Including China in multinational clinical trial programmes can reduce sample sizes, cut development costs and shorten drug registration times both locally and in either regional or international markets, says Parexel’s vice president and general manager for the Asia Pacific region.
Speaking at the 7th Annual Partnerships in Clinical Trials Congress in Berlin earlier this month, Albert Liou explained how in the past sponsors could not secure approval to start a clinical trial in China until they had obtained a Certificate of Pharmaceutical Product (CPP) from the source country. The CPP indicates that the product concerned is marketed in the country of origin and that the producer complies with Good Manufacturing Practice and is inspected regularly by the national health authorities.
As Liou pointed out, it then takes four to seven years to complete the cycle of local clinical trials and product registration in China. While regulatory timelines have improved, just getting a Clinical Trial Application (CTA) cleared is a matter of six to 12 months.
Under current regulations, though, if China is part of a multinational trial the source-country CPP is not required for submission of an investigational new drug application (IND), Liou noted. In that case, the sponsor benefits from faster patient recruitment times in China, with the knock-on effect of accelerating development and approval times for the global study. It also has a subset of global clinical trial data from China to be used for local product registration.
In 2006 China had a population of 1,313.9 million, 62,690 hospitals and 674,680 specialised medical doctors, compared with a population of 1,095.3 million, 18,575 hospitals and 197,459 specialised doctors in India. The corresponding figures for Japan were 127.5 million, 9,095 and 183,169.
Liou gave the example of an international oncology trial conducted by Eli Lilly in which the patient enrolment rate (per site per month) was 0.60 for China, slower only than Turkey (1.10), Korea (0.90) and Taiwan (0.67). Enrolment rates for India and Brazil were 0.50 patients and 0.46 patients per site per month respectively. Germany scored 0.44, Italy 0.16 and the US 0.08.
Integrating China into a global clinical trial is only possible if there are no differences in drug dosages between the Japan/Asia arm and the US/EU, Liou noted. For products meeting that criterion, though, the advantages can be substantial.
Using this approach for its anticancer Nexavar (sorafenib) in renal cell carcinoma, Bayer Schering Pharma achieved the fastest product launch on record in China – less than two months after US approval. China was included in a multinational Phase III trial for Nexavar and the same data were used for Chinese registration after a US CPP was obtained.
If drug dosages are not consistent between Japan/Asia and the US/EU, China can still be integrated into an Asia Pacific regional trial including Japan, Korea and Taiwan, which accept bridging studies.
In a case study presented by Liou that involved combining protocols for a Type II diabetes drug in, respectively, China/Taiwan/Korea/India and Japan for Asian registration, the sample size was reduced by more than 20%, the necessary human resources by over 30% and the study budget by more than 40%. The gain on completion time for the Asia Pacific trial was over 50%.
