BB&T Executive Editor

SAN FRANCISCO — Concerns over phy-sician/industry relationships started long before last year's Department of Justice (DoJ) probes that resulted in several of the big-hitter companies in the orthopedic arena becoming parties to big-dollar negotiated settlements (north of $300 million). But interest in those relationships clearly is heightened these days, as shown by both attendee and media response to a pair of sessions held during the American Academy of Orthopaedic Surgeons (AAOS; Rosemont, Illinois) annual meeting, earlier this spring.

First, a crowd estimated at some 800 strong packed one of the Moscone Convention Center meeting rooms for a lengthy give-and-take from a panel of speakers from both the legal and industry sides of the fence. Then those same panelists drew the week's largest crowd of media types to a briefing following the formal session.

The level of interest was not surprising. Like the proverbial train wreck, having industry giants such as Zimmer (Warsaw, Indiana), DePuy Orthopaedics (Raynham, Massachusetts), Biomet (Warsaw, Indiana), Smith & Nephew (London) and Stryker (Kalamazoo, Michigan) involved in settlements of one sort or another ratchets up interest in a hurry.

Media attendees especially appeared to be taking their watchdog role to heart. One reporter even demanded having all relevant panelist disclosures in hand before briefings even started.

The surgeon attendees had their own reasons for crowding into the first morning session, perhaps to avoid being painted with the same brush as their brethren accused of inappropriate relationships with the companies that supply their hip and knee implants — and other "working metal," as one physician wryly termed it.

Leading roles were played in both sessions by Lewis Morris, deputy inspector general in the Office of the Inspector General of the Department of Health and Human Services; Christopher White, executive VP and general counsel at the Advanced Medical Technology Association (AdvaMed; Washington); and Howard Young, a partner in the law firm of Sonnenstein, Nath and Rosenthal and an expert in fraud and abuse cases.

'Main Justice'-driven

Morris noted that within the Doj, "you have the Attorney General and what we call 'Main Justice.' Some investigations are driven by Main Justice," while others are driven by district offices of the Attorney General. He added that as far as coordination of such activities is concerned, "There are times when there is good, healthy competition between districts and sometimes between districts and Main Justice."

Fraud-and-abuse cases, such as those involving the big orthopedic firms, tend to be driven by investigators in given regional offices of the Attorney General, with the Philadelphia and Boston offices "historically having driven medical cases," Morris said. However, he noted that cases don't necessarily end up in just those two venues.

"For most of the major medical-products manufacturers, [the DoJ] can establish venue in just about every [district]." Right now, Morris said, the New Jersey district office in Newark "seems to have the medical device field covered."

Regarding the potential for broader fraud-and-abuse questions, he cautioned that it's important for companies "to do self-examinations to be on top of these issues."

Young, a former senior attorney and deputy branch chief with the Office of Counsel to the HHS Office of the Inspector General whose responsibilities included coordinating with the DoJ, state attorneys general and the Centers for Medicare & Medicaid Services on criminal and civil healthcare fraud matters, said there's also "a healthy level of competition between state attorneys general in prosecuting such cases."

He cited the "sheer volume" of such cases at both the state and federal levels, saying "there are so many that it's going to take many years for these cases to move forward.

"There are a lot of ongoing investigations," he said. "I think there's a lot more to come."

Feeling 'unsettled'

As for the feeling from the company side, he said, "I think there's still a bit of an unsettled feeling in the industry."

Morris chimed in with agreement that it's not just a matter of having to deal with the federal government. "More and more states are getting into this. States now have a growing financial interest [in launching such investigations]."

He noted that those on the prosecutorial side, whether from the Attorney General, Main Justice or HHS Inspector General ranks, are more and more getting into the training of their across-departmental-lines colleagues on these issues.

"We share information in order to boost our resources," Morris said.

To a reporter's question concerning the possibility of a situation in which these types of cases are "swept under the rug," both Morris and White gave resounding "No" answers.

'Afoot' — a lot of change

And Young termed the level of fraud-and-abuse investigation activity "astounding,' adding: "There's a lot of change afoot in the industry."

As for the importance of the issue from the AAOS perspective, outgoing president James Beaty said, "Every member and exhibitor got a letter from me on the issue. We're doing everything we can to educate our 30,000 members on this." And the academy "has put in place a mechanism to discipline our members. If a member is found to do something that we think is illegal, we think that member should be disciplined."

