With large patient populations and enhanced regulation and standards, China is taking an increasingly pivotal role in the conduct of clinical trials – a development supported by the country’s booming economy and skilled workforce.

GlobalData’s white paper, ‘Clinical Trials: Enrollment Trends in Emerging Markets – China’, provides a valuable overview of phase I–III trials with locations in the region, offering key insights into the comparative enrolment rates and efficiencies of single-country and multinational trials, therapy, indication areas and trial phases.

The report covers trials conducted between 1 January 2001 and 9 April 2018, and encompasses those that were led exclusively in China as well as multinational trials that included the country. The data for this review was derived from the Enrollment Database of GlobalData’s Pharmaceutical Intelligence Center, which includes company-sponsored clinical trials with completed, ongoing, planned and terminated statuses. A small number of phase I/II and II/III trials were combined with phase II and III ones, respectively.

The document shows a concentration of activity in late-stage trials. Phase III make up the largest proportion of those analysed in the paper at 54.8%; 25.1% were for phase I and phase II trials had 20%. The number of subjects was also much larger for phase III, with an average of 1,209 recruited. This was compared with an average of 153 subjects for phase II and 52 for phase I.

Enrolment analysis

In addition, the report found that phase III trials had the longest trial duration and required more time to enrol patients than phase I or phase II. Phase I had the shortest average study duration – one year – and the shortest average enrolment period at 10.3 months – a result in keeping with expectations, as phase I trials tend to recruit healthy patients in small numbers (see Figure 1).

On average, enrolment rates for single-country and multinational trials that include China decrease from phase I to phase III. The former enrolled an average of 15.5 subjects/ site/month, while phase III had an average of 4.4.

Overall, clinical trials in China have high enrolment efficiency regardless of the developmental phase, with the lowest enrolment efficiency coming in at 94.3% for phase II. Phase I enjoyed the highest rate at 101.2%, reflecting the low average number of subjects. A key finding from the report was the startling variation in enrolment rate between single-country trials and multinational endeavours.

For every stage, the enrolment rate was significantly higher for trials conducted solely in China; this was seven times higher than that of multinational trials in phases I and III, and 12 times greater for phase II trials. These figures reflected the more streamlined nature of a trial where only one regulatory and ethical authority is involved, as well as a high availability of subjects meeting the trial inclusion criteria (see Figure 2).

The impact of site numbers

GlobalData found that in multinational and single-country trials run in China, the higher the number of sites there were in a trial, the lower the enrolment rate would be. For the single-site trials, this was 19.3 subjects/site/month compared with only 0.7 subjects/site/month for those with a site count of higher than 50 (see Figure 5).

When only single-country trials were considered, the enrolment rate trend remained the same, falling when more sites were added to a trial. However, while the largest proportion of multinational trials had a site count of more than 50 – 31.4% of the total – the opposite was true when considering single-country trials, which accounted for 46.8%.

The most popular therapies

Turning to the focus of trials conducted in China, the report’s analysis found oncology to be the largest therapy area – followed by infectious disease, cardiovascular, metabolic disorders and central nervous system – but also to have the slowest overall enrolment rate of these five top fields.

One of the reasons for this slow rate was because oncology presents the longest average study duration (37.3 months) and the longest enrolment period (22.3 months); the converse was true of infectious disease, which had the fastest enrolment rate, as well as the shortest study duration and enrolment period (see Figures 3 and 4).

Oncology trials often require invasive procedures like biopsies to determine eligibility, a process that potential subjects may be unwilling to undergo if they have no guarantee of inclusion in the study. Another issue that may account for this low enrolment rate could be intense competition for patients, due to the high number of oncology trials taking place in China.

When only single-country trials in the region were analysed in these top five therapeutic areas, the overall enrolment rate increased between 1.5 and two times in all fields except infectious disease, which remained the same. This implied that one of the reasons infectious disease trials found it far easier to accrue participants is because most were single-country trials. As demonstrated above, these particular trials boasted far higher enrolment rates than those that included more than one nation.

GlobalData found that 70% of infectious disease trials were singlecountry ones, while only 50% of the trials in the oncology and cardiovascular areas were single-country. The low enrolment rate for oncology and cardiovascular trials, therefore, could be attributed to the increased number of multinational trials for them.

When analysing the clinical trials by indication, GlobalData discovered that the most studied was type 2 diabetes, with the others being – by number of clinical trials – non-small cell lung cancer, hepatitis B, breast cancer and rheumatoid arthritis. Type 2 diabetes also presented the highest enrolment rate of the top five indications at 9.1 subjects/site/month; the lowest enrolment overall rate was breast cancer at 2.3 subjects/site/month.

Type 2 diabetes also featured the highest average enrolment efficiency of the top five indications at 103.6%. As it had the highest clinical trial count, it is not surprising that the metabolic disorder also had the greatest average number of subjects enrolled at 953 participants.