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@#Virtual clinical trials are clinical trials conducted through computer simulation technology, which breaks through the limitations of traditional clinical trials and has the advantages of saving time, reducing costs, and reducing the risk of human trials. With the application of new computer technologies such as population pharmacokinetics, physiologically-based pharmacokinetics, quantitative systems pharmacology, and artificial intelligence, the field of virtual clinical trials in healthcare has become an important development direction. This article will give a preliminary review of the connotation, methods and future development trends of virtual clinical trials, aiming to provide reference for the application of new technologies and methods in clinical trials.
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In the process of exploring standardized and efficient ethical review models for multi-center drug clinical trials, the ethical review alliance emerged as the times require. Compared with mature ethics committees, higher requirements have been put forward for the "young" ethics committees. By analyzing problems existing in review work of "young" ethics committees in the ethics review alliance, this paper discussed the measures to improve the review quality of "young" ethics committees and promote the standardized and efficient operation of the alliance, and put forward countermeasures and suggestions for improving the homogenization of ethics review and accelerating the clinical research process of innovative drugs.
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Children with rare disease belong to a vulnerable group. When China’s current medical security system cannot provide comprehensive health care, they not only face physical and mental torture, but also have a higher risk of children participating in clinical trials than adults. So, adequate protection of children’s safety and rights is the key to ethical review. This paper analyzed the current status of drugs clinical trials for rare disease in children, including trial difficulties and guarantee system; explained the ethical principles that should be followed in clinical trials, such as the principle of informed consent and the principle of no harm; and discussed the path of protecting children’s safety and rights, so as to raise awareness and attention of the importance of ethical review of clinical trials.
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To ensure the rights and safety of the subjects and improve the quality of clinical trials, the author analyzed and discussed the deviation type and typical cases from 184 cases of protocol violation reviewed by the ethics committee in 56 clinical trials in a tertiary hospital in 2020. Among the 184 cases of violating the protocol, there were 29 major protocol violation cases and its proportion is 16%; 99 cases (54%) violated the GCP principle; 56 cases of other violations of the protocol that require to be reported, accounting for 30%. Through the case analysis of the researcher gave the wrong doses to subjects without following the protocol and drug administration did not conform to the rules, analyzed and discussed from the five perspectives of the research protocol design, the researcher, the clinical trial institution, the sponsor and the ethics committee, and put forward solutions and suggestions, so as to provide reference to improve the compliance of clinical trial protocol, reduce the risk of subjects and protect their rights and safety and ensure the successful progress of clinical trials.
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OBJECTIVE To provide a reference for improving the relevant standard operating procedures （SOP） and biological sample management in drug clinical trials. METHODS According to Good Clinical Practice， Data On-site Verification Points of Drugs Clinical Trials， Human Genetic Resources Management Regulations Implementation Rules， Qualification Examination Rules of Drug Clinical Trials Institution， based on the experience of managing clinical trials programs， the irregularities in biological samples management were analyzed by using statistical quality control tables and protocol deviation （PD） reported by sponsors， in the context of the quality control of drug clinical trials projects managed by the author from July 2016 to May 2023. The precautions in various aspects of sample management were put forward. RESULTS & CONCLUSIONS A total of 101 biospecimen- related irregularities were found in the 60 drug clinical trials projects. Biological sample collection， preservation， and handling were the aspects with the highest incidence of irregular operations in biological sample management， accounting for 37.62%， 25.74%， and 21.78%， respectively. Regulating the management of biospecimens requires multiple efforts. The institutional office and the ethics committee carefully reviewed the consistency of the protocols， informed consent， and genetic office application involving biospecimen collection and handling when the project was initiated. Institutional office quality controllers should pay attention to the attendance and training of authorized personnel at project initiation. The principal investigator， research nurse， collector， handler， transporter， relevant personnel of the central laboratory， and institutional office quality controller have their roles during the project implementation phase. On this basis， all parties involved in the management of biological samples should do a good job of effective communication， find problems and report them in time， and conduct special studies on key aspects.