From the industry perspective, White said that since the orthopedic company settlements, companies have taken a different stance. While he didn't use the word "cavalier" to describe earlier positions companies might have taken, he made it clear that the seriousness of the issue is well understood by all companies in the device sector today.

Perhaps that's because, as Morris noted, "some companies now are two- and three-time losers," which makes taking the ethically correct stance even more important to those who haven't yet been charged with wrongdoing.

Gender-specific: hype — or real need?

The interesting title of a panel — "X-Why? The Gender Implant" — also lured a considerable crowd of journalists to the media briefing room at the AAOS meeting. And the discussion that followed lived up to the energy of the ongoing debate and the pre-briefing hype.

The panelists seemed mostly of one mind: the recent trend toward gender-specific implants by some orthopedic manufacturers is more marketing hype than a matter of clinical necessity.

One dissident, Andrew Glassman, MD, of Ohio State University Medical Center (Columbus), held up the "pro" end of the discussion, saying, "In some instances, gender-specific implants are useful." He said that "enormous strides have been made" in sizing of implants to better accommodate the differences between men and women, but answered his rhetorical question, "Does this mean we're done and should stop trying?" with a resounding "no." "We need greater recognition of the differences between male and female hips, and need more attention paid to pre-operative planning."

Glassman acknowledged: "We don't have any scientific data to demonstrate gender-specific differences in the survivorship of THR [total hip replacement} implants, or widely recognized differences in the clinical outcome of THR in females versus males."

But, "what we do have is indisputable scientific proof of significant differences between the male and female anatomy." He said also that those patients at the periphery of anatomic norms would benefit most from gender-specific implants.

Taking a definitely op-posing view was Robert Bourne, MD, of London Health Sciences Centre and the University of Western Ontario (London, Ontario), who cited results of a study of 1,735 patients to assess gender differences in implant size, neck length, offset and associated fractures. "Based on this study," he said, "there seems to be little clinical need for gender-specific primary THRs."

Timothy Brox, MD, of Kaiser Permanente, said that at the 2007 AAOS meeting, "we were told that women were not doing as well as men were with implants [but] it was our impression that this wasn't necessarily true." He and his Kaiser Permanente orthopedic colleagues nationwide developed a registry modeled on the Swedish National Joint Registry, in operation since 2001. The Kaiser registry potentially enrolls all patients for total knee implant procedures across the provider's nationwide facilities.

The primary role of the registry, Brox said, is to look at safety, quality and post-implant survival of the implant. "The population was all TKR surgeries done in our facilities between 2001 and 2006." That population totaled 13,250 women and 7,468 men.

Among complications studied, the researchers found there was no gender difference in deep infection rate and implant revision rate. Nor were the marked differences in range of motion between genders at greater than nine months' follow-up. And patient satisfaction between men and women "was similar at greater than nine-month post-op," Brox said.

The conclusion, he said, was that "we don't advocate use of gender-specific knee implants," which can run about $1,000 more than traditional unisex knees. "When I sit and talk with my patients, I simply can't advocate spending $1,000 more for a gender-specific product."

Scott Sporer, MD, of Rush University Medical Center (Chicago), cited reports from an AAOS technology overview showing differences between male and female patients, including that men have larger femurs than women, that there are differences in the rotation of the trochlear groove in women, and that women have more laxity in their knee ligaments, along with a higher incidence of ACL injury, higher incidence of osteoporosis and osteoarthritis.

Can industry and physicians do better with development of knee implants? "Yes, we can do better," Sporer said. "The question is, 'If you change a variable [that is, add a gender-specific implant], is the outcome better?'"

Broader randomized studies are needed, he said, "as well as outcome scales in order to measure subtle differences."

Hip resurfacing, THR making inroads

On the surface (the pun only serindipitous), the question of hip resurfacing or hip replacement wouldn't seem to be too difficult a choice. But there's clearly more to this than meets the eye.

Hip resurfacing is a bone-conserving alternative to traditional THR for patients suffering from abnormalities of the hip, including osteoarthritis. Segment leader Smith & Nephew's Birmingham implant replaces the hip joint with a metal ball and cup. Surgeons cut away a tiny amount of the top of femur, conserving bone, vs. the more invasive total hip replacement.

As a panel discussing the question at AAOS found, there is no simple answer to the resurfacing-vs.-replacement question.

