Report Claims Clinical Trials Miss Many Populations
Women, elderly, minorities among those routinely excluded or under-represented, researchers say

By Alan Mozes
HealthDay Reporter

TUESDAY, April 1 (HealthDay News) -- A new analysis of the American clinical trial process suggests that the system for testing new drugs has routinely excluded or under-represented women, older people, minorities, disabled individuals and rural populations for decades.

"We've got a big problem," said Daniel S. Goldberg, chief policy adviser for the report. "And it's extremely urgent that we fix it. Because we're trying to figure out how to streamline health care and make people healthy, of course. And the fact that we have under-representation in clinical trials undermines both of these goals and undermines the quality of the evidence we come up with."

The report was conducted by the Chronic Disease Prevention & Control Research Center at Baylor College of Medicine in conjunction with the Intercultural Cancer Council, both based in Houston.

Part of a team of more than 300 analysts led by Armin D. Weinberg, Goldberg and his colleagues spent four years conducting an in-depth review of policy positions held by public, private and nonprofit clinical trial sponsors in the United States. Their research was funded by what is described as an "unrestricted educational grant" provided by Genentech Inc.

The team noted that about 80,000 clinical trials are conducted in this country each year, and that less than 1 percent of the American population -- 2.3 million men and women -- participate in such trials.

Additional trial problems, such as the lack of adequate training for members of institutional review boards, who are legally obligated to assess the structure of a proposed trial, were cited.

The report also admonished against the wasting of limited resources that results when government institutions and private industry duplicate each other's efforts in conducting trials focused on the same disease or treatment.

However, it is the continuing absence of specific constituencies in many trial populations that gets the lion's share of the criticism.

The research looked at cancer clinical trials and found that only 25 percent of patients in such trials were over the age of 65. In addition, older people were often excluded from studies focused on Alzheimer's, arthritis and incontinence, the researchers noted.

As evidence of the problem, Weinberg and his colleagues honed in on a study of clinical trial composition that found that, between 1995 and 1999, blacks, Asian-Pacific Islanders, Hispanics and Native Americans together made up for less than 10 percent of patients included in new cancer drug trials.

Under-representation of this sort, they say, leads to results that do not account for a host of factors -- genetic, cultural, racial, religious, linguistic, as well as variables related to age and gender -- that could have a huge impact on how well new drugs do in the real world.

To address these shortcomings, the team proposed nine policy solutions:

  • government regulatory changes;
  • increased collaboration between government and private industry on clinical trial design;
  • increased community involvement in patient participation;
  • scientific journal oversight of patient breakdowns;
  • new, specialized training for review boards;
  • reallocation of research funding to avoid duplication and address disparities;
  • increased public education;
  • increased focus on easing the patient participation process;
  • guaranteeing insurance coverage for all related costs.

"The bottom line is there has been a lot of discussion and attention paid in recent years to how clinical trials are put together, and, in particular, the need to account for differences in study patient populations," said Weinberg. "And that's the good news. But the bad news is that as a practical matter, it has yet to have a real impact on studies themselves."

"And the problem is that many people, when they take a pill, don't realize that it didn't come out of thin air," added Weinberg. "So, we hope that our work will help people appreciate how the process works, and that what we're talking about is the next generation and how we improve the products and type of therapies that we will have in the future."

Adil Shamoo, a professor of biochemistry and bioethics at the University of Maryland School of Medicine in Baltimore, agreed that trials must ensure proper patient representation. And he stressed that the problem stems from a lack of structural focus, rather than from any lack of potential volunteers.

"We have an extremely willing volunteer population in this country, so there is no question that proper trial representation is doable," said Shamoo, who is also the co-founder of the nonprofit Citizens for Responsible Care and Research, based in Columbia, Md. "And medicine is going to be given to millions of different people, so you do need that representation. Otherwise, you can have risks that you won't know about."

Other reports released this week buttress the findings of the Baylor team.

On Monday, Duke University researchers reported at the American College of Cardiology meeting in Chicago that although more women are being included in clinical cardiology trials, their numbers are still so low that it's questionable whether the results can actually be applied to women. And a commentary in the April issue of The Lancet Oncology stressed that more teens and young adults need to be included in trials of new cancer drugs, because they are currently under-represented.

More information

For additional information on clinical trials, visit the U.S. National Institutes of Health .


Advertising may have more influence on prescriptions than science

CARLY WEEKS Globe and Mail

March 31, 2008 at 9:35 AM EDT

Few Canadians are taking a controversial new cholesterol-lowering drug compared with millions in the United States, where the medication has been heavily promoted, according to a new study that suggests advertising may have a greater influence on the use of a medication than scientific evidence.

More than 33 million prescriptions for ezetimibe, sold under the brand names Zetia, Ezetrol and Vytorin, were issued in the United States in 2006, compared with just 824,000 in Canada during the same period.

The drug accounted for more than 15 per cent of all prescriptions for cholesterol-lowering medication in the United States that year, but only 3.4 per cent in Canada.

The results of the study, conducted by Toronto's Institute for Clinical Evaluative Sciences, Connecticut's Yale University and California's Western University of Health Sciences, were published online Sunday by The New England Journal of Medicine.

Ezetimibe is not recommended by health authorities as the first option for patients seeking to control cholesterol in Canada or the United States, according to the study, and has been the subject of growing debate over its effectiveness compared with other medication.

That has led researchers to believe that other factors - particularly heavy promotion to U.S. consumers - have contributed to its rapid sales growth in that country and its sluggish performance here.

In Canada, drug companies are not allowed to directly advertise a medication and its benefits to the public, but they can promote their products to physicians.

They have much more freedom to publicly promote drugs in the United States, which many medical experts say has a major impact on the types

of medications that are being prescribed.

The study provides a significant glimpse of the possible impact of direct-to-consumer advertising that comes as the Supreme Court of Canada is deciding whether to lift restrictions here.

"I think this example serves as a cautionary tale, about the potential downsides of that practice," should it be legalized in Canada, said Jack Tu, lead author of the study and a senior scientist at the Institute for Clinical Evaluative Sciences.

"It has broader implications beyond this specific example," Dr. Tu said.

"It shows the potential downsides to ... too much advertising, without the evidence behind it."

The study said that more than $200-million (U.S.) was spent on direct-to-consumer advertising for Vytorin in 2007 and that sales of the drug recently eclipsed $5-billion.

Many medical experts and consumer advocates worry that direct-to-consumer advertising will result in patients asking their doctors for prescriptions for heavily promoted drugs even though the medications may not be the best health choice.

Dr. Tu said the new study may provide some credence to that theory, considering ezetimibe prescriptions skyrocketed in the United States even though it has less clinical data than other cholesterol-lowing drugs.

"I think there's some real serious risks, both in increasing the costs to the health care system and exposing patients to interventions where there isn't as much scientific data behind it as there should be," he said.

In the study, researchers examined data for prescriptions of all cholesterol-lowering drugs in Canada and the United States from January, 2002, to December, 2006. They found that prescriptions for cholesterol drugs rose in both countries during the study period.

Advertising may be one factor contributing to the success of ezetimibe, but differences in drug availability and insurance coverage also contributed to its popularity in the United States, Dr. Tu said.