Fine-Tuning Electron-Donor Capability in the Basic Anion of Poly(ionic liquid) Frameworks for Revolutionizing Catalytic Synthesis of Ethyl Methyl Carbonate with Both Ultrahigh Catalytic Activity and Selectivity.

Ethyl methyl carbonate (EMC) is a crucial solvent extensively utilized in lithium-ion battery electrolytes; the transesterification of dimethyl carbonate (DMC) with ethanol is a pivotal reaction for EMC production. However, this reaction faces challenges due to the trade-off between catalytic activity and selectivity from the basic catalysts. In this issue, we report an innovative strategy through fine-tuning the electron-donor capability of the basic phenolate anion ([PhO]) in a novel poly(ionic liquid) (PIL) framework, as synthesized via an alkylation reaction between 1,3,5-tris(bromomethyl)benzene, biphenyldiimidazole, and N,N'-carbonyldiimidazole (CDI) to trigger targeted basicity that can directionally catalyze the transesterification of DMC with ethanol, so as to achieve both ultrahigh catalytic activity and selectivity toward EMC. By varying the substituent groups with electron-withdrawing and electron-donating effects on the phenolate anion, the PILs show expected changes in the catalytic performance, following well with the trend of charge density on these substituted phenolate anions. The optimized catalyst [CPIL-CDI][MeOPhO], induced by p-methoxyphenolate anions, allows an extraordinary EMC yield of 72.19% and an EMC selectivity of 91.48% under mild conditions without any process intensifications, suppressing all of the reported catalysts reported to date. Outcomes and approaches shown in this work have the potential to expedite the systematic design of cations and anions within PILs for industrial-scale EMC production through environmentally friendly transesterification processes.

Quantitative evaluation of the impact of relaxing eligibility criteria on the risk-benefit profile of drugs for lung cancer based on real-world data.

INTRODUCTION: Restrictive eligibility criteria in cancer drug trials result in low enrollment rates and limited population diversity. Relaxed eligibility criteria (REC) based on solid evidence is becoming necessary for stakeholders worldwide. However, the absence of high-quality, favorable evidence remains a major challenge. This study presents a protocol to quantitatively evaluate the impact of relaxing eligibility criteria in common non-small cell lung cancer (NSCLC) protocols in China, on the risk-benefit profile. This involves a detailed explanation of the rationale, framework, and design of REC. METHODS: To evaluate our REC in NSCLC drug trials, we will first construct a structured, cross-dimensional real-world NSCLC database using deep learning methods. We will then establish randomized virtual cohorts and perform benefit-risk assessment using Monte Carlo simulation and propensity matching. Shapley value will be utilized to quantitatively measure the effect of the change of each eligibility criterion on patient volume, clinical efficacy and safety. DISCUSSION: This study is one of the few that focuses on the problem of overly stringent eligibility criteria cancer drug clinical trials, providing quantitative evaluation of the effect of relaxing each NSCLC eligibility criterion. This study will not only provide scientific evidence for the rational design of population inclusion in lung cancer clinical trials, but also establish a data governance system, as well as a REC evaluation framework that can be generalized to other cancer studies.

A call to rethink the necessity of and challenges facing academic research organizations in the new era of drug innovation in China.

The objectives of drug R&D in China have shifted toward innovation and globalization, highlighting the ecological imperative to involve innovative partner-like academic research organizations (AROs). AROs are led by academic institutions and, when compared to contract research organizations (CROs), their strengths lie in promoting academic excellence, knowledge sharing, independence, collaborative networks and industry partnerships. Our desk-based analysis shows that although the service scope of Chinese AROs is similar to that of AROs in the US, they lack experience in broad service provision for innovative drugs, institution-institutional platforms and industry partnerships. We make several suggestions about how to achieve the synergy of academic institutions and industry-based organizations in drug innovation by using a ARO-CRO hybrid service model.

Integrating China in the International Consortium for Personalized Medicine: A Position Paper on Personalized Medicine in Sustainable Healthcare.

