Amend protocols to participants' needs

Add flexibility to inclusion/exclusion criteria

Clinical trial professionals and investigators should reconsider the inclusion/exclusion criteria and other factors to meet the needs of their study participants, an expert suggests.

"Some of the criteria we like to think can be used generally, and that's our goal, but in reality it might be difficult for sites to enroll under those criteria," says Erin J. Iturriaga, RN, CCRC, a nurse consultant and project officer for the National Institutes of Health (NIH) in Bethesda, MD.

For example, a clinical trial enrolling people who use methamphetamines might exclude enrollment of people who are infected with HIV because of potential drug interactions with the study drug and the antiretroviral treatment received by this population, Iturriaga explains.

"But while some of the medications HIV-infected people are on might be exclusionary, the HIV treatment field is changing so rapidly that it might not be necessary to exclude all of the people receiving medications used to treat HIV/AIDS," Iturriaga says.

"If you did a study two years ago, and this was the exclusion criteria then, the science might have changed so rapidly that you will now need to look at the exclusion criteria and change it," she adds. "Maybe two years ago when a new HIV medication came on the market we didn't know much about it, but now we have a much larger safety profile."

Therefore, the trial should be designed with enough flexibility to permit enrollment of HIV-infected participants who are being treated with antiretrovirals that would not compound health problems or cause drug interactions in the study.

The reason CT sites and researchers will want to be more flexible and think of inclusion/exclusion criteria more on an individual basis is because in some studies it will be very difficult to enroll enough subjects if the inclusion/exclusion criteria are very strict.

The NIH encourages investigators to collaborate when deciding inclusion/exclusion criteria and to take into consideration their own potential study population and its needs, Iturriaga says.

"We try to collaborate with investigators to have a better understanding of what the standard of care is out there in the community," she says. "It might be very different on the East Coast versus the West Coast."

Such information about variations in the standard of care might be as important as historical information about similar clinical trial experiences a few years earlier, Iturriaga notes.

Sometimes science moves more quickly than do clinical trials.

This is why CT sites also need to be aware that a promising study drug might be seen as worse than standard of care a couple of years into a study, Iturriaga says.

When investigators begin studying methamphetamine addiction in a trial, there maybe no standard of care therapy available, she explains.

"But during the trial, the standard treatment could be improved, and this could kill your trial if the new treatment is a really good drug," Iturriaga says.

Clinical trial professionals need to assess the latest treatment trends, science, and other information in their fields of study, and they should make adjustments to their ongoing trials as new information comes to light, she adds.

At the very least, when a new treatment comes on the market while a clinical trial of a competing treatment is underway, the informed consent form should be updated, Iturriaga says.

"You need to inform subjects of the new treatments that are available," she says. "That may change the mind of a study participant of whether or not they want to continue in the study because of the new information that's available."

Another thing for investigators and CT sites to keep in mind is that they need to anticipate subject retention problems before they write the informed consent and begin enrolling participants, Iturriaga says.

"You may have subjects who are impaired due to drug use, or they could be incarcerated, so how do you deal with that?" she says. "A lot of them are vulnerable populations; they live in substandard housing or have no access to transportation, and these are all hurdles you need to overcome to keep them in your trial."

CT sites need to think about how research coordinators will obtain informed consent if a potential participant arrives intoxicated or high from some illegal substance. They need to have contingency plans for when subjects become homeless or are incarcerated, Iturriaga says.

"There are many different types of sensitive therapeutic areas, so whatever study you're conducting, you should look at the hurdles for recruitment and retention," she advises. "Think about it up front when you're writing the protocol rather than waiting six months down the road and then being stuck."