Characteristics of clinical trials of new oncology drugs approved in China.

BACKGROUND: Since reforms were introduced to incentivize drug innovation in 2015, the Chinese pharmaceutical market has experienced unprecedented prosperity, with more new drugs than ever before, especially anticancer treatments. In 2021, Chinese regulatory agencies issued the new guideline for clinical research and development of antitumor drugs, triggering a series of responses on the drug market. Limited research has outlined the nature of the original new drugs in China to understand the dynamic response of the market. METHODS: The objective of this article was to map the clinical development of approved new oncology drugs in China from 2015 to 2021 and differed from previous studies by focusing on original new drugs, using the United States as a benchmark, and elaborating the endogenous features of clinical trials. RESULTS: Clinical trials conducted in China have risen to a level similar to that of the United States in many aspects of trial design, but there is still distance between the implementation and operational details of clinical trials. In the meantime, China has made significant breakthroughs in drug approval. Greater than 60% of novel anticancer drugs in China received accelerated approved for their first listing. Approximately 90% of the pivotal clinical trials supporting initial drug approval used surrogate measures as end points, and one half were nonrandomized or did not have a control group. However, duplicate development without evidence of a clinical advantage compared with current therapies was widely observed. CONCLUSIONS: By presenting a multidimensional landscape of clinical trials and approvals in the real world, this review allows interested researchers, developers, and even regulators to understand what has been done and what should be done next in anticancer drug development in China.

Drug approval delays in hematologic malignancies between Europe and the US and between Japan and the US: a clinical perspective.

OBJECTIVE: Since novel therapeutic agents for malignancies are developed rapidly mainly in the US, the interval of approval timing between the US and other countries is an important issue. Among them, drugs for hematologic malignancies tended to have a particularly long delays in Japan, but its characteristics have not been fully understood. This study assessed the approval delays in drugs for hematologic malignancies in Japan compared with that in Europe. METHODS: Using the public database of Europe, Japan and the US, we analyzed the differences in drug approval delays between Europe and the US and between Japan and US according to disease. New molecular entity drugs for hematologic malignancies that were already approved in the US and were approved from April 2010 to March 2022 in Europe or Japan were identified. RESULTS: The results showed the longer drug approval delays in Japan compared with that in Europe (29 vs. 9.4 months, median), presumably due to the lower proportion of participation in global clinical trials (37 vs. 94%). Notably, the participation rate in global clinical trials varied widely by disease in Japan, resulting in a greater difference in drug approval delays by disease. In contrast, when focusing on early phase trials, Japanese participation was uniformly very limited regardless of the disease. CONCLUSIONS: The current study provided data that can be used as a basis for discussion on how to improve drug approval delays in drugs for hematologic malignancies.

Regional Disparity in First-in-Class Anticancer Drug Development in the US, EU, and Japan.

A cancer diagnosis is devastating for both patients and their caregivers. With high morbidity and mortality, cancer is a serious disease area with unmet medical needs. Thus, innovative anticancer drugs are in high demand worldwide but are unequally available. Our study focused on first-in-class (FIC) anticancer drugs and investigated their actual development situation in the United States (US), European Union (EU), and Japan over the last two decades to obtain fundamental information for understanding how the aforementioned demands are met, especially to eliminate drug lags among regions. We identified FIC anticancer drugs using pharmacological classes for the Japanese drug pricing system. Most FIC anticancer drugs were first approved in the US. The median approval time for anticancer drugs in new pharmacological classes during the last two decades in Japan (5072 d) was significantly different (p = 0.043) from that in the US (4253 d), though it was not significantly different from that in the EU (4655 d). Submission and approval lags between the US and Japan were more than 2.1 years, and those between the EU and Japan were more than 1.2 years. However, those between the US and the EU were less than 0.8 years. The development rate of FIC anticancer drugs in Japan is slower than in other regions. Even among developed countries, FIC anticancer drug lags exist. Considering the high impact of FIC anticancer drugs on society worldwide, we should work together to reduce drug lag among regions using an improved international cooperative framework.