INTRODUCTION: Over the last decade, the emergence and spread of personalized medicine (PM) have defined a substantial revolution in healthcare. In principle, healthcare system sustainability is challenged by the investments required for research and development, as well as the adoption of PM techniques in routine clinical care. The "Integrating China in the International Consortium for Personalized Medicine" (IC2PerMed) EU-funded project aims to integrate China into the "International Consortium for Personalized Medicine" (ICPerMed). IC2PerMed aims to align the EU and China's research agendas in this field to enable a swift development of approaches in the EU and China with strong leverage upon EU-Chinese collaborations. METHODS: Within this project, we first mapped relevant policies on PM in both the EU and China, and then we involved European and Chinese experts in PM in workshops and Delphi surveys in order to identify relevant priorities for the implementation of PM in sustainable healthcare. RESULTS: As a result of this process, we identified nine overarching priorities, each addressing specific aspects of the sustainability of healthcare systems and PM implementation, with the main goal of supporting policymakers in integrating PM approaches in the EU and China. DISCUSSION/CONCLUSION: The implementation of PM in health systems is appealing in terms of improved accuracy in diagnostics, treatment, and prevention of disease, as well as reduction of the side effects resulting from inefficient use of drugs. Research, development, and implementation of needed techniques require time and resources that can slow the adoption of PM in healthcare systems. The nine priorities we identified address some of the most critical points, trying to lay the foundations for a comprehensive approach.

Comparison of the new self-contained darkroom refractive screener versus table-top autorefractor and cycloplegia retinoscopy in detecting refractive error.

PURPOSE: By comparing the results of the new self-contained darkroom refractive screener (YD-SX-A) versus table-top autorefractor and cycloplegic retinoscopy, to evaluate the performance of the YD-SX-A in detecting refractive error in children and adolescents and then judge whether it can be used in refractive screening. METHODS: Cross-sectional study. 1000 participants between the ages of 6 and 18 who visited the Optometry Center of the People's Hospital of Guangxi Zhuang Autonomous Region from June to December 2022 were selected. First, participants were instructed to measure their diopter with a table-top autorefractor (Topcon KR8800) and YD-SX-A in a noncycloplegic setting. After cycloplegia, they were retinoscopy by a professional optometrist. The results measured by three methods were collected respectively. To avoid deviation, only the right eye (1000 eyes) data were used in the statistical analysis. The Bland-Altman plots were used to evaluate the agreement of diopters measured by the three methods. The receiver operating characteristic (ROC) curves was used to analysis effectiveness of detecting refractive error of YD-SX-A. RESULTS: The average age of participants was 10.77 ± 3.00 years, including 504 boys (50.4%) and 496 girls (49.6%). When YD-SX-A and cycloplegia retinoscopy (CR) were compared in the myopia group, there was no statistical difference in spherical equivalent (SE) (P > 0.05), but there was a statistical difference in diopter spherical (DS) and diopter cylinder (DC) (P < 0.05). Comparing the diopter results of Topcon KR8800 and CR, the difference between each test value in the myopia group was statistically significant (P < 0.05). In the hyperopia group, the comparison between YD-SX-A and CR showed no statistically significant differences in the DC (P > 0.05), but there were significant differences in the SE and DS (P < 0.05). In the astigmatism group, the SE, DS, and DC were statistically different, and the DC of YD-SX-A was lower than that of CR and Topcon KR8800. Bland-Altman plots indicated that YD-SX-A has a moderate agreement with CR and Topcon KR8800. The sensitivity and specificity of YD-SX-A for detecting myopia, hyperopia and astigmatism were 90.17% and 90.32%, 97.78% and 87.88%, 84.08% and 74.26%, respectively. CONCLUSION: This study has identified that YD-SX-A has shown good performance in both agreement and effectiveness in detecting refractive error when compared with Topcon KR8800 and CR. YD-SX-A could be a useful tool for large-scale population refractive screening.

Clinical development of mRNA therapies against solid tumors.

