BB&T
and DON LONG
BB&T Executive Editor

WASHINGTON — The under-representation in clinical trials of women, racial and ethnic minorities, the elderly, the disabled, and rural populations is at odds with objective medical science, such as drug discovery and the new emphasis on personalized medicine, a group of researchers and physicians argue in a new report.

Despite the implementation of federal and state policies and guidelines pushing for expanded inclusion of such groups, the exclusions persist. They put this problem largely on drugmakers that fund the majority of clinical trials drugmakers and the inconsistency of policies between the FDA and the National Institutes of Health (NIH). But device trials are also marked by a focus on white male populations.

The group, pushing an initiative called Eliminating Disparities in Clinical Trials (EDICT), is developing a plan involving government, industry, healthcare and communities to tensure that those patients who are most representative of the diseases being studied are included in the trials.

More than 300 federal and state public health officials, medical researchers and patient advocates have joined the Chronic Disease Prevention and Control Research Center and the Intercultural Cancer Council of Baylor College of Medicine (Houston) to develop the plan, outlined in a 34-page report.

During a briefing at the National Press Club, Armin Weinberg, a professor at the college of medicine and EDICT's principal investigator, said that the point is not "to reinvent the wheel" but rather to build on work already underway by others, such as the Robert Wood Johnson Foundation (Cambridge, Massachusetts), the Society for Women's Health Research (Washington) and the National Research Center for Women & Families (Washington),to bring new approaches to this issue.

James Powell, principal investigator for the Increasing Minority Participation and Awareness in Clinical Trials initiative of the National Medical Association (Washington) — aimed at educating physicians to become clinical trial investigators and informing communities about the value of medical research — said that the NIH Revitalization Act, passed in 1993 requires the inclusion of women and minorities as participants in federally funded clinical research, but that under-representation contiues.

Among participants in clinical trials for new cancer drugs from 1995 to 1999, fewer than 10% were African-Americans, Asian-Pacific Islanders, Hispanics and Native Americans, according to the FDA. In publicly funded cancer clinical trials conducted from January 2003 to June 2005, 8% were black, 5.6% were Hispanic, 2.8% were Asian-Pacific Islander and fewer than 1% were Native American, according to the National Cancer Institute.

In medical devices, the cardiovascular sector is the arena most often cited as not involving women, a critical absence given the differences between men and women concerning the presentation of heart disease symptoms.

Powell said that though the FDA Modernization Act of 1997 includes guidelines on standardizing data collection of racial and ethnic groups in clinical trials, it does not address what racial and ethnic inclusion is appropriate; and that while the FDA's 2005 clinical trials guidance document calls for study sponsors to document race and ethnicity of patients, it does not address the level of participation.

The FDA, according to the EDICT report, "views the NIH as the sole agency responsible for addressing disparities in clinical trials" and that drug regulators do not evaluate whether a clinical trial is inclusive of women, minorities or other under-represented groups in its medication approval process.

Without a requirement from the FDA to include women, minorities and other under-represented groups in all clinical trials — not just those funded by the federal government — "you are starting from a difficult situation," said Diana Zuckerman, president of the National Research Center for Women & Families.

Congress should consider further legislation that would require drugmakers to include under-represented groups in clinical trials, Weinberg said. He noted that a group from the EDICT initiative was meeting Tuesday with some Texas lawmakers or their staffers to discuss the report.

The group is proposing that the NIH should provide more detailed instruction on the inclusion plans for under-represented populations in clinical trials, with substantial incentives for investigators to implement such plans. In addition, the FDA needs to "harmonize" its inclusion policy with the NIH and implement penalties for sponsors of clinical trials that fail to comply with those policies, the EDICT report states.

Because of past unethical study practices, such as the notorious Tuskegee Study of Untreated Syphilis in the Negro Male, in which 399 poor and mostly illiterate black males were denied treatment for syphilis during a 40-year experiment, and the sterilization campaign of Hispanic women in New York's Spanish Harlem, many minority groups have a fear of the medical establishment, said Venus Gines, a cancer survivor and founder of Dia de la Mujer Latina (Duluth, Georgia). Therefore, she said, recruiting minorities for trials is best done through a person's own trusted physician, who speaks the same language as the patient and is familiar with or was raised in a similar cultural background.

Phyllis Greenberger, president/CEO of the Society for Women's Health Research has said that there need to be different approaches to the non-white male patient populations. "Your method of approach has to be tailored to the people you want to get the message to," she told Biomedical Business & Technology earlier this year ("BB&T interview," January 2008).

Some of the barriers to inclusiveness include confusing paperwork, language differs and the failure to implement guidelines for improving the accessibility of clinical settings, the EDICT report says.

