Editor's Note: The raw links look bad but that's how they got sent.

Thank you,

Sandy Frost 10/5/2010

Today's news is that an online search of FDA tissue bank registrations does not include the skin and tissue lab at Shriners Hospital for Children (SHC) in Cincinnati. The online search lists the skin and tissue labs at SHC Boston and SHC Galveston but not the lab at SHC Cincinnati.

Could it be that federal inspectors, regulators and auditors missed this, though their focus was on the mounting pile of problems that led the FDA to shut down a study to develop a burn treatment at SHC Cincinnati?

Does this mean that any work done in this allegedly unregistered lab would be considered useless for research, grant application and/or investment purposes?

Does this mean that work done at such an unregistered lab would render moot research done on compassionate use patients as well as efforts to commercialize products developed in said lab?

Additionally, officials at the Ohio Board of Medicine have confirmed that an online search reveals that Dr. Steven Boyce is not an MD but is instead a biologist with a PhD. It has yet to be confirmed if Dr. Richard Kagan disclosed to the medical board that he got an FDA warning letter that led the agency to shut down the same study he was charged with overseeing.

Finally, a spokesman for the OHRP has confirmed that no one reported these events to the agency as required in an April, 2003 final letter of determination stating "We have no record of events related to the described research having been reported to our office by the University of Cincinnati or Shriner’s Children’s Hospital. After consultation with the FDA, however, we are confident that the matter is being handled adequately by that agency."

The following questions were asked about the clinical study used to develop a cultured skin substitute trademarked PermaDerm ™. This burn treatment was developed by doctors at SHC Cincinnati through a clinical research study so bad that the FDA issued three Warning Letters before finally shutting it down. The FDA warning letters were sent to Dr. David Greenhalgh, Chief of Burns at SHC Sacramento, Dr. Richard Kagan , Chief of Staff SHC Cincinnati and Dr. David Stern, Dean, University of Cincinnati School of Medicine. A month later, in February, 2007, the FDA sent Dr. Stern an Integrity Hold Letter, informing him that the study was being shut down.

To make matters worse, the FDA denied an application for compassionate use last June that asked to include a badly burned boy in the same study though it had been shut down. The FDA denial letter stated an appeal would be considered and that:

“FDA would welcome the opportunity to learn more about the safety of this product, if you can identify clinicians who are knowledgeable about Autologous Cultured Skin Substitute. Because considerable concern exists about the validity of the data generated under this IDE, we believe that these knowledgeable clinicians should be independent from the two investigators performing this study and their understanding of the product should be derived from experience other than this IDE study or publications by Drs. Kagan or Boyce.”

In contrast, the past few months have seen a much publicized effort to somehow get this same product through FDA approval for a market estimated at $3 billion.

Some of these questions ask why those trying to commercialize this product don’t appear to be disclosing these material facts to the SEC, investors or others who need to know? Shouldn’t they be told that doctors consistently failed to report hundreds of adverse events? Shouldn’t they be provided with a copy of these documents, including the audit that documents hundreds, if not thousands, of FDA violations?

To date, all of the following questions remain unanswered.

“Media Request” sent on Weds. July 7, 2010 to lsears@shrinenet.org, shrinepr@shrinenet.org

Dear Shriner PR officials,

My name is Sandy Frost. I am an online investigative journalist who has been reporting about problems found by the Office of Human Research Protection and FDA with a burn treatment study at SHC Cincinnati since

Thank you in advance for answering the following questions.

Sandy Frost

Question for Shriners HQ about FDA/SHC Cincinnati situation:

1) At what point were officials with oversight authority notified about warning letters from the Office of Human Research Protection and the FDA? Such authorities include Boards of Governors for SHC Cincinnati as well as corporate, CEO of hospitals, Chairman of the Board of the Hospitals and then Imperial Potentate?

2) At what point were the same officials notified about and provided copies of the FDA’s Establishment Inspection Report?

3) AT what point were the same officials notified about and provided copies of the FDA’s Integrity Hold letter that suspended the clinical study at SHC Cincinnati?

4) What happened after both Shriner boards learned of the warning letter, the EIR and Integrity Hold letter?

5) What is now being done about this?

6) Do members of the boards have current conflict of interest statements? If so, do they include financial interests in any pharmaceutical or burn treatment or orthopedic companies?

7) Per IRS disclosure rules, please provide a copy of the SHC conflict of interest statement to this same email address.

