Analysis of ethical review issues of informed consent form for clinical trials of registered anti-tumor drugs in our hospital / 中国药房

OBJECTIVE To promote the standardization and integrity of the informed consent form for clinical trials of registered anti-tumor drugs， and to protect the legitimate rights and interests of the subjects. METHODS The ethical review resolutions of clinical trial projects of registered anti-tumor drugs that were initially reviewed by the Ethics Committee of our hospital from July 1st， 2020 to July 1st， 2022 were summarized to statistically analyze the problematic items according to the “Quality Analysis Form of Informed Consent” prepared by our hospital. RESULTS Of the 316 clinical trials of registered anti- tumor drugs that were initially reviewed， 257 （81.3%） had problems with the contents of informed consent form， mainly domestic multi-center trials and phase Ⅲ trials. The main problems included the vague notification of the test fee bearer （68.5%）， the incomplete notification of the test content （59.1%）， the insufficient notification of rights and interests and risks （58.4%）， the insufficient notification of personal information protection （56.0%）， and the nonstandard expression of the informed consent form （52.5%）. CONCLUSIONS There is still a gap between the informed consent form of the clinical trials of registered anti-tumor drugs in our hospital and the requirements of the new version of Good Clinical Practice for Drugs （GCP）. The parties involved in the test can take a number of measures to improve the standardization and integrity of the informed consent form， and the research team should design the informed consent form in strict accordance with the requirements of the new GCP and pay attention to the comprehensive notification about the test. The Ethics Committee can provide the sponsor and researcher with the template of informed consent form and the key points of writing， continue to strengthen the examination ability， improve the examination quality， and effectively protect the safety and interests of the subjects.

Analysis of problems and countermeasures faced by the ethics committee in the context of the 2020 version Good Clinical Practice / 中华医学科研管理杂志

Objective:According to the requirements set forth by the " regulations on the management of drug clinical trial institutions" and the 2020 version of Good Clinical Practice, problems faced by the construction of Institutional Review Board (hereinafter referred to as the IRB) in the implementation of the filing system is solved.Methods:According to the study of laws and regulations, combined with problem analysis during the early construction of IRB, problems during the IRB filing are identified and analyzed.Results:The IRB faced many problems that including the organizational structure, continuing review, informed consent and multicenter ethical review. We can gradually improve the ability of ethical review through continuous in-depth study of relevant laws and regulations, so as to ensure the scientific validity and ethical acceptability of drug clinical trials.Conclusions:It is of great significance for the high-quality development of IRB to improve its organizational structure, optimize its review mechanism and improve its review efficiency.

Talking about the Key Points and Notices of Drug Management in Clinical Trials / 中国药房

OBJECTIVE： To provide references for improving the standard operating procedures of drug management in clinical trials and drug management in clinical trials. METHODS： According to Good Clinical Practice （GCP）， Data On-site Verification Points of Drugs Clinical Trial， Qualification Examination Rules of Drug Clinical Trial Institution， based on the quality control project carried out in our hospital since July 2016， the matters needing attention in the non-standard operation and key process of drug management in clinical trial were summarized， and the improvement measures were discussed. RESULTS & CONCLUSIONS： Non-standard drug management is a high-incidence link of non-standard operation in the trial process. Among them， the acceptance， distribution and use of drugs are the three links with the highest incidence of non-standard operation of drug management in the trial process. Therefore， when formulating the relevant management system， each institution should pay attention to it according to its own situation； such as， when accepting drugs in clinical trials， attention should be paid to checking the intact degree of drug packaging； drugs transported in cold chain should also be checked for temperature records and rejected in case of over-temperature； the copies of the waybill should be kept in file with the original to avoid fading of the thermosensitive paper； whether the relevant characteristics of the control drugs and placebos meet the requirements. Institutions can standardize the key links of drug management in the trial process， the time of project establishment， project start-up， quality control and supervision， formulate and constantly improve the relevant drug management system and standard operating procedures （SOP）. For example， when starting a project， attention should be paid to the participation of drug administrators in the training and signature of start-up meeting， whether the design of the form is complete， standardized and operable. It is necessary for clinical trial institutions to pay attention to the standardization and precision of drug management and the key links in clinical trials.

Influence and Reflections on the Work of Drug Clinical Trial Institutions in China after Joining in ICH / 中国药房

OBJECTIVE： To summarize the problems and countermeasures which the construction of drug clinical trial institutions face after China Food and Drug Administration （CFDA） join in ICH， and its effects on clinical study management in China. METHODS： Combined with the experience on Good Clinical Practice （GCP） in our hospital during recent years， reviewing related content of ICH-GCP， the differences between China’s GCP （CFDA-GCP） and ICH-GCP， the problems faced by drug clinical trial institutions after joining in ICH， and the thinking of China’s clinical research were discussed. RESULTS & CONCLUSIONS： There were differences between CFDA-GCP and ICH-GCP in the management concept of clinical drug trials， the structure and function of ethical committees， the protection of the rights and interests of subjects， the choice of researchers and research institutions， management requirements of experimental drugs and the management of documents and data. After joining in ICH， the current organization and management structure， system and standard operating procedures， ethics committee， GCP training and continuing education， professional quality control system， experimental drug management， data management and information system construction and upgrading， clinical research coordinator management and other aspects of the drug clinical trial institutions were far from the requirements of ICH. The standardization of drug clinical trial institutions in China can be further promoted by revising regulations and guidelines， formulating standard operating procedures in line with ICH-GCP， building standardized ethics committees， implementing GCP training and continuing education， improving quality control system and drug management in clinical trials， strengthening hardware and software construction and clinical coordinator management， etc. At the same time， problems such as fewer full-time personnel and weak implementation of the system can be improved by strengthening project management， improving the quality of employees and building normal cross-regional cooperation.

