CD&D Washington Writer and Staff Reports

With the Democrats taking the White House and making big gains in both the House and Senate last month, congressional oversight of medical product safety will shift from the FDA to industry, and device and drug makers should be prepared to be in the crosshairs, said John Manthei, global co-chair of the healthcare and life sciences practice at the Washington law firm Latham & Watkins.

"Congressional oversight is an intensely political process," Manthei said in a post-election call with reporters.

The current Democratic chairmen of the healthcare-focused congressional committees have done a "remarkable job" in highlighting the failures of FDA under the Bush administration, he said. "I don't think the Democratic congressional investigators are going to be anxious to pull up the Obama political appointees and subject them to the same level of criticism," he said.

Instead, Manthei said, the 111th Congress will be focused on making sure manufacturers are forthcoming with regulators about emerging safety data related to their products and that the industry is "playing its role within the fundamental integrity of the FDA regulatory process."

Gone are the days of the "five-year comfort zone" of major FDA reform, which over the past two decades has been tied to the passage of bills reauthorizing drug and device user fee programs, said Manthei, majority counsel to the House Energy and Commerce Committee from 1998 to 2000.

He predicted that bills affecting FDA and medical product makers will now come to the floor more rapidly, being passed yearly rather than waiting to be attached to a larger piece of reform legislation, such as the Prescription Drug User Fee Act, which has come up for renewal every five years since 1992.

Therefore, Manthei said, the medical product industry is going to need to be more engaged with the legislative process and "watch it closer than they have in the past."

Legislation creating a regulatory pathway for the FDA to approve follow-on biologics, also called biosimilars, is going to be "front and center" on Congress' agenda early next year, Manthei surmised.

He said he also expects lawmakers to take action fairly quickly on re-importation bills – legislation that would allow drugs produced by U.S. manufacturers that are shipped and sold in Canada and Europe to be re-imported by U.S. patients into this country – given that President-elect Barack Obama (D-Illinois) has shown support for the legislation in the senate.

Additional funding for the FDA also will be a top priority for the Democrats in 2009, he said.

Saying it is "too early" to know who will be placed in the FDA commissioner's job, Manthei said he is unaware of anyone specifically on Obama's list for consideration. He noted that Susan Alpert, senior vice president and chief regulatory officer for Medtronic (Minneapolis) and a former high-ranking official in the agency's Center for Devices and Radiological Health, has been mentioned in certain circles as a potential contender.

However, Manthei emphasized that as far as he knows, Alpert is not on any definite list and no one has emerged as an early candidate for the FDA chief's job.

He noted that Sen. Edward Kennedy (D-Massachusetts), chairman of the Senate Health, Education, Labor and Pensions (HELP) Committee, has indicated that he did not want anyone from the drug or device industries to fill that slot.

"It will be interesting if that selection criteria will still hold," Manthei said. "That obviously is going to eliminate a number of potentially very qualified applicants."

He said the outcome of the election will bring little change to key congressional healthcare committees in the 111th Congress, since the Democrats already hold the chairmanships.

Coalition wants Obama to focus on quality

Although the economy and national security are Obama's first concerns, most Americans will still say healthcare also is a top priority in need of immediate attention. Partnership for Quality Care (PQC; New York) is taking the opportunity to address the new administration with its primary mission, which is that the best way to reduce healthcare costs and improve services is to focus on quality as a key metric, particularly when it comes to treating millions of people with chronic diseases.

PQC claims it's the nation's largest joint labor-management healthcare coalition, with heavyweight members such as Kaiser Permanente (Oakland, California), representing about 50 million patients. PQC released a report last month on how to tackle the escalating social, economic and individual costs of treating and managing chronic disease, specifically timed for receipt by the new presidential administration.

"The genesis of this report was during a meeting last March in Washington," PQC Executive Director Kate Navarro McKay told Cardiovascular Devices & Drugs. "It was attended by advocates of healthcare reform and we talked about the question of choosing between access, quality and cost. We say that the best way to get a handle on costs is to focus on quality. There are a lot of things we could be doing more effectively and efficiently on direct medical costs. The key metric to look at when reforming healthcare is 'Does this improve quality?'"

Titled Quality, Cost Control, Universal Healthcare, the report shares success stories from providers throughout the country such as Kaiser Permanente, the Mayo Clinic (Rochester, Minnesota) and Massachusetts General Hospital (Boston).

"Exit polls have shown that 10% of voters say healthcare is a top issue and two-thirds say they are worried about being able to afford healthcare," McKay said. "Part of economic recovery is addressing the huge access to healthcare problems. We can't wait to start working on a solution. Our message to Obama is that the longer we delay, the more difficult it will be to address it. There's overwhelming support for healthcare reform."

The group believes that a focus on quality is the correct way to achieve those goals. "Americans also face a crisis of quality that is inextricable from the problems of cost and access," according to the PQC report. "The U.S. has extraordinary healthcare workers and hospitals, but care is too often uncoordinated, fragmented, and inconsistent with patients' needs."

Sleep apnea link to heart disease found

It has been known for some time that those individuals suffering sleep apnea are at significantly higher risk for heart disease and, too frequently, heart attack and death. Exactly why has been a matter of surmise.

