I am happy to announce that Dr. Scott Blumenthal and Dr. Rudolph Bertagnoli have joined APF as board members.”  (post)

1.       “My goal is to raise $50,000 by March 31st. Your contribution will be tax-deductible for 2007”  ( posted, January 19th 2007).

4.       http://www.prodisc-study.info/forums/2007-Richard%20Longland.pdf

1.       Coincidentally, Mr. Richard Longland (aka Harrison on ADR Support . org), reports a $50,000 grant in his 990-EZ tax reports.

2.       {Who provided this $50,000 grant?  Was it a surgeon on his board?}

5.       Here, Mr Longland (aka Harrison) suggests Dr. Bertagnoli for a patient’s multi component issues (post) … there are others.

 

25.   Are financially interested spine surgeons involved in the selection of articles posted to journals?

o    Medtronic Ties Not Disclosed by Editor of Spine Journal

o    “According to The Milwaukee Journal-Sentinel, Thomas Zdeblick took over the editorship of the journal in 2002. Since then, the patent royalties Zdeblick received from Medtronic have amounted to more than $20 million.” … “during Zdeblick’s tenure, the publication became ” a conduit for positive research articles involving Medtronic spinal products.” …. 70 articles in 56 issues!

o    Charles Burton, vice president of the Association for Ethics in Spine Surgery, questioned the propriety of Zdeblick’s articles being published in his own journal. He likened Zdeblick’s editorship to “fox in charge of the chicken house.”

o    "To exert this influence, companies often pay large sums of money, sometimes in the millions, to high profile spine surgeons who can write favorable papers about their products under the guise of unbiased research.  … Many such surgeons are also in governance positions of the professional societies and on the editorial boards of journals.  This allows them to influence the choice of presentations in society meetings, choice of educational workshops, as well as papers chosen for publication." Dr. Charles Rosen testimony to U.S. Congress: http://aging.senate.gov/events/hr188cr.pdf

IV.                CRIMINAL INDICTMENTS, LAWSUITES AND SHADY DEALS

26.   Is there a lawsuit regarding the Prodisc / FDA fraud still in court? 

o       http://docs.justia.com/cases/federal/district-courts/texas/txsdce/6:2008cv00004/549421/87/

o       http://dockets.justia.com/docket/texas/txsdce/6:2008cv00004/549421/

 

27.   Would the Viscogliosi investors have recouped their investments and more, if the Prodisc FDA trials had failed (and $175 Million not awarded)?

28.   Did Venture capitalists recruit surgeons to invest in the Prodisc before the FDA trials, knowing there would be a huge payout?

o   The confidential documents show that Dr. Zigler invested at least $25,000 in early 2002 in a Viscogliosi Brothers fund created to finance Spine Solutions.

o   By the end of 2001 Dr. Cammisa had invested a total of $250,000. The hospital itself owned stock directly in Spine Solutions.

o   In a deposition, Dr. Balderston, who said he had invested about $500,000 with Viscogliosi Brothers, said the Synthes deal increased the value of his investment by "about 10 percent, 20 percent, something like that."  Dr. Balderston was already an investor when he was recruited for the F.D.A. studies by Spine Solutions, according to his deposition. He failed to disclose those ties, according to the court records, which indicate that the clinical investigator form he filled out did not mention his investments. Dr. Balderston said in the deposition he did not believe that he was required to disclose his holdings in the funds. "There were a lot of people who invested," he said, "so my small number was not a significant number."

o   V-Bros:  “We are proud of the fact that so many distinguished surgeons have invested in our funds and it validates their individual views on Prodisc as a highly effective technology.”  http://www.ethicaldoctor.org/articles/nytimes3.htm

o   (Here, the V-Bros clearly state that the surgeons who invested had a pre-conceived opinion of the effectiveness of the Prodisc device)

29.   Are clinical trials being migrated to off-shore sites, which have lax regulations, and little patient protection?

30.   Is the Device Maker, Synthes, under a Corporate Integrity Agreement (CIA) due to Criminal charges?

31.   Has the company Synthes, been indicted for illegal experimentation without disclosure?

 

