Comments on: Who Is Excluded From Clinical Trials? Who Isn’t?

By: Joana Ramos

Joana Ramos — Thu, 03 Apr 2008 16:14:44 +0000

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.

By: jim

jim — Thu, 03 Apr 2008 02:51:10 +0000

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?

By: ol cranky

ol cranky — Thu, 03 Apr 2008 02:37:44 +0000

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.

By: jim

jim — Thu, 03 Apr 2008 01:56:50 +0000

Ol Cranky,
The labeling hasn’t changed in nearly 10 years…how long does it take?

By: ol cranky

ol cranky — Wed, 02 Apr 2008 23:10:44 +0000

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.

By: jim

jim — Wed, 02 Apr 2008 17:27:06 +0000

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.

By: James

James — Wed, 02 Apr 2008 16:17:59 +0000

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.

By: Bob Freeman

Bob Freeman — Wed, 02 Apr 2008 15:59:36 +0000

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.)

By: Kelly

Kelly — Wed, 02 Apr 2008 15:16:42 +0000

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.

By: Craig Niedenthal

Craig Niedenthal — Wed, 02 Apr 2008 14:38:11 +0000

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!!”.