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ObjectiveTo evaluate the clinical efficacy and safety of Tongluo Mingmu capsules in the treatment of diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome. MethodA randomized， double-blind， positive-control， and multi-center clinical trial design method was used. 416 patients with diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome in four test centers were included （the ratio of the treatment group to the control group was 3∶1）. On the basis of standardized hypoglycemic treatment， the treatment group was given both four Tongluo Mingmu capsules and two Calcium Dobesilate capsule agents three times a day， while the control group were given both two Calcium Dobesilate capsules and four Tongluo Mingmu capsule agents three times a day. The course of treatment was 12 weeks. The curative effect of Tongluo Mingmu capsules was evaluated by comparing the comprehensive curative effect of diabetic retinopathy， traditional Chinese medicine（TCM） syndrome score， corrected visual acuity， fundus changes， fundus fluorescence angiography， and other curative effect indexes before and after treatment in the two groups. At the same time， general examination， laboratory examination， and adverse events were performed to evaluate the safety of the drug. ResultThe baseline demographic data and disease characteristics of the treatment group and the control group were balanced and comparable， with the difference not statistically significant. After 12 weeks of treatment， the total effective rate of the comprehensive curative effect of diabetic retinopathy in the treatment group （61.0%， 189/310） was better than that in the control group （44.1%， 45/102）， and the difference was statistically significant （χ2=8.880， P<0.01）. The total effective rate of TCM syndromes in the treatment group （88.4%， 259/293） was better than that in the control group （69.9%， 65/93）， and the difference was statistically significant （χ2=17.927， P<0.01）. The disappearance rate of dry eyes （χ2=8.305）， dull complexion （χ2=4.053）， lassitude （χ2=10.267）， shortness of breath （χ2=8.494）， and dry stool （χ2=8.657） in the treatment group was higher than that in the control group， and the difference between the groups was statistically significant （P<0.05， P<0.01）. In terms of improving corrected visual acuity （χ2=8.382）， fundus changes （χ2=6.026） ， the treatment group was significantly better than the control group （P<0.05）. During the trial， the incidence of adverse events in the treatment group and the control group was 1.3% and 2.9%， respectively. There was no significant difference between the two groups. In addition， there were no serious adverse events and adverse events leading to withdrawal in both groups. ConclusionTongluo Mingmu capsules can improve the comprehensive curative effect of diabetic retinopathy and enhance the efficacy of TCM syndromes， visual acuity， fundus changes， and fundus fluorescein angiography， with great safety. Therefore， it can provide a new alternative therapeutic drug for patients with diabetic retinopathy.
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The quality evaluation of the blind method is to evaluate the clinical blind data obtained from clinical trials adopting the blind method and judge the effectiveness of the blind method by investigating the blind effect of different blind objects. A successful blind method can avoid the influence of subjective factors on the test results of subjects and researchers to a certain extent. The quality evaluation of the blind method can reflect not only the effectiveness of the blind method but also the accuracy and credibility of clinical trial results. In recent years， randomized controlled trials have been widely used in the evaluation of the clinical efficacy of traditional Chinese medicine （TCM）， but the quality of the implementation of blind methods is uneven， and the evaluation criteria have not yet been formed. In this paper， the data collection methods， calculation principles， advantages， and disadvantages of two quantitative quality evaluation methods of blind methods， namely James Blinding Index （JBI） and Bang Blinding Index （BBI）， were introduced. The two indexes were analyzed in a randomized controlled trial of acupuncture and moxibustion to relieve postoperative oral pain. The calculation process of the results was demonstrated by R software and visualized by forest map. At the same time， a tool table was designed to facilitate the collection of evaluation data of blind methods in TCM clinical trials at different stages. Finally， the necessity and feasibility of quality evaluation of blind method in TCM research were discussed to provide a basis for evaluating and improving the quality of blind method implementation in TCM clinical trials.
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ABSTRACT BACKGROUND: Although the concept of an "ongoing study" seems self-explanatory, it is difficult to determine whether a trial is underway. OBJECTIVE: To analyze the definitions of "ongoing clinical trial" across different clinical trial registries, methodological guidelines, and other sources. DESIGN AND SETTING: This meta-research study was conducted at the Universidade Federal de São Paulo (UNIFESP), Brazil. METHODS: We performed a cross-sectional analysis of relevant clinical trial registry databases, methodological guidelines for conducting systematic reviews, and other sources that would define or regulate clinical trials. RESULTS: We identified various heterogeneous definitions used by eligible sources at both the start and end of a clinical trial. The starting criteria used were as follows: when the team is planning the protocol, when permission is given to conduct the study, or when the first participant is enrolled. Some sources used the time at which the last outcome data was collected as a criterion to determine the end of the trial. The International Committee of Medical Journal Editors stated that a study is still "ongoing" during the analysis process. Several sources use a vague definition or present no clear criteria for defining the start or end of a study. CONCLUSION: The concept of "ongoing clinical trials" lacks a transparent and homogeneous definition across relevant sources. A consensus on this concept is important to facilitate the evaluation of available evidence and conduct research synthesis. Further efforts are necessary to determine the best definition for the start and end of a clinical trial.