32.   Did the same Synthes executives, criminally charged for Norian XR, make it a company policy to obtain 300 to 400 ‘perfect {Prodisc} surgeries’?

o   http://www.healthpointcapital.com/research/2006/08/16/synthes_1h06_results_sales_up_15/

o   {The above statement ‘get a few sites to perform 60-80 procedures ..." sounds a lot like the following statement regarding the Prodisc:}

o   Yesterday Synthes reported consolidated 1H:06 financials with sales of $1.2 billion, representing an increase of 14%.  In the spine segment, the ProDisc®-L Total Disc Replacement received FDA approval on Monday. Synthes plans to roll out this product slowly and with considerable sales force, surgeon and customer training. Management aims to perform from 300 to 400 "perfect surgeries," which can be facilitated by doctor training and patient selection

V.                  BLOODY FEEDING FRENZY

33.   How many surgeons and medical device manufacturers are involved in the feeding frenzy?

o   UBS analyst Martin Wales last month started recommending the company's stock, which trades mostly in Europe, in part because of that new opportunity. Wales is looking for the company's ProDisc to secure the FDA's blessing and rack up sales of $40 million in 2006 before going on to generate $400 million annually by the end of the decade.  Hope Slips for Disc Implants

o   Surgeon's routinely fail to disclose Financial Ties : 41 orthopedic surgeon researchers ... received 62% of company expenditure of $248 million ... or $153.75 million. range $1 to $8.8 million. Average $3.75 Million.

o   New Focus of Inquiry Into Bribes: Doctors, New York Times, March 22, 2008, Barnaby J. Feder

o   {Stryker, DePuy Orthopedics, Smith & Nephew, Zimmer Holdings} agreed to pay $310 million in fines to settle civil charges.

o   The companies were required to disclose on their web sites, compensation to Doctors – but apparently halted nearly all such payments for the 18 months.

o   Highest-Paid U.S. Doctors Get Rich With Fusion Surgery Debunked by Studies: “Fusion has helped spine surgeons become the best paid doctors in the U.S. Their average annual salary is $806,000, more than three times the earnings of a pediatrician, according to the American Medical Group Association, a trade organization for doctor practices.”, British and Norwegian researchers found fusion no better than physical therapy for disc-related pain in three studies, totaling 473 patients, published in the journals Spine, Pain and the British Medical Journal between 2003 and 2006. A 2001 Swedish study of 294 patients in Spine found fusion better than physical therapy that was less structured than the kinds used in the other studies.

o    "John Regan of Los Angeles has performed nearly 200 Charité surgeries and says patients "do consistently better than patients of any other surgery we do." He says he receives royalty payments from J&J in connection with his work on Charité but they don't influence his professional judgment. Dr. Regan's patients were treated at Cedars-Sinai Medical Center in Los Angeles, which promotes artificial disk replacement in radio advertisements."

1.       http://www.ethicalspinesurgeon.com/articles/WSJRosen.htm

o   "The absolute ideal from a drug or device company is everyone is covered," he said. "And what they have it covered with is money."

1.       http://www.ethicaldoctor.org/articles/nytimes3.htm Dr. Drummond Rennie, Professor of medicine, University of California, San Francisco

34. Whom were the surgeons involved in the FDA Prodisc Trials?

 

VI.                Et cognoscetis veritatem et veritas liberabit vos!

35.   Did Dr. Charles Rosen’s advocacy for Ethics sink his nomination for Surgeon General?

36.   What, if anything, has the FDA done to implement the demands of the New Jersey AG.

o    ?

37.   What, if anything, has Synthes done to comply with the terms of the Settlement with the NJ AG?.

o    Medical Device Maker Settles Conflict Inquiry in New Jersey (NY Times article)

o   "It is outrageous that doctors who are testing, and in many cases, recommending the use of certain high-risk medical devices are being compensated with stock in the very companies that make these devices," the attorney general, Anne Milgram, said in a statement.

o   "All patients , but especially those considering high-risk devices such as spinal disc replacements -- deserve honest, objective clinical trial information about the products available."

o   The settlement, announced on Tuesday, calls for Synthes, the maker of the ProDisc artificial spinal disk, to disclose any future payments or investments held by doctors involved in researching its products.

