Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis

BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety of TOF treatment for UC,including clinical issues.METHODS We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center.All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled.Patients were followed up until August 2020.The primary outcome was the clinical response rate at week 8.Secondary outcomes included clinical remission at week 8,cumulative persistence rate of TOF administration,colectomy-free survival,relapse after tapering of TOF and predictors of clinical response at week 8 and week 48.RESULTS The clinical response and remission rates were 66.3%and 50.5%at week 8,and 47.1%and 43.5%at week 48,respectively.The overall cumulative clinical remission rate was 61.7%at week 48 and history of anti-tumor necrosis factor-alpha(TNF-α)agents use had no influence(P=0.25).The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8(30.9%vs 88.1%;P<0.001).Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8(odds ratio:0.61,95%confidence interval:0.45-0.82,P=0.001).Relapse occurred in 45.7%of patients after TOF tapering,and 85.7%of patients responded within 4 wk after re-increase.All 6 patients with herpes zoster(HZ)developed the infection after achieving remission by TOF.CONCLUSION TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-αagents.Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF.Special attention is needed for tapering and HZ.

Clinical manifestation,lifestyle,and treatment patterns of chronic erosive gastritis:A multicenter real-world study in China

BACKGROUND Although chronic erosive gastritis(CEG)is common,its clinical characteristics have not been fully elucidated.The lack of consensus regarding its treatment has resulted in varied treatment regimens.AIM To explore the clinical characteristics,treatment patterns,and short-term outcomes in CEG patients in China.METHODS We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology.Patients and treating physicians completed a questionnaire regarding history,endoscopic findings,and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment.RESULTS Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included.Epigastric pain(68.0%),abdominal distension(62.6%),and postprandial fullness(47.5%)were the most common presenting symptoms.Gastritis was classified as chronic non-atrophic in 69.9%of patients.Among those with erosive lesions,72.1%of patients had lesions in the antrum,51.0%had multiple lesions,and 67.3%had superficial flat lesions.In patients with epigastric pain,the combination of a mucosal protective agent(MPA)and proton pump inhibitor was more effective.For those with postprandial fullness,acid regurgitation,early satiety,or nausea,a MPA appeared more promising.CONCLUSION CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms.Gastroscopy may play a major role in its detection and diagnosis.Treatment should be individualized based on symptom profile.

Clinical outcomes of second-line chemotherapy in patients with advanced pancreatic adenocarcinoma:a real-world study

Objective:Little progress has been made in recent years using first-line chemotherapy,including gemcitabine combined with nab-paclitaxel,FOLFIRINOX,and NALIRIFOX,for advanced pancreatic adenocarcinoma(APC).In addition,the optimal second-line chemotherapy regimen has not been determined.This study aimed to compare the effectiveness of different types of second-line chemotherapy for APC.Methods:Patients with APC who received first-line treatment from January 2008 to January 2021 were considered eligible for this retrospective analysis.The primary and secondary endpoints were overall survival(OS)and progression-free survival(PFS),respectively.Results:Four hundred and thirty-seven and 617 patients were treated with 5-fluorouracil-and gemcitabine-based chemotherapy as first-line treatment,respectively.Demographic and clinical features,except age and liver metastasis,were comparable between the two groups(P<0.05).The median OS was 8.8 and 7.8 months in patients who received a 5-fluorouracil-and gemcitabine-based combined regimen for first-line therapy,respectively(HR=1.244,95%CI=1.090–1.419;P<0.001).The median OS was 5.6 and 1.9 months in patients who received second-line chemotherapy and supportive care,respectively(HR=0.766,95%CI=0.677–0.867;P<0.001).The median PFS was not significantly differently between gemcitabine or 5-fluorouracil monotherapy and combination therapy.Conclusions:A 5-fluorouracil-or gemcitabine-based combined regimen was shown to be as effective as a single 5-fluorouracil or gemcitabine regimen as second-line therapy for patients with APC.