Oncology drug lag in Japan: has it improved over the last decade?

BACKGROUND: Existing studies and statistics on the drug lag between Japan and the United States (US) for anti-cancer drugs indicate that it has decreased, whereas more drugs are left unapproved in Japan. This study aimed to quantify the impact of unapproved drugs on the drug lag. METHODS: Information on 136 anti-cancer drugs approved in the US between 2011 and 2022 was collected. The approval lag, defined as the number of days from the date of approval in the US to the date of approval in Japan, was calculated for all selected drugs, and the median was calculated using the Kaplan-Meier method. The approval lag for drugs not approved in Japan was treated as censored data. Factors potentially associated with the approval lag were explored using Cox regression analysis. RESULTS: The median approval lags for the first half-period (2011-2016) and the last half-period (2017-2022) were 961 days (2.6 years) and 1547 days (4.2 years), respectively (Log-rank test: p = 0.0687). The participation of Japan in the global pivotal trial was associated with a shorter approval lag, and new drug applications by non-Japanese companies that did not rank in the global sales top 20 were associated with a longer approval lag. CONCLUSIONS: Drug lag has not decreased over the last decade. The percentage of pivotal trials for US approval that included Japan has increased but should be further increased in the future. Japan may require a scheme to encourage smaller non-Japanese companies to include Japan in their global clinical development plan.

How are new drugs disseminated in Japan? Analysis using the National Database of Health Insurance Claims of Japan.

Drug lag refers to the difference in the time of a new drug's approval in different countries; the dissemination of the new drug after approval within the countries is another problem. We examined the nationwide dissemination of 11 cancer drugs approved in Japan between 2011 and 2015 using the National Database of Health Insurance Claims data. We extracted data on the number of cancer drug prescriptions from 47 prefectures and associated demographic information, such as age and sex. Eight diabetes drugs were also examined for comparison. We observed a lag between the marketing approval date of the drugs and their first use. To further explore the rise and pattern of each drug's dissemination, we analyzed the trend of the cumulative number and total of new prescriptions for each prefecture. The results showed that the first month of new cancer drug prescriptions varied across prefectures. On average, they lagged by up to 2 months in the slowest prefectures, whereas the variation was almost nonexistent for diabetes drugs. The patterns of dissemination varied more among cancer drugs across the seven Japanese geographical regions. After the initial prescription, the number of prescriptions showed a steep rise for most cancer drugs, whereas the increase was gradual for diabetes drugs. In conclusion, the dissemination of cancer drugs had a greater lag time than that of diabetes drugs. Further research is needed to explore the causative factors to ensure that all effective drugs are equally accessible for those who need them.

Lag Time for New Innovative, First-in-Class, Drug Approval in Japan.

Early access to novel drugs, regardless of regional differences, is significant for patients worldwide. Although various efforts have been made to reduce the drug lag, it still exists in some regions, including Japan. In this study, we focused on the drug lag of first-in-class drugs in Japan and obtained fundamental information because we considered that first-in-class and me-too drugs are essentially different and should be treated separately. We analyzed 97 first-in-class and 176 me-too drugs in new molecular entity (NME)-approved drugs in Japan and the United States during the fiscal years between 2009 and 2019. Since government policy and the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs (the Committee) have a huge impact on drug lag, we distinguished NMEs developed at the Committee's request. First-in-class drugs were developed at the Committee's request significantly more than the me-too drugs (p = 0.0034). Although it was not statistically significant, the approval lags were 498.0 d for first-in-class drugs and 535.0 d for me-too drugs. Multiple regression analysis showed that multi-regional clinical trial (MRCT) development strategy (p = 0.0043) and foreign origin drugs (p = 0.0072) were a reducing factor and a prolonging factor of drug lag, respectively. In conclusion, the drug lag for first-in-class drug approval was one year. Global drug development using MRCT is one of the most effective development strategies for reducing drug lags.

The drug lag and associated factors for orphan anticancer drugs in Japan compared to the United States.