Members of institutional review boards (IRBs), which are required to approve the research design and protocol and maintain oversight of a clinical trial, often lack the training needed to recognize how disparities may manifest themselves in research protocols, the EDICT authors maintained. Thus, they said, IRBs regularly approve research protocols that do not provide for inclusion of under-represented populations.

In addition, the EDICT report asserts that although medical journals have developed explicit policies for articles and have been on the forefront in advancing issues such as improved reporting practices for clinical trials, discussions of diversity, inclusion and representation in medical studies are rarely reported in published studies.

Ensuring that women, the elderly, minorities and other groups are included in clinical trials is more than a question of fairness, said Barbara Pence, professor of pathology at the Health Science Center School of Medicine of Texas Tech University (Lubbock, Texas).

Having different types of people included in a study, she said, can ensure that effective treatments are directed at the right populations, rather than a one-size-fits-all approach that extrapolate to unstudied groups and can result in treatment harm.

Competitive Medicare set to lower prices by up to 26%

Taxpayers and Medicare beneficiaries stand to save more than $1 billion a year with the implementation of proposed reductions in spending on oxygen supplies, power wheelchairs and other durable medical equipment (DME), according to the Centers for Medicare & Medicaid Services. But that's not good news for manufacturers.

CMS said that prices for these supplies will be 26% lower on average under the first phase of a competitive bidding program for DME, prosthetics, orthotics and supplies. "It's clear that we've been paying too much for medical equipment and supplies," CMS acting Administrator Kerry Weems said during a conference call. In some cases, the prices based on the bids will be substantially lower than Medicare pays through its current pricing formula, the agency said. At present, for example, Medicare pays $199.28 per beneficiary each month, on average, in rental/service fees to suppliers of stationary oxygen concentrators placed in patients' homes. The competitive bid prices are 22% to 32% lower, with the average being $140.82.

Because beneficiaries pay for 20% of the cost of these supplies, patients will get their equipment "at substantially lower prices than they are paying now," Weems said. The new prices take effect July 1. Under the first phase of the program, suppliers seeking to provide 10 different kinds of equipment to patients in 10 metropolitan areas were asked to submit bids. CMS will begin expanding the program to 70 additional metropolitan areas in July.

Weems projected savings of $1 billion annually with full implementation of the program.

Many have expressed strong misgivings about CMS's handling of the competitive bidding program, mandated by Congress in 2005. Sens. Blanche Lincoln (D-Arkansas), Pat Roberts (R-Kansas) and Reps. John Tanner (D-Tennessee) and Phil English (R-Pennsylvania) have sent a letter to the administration criticizing the program.

"Although CMS and the Small Business Administration raised special considerations for small suppliers during the rulemaking process, we continue to believe that these steps will not guarantee adequate participations for small businesses," the House letter said. "This will result in a number of small medical device providers going out of business, severely impacting patient access to necessary equipment and quality care."

"Small suppliers pay close attention to local, specialized service as a commonsense means of reducing medical errors, equipment-related injuries, and returned equipment. This in turn reduces Medicare costs," the Senate letter said.

Stephen Ubl, president/CEO of AdvaMed (Washington) said in a statement that the organization is concerned that patient access to DME "may be compromised" by the program. "We urge CMS to postpone expansion of the program ... until it fully evaluates the impact on patient access to the most appropriate treatment. Moreover, this system may discourage investment in new, superior products."

Weems sought to allay these concerns, saying that more than 6,300 companies submitted bids, that the supplies being offered are "nationally known, brand name, quality products," and that 64% of the winning bids came from small suppliers (those with gross annual revenues of $3.5 million or less).

The first phase of the program will occur in Charlotte, North Carolina; Cincinnati; Cleveland; Dallas; Kansas City, Missouri; Miami; Orlando, Florida; Pittsburgh; Riverside, California; and San Juan, Puerto Rico.

Joining the chorus of critics, the American Association for Homecare (AAH; Arlington, Virginia) in early April said that it "hundreds of DME providers" have told them that they have been improperly disqualified from the bidding process. The disqualification shuts them out of the bidding process for three years and will put them out of business, AAH said.

The organization said that reimbursement rates for oxygen have already been cut by nearly 50% over the past 10 years, reducing "the focus on service, and harm patient access to care."

"We're alarmed about the volume of the mistakes made by Medicare's contractor tasked with evaluating bids and implementing the bidding program," said Heather Allan, executive director of the Florida Association of Medical Equipment Services (Orlando). "A process this obviously flawed needs to be stopped, analyzed and corrected if it can't be done away with altogether."

"The Secretary of Health and Human Services has called home-based healthcare 'radically' more efficient than institutional care, yet the federal government is determined to aggressively dismantle the nation's homecare infrastructure at a time when our healthcare system needs it the most," said Tyler Wilson, president of AAH.

He said that DME spending is less than 2% of Medicare spending "and is the slowest-growing segment. Taxpayers may ultimately face higher costs as hospital stays lengthen due to more complicated hospital discharge logistics, more emergency room visits, and cost-shifting from Medicare Part B to Part A services."