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Resumen Introducción : Existe poca información sobre la pre sencia de COVID-19 en participantes de ensayos clínicos. El objetivo del estudio fue evaluar la tasa de infección acumulada por SARS-CoV-2 en esta población. Además, investigamos el riesgo, letalidad y mortalidad por CO VID-19. Métodos : Diseño observacional retrospectivo que incluyó adultos participantes en ensayos clínicos de intervención aprobados por nuestro comité de ética du rante los dos primeros años de la pandemia (31/3/2020 a 31/3/2022). Se excluyeron protocolos pediátricos, obser vacionales, de corta duración y con sujetos internados. Resultados : Se incluyeron 513 sujetos adultos que participaron en ensayos clínicos durante ese período de la pandemia por COVID-19. Los pacientes con CO VID-19 se caracterizaron por tener una edad de 59.7 ± 13.7 años (50% sexo femenino) y el 92% presentó riesgo incrementado de letalidad por COVID-19. La tasa acu mulada de COVID-19 fue de 9.74% (IC 95%: 7.32-12.64%) que se situó por debajo del 17% de la población de 60 a 69 años de la Argentina (p<0.0001). La tasa de letalidad por COVID-19 fue de 14% (IC 95%: 5.8-26.7), que se situó por encima del 2.45% de la población de 50 a 69 años de la Argentina (p<0.0001). Conclusión : La tasa de COVID-19 en los sujetos adultos participantes de ensayos clínicos estuvo por debajo de las cifras de la población argentina de simi lar edad. La tasa de letalidad estuvo por encima de las cifras poblacionales y se explica por el alto riesgo de esa población.
Abstract Introduction : There is little information on the pres ence of COVID-19 in clinical trial participants. The objec tive of the study was to evaluate the cumulative infec tion rate for SARS-CoV-2 in this population. Additionally, we investigated the risk, lethality, and mortality from COVID-19. Methods : The design was observational retrospective that included adult subjects participating in clinical intervention trials approved by our ethics committee during the first two years of the pandemic (March 31, 2020 to March 31, 2022). Pediatric, observational, short-term, and inpatient protocols were excluded. Results : We included 513 adult subjects who par ticipated in clinical trials during the first two years of the COVID-19 pandemic. Patients with COVID-19 were characterized as being 59.7 ± 13.7 years old (50% fe male), and 92% had an increased risk of fatality from COVID-19. The cumulative rate of COVID-19 was 9.74% (95% CI: 7.32-12.64%) and its confidence intervals were below 17% of the population aged 60 to 69 in Argentina (p<0.0001). The case fatality rate for COVID-19 was 14% (95% CI: 5.8%-26.7%) and its confidence intervals were above 2.45% of the population aged 50 to 69 in Argentina (p< 0.0001). Conclusion : The rate of COVID-19 in adult subjects participating in clinical trials was below the figures for the Argentine population of similar age. The fatality rate was above the population figures, and it is explained by the high risk of the population.
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Resumen La terapia génica ha logrado avances significativos en el tratamiento de enfermedades genéticas, especial mente en enfermedades raras y monogénicas. Se han desarrollado y aprobado terapias génicas para tratar en fermedades como la atrofia muscular espinal, brindando esperanza a los pacientes y demostrando la eficacia de esta terapia. Actualmente, se están realizando numerosos ensayos clínicos para evaluar la seguridad y eficacia de la terapia génica en diversas enfermedades, particularmente en el campo de la neurología pediátrica. Estos estudios están generando datos alentadores y contribuyen al conoci miento sobre cómo mejorar las técnicas de terapia génica. A pesar de los avances, la terapia génica enfrenta desafíos importantes. Es una terapia costosa y téc nicamente compleja, lo que limita su accesibilidad. Además, aspectos como la entrega eficiente de genes, la respuesta inmunológica a los vectores y la duración de la respuesta terapéutica requieren mejoras. se está investigando activamente. En cuanto al futuro de la terapia génica, se espera que los avances en tecnología de edición génica, como CRISPR-Cas9, permitan una mayor precisión y eficiencia en la modificación de genes. Se espera que la investigación en vectores de terapia génica mejore la capacidad de entrega y la seguridad de los tratamientos. Se están desarrollando nuevas ge neraciones de vectores virales y no virales que podrían superar las limitaciones actuales y permitir una admi nistración más eficiente y precisa de genes terapéuticos.