“A Few More Questions” sent on July 31, 2010 to officials at University of Cincinnati including " Janice (adamjc)Adams" ADAMJC@UCMAIL.UC.EDU, "Richard (puffra)Puff" puffra@UCMAIL.UC.EDU, "Douglas (nienabdj)Nienaber" NIENABDJ@UCMAIL.UC.EDU regarding a grant application to the U.S. Army.

1) Page 141 of the Morley audit states that the IRB can terminate an investigator's participation in a study. Has the U of C terminated Dr. Boyce or Dr. Kagan from the CSS/ESS studies, to include the study funded by the Army's AFFIRM program? Are there plans to suspend either doctor? If not, why not?

2) Since the grant application to the U.S. Army's AFFIRM program is based on Dr. Boyce's research and he's named as principal investigator on the grant application, is anyone at the U of C going to revisit the application or alert the U.S. Army that Dr. Boyce's research was excluded by the FDA as unreliable?

3) Page 145 of the Morley audit states that Dr. Strasser sent a formal notification to Dr. Boyce to suspend any presentations, publications and/or media relations regarding the IDE project until FDA removes the Integrity Hold. When was this notification sent, please? I am curious because there have been regulatory registrations and websites promoting this product with representations that Dr. Boyce's product is without issue, in violation of Dr. Strasser's notification, link here:

http://www.mccoyllc.com/Skin.html

This is a June 22, 2010 patent that seems to make the same representation that the product is without issue or regulatory suspension:

http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=8&f=G&l=50&co1=AND&d=PTXT&s1=steven&s2=boyce&OS=steven+AND+boyce&RS=steven+AND+boyce

Since the University of Cincinnati is listed on the patent and the FDA excluded Dr. Boyce's research from compassionate use requests, wouldn't it be fair to assume that the research on which the patent/s are based have been deemed unreliable by the FDA and the patent/s should have been withdrawn or resubmitted with otherwise reliable and/or credible research? By association, isn't the U of C making the same representations?

Is the University of Cincinnati going to alert the patent office about the regulatory problems and through this disclosure, request a resubmission once the Integrity Hold has been lifted?

Here is a link to an 8K SEC filing for the company recently formed to bring PermaDerm to the market:

http://www.faqs.org/sec-filings/100721/Windstar-Inc_8-K/

http://biz.yahoo.com/e/100722/wdst.ob8-k.html

This filing also names the U of C in terms of having licensing rights.

Are you aware that this 8K filing states that "the HUD designation has already been received and, upon completion of the Lonza Transaction, will be transferred to us (Regenicin) as part of a licensing agreement with the University of Cincinnati, which will allow immediate manufacture and sale of PermaDerm for treatment of catastrophic burns"?

How, on one hand, can the president of the U of C stand by a compassionate use exception and guarantee oversight after the FDA excluded Dr. Boyce's research and then seem to participate in an effort to bring the same product to market as well as benefit from the sales of this product by participating in an 8K filing with the SEC, when Regenicin is relying on Dr. Boyce's excluded research?

Dr. Boyce's company, Cutanogen, is referenced with a $2 million dollar payment in the 8K SEC filing. Did Dr. Boyce disclose this on an updated COI that he, through a transaction with his company Cutanogen, is expecting $2 million? This SEC filing fails to disclose warning letters from the OHRP and the FDA, the clinical research study's suspension by the FDA and results of the third party audit. The filing represents PermaDerm as having no regulatory problems and that FDA approval is expected. Since product representations would come from Dr. Boyce/Cutanogen, would this violate Dr. Strasser's notification that Dr. Boyce not make public representations and/or representations to others (McCoy/Regenicin, SEC via 8K filing, U.S. Patent office which would qualify as public) until the FDA Integrity Hold is removed?

Was the U of C consulted in any way during the patenting process or the 8K filing process to reduce any potential liability due to statements and/or omissions by Dr. Boyce in the patent process and/or Randall McCoy through his Regenicin 8K filing?

And again, is the U of C going to communicate any of these issues with the U.S. Army since Dr. Boyce's research was excluded by the FDA?

Thank you,

Sandy Frost

Note: It has been since learned that those patients used as the only examples in the grant application, #130 and #131, were also included in the audit's FDA violations. These include not being reconsented, inconsistent case report forms, inability to show that #130 did not have sepsis upon admission, inconsistent comparative graft sites, too few dressing changes, grafts placed in dry dressing instead of CSS irrigation, multiple reports of deviations of the CSS being placed on contaminated wound beds, no unanticipated device event reported for Leukopenia in #130 and lack of records for reporting event adverse events for #130 and 131 including graft loss.