o   Announcement: http://www.nj.gov/oag/newsreleases09/pr20090505a.html

38.   Are there other Prodisc Trials in other countries, by surgeons who do not have a vested interest?

o    The Norwegians began an Prodisc vs. conservative therapy in 2006. What are the results?

o    http://www.medpedia.com/clinical-trials/NCT00394732  jens.ivar.brox@rikshospitalet.no

39.   Whom is responsible for oversight of physician/company relationships? Who set the rules, laws?

o    http://spineblogger.blogspot.com/2009/09/has-spine-industry-rebounded.html

o    "Who is responsible for providing oversight, or, policing the industry? The Companies themselves? NASS? AdvaMed? The DOJ?

o    “The bigger question that must be asked is; does anyone play by the rules anymore?”

40.   If a patient does thorough research, a complete comparative analysis, what have they learned?

 

41. Why does Synthes not list all the FDA trial exclusions as contraindications?

o    Synthes Professional Device Labeling: p050010c.pdf  (Note:  ‘Facet Arthrosis is NOT listed as a contraindication)

o    "The safety and effectiveness of this device has not been established in patients with the following conditions:"   -> facet joint disease or degeneration

o    The following potential adverse events (singly or in combination) which may be expected to occur, but were not observed in the clinical trial, could also result from the implantation of the PRODISC®-L Total Disc Replacement:  -> Facet joint degeneration

o    Contraindications The PRODISC®-L Total Disc Replacement should not be implanted in patients with the following conditions:

·         Active systemic infection or infection localized to the site of implantation

·         Osteopenia or osteoporosis defined as DEXA bone density measured T-score < -1.0

·         Bony lumbar spinal stenosis

·         Allergy or sensitivity to implant materials (cobalt, chromium, molybdenum, polyethylene, titanium)

·         Isolated radicular compression syndromes, especially due to disc herniation

·         Pars defect

·         Involved vertebral endplate dimensionally smaller than 34.5 mm in the medial-lateral and/or 27 mm in the anterior-posterior directions

·         Clinically compromised vertebral bodies at affected level due to current or past trauma

·         Lyric spondylolisthesis or degenerative spondylolisthesis of grade > 1

 

o    FDA Clinical Studies

o    Exclusions  Note: ‘Facet Arthrosis IS listed as a contraindication

·         No more than I vertebral level may have DDD and all diseased levels must be treated

·         Patients with involved vertebral endplates dimensionally by smaller than 34.5 mm in the medial-lateral and or 2-mm in the anterior-posterior directions

·         Known allergy to titanium, polyethylene, cobalt. chromium or molybdenum

·         Prior fusion surgery at any vertebral level

·         Clinically compromised vertebral bodies at the affected level due to current or past trauma

·         Radiographic confirmation of facet joint disease or degeneration

·         Lyric spondylolisthesis or spinal stenosis

·         Degenerative spondylolisthesis of grade > 1

·         Back or leg pain of unknown etiology

·         Osteopenia or osteoporosis: A screening questionnaire for osteoporosis, SCORE (Simple Calculated Osteoporosis Risk Estimation). will be used to screen patients to determine if a DEXA scan is required. If DEXA is required, exclusion will be defined as a DEXA bone density measured T score < -2.5.

·         Paget's disease, osteomalacia or any other metabolic bone disease (excluding osteoporosis which is addressed above)

·         Morbid obesity defined as a body mass index >40 or a weight more than 100 lbs. over ideal body weight

·         Pregnant or interested in becoming pregnant in the next 3 years

·         Active infection - systemic or local

·         Taking medications or any drug known to potentially interfere with bone/soft tissue healing (eg.. steroids)

·         Rheumatoid arthritis or other autoimmune disease

·         Systemic disease including AIDS. HIV. Hepatitis

·         Active malignancy: A patient with a history of an, invasive malignancy (except non-melanoma skin cancer), unless he/she has been treated with curative intent and there has been no clinical signs or

·         symptoms of the malignancy for at least 5 years

 

