Blood substitute companies and others developing emergency-use products might be facing new clinical study regulations. The FDA said last month that it is looking at the rule that allows for clinical emergency research, specifically in those situations where informed consent cannot be obtained or is difficult to maintain. That regulation, 21 CFR 50.24, lets studies test experimental emergency treatments such as medical devices, biological products and drugs on patients with specific life-threatening medical conditions such as head trauma, cardiac arrest and stroke, even though neither patients nor their families are available to give informed consent.

In those cases, patients in life-threatening situations have been enrolled in research studies before arriving at a hospital, sometimes receiving treatment while in an ambulance or in the emergency room. Since the rule went into effect in 1996, the FDA has received about 60 requests to conduct clinical investigations, but “many fewer” have been conducted, said Sara Goldkind, a bioethicist at the FDA, during a conference call. The agency has issued a new draft guidance for therapeutic companies working in the field of emergency medicine, institutional review boards and clinical investigators.

“We’ve had 10 years since the publication of this regulation,” said Janet Woodcock, the FDA’s deputy commissioner for operations, “and we would like to have a public evaluation and discussion of the outcomes of this.”

In its review of the emergency-research rule, the FDA was seeking input at a public hearing in September. In its Federal Register announcement, the agency included a number of questions on the matter and identified challenges related to this type of research, such as consulting with representatives of the communities in which the studies will take place and from which the subjects will be drawn, public disclosure prior to initiation, as well as results after the study ends.

The FDA’s draft guidance better defines the oversight roles and responsibilities of sponsor companies, institutional review boards and clinical investigators than previous guidance, includes a section on in vitro diagnostics and “gives additional points to consider” on responsibilities around community consultation and public disclosure, Goldkind said.

Since adopting the regulation a decade ago, the FDA has reviewed concerns expressed by investigators, ethicists and other interested parties, in addition to issues raised in the literature and its own experiences.

Particular targets of criticism have been companies developing blood substitutes. Critics have questioned both Northfield Laboratories (Evanston, Illinois) and Biopure (Cambridge, Massachusetts) for studies in trauma care where the patients may not be able to provide informed consent or may be in no condition to understand the risks agreed to in the consent.

Regulators said they plan to use the information obtained at the public hearing to help develop strategies to address challenges that have been identified and will consider comments received on the draft guidance, as well as comments and suggestions received at the public hearing to determine whether the regulation’s current framework is adequate or if modifications are needed.

The agency is carrying out the review as part of its Human Subject Protection and Bioresearch Monitoring Program, an ongoing effort to ensure scientific and ethical rigor in clinical research. More broadly, the initiative includes a series of new policy and regulatory developments aimed at strengthening its oversight and protection of study patients and the integrity of resulting data to facilitate the modernization of the regulation of clinical trials and bioresearch monitoring.

New FDA task force on tissue safety

Tissue banks and the harvesting of human cadaver tissue continues to be a magnet for expos -style headlines. In response, the FDA said it will assemble a multidisciplinary task force to look into its regulatory approach to this industry. Jesse Goodman, MD, director of the Center for Biologics Evaluation and Review (CBER), said that the task force’s main goal “is to identify whether any additional steps are needed to further protect the public health while assuring the availability of safe products.” It will focus specifically on whether last year’s revamp of tissue regulations, coded as 21 CFR Part 1271, is adequate to keep track of non-organ donations.

The most recent report of illicit tissue sales names Philip Joe Guyett Jr., of Raleigh, North Carolina, as the object of an investigation concerning violation of screening and record-keeping regulations. The agency reported the closure of his operation, Donor Referral Services (also Raleigh), Aug. 18. Over a two-year period, Guyett purportedly harvested hundreds of specimens from an unsterile room within a funeral home that he sold to the Cooperative Human Tissue Network, part of the National Cancer Institute.

Much of the hand-wringing over Guyett stems from his previous brushes with the law, a habit of exaggerating his expertise to pull in customers and the failure of organizations to recognize his deception. His resume was said to have indicated he did a stint as an anatomy instructor at Mount San Antonio College (Walnut, California) between 1997 and 1999, but the school’s records do not confirm that claim.

He also described himself as a “forensic specialist” at the Clark County, Nevada, coroner’s office, but the office indicated that his position there was part-time and voluntary. Guyett was charged in 2000 with pocketing $1,100 after selling a cadaver that had been willed to Western University (Pomona, California) to another school. The Los Angeles District Attorney’s office dropped the charges in exchange for community service, including highway clean-up work and three years of probation, but this experience apparently did not blunt his interest in the tissue donation industry.

The agency forced Biomedical Tissue Services (Fort Lee, New Jersey) to close operations in February after the Kings County, New York, district attorney’s office filed charges that the company had engaged in unauthorized harvesting of body parts. The company’s founder, Michael Mastromarino, and three others were charged with enterprise corruption, grand larceny and unlawful dissection.