The approval of orphan anticancer drugs in Japan has increased to meet high social demand. Drug lag, namely the approval lag of new drugs, is recognized as a social issue in Japan. We investigated the approval lag and its components, submission lag and review-time lag, between Japan and the United States (US) to reveal whether an approval lag still exists, and to identify potential factors that may contribute to reducing the approval lag. Anticancer drugs approved in Japan between April 2004 and November 2017 were investigated using publicly available information. Results showed that the median approval lag of orphan anticancer drugs in 2016-2017 was 727.0 days (interquartile range, IQR, 310.0-1054.3). The approval lag was significantly correlated with the submission lag (correlation coefficient = 1.00, P < 0.001) but not with the review-time lag (correlation coefficient = -0.16, P = 0.22). The submission lag was significantly longer for orphan anticancer drugs than non-orphan drugs (median, 712.5 days [IQR, 186.0-1448.3] vs. 387.0 days [92.8-1096.0], P = 0.023). External collaboration in drug development was associated with a longer submission lag (coefficient = 762.1, P = 0.017), while breakthrough therapy designation in the US was associated with a shorter submission lag (coefficient = -832.8, P = 0.035). In conclusion, we revealed that an approval lag for orphan anticancer drugs still existed in 2016-2017. A submission lag for orphan anticancer drugs was the main component affecting the approval lag, and was longer than that for non-orphan drugs. External collaboration in drug development may be a potential factor in reducing the submission lag for orphan anticancer drugs.

Recent trends for drug lag in clinical development of oncology drugs in Japan: does the oncology drug lag still exist in Japan?

BACKGROUND: This study exhaustively and historically investigated the status of drug lag for oncology drugs approved in Japan. METHODS: We comprehensively investigated oncology drugs approved in Japan between April 2001 and July 2014, using publicly available information. We also examined changes in the status of drug lag between Japan and the United States, as well as factors influencing drug lag. RESULTS: This study included 120 applications for approval of oncology drugs in Japan. The median difference over a 13-year period in the approval date between the United States and Japan was 875 days (29.2 months). This figure peaked in 2002, and showed a tendency to decline gradually each year thereafter. In 2014, the median approval lag was 281 days (9.4 months). Multiple regression analysis identified the following potential factors that reduce drug lag: "Japan's participation in global clinical trials"; "bridging strategies"; "designation of priority review in Japan"; and "molecularly targeted drugs". CONCLUSIONS: From 2001 to 2014, molecularly targeted drugs emerged as the predominant oncology drug, and the method of development has changed from full development in Japan or bridging strategy to global simultaneous development by Japan's taking part in global clinical trials. In line with these changes, the drug lag between the United States and Japan has significantly reduced to less than 1 year.

Relationship between drug lag and factors associated with clinical trials in Japan.

WHAT IS KNOWN AND OBJECTIVE: Drug lag is a major public concern in Japan. During the development of new drugs, some factors related to clinical trials in the marketing application package, such as trial design and the number of trials, can affect drug approval. The aim of this study was to determine whether those clinical trial factors were associated with drug lag in Japan. METHODS: We investigated new drug applications for new molecular entities that were approved in Japan between April 2009 and March 2012. We collected information on clinical trials in the marketing application package from review reports. RESULTS AND DISCUSSION: We constructed a multiple regression model to predict drug lag using the review period, use of foreign clinical trial data, the number of confirmatory trials, the design of the pivotal trial, failures of confirmatory trials and the death rate (n = 59). No use of foreign trial data was significantly associated with a longer drug lag (84% increase; 95% confidence interval [CI], 1·03-3·29). Compared to the open-label, one-armed design, drugs that underwent pivotal trials of placebo-controlled superiority, active-controlled superiority and active-controlled non-inferiority designs had a significantly shorter drug lag (74% decrease, 95% CI: 0·08-0·83; 74% decrease, 95% CI: 0·07-0·99; and 85% decrease, 95% CI: 0·04-0·58, respectively). WHAT IS NEW AND CONCLUSION: Our findings suggest that new drug application packages that do not use data from foreign clinical trials and that involve pivotal trials of open-label, one-armed design contribute to drug lag in Japan. To reduce this lag, improved strategies for the development of new drugs should be identified.

