The growing number of clinical trials conducted overseas, which drugmakers are pursuing to hold down costs, has increasingly raised concerns about proper regulatory oversight and the welfare of enrolled patients. Over the last couple of years, for instance, GlaxoSmithKline and Wyeth briefly ran into difficulties in other countries (seehere and here). And Pfizer recently paid $75 million to settle civil and criminal charges brought by a state government in Nigeria over the 1996 Trovan scandal ( back story).
Now, though, a new report quantifies the extent to which drugmakers are researching their meds in other countries and the results suggest the concerns will not go away - 80 percent of drugs approved in 2008 had trials in foreign countries, and 78 percent of all patients were enrolled at foreign sites, according to the US Human & Health Service Inspector General. And 10 drugs approved in 2008 were tested entirely abroad with no patients in the US. Meanwhile, the FDA inspected 1.9 percent of domestic clinical trial sites and just 0.7 percent of foreign sites. And while Western Europe accounted for most foreign trial subjects and sites, Central and South America had the highest average number of subjects per site.
The issue and ensuing worries are not new, of course. An HHS OIG report in September 2001 found that "sponsors have expanded research sites into many countries that appear to have limited experience in clinical trials" and the "FDA cannot assure the same level of human subject protections in foreign trials as domestic ones." In its latest report, the HHS suggests the FDA should require standardized electronic clinical trial data, create an internal database, inspect trials in more countries and monitor trends in foreign clinical trials not conducted under Investigational New Drug applications. But critics say the findings illustrate the ongoing problems plaguing the FDA.
The report "highlights a very frightening and appalling situation,” Congresswoman Rosa DeLauro, a Connecticut Democrat, tells The New York Times. “By pursuing clinical trials in foreign countries with lower standards and where FDA lacks oversight, the industry is seeking the path of least resistance toward lower costs and higher profits to the detriment of public health.” Adil Shamoo, editor of Accountability in Research, adds that "I think this report just confirms the potential problems with foreign trials. There is less liability, patient recruitment is far easier, the concept of informed consent is not well established, and it’s cheaper.”
Drugmakers and clinical research operators, however, argue that rising costs are a legitimate concern and, moreover, clinical investigators in the US appear less interested in participating in studies. As if the HHS study was anticipated, in fact, a recent survey by the Association of Clinical Research Organizations found that between 2004 and 2007, the number of clinical trial investigators who are regulated by the FDA fell 5.2 percent in the US and 6.1 percent in Western Europe, while increasing 16 percent in Eastern Europe, 12 percent in Asia and 10 percent in Latin America.
The reasons cited by US investigators: regulations make trials difficult to manage, medical liability, and conflict of interest mandates that docs disclose financial relationships with pharma. In fact, 24 percent of US investigators are less likely to participate in trials if they are required to disclose income. And US investigators are more concerned with making money - 68 percent say this is a “very important” factor in their participation (read more here).
UPDATE: At about 4:30 pm EST, the PhRMA trade group writes us to say that the same regulatory standards apply to foreign trials as those conducted in the US. "Is it ethical to conduct such studies outside of the US? In a word: Yes. Whether the clinical research occurs in the US or outside its borders, our member companies must adhere to Good Clinical Practice guidelines. “In fact, PhRMA has conducted educational seminars and symposiums – at times, in conjunction with the FDA – in other countries to educate potential clinical trial principal investigators about Good Clinical Practices, ethics oversight by outside review boards, and the need to maintain the highest standards for data quality. “Regardless of the location, however, companies seeking US approval must maintain the FDA’s high standards for conducting the trial. For instance, any related trials conducted outside the U.S. must comply with FDA requirements covering Good Clinical Practices, in addition to meeting the requirements mandated in these important emerging markets." Here is the complete PhRMA statement.