Part 1271, which was effective May 25, 2005, is designed to clamp down on disease transmission and covers establishment registration, donor eligibility, current good tissue practices, labeling, adverse-event reporting, and inspection and enforcement. Under 1271, inspections of tissue establishments are still based on risk, which can leave an entity operating under the radar screen for a number of years. According to the September/October 2001 edition of Orthopedic Technology Review, the agency had not inspected “at least 36” of the 154 tissue banks in operation at that time.

In 2003, Goodman, as CBER chief, testified before Congress that in fiscal 2001, 51 of the 132 inspected tissue establishments received a Form 483, an official report of regulatory violations to which recipients must respond within 30 days. The following fiscal year, the number of inspections rose to 165, 48 of which generated 483s. Goodman noted that these inspections “resulted in 10 regulatory actions, including a mandatory recall” for CryoLife (Kennesaw, Georgia). Cryolife tissues were implicated in several problems, including a tissue donee testing positive for Staphylococcus epidermis after receiving a heart valve provided by the company.

At present, the states of New York and Florida have regulations calling for registrations and inspections of facilities, and the American Association of Tissue Banks (AATB; McLean, Virginia) published a set of accreditation standards in 1986.

Bob Rigney, president of AATB, told Biomedical Business & Technology that members must be accredited and that the FDA drew on the association’s standards in devising its regulatory scheme. Rigney also told BB&T that the association would “like to see tighter enforcement activity with banks not accredited by AATB,” but that he is under the impression that the agency’s resources have not always been up to the task. However, he said that the budget for fiscal 2007 includes sufficient funds to hire 18 full-time equivalents dedicated to enforcement of tissue regulations.

Rigney insisted, however, that “other than the two [cases cited above], the record has been pretty clean” for the tissue industry. He noted that most tissues are “pretty heavily processed, reducing the risk that diseases will be transmitted.”

According to the agency’s statement, the task force will “develop an action plan and, where necessary, propose changes to existing policies, as well as generate a set of recommendations, identify what resources are needed to support these actions and report on how the agency can immediately implement its action plan.” Goodman stressed that the new task force “underscores FDA’s recognition that compliance with the rules in place to ensure recipient safety is our highest priority.”

AMA taking its case to voters

Election years often highlight the leverage that various elements of society have with each other, and this year is no different. In response to the impending reductions to the Medicare Part B physician fee schedule, doctors are threatening to take their case to the voting public.

A cadre of physicians appeared at a press conference with Cecil Wilson, chairman of the American Medical Association (AMA; Washington), announcing their opposition to those cuts and to the prospect that Congress will not take this issue up until after the elections.

Speaking for AMA members, Wilson stated that “[w]e believe it’s critical that it happen before the election.”

Bill Thomas (R-California), the chair of the House Ways and Means Committee, has offered a rewrite of a stalled estate tax cut bill that would include language to block the Medicare cuts, but whether Democrats would be willing to make such a bargain is up in the air.

AMA has indicated that it is prepared to act should Congress fail to deal promptly with the Medicare cuts, threatening to roll out an ad campaign designed to convey a message to voters that “time is running out.” The association has allocated roughly $1.5 million for the campaign, which may appear in nationally distributed publications such as Newsweek and U.S. News & World Report.

The Military Officers Association of America (Alexandria, Virginia) also chimed in at the press briefing, with Steve Stobridge, the association’s director of government relations, framing the issue as one that could affect national security. Pointing out that Tricare’s physician payments are pegged to Medicare payment rates, he stated that the cuts would create recruiting and retention problems because military personnel are already having difficulty getting appointments with doctors who accept Tricare.

NCI selects repositories for genome project

The National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) announced that they have selected the first three cancers they will investigate as part of The Cancer Genome Atlas (TCGA) project. The three cancers are those of the ovaries, the lungs and the most common of brain tumors, the glioblastoma. The three were selected partly because large tissue banks already exist for them and are said to account for more than 210,000 cases of cancer each year.

Acting NCI Director John E. Niederhuber, MD, said that the long-term goal of the atlas “is to delve more deeply into the genetic origins … in order to enable the discovery and development of a new generation of therapies, diagnostics, and preventive strategies for all cancers.” He added that results from the project may enable medical science to “detect cancer early, in its most treatable stage, and provide new targets for the development of specific therapies.”

TCGA was launched in December 2005 as a feasibility study to test whether researchers could use large-scale genomic analysis to track genetic changes that are involved in cancer. The three-year pilot recruited tissue banks based on adherence to standards for ethics, technological sophistication, bioinformatics standards and several others. At present, the facilities are the M.D. Anderson Cancer Center (Houston) for glioblastomas, Children’s Hospital of the Ohio State University (Columbus) for ovarian cancers, and Brigham and Women’s Hospital (Boston) for lung cancers.

