Medical Device Daily Washington Editor
Rep. Maurice Hinchey (D-New York) has never shied away from proposing legislation to modify the way FDA does its business, and this last year of the 111th Congress is no exception. Hinchey recently reintroduced H.R. 4816, the FDA Improvement Act of 2010, which would strip user fees out of the agency's direct funding source and put them into the U.S. Treasury's general fund, but the language of the bill also appears to address pre-emption of state regulatory law for PMA devices.
According to the text of the bill posted at www.govtrack.us, H.R. 4816 would also put an end to negotiations between industry and FDA regarding review times for the various kinds of applications that are subject to user fees. These provisions would be in effect as of Sept. 30, should the bill pass.
However, it also appears that Hinchey has no co-sponsors for the bill, although the chairman of the House Energy and Commerce Committee, Henry Waxman (D-California), made it known through a legislative staffer at the FDA/FDLI Annual Conference last year that he sees overturning pre-emption as a “very high priority item“ (Medical Device Daily, April 27, 2009). Rep. Frank Pallone, chairman of the Energy and Commerce Health Subcommittee, has expressed similar sentiments and introduced the Medical Device Safety Act of 2009 last year with more than 100 co-sponsors. The late Sen. Ted Kennedy sponsored a similar bill in the Senate in 2009, but won over only 23 co-sponsors.
Recent case law has continuously confirmed the Supreme Court decision in the case of Riegel v. Medtronic, which has been applied to PMA supplements as well as to full PMAs. The applicability of pre-emption to PMA supplements overturned the decision in the U.S. Eleventh Appeals Court in Goodlin v. Medtronic, a decision that did not offer pre-emption for a PMA supplement because FDA's requirements were not seen as sufficiently specific to justify pre-emption.
Under Hinchey's bill, FDA would be able to require manufacturers to make changes to product labels in the event that new risk information arises, and the bill would also mandate information on adverse events seen in clinical trials to be presented in product labels, which would also have to be written so as to be intelligible to laypersons.
The bill would forbid those with any discernible financial conflicts of interest from taking part in FDA advisory committees, and would also require a consent form for off-label use of drugs, a provision that is apparently not applied to medical devices.
Kurt Karst of the law firm of Hyman Phelps & McNamara (Washington), the author of a blog entry on the bill at FDALawblog, confirmed to Medical Device Daily that the bill would indeed end pre-emption. “It would amend the FDC act to legislatively overturn the Riegel decision. It's a response to the Riegel decision,“ he said.
“After Riegel came down, Waxman said he wanted to make it a priority,“ as did Pallone, Karst noted. Despite any hubbub associated with the bill, however, Karst said the bill's chances are probably somewhere between slim and none. “I certainly thinks its possible for him to find supporters, but I don't give the legislation much of a chance,“ he said.
Eucomed says Brazil, Mexico pay faster
Everyone wants to be paid in full and to be paid promptly, but reality often fails to live up to these twin expectations. The European Medical Technology Industry Association (Eucomed; Brussels, Belgium) released a statement yesterday indicating that Mexico and Brazil, two nations not known for having state-of-the-art regulatory and reimbursement mechanisms, are quicker to pay than many EU nations.
According to Eucomed's March 18 statement, Brazil and Mexico “are putting many European countries to shame by paying their suppliers within 55 days,“ while nations such as Spain and Italy typically need 250 days to pay their bills. The Eucomed statement notes, however, that the turn-around time “exceeds 600 days “ in some EU nations, although the report notes that Spain's legislature is looking at a bill that will provide a 30-day payment policy. Also on board with efforts to bring some zip to the pace of payouts is the government of the UK, which the Eucomed statement says “has committed . . . to pay within 10 days“ in some cases.
John Wilkinson, Eucomed's CEO, said in the statement that small device makers “are waiting up to 700 days to be paid by public bodies“ in Europe, which has created a situation “so severe that some companies are facing bankruptcy or may consider to exit the market.“ Wilkinson also said that the withdrawal of products from the EU market would “have the effect to adding to health inequalities across Europe.“
Boston Scientific soldiers on despite recall
The recall announced earlier this week by Boston Scientific (Natick, Massachusetts) did not deter the firm from making a strong argument for an expansion of indications for its line of resynchronization/defibrillator (CRT-D) units at an advisory committee yesterday, which will be reviewed in greater detail in Monday's edition of MDD. Boston Scientific seeks to expand the indications for CRT-D use from left ventricular ejection fraction of less than or equal to 35% and a QRS interval of longer than 120 milliseconds to an LVEF of less than or equal to 30% and a QRS interval lasting 130 milliseconds or longer.
Ken Stein, MD, the company's chief medical officer, told the panel that “heart failure is associated with a five-fold increase in mortality“ for five years after diagnosis, and that the rationale for the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy) trial was that those who are asymptomic or mildly symptomatic for heart failure do not from ICD therapy other than to ward off sudden cardiac death. This fact, he asserted, suggests “a potential role for CRT-D earlier in the process,“ with an eye toward “slowing the progression“ of the disease into profound heart failure.
Arthur Moss, MD, the lead investigator for MADIT-CRT, said double-blinding was deemed “impractical if not impossible“ when the study was designed six years ago because patients with such implants must have a card identifying their units for providers. However, an external committee charged with adjudicating adverse event reports was said to be unaware of assignment. “To my knowledge, there was total and complete blinding“ of this committee, Moss said.
Kimberly Selzman, MD, of the Office of Device Evaluation, who is also the chief of electrophysiology at the Salt Lake City Veterans Administration Hospital (Salt Lake City, Utah) told the panel that “the sponsor did meet with FDA during the course of the trial and did incorporate“ some of the feedback from the agency.
Selzman said that beta blockers were used by 90% of the patients overall, but that 30% or less of the patients in each arm of the study were at the appropriate dose of 150 milligrams a day of carvedilol (Coreg). She also cited “a fairly small representation of class I [heart failure] subjects,“ “which may have affected the combined results,“ including mortality. She also said the lack of blinding prejudiced the outcomes, despite the blinding of those who adjudicated adverse events.
Selzman noted that the statistical significance for secondary endpoints was not ascertainable because the study was not powered to fully examine them, but of the primary endpoints, she said there was no beneficial effect seen in class I patients, perhaps “due to a small sample size.“ Only a total of 13 patients in class I made it to 48 months, suggesting “a need for more data“ for this population.
Blockage of the nerves of the left ventricular bundle branch was associated with an improvement in the study arm, but while “those with the left bundle showed a treatment benefit“ across the entire study, this did not seem to be the case for those in class I heart failure, Selzman remarked.
Selzman acknowledged the greater benefit seen in women, but noted that the “cause of this is not readily apparent.“ Women in the trial were twice as likely to be non-ischemic and substantially more likely to suffer from left bundle branch block, although women in MADIT-CRT were also more likely to have checked into a hospital prior to enrollment. Whether ischemia and bundle branch blockage are the sources of the better performance in women “is not clear,“ Selzman said, but she mused that the difference but might be due to differences in medical therapy. “There were no differences in complications“ between the two sexes, she said.
EMEA to meet on nanotherapies
The European Medicines Agency has announced it will hold a two-day meeting next month to address nanoscale materials in therapeutics. The announcement, which does not indicate the location of the meeting, indicates that the meeting will take place April 26 and 27 and will address issues such as nanoscale materials already on the market and the characterization of nanoscale materials. Those who wish to participate can contact info@ema.europa.eu.
Mark McCarty, 703-268-5690