Now, sleep medicine and cardiovascular researchers at The Ohio State University Medical Center (Columbus) say they have identified the link between the two, examining what would happen to fat cell secretion of certain substances when sleep apnea was simulated.

They began by observing that most of the substances secreted by fat cells have undesirable effects, while others, such as a substance called adiponectin, may have the opposite action and even prevent atherosclerosis.

The findings, published in the journal Experimental and Clinical Endocrinology & Diabetes, showed that when fat cells were exposed to the repetitive dipping of oxygen levels, similar to that found in patients with obstructive sleep apnea, the secretion of adiponectin by the fat cells was decreased.

Obstructive sleep apnea affects 12 million Americans, with the repetitive disruptions of breathing that they experience lead to drops in oxygen levels, called intermittent hypoxia (IH).

The researchers hypothesized that IH would result in the dysregulation of APN expression and secretion. 3T3-L1 adipocytes were exposed to IH at 12 cycles/h for 6 h/d to simulate the IH condition, and mimicking what happens in sleep apnea. Control adipocytes were exposed to 21% O₂ under identical conditions.

After 48 hours of incubation, IH caused a decrease in the secretion of total and HMW APN in spite of a significant upregulation of APN mRNA expression by adipocytes. "Since adiponectin appears to prevent atherosclerosis, this finding could potentially explain why patients with obstructive sleep apnea are predisposed to develop heart disease," said lead author Ulysses Magalang, MD, of the division of pulmonary, critical care, allergy and sleep medicine at OSU and director of its sleep medicine program.

He said that further studies are necessary "to determine exactly how intermittent hypoxia reduces the release of adiponectin by fat cells."

The study was supported by funds from the National Institutes of Health and Davis-Bremer Medical Research.

Stress testing prior to PCI lacking

Researchers at the University of California, San Francisco (SCSF) investigating the procedures to open narrowed coronary arteries – such as angioplasty and stenting – found that less than half of Medicare patients had documented noninvasive stress testing prior to elective percutaneous coronary intervention (PCI).

The team analyzed a 20% random sample of 2004 Medicare claims data, amounting to 23,887 patients who were 65 years or older. The researchers found that 44.5% of the study population underwent stress testing within 90 days prior to receiving elective PCI. While PCI can provide quicker relief than medical therapy alone, researchers say, but it carries an increased risk of repeat revascularization, late-stent thrombosis and a decreased quality of life if performed in patients with minimal symptoms. The findings are reported in the Oct. 15 issue of the Journal of the American Medical Association.

Rita Redberg, MD, corresponding author on the paper, a cardiologist at UCSF Medical Center and director of Women's Cardiovascular Services at the UCSF National Center of Excellence in Women's Health, said, "With the increasingly widespread use of PCI in patients with stable coronary artery disease, it is important that the procedure is being done in patients for whom there is reasonable expectation of benefit, patients with documented ischemia or its symptoms."

According to previous studies published in the journal Circulation, patients with stable coronary artery disease now account for the majority of PCIs done in the U.S. Given this shift, the researchers note, various association guidelines recommend that any vessels to be dilated for patients with stable angina must be shown to be "associated with a moderate to severe degree of ischemia on noninvasive testing." Previous studies have shown that patients who receive PCI in accordance with these guidelines have better outcomes.

"This means, in most patients who are not having a heart attack, a noninvasive stress test should take place before physicians make the decision to go forward with invasive procedures like stenting and angioplasty," said Grace Lin, MD, lead author on the paper and associate adjunct professor of medicine at UCSF. "We undertook this study to scrutinize a common procedure to learn how best to direct our resources."

The researchers found that there was significant geographic variation in the rate of stress testing by hospital referral region, with rates ranging from a low of 22.1% to a high of 70.6%. And patients who had a prior cardiac catheterization were less likely to undergo stress testing prior to elective PCI.

Ejection fraction via blood volume measure

A comparison study of the blood volume and anemia characteristics in heart failure patients, reported in the October issue of The American Journal of Cardiology, categorized heart failure patients on the basis of whether they had a normal ejection fraction vs. a low ejection fraction. Dmitry Abramov, MD, and Mathew Maurer, MD, et al. at Columbia University Medical Center (New York) utilized the Blood Volume Analyzer BVA-100 from Daxor (New York) to study the blood volume and the presence of anemia in these heart failure patients.

Main findings of the study were two-fold: 88% of the patients with a normal ejection fraction had red cell deficits (true anemia), compared to 59% of the patients with a decreased ejection fraction; and in contrast to patients with a low ejection fraction, patients with a normal ejection fraction could be hypovolemic (low blood volume), normovolemic (normal blood volume), or hypervolemic (high blood volume).

The authors said that the standard test for anemia, the hemoglobin or hematocrit, correlated very poorly with a direct measurement of the red cell volume status of the patient. Better was a direct blood volume measurement for diagnosing these various blood volume conditions. Daxor said that the study "confirms previous studies from Columbia University demonstrating that only a measured blood volume can accurately determine the volume status of a heart failure patient."