Performance evaluation of seven multi-label classification methods on real-world patent and publication datasets

Purpose:Many science,technology and innovation(STI)resources are attached with several different labels.To assign automatically the resulting labels to an interested instance,many approaches with good performance on the benchmark datasets have been proposed for multi-label classification task in the literature.Furthermore,several open-source tools implementing these approaches have also been developed.However,the characteristics of real-world multi-label patent and publication datasets are not completely in line with those of benchmark ones.Therefore,the main purpose of this paper is to evaluate comprehensively seven multi-label classification methods on real-world datasets.Research limitations:Three real-world datasets differ in the following aspects:statement,data quality,and purposes.Additionally,open-source tools designed for multi-label classification also have intrinsic differences in their approaches for data processing and feature selection,which in turn impacts the performance of a multi-label classification approach.In the near future,we will enhance experimental precision and reinforce the validity of conclusions by employing more rigorous control over variables through introducing expanded parameter settings.Practical implications:The observed Macro F1 and Micro F1 scores on real-world datasets typically fall short of those achieved on benchmark datasets,underscoring the complexity of real-world multi-label classification tasks.Approaches leveraging deep learning techniques offer promising solutions by accommodating the hierarchical relationships and interdependencies among labels.With ongoing enhancements in deep learning algorithms and large-scale models,it is expected that the efficacy of multi-label classification tasks will be significantly improved,reaching a level of practical utility in the foreseeable future.Originality/value:(1)Seven multi-label classification methods are comprehensively compared on three real-world datasets.(2)The TextCNN and TextRCNN models perform better on small-scale datasets with more complex hierarchical structure of labels and more balanced document-label distribution.(3)The MLkNN method works better on the larger-scale dataset with more unbalanced document-label distribution.

A hierarchical enhanced data-driven battery pack capacity estimation framework for real-world operating conditions with fewer labeled data

Battery pack capacity estimation under real-world operating conditions is important for battery performance optimization and health management,contributing to the reliability and longevity of batterypowered systems.However,complex operating conditions,coupling cell-to-cell inconsistency,and limited labeled data pose great challenges to accurate and robust battery pack capacity estimation.To address these issues,this paper proposes a hierarchical data-driven framework aimed at enhancing the training of machine learning models with fewer labeled data.Unlike traditional data-driven methods that lack interpretability,the hierarchical data-driven framework unveils the“mechanism”of the black box inside the data-driven framework by splitting the final estimation target into cell-level and pack-level intermediate targets.A generalized feature matrix is devised without requiring all cell voltages,significantly reducing the computational cost and memory resources.The generated intermediate target labels and the corresponding features are hierarchically employed to enhance the training of two machine learning models,effectively alleviating the difficulty of learning the relationship from all features due to fewer labeled data and addressing the dilemma of requiring extensive labeled data for accurate estimation.Using only 10%of degradation data,the proposed framework outperforms the state-of-the-art battery pack capacity estimation methods,achieving mean absolute percentage errors of 0.608%,0.601%,and 1.128%for three battery packs whose degradation load profiles represent real-world operating conditions.Its high accuracy,adaptability,and robustness indicate the potential in different application scenarios,which is promising for reducing laborious and expensive aging experiments at the pack level and facilitating the development of battery technology.

Real-world clinical efficacy of tofacitinib in moderate-to-severe ulcerative colitis

Tofacitinib is an oral small-molecule Janus kinase(JAK)inhibitor that preferentially inhibits JAK1 and JAK3.Its efficacy in inducing and maintaining remission in ulcerative colitis(UC)as well as its safety profile has been demonstrated in multicenter,randomized,double-blind,placebo-controlled trials.Additionally,real-world studies evaluating the effectiveness and adverse effects of tofacitinib have been conducted,affirming its clinical efficacy in moderate-to-severe UC.

