Clinical Trials in China: A Double Standard?
James Fan, MD • Director Medical & Safety Services, ICON Clinical Research – Singapore
As increasing numbers of clinical trials take place in China – the site of numerous, well-publicized quality issues in the pharmaceutical manufacturing business – it is time to ask: Are there any differences in the quality standards of local vs. global trials conducted in China? What might be the reasons for any apparent differences? And, finally, should both types of studies be held to the same standards?
To gather qualitative insights on the issue, we asked the opinions of clinical-trial professionals through an online survey. The results suggest that local and global trials are indeed conducted to different quality standards in China, albeit for reasons that are often unrelated to the capabilities of the research organizations involved. In fact, the principle reason is actually quite logical from a regulatory point of view.
Clinical Trial Trends
China is a growing "hot spot" for conducting clinical trials within an already popular Asia Pacific region. According to the US National Institutes of Health, the number of trials being conducted in China is 2,409. Applied Clinical Trials reported in its September 2010 edition that: "…China continues its emerging status with an uptick in activity," and the publication has described China as "the last frontier" for clinical research.
It seems logical to assume that this trend will accelerate, providing China's State Food & Drug Administration is successful in improving the timelines for regulatory review, which currently often approach a year and is one of the drawbacks to using China for clinical studies.
Defining Local vs. Global Studies
"Local" trials are those conducted to gain local marketing approval for products already marketed in the US and/or the EU. The efficacy and safety of such products have already been demonstrated, and the product development is typically in Phase III and IV.
"Global" trials ar those undertaken in China to gain marketing approval from the US Food & Drug Administration or the European Medicines Agency. These trials are generally for products in Phase II and III, and the drug's sponsors are merely taking advantage of China's favorable environment for clinical trials. The advantages of conducting trials in China include lower costs, rapid patient recruitment, the availability of worldclass investigative sites and a massive market. According to IMS Health, China is now the third largest pharmaceutical market in the world.
The CRO Environment in China
Within China, there is fairly clear delineation between CROs that conduct local trials and those that conduct global trials. Almost without exception, international CROs with operations in China conduct global trials for multinational pharmaceutical companies. (Local CROs lack the global presence and experience to manage trials on a global level.) Conversely, local CROs in China generally perform the local studies, and competition among them is intense. They work for organizations that do not have in- house medical departments and therefore depend on local CROs for cost-effective trial management. These include Chinese national pharmaceutical companies, the local affiliates of multinational pharmaceutical/ medical device companies, some small, multinational companies, and academic institutions.
The Verdict on Quality
Although the vast majority (90%) of respondents to the survey maintain that local trials should have the same quality standard as global trials, the study strongly suggests that there are, in reality, different quality standards for local and global trials. Most survey participants (71%) believe that local trials do not achieve the same standards as global trials. A further 14% state that the quality standard for both types of trials is the same, while only 3% suggest the standard for local trials is higher.
The 71% who stated that local trials were not on par with global trials specified the following areas in which local studies were substandard: study monitoring, the lack of insurance or an indemnity policy, relatively simple study design, and data quality/ management. (See Fig. 1: Substandard Aspects of Local Studies)
Explaining the Difference
When respondents were asked to identify the reasons behind the perceived difference in quality standards for local and global studies, they most often named trial funding, followed by amount of study grant, site/investigator's interest in the trial, training of site staff, and different regulatory standards. (See Fig. 2: Reasons for Quality Differences)
Interestingly, the respondents who disagreed that the same standards should apply to both types of trials gave as their rationale the fact that local trials simply do not need to meet the same standards as global trials. Local trials are conducted on products that are already marketed overseas and have established safety and efficacy records. Thus, local regulatory requirements are lower, and study funding is critical.
From a regulatory point of view, it could be argued that local trials, which are mainly Phase III and IV studies, should not be subject to the same strict controls and high quality standards as global trials that are primarily Phase II and III studies. From a business and scientific point of view, however, it is easy to argue against a double standard; clinical trials, whether they are local or global, should adhere to GCP standards.
The latter view is clearly the most common among the study participants. Given their responses, the quality of local trials should be improved in a number of areas, including study monitoring, insurance, data quality/management, trial funding, and training of site staff. Clearly there is a business opportunity for the local CRO that can increase study quality at prices the local market is willing to pay.
To the extent that quality issues with local studies are related to the caliber of the local CRO, study sponsors can avoid potential problems by contracting with local research organizations that are part of widely established, international organizations. The management, resources, procedures, and standards of the international firm thus become those of the local organization and study sponsors benefit from "the best of both worlds."
Patient Interest in Local vs. Global Studies
At the same time, we wondered: Do Chinese patients have a preference for the type of study in which they participate?
Most respondents (42%) believe that the recruitment rate is better in global trials than for local trials, while another 31% indicate that they see no difference. The reasons given for any perceived difference included the use of larger hospitals with a bigger patient population and the payment of transportation expenses.
Over a third of respondents (37%) believe that patients are more willing to participate in a global trial than a local trial, as global trials provide advantages such as insurance, a "free" new drug, a "free" laboratory test and monetary incentives (e.g. transport expenses). However, a similar proportion (38%) of respondents felt that there is no difference between global and local trials with respect to the patients' motivation to participate.
Again, respondents were evenly divided on the question of retention and compliance in global vs. local trials. Survey participants who stated that global studies are superior suggested that was the case because of superior study design and patient follow-up as well as heightened motivation on the part of the investigator due to increased study funding.
About the Survey
|The survey conducted by ICON Medical & Safety Services consisted of 17 questions fielded on a clinical-trial website (www.druggcp.net) between October 2009 and April 2010. A total of 273 clinical-trial professionals responded. Two-thirds (38%) worked for CROs, another 28% for pharmaceutical companies, and the remainder (21%) for academic/medical centers or healthcare organizations. Half (51 %) were involved only with local trials, while 30% were involved with both local and global trials. A small percentage (8%) worked only on global trials. More than half of the respondents (57%) hold a medical degree, while 17% hold a master's degree and 22% a bachelor's degree.||