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Monitoring program finds common mistakes
CR site's audits show trends
The University of Virginia in Charlottesville, VA, identifies clinical trial compliance deficits and other trends fairly quickly because of a post-approval monitoring program.
"The post-approval program has been in place for around four years, and it's amazing to watch," says Susie Hoffman, RN, BSN, CIP, director of the IRB for health sciences research.
"Once we get a report we get together and review reports, looking for trends and the types of things a lot of people might get wrong," Hoffman explains. "Maybe investigators didn't understand an issue, or maybe there's confusion about the information we're giving them and so we need to provide more education on a topic."
Sometimes there will be a new person at the CT helm, and this person doesn't fully understand the process and might need one-on-one educational support.
"So we might go in a lot of different directions with the information we find out," Hoffman says. "Then, depending on the seriousness of the findings, we might revisit the study team and make sure they understand the information we're sharing with them."
The post-approval monitoring process has identified some of the more common mistakes investigators and CT staff make. They are as follows:
• Failing to obtain two parent/Guardian signatures: Federal regulations, under 45 CFR 46.408(b), require both parents or guardians to sign the informed consent when a child is enrolled in a clinical trial that has more than minimal risk and no potential for benefit, Hoffman says.
Investigators might submit informed consent forms with only one signature or signatures from at least one person who is not a legal guardian.
The regulations state that both parents must give permission where "research is covered by 46.406 and 46.407 [for research with greater than minimal risk and no prospect of direct benefits to individual subjects and research that is not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affect the health or welfare of children].
Exceptions can be made in cases where one parent is deceased, unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the child's care and custody.
So if investigators obtain only one parental signature, then the reason why it qualifies as an exception should be well-documented.
• Confusion about privacy plans: Under HIPAA, investigators are asked to have a privacy plan if there's an informed consent waiver, Hoffman says.
"When HIPAA went into effect, we instituted a privacy plan for those studies with waivers of consent, and we started audits on those 1.5 years ago," Hoffman says. "We found that people didn't really understand this, so we put together education on the topic, which we call Learning Shots."
Later, the institution required that all protocols have privacy plans.
"But we feel it's important to have a privacy plan for all of your protocols, and we want the plan to be similar to the template for HIPAA privacy plans," she says.
For instance, CT staff and investigators are asked to answer these questions:
— How will identifiers be stored?
— Does it include health information?
— Where is the information kept?
— Are the identifiers kept separate from the health information so that even if the computer is hacked into the identifiers won't be found?
— Is the information stored on a computer behind a firewall and password encryption, or is it on a laptop or memory stick?
"We don't recommend investigators keep the information on their laptop or on a memory stick because they'll run into issues if it's stolen," Hoffman says.
• Enrolling subjects in more than one protocol: "In some situations this is fine," Hoffman says. "You might have a situation where one study is a drug study, and the other study involves a questionnaire that doesn't affect the first study."
But in some cases the protocols do not permit dual enrollment, she adds.
"Also, you might have a subject in two IND studies, which could really cause a lot of difficulty with the results and reliability," Hoffman says.
So investigators need to make certain that potential subjects are not already enrolled in another clinical trial, particularly when a study protocol prohibits dual enrollment as part of the exclusion criteria.
And researchers conducting investigator-initiated studies should think about writing into inclusion/exclusion criteria a requirement regarding dual enrollment, Hoffman suggests.
• Deviating from protocol: Protocol deviations vary in seriousness, but minor protocol deviations are common, Hoffman notes.
If the investigator miscalculated the investigational dose of the drug and gave the subject three times the dose, the protocol deviation would be serious.
More commonly, a subject may miss a study visit date by one day, or the CT site might fail to obtain lab results at one visit, which could be benign or serious, depending on the study, she adds.
"If we find that a study has a lot of deviations, we'll probably ask our post-approval, compliance monitors to go in and do a visit and then to send a report to the IRB," Hoffman says. "Then we'd determine what action would be required."