The mRNA-based therapeutics have become the hot spot of biopharmaceutical industries in recent years. The landscape of this area is expanding from infectious disease to cancer, which needs to be summarized to provide data supports for industries and research institutions. Based on the Trialtrove database, a total of 108 clinical trials from 1999 to 2021 were retrospectively analyzed. We have demonstrated that the clinical development of mRNA therapies against solid tumors is still at an early stage. There are evolutions in delivery systems from the dendritic cell to the lipid-based platform and in encoding strategies from the fixed tumor antigens to the personalized neoantigens. The adjuvant or maintenance therapy and the combination treatment with checkpoint inhibitors are becoming the major clinical development orientation.

Integrating China in the international consortium for personalised medicine. a position paper on healthcare professionals' education and citizens' empowerment in personalised medicine.

BACKGROUND: Personalised medicine (PM) has been fostered by technological and medical advances, but all stakeholders, including healthcare professionals, citizens and policy makers, should achieve adequate health literacy to promote PM implementation. The "Integrating China in the International Consortium for Personalised Medicine" (IC2PerMed) project, funded by the International Consortium for Personalised Medicine, focuses on this issue by highlighting the need to educate healthcare professionals and empower citizens. Within the aforementioned project, building on a mapping of European and Chinese policies in PM, experts in the field of PM participated in an online workshop and a following two-round Delphi survey, in order to identify the priority areas of intervention for healthcare professionals' education and curricula, engagement and empowerment of citizens and patients. RESULTS: Nine experts completed the survey and reached a consensus on seventeen priorities: seven were related to health professionals' education and curricula, whereas ten on citizen and patients' awareness and empowerment. CONCLUSION: These priorities emphasized the importance of education and health literacy, multidisciplinary and international collaboration, public trust, and consideration of ethical, legal, and social issues. The present experience highlights the relevance of the involvement of stakeholders in informing decision-makers, developing appropriate national plans, strategies, and policies, and ensuring the adequate implementation of PM in health systems.

Adverse events of PD-(L)1 inhibitors plus anti-VEGF(R) agents compared with PD-(L)1 inhibitors alone for cancer patients: a systematic review and meta-analysis.

Background: Anti-PD-(L)1 antibody monotherapy or in combination with VEGF(R) blockade has been applied widely for cancer treatment. Whether combination therapy increases irAEs still remains controversial. Methods: A systematic review and meta-analysis comparing PD-(L)1 and VEGF(R) blockade combination therapy with PD-(L)1 inhibitors alone was performed. Phase II or III randomized clinical trials reporting irAEs or trAEs were included. The protocol was registered with PROSPERO, CRD42021287603. Results: Overall, 77 articles were included in the meta-analysis. A total of 31 studies involving 8,638 participants were pooled and an incidence for PD-(L)1 inhibitor monotherapy with any grade and grade ≥3 irAEs of 0.25 (0.20, 0.32) and 0.06 (0.05, 0.07), respectively, were reported. Two studies with 863 participants pooled for PD-(L)1 and VEGF(R) blockade showed that an incidence of any grade and grade ≥3 irAEs were 0.47 (0.30, 0.65) and 0.11 (0.08, 0.16), respectively. Regarding pairwise comparisons for irAEs, only one study was included, indicating no significant difference between the two regimens in terms of colitis, hyperthyroidism, and hypothyroidism for any grade and grade ≥3, while there was a trend of higher incidence for any grade hyperthyroidism under the combination therapy. The incidence of reactive cutaneous capillary endothelial proliferation (RCCEP) was as high as 0.80 under camrelizumab monotherapy. Conclusion: Total incidences of any grade and grade ≥3 irAEs were higher in the combination treatment group. Direct comparisons indicated no significant difference between the two regimens for any grade and grade ≥3 specific irAEs. RCCEP and thyroid disorders need to be paid attention to clinically. Moreover, trials with direct comparisons are needed and the safety profiles of the two regimens should be further explored. Exploration of the mechanism of action and regulatory management of adverse events should be enhanced. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=287603, identifier CRD42021287603.

Rare tumors: a blue ocean of investigation.

Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients' prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.

Comparing a PD-L1 inhibitor plus chemotherapy to chemotherapy alone in neoadjuvant therapy for locally advanced ESCC: a randomized Phase II clinical trial : A randomized clinical trial of neoadjuvant therapy for ESCC.