A Comparative Study of Metaheuristic Optimization Algorithms for Solving Real-World Engineering Design Problems

Real-world engineering design problems with complex objective functions under some constraints are relatively difficult problems to solve.Such design problems are widely experienced in many engineering fields,such as industry,automotive,construction,machinery,and interdisciplinary research.However,there are established optimization techniques that have shown effectiveness in addressing these types of issues.This research paper gives a comparative study of the implementation of seventeen new metaheuristic methods in order to optimize twelve distinct engineering design issues.The algorithms used in the study are listed as:transient search optimization(TSO),equilibrium optimizer(EO),grey wolf optimizer(GWO),moth-flame optimization(MFO),whale optimization algorithm(WOA),slimemould algorithm(SMA),harris hawks optimization(HHO),chimp optimization algorithm(COA),coot optimization algorithm(COOT),multi-verse optimization(MVO),arithmetic optimization algorithm(AOA),aquila optimizer(AO),sine cosine algorithm(SCA),smell agent optimization(SAO),and seagull optimization algorithm(SOA),pelican optimization algorithm(POA),and coati optimization algorithm(CA).As far as we know,there is no comparative analysis of recent and popular methods against the concrete conditions of real-world engineering problems.Hence,a remarkable research guideline is presented in the study for researchersworking in the fields of engineering and artificial intelligence,especiallywhen applying the optimization methods that have emerged recently.Future research can rely on this work for a literature search on comparisons of metaheuristic optimization methods in real-world problems under similar conditions.

Real-World Evidence in Localized Pancreatic: Coping with Uncertainty in Unselected Populations

Background: Localized pancreatic cancer, including resectable (R), borderline resectable (BR) and locally advanced unresectable disease (LAU), is considered in clinical guidelines for diverse treatment options based on clinical trials in selected populations. Hence, exploring with real world evidence (RWE) clinicians’ preferences for treatment options and their results seems pertinent. Methods: In a set of consecutive patients with localized pancreatic cancer assisted in a third level hospital from January 2013 to December 2022, medical records, symptoms, diagnostic process, distribution between subtypes, and treatment plans, with safety and efficacy results, were assessed. Results: A total of 152 patients with localized disease were included (43.4% R, 21.0% BR, 33.6% LAU). The population characteristics exemplified differences between daily practice and clinical trials. Tumor location and symptoms were as expected. Treatment plan was conditioned by PS or comorbidities in 23.0% of patients. In patients with R disease, surgery followed by different adjuvant chemotherapy (CT) regimes was the antineoplastic treatment of choice (64.8%) with efficacy results (OS 37.5 months;95% CI 18.4 - 56.7), in the range of contemporary standards. The common use of neoadjuvant CT for BR disease (94.4%), with surgery in 50% of them, and its results (OS 30.8 months;95% CI 10.5 - 51.2) reflected current controversies of treatment recommendations and evolution in this scenario. Paliative CT with or without radiotherapy was the standard specific treatment in LAU disease (95.1%) with survival results (PFS: 10.8 months;95% CI 8.8 - 12.7. OS: 20.3 months;95% CI 13.5 - 27.2) that justify the distinct character and the specific study of this entity. Conclusion: RWE for localized pancreatic cancer aroused from the analysis of this population confirms the distinct nature of patients assisted in daily practice, as well as mirrors the complexity of decision making in clinical assumptions in which achieving stronger evidence should be paramount.

Utilization of Real-World Data in Drug Development

With the rapid development of modern science and technology, traditional randomized controlled trials have become insufficient to meet current scientific research needs, particularly in the field of clinical research. The emergence of real-world data studies, which align more closely with actual clinical evidence, has garnered significant attention in recent years. The following is a brief overview of the specific utilization of real-world data in drug development, which often involves large sample sizes and analyses covering a relatively diverse population without strict inclusion and exclusion criteria. Real-world data often reflects real clinical practice: treatment options are chosen according to the actual conditions and willingness of patients rather than through random assignment. Analysis based on real-world data also focuses on endpoints highly relevant to clinical benefits and the quality of life of patients. The booming big data technology supports the utilization of real-world data to accelerate new drug development, serving as an important supplement to traditional clinical trials.