Congress wants HIT for fed workers

As the House and Senate wait to hash out differences in their respective healthcare IT (HIT) bills, a House subcommittee is looking at a bill that would push HIT along for providers who see to the federal workforce.

Rep. Jon Porter (R-Nevada) introduced H.R. 4859 to the Government Reform Subcommittee on Federal Workforce and Agency Organization this week, lining up a bipartisan list of co-sponsors, including Daniel Lungren (D-California) and Dan Burton (R-Indiana). These two were among the first of Porter’s 13 co-sponsors, signing on to the effort in the second week of March.

The bill would force payers participating in the Federal Employees Health Benefits (FEHB) program to go completely electronic within five years, but not all stakeholders are enamored of the idea.

Elijah Cummings (D-Maryland) argued in a June hearing that H.R. 4859 would “prematurely mandate health [information technology] for federal employees, creating a rift in the health care system by mandating health IT for the public sector before the private sector even got started.” Cummings is among several Democrats who, along with labor unions, are opposed due to concerns that such a move could result in privacy violations. In response to concerns raised by federal employees, Porter inserted language that would bar premium increases by payers and dropped a provision that would allow payers to use money from FEHB funds to pay for the cost of creating an electronic health record system.

Population ‘hourglass,’ driving healthcare change

On the final day of the National Health Promotion Conference hosted by the Centers for Disease Control and Prevention (CDC; Atlanta), futurist Andrew Zolli painted a view of the healthcare needs that the U.S. will be facing by 2050 as very different, with healthcare delivered differently than today. Zolli — futurist-in-residence at Popular Science and American Demographics magazines, a consultant to corporations, and a fellow at the National Geographic Society (Washington) — said that tools and approaches are changing so rapidly that it is unsettling to some individuals.

Even more important will be the natural process of aging. In the U.S., “we are headed toward an hourglass” in age distribution for the first time ever in our country, whereby there are both more seniors and younger people than there are middle-range wage earners to pay for all the services they will need. The growing number of older individuals tends to be more conservative and vote conservatively, Zolli said, while consumer companies want to market to the expanding numbers of those who grew up under the influence of pop songstress Britney Spears.

Also, more people are going to be outliving their retirement savings or income, even when at the same time they want a high quality of healthcare services and there are more and more drugs targeted to this age group, Zolli said. MetLife, a large insurer, for example, is now selling policies for individuals who outlive their means and end up with no money for necessities, he noted.

“The fastest growing segments of our society for the next 10 years will be ‘Married with Parents’ and ‘Married with No Children,’ the latter the result of the difficulty of affording children while caring for older parents. That, in turn, will “change the economics of health,” Zolli said, adding later, “You can’t run an hourglass society for too long without outsourcing” because there won’t be enough people to produce all the products and services we as a society want to consume.

Payers not waiting for CMS P4P validation

Pay-for-performance (P4P) is gradually taking root in a number of health systems across the U.S., and a recent article in the American Journal of Managed Care shows that while speed bumps are plenty, P4P is taken seriously by health plans. The article also makes clear that despite the seemingly lumbering pace of adoption at the Centers for Medicare & Medicaid Services (CMS; Baltimore), the private sector is forging ahead.

The authors, Trude, Au and Christianson, designed a study to look at “planning, development and implementation of pay-for-performance programs ... at the community level.” It was a fifth round of site visits conducted in the first half of 2005.

The team interviewed health plan executives employed by 35 plans serving a dozen communities and discovered that while many health plans are rolling out P4P programs, they demonstrate “substantial design variation within and across markets.” These designs are said to reflect “local conditions that include information technology capabilities, data availability, relative leverage of health plans and providers, willingness of providers to participate, and employer influence.”

The authors noted that during the 2003 review, providers had rolled out plans in seven of the 12 communities, but that at least one provider now is using P4P in each of the 12 test communities. These include Boston; Miami; Cleveland; Seattle; Lansing, Michigan; and Little Rock, Arkansas. They described the plans in Boston as sophisticated, reflecting “previous experience in hospital and physician contracting.” The P4P plans use one or more of three measurement strategies: performance compared with peers; absolute performance targets; and improvement in performance.

The authors noted that “the amount of money that health plans put at stake ... range from nominal amounts to substantial sums,” but some of the executives they interviewed were of the opinion that “plans must tie in at least 10% of provider compensation to performance to change physician practices.”

The degree of customization of P4P plans seems to present opportunities and tripwires. Trude, et al, point out that local conditions can influence the way P4P is deployed, but development of a national consensus may be more than difficult if only because “many plans seek a competitive advantage” with their P4P programs. While Medicare is still often seen in some quarters as the 800-lb. gorilla of P4P, the paper notes that “our finding suggests that additional CMS leadership is probably not needed to convince the private sector to pursue” P4P.