William Maloney, MD, professor of surgery and chair of the department of orthopedic surgery at Stanford University (Stanford, California), who chaired the panel at an AAOS media briefing, said the question is being asked with increasing frequency by patients coming into his and other surgeons' offices.

He said that with more information on hip resurfacing finding its way onto the Internet, as well as in direct-to-consumer advertising, "Patients are coming into our offices and asking for the procedure without really understanding what is involved or even if they are a suitable candidate." He added that in its bid to gain market penetration, hip resurfacing is running into THR, terming the latter "one of the most cost-effective innovations in medicine."

Panelist Robert Trousdale, MD, of the Mayo Clinic (Rochester, Minnesota), took the "pro-resurfacing" position, saying that such a process "provides reliable pain relief and function, with the benefit of preserving the femoral bone stock." He said he will "consider" resurfacing in younger patients (under 60 years of age — "young" by orthopedic redo standards), those who are at an end stage of their arthritic hip disease and thus would be candidates for an arthroplasty, are acceptable candidates for metal-on-metal bearing surface, have good femoral neck bone stock, and no major leg length or offset problems.

Trousdale said that, generally speaking, men seem to be better candidates for this than women, in part because "women tend to shy away from resurfacing." Regardless of gender, "we have found that patients' perceptions of resurfacing ... are inconsistent with the known peer-reviewed advantages/disadvantages of the procedure."

Tom Schmalzried, MD, of the Joint Replacement Institute at Othopaedic Hospital (Los Angeles), noted that hip resurfacing is much bigger in Europe than in the U.S. In Europe, he said, "more than 50% of orthopedic surgeons do resurfacing," while in the U.S., the number is "less than 10%, but [is] rapidly growing."

He echoed fellow panelists' points concerning patient selection, saying that "light, small women are at higher risk in hip resurfacing," because tending to have insufficient femoral bone neck stock to avoid fracture problems later. "The real variable is bone density," he said. "As the bone density goes down, the risk of femoral neck fracture goes up."

At an earlier orthopedic meeting in Hawaii, Schmalzried said that it is the job of physicians to distinguish which patients are better served with a total hip replacement and which would benefit more from resurfacing. "I think that the right way of thinking of this is not as competing technologies, but when is total hip in aggregate better and when is resurfacing ... better?" he said.

"The results are really, really good with total hip replacement," he said at the AAOS session, "so to back resurfacing, you need good arguments and data." And he noted that one of the key outcomes for a THR patient is improvement in range of motion, and that range of motion is not something that can be improved via resurfacing.

New THR technologies

Fellow panelist Paul Lachiewicz, MD, of the University of North Carolina (Chapel Hill), discussed the new technologies being seen in the total hip replacement space, citing cementless acetabular components, polyethylene bearing surfaces and stemmed femoral components, both uncemented and cemented.

"Those technologies will result in excellent pain relief," he said, "and [will] function for at least 10 to 15 years in the vast majority of patients." Lachiewicz cited improved bearing surfaces, including polyethylene, ceramic and metal varieties, as well as new tantalum and titanium ingrowth surfaces.

He noted that with use of highly-crosslinked polyethylene, "most studies have shown 50% to 70% reduction of wear, even in younger [and thus more active] patients."

In his view, "we're in a revolution" as far as total hip arthroplasty is concerned. "THA can be used in all age groups, diagnoses, body-mass index, and the vast majority of hip shapes," Lachiewicz said. "There are no concerns about early or late femoral neck fractures, metal ions or hypersensitivity." Unsurprisingly, he said, "I continue to use a modern stemmed THA in all my ptients."

For his part, Paul Beaule, MD, of University of Ottawa Hospital in Canada's capital city, said the heightened consumer interest in the hip-resurfacing alternative is driven by such patients being "more demanding" in their expectations following hip surgery.

He said the so-called "Millennium patient" is "more focused on function post-operatively." They are "unaccepting of restrictions," and have high expectations for "lifestyle preservation," which Beaule said "is a very important part of what we do" as surgeons. "New technology is not the answer to everything," and surgeons "need to re-educate themselves" to reconnect with the hip-resurfacing option.

Smith & Nephew's Orthopaedic Reconstruction division has the clear lead in the domestic hip-resurfacing sector, having received FDA approval of the Birmingham system in May 2006.