Abstract Gene therapy has achieved significant advancements in the treatment of genetic diseases, especially in rare and monogenic diseases. Gene therapies have been de veloped and approved to treat diseases such as spinal muscular atrophy, offering hope to patients and dem onstrating the effectiveness of this therapy. Currently, numerous clinical trials are being conduct ed to evaluate the safety and efficacy of gene therapy in various diseases, particularly in the field of pediatric neurology. These studies are generating encouraging data and contributing to the knowledge on how to im prove gene therapy techniques. Despite the advancements, gene therapy faces significant challenges. It is a costly and technically complex therapy, limiting its accessibility. Addition ally, aspects such as efficient gene delivery, immune response to vectors, and duration of therapeutic re sponse require improvements and are actively being investigated. Regarding the future of gene therapy, advances in gene editing technology, such as CRISPR-Cas9, are ex pected to allow for greater precision and efficiency in gene modification. Research on gene therapy vectors is expected to en hance the delivery capacity and safety of treatments. New generations of viral and non-viral vectors are be ing developed that could overcome current limitations and enable more efficient and precise administration of therapeutic genes.
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Los ensayos clínicos en Fase I se realzan con la participación de voluntarios sanos de prueban la seguridad y tolerabilidad de los productos farmacéuticos en investigación. En ellos, los participantes están expuestos a riesgos de medicamentos del estudio sin la posibilidad de un beneficio médico directo y, por lo general, deben pasar días o semanas en un centro de investigación. Los incentivos, como pagos monetarios se utilizan para incentivar la inscripción y compensar a los participantes por su tiempo. Estas características de los ensayos voluntarios sanos de fase I crean un contexto de investigación que difiere notablemente de la mayoría de las otras investigaciones clínicas, pues la mayoría de ellos son personas vulnerables económicamente. Este artículo presenta el objetivo de analizar factores bioéticos que inciden en el otorgamiento de incentivos a participantes voluntarios sanos en investigaciones Fase I.
Phase I Clinical Trials are conducted with the participation of healthy volunteers to test the safety and tolerability of pharmaceutical products. In them, participants are exposed to study drug risks without the possibility of direct medical benefit and usually must spend days or weeks at a research site. Incentives such as monetary payments are used to encourage enrollment and compensate participants for their time. These characteristics of Phase I healthy volunteer trials create a research context that differs markedly from most other clinical research, as most of them are financially vulnerable individuals. This paper aims to analyze bioethical factors that influence the granting of incentives to healthy volunteer participants in Phase I research.
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RESUMEN En este artículo se introducen los ensayos clínicos aleatorizados y conceptos básicos de la inferencia estadística. Se presenta como calcular el tamaño de muestra por tipo de desenlace e hipótesis a probar, junto con el código en el lenguaje de programación R para realizar su aplicación. Se presentan cuatro métodos para realizar el ajuste del tamaño de muestra original, cuando se planean análisis interinos. De una manera sencilla y concreta se busca realizar una introducción a estos temas, considerando las expresiones matemáticas que soportan los resultados y su implementación en programas estadísticos disponibles. Con el fin de acercar a los estudiantes de áreas de la salud a la estadística y al uso de programas estadísticos, aspectos poco considerados en su formación.
ABSTRACT This article introduces randomized clinical trials and basic concepts of statistical inference. We present methods for calculating the sample size by outcome type and the hypothesis to be tested, together with the code in the R programming language. We describe four methods for adjusting the original sample size for interim analyses. We sought to introduce these topics in a simple and concrete way, considering the mathematical expressions that support the results and their implementation in available statistical programs; therefore, bringing health students closer to statistics and the use of statistical programs, which are aspects that are rarely considered during their training.
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Abstract Objective: To describe the behavior of total alkaline phosphatase (tALP) in patients with metastatic castration-resistant prostate cancer receiving radium-223 therapy, in a real-world scenario, and to describe overall survival (OS) among such patients. Materials and Methods: This was a retrospective study involving 97 patients treated between February 2017 and September 2020. Patients were stratified by the baseline tALP (normal/elevated). A tALP response was defined as a ≥ 30% reduction from baseline at week 12. For patients with elevated baseline tALP, we also evaluated treatment response as a ≥ 10% reduction in tALP after the first cycle of treatment. We defined OS as the time from the first treatment cycle to the date of death. Results: There was a significant reduction in the median tALP after each cycle of treatment (p < 0.05 for all). Data for tALP at week 12 were available for 71 of the 97 patients. Of those 71 patients, 26 (36.6%) responded. Elevated baseline tALP was observed in 47 patients, of whom 19 (40.4%) showed a response. Longer OS was observed in the patients with normal baseline tALP, in those with elevated baseline tALP that showed a response to treatment (≥ 10% reduction), and in those who received 5-6 cycles of therapy. Conclusion: The tALP may be used to predict which patients will benefit from treatment with a greater number of cycles of radium-223 therapy and will have longer OS.
