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.

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.

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.

Real-world evidence on adjuvant chemotherapy in older adults with stage II/III colon cancer

Colon cancer represents one of the most common cancers diagnosed in older adults worldwide.The standard of care in resected stage II and stage III colon cancer continues to evolve.While there is unequivocal evidence to suggest both disease free and overall survival benefits with the use of combination chemotherapy in patients with stage III colon cancer,data regarding its use in patients with stage II colon cancer are less clear.Further,although colon cancer is a disease that affects older adults,there is considerable debate on the value of adjuvant chemotherapy in the aging population.In particular,many older patients are undertreated when compared to their younger counterparts.In this review,we will describe the clinical trials that contributed to the current adjuvant chemotherapy approach in colon cancer,discuss representation of older adults in trials and the specific challenges associated with the management of this subpopulation,and highlight the role of comprehensive geriatric assessments.We will also review how real-world evidence complements the data gaps from clinical trials of early stage colon cancer.

The applications of Bayesian models in real-world studies of traditional Chinese medicine:a primer

Real-world study is valuable for traditional Chinese medicine.However,there are no gold standards of statistical approaches for analyzing data from real-world study of traditional Chinese medicine.With the development of computer technology,researchers have increasingly paid attention to Bayesian statistics in the biomedical field.In present study,real-world study and Bayesian statistics were introduced.It was discussed that why and when to use Bayesian analysis and the challenge in the real-world study of traditional Chinese medicine.

Application of Real-World Evidence in Regulatory Decision-Making for Medical Devices

Objective To understand the real-world study(RWS)and its application in domestic and foreign pharmaceutical device regulatory decision-making,so as to promote its further application in the decision-making of medical devices supervision in China.Methods Literature analysis and comparative analysis were used to compare the real-world evidence(RWE)and randomized controlled trials to obtain the development status of medical devices in China and the United States.Results and Conclusion It is found that the application of RWS in the field of medical devices has many advantages,which can make up for the deficiencies of traditional clinical data.In addition,the RWE has a wide range of applications in the field of medical devices in China.In recent years,the RWE has received extensive attention in the medical field in the United States.The FDA has issued related guidelines,and its applications have gradually formed a complete system.Research on RWE will become the development trend of clinical evaluation of medical devices in the future.While attaching importance to the development of the RWE,China should learn from the specifications of relevant foreign organizations to improve its development in the field of health.

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.

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.

How Real-World Evidence Supports Healthcare Decisions in EU and Its Enlightment to China

Objective To summarize the concept,background,application value of real-world evidence(RWE)and its enlightenment to China based on the analysis of the information about the RWE supporting health decision in the European Union,and to provide a reference for Chinese health departments.Methods Through literature research and data collection,the requirements of EU countries,especially some typical countries,for clinical evidence in health decision were obtained,and the application of RWE in supporting health decision in EU was analyzed with specific cases.Results and Conclusion RWE plays an increasingly important role in supplementing the evidence base of clinical trials,verifying the safety and effectiveness of medical devices,and accelerating the market access of new drugs.With the improvement of RWE quality,RWE will not only be used in the evaluation of biological agents and chemical drugs,but also play an important role in the evaluation of traditional Chinese medicine and the post-marketing evaluation of medical devices.

EU Real-World Evidence Supports the Expansion Indications for Drugs and Its Enlightenment to China

Objective To analyze the value of EU real-world evidence(RWE)in supporting the expanded indications for drugs and to provide reference for the decision-making of expanding drug indications supported by RWE in China.Methods By searching relevant domestic and foreign literature and case analysis,the practice of the RWE of EU to support the expansion indications for drugs was investigated.Results and Conclusion The EU uses RWE to carry out adaptive path research,which provides a new idea for drug R&D and approval.Besides,it also provides evidence in supporting the research of expanded indications for drugs.With the increasing cognition of RWE,it will play a key role in medical and regulatory decisions in China.

EU Real-World Evidence Supporting Drug Regulatory Decision and Its Enlightenment to China

Objective To provide references and suggestions for the application of real-world evidence in the decision-making of drug regulation in China.Methods The application of EU real-world evidence in drug regulatory decision support was analyzed through literature research and other methods,and the specific operation of its application was demonstrated by case studies.Results and Conclusion The application of EU real-world evidence in drug regulatory decision-making has achieved certain results and is in a stable development stage.The application of real-world evidence in China’s drug regulation is feasible.The successful application of EU real-world evidence can provide reference for China.

The Enlightenment of EU Real-World Evidence Supporting the Inclusion of Rare Disease Drugs in Medical Insurance Decisions to China

Objective To study the use of real-world evidence by EU and its member states for establishing a strategy for rare diseases and provide references for the inclusion of orphan drugs in China’s medical insurance.Methods A case analysis method was used to introduce the EU’s decision to include rare disease drugs in medical insurance by using real-world evidence because clinical data of rare diseases were difficult to obtain.Results and Conclusion China can use real-world evidence to make medical insurance decisions based on the experience of the EU and continue to invest more in rare diseases,which can solve the problem of few drugs for patients with rare disease.

EU Real-World Evidence Supports New Drug Research and Development Decisions and Its Implications for China

Objective To analyze the application of EU real-world evidence in the decision-making of new drug research and development(R&D),and to provide policy recommendations for China’s government to make new drug R&D decisions.Methods The relevant policy documents of the EU on the development of new drugs and other domestic and foreign literature on the real-world evidence were analyzed to obtain the role and application of the current EU real-world evidence in the implementation of new drug development policies.Results and Conclusion At present,the EU is carrying out the national synchronous scientific advisory policy,urging the formation of a European innovation framework,and providing decision-making for new drug R&D selection and program design based on real-world evidence.It is recommended that China build a real-world medical database and design a new drug screening platform to help companies,scientific research institutions assess target drugs.In addition,a national scientific advisory platform should be set up to integrate scientific research strength and provide technical support for new drug R&D institutions.