Current Situation and Prospect of the Application of Real-World Evidence in Health Care

Objective To summarize the application of real-world evidence(RWE)in the medical and healthcare field of various countries,including relevant policies,application scenarios and application methods.Methods Relevant policies and application scenarios were obtained by consulting the official websites and public documents of various countries’healthcare institutions.Systematic literature retrieval was adopted to search PubMed,EMBASE,Cochrane Library,CNKI,CBM and Wanfang databases,and all papers related to real-world study and application were included.Then,these papers were classified and analyzed by country and application method.Results and Conclusion The RWE was mainly applied to supporting the preliminary approval of a new drug,expanding drug indications,accelerating approval or supporting conditional marketing authorizations and drug safety evaluation,etc.The United Kingdom,the United States,Germany,the Netherlands,Italy,Sweden,and France admitted RWE,but they treated the data obtained from RWE with caution.After systematic literature retrieval,a total of 701 articles were obtained,including relevant studies from 36 countries,among which the United States published 264 in total.The most common study was about using real-world data(RWD)to calculate treatment-related costs,which had a total of 259 studies.Secondly,158 articles were used for epidemiological analysis.Then,138 articles were about establishing risk models to analyze disease risk factors.A total of 70 articles were real-world efficacy evaluation of the drug treatment schemes,54 articles were about pharmacoeconomic evaluation with RWD as parameters.A total of 29 articles used RWD to build predictive models,and 15 articles used RWD to evaluate the health-related quality of life in patients.The application of RWE has been used widely in the medical and healthcare field of various countries.The application scenarios are gradually diversified,the application methods of RWD become mature,and the evidence quality of RWE is also improved greatly.

Question classification in question answering based on real-world web data sets

To improve question answering （QA） performance based on real-world web data sets,a new set of question classes and a general answer re-ranking model are defined.With pre-defined dictionary and grammatical analysis,the question classifier draws both semantic and grammatical information into information retrieval and machine learning methods in the form of various training features,including the question word,the main verb of the question,the dependency structure,the position of the main auxiliary verb,the main noun of the question,the top hypernym of the main noun,etc.Then the QA query results are re-ranked by question class information.Experiments show that the questions in real-world web data sets can be accurately classified by the classifier,and the QA results after re-ranking can be obviously improved.It is proved that with both semantic and grammatical information,applications such as QA, built upon real-world web data sets, can be improved,thus showing better performance.

Real-World Data for the Drug Development in the Digital Era

Randomized clinical trials(RCTs)have long been recognized the gold standard for regulatory approval in the drug development.However,RCTs may not be feasible in some diseases and/or under certain situations,and findings from RCTs may not be generalized to real-world patients in routine clinical practice.Real-world evidence(RWE),which is generated from various real-world data(RWD),has become more and more important for the drug development and clinical decision-making in the digital era.This paper described RWD and real-world data studies(RWDSs),followed by the characteristics and differences between RCTs and RWDSs.Furthermore,the challenges and limitations of RWD and RWE were discussed.Finally,this paper highlights that the efforts must be made during RWE generation from data collection/database selection,study design,statistical analysis,and interpretation of the results to minimize the biases and confounding effects.

The Enlightenment of FDA’s“Real-World Evidence Program Framework”to China

Objective To provide a reference for China to use real-world evidence(RWE)in drug approval and regulatory decision-making system.Methods The main content of“Real-World Evidence Program Framework”issued by the FDA was summarized by literature research method,and the related system construction in China was analyzed.Results and Conclusion To promote the use of real-world study(RWS)for drug regulatory decisions,China should issue guidelines on RWS.Besides,the construction of data standards and the shared database should be strengthened.Then,the demonstration projects should be introduced extensively and the guidance for RWS of enterprises must be enhanced.Meanwhile,close attention should be paid to dealing with the relationship between stakeholders.

