When IRBs review multisite studies, particularly when the sites are at different research institutions — and in different states — there is a question about how faithfully each site sticks to the protocol and avoids deviations.

With large, multisite, non-biomedical studies, fidelity — or maintaining protocol compliance — requires considerable resources.

A new study found that when fidelity and other challenges are addressed, the study’s scientific rigor and reproducibility are improved. It also found that multisite studies’ findings are more likely to provide evidence that can transform clinical practice and policy.1

This fidelity to the protocol is something human research protection offices should monitor, experts say.

Fidelity is a concern, says Laureen Smith, PhD, RN, FAAN, associate professor at The Ohio State University. Smith is a co-author of the study on multisite trials.

“If you have a trial going on in different states, then you have to build into your systems ways of monitoring that fidelity and who is responsible for that,” Smith says.

“The challenge with having a single IRB of record is getting everyone on board to do the same thing,” adds Sonia A. Duffy, PhD, RN, FAAN, Mildred E. Newton Endowed Chair at The Ohio State University College of Nursing.

IRBs might assume that everyone is following the protocol faithfully, but they cannot be certain of this unless there are procedures to check that every site is performing the protocol activities in precisely the same way.

“Everything has to be spelled out from the beginning so sites know exactly what they’re signing up for,” Smith says.

From the perspective of study participant safety, IRBs want to ensure everyone is being treated the same and that everyone is following the same protocol. Researchers have to tell the IRB who is responsible at each site for the protocol activities, Smith notes.

Multistate and multisite trials also pose other issues. For instance, investigators have to answer to each site’s questions and rules, particularly with community-based research such as studies performed in schools, Smith says.

“I do community-based research, school-based research, and even though I have multiple sites and locations and one IRB of record, I still have to get the approval of each individual school district before conducting my study,” she explains. “They have their own autonomy to say ‘yes’ or ‘no.’”

One of Smith’s most recent studies involved more than a dozen schools, and their concerns and questions varied. For instance, some schools only wanted to see a copy of the IRB’s approval letter, and others wanted additional information. Some asked what kind of measures would be taken with the children and how invasive the work would be. They also questioned data collection, privacy measures, and confidentiality, she adds.

Researchers should be prepared for roadblocks to consistent protocol adherence due to varying state laws. The approved protocol should reflect those differences.

For example, Duffy was part of a smoking cessation study with sites across the country. Investigators ran into a barrier involving how to obtain data and informed consent of study participants with a specific comorbidity. States had different rules about how to access those data and what type of consent was required.

Researchers sometimes will need to drop a site because of state laws that make it difficult for the site to fully participate in the study and faithfully follow the protocol.

Duffy also conducted fidelity monitoring for a study that involved a nursing procedure with patients.

“I trained nurses in hospitals on how to make sure we are all doing the same thing,” she says. “You go in and watch them work with the patient and follow a checklist about whether they covered medication and behavior, and you try to make sure people are all doing it the same way.”

Fidelity monitoring is another layer of bureaucracy, and research institutions should be willing to negotiate and be as flexible as possible — but not flexible in a way that compromises the protocol, Duffy says.

“You need to figure out how you can work with the organization within their rules, and be open-minded to other options without compromising the study,” she adds.

REFERENCE

  1. Smith L, Tan A, Stephens JD, et al. Overcoming challenges in multisite trials. Nurs Res. 2019 May/Jun;68(3):227-236.doi:10.1097/NNR.0000000000000324.