BACKGROUND: A Phase II study was undertaken to evaluate the safety and efficacy of the neoadjuvant socazolimab, a novel PD-L1 inhibitor, in combination with nab-paclitaxel and cisplatin for locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Sixty-four patients were randomly divided between the Socazolimab + nab-paclitaxel + cisplatin (TP) arm (n = 32) and the control arm (n = 32), receiving either socazolimab (5 mg/kg intravenously (IV), day 1) or a placebo with nab-paclitaxel (125 mg/m2 IV, day 1/8) and cisplatin (75 mg/m2 IV, day 1) repeated every 21 days for four cycles before surgery. The primary endpoint was major pathological response (MPR), and the secondary endpoints were pathological complete response (pCR), R0 resection rate, event-free survival (EFS), overall survival (OS), and safety. RESULTS: A total of 29 (90.6%) patients in each arm underwent surgery, and 29 (100%) and 28 (98.6%) patients underwent R0 resection in the Socazolimab + TP and Placebo + TP arms, respectively. The MPR rates were 69.0 and 62.1% (95% Confidence Interval (CI): 49.1-84.0% vs. 42.4-78.7%, P = 0.509), and the pCR rates were 41.4 and 27.6% (95% CI: 24.1-60.9% vs. 13.5-47.5%, P = 0.311) in the Socazolimab + TP and Placebo + TP arms, respectively. Significantly higher incidence rates of ypT0 (37.9% vs. 3.5%; P = 0.001) and T downstaging were observed in the Socazolimab + TP arm than in the Placebo + TP arm. The EFS and OS outcomes were not mature. CONCLUSIONS: The neoadjuvant socazolimab combined with chemotherapy demonstrated promising MPR and pCR rates and significant T downstaging in locally advanced ESCC without increasing surgical complication rates. TRIAL REGISTRATION: Registration name (on clinicaltrials.gov): A Study of Anti-PD-L1 Antibody in Neoadjuvant Chemotherapy of Esophageal Squamous Cell Carcinoma. REGISTRATION NUMBER: NCT04460066.

Unfair older patients restriction in cancer drug trials in mainland China and corresponding solution.

BACKGROUND: Older adults are a growing segment of oncology population in China and beyong. However, older cancer patients were vastly underrepresented in clinical trial. To facilitate that all patients with cancer have equal access to the cutting edging treatment and receive evidence-based medication in mainland China, it's of particular importance to fully grasp the proportion of upper age restriction in cancer clinical trials, as well as associated factors. METHODS: Based on clinical trials registered on the China Food and Drug Administration Registration and Information Disclosure Platform, we sought to characterize the overall proportion and trajectory of upper age-restriction among registered cancer drug trials in mainland China from 2009 to 2021, and potential influencing factors were determined by multivariate logistic regression. RESULTS: According to the 3485 trials, upper age restriction proportion of cancer drug trials for patients over 65 years and 75 years was 18.8% (95% CI = 17.5%-20.1%) and 56.5% (95% CI = 51.3%-54.6%), respectively. Phase IV trials, international multicenter trials, or trials initiated by global companies seldom excluded patients over 65 years compared with phase I trials, domestic trials and trials initiated by Chinese enterprise, similar for 75 years and above. Both of 65 and 75 years old age limit sponsored by domestic enterprises showed slowly downward trend, while no such trend was observed for that of foreign companies. Solution to upper age eligibility of cancer drug trials was also provided. CONCLUSIONS: Although there is a certain downward trend, use of eligibility criteria that explicitly exclude older cancer patients in mainland China was remarkably high, especially for trials initiated by domestic enterprise, domestic trials and early-phase trials. Action is urgently needed to promote treatment equity in the older patients while obtaining adequate evidence in clinical trials.

Geriatric drug trials on solid tumor are scarce worldwide.

