Here’s a simple question: Is the race to conduct clinical trials overseas a good thing? Certainly, there are several reasons to say ‘yes.’ After all, costs are generally lower. Treatments may be made available to patients who would otherwise not have access. Forging relationships with investigators in other countries is a plus. And overall, drug and device development time should generally shrink.

But of course, nothing is that simple, and here’s why: Standards can vary widely among countries. And that can raise questions about the qualifications of individual investigators and review boards, the commitment of local regulatory authorities and the ability of patients to fully understand the implications of the testing. In other words, the globalization of clinical trials may offer benefits but the trend does not come without sobering problems.

A few notable examples made headlines over the past year. The most notorious was the ongoing controversy over the 1996 clinical trial in Nigeria of Pfizer’s Trovan antibiotic, which was blamed for the deaths of 11 youngsters and serious injuries to many others. A settlement with numerous Nigerian families may be near, but in January they won the right to sue the drug maker in U.S. courts.

Last fall, Wyeth was forced to halt a vaccine trial in India after an infant died, prompting a probe by regulators into inclusion criteria; the drugmaker maintained rules were followed properly. And GlaxoSmithKline was criticized in Argentina for a vaccine trial involving children from families who may not have fully understood consent forms, although the drugmaker insisted international standards were followed.

Although there will always be problematic episodes – no process is perfect – a recent piece in The New England Journal of Medicine argued that various scientific and ethical concerns are, in fact, mounting. In their article, which appeared in February, researchers at Duke University School of Medicine wrote that international standards and corporate and academic oversight must be improved to ensure research goals are achieved and societal needs are met.

“Regulatory bodies are often structured to monitor the quality of clinical trial data and the safety of drugs and devices in their domestic markets. (But) they have limited information on many aspects of research conducted outside their jurisdictions or countries, including the sites, investigators and participants and the quality of trial data,” the team wrote. “Thus, we know little about the conduct and quality of research in countries that have relatively little clinical research experience.”

There’s more. They maintain that hospital and clinic infrastructure, treatment choices and quality of care vary widely among countries. Investigators in developing countries are generally less experienced and less familiar with transparency guidelines. Geographically distinct populations can have different genetic profiles, which can affect safety and effectiveness results. And they argue there is an insufficient number of trials for medicines that would treat diseases that disproportionately afflict local populations.

To underscore the trend, a recent report from the Tufts Center for the Study of Drug Development found that, in 1997, 86% of principal investigators registered were the FDA were based in the U.S., but that number fell to 54% in 2007.

So is the head-long rush overseas just too much, too fast? And what exactly should be done? The Duke researchers say international guidelines need to be upgraded in order to avoid vague interpretations. As an example, how does one define an “adequately monitored” trial? They also maintain that drug and device makers, clinical research organizations and academics all bear some responsibility for increasing collaboration, supervision and documentation.

“The problem is the cost pressure; because regulators demand more trials, there’s a push to get more global data,” said Faiz Kermani, a former marketing manager at Chiltern International, a clinical research organization. “Over the years, we have developed very regulated systems in the U.S., parts of Europe and Japan. You can’t say the same for China, India and other places. So you can’t just go into these countries and start recruiting patients.

“But there’s a need for more direction from regulators. . . . They need to audit sites. If you have a fear of regulators, industry may react. They need to feel pressure. And to win business, academic centers must up their game. . . .The NEJM piece was useful because it got everyone talking. Someone has to raise these issues.”

The discussion has placed some on the defensive. Not surprisingly, the Association of Clinical Research Organizations agrees with the Duke researchers that international standards need revisions and more should be demanded of regulators.

“Perception is certainly an issue. There’s no question that a single reported episode is very much concerning for the companies and individuals trying to maintain quality,” said Doug Peddicord, ACRO’s executive director. “But how do you begin to ensure that quality is consistent and standards are met? I don’t think complaining about regulatory burden makes a lot of sense. We do say that regulators who help to ensure patient safety and data integrity are at the heart of the process.”

However, the trade group argues overseas expansion is a reflection of not only a need to save money, but also reflects difficulties in recruiting and retaining patients in the U.S., as well as insufficient patient awareness of clinical trials for which they may be eligible. For these reasons, ACRO says industry has no choice but to go abroad. As far as the trade group is concerned, costs and regulatory requirements are only part of the story.

To make its case, ACRO cites various surveys, including one that found delays in patient recruitment account for an average of 4.6 months lost for each trial. Another revealed that 80% of all trials are delayed at least one month due to inadequate enrollment. And a survey last year by the Society for Women’s Health Research noted that 94% of Americans have never been informed by their doctors of clinical trials in which they might participate.

Just the same, one expert who has industry’s ear says that drug and device makers, CROs and institutional review boards (IRBs) can do a better job of sharing data that has been collected for more than a dozen years from the numerous overseas clinical trials that have been conducted overseas. Such an undertaking would, presumably, yield comparative data about product performance as well as ethical concerns.

“Unfortunately, change doesn’t come about unless there’s a crisis, but this isn’t necessarily a project that’s front and center,” said Ken Getz, a senior research fellow at the Tufts Center for the Study of Drug Development. “The FDA does have a lot of good inspection data, but has really relied on infrastructure in place – local regulatory authorities, IRBs and professionals on the ground. There’s hasn’t been enough of a compelling reason to look at their own data.

“I will say that, based on data I’ve seen, this problem is not so worrisome to warrant shooting a flare in the sky. A lot of the inspection data suggests the level of compliance in regions aboard is comparable to the U.S.”

Mr. Getz added, “That said, this is something we need to be concerned about worldwide basis, because we do hear reports from IRBs that they really do have concerns about investigators in certain parts of the world and these are just starting to catch our attention. We’re entering a period where we need to take a closer look at this. There are conflicting pieces of evidence. And so we need to do more robust studies to understand what’s going on.”

Indeed, overseas clinical trials are not going to be curtailed. And the surge into so-called emerging markets and less-developed nations will, at some point, lead to more instances where questions are raised and heightened scrutiny is applied. If Mr. Getz is correct, then there’s no reason to delay. In fact, paying closer attention is in everyone’s interest – industry and patients.

Ed Silverman is a prize-winning journalist who has covered the pharmaceutical industry for The Star-Ledger of New Jersey, one of the nation’s largest daily newspapers, for more than 12 years. During that time, he has closely followed a variety of topics of concern to those who work for, and with, pharmaceutical manufacturers – drug development, mergers and acquisitions, regulatory oversight, safety and pricing controversies, and marketing issues. For the past two years, Ed blogged about the drug industry at Pharmalot. Prior to joining The Star-Ledger, Ed spent six years at New York Newsday and previously worked at Investor’s Business Daily, among other newspapers.