Revised GPP guidelines improve user engagement

International studies can avoid trust problems

IRBs dealing with international or high-risk research can find some guidance on how to handle all stakeholders in studies in the recently-revised Good Participatory Practice Guidelines for Biomedical HIV Prevention Trials (GPP).

The GPP guidelines offer insight into strategies for improving human subjects protection in studies involving international and/or vulnerable populations. They were developed by a working group formed by the AIDS Vaccine Advocacy Coalition (AVAC) and UNAIDS after two international trials of pre-exposure prophylaxis tenofovir were closed due to activist pressure in Cambodia and Cameroon. The incident raised concerns among researchers, IRBs, and others in the human subjects research community that many other international studies could be similarly impacted by negative publicity and activist pressure.

"These two trials were suspended following regulatory approval by the highest political leaders in their countries," says Catherine Hankins, chief scientific advisor to UNAIDS. "There was concern that the issues raised during these suspensions could jeopardize all HIV prevention trials," she adds. "What became evident to everyone was we were not operating in a silo; what could happen at one site in one field could happen to all of us."

The good news was the Cambodian/Cameroon trial problem led to the formation of the GPP guidelines in 2007, which serve as a thorough and thoughtful roadmap to engaging study stakeholders in preparation of a new study.

IRBs can use the GPP guidelines to discuss with investigators how they'll address issues raised in international studies, suggests Lori Miller, MHS, senior program manager of AVAC in New York, NY.

The guidelines also provide detailed information for how investigators can raise awareness of their studies and engage with members of the community.

Twelve organizations were involved in a year-long process of sharing the guidelines, holding meetings and consultations about them, and seeing which parts made sense and which parts should be improved and revised, Miller says.

"We compiled all results from the consultation and there was a lot of consistency in the feedback we received," she adds. "The guidelines needed to be revised to have greater human rights perspective and they needed to be simpler and clearer."

The revised guidelines discuss some of the most important issues and, sometimes, sources of contention, between communities and researchers. Here are some examples from the revised guidelines:

• Power inequalities: The organizations and nations funding research are perceived by communities to have a power inequality with their leaders who are drawn into the trial start-up process and with their citizens, who are being asked to participate in studies. This perceived inequality can impact the decision-making process, priority setting, control of resources, and recognition of input. Also, there can be power inequality with regard to literacy, education, economic resources, and the provider-patient relationship.

• Scientific and ethical integrity: Human subjects research should maintain the highest standards of scientific and ethical integrity, maximizing the benefits for the trial community and advancing global science, the revised guidelines say.

To achieve this, there should be transparency in the form of open, timely, and clear communication between researchers and stakeholders. And there needs to be accountability to stakeholders through the use of GPP and responding to stakeholders' input.

One of the changes in the revised guidelines is a shift from using the term "community" to the term "stakeholders," Miller notes.

"That was a very purposeful change in response to a lot of feedback we received in consultations," she says. "A number of groups said we have to be thinking about all stakeholders, not just the community stakeholders."

For instance, stakeholders also include the government, the media, and others.

"Trial sites should have a stakeholder engagement plan that addresses who the possible stakeholders are and how best to work with different groups," Miller says.

The guidelines also address how a study might be closed in the event of evidence of harm or for unforeseen circumstances, such as administrative or financial reasons. And, researchers should consult with relevant stakeholders to develop a plan for disclosing study results, the guidelines say.

Study closure is important for researchers and IRBs to consider for a variety of reasons, including one that often is overlooked: the same research institution might use the particular site again for different studies.

"The conclusion of the GPP guidelines discusses site maintenance between trials, and that's a very important issue," Miller says. "If research teams invest a lot in a site, working with stakeholders, and building a relationship, then it's not ideal to have that relationship dissolve when the trial ends."

Any new trials would have to start all over again, building up trust and rapport with stakeholders, she adds.

"It's important to maintain the relationship and keep core staff to continue those relationships," Miller says. "That's something where we think about applying pressure to sponsors who have the money to make sure that maintenance between trials can happen."

For more information about the GPP guidelines, visit the website at