CD&D European Editor and Staff Reports

William Wijns, MD, is one of the most prominent European leaders for interventional cardiology and on his watch as president of the European Association for Percutaneous Coronary Intervention (EAPCI) the practice of PCI has seen spectacular growth, been buffeted by alarming criticisms, and firmly established the medical effectiveness of the procedure.

Yet recently Wijns has used his position to chastise colleagues for having lost credibility within the medical community, allowing themselves to be characterized as "spoiled children playing with toys," just at the moment where the practice of PCI is reaching maturity.

In an effort to restore professional leadership, Wijns, of Cardiovascular Center Aalst (Aalst, Belgium), has pushed for the creation of the Stent for Life program to reassert the medical value PCI over the fascination with technology, "that got us into trouble where the value of PCI is being strongly challenged, if not questioned.

"We have been so in love with these wonderful tiny devices," he told Cardiovascular Devices & Drugs, "we have marveled at sophisticated elution and resorption rates, which are indeed fantastic and very much needed. But this is not the way we need to be speaking about PCI.

"We need to restore the image of PCI and the doctors performing these interventions by returning to a focus on the patients," he said.

"Timely PCI can be life saving, it reduces morbidity. It is now undisputable that there is a benefit for emergency revascularization. The evidence is there. And now that it becomes the right thing to do, everyone should be interested in and take part in making Stent for Life happen," he said, especially industry.

"The magic is gone," from PCI as a therapy, Wijns wrote in an editorial published in EuroIntervention, from which the following extracts are drawn:

"The excessive focus on technicality and the never-ending public controversies on the respective merits of discrete products have contributed to devaluate PCI as a therapy and those who practice it, as a professional group.

"The late recognition of the rare safety issues that are associated with drug-eluting stents has triggered a period of intense scrutiny, skepticism and sometimes animosity on behalf of non-interventional cardiologists, cardiac surgeons, journalists or lawyers. The publication of randomized trials that do not favor indiscriminate use of PCI fuelled opposition even further.

"Allegedly too, patients are submitted to device-based therapies, some of which are either insufficiently validated or poorly indicated. . . . The scientific validity of the evidence that we have accumulated is shaken. The robustness, the relevance, if not the honesty of the reported data are questioned altogether."

"A healthy dose of skepticism needs to be re-introduced. Physicians should refrain from compromising with the agenda of the industry. In the long term, confusion of interest is potentially damaging for everybody, including our industrial partners, as demonstrated by the current situation.

"We ourselves have allowed the scope of our field to shrink down to material trivia while failing to promote the life-saving indications of these procedures. When applied to patients with acute presentations of the disease, PCI is indeed reducing mortality, non-fatal infarction and stroke, with treatment effects superior to any other strategy. Providing this service to the community, improving procedural outcome through innovation and promoting implementation and proper funding with regulatory bodies and payers shall be the principal focus of our action."

Caution and prudence urged

This annual EuroPCR meeting for cardiac interventionalists in Europe has traditionally been focused on angioplasty and stenting of coronary arteries, an emphasis reflected in the original name of the event, the Paris Course on Revascularization (PCR).

The acceptance and adoption of percutaneous cardiac intervention (PCI) has seen not only rapid growth but an expanded application, for example to peripheral arteries in the leg, which is another emerging area of practice now covered at EuroPCR.

The move to valve replacement and repair using PCI techniques holds the potential to be just as disruptive for cardiac surgery, which has already seen interventional cardiologists claim with stenting a significant share of procedures that previously would have been treated with by-pass surgery.

For the moment, TAVI is restricted to patients who are denied open heart surgery and the procedure has given new hope to this class of patients and a justification of responding to an unmet medical need for interventionalists.

In other words, TAVI is beginning with the sickest of patients who are typically over 75 years old and have co-morbidities such as pulmonary and renal dysfunctions and arterial complications.

But as techniques and patient outcomes improve, it is clear that TAVI could pose an alternative for younger and less severely ill patients who today are accepted for traditional aortic valve replacement.

Where TAVI today is restricted to patients with Euroscores higher than 20, there is a trend, if not a pressure, to move to patients with lower scores, acknowledged Serruys.

In his presentation of the SOURCE registry, Thomas commented that "there are procedures being done in Europe with Euroscore less than 20 in significant numbers."

In sharp contracts with the competition between surgeons and interventionalists in stenting, many cardiac surgeons have been among the early adopters of TAVI, and these surgeons already replace valves for patients as young as 70 years and with a Euroscore below 20.

In his presentation on the "Future Evolution of TAVI in Europe," Serruys returned to his call for a large-scale study, saying, "If TAVI is not evidence-based medicine and does not take into account the health economic factors, it will not be considered legitimate or justified in the eyes of the health authorities and therefore not reimbursed.