Discussion on the Application of Real-World Study in the Inheritance and Development of Empirical Prescriptions of Traditional Chinese Medicine

Objective To study the research on real-world data and to provide new ideas and methods for the inheritance and development of empirical prescriptions of traditional Chinese medicine(TCM).Methods The disadvantages of using randomized controlled trials for empirical prescriptions of TCM and the advantages of using real-world study(RWS)were analyzed by summarizing the previous RWS and the empirical prescriptions.Meanwhile,the methods for marketing of new TCMs derived from empirical prescriptions of TCM,the data source and trial design of the RWS were discussed.Results and Conclusion RWS can provide new ideas for the listing of new TCMs.With the improvement of relevant laws and regulations,RWS will promote the development of TCM greatly.To promote the application of RWS in the inheritance and development of empirical prescriptions of TCM,the government should improve laws and regulations as soon as possible,and enterprises and research institutions should strengthen patient privacy protection and clarify the responsible parties.

Real-world vehicle emission factors in Chinese metropolis city—Beijing

The dynamometer tests with different driving cycles and the real-world tests are presented. Results indicated the pollutants emission factors and fuel consumption factor with ECE15+EUDC driving cycle usually take the lowest value and with real world driving cycle occur the highest value, and different driving cycles will lead to significantly different vehicle emission factors with the same vehicle. Relative to the ECE15+EUDC driving cycle, the increasing rate of pollutant emission factors of CO, NOx and HC are -0.42—2.99, -0.32 —0.81 and -0.11—11 with FTP75 testing, 0.11—1.29, -0.77—0.64 and 0.47—10.50 with Beijing 1997 testing and 0.25—1.83, 0.09—0.75 and -0.58—1.50 with real world testing. Compared to the carburetor vehicles, the retrofit and MPI+TWC vehicles' pollution emission factors decrease with different degree. The retrofit vehicle(Santana) will reduce 4.44%—58.44% CO, -4.95%—36.79% NOx, -32.32%—33.89% HC, and -9.39%—14.29% fuel consumption, and especially that the MPI+TWC vehicle will decrease CO by 82.48%—91.76%, NOx by 44.87%—92.79%, HC by 90.00%—93.89% and fuel consumption by 5.44%—10.55%. Vehicles can cause pollution at a very high rate when operated in high power modes; however, they may not often operate in these high power modes. In analyzing vehicle emissions, it describes the fraction of time that vehicles operate in various power modes. In Beijing, vehicles spend 90% of their operation in low power modes or decelerating.

Adjuvant radiotherapy in central hepatocellular carcinoma after narrow-margin hepatectomy:A 10-year real-world evidence

Objective:A prospective randomized control study investigated the feasibility and efficacy of adjuvant radiotherapy on patients with central hepatocellular carcinoma(HCC)after narrow-margin hepatectomy(<1 cm).This study presents an updated 10-year real-world evidence to further characterize the role of adjuvant radiotherapy.Methods:Patients with central HCC after narrow-margin hepatectomy(<1 cm)were prospectively assigned to adjuvant radiotherapy group and control group.Patients'outcome,adverse events,long-term recurrence and survival rates were investigated.Results:The 1-,5-,and 10-year recurrence-free survival(RFS)rates were 81.0%,43.9%,and 38.7%,respectively in adjuvant radiotherapy group and 71.7%,35.8%,and 24.2%,respectively in control group(log-rank test,P=0.09).The 1-,5-,and 10-year overall survival(OS)rates were 96.6%,54.7%,and 42.8%,respectively in adjuvant radiotherapy group and 90.2%,55.1%,and 30.0%,respectively in control group(log-rank test,P=0.20).The 1-,5-,and 10-year RFS rates for patients with small HCC(≤5 cm)were 91.1%,51.6%,and 48.4%,respectively in adjuvant radiotherapy group and 80.0%,36.6%,and 26.6%,respectively in control group(log-rank test,P=0.03).Landmark analysis demonstrated that patients with small HCC in adjuvant radiotherapy group had a significantly improved OS in second five years after treatment in comparison to patients in control group(log-rank test,P=0.05).Conclusions:Our updated results showed a sustained clinical benefit on reducing recurrence,improving longterm survival for small central HCC by adjuvant radiotherapy after narrow-margin hepatectomy.Long-term survival data also indicated that hepatectomy is an optimal treatment for selected patients with central HCC.