Resumo Objetivo: Descrever o comportamento da fosfatase alcalina total (tALP) em pacientes com carcinoma de próstata metastático resistente a castração, submetidos a terapia com rádio-223 em um cenário do mundo real, e a sobrevida global (SG) desses pacientes. Materiais e Métodos: Estudo retrospectivo envolvento 97 pacientes, no período de fevereiro/2017 a setembro/2020. Os pacientes foram estratificados de acordo com a tALP basal (normal/elevada). A resposta à tALP foi definida como uma redução em relação à linha de base de ≥ 30% na semana-12. Para pacientes com tALP basal elevada, também foi avaliada a resposta ao tratamento como uma redução de ≥ 10% de tALP após o primeiro ciclo. A SG foi definida como o tempo entre o primeiro ciclo e a data do óbito. Resultados: A redução da tALP média após cada ciclo foi significativa (p < 0,05). A tALP na semana 12 estava disponível para 71 dos 97 pacientes. Desses 71 pacientes, 26 (36,6%) responderam. Dezenove (40,4%) dos 47 pacientes com tALP elevada apresentaram resposta. Foi observada uma SG mais longa nos pacientes com tALP basal normal, nos pacientes com tALP basal elevada que apresentaram resposta ao tratamento (redução de ≥ 10%) e nos pacientes que receberam 5-6 ciclos. Conclusão: A tALP pode ser usada para prever parte dos pacientes que se beneficiarão do tratamento com um maior número de ciclos e uma SG mais longa.
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This review article explores the potential bene?ts and challenges of using telecommunications technology, including telemedicine and mobile health apps, in cancer clinical trials. The author conducted a search of four electronic databases for studies published in English between 2010 and 2021 that evaluated the use of telecommunications technology in adult cancer patients and reported patient outcomes. The studies were grouped based on the type of telecommunications technology used, and the outcomes were synthesized to provide an overview of the potential impact of telecommunications technology on cancer clinical trials. Telecommunications technologies were found to improve patient access and recruitment, data collection, management, and analysis, and enable real-time monitoring of patients' health and adherence to treatment. Telecommunications technologies can also reduce trial costs by minimizing the need for in- person visits and other expenses. However, the implementation of telecommunications technologies in clinical trials is not without challenges, including technical issues, patient acceptance and adherence, regulatory and legal approvals, and variability in healthcare systems. The author suggests that addressing these challenges could lead to improved patient outcomes and better overall health outcomes for cancer patients
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Objetivo: Discutir o uso dos progestagênios em mulheres com perda gestacional de repetição (PGR) sem causa aparente, abordando tipos de progestagênios e resultados de ensaios clínicos, revisões sistemáticas e metanálises. Métodos: Trata-se de uma revisão não sistemática de artigos publicados nas bases eletrônicas PubMed, Cochrane e SciELO nos últimos cinco anos, utilizando-se os seguintes descritores: "progesterone", "dydrogesterone", "recurrent pregnancy loss" e "recurrent abortion". Resultados: Duas grandes metanálises encontraram uma redução da taxa de abortamento e aumento da taxa de nascidos vivos com o uso do progestágeno sintético em pacientes com PGR inexplicada, porém essa conclusão foi contestada em uma metanálise mais recente. Entretanto, a progesterona vaginal micronizada poderia aumentar a taxa de nascidos vivos em mulheres com ameaça de aborto e com história de um ou mais abortos anteriores (risco relativo [RR]: 1,08, intervalo de confiança [IC] de 95%: 1,02-1,15). O benefício foi maior no subgrupo de mulheres com três ou mais perdas anteriores. Conclusão: Ainda restam dúvidas sobre o uso de "progesterona" nas pacientes com PGR inexplicada. Sua administração deve ser discutida individualmente com cada mulher, levando-se em conta especialmente a idade materna, o número de abortos prévios e a história de sangramento na gestação em curso, evitando-se tratamentos que trazem custos e não são isentos de efeitos colaterais.(AU)
Objective: To discuss the use of progestins in women with recurrent pregnancy loss (RPL) with no apparent cause, addressing types of progestins, and results of clinical trials, systematic reviews, and meta-analyses. Methods: This is a non-systematic review of articles published in the PubMed, Cochrane, SciELO electronic databases in the last five years, using the following descriptors: "progesterone", "dydrogesterone", "recurrent pregnancy loss", and "recurrent abortion". Results: Two large meta-analyses found a reduction in the rate of miscarriage, and an increase in the rate of live births with the use of synthetic progestin in patients with unexplained RPL, but this conclusion was challenged in a more recent meta-analysis. However, micronized vaginal progesterone could increase the rate of live births in women with a threatened miscarriage and a history of one or more previous miscarriages (RR: 1.08, 95% CI: 1.02-1.15). The benefit was greatest in the subgroup of women with three or more previous losses. Conclusion: There are still doubts about the use of "progesterone" in patients with unexplained RPL. Its administration should be discussed individually with each woman, taking into account especially the maternal age, number of previous abor tions, and history of bleeding during pregnancy, avoiding treatments that bring costs and are not free from side effects.(AU)
