Distant Shores
by Lisa Zamosky
June 2007
Clinical trial sponsors conducting trials in non-Western countries are employing innovative strategies to optimize site management and patient recruitment.
Since clinical trial enrollment rates have dropped precipitously in the West, drug developers increasingly are looking to countries in Asia, Eastern Europe and South America to bring in large, interested patient populations. Biopharmaceutical companies are employing strategies such as selecting trial sites with a significant patient volume and training and deploying country-specific regulatory experts in an effort to maximize their research investment.
“Setting up a trial site requires an incredible effort in terms of people, time and dollars, regulatory and filed paper work, contracts, investigator meetings, ongoing monitoring, drug supply and inventory control,” says Dr. Robert Maguire, vice president of clinical development for the clinical trial operations group at Wyeth Pharmaceuticals, in Collegeville, Pa., USA. “With all of the resources required to establish a trial site, it’s no surprise that companies want greater assurance that their efforts will yield results.”
Dry Wells
Most pharmaceutical and biotechnology companies have been conducting clinical trials outside the United States and Western Europe for some time. This trend continues to grow because of intense competition for eligible patients, says Judy Siegel, Ph.D., vice president of pharma development operations at Hoffmann-La Roche Inc., in Nutley, N.J., USA. “The number of drugs now being researched, and the number of companies doing research has exploded,” Siegel says. “The appropriate patient pool for clinical trials in the United States and Western Europe cannot accommodate all the drugs there are to be tested.”
Improvement in patient care and available drug treatment options adds to the competition for patients and is another reason for the reduction of available patients in the West, Siegel says. Diseases are better managed today, so it can be difficult to find and enroll patients who have never received treatment for the condition being studied. “If you are looking for early diabetes patients, for example, you will have a harder time finding people in the West who did not receive treatment early on,” she says.
Lack of available treatments is one of the main attractions of conducting clinical trials in Asia and South America, says Dr. Evan Loh, vice president of research and development at Wyeth. “Going to countries outside of the United States and Western Europe, you would expect the standard of care to be different, allowing you to treat patients who are likely not taking other medications that get in the way of the drug you’re trying to study,” he says.
Volume Control
In addition to the large number of patients eager to participate in clinical research as a means of gaining access to medications they probably would not obtain otherwise, many non-Western countries also have the requisite level of highly trained and skilled physicians capable of managing trials to Western standards. Selecting large, world-class medical centers in non-core countries as clinical trial sites can make trials proceed more quickly, Loh says. In Korea and China, for example, a 3,000 to 4,000-bed hospital is common, he says. “We were studying a new kidney cancer drug, and we averaged 20 to 40 patients [per site] in Hong Kong, whereas we only averaged about five patients per site in the United States because hospitals are more available [in the United States],” he says.
Although patient volume certainly is important for efficient recruitment, patient selection also must be managed carefully to achieve a cultural balance in the study population, says Siegel. “If allowed to enter patients at the available rate, countries like China could overwhelm a study’s patient population,” she says. “With a global trial, it is preferable to involve a mix of patients from all over the globe.”
When taking a clinical development program global, trial sponsors are presented with a whole new set of complexities. Conducting trials in multiple countries simultaneously makes managing the regulatory processes and clinical research laws of each country a challenge. “In some countries, it is critical to have our own employees working closely with the local health authorities to ensure that our applications move through the system in a reasonable timeframe,” Siegel says.
Having trained personnel on location in each country can alleviate some of the legal and regulatory frustrations faced by trial sponsors. Wyeth has sought to optimize the regulatory process, in part by establishing a dedicated clinical trial operations team, says Mark Ridge, director of global enrollment planning and performance at Wyeth. “We’ve set up clear roles and responsibilities in each of the countries with different groups within the organization,” he says. “Once we have final protocols for foreign countries and have them translated, we can move.”
Picking and Choosing
As a long-term strategy, Wyeth is working to establish relationships with large medical centers that have motivated and experienced investigators on staff to support trial research. Wyeth has 400 to 500 sites around the world involved in Phase II studies, and is in the process of dramatically reducing that number, Maguire says. Instead of maintaining a massive network of sites, each of which may only enroll a minimal number of patients, Wyeth’s current strategy is to establish relationships with about 15 global sites that can generate the volume, quality and efficiencies the company requires. To that end, the company is creating a limited number of early clinical development centers that are able to attract a large volume of patients for Phase II studies. One such site sees 9,000 patients daily on an outpatient basis, Maguire says. “The goal is to mitigate risk by establishing close relationships with sites throughout the world that are closely aligned and able to be successful,” he says.
The demand for patient participation in clinical trials will not diminish, so companies must continue to seek out patient populations in countries that have not traditionally contributed, Siegel says. “This will challenge the pharma industry to develop innovative networks and processes to ensure that patients in these countries can be recruited, treated and managed as per the standards that exist in countries that have traditionally been involved in clinical research.”
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