“Questions about Regenicin 8K filing?” sent on Tuesday August 3, 2010 to Randall McCoy at rmccoy18@optonline.net.

Dear Mr. McCoy,

My name is Sandy Frost and I am an online investigative reporter. You can find my work at http://sandyfrost.newsvine.com.

I've been doing research into the introduction of PermaDerm to the market place and have a few questions for you please?

Prior to filing the 8K with the SEC for Regenicin, INC., were you aware that the study on which Cutanogen’s research is based was suspended by the FDA?

Were you aware that the FDA recently excluded Dr. Boyce’s research from any compassionate use applications because of the hundreds of FDA violations found in their inspection and a recent year long audit found that Boyce’s research was unreliable?

You cited results expected from an Army study to show the product’s viability. Are you aware that the grant application to the U.S. Army is based on the same suspended study and excluded research?

In other words, did you file the 8K with the SEC without knowing that the product you expect to market and anticipate FDA approval of had the study suspended and research excluded by the FDA?

Thank you,

Sandy Frost

“Questions regarding SHC Cincinnati.” sent on Tuesday, August 3, 2010 to Shriners HQ, CEO, board members and staff including rsemb@shrinenet.org, shrinepr@shrinenet.org, gbracewell@shrinenet.org, dmaxwell@shrinenet.org, mlagina-kleine@shrinenet.org, ResearchHighlights@shrinenet.org, bbede@shrinenet.org, cclaypool@shrinenet.org, gdunwoody@shrinenet.org, rfrevel@shrinenet.org, bsimmons@shrinenet.org, gmitchell@shrinenet.org, amadsen@shrinenet.org, blemieux@shrinenet.org, lspieler@shrinenet.org, vnicely@shrinenet.org, mandrews@shrinenet.org, sandyleefrost@yahoo.com

All,

As you may or may not know, I have been investigating your organization the past four years. I have submitted countless questions, most of which remain unanswered; including requests for tax related documents as well as questions about your secret sub-group, the Royal Order of Jesters.

Here are some questions about an effort to commercialize a burn treatment named PermaDerm. It was developed at SHC Cincinnati by Drs. Steven Boyce and Richard Kagan. As you may or may not know, the FDA suspended the product’s study shortly after issuing a warning letter in January, 2007. The FDA’s inspection, inspection reports and subsequent warning letter were preceded by letters of noncompliance from the Office of Human Research Protection that required an audit of patient records for proper informed consent.

The FDA’s inspection found that this had not been done.

The FDA’s inspection found hundreds of clinical research violations that led to the study’s suspension as well a call for a third party audit. The FDA’s violations were organized into six categories. The third party audit’s violations were organized into nearly 50 categories.

The results of the yearlong audit detail how patients were not only endangered but how the study’s principal investigator refused to heed warnings from the OHRP, the FDA and the University of Cincinnati, even after the study had been suspended and while the third party audit was being conducted.

Shriners Hospital for Children is named as a beneficiary in an 8K SEC filing submitted by Randall McCoy in an effort to launch a company named Regenicin and raise about $16 million to bring the burn treatment, PermaDerm, to market.

Are you aware that this happened?

The SEC filing also names Dr. Boyce’s company, Cutanogen. Were you aware that the study on which Cutanogen’s research is based was suspended by the FDA? Were you aware that the third party audit led to the FDA’s denial of this same product for compassionate use?

Were you aware that the FDA recently excluded Dr. Boyce’s research from any future compassionate use applications and/or appeals because of the hundreds of FDA violations found in their inspection as well as the audit’s findings? Were you aware that the recent year long audit found that Boyce’s research, and by extrapolation SHC’s research, was unreliable?

The 8K SEC filing cited results expected from an Army study to show the product’s viability. Are you aware that the grant application to the U.S. Army was based on the same suspended study and excluded research?

Have any SHC board or other Conflict of Interest statements disclosed investments with Regenicin, Inc or any other commercial ventures associated with PermaDerm?

What oversight did Dr. Bernard Lemieux or Dr. Brandt Bede or anyone else at SHC headquarters exercise as heads of Shriner’s research or those in positions of authority? Did anyone there counsel Drs. Boyce and Kagan to comply with the warning letters or did you even know about them?

If anyone there at SHC HQ knew about the warning letters, why was the study funded year after year though there were problems?