Comparative Assessment of Drug Lag for Approved Oncology Targeted Therapies Between Saudi Arabia, the United States, and the European Union.

INTRODUCTION: Pharmaceutical regulation on a global scale is a complex process, with regulatory bodies overseeing various aspects, including licensing, registration, manufacturing, marketing, and labeling. Among these, the USFDA plays a crucial role in upholding public health. The pharmaceutical industry contributes significantly to well-being by developing and distributing therapeutic agents. The journey of evaluating new pharmaceuticals involves meticulous examination through several phases, from safety and efficacy assessments to toxicity evaluation. Drug approval involves submitting New Drug Applications (NDAs) to regulatory agencies like the USFDA and EMA. However, disparities in durations contribute to the phenomenon known as "drug lag." This lag refers to delays in a pharmaceutical product's availability in one market compared to another. Addressing this issue is crucial, given its impact on patient access to treatments. METHOD: This study aims to analyze the extent of drug lag, focusing on newly approved oncology targeted therapies in Saudi Arabia, the United States, and the European Union. Data for cancer treatments authorized by the USFDA, EMA, and SFDA from January 1, 1997, to December 31, 2022, were collected from regulatory agency websites. The data sources included authorization letters, prescription information, and evaluation documents. We conducted a comparative assessment of drug lag for approved oncology targeted therapies between Saudi Arabia, the US, and the EU. RESULT: Our analysis identified 135 newly approved oncology-targeted drugs within the specified timeframe. Of these, 71 received approval in all three regions, while disparities were evident in others. The USFDA consistently had the highest number of approved drugs, with 98.5% of drugs initially approved there. In contrast, Saudi Arabia had the lowest number of approved drugs and a significantly longer median drug lag, indicating substantial delays in drug availability. CONCLUSION: This study highlights the significance of mitigating drug lag to enhance global healthcare outcomes and patient access to innovative therapies. Further research and collaborative efforts are essential to bridging these disparities and promoting equitable healthcare worldwide.

Different Development Strategies Affecting Japan's Drug lag between Japan-Based and Foreign-Based Companies.

We examined the development strategies of new molecular entities approved during a 10-year period (fiscal years of 2012-2021) in Japan to determine the differences in drug lag between Japan and foreign companies. The results demonstrated a clear difference in development strategies. For example, products were usually developed through a "only-Japan" strategy by Japan companies (51.1% of products), compared to a "MRCT (multi-regional clinical trials)" strategy by foreign companies (54.9% of products). Regarding types of licenses, for Japan companies, the percentage of original products was higher in the category of less drug lag, such as "no approval in the US and EU" (59.1%), whereas the percentage of "license-in" products was markedly higher in the "drug lag ≥ 5 years" category (52.5%). Such differences were not observed for products developed by foreign companies. Of 64 license-in products developed by Japan companies with a drug lag > 5 years, 51 (79.7%) had already been approved in the US or EU at initiation of clinical development in Japan. The origin of approximately half (34) of the products was from the emerging companies (non-member foreign companies of the Japan Pharmaceutical Manufacture Association). These results suggest that more global cooperation of Japan companies, particularly with emerging foreign companies, is necessary in terms of the earlier timing of license-in and development strategies of products to promote drug development without drug lag or drug loss in Japan.

Access to Innovative Medicines: Regulation Change and Factors Associated with Drug Approval Lag in Malaysia.