Background: Conducting geriatric trials is the most feasible way to address the vast underrepresentation of older adults in clinical trials of cancer therapies. This study is a globally comprehensive examination of geriatric trials for solid tumor worldwide over the last decade. Methods: Up-to-date information on cancer drug trials in older adults aged over 59 years from the beginning of 2012 to the end of 2021 was collected from Trialtrove and Pharmaprojects. The number of identified trials was the dependent variable and corresponding analysis was conducted from the perspective of time trend, status quo and comparisons by region and country, sponsor type and cancer type, study status and phase. Results: A total of 292 geriatric cancer drug trials were identified, of which 287 were single-region studies, 219 were initiated by academic groups, and 55 (18.8%) were terminated. Decreasing trends in the annual number of all trials (-9.2% per year) and the annual number of trials by academic groups (-9.4%) were observed over time. Of the geriatric trials, 183 were conducted in Asia; this number was significantly higher than that in Europe (74), North America (37), Oceania (4), and South America (1). Similar difference was found in participation rate in trials by academic groups ranging from 71.7% in Asia to 0.5% in South America. Of the trials, 19 and 97 were initiated before drug and indication approval, respectively, and the remaining 176 were initiated after indication approval. Phase II trials accounted for the highest proportion of trials (213, 72.9%), while phase I trials accounted for the lowest proportion (14, 4.8%). Trials by academic groups had a higher termination rate (21.5% vs. 11.0%) and fewer were phase IV trials (8.2% vs. 21.9%). Treatment was explored for 16 different cancers, with lung, colorectal and breast cancers being the most common. Conclusion: Geriatric trials of solid tumor drugs are scarce and partially prematurely terminated. Moreover, the number of geriatric trials has decreased and differs according to region. Global guidance and regulatory supervision are needed to facilitate the acquisition of adequate evidence on drug risk-benefit profiles in older adults, and thus to achieve high-quality care and safe medication.

HLA and tumour immunology: immune escape, immunotherapy and immune-related adverse events.

PURPOSE: As molecules responsible for presenting antigens to T lymphocytes, leukocytes antigens (HLAs) play a vital role in cancer immunology. This review aims to provide current understanding of HLAs in tumour immunology. METHODS: Perspectives on how HLA alterations may contribute to the immune escape of cancer cells and resistance to immunotherapy, and potential methods to overcome HLA defects were summarized. In addition, we discussed the potential association between HLA and immune-related adverse events (irAEs), which has not been reviewed elsewhere. RESULTS: Downregulation, loss of heterogeneity and entire loss of HLAs are responsible for the immune escape of tumour cells. The strategies to overcome the HLA defects can be effective therapies of cancer. Compared with classical HLA-I, non-classical HLA-I molecules, such as HLA-E and HLA-G, appear to be more reliable predictors of prognosis, as they tend to play immunosuppressive roles in antitumor response. Relative diversified or high expression of classical HLA-I are potential predictors of favourable response of immunotherapy. Certain HLA types may be associated to enhanced affinity to self-antigen-mimicked tumour-antigens, thus may positively correlated to irAEs triggered by checkpoint inhibitors. CONCLUSIONS: Further studies exploring the relationship between HLAs and cancer may not only lead to the development of novel therapies but also bring about better management of irAEs.

Targeting rare tumors: new focus for clinical research in China.

Rare tumor has a huge unmet medical need without standard regimens, calling for novel therapeutic interventions. The National Cancer Center of China identified a threshold of incidence for rare tumor as 2.5/100,000, based on the characteristics of Chinese population. Molecular profiles for rare tumor patients in China further provided prospects for precise and individualized targeted treatment. An ongoing phase II clinical trial, the PLATFORM study, is the first trial tailored for rare solid tumors in China, featured by molecule-guided therapeutics. With the promulgation of supportive policies to encourage the development of innovative drugs for rare tumors in China, opportunities will be provided for these patients and the gap will be filled in the treatment of rare tumors.

The reliability and integrity of overall survival data based on follow-up records only and potential solutions to the challenges.

