Medical network - on December 28, with the new drug development and globalization, the international multicenter clinical trial (Multi - regional clinical trual, MRCT) has been widely used, and become the main source of new drug clinical trial registration data, used for new drug application in different countries.
As a new drug clinical trials in the process of global research and development of a form of organization, MRCT in such aspects as design, implementation, analysis, management is more complex than the general clinical trials. In MRCT, drug treatment effect differences in different areas, one of the biggest difficulties is often explain MRCT results, it is also the difficult point in drug approval decision. As regulators face the increase in the number of new drug application MRCT data, design, implementation and evaluation MRCT still highly challenging.
Declare how to try to break through the "pain points", the auxiliary review department, accelerate MRCT data declaration approved quickly? At the recent Beijing hospital clinical trials research center set up congress and "clinical research and drug development and risk management in 2016 peak BBS", shenyang pharmaceutical university professor, eli lilly Asia fund risk partner Su Ling suggestion: first, MRCT plan more early, more comprehensive, MRCT advantage have the opportunity to get more, but the difficulty is bigger also. Can determine beforehand, emphatically in the planning design phase and stressed that encourages early exploratory research, strengthening the drug regulatory department and the related areas of communication and consultation. Second, MRCT clinical researchers and experts in the related regions participate in the test plan and design, make the MRCT design is in line with the specific situation of the related areas and medical practice, meet the requirements of regulatory authorities, guarantee the reliability of the GCP compliance and clinical trials and data quality.
The mount guiding principles
In November, ICH international coordination meeting held in Tokyo, according to data released in Japan based on MRCT listed for approval of new drugs increased year by year, 2015, 2015 new drugs approved in 23 data based on MRCT, 20%; MRCT accounts for higher in 2014, 119 new drugs approved in 32, accounted for 26.9%; But in 2008, approval of new drugs based on MRCT data also is almost zero.
Member of Chinese academy of sciences, Beijing hospital yi-xin zeng pointed out that although MRCT can reduce repeated clinical trials on the one hand, driving the global synchronous development, improve the efficiency of new drug research and development, make the patients as early as possible for new drug therapy; Have the opportunity to study drug, on the other hand, similarities and differences in different regions or the crowd, but from the point of the regulation implementation, MRCT guidelines are not perfect in our country at present stage, while the us and Europe, the strength of the support MRCT data is larger.
In response, the Chinese academy of engineering, major national major projects drugs oriented technology, the total teacher sang guowei said: "in recent years, although our country's new technology got rapid development, but the quantity we participate in MRCT is relatively limited, this and our ability to conduct clinical trials at present levels are closely related. 'much starker choices-and graver consequences-in period, we are still support the general direction of GCP centers, set up 10 ~ 15 GCP guidelines on a national demonstration center."
The United States for foreign the requirements of clinical trial data are divided into two kinds: first, use foreign IND IND or NDA clinical trial data to support the United States. Clinical trials in accordance with GCP standards and requirements, and the FDA can conduct site inspection, when think need to verify the reliability of the test data. The second, all with foreign clinical trial data to support the NDA. Data is suitable for the American people and American medical practice, clinical trials completed by researchers have recognized qualifications, and data believed to be reliable without through on-site inspection, the FDA can also confirmed its reliability by site inspection or by other means.
At present, the eu has issued "on the eu clinical trials corollary to the crowd outside the territory of opinions", analyzes the November outside the eu clinical trials in the examination and approval extrapolation to eu listed drug review when they are in trouble. They are listed on the drug review concerns is that clinical trial is in line with the ethical principles and GCP requirements, data quality is guaranteed, the results whether apply for eu people.
Japan emphasized must strictly conform to the requirements of the ethical principles and GCP, PMDA can in a clinical trial for any institution to do so. Will evaluate the results of clinical trials, efficacy and safety of the structure and the Japanese subgroup conformity assessment results, but the requirement MRCT Ⅰ stage of clinical trials in Japan. Overall, Japan encourage drug research and development institutions to participate in global early exploratory experiments, including dose experiment.
Effectively circumvent the test error
Sang guowei, points out that from the perspective of the regulation application MRCT data support to register need to be reviewed from three aspects: one is the acceptability, test design scheme is not only to reasonable, data quality is higher, and ethical principles and the GCP requirements; Second, applicability, curative effect and safety of results can be used in the region of patients; 3 it is consistency, the consistency of interval around the drug effect.
Su Ling, also thinks MRCT test is the most ideal situation all areas and their regulators have agreed on a single end index or index group, so that it can be to the success of the clinical trials have clear judgment. In the different regions may have different understanding or measurement to give special attention to the end of the indicators, such as hospital, scale. In different regions of the consensus, assesses the primary end point of different index, diversity in the statistical analysis at the same time that don't have to adjust.
So, on the choice of confirmed sex MRCT dose should be how to do? Confirmed Su Ling said that all the participants in sexual MRCT district in principle should use the same dosage. In the research and development of Ⅰ ~ Ⅱ period clinical should undertake the corresponding PK/PD research, to determine whether important regional differences. If early studies have demonstrated that in a certain region or exposure dose of drug or concentration-response relationship is significantly different, in this dose can produce similar treatment effect and have acceptable security under the premise of can consider to use in the region of different doses of experiment.
In addition, in MRCT on the total number of cases and regional distribution of the number of cases, Beijing hospital, director of the center for clinical trials ke-xin li pointed out that the calculation of the total number of cases all parts should be based on the summary of data, is the overall effect of drug treatment of statistical tests to determine. At present, the regional distribution of the number of cases there are five possible: 1. All regions have enough number of cases show that treatment result was trend consistency between regions; 2. Each region has a sufficient number of cases shows treatment result and the overall result is a certain proportion, such as the outcome of a certain area is 50% of the overall result; 3. The regional distribution proportion of the cases according to the prevalence of high and low, 4. Have enough number of cases in one or more of the region to achieve statistically significant; 5. In one or more areas has a minimum number of cases.
At the same time, to plan the number of cases and evaluate the consistency between regions, in the planning and designing MRCT, if you can determine in advance some areas on the inner and outer factors is similar, some areas can be merged, becoming merged regions, such as east Asia, Europe, North America, etc. Or will a combination and in some areas, population of merger, such as the Chinese living in Asia and the americas, whites living in North America and Europe, etc., but these mergers must be determined in advance and write clinical trial scheme. |