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Humanos , Feminino , Gravidez , Progesterona/uso terapêutico , Aborto Habitual/tratamento farmacológico , Protocolos Clínicos , Metanálise como Assunto , Fatores de Risco , Ensaios Clínicos como Assunto , Bases de Dados BibliográficasRESUMO
AIM: Exploring medical device clinical trial quality management indicator system to continuously improve medical device clinical trial quality system construction. METHODS: Through literature research and Delphi method, we summarized the risks of medical device clinical trials in various aspects such as quality management, clinical trial data, and clinical trial research personnel construction, analyzed the risks and proposed a clinical trial quality management index system, as well as corresponding quality improvement measures. RESULTS: To establish an appropriate medical device clinical trial quality evaluation management tool for quality risk monitoring and management, and to support and help the construction of a medical device clinical trial quality management system. CONCLUSION: To identify risks in various aspects of clinical trials and establish a preliminary assessment index system to provide a reference for the evaluation of the effectiveness of clinical trial quality management.
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Palbocicril, the first cyclin-dependent kinases 4 and 6 inhibitors, is a crucial milestone in the development history of antineoplastic drugs. It combined with aromatase inhibitor or fulvestrant as first-line, second-line or post-line therapy has good efficacy and safety for hormone receptor-positive, human epidermal growth factor receptor-2 negative locally advanced or metastatic breast cancer, which has a good application prospect. This article summarizes the clinical trials and safety studies related to palbociclib.
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Rare diseases are a group of diseases with low incidence, complex conditions, difficulty in diagnosis and poor treatment accessibility. With the growing attention on rare diseases in China in recent years, relevant policies are gradually improved, rapid progress have been made in the treatment of rare diseases and the development of orphan drugs, but there are still challenges. Based on the development status of rare disease treatment and orphan drugs, this paper elaborates on the development path of rare disease diagnosis, and provides reference for the rare disease treatment, orphan drug development and policy formation in China.
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In recent years, the development of bispecific antibodies (bsAbs) has been rapid, with many new structures and target combinations being created. The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China. However, there is a high degree of similarity in target selection, which could affect the development of diversity in bsAbs. This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies (mAbs). Through database research, we have identified the preferences of available bsAbs combinations, suggesting rational target selection options and warning of potential wastage of medical resources. We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.
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Neurodegenerative and neuropsychiatric diseases are increasingly affecting individuals' quality of life, thus increasing their cost to social and health systems. These diseases have overlapping mechanisms, such as oxidative stress, protein aggregation, neuroinflammation, neurotransmission impairment, mitochondrial dysfunction, and excitotoxicity. Currently, there is no cure for neurodegenerative diseases, and the available therapies have adverse effects and low efficacy. For neuropsychiatric disorders, such as depression, the current therapies are not adequate to one-third of the patients, the so-called treatment-resistant patients. So, searching for new treatments is fundamental. Medicinal plants appear as a strong alternative and complement towards new treatment protocols, as they have been used for health purposes for thousands of years. Thus, the main goal of this review is to revisit the neuroprotective potential of some of the most predominant medicinal plants (and one fungus) used in traditional Chinese medicine (TCM), focusing on their proven mechanisms of action and their chemical compositions, to give clues on how they can be useful against neurodegeneration progression.