Fair benchmarking key to CMS Coverage

Software is a vital part of any modern endeavor in healthcare, but its influence on skeptics in the medical establishment is not always what federal agencies would like.

Such was one conclusion to be drawn from the discussion of current computer programs that benchmark the performance of physicians by a recent advisory committee of the Centers for Medicare and Medicaid Services (CMS; Baltimore). And this would lead observers of the effort less than elated at the prospects for payment reform.

Thomas Valuck, MD, a medical officer at the Center for Medicare Management at CMS, went out of his way to ensure the Physician Payment Advisory Commission (PPAC) that the desired state of efficiency “is not arbitrary cost cutting,” but is a patient-centered effort to cut down on “waste, overuse and misuse of medical resources.” The CMS benchmark will consist of a ratio of actual resources used by a physician to expected resources, assuming an “equivalent high quality of care.”

CMS said it intends to make any and all measurements of physician practices fair by factoring in “relevant practice differences that the physician cannot control.”

Valuck also mentioned that the Medicare Payment Advisory Commission (MedPAC) had turned in its report on the physician-level evaluation of “grouper” software to Congress, a study based on a sampling of 5% of Medicare beneficiaries. The next stage of the program for evaluating the two computer programs will be to analyze all Medicare claims “for some region for some period of time.”

Valuck described grouper evaluations as those that “organize claims data into a set of clinically coherent and easily compared [treatment] episodes,” but with the method of organizing them in this manner proprietary to the software involved. CMS will also take a close look at the underlying logic to the means of organizing episodes.

In its June report to Congress, MedPAC noted that the two grouper programs “differ in their logic but have some similarities.” They both are said to “acknowledge disease severity and complexity when creating episodes, but the Medstat Episode Groups (MEG) program (Ann Arbor, Michigan) can break down a single episode “into three stages, based on the progression of the condition.”

The other program, Episode Treatment Groups (ETG), is published by Ingenix (Eden Prairie, Minnesota).

MedPAC indicated that “for certain conditions, the two groupers agree fairly well on the number of episodes created” but that they diverge fairly sharply in the case of a couple of conditions, including urinary tract infection.

Using CMS’s data, the ETG program reported more than 137,000 episodes, a sharp contrast to the 106,900 reported by the MEG software. ETG also is said to “have higher — sometimes substantially higher — average total payments per episode,” including “more than twice those of MEG” for congestive heart failure (from $3,161 to $1,394).

Another measure of interest is one that gauges the use of imaging equipment, with echocardiograms of the heart serving as the testbed for this first round (the second round to compare the use of MRI with that of computed tomography for evaluation of chest pain).

According to Valuck, the program objective is to determine the feasibility of “disseminating confidential, claims-based resource use reports to physicians,” a recommendation made by MedPAC.

The echocardiography study, which is focused on a much smaller set of disease states than the grouper software study reported by MedPAC, is ongoing in Wisconsin and Ohio, with vetting by the Cleveland Clinic (Ohio) and the University of Wisconsin-Madison. From that vetting effort, CMS discovered that similar reports sent to providers by private payers “get a cursory look and then go into the round file.” Physicians also felt that the CMS data reports they saw did not appear accurate, which, according to Valuck, led doctors to conclude that they “can’t trust them.”

These reports on use of imaging resources led the agency to several conclusions, one of the more obvious being that “physicians understand their practices from a patient-by-patient perspective, not from an aggregate statistical perspective.”

Another conclusion was that the claims data reports are largely “not meaningful or actionable for physicians.”

However, one unexpected outcome from the imaging resource use reports is that the cost of crunching data and the resultant disseminating reports is greater than the savings CMS might yield. “That’s why I’m curious as to why private payers continue to do this,” Valuck mused.

CMS administrator Mark McClellan dashed in for a briefing in the afternoon session — “dash” speed being his usual MO — and he described the PPAC advisory council as “more important than ever before.”

“What I’ve found particularly valuable from your input,” he said, “is that not only have you broadened the perspective of practicing physicians to the agency, but you’ve done it in a way that helps us take rapid action. I think that this close interaction is going to be even more important going ahead.”

McClellan noted that while the issues of appropriate payments will not get any easier, the work of the dvisory committee is meant to ensure continued progress.

Over the next couple of months, “I see the agency being very involved in legislative interests toward getting a better payment system for physicians,” he assured committee members in his most reassuring tone.

He forecast that CMS is “continuing to make progress toward being what I like to call a public health agency because you cannot be the largest health payer in the world and not recognize that your actions have a big impact on the way that healthcare is provided.” However, McClellan did not elaborate on that rather sweeping assessment.

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