Going global? Watch out for cultural divide
Respect for differences a good first step
When clinical trial administrators and staff are dealing with multisite trials that include international locations, there is a lot to consider, including time and language differences.
"You encounter issues with communication and people who don’t speak English and the translation of study materials, and that’s one aspect of it," says Jennifer Yahne, contracting projects manager for the HIV Vaccine Trials Network, which is based at Fred Hutchinson Cancer Research Center in Seattle.
Multisite trials that involve international sites require a great deal of flexibility on the part of the coordinating center site staff because time differences can be substantial. For instance, clinical trial sites in Thailand are 15 hours ahead of Pacific Coast time, she says.
"So doing conference calls requires flexibility just to get everyone on the phone at the same time," Yahne says. "Communicating with a group of that size and spread geographically has its challenges."
Yahne arrives at work at 6:30 a.m. and will work late when it’s necessary to schedule a telephone call at 4 p.m. to include East Coast clinical trial staff at 7 p.m. their time and Thailand clinical trial staff at 7 a.m. their time.
Good will goes a long way
Other issues to consider include cultural differences and political obstacles to conducting international clinical trials, says Banks Warden, MHA, chief operating officer of the HIV Vaccine Trials Network.
"Some things we’ve learned is that no matter how good your principal investigator is in a particular location, if you don’t have political good will in the country then, in general, it’s very hard to have a successful operation," he says.
By political good will, Warden refers to having the cooperation of the country’s ministry of health or other high-ranking government officials who have influence over research conducted in the country.
"A lot of countries have regulatory operations that are well developed, and they have to be convinced that we’re doing ethical research and that we’re doing it in a way that protects the safety of the citizens of their country," he says.
To satisfy these concerns, it’s important to conduct an exploratory visit prior to developing a site and meet with the people whom the principal investigator has identified as being key in establishing political good will, Yahne says.
This includes ministries of health officials and representatives of nongovernmental organizations in the community, she notes.
"We also try to place trials in places where they have a basic lab and other infrastructure, but that’s not always possible," Warden says.
Once a site has been selected, the next step is to develop a community advisory board for the clinical trial, he says.
The community advisory board is separate from the IRB, which also is established at the local trial site, Yahne notes.
"We find that has been a very successful part of our strategy to make sure the community knows what we’re doing," Warden says. "The community advisory board is there to provide insight into what the community is thinking and insight into cultural issues that we may not have appreciated when we first went there."
Also, a local board can help educate the community about the disease associated with the clinical trials, such as HIV in areas where HIV clinical trials are conducted, Yahne says.
"The board also is there to help us identify the populations from which we could recruit participants for the trials and to make sure we’re treating them fairly and answering ethical concerns," she adds.
For some international trials, such as the HIV/AIDS Vaccine Trials with which Yahne and Warden are familiar, there are recruitment and screening challenges.
"In early trials, we looked for people who are at low risk of acquiring HIV, so reaching out and bringing in those populations is challenging at times because some of the same sites also are used for recruiting people who are at high risk for HIV infection," Yahne says. "And we have a vigorous screening policy; so even if you qualify initially, you could be turned down as screening progresses."
Of course, the IRB is the chief body to review ethical concerns, she adds.
"There can be multiple IRBs for a given site, especially internationally where the funding is going through the United States and a local institution, which still has to get approval in the U.S. and at the international site," Yahne explains. "And usually in other countries, there’s a governmental level approval necessary at the ministry of health level, so it can take quite a while to get all approvals in place."
When economies clash
Contract negotiations also can be tricky when an institution’s dealing with international sites, Warden says.
"One thing we’ve run into fairly recently is the exchange rates," he explains. "We can negotiate contracts for certain amounts of dollars, but then our study will run for 18 months to five years."
If there are dollar fluctuations as there has been in recent years, then the value in exchange rate can create problems, such as undermining the value of what has been negotiated for pay at international sites, Warden says.
"This last period has been more difficult because the dollar has been devalued so much against so many other currencies, so if a site really is having difficulty with the financing we’ll go back to work with them over their finances," he notes.
Still, when the contract amount is fixed, clinical trial administrators have to be creative in finding solutions, such as reducing some expenditures at the core office so that the site might receive a little more funding, Warden says.
"Any manager in this business will need to have some sort of small contingency fund because you’re always going to have problems you didn’t expect," he adds.
Other problems might include the logistics of getting supplies and equipment into foreign countries, Yahne says.
For instance, it’s very difficult to get equipment through customs in Haiti; this makes timing a clinical trial more difficult, she notes.
"So it’s important to plan ahead for trials and know what sorts of items they need, and if the item is a special freezer then you need to know ahead that it could take six months to get it through customs," Yahne says. "All of these logistical issues are just a matter of planning ahead and communicating with the site to make sure you get items to them and the things they need."