Stryker expected to be nipping at S&N's heels during the first half of this year as U.S. distributor of the Cormet 2000 hip resurfacing system made by the Corin Group (Cirincester, UK), while both Wright Medical and Biomet are angling for a piece of whatever pie exists now and set to expand.

An orthopedic 'triple play'

"Triple play," a term found ordinarly as a defensive sparkler in baseball, has a different meaning at an AAOS meeting. A group of orthopedic surgeons discussed what they referred to as "the 21st Century triple play" — stem cells, tissue engineering and gene therapy — at a press briefing. And panel moderator Thomas Einhorn, MD, chairman of the department of orthopedic surgery at Boston University, was an appropriate choice to lead the discussion. Just last year, he performed his initial revision hip replacement procedure using the emerging procedure of harvesting the patient's own stem cells.

"This area of musculoskeletal medicine shows great promise for the use of stem cells, tissue engineering and stem cells, Einhorn said in an AAOS statement. During the briefing, he cited the "exciting advances" in the field, noting that with them, orthopedists "now can use the microvascular surgical methods that have been developed over the past decade, but now can use stem cells" to make the outcomes even more dramatic.

He said that in the hip-revision case, the use of the 50-year-old male patient's own stem cells from bone marrow solved what he termed the "severe loosening" of the femoral component of a total hip replacement. "As orthopedic scientists, researchers and surgeons, we treat bones, joints, tissues and muscles — the exact areas where stem cells are meant to be put to use," Einhorn said.

He and others on the panel noted that today, stem cell technology is being used almost exclusively for fracture repair and bony defects, but they described advances that show the implications for the triple play approach are limited only by the imagination —which means they aren't limited at all. "One day soon," he said, "we may be able to harvest the stem cells of arthritic patients and direct those cells to the damaged and degenerative cartilage ... [the cause of] the arthritic pain."

Biologics 'very helpful'

Panelist (UPMC), said that biological solutions to musculoskeletal problems "can be very helpful ... that has been proven over the past 10 years." "A number of us [orthopedic surgeons] have begun to combine this work under the banner of regenerative medicine. Much progress has been made over the past five years," he said.

Huard cited the development of muscle-derived stem cells (MDSCs), noting that they have skeletal applications in muscle repair, bone and cartilage repair, cardiac repair, and spinal cords and nerve repair. And he cited a study conducted in the alleviation of urological dysfunction with 30 patients treated with MDSCs thus far and one-year follow-up. That has led to FDA approval for a 100-patient trial that will be conducted by UPMC this year.

"MDSC displays an improved regenerative capacity, Huard said. "Among other things, they appear able to reduce scar tissue formation and induce neuroangiogenesis." He added that regenerative medicine "is coming," and that "autologous cell culturing is key." MDSCs can be used, Huard said, to repair ligaments, cartilage, muscle and meniscus.

Fellow panelist Scott Boden, MD, of the Emory Spine Center (Atlanta), touched on spine fusion and bone applications, saying that "spine fusion is one of the toughest places in the body to try to generate bone formation," so use of stem cells offers great potential. However, he said, "For the spine, you may need 100 million cells" to make it work.

Boden said that a lot of the advances being made in the field are in terms of the platform — "the type of scaffold used." The exciting thing, he said, "is that if you use the right growth factor, you will be able to grow bone." The key issue, he said, is "What's the right combination?" or put another way, "How do you induce growth?"

Gene therapy — just routine?

The question, Boden said, "is whether the use of gene therapy should be applied to routine use, or just difficult bone-growth cases." For now, the latter seems the likely choice.

Also on the panel was Scott Rodeo, MD, of the Hospital for Special Surgery (New York) and associate team physician for the Super Bowl champion New York Giants.

Discussing rotator cuff surgery, he said tendon-to-bone healing "is an imperfect process ... this is a big clinical problem for us." Noting that "we have learned some lessons from embryonic stem cell development," he cited some sheep studies involving the use of BMP-12 in which repairs were two to 2-1/2 times stronger than native rotator cuffs.

His conclusion on the future of such therapeutic approaches? "Advances in understanding will lead to novel treatments to improve healing."

To audience questions about availability of stem cells and safety of their use, the panelists were of one thought: Yes, there are ample sources of cells, and certainly, safety in their use is of the highest priority.

Rodeo said, "I'm confident that there are enough sources of stem cells," and Boden said, "Safety is critical - it is our No. 1 concern."