Research on Retrospective Studies of Real-World Study and Its Selection Bias

Objective To provide references for improving the authenticity and reliability of the retrospective study results,thus improving the quality of evidence in the real world and strengthening drug supervision and decision-making.Methods Literature review was used to study the data sources,the characteristics of retrospective research,the sources and the corrections of selective bias in the real world.Results and Conclusion The biases in retrospective study mainly come from admission rate bias,patient rate bias,survivors bias,health user bias and symptom bias.

Research on Real-World Evidence and Application in EU and Its Enlightment to China

Objective To analyze the research and application status of real-world evidence(RWE)in the European Union(EU)and provide a reference for China’s government.Methods By consulting the policy guidelines issued by EU EMA and the documents of European countries at home and abroad,the basic principles and case notes of EU RWE implementation were comprehensively analyzed.Results and Conclusion Research on RWE in EU is mainly carried out from four aspects:R&D decision,application of expanded trial certificate,medical insurance decision,and supervision decision,which plays an important role in the progress of European clinical medicine.Therefore,researchers in China should draw lessons from these four perspectives and design reasonable research directions and programs.

Real-World Evidence Supporting New Drug Review and Approval in European Union and Its Enlightenment to China

Objective To analyze the application of real-world evidence(RWE)in the field of medicine in European Union,and provide suggestions for RWE supporting the review and approval of new drugs in China.Methods The European Medicines Agency(EMA)and other databases were used to search relevant documents for analyzing the European Union’s new drug review and approval process with the support of RWE.Results and Conclusion The European Union carrying out new drug review and approval with the support of RWE has just begun.The decision-making process includes three stages such as new drug research and development,review,and approval.However,there are some challenges in data quality,research methods,evidence sufficiency,and research process of RWE supporting the European Union in reviewing and approving new drugs.At present,RWE can accurately grasp the clinical effects of drugs and improve the safety and effectiveness in the process of assisting the review and approval of new drugs.At the same time,RWE also can promote the development and application of Traditional Chinese Medicine(TCM)and help find out the potential value of TCM such as new indications.

Experimental Design of Observational Studies in Real-World Study

Objective To introduce the design of observational trials under real-world study(RWS),and to provide guidance for clinical development of new research trials and reference for real-world researchers.Methods Relevant literature of RWS and observational experiments at home and abroad were reviewed and analyzed,and then the design of observational studies was summarized under RWS.Results and Conclusion The data and information provided in observational studies not only help to further verify the clinical study results obtained by randomized controlled trial(RCT)in clinical practice,but also objectively reflect the real situation in the process of clinical research and application.

Clinical features of multiple gastrointestinal stromal tumors:A pooling analysis combined with evidence and gap map

BACKGROUND Multiple gastrointestinal stromal tumors(MGISTs)are a very rare type of gastrointestinal stromal tumor(GIST)and are usually observed in syndrome.AIM The paper aimed to describe the clinical and oncological features of MGISTs and to offer evidence for the diagnosis and treatment.METHODS Data of consecutive patients with MGISTs who were diagnosed at Peking University People’s Hospital(PKUPH)from 2008 to 2019 were retrospectively evaluated.Further,a literature search was conducted by retrieving data from PubMed,EMBASE,and the Cochrane library databases from inception up to November 30,2019.RESULTS In all,12 patients were diagnosed with MGISTs at PKUPH,and 43 published records were ultimately included following the literature review.Combined analysis of the whole individual patient data showed that female(59.30%),young(14.45%),and syndromic GIST(63.95%)patients comprised a large proportion of the total patient population.Tumors were mainly located in the small intestine(58.92%),and both CD117 and CD34 were generally positive.After a mean 78.32-mo follow-up,the estimated median overall survival duration(11.5 years)was similar to single GISTs,but recurrence-free survival was relatively poorer.CONCLUSION The clinical and oncological features are potentially different between MGISTs and single GIST.Further studies are needed to explore appropriate surgical approach and adjuvant therapy.

EVIDENCE-BASED MEDICINE AND THE CLINICAL STUDY ON ACUPUNCTURE AND MOXIBUSTION

In this article, the authors hold that the evidence based medicine(EBM) is a new medical action produced at the historic moment in clinical practice, which is promoting development of the medicine and even the whole life science in a fully new train of thought and method. Further the briefly introduced contents are the effect of EBM, the difficulty of utilizing in the acupuncture clinical practice and how to resolve them. It is highly recommended that the doctors of the acupuncture science field should study EBM and its effect and difficulties in practice as earlier as possible, insistently assimilate new knowledge and keep abreast of the times’ progress to facilitate the further development of acupunctology.

Calling into Question the Efficacy of Evidence-Based Medicine: Is It Always the Best Approach? Is That Really the Placebo Effect?

The techniques of evidence-based medicine (EBM) are being frequently used recently. The generally accepted theory is that if a medicine is not absorbed by the body, it will have no effect. However, the author has noticed that even when substances, including medicines, are not absorbed by the body, they can have a marked effect. In some cases, just bringing the substance close to the body can have an effect;in such cases, the efficacy of EBM for estimating the therapeutic value of medicines may be debatable. Therefore, a more accurate evaluation method should be devised. The author proposes that another group be introduced into trials. This group would include subjects who were exposed to but did not have an opportunity to absorb the medicine being tested.