Sent Monday September 13, 2010 to Jay Strell at strell@sunshinesachs.com after he announced interviews before and after a Regenicin media event.

Dear Jay,

My name is Sandy Frost and I am an online investigative journalist who has been investigating the Shriners for the past four plus years.

My site is at http://sandyfrost.newsvine.com, including five articles about the development of PermaDerm ™ that you might find interesting.

I have a question for the Regenicin media event but feel free to get an answer from your clients ASAP.

Did product developers or anyone at Regenicin disclose to their investors, the SEC, the Patent Office, Lonza, the Office of Human Research Protection (OHRP) and/or the board members:

• Letters of noncompliance from the OHRP and FDA sent to those in charge of developing PermaDerm ™
• The hundreds of adverse effects associated with the clinical study to develop PermaDerm ™
• That the FDA shut down the PermaDerm ™ clinical research study due to thousands of clinical research violations
• That the FDA recently excluded the research and publications of the doctors who developed PermaDerm ™ from compassionate use consideration

Thank you,

Sandy Frost

All copies of material reprinted or duplicated from "by Sandy Frost" must include the following credit line: From http://sandyfrost.newsvine.com/ Copyright © 2010 by Sandy Frost. Used by permission.

Editor's Note: The burn treatment described below is the same as "PermaDerm" (tm), a cultured skin substitute developed at Shriners Hospital in Cincinnati. PermaDerm (tm) is currently being brought to market by a new company named Regenicin. It is not clear if the product's developer or those at Regenicin have disclosed the below information, especially about the adverse effects, including death, and that the study was shut down by the FDA due to thousands of clinical research violations, to their investors, the SEC, the Patent Office, the Office of Human Research Protection (OHRP) and/or the high profile, influential board members who have come aboard to help get FDA approval for this burn treatment as it heads towards a market worth $3 billion.

Sandy Frost, Starbucks, WA September 13, 2010

A twenty-year clinical study to develop a burn treatment conducted by doctors at the Shriners Burn Hospital (SHC) in Cincinnati and overseen by the University Of Cincinnati (U of C) School Of Medicine Institutional Review Board was such a mess that:

• The Office of Human Research Protection (OHRP) issued warnings in August, 2000
• FDA conducted a "for cause, high priority inspection" from March 7 – June 21, 2006
• FDA's June 23, 2006 Establishment Inspection Report listed hundreds of violations
• FDA sent warning letters to both SHC and U of C in January, 2007
• FDA issued Integrity Hold letter on February 2, 2007 that suspended the study
• Two independent audits found hundreds more violations, even after suspension
• FDA recently denied a compassionate use exemption for a badly burned boy

Two weeks ago, on June 15, the FDA denied a compassionate use request from the U of C to use an experimental cultured skin substitute (CSS) on eight year old Alfred Real, who’d been admitted to the Shriners Burn Hospital after playing with gasoline and suffering burns over 80% of his body.

News outlets mistakenly blamed the FDA for initially denying the burn treatment without correctly reporting that it was doctors and officials at both SHC and U of C who gave the agency cause to suspend the study. The FDA suspended the SHC study in February, 2007 for “lack of data integrity, system wide failures in the methods for conducting and managing clinical trials and patient safety violations.”

The FDA’s letter stated “We regret to inform you that your request (for compassionate use) is not approved and you may not treat this patient with the above cited investigational device.” It explained that the U of C’s compassionate use request failed to prove how using the burn treatment was less dangerous than the burn patient’s condition and failed to convince agency officials why the experimental cultured skin substitute should be used when FDA approved alternative treatments were already being used by doctors in burn units.

The letter continued:

“Given the availability of the above-mentioned alternatives and the lack of sufficient credible information about the investigational device FDA cannot assume that the probable risk of using the investigational device is not greater than the probable risk from the disease condition. FDA would welcome the opportunity to learn more about the safety of this product if you can identify clinicians who are knowledgeable about the Autologous Cultured Skin Substitute because considerable concern exists about the validity of the data generated under this IDE, we believe that these knowledgeable clinicians should be independent from the two investigators performing this study and their understanding of the product should be derived from experience other than this IDE study or publications by Drs. Kagan and Boyce.”

In other words, the FDA would and did consider a second compassionate use request as long as it excluded research from or publications produced by the doctors in charge of the suspended study. The FDA did grant a compassionate use application to the U of C on June 28 after the school accepted total responsibility for the procedures and the patient’s safety.