Efficacy and safety of lenvatinib for patients with advanced hepatocellular carcinoma: A retrospective, real-world study conducted in China

BACKGROUND Lenvatinib has become an indispensable part of treatment regimens for patients with advanced hepatocellular carcinoma(aHCC).Several recent real-world studies appear to have confirmed this;however,there are etiological differences.This necessitates further real-world studies of lenvatinib across diverse populations,such as in China.AIM To investigate the efficacy and safety of lenvatinib in a Chinese HCC patient population under real-world conditions.METHODS This is a retrospective and multiregional study involving patients with aHCC receiving lenvatinib monotherapy.Efficacy was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.Baseline characteristics and adverse events(AEs)were recorded throughout the entire study.RESULTS In total,54 HCC patients treated with lenvatinib monotherapy were included for final analysis.The objective response rate was 22%(n=12)with a progressionfree survival(PFS)of 168 d;however,AEs occurred in 92.8%of patients.Multivariate analysis showed that the Barcelona Clinic Liver Cancer stage[hazard ratio(HR)0.465;95%CI:0.23-0.93;P=0.031],portal vein tumor thrombus(HR 0.38;95%CI:0.15-0.94;P=0.037)and Child-Pugh classifications(HR 0.468;95%CI:and specificity(83.3%)of decreasing serum biomarkers including alphafetoprotein were calculated in order to predict tumor size reduction.Gene sequencing also provided insights into potential gene mutation signatures related to the effect of lenvatinib.CONCLUSION Our findings confirm previous evidence from the phase III REFLECT study.The majority of patients in this Chinese sample were suffering from concomitant hepatitis B virus-related HCC.However,further analysis suggested that baseline characteristics,changes in serum biomarkers and gene sequencing may hold the key for predicting lenvatinib responses.Further large-scale prospective studies that incorporate more basic medical science measures should be conducted.

Clinical outcomes of atezolizumab in combination with etoposide/platinum for treatment of extensive-stage small-cell lung cancer:A real-world,multicenter,retrospective,controlled study in China

Objective:Atezolizumab along with chemotherapy has prolonged the survival of patients with extensive-stage small-cell lung cancer(ES-SCLC)worldwide,although real-world(RW)data are lacking in China.This study was designed to evaluate the efficacy and clinical outcomes of atezolizumab plus etoposide/platinum(EP).Methods:Data obtained in this retrospective study were captured from six oncology units of five medical facilities from January 2019 to April 2022.For first-line treatments,atezolizumab combined with EP vs.EP alone,we primarily evaluated progression-free survival(PFS);other efficacy indicators,including overall survival(OS),objective response rate(ORR),and patterns of SCLC progression and adverse events(AEs)were assessed.Results:The primary analysis included data from 225 patients,of whom 133 received EP along with atezolizumab(atezolizumab group)and 92 received EP alone(EP group).The PFS duration of the atezolizumab group[7.10 months;95%confidence interval(95%CI),6.53-9.00]exceeded that of the EP group(6.50 months;95%CI,4.83-7.53).Overall,the hazard ratio(HR)was 0.69(95%CI,0.49-0.97)(P=0.029);particularly,the HR was 0.54(95%CI,0.36-0.80)among patients undergoing≥4 chemotherapy cycles and 0.33(95%CI,0.20-0.56)among individuals with atezolizumab maintenance.The ORR and disease-control rate(DCR)were similar between the two groups.Because of incomplete OS data,the median OS was not determined for either group.Bone marrow suppression was the most common AE detected(58.6%)in the atezolizumab group.Immune-related AEs occurred in 19 patients in the atezolizumab group(14.3%),with only one case of grade 3 encephalitis.Conclusions:This RW study in China demonstrated improved clinical outcomes of atezolizumab along with EP for ES-SCLC,particularly in the chemosensitive population.These results align with the results of the IMpower133 study,although the impact of this treatment modality on OS warrants additional follow-up studies.