42. Why are the Prodisc Device Labeling, and Supplemental information conflicting?

o   In the device labeling, it is claimed that ‘facet joint degeneration’ was not observed in the clinical trial.  In the Supplemental Information, it is revealed that a patient was forced into a posterior fusion due to facet disease at the implanted level.  Given that patients with ‘radiographic confirmation of facet joint disease or degeneration’ were excluded from the study, we can only assume that the revision subject’s facet disease occurred after the surgery.

o   Synthes Professional Device Labeling: p050010c.pdf 

·         The following potential adverse events (singly or in combination) which may be expected to occur, but were not observed in the clinical trial, could also result from the implantation of the PRODISC®-L Total Disc Replacement:  -> Facet joint degeneration

o   FDA Prodisc-L Supplemental Information:   

·         “Additionally, one PRODISC®-L subject underwent revision because the polyethylene inlay had been inserted backwards; and one PRODISC®-L subject underwent posterior supplemental fixation (fusion) for facet disease at the implanted level”

 

VII.         III.      PRODISC TRIALS CONCERNS:

 

·         The Fusion patients were exposed to operations in which their failure or sub-par performance would profit the physician.

·         The F.D.A.'s opinion may have been partially based upon reports from E.U. surgeons claiming 96 to 98.2% success - whose data are self-monitored (according to German surgeons we spoke with), and who have direct and enormous financial interest in the Prodisc's F.D.A. approval.  In particular, I refer to a surgeon from France, and from Germany, who claim phenomenal successes.  Both share authorship of the Prodisc patents, and would probably profit from the $175 Million to be awarded upon F.D.A. approval of the Prodisc. 

·         The Prodisc's Professional Labeling does not describe 'facet arthrosis' as an absolute contraindication, while it was a critical and specific exclusion in the patient selection for the Prodisc trials.  Thus, it appears many surgeons are overlooking this important condition.  Several reports indicate that Facet Arthrosis is the leading cause of revision (removal) of the Prodisc.  Other reports indicate that the Prodisc contributes to facet arthrosis in up to 32% of patients.

·         Synthes has not addressed the matter of revision of the Prodisc in the brochures seen so far, nor warned the public of the dire consequences in the case of late-stage revision.  A report by Dr. Andre van Ooij, who has removed 75 artificial discs (Charite), found that removing the devices reduced the patients pain, on average, from 8/10 to 5.6/10, while leaving the devices in resulted in 6.3/10.  Thus we learn two things: Revision of a failed ADR is unlikely to return the patient to a manageable pain level, and removal of the device is the better option.  But, removal of the Prodisc is seriously exacerbated by the large keels embedded into the above/below vertebral bodies.  If you can not remove it anteriorly (due to vascular scarring - which is the likely case), then you must remove it laterally.  This is like removing a boat from a garage sideways through the wall.  Furthermore, lateral approach necessitates trans-psoas access, which is likely to lead to damage or severing of the genito-femoral nerve.

·         In the brochures seen so far, Synthes does not specify a minimum natural disc height.  The Prodisc has a minimum central height of 11mm.  For petite women with natural disc heights of, say 8mm, this can be catastrophic. 

·         The Prodisc does not, in our opinion, 'maintain the physiologic range of motion in the spine'.  It is clearly and specifically shown in the device specs, that the Prodisc exaggerates natural rotations by  20 degrees vs. 15 degrees in A/P rotation (133%), 20 degrees vs 10 degrees in lateral rotation (200%), and 360 degrees vs. 6 degrees in axial rotation, or 6000% (to which the facet joints are most sensitive).

 

VIII.      FURTHER STUDIES IN PROGRESS

 

A structured, unbiased study must be executed with respect to the following topics:

 

a.       What are the indications and contraindications for the Prodisc, according to Synthes, FDA and EU parties.

b.      What are the success rates of Prodisc, according to biased, unbiased investigators

1.      Lemaire’s initial un-controlled, unmonitored study,

2.      Delamarter’s early study, which reported equal results between fusion and Prodisc at 6 months

3.      Bertagnoli’s amazing 98.2% success rates, and questioning of this by his German peers

4.      FDA trial results:  Most surgeons were heavily invested in the Prodisc.  Can you trust them?

5.      Other trial results: Korea, India, etc.

c.       What are the advantages & disadvantages of Prodisc ADR vs. contemporary Fusion (rh-BMP2).