BACKGROUND: Drug approval lag is the time difference for new medicine to obtain marketing authorization approval in the study country compared to the first global approval. Drug approval lag delays the availability of innovative medicine to patients. This may lead to delay in treatment and severe public health implications. The study aimed to determine drug approval lag in Malaysia, the factors associated with drug approval lag (drug characteristics, regulatory factors and applicant type) and the association of the submission lag and review time with the regulation change. METHODS: All new pharmaceutical products approved between January 2015 and March 2021 were examined (n = 136) using publicly available information. Factors associated with drug approval lag were determined using multiple linear regression. RESULTS: The median drug approval lag was 855 days. Drug approval lag was associated with drug characteristics and regulatory factors. Median submission lag and median review time for products which fulfilled the requirement for the new regulations (Conditional Registration/ Facilitated Registration Pathway) were shorter compared to products which did not fulfil the requirement. CONCLUSION: Drug approval lag may delay the access of innovative medicine to patients, and this may lead to an increase in morbidity, mortality and healthcare costs. Good Regulatory Practices ensure efficient and transparent regulatory system which support the public health policy objectives in the most efficient way. The new regulations in Malaysia reduced the median submission lag and review time. The findings may be useful for regulators to consider for future policy development for medication access.

International comparison of availability for orphan drugs: focused on approved orphan drugs in South Korea.

Introduction: In this study, we aimed to comparatively analyse the indicators of availability to orphan drugs in South Korea, the United States of America, Europe Union, and Japan. Methods: For 169 drugs designated as orphan drugs in South Korea between 2012 and 2021, information on the drugs designated as orphan drugs from each jurisdiction was extracted by country. Then, the availability indicators (approval time, drug lag time, and designation gap) were analysed for the drugs approved in each jurisdiction. Results: The approval rate of drugs designated as orphan drugs were 11.22% and 6.31% in the USA and EU, respectively, which was lower than that of orphan drugs in South Korea and Japan. The highest number of approved drugs was in the USA (87 drugs), EU 27 drugs, Japan 22 drugs and Korea 21 drugs. Furthermore, the approval time significantly differed between South Korea and the other countries. South Korea had a significantly different drug lag time and designation gap compared with the USA and EU. Conclusion: Our findings show that to fundamentally improve the access to treatments for rare disease, a policy of regulatory science that can comprehensively support the early stages of research and development and commercialisation is needed.

Increasing orphan drug loss in Japan: Trends and R&D strategy for rare diseases.

Rare disease (RD) patients face significant unmet therapeutic needs worldwide. However, orphan drugs approved in the United States, but not approved or developed in Japan, have increased rapidly with recently increasing US approvals, indicating greater RD drug loss in Japan. US/EU-based startups have become key players in RD drug R&D, significantly contributing to this drug loss trend. They successfully develop drugs in the United States by combining in-licensing with in-house drug discovery. Out-licensing to Japanese companies or large pharma is critical for expansion into Japan, with successes attributed to drug innovation, target indications, and transactional capabilities. These findings highlight the need to foster partnerships with startups and cultivate an ecosystem in Japan that nurtures local startups, to address drug loss and ensure access to promising drugs.

Review time of oncology drugs and its underlying factors: an exploration in China.

Introduction: How the launch delay of drugs and other factors of interest can influence the length of the review period by drug agencies is still unknown, and understanding this can help better strike the trade-off related to review speed. Methods: We included all new oncology drug applications submitted to China's National Medical Product Administration (NMPA) between 1 January 2018 and 31 December 2021, and ultimately succeeded in achieving marketing approval. For each drug, the length of the NMPA review process and other major characteristics were collected, including the registration class, approval class, priority review designation, and launch delay relative to the United States, as well as the number of patients enrolled, comparator, and primary endpoint of the pivotal trials supporting the approval. Linear regression model was employed to analyze the effects of factors of interest on the NMPA review time. Results: From 2018 to 2021, NMPA received 137 oncology applications that were ultimately approved. Half of the approvals [76 (55.5%)] were first licensed in the US, leaving a median launch delay of 2.71 years (IQR, 1.03-5.59) in China. In the pivotal studies, the median enrollment was 361 participants (IQR, 131-682), and the use of control groups [90 (65.7%)] and surrogate endpoints [101 (73.7%)] was prevalent. The median review time was 304 days (IQR, 253-376). Multivariate analysis for log-transformed review time showed that larger enrollment (> 92) was associated with a drop of 20.55% in review time (coefficient = -0.230; 95% CI, -0.404 to -0.055; p = 0.010); and a short delay (0 < delay ≤ 1.95 years) was associated with a drop of 17.63% in review time (coefficient = -0.194; 95% CI, -0.325 to -0.062; p = 0.004). Discussion: The short launch delay relative to the US was one important driver to the review speed of NMPA, which might suggest its latent regulatory reliance on the other global regulator during the post-marketing period when new information on the drug's clinical benefit was still lacking.