Virtual colon scan included in guidelines for colon cancer

Although the dreaded bowel cleansing routine is still required for virtual colonoscopy, new guidelines from the American Cancer Society (ACS; Atlanta) for colorectal cancer screening now include computed tomography colonoscopy (CTC), a 15-minute test that not requiring sedation, invasive scopes or recovery time. ACS said this additionis an effort to encourage more people to do colon cancer screening to reduce the second leading cause of cancer death in the U.S.

Both CTC and stool DNA testing were added to the ACS' screening guidelines, which were developed in collaboration with the U.S. Multi Society Task Force on Colorectal Cancer and the American College of Radiology (Reston, Virginia).

"There is finally, over the last four to five years, enough accumulated evidence supporting the ability of CTC to detect both colon polyps and cancers at a high rate," Durado Brooks, MD, ACS' director, Prostate and Colorectal Cancer, Cancer Control Science Department, told BB&T. ACS said that half of all Americans who should be getting screened for colon cancer are not.

If CTC or DNA testing reveals a suspicious site, a colonoscopy still must be performed.

Until insurers and Medicare implement reimbursement strategies in line with the new guidelines, adoption of the test may be slow, Brooks said.

"Medicare reimbursement for traditional col-onoscopy is significantly lower than what is charged by most colonoscopy facilities," Brooks said. "If you talk with patients, particularly those outside of the Medicare system, the charges vary wildly so it's difficult to put an average cost on colonoscopy. With CTC, it's further complicated because up to this point almost no insurers pay for it as a screening tool."

There's also the question of qualified CTC providers. Although there are no statistics on how widely available CTC is, Brooks said he believes it is readily available beyond just academic research centers.

"One of the points we went to great pains to make is the importance of a number of different quality factors in having a CTC as a primary method of screening." Brooks said. "It requires that a certain level of equipment is available. The American College of Radiology has over the last few years developed a number of different quality standards and provides a training center for their membership. While overall access to high quality CTC is somewhat limited, over the next few years you're likely to see an expansion in availability."

Brooks said the test is done with high performance CT scanners with 16-slice capability and, "Most, if not all, radiologists will want to have very good standard 2-D and 3-D software systems to perform CTC," he said.

Multidetector CT permits image acquisition of 1 mm to 2 mm slices of the entire large intestine well within breath-hold imaging times. Computer imaging graphics allow for visualization of 3-D endoscopic flight paths through the inside of the colon, which are simultaneously viewed with interactive 2-D images. The integrated use of the 3-D and 2-D techniques allows for ease of polyp detection, as well as characterization of lesion density and location.

A study last fall comparing CTC with traditional optical colonoscopy found that the tests yielded similar results.

The study, published in the New England Journal of Medicine, concluded that "primary CTC and OC screening strategies resulted in similar detection rates for advanced neoplasia, although the numbers of polypectomies and complications were considerably smaller in the CTC group."

Physician offers caveats to genomic tests for 'at home' use

The recent marketing of "at home" genomic tests for disease risk may be premature, according to Dr. Kenneth Offit, MD, MPH, Chief of the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center (MSKCC; ).

"Health professionals are now faced with the prospect of their patients coming to the office, a DNA profile in hand, asking for preventative management tailored to their specific disease risks," Offit writes in the March 19 special genomics issue of the Journal of the American Medical Association.

In recent years, more than two dozen companies have been marketing a range of genetic tests directly to consumers concerned about genetic conditions. These conditions include those related to risks for disease, other genetic traits, and ancestry. Some of these companies have marketed "whole genome scans," assessing the risk for various health conditions, from the type of earwax an individual forms to the risks for diseases including cancer, diabetes, and blindness.

In his JAMA commentary, Dr Offit offers several caveats and recommendations to help doctors and counselors as they consider offering these research-based tests in clinical practice. Dr Offit voices concerns about the scientific accuracy of some of these tests, because "they have not yet been validated in forward looking clinical studies." In addition, he writes, the laboratory accuracy of these tests may vary.

A second issue voiced in the commentary is the "direct to consumer" aspect of the marketing of these tests, which excludes guidance from healthcare professionals.

According to Offit, this limits the sources of information available to consumers about these tests and their accuracy from those marketing the tests. "This critical lack of information," he says, "raises concerns that patients/individuals may not have the resources to make unbiased decisions regarding whether to proceed with genetic testing."

Offit also expresses a concern that once these self- ordered test results are relayed, individuals receiving the results may not also receive counseling regarding appropriate medical interventions for prevention and early detection of genetic disorders. The article reminds readers that certain state health departments, New York's for instance, have indicated that genetic testing for disease risk must be requested by a licensed healthcare professional performed in an approved clinical laboratory.