Overall survival (OS) is considered the standard clinical endpoint to support effectiveness claims in new drug applications globally, particularly for lethal conditions such as cancer. However, the source and reliability of OS in the setting of clinical trials have seldom been doubted and discussed. This study first raised the common issue that data integrity and reliability are doubtful when we collect OS information or other time-to-event endpoints based solely on simple follow-up records by investigators without supporting material, especially since the 2019 COVID-19 pandemic. Then, two rounds of discussions with 30 Chinese experts were held and 12 potential source scenarios of three methods for obtaining the time of death of participants, including death certificate, death record and follow-up record, were sorted out and analysed. With a comprehensive assessment of the 12 scenarios by legitimacy, data reliability, data acquisition efficiency, difficulty of data acquisition, and coverage of participants, both short-term and long-term recommended sources, overall strategies and detailed measures for improving the integrity and reliability of death date are presented. In the short term, we suggest integrated sources such as public security systems made available to drug inspection centres appropriately as soon as possible to strengthen supervision. Death certificates provided by participants' family members and detailed standard follow-up records are recommended to investigators as the two channels of mutual compensation, and the acquisition of supporting materials is encouraged as long as it is not prohibited legally. Moreover, we expect that the sharing of electronic medical records and the legal disclosure of death records in established health registries can be realized with the joint efforts of the whole industry in the long-term. The above proposed solutions are mainly based on the context of China and can also provide reference for other countries in the world.

Accelerating the integration of China into the global development of innovative anticancer drugs.

The aim of this Policy Review was to compare China's overall and synchronous participation in clinical trials for innovative anticancer drugs with that of the USA, the EU, Japan, and South Korea, and to assess changes in the participation rate trends in these five regions. Relevant data from the top 20 international pharmaceutical companies from 2011 to 2021 were systematically collected from the Trialtrove and Pharmaprojects databases. Among the 8260 trials for 954 new anticancer drugs identified, China was involved in 8·8% of the trials and with 20·4% of the drugs being trialled. These participation rates are significantly lower than those for South Korea (14·5% of trials and 36·3% of drugs), Japan (16·1% of trials and 38·7% of drugs), the EU (40·6% of trials and 67·7% of drugs), and the USA (65·7% of trials and 91·2% of drugs; p<0·0001 for all). Similar results were found for the synchronous participation rate, defined as the proportion of drugs or trials at the highest development stage internationally, for the 803 tested drugs, which ranged from 9·0% in China to 87·7% in the USA. China's participation rate in early phase trials (4·4%) and in synchronous trials (5·4%) was even lower, in stark contrast to that of the USA (66·1% for early phase trials and 89·1% for synchronous trials). The fastest growing annual rate of participation in trials was observed in China (15·7%), followed by South Korea (8·2%) and Japan (6·8%); no change was detected in the USA or the EU. This Policy Review shows that Chinese participation in the clinical development of innovative cancer drugs by international pharmaceutical companies has increased over the past decade, but an obvious gap persists in comparison with the USA, the EU, Japan, and South Korea, especially in its synchronous participation and early participation rates.

[Progress and Application of Bayesian Approach in the Early Research and Development of New Anticancer Drugs].

Bayesian statistics is an approach for learning from evidences as it accumulates, combining prior distribution with current information on a quantity of interest, in which posterior distribution and inferences are being updated each time new data become available using Bayes' Theorem. Though frequentist approach has dominated medical studies, Bayesian approach has been more and more widely recognized by its flexibility and efficiency. Research and development (R&D) on anti-cancer new drugs have been so hot globally in recent years in spite of relatively high failure rate. It is the common demand of pharmaceutical enterprises and researchers to identify the optimal dose, regime and right population in the early-phase R&D stage more accurately and efficiently, especially when the following three major changes have been observed. The R&D on anticancer drugs have transformed from chemical drugs to biological products, from monotherapy to combination therapy, and the study design has also gradually changed from traditional way to innovative and adaptive mode. This also raises a number of subsequent challenges on decision-making of early R&D, such as inability to determine MTD, flexibility to deal with delayed toxicity, delayed response and dose-response changing relationships. It is because of the above emerging changes and challenges that the Bayesian approach is getting more and more attention from the industry. At least, Bayesian approach has more information for decision-making, which could potentially help enterprises achieve higher efficiency, shorter period and lower investment. This study also expounds the application of Bayesian statistics in the early R&D on anticancer new drugs, and compares and analyzes its idea and application scenarios with frequentist statistics, aiming to provide macroscopic and systematic reference for all related stakeholders.
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