In exclusively treating end-of-life patients, there is for the moment an open question regarding TAVI as to whether it is cost-effective and justifiable for the healthcare systems of European countries to offer an expensive surgery that extends the quality of life for a patient population with a limited life expectancy.

FDA making progress after external science review

Gail Cassell, a microbiologist and Eli Lilly Distinguished Scholar, played a major role in convincing the FDA that it was in need of an external review, because "all centers should have external review bodies, as other agencies, to encourage improvement."

FDA approval for the report was a coup, because it was only "the second time its science had been reviewed as an entire entity in the agency's 100 years," she said. She collected a review panel of scientists at the highest levels in academia and corporations, a Nobel laureate, and one lawyer, Peter Barton Hutt, formerly chief counsel at the FDA. The task: to investigate areas of research, but not individual programs or individual scientists.

Demands on the FDA had soared, said Cassell during a progress update at the BIO 2009 conference in Atlanta in May, but "resources had not." More than 400 ports of entry in the U.S. relied on only 100 FDA inspectors. The FDA also is currently responsible for over 300 sites in 100 countries. As a consequence, the report found that there is a "fire-fighting" regulatory posture in the agency, vs. "proactive regulatory science," she said. Cassell added, "Individuals are stretched very thin." The review found that agency scientists were unable to keep up with advances within regenerative medicine, genomics, nanotechnology, medical imaging, robotics and wireless healthcare devices.

Peter Barton Hutt was the single regulatory lawyer amid 32 scientist-reviewers. He eventually made the agency cough up budgetary statistics and also performed a review of the agency's responsibilities from a legal standpoint. He found that the FDA's mandates had been amended 225 times since its inception.

When he looked at the last 20 years, he found there were about six new laws a year: six new mandates for the FDA. "There is no other agency that has had this kind of obligation set on them by Congress," he said. In terms of resources; however, he found that in 20 years the FDA's financial support had not even kept up with inflation and "they did not get one extra person" to do the added tasks. He said some congressionally-mandated projects still remain unfinished even ones from the 1960s and 1970s

Hutt does not blame the FDA. "You can't expect to tell an agency to do more, with less," he said. "That's hollow government." He added, "This is what happens when you squeeze an agency to death."

The National Institutes of Health budget occurs largely due to lobbying by both scientists and nonprofits. People benefit from FDA strength, Hutt said. "Why aren't people marching in the streets for the FDA?"

Coalition makes case for personalized medicine

A total personalized medicine approach might be far from becoming a definite reality in the U.S. at the moment, but the method, which could eliminate the current one-size fits all philosophy in administering care, is rapidly gaining ground.

From the discussions on Capital Hill about comparative research over studying disease affects on a general population, to greater effort and funding being put into molecular diagnostics- the case for personalized medicine is moving forward.

"We're seeing more interest and less skepticism toward [Personalized Medicine],"Ed Abrahams, executive director of the Personalized Medicine Coalition (Washington), told Biomedical Business & Technology. "We're clearly seeing movement . . . greater investments and a larger number of products available on the market."

Recently the Personalized Medicine Coalition (Washington) released the 2nd edition of its 2006 report, The Case for Personalized Medicine, in hopes to further bolster the need to truly turn to this method and perhaps to enter into the current healthcare discussion.

The robust report, which is a living document and subject to more changes in the future, remains true to its namesake and builds a case for personalized medicine, at a time when the nature and future of healthcare are center stage in what promises to be a contentious political debate.

"We hope that the [report] captures the attention of policy makers and that they see what they do now has an impact on healthcare," Abrahams said.

The report specifically focuses on where the country has come and where it could go given the current interest in personalized medicine. It also shows what advances have been made since the 2006 report was released.

Since that time, the number of prominent examples of personalized medicine treatments and diagnostics has increased from 13 products (69% of which were for cancer) to 37 products (56% of which are for cancer).

Some of those products such as Caris Diagnostics' (Irving, Texas) Target Now, an oncology testing service and Applied Biosystems' (Carlsbad,California) SOLiD system, which identifies methylation patterns across the genome, were discussed at length during the 100th annual meeting of the American Association for Cancer Research (AACR; Philadelphia) in Denver.

The report gives other real-world examples of personalized medicine in action and has insights from leading members of industry and government.

Geoffrey Ginsburg, MD, PhD, director of the Center for Genomic Medicine at the Duke Institute for Genome Sciences & Policy (Durham, North Carolina), remarked on how such practices and approaches impacted research at Duke.

"Personalized medicine approaches are beginning to affect patients, researchers, and clinicians in very significant ways," Ginsburg said. "At Duke, we are conducting a series of genome-guided clinical trials that rely on the genomic fingerprints of disease to predict the best course of treatment for each patient with lung, prostate, and breast cancer. As described in this landmark report from the Personalized Medicine Coalition, such individualization of treatment will become more commonplace in coming years, leading to improvements in clinical outcomes."