1.      Adjacent Segment Degeneration: Is it a myth, hype, or proven?

2.      Longevity: Wear analysis, subsidence, ossification, fibrosis

3.      Short-term surgery morbidity and recovery time

d.      Who was involved in the fraud of the FDA trials of the Prodisc, its investigation, and what are the ramifications

1.      Viscogliosi Brothers and Spinal Solutions

2.      Most of the US FDA trial surgeons, non-disclosure of financial conflict of interest

3.      Charles Grassley investigation

4.      New Jersey Attorney General investigation

e.      What are the causes of Prodisc failure (clinical and mechanical)

1.      What are the potential biomechanical problems with the Prodisc

f.        What are the options, restrictions, dangers and results of Prodisc revision

1.      Fusion in-situ

2.      Anterior extraction

3.      Lateral extraction

4.      Clinical results of Prodisc and other TDR device revisions

g.       What and Who are the drivers behind the Prodisc

1.      Who is promoting the Prodisc, and how

2.      Which public forums promote the Prodisc

h.      Testimonials of Prodisc recipients

1.      Success stories

2.      Failure stories

a.       3 level disc replacement in Germany with Dr. B. In pain and suicidal.
b.       .

3.      Surgeon opinions

 

IX.             REFERENCE ARTICLES

 

 

ARTICLES / MEDIA

o    The Spine as a Profit Center

 

ARTICLES / MEDIA ON CHARITE’

o    http://www.thestreet.com/stocks/healthcare/10289585.html

o    http://www.thestreet.com/stocks/melissadavid/10223280.html

 

SENATE INVESTIGATION

o    Subpoenas issued to Prodisc Makers

o    Senator Queries F.D.A. and Spinal Disc Maker

o    Senator Grassley letter to FDA

o    Senator Grassley's letter to Synthes

o    Prodisc Manufacturer Synthes and FDA Drilled Over Artificial Spinal Disk Approval

o    Regence Medical Policy

o    Aching Backs get support of FDA, but not of Payors

o    Surgeon's routinely fail to disclose Financial Ties

o    Prodisc Clinical Trials Scrutinized by Lawmaker | NewsInferno

 

Synthes/Norian Indictment

o   Indictment:  09cr00403_indictment.pdf

o   Settlement agreement:  synthesnorian_settlementagreement.pdf

o   http://hcrenewal.blogspot.com/2009/06/synthes-indicted.html

o    

New Jersey Attorney General

o    NJ Settles with Synthes in Landmark Deal over Prodisc Conflicts | NewsInferno

FDA

o    http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm077620.htm

o    FDA Prodisc PMA Approval Order: http://www.accessdata.fda.gov/cdrh_docs/pdf5/P050010a.pdf

o    FDA Prodisc Summary:   http://www.accessdata.fda.gov/cdrh_docs/pdf5/P050010b.pdf

o    FDA Prodisc Professional Labeling:  http://www.accessdata.fda.gov/cdrh_docs/pdf5/P050010c.pdf

o    FDA Prodisc Patient Labeling: http://www.accessdata.fda.gov/cdrh_docs/pdf5/P050010d.pdf

o    Zigler J, Delamartar R, Spivak JM, et al. Results of the prospective, randomized, multicenter Food and Drug Administration investigational device exemption study of the ProDisc-L total disc replacement versus circumferential fusion for the treatment of 1-level degenerative disc disease. Spine 2007;32(11):1155-62; discussion 1163

ADVERSE EVENTS

o    Mathew P, Blackman M, Redla S, et al. Bilateral Pedicle Fractures Following Anterior Dislocation of the Polyethylene Inlay of a ProDisc® Artificial Disc Replacement; A Case Report of an Unusual Complication. Spine 2005;30(11) 30:E311–E314

o    Schulte TL, Lerner T, Hackenberg L, et al. Acquired spondylolysis after implantation of a lumbar ProDisc II prosthesis: case report and review of the literature. Spine (Phila Pa 1976). 2007;32(22):E645-8

o     

 

 

Copyright 2011, Prodisc-study.info.

All comment herein, which are not direct quotations, are the author’s opinion only.