Exploratory Analysis of Drug Lag in New Oncology Drugs Between Japan and the US.

BACKGROUND: Drug lag in Japan has greatly decreased over the past decades; however, new instances of drug lag have appeared along with changes in the circumstances of oncology drug development. We aimed to investigate the factors associated with the approval lag for new oncology drugs between Japan and the United States (US) over the past decade by comparing approval dates and modalities, lead indications, approval types, and phase I strategies for earlier approval in Japan. METHOD: We descriptively evaluated the characteristics of 117 new oncology drugs approved in either Japan or the US from January 1, 2011, to December 31, 2020. RESULTS: Seventy-one drugs were approved in Japan, 112 in the US, five only in Japan, and 46 only in the US. Interestingly, new oncology drugs were predominantly developed by the top 20 pharmaceutical companies in Japan; however, the opposite was true for drugs that were not yet approved in Japan. However, no clear trend was observed in the relationship between drug lag and the studied factors, except for the phase I strategy. There was a numerical but clear trend in which a higher percentage of phase I multiregional clinical trials (MRCTs) in the drug development strategy was observed for drugs with earlier approval in Japan. CONCLUSION: Participation in global drug development during the early stages, such as during phase I MRCTs, is one of the keys to successfully minimizing this new instance of drug lag in Japan.

Trends and Characteristics of New Drug Approvals in China, 2011-2021.

BACKGROUND: In the past decade, the Chinese drug regulatory system has undergone many changes. A major reform starting in 2015 has significantly reshaped the regulatory processes. It was important to assess the impact of the reform on new drug approvals in China. METHOD: We analyzed the temporal trends of regulatory characteristics of the new drugs approved by the Chinese regulatory agency from 2011 to 2021, using data collected in the Pharmcube database. RESULTS: A total of 353 new drugs were approved, including 220 small molecule drugs, 86 biological products and 47 vaccines. The annual number of new drug approvals increased dramatically since 2017, reaching a record high of 70 in 2021. The median NDA approval time was 15.4 months in 2017-2021, the shortest in the decade, and was significantly shorter than that in the pre-reform period. The newly instituted expedited pathways such as priority review (PR) and accelerated approval for urgently needed overseas drugs (UNOD) significantly reduced new drug application (NDA) approval times compared with standard review. For imported drugs, in 2017-2021, the median time difference between the first approval in the world and the approval in China was 5 years, representing significant "drug lag". However, the proportion of the imported drugs approved in China within 3 years of its first foreign approval has increased to 24.4% in 2017-2021. CONCLUSION: The regulatory reform has produced significant, positive immediate outcomes in several metrics of drug regulatory approval. China's regulatory system will continue to evolve as there still are many areas requiring further reform and improvement.

Changes in the Review Period of Drug Application and a Drug Lag from the FDA and the EMA: An Industry Survey in South Korea Between 2011 and 2020.