Effectiveness of second-line anti-HER2 treatment in HER2-positive metastatic breast cancer patients previously treated with trastuzumab:A real-world study

Objective:Several studies have demonstrated different benefits for patients whose disease progressed despite previous trastuzumab treatment.Due to limited real-world data,we evaluate the effectiveness of anti-human epidermal growth factor receptor 2(HER2)therapy(lapatinib or trastuzumab)plus chemotherapy or chemotherapy alone in patients who were previously treated with trastuzumab-containing regimens and investigate factors associated with effectiveness.And we further show the effectiveness of the two anti-HER2 therapy groups.Methods:A total of 342 HER2-positive metastatic breast cancer(MBC)patients whose disease progressed during prior anti-HER2(trastuzumab)and standard chemotherapy therapy from Department of Breast Oncology,the Fifth Medical Center of Chinese PLA General Hospital,from August 2010 to December 2016 were included.Seventy-eight patients received standard chemotherapy only,148 patients continued to receive trastuzumab and switched to other chemotherapy drugs,and 116 patients received tyrosine-kinase inhibitors(TKIs;lapatinib)and chemotherapy.The main outcome measures were progression-free survival(PFS),overall response rate(ORR),and clinical benefit rate(CBR).Subgroup analyses were conducted to identify patient characteristics associated with the greatest clinical benefit.Results:After a median follow-up of 26.2(range,2.0-56.0)months,PFS significantly improved with anti-HER2 therapy compared with chemotherapy alone:median 6.0 months with lapatinib[95%confidence interval(95%CI),4.53-7.47],4.5 months with trastuzumab(95%CI,3.99-5.01)vs.3.0 months with chemotherapy alone(95%CI,2.42-3.58);stratified hazard ratio(HR)=0.70,95%CI,0.60-0.81;P<0.0001.The ORR values were 33.6%,25.0%and 12.8%,respectively,the CBR values were 60.3%,48.6%and 26.9%,respectively.The effectiveness of lapatinib group and trastuzumab group were further analyzed.In multivariate analysis,lapatinib group was associated with a longer PFS,after controlling other potential confounders(HR=0.68,95%CI,0.52-0.90;P=0.006).Conclusions:The combination of TKIs and chemotherapy was effective in this cohort previously treated with trastuzumab treatment.Therefore,TKIs combined with chemotherapy is an option for Chinese HER2-positive MBC patients previously treated with trastuzumab treatment.

Real-world studies: bridging the gap between trial-assessed efficacy and routine care

Even though randomized controlled clinical trials(RCTs)have been accepted as the gold standard for official assessment of novel interventions,there is a substantial gap between the efficacy observed in RCTs and the impact on clinical practice and in terms of patient benefit.While real-world studies(RWS)are emerging to confer valuable complementing evidence in this regard and beyond,the evolving role of RWS is yet to be agreed.This article delineates an updated profile of RWS covering effectiveness verification,rare adverse effects discovery,indication repurposing,to name a few.RWS tends not only to improve the efficiency of clinical investigations for regulatory approval,but also optimizes the whole-life cycle evaluation of biomedical/pharmaceutical products.