The FDA’s denial letter spelled out three areas of concern, even after U of C and SHC doctors, officials and staff have had over three years to resolve these failures, including:

Problems with data integrity

• Failures to maintain accurate, complete, and current records regarding each subject’s case history and exposure to the device, including all relevant observations.

• Failures to report unanticipated adverse device effects to the sponsor and reviewing IRB.

• Failures to maintain accurate, complete, and current records regarding the receipt, use, and disposition of a study device and failure to maintain each subject’s case history and exposure to the device, including all relevant observations.

• Failures of the investigator to maintain records of protocol deviations.

• Failures to obtain approval of significant changes to the protocol from the sponsor and reviewing IRB.

System wide failures in the methods of conducting and managing clinical trials

• Failure to ensure investigator compliance with the signed investigator agreement; investigational plan, and applicable federal regulations, (e.g., diagnostic procedures/assessments were not performed and unanticipated adverse device effects were not documented and reported).

• A lack monitoring procedures and the absence of monitoring clinical studies.

• Deficient records of device accountability.

• Failure to submit IDE progress reports at regular intervals and at least yearly to FDA and reviewing IRBs.

These Patient safety issues were called out in a third party audit submitted to the FDA on March 25, 2010

• Auditors determined that only 5 of 24 subjects which should have received additional informed consent information, were properly re-consented, (page 10).

• Auditors found that the sites did not understand the reporting of adverse events (page 44).

• Based on the definition of unanticipated adverse device effects and serious adverse effects developed by your Data Safety Monitoring Board (DSMB), 1782 out of a total of 7331 adverse events were reported. An additional 5547 AEs were extracted by the auditors based on the DSMB-generated list of adverse event reports (page 77).

• In the 2007 annual report (i.e., after issuance of the Warning and Integrity Hold letters), only 8 adverse events (AEs) were reported. During the independent audit a total of 695 reportable AEs were identified. In the 2008 annual report 36 unanticipated adverse device events were reported. In contrast, the auditors identified 760 such events (page 144).

• The case report forms (CRFs) for 33 of 44 subjects audited from 2003 – 2009 were not properly completed. Individual pages were incomplete and follow- up visits were not documented, even when subjects were being seen in the outpatient clinic (page 16).

• Less than half of the subjects had results from the pre-treatment serum antibody tests (page 40) and 119 of 159 antibody tests required by the protocol at POD 28 were not performed (page 60). This led auditors to conclude that “the results of the serum antibody studies were virtually impossible to identify. The records were maintained in an extremely poor manner and not sufficient for auditor review” (page 40).

• While documentation states that the principal investigators (PIs) did not check the “Post Operative Date Completion for all Sets” CRFs until the subject completed the initial year, some of these “checks” were signed up to two or three years after the closure of the subject’s initial year on study (page 44).

• Regarding microbial cultures, the auditors noted a decline in data collection the longer the time period after treatment. For example, the number of completed samples was 120/159 (pre-operation), 119/159 (POD 0), 111/159 (POD7) and 77/159 (POD 14) (page 52).

• The audit report states (page 177) that a uniform protocol was not used at all of the study sites. Dr. Boyce stated that the same protocol was not used at each of the Burn centers and protocols had variations that were site specific. This suggests that the study was performed with protocols that were not reviewed or approved by FDA.

• There was no evidence that appropriate data safety monitoring was put into place as part of the research plan, thereby ensuring that appropriate risk assessments were being made as part of the screening process (page 22).

• Regarding device quality assurance testing, the auditors determined that:

1. Only 67/155 (43%) histological exams were completed and could be verified by source documents.

2. There was not sufficient documentation with respect to the storage, shipment, handling or disposition of the device used in the study.

3. While sterility tests were to be performed both five days before and on the day of surgery, only 10/159 (6%) tests were completed five days before surgery. The majority of the sterility tests were performed 7-10 days before surgery. 43 of 159 tests (27%) were not done on the day of surgery. Five additional samples had incomplete data or could not be verified. (page 121 - 122).

The letter concluded “FDA believes it is appropriate to stop further enrollment of compassionate use subjects” until the U of C submitted a Corrective Action Plan that addressed unresolved concerns, three years after the fact.

The following illustrates events that gave the FDA cause to suspend the study as well as exclude the doctors in charge from compassionate use consideration.

