Start-up consultations improve site compliance

Ensure informed consent, documentation correct

Researchers often criticize IRBs and see them as barriers to research. One way to turn that attitude around is through the creation of a study start-up consultation. This has another advantage: it can improve clinical trial site compliance with human subjects protection regulations and policies.

This type of consultation has human subjects research (HSR) regulatory experts working with researchers to ensure their study site's documentation and consent processes are in order.

"We've worked hard to collaborate with researchers and work with our research community to provide sound, ethical research," says Sandra L. Alfano, PharmD, FASHP, CIP, chair of the human investigation committee I and III, and co-chair of the embryonic stem cell research oversight committee at Yale University in New Haven, CT.

"We view ourselves as facilitators of human subjects research and not as barriers or hurdles that researchers have to get over," Alfano says. "The study start-up consultation is clearly an illustration of that collaborative effort."

Yale started the study start-up consultation with the idea that new and inexperienced investigators would benefit from regulatory assistance before they start their study. From a compliance perspective, a preventive effort is preferable to an audit and punitive action when mistakes are found, she notes.

"We'd like to work with people early on to help them think through different issues and put processes in place at the outset," Alfano says.

While the initial focus was on new investigators, the consultation also has proven popular with experienced investigators, says Tracy Rightmer, JD, CIP, compliance manager of the human research protection program at Yale University in New Haven, CT.

"Experienced investigators are asking for it as well," she says. "They say they want to get a better handle on various regulations and policies and requirements."

Investigators want to do the right thing, but they're not always sure they are in full compliance, Rightmer adds.

Typically a researcher will request the study start-up consultation after seeing an educational session where it is mentioned. Sometimes Rightmer might recommend the consultation when an investigator demonstrates the need for closer oversight after study problems arise.

Here's how the study start-up consultation process works:

1. Compliance manager reviews protocol and IC paperwork. "Before the start-up visit, I look at the protocol and consent documents to get an understanding of the study and to identify areas of potential noncompliance," Rightmer says.

For instance, some common problem areas involve the informed consent process, subject payments, medication compliance and storage, she says.

"I encourage investigators to come up with questions, and I have templates and forms for them that are available on our website," she adds. "These include enrollment logs, inclusion/exclusion criteria, checklists, staff responsibility log, regulatory documentation sheets, staff training checklist, and a few others."

2. Consultation visits provide education, advice.Rightmer and a coordinator who works part-time on compliance issues typically conduct start-up consultation visits within a few weeks of the request from investigators.

"We want to have this consultation before they have their first study visit," Rightmer says. "We will take one to two hours on the consultation, depending on the study's complexity."

The consultants will ask to see checklists and other documents, including source documents, case report forms, enrollment logs, inclusion/exclusion criteria, site signature and responsibility logs, etc.

"Then we go over areas that might be problematic for their particular study," she says.

When the consultant finds a potential problem, she discusses it with the investigator.

For example, in one study start-up consultation, Rightmer asked the investigator and study staff how they would verify medication adherence since they didn't have a process in place.

"I asked, 'How are you going to count pills, use a subject diary?'" she says. "I provided them with information about medication adherence."

3. Look closely at informed consent. The study start-up consultation almost always focuses on informed consent.

"If the study involves minors or those with decisional impairment then you certainly want to go over the consent process and safeguards for those vulnerable populations with investigators," Rightmer says. "If it's a medication study, then I'd want to know how they store medications and verify it."

Another important area involves subject payment. Consultants want to ensure study staff and investigators are documenting when subjects are paid.

"We take a good close look at the protocol," Rightmer says. "Then we identify areas that are problematic for investigators and address those during the meeting."

4. Educate CT staff on adverse events and unanticipated problems. During the consultation, Rightmer will define unanticipated problems and serious adverse events (SAEs) for investigators and study staff.

"A lot of industry studies want all adverse events reported, while the Office for Human Research Protection (OHRP) wants only serious and related events reported," Rightmer says. "There can be discrepancies between the two."

The IRB follows OHRP's guidance on the issue, but sometimes receives too many reported unanticipated problems, she notes.

"So if I'm meeting with an investigator who has an industry sponsor, I find out what the sponsor wants and what is required by the IRB," Rightmer explains. "Sometimes the investigator will have to report the AE to the sponsor but won't have to report it to the IRB."