BACKGROUND: The Korean regulatory authority has enacted legislation to expedite the new drug approval (NDA) process. However, the effectiveness of such efforts in reducing review time and drug approval delays between Korea and the USA/EU remains to be evaluated. METHODS: We investigated NDA trends in Korea from 2011 to 2020 using approval information from pharmaceutical companies. We compared the changes in the actual review duration according to active ingredient (chemical vs. biological), orphan status, therapeutic class, and NDA review process. We estimated the submission and approval gaps of new drugs between Korea and the US and EU across the study period. RESULTS: For 235 new drugs, the median NDA review time was 315 days, with a significant increase in the delay (average 15.4 days) over time. Biological drugs had a 43.2-day delay for approval than the time taken for approving chemical drugs. The median NDA review time for orphan drugs was 130.4 days faster than that for others, although the difference diminished after 2016. Good manufacturing practice reviews played a crucial role in delaying review time. The median submission and approval gaps in Korea were 493 and 551 days, respectively, compared to those of the US and EU. CONCLUSIONS: Despite recent legislative initiatives, the delay in the NDA review timeline has steadily increased over 10 years in Korea. Delays in orphan drugs reviews increased after the enactment of the 'Rare Disease Management Act' in 2016. Careful enforcement of relevant laws and supplementary actions is required to increase new drug accessibility.

Bridging the new drug access gap between China and the United States and its related policies.

Introduction: The access gap for novel pharmaceuticals between China and the developed countries is a major public health issue in China. It is crucial to understand the determinants of this gap to ensure timely access to new drugs and enhance patient health. Methods: We included all new drugs approved by the US Food and Drug Administration (FDA) between 2012 and 2019, and collected their approval timings in China. Major factors of interest comprised orphan designation and expedited review pathways granted by the FDA, along with the proportion of Asian subjects in the pivotal trial supporting the FDA approval and whether the trial included study sites in China. The elapsed time from the FDA approval to the market authorization in China constituted the time-to-event outcome, and Cox proportional-hazards regression was used for multivariate analysis. Results: A total of 327 new drugs were approved by the FDA between 2012 and 2019, among which 41.3% were found to be authorized in China as of 1 November 2023. The median lag time for the mutually approved drugs was 3.5 years. The Cox model found that orphan drugs had lower likelihood of being approved in China (HR = 0.59, 95% CI 0.39-0.89; p = 0.011), while the FDA's Breakthrough-Therapy drugs (HR = 2.33, 95% CI 1.39-3.89; p = 0.001) and Fast-Track drugs (HR = 1.58, 95% CI 1.05-2.38; p = 0.028) had shorter lag times. In the pivotal trials that supported the FDA approvals, a higher proportion of Asian subjects was associated with faster drug entry into the Chinese market (HR = 1.02, 95% CI 1.01-1.03; p < 0.001), and the inclusion of study sites in China mainland was likewise conducive to reducing the drug lag (HR = 5.30, 95% CI 3.20-8.77; p < 0.001). After the trials with China-based sites supported the FDA approvals, 77.8% of the trials also supported the subsequent approvals in China. Discussion: China's involvement in global drug co-development can streamline clinical development, by reducing repeated trials solely in the Chinese population. This is primarily due to the openness of the Chinese drug agency towards overseas clinical data and is a positive sign that encourages global drug developers to include Chinese patients in their development plans as early as possible.

An Empirical Analysis of Japan's Drug Development Lag Behind the United States.

The "drug lag" (ie, the approval lag for new drugs) hinders patients' access to innovative new medicines. The drug lag was heavily debated in Japan from the late 2000s to the early 2010s. It consists of "development lag" (ie, the submission date lag for new drug applications) and "review lag" (ie, the difference in review periods). As the 2 lags have different causes and display significantly different recent trends in Japan, we focus on the development lag-in contrast with most previous literature-between Japan and the United States, based on a database we created for all new drugs from 2008 to 2018 using publicly available data sources. First, we found that Japan's development lag relative to the United States did not shrink in terms of the overall distribution rather than the median, which was the focus of most prior studies. Second, we examined the factors (product characteristics) that significantly affected the development lag and found that products that underwent multiregional clinical trials and those that were certified as "breakthrough therapies" in the United States had significantly shorter development lags with high robustness, whereas products receiving price premiums did not. Finally, we discussed the policy implications of these results. For instance, innovative new drugs that are presumed to receive price premiums require enhanced policy support for early application from the initial stages of clinical trials. It is also essential to promote information sharing regarding evaluations by foreign reviewing authorities for efficient use in the home country.