Who Is Excluded From Clinical Trials? Who Isn’t?
10 CommentsBy Ed Silverman // April 2nd, 2008 // 10:14 am
Let’s see. How about women, older folks, minorities, the diabled and people who live in the sticks. That’s the conclusion of a new analysis of the American clinical trial process for testing new drugs, which found these groups are routinely excluded or under-represented for decades.
“We’ve got a big problem,” Dan Goldberg, chief policy adviser for the report, tells Health Day. “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 a team of more than 300 analysts who spent four years conducting an in-depth review of policy positions held by public, private and nonprofit clinical trial sponsors in the US. Their research was funded by an “unrestricted educational grant” provided by Genentech, and was conducted by the Chronic Disease Prevention & Control Research Center at Baylor College of Medicine in conjunction with the Intercultural Cancer Council, both of which are based in Houston.
They noted that about 80,000 clinical trials are conducted in the US each year, but less than 1 percent of the American population - 2.3 million men and women - participate. The research looked at cancer clinical trials and found that only 25 percent of patients were over the age of 65. In addition, older people were often excluded from studies focused on Alzheimer’s, arthritis and incontinence, Health Day writes.
As evidence of the problem, the researchers focused on a study of clinical trial composition and 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, Health Day writes. Under-representation, Health Day adds, can lead 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 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 patient participation; and 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,” Armin Weinberg, the lead researcher, tells Health Day. “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,” he adds. “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 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,” Shamoo, who is also co-founder of the nonprofit Citizens for Responsible Care and Research, tells Health Day. “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, Health Day notes. On Monday, Duke University researchers reported that, although more women are 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.
They found other issues, 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. And 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.
Source: Health Day
Craig Niedenthal
This fits in perfectly with my comments about the Crestor study. They choose study participants who had no evidence of heart disease and then found after a certain period of time, they had no events….as i use to say when i was a kid…”no duh!!”.
Kelly
It is tough to include the elderly when they may have co-existing health issues that would cloud results. However, that doesn’t explain the gender and race gaps. I’d be curious to know what approaches and tools are used to recruit volunteers — it seems they could use some techniques from non profit volunteer recruitment and educational institutional recruitment.
Bob Freeman
CROs and pharma companies use a number of recruitment tools ranging from announcements on web sites, radio spots, newspaper ads, and clinical research sites’ direct recruitment of existing patients into trials. Advocacy groups also help in recruitment and the NIH web site has a listing of trials seeking patients.
In some drug trials (hypertension, e. g.) you have the phenomenon of “professional” patients or test subjects. Their familiarity with their disease and alternative therapies is translated into volunteering at very high rates. Interestingly, many of the protocols want patients naive to therapy as one of the criteria. (Alternatively, you have to wean them from existing therapy and allow a wash out period.)
James
Industry has had difficulty to get certain minorities, especially the African American population, to participate in clinical trials. Much of this was based on the perception that, for historical reasons (e.g. Tuskegee Syphilis experiment) African Americans would not participate. However, as more drug companies have made concerted efforts to reach out to them with relevant messages in appropriate media, they have had some success.
Pharma, as a general rule, wants to have participation from all classes, genders and races because they have difficulty getting recruits.
jim
There is a clinical trial on a medical device that is currently being conducted that eliminates all people with known allergies to its primary ingredient even though the medical device’s labeling doesn’t include warnings against allergies to that ingredient. Previous clinical trials for this medical device have not included this exclusion but, since it has had many adverse events reported since it hit the market, I guess the device company is insuring a positive result by eliminating the probable cause…scary, scary stuff.
ol cranky
Actually, I had no difficulty getting people of color to participate in trials and, despite the thought that Tuskegee is still causing a significant lack of black people to participate, I read recently that this is no longer a significant barrier to recruitment. My biggest problem was actually women, many of whom were ticked off that those of childbearing potential had to practice an effective method of birth control (the ones who got angry were typically well educated who saw this requirement as sexist instead of understanding the logic behind it).
The problem with recruitment for many trials (barriers for eligible subjects) are generally the inconvenience of frequent visits, study procedures that may be invasive/annoying/take up time (patient compliance is key to obtaining accurate quality data) and the length of some of those visits. In other cases, sponsors are frequently myopic with regard to eligibility criteria and often put in criteria that are not really necessary to be able to evaluate efficacy criteria (the nice to have, but not mandatory to meet study objectives) or to ensure safety - these do create barriers to recruitment and retention of study subjects.
JIM:
Exclusion of patients who have a known or suspected allergy to any ingredient (active or inactive) of a product is standard for clinical trials. This does not skew results, it ensures subject safety and any IRB that would approve a study that didn’t include such an exclusion criteria would be held liable for not ensuring adequate safety measures were mandated in a protocol. If there have been many reports of allergic reaction to something in this device, it would be negligent to expose a patient to this risk - chances are that the labeling will change.
jim
Ol Cranky,
The labeling hasn’t changed in nearly 10 years…how long does it take?
ol cranky
If there are significant reactions that have been reported, the FDA should have requested changes in the labeling to address the potential for allergic reaction (if nothing is already contained in the physician info). Have there been a lot of reactions from the outset or are there a lot of reactions being reported now? If so, were they significant and with a high enough incidence to require changes to labeling? Also, since it’s a device, have you seen the information provided to the physician and does it include information regarding the coating (or whatever is causing allergic reactions)?
Regardless, exclusion of subjects with a known or suspected allergy to any part of the product is Good Clinical Practice and does not ensure positive results or skew the study in any way.
jim
ol cranky,
If one of the points of a clinical trial is to find out if a medical device or drug is safe, how can eliminating the cause of adverse events(the ingredient that causes allergic reactions) make it a valid trial? Eliminating people with a know allergy to an ingredient may ensure their safety, but what about all of the people that the drug or device will be used on in the future?
Joana Ramos
Those of us, like myself, who are actively involved in health equity work– both direct service and on the policy level– are inundated with appeals to help recruit a more diverse cross-section of patients into trials, to participate in various educational offerings and meetings on the topic, etc. But what almost never gets discussed are the almost insurmountable socio-economic barriers in treatment trials. Note that the synopsis of the study in Health Day did not distinguish between prevention trials and treatment trials, the latter being the standard in hematology-oncology.
While prevention trials may be offered at no charge to participants, and some may offer compensation, medical centers offering treatment trials– with the exception of those offered at the NIH Clinical Center and at St. Jude ( children only) — require guarantee of payment. Often patients will have to put down an upfront deposit of one-third to one-half the total estimated cost. In these days of rapidly rising uninsurance and under-insurance, it is not enough to say that “participation in clinical trials should be covered by insurance.” For starters, we need to take a look at the statistics on insurance, which show huge disparities in who has coverage by demographics of race/ethnicity and income., To understand the effect, take the example of a blood & marrow transplant ( BMT). Almost all BMTs are done as clinical trials, and a very conservative average price just for the hospitalization part is at least $350,000. If patient’s insurance plan covers 80% of the charges, it’s not hard to do the math to see how much the patient responsibility is.
In order to level the playing field so that all may ostensibly benefit from clinical trials, we have to tackle the economic issues head-on. Not only have many drugs under study derived from tax-payer funded research, but many research centers receive public funding and many also hold tax-exempt status as nonprofit institutions. Completely apart from patient issues, some drugs have received orphan drug status from the FDA, as they treat diseases considered rare. OD status entitles drug makers to a 50% rebate on costs incurred in running clinical trials. To make it possible that all can participate in trials, the public must be able to benefit from public investments.