In 1998, Dr. Steven Boyce began developing a burn treatment otherwise known as a cultured skin substitute while working at both U of C and SHC. The study was conducted at the Shriners Burn Hospital under the oversight of the University of Cincinnati’s School of Medicine’s Institutional Review Board or IRB. According to a Shriner fact sheet:

"The Cincinnati Shriners Cultured Skin Substitute was developed through nearly two decades of research by Dr. Steven Boyce. The process begins when a business card size piece of skin is taken from the burned child and is cultured to grow in about three weeks to the size of 100 business cards. The cultured skin substitute is then taken to surgery for application to the burn site.”

Problems with the study were first noticed by the Office of Human Research Protection or OHRP between 4/15/98 – 7/17/00 when the agency found that the informed consent documents used by the first 28 subjects enrolled between these dates that received cultured skin substitute (CSS) in this study did not have IRB approval. The first IRB approved consent form was dated 09/06/00.

On August 7, 2000, the OHRP presented SHC doctors an allegation from the Mother of a badly burned child who claimed that she was urged by a nurse to sign the informed consent document because "The Doctors need these papers signed immediately. If she has any chance at all, this is the only chance she has." It further explains "No one at any time explained the documents to her and/or that they were consent for Experimental Programs." This same OHRP letter further detailed how an otherwise excluded pregnant woman was enrolled as a research subject, to include the "collection of skin tissue for preparation of grafts as part of the research." It continues that the OHRP was presented another allegation "that the investigators continued to conduct research on a subject after the subject's family withdrew permission for her participation in research." The letter explains that though only the pregnancy allegation could be substantiated, guidance suggested changes in protocol and informed consent language so as to not inflate potential benefits to the research subjects.

On November 21, 2002, the OHRP sent a letter of noncompliance to U of C regarding Shriners’ CSS study.

An April, 21, 2003 OHRP letter noted that "the University of Cincinnati has required the investigators in the above-referenced research to conduct an audit of research subjects enrolled to ensure that no additional protocol violations had occurred. In addition, OHRP notes that the investigators have been made aware of the requirement to request changes to a protocol approved by an IRB prior to the initiation of such changes, except when necessary to eliminate apparent immediate hazards to the subject. OHRP recommends that UC also consider reminding all investigators of the regulatory requirements to obtain IRB approval for changes in approved research during the period for which the IRB approval has already been given."

In other words, the OHRP asked that the doctors in charge of the study audit patient records for proper informed consent and to make sure protocol changes got IRB approval.

Three years later, the FDA conducted a “high priority, for cause” inspection and found that doctors had not complied with the OHRP’s requirements in addition to discovering hundreds of other violations detailed in the inspector’s Establishment Inspection Report (EIR) issued on June 23, 2006.

The EIR explained that “Dr. Kagan is the principal investigator for this trial and as such, is responsible for overseeing initial patient assessments, planning surgeries, estimating the amount of cultured skin substitute needed, performing surgeries and assessing healing and progress.”

It further stated that:

“Dr. Kagan did not complete, review or sign any case report forms. He is the principal investigator of the trial, but he did not seem to have the most knowledge of the trial…Dr. Steven Boyce and Dr. Richard Kagan stated that they did not realize the importance of following the investigational plan exactly. They misunderstood the requirements for operating the IDE. They felt that though this inspection revealed numerous deficiencies that patient safety was never put at risk. I (the FDA inspector) explained the provisions that the FDA has available to them as a follow-up to the inspectional observations, which included a warning letter, disqualification or criminal prosecution. Dr. Kagan and Dr. Boyce are extremely concerned with addressing all observations and continuing to operate this IDE. They feel this trial is extremely important to the Shriner's patients and community and they will do all they can to meet all FDA concerns and regulations."

Six months later, on January 12, 2007, the FDA sent a warning letter to Dr. Richard Kagan, chief of staff at SHC Cincinnati.

Two weeks later, on February 2, 2007, an FDA Integrity Hold Letter formally suspended the study.

March 25, 2010 audit submitted to FDA.

June 15, 2010 FDA denies compassionate use request from U of C.

The audit showed that though the study had been suspended, violations continued. The audit found that:

• Only 19% of adverse events as defined by the Data Safety Monitoring Board were reported.
• The 2007 annual report reported only 1% of adverse events even after the warning and integrity hold letters.
• The 2008 annual report reported only 2% of adverse events.
• Case forms for 33 out of 44 subjects audited from 2003 to 2009 were not properly completed.

All copies of material reprinted or duplicated from "by Sandy Frost" must include the following credit line: From http://sandyfrost.newsvine.com. Copyright (c) 2010 by Sandy Frost. Used by permission.