Qualitative features in clinical trials: coordinates for prevention of passive and active misconduct

For many years, the quality concept in clinical trials has been discussed and recommended by Good Clinical Practice (GCP) guidelines. Regulatory Authorities and also the Public Involvement anticipate that the pharmaceutical industry will concentrate on creating quality frameworks amid the arranging and leading of conventions of controlled protocols. Nevertheless, many factors have been suggested as contributing to the occurrence of scientific misconduct within the research field, such as: personal and financial interests, site monitoring, available resources, workload, competition among investigators, and the implicit consent of sponsors. The negligence on data fraud represents not only omission but misconduct as well, in this case, a passive attitude intrinsically related to the act of transgression. A properly culture of research must be based on a fundamental ethos of integrity, openness and honest work of high quality in all parts of the research process. There is a need to change the focus from inspection-based quality improvement to planned systematic quality management within clinical trials. In search for a monitoring improvement, a full statistical  way to deal with information recognition comprises of executing however many measurable tests as could be allowed on whatever number clinical information factors as could be expected under varied circumstances. Adoption of specific and preventive clinical trial monitoring procedures can identify potential misconduct and data fraud leading to improvement in overall data quality and scientific reports.

La investigación clínica. Un primer acercamiento

La investigación clínica es la actividad encaminada a conocer el resultado de una intervención o un producto para el diagnóstico o la terapéutica en los seres humanos. El ensayo clínico es el principal exponente de la investigación clínica y toda evaluación experimental de una sustancia o medicamento en seres humanos. En Cuba, existe un desarrollo importante de la biotecnología y de los centros de investigación que necesitan de ensayos clínicos según estándares nacionales e internacionales. En el presente trabajo se exponen aspectos relacionados con la evolución histórica de la Investigación Clínica, el Ensayo Clínico y su contexto en el país como un primer acercamiento al tema...

Clinical research is just that activity to know the potential diagnostic or therapeutic nature of an intervention or a product in humans. The clinical trial is the leading exponent of clinical research and the whole experimental evaluation of a substance or drug in humans and has revolutionized medical practice around the mundo.Sus precursors date back to the XVII and XVIII centuries and evolved since this methodology until the randomized controlled clinical trial. From the fifties significant regulatory and ethical changes appear. In Cuba, there is a significant development of biotechnology and research institutions that require clinical trials to national and international standards. This paper aims to clarify aspects of the historical development of Clinical Research, Clinical Trial in Cuba and its context as a first approach to the subject...

Practice and Experience of Application and Report for the Accreditation of Drug Clinical Trial Institution Qualification of Our Hospital / 中国药房

OBJECTIVE:To introduce the experience of application and report for accreditation of drug clinical trial institution qualification of our hospital,to provide a reference for other hospitals. METHODS:From the building of institution,drug clinical trial ethics committee,clinical trials of listed drugs,simulated qualification accreditation,and other aspects,the experience and key points of application and report for accreditation of drug clinical trial qualification of our hospital were summed up. RESULTS& CONCLUSIONS:Priority should be given to staffing(particularly the leaders of the institution),the installation of software and hardware (for system development,training,institution office and specialized department),and the building of ethics committee. Departments should share work experience of clinical trials of listed drugs and set up a self-inspection group to simulate qualifica-tion accreditation. Work procedures and methods of qualification accreditation should be clearly understood,the requirements of Good Clinical Practice,the standards for qualification accreditation,should be known well;Good Clinical Practice should be seri-ously implemented and the subjects’rights and interests should be protected,which will contribute to the successful completion of application and report for qualification accreditation.

Certificación en Buenas Prácticas Clínicas de un sitio clínico / Certification of Good Clinical Practice of a clinical center

El mundo desarrollado con su creciente competitividad impone aún mayores exigencias en el cumplimiento de los estándares para el registro de los productos médicos y ha comenzado la certificación de los sitios clínicos para la realización de los ensayos clínicos, lo cual le brinda mayor credibilidad a los resultados obtenidos de las investigaciones realizadas en ellos y por ende, le da mayor prestigio y competitividad al producto. El objetivo de este trabajo es mostrar la implementación de un sistema de Buenas Prácticas Clínicas en la ejecución de los ensayos clínicos para la Certificación en Buenas Prácticas Clínicas. Se realizó un estudio descriptivo en el Hospital General Dr Juan Bruno Zayas Alfonso en Santiago de Cuba, entre Junio 2010 y Agosto 2011. La investigación constó de tres momentos y abarcó todas las acciones realizadas durante la implementación. Finalmente se estableció un sistema de Buenas Prácticas Clínicas que resultó en la Certificación del Hospital en Buenas Prácticas Clínicas por parte del Centro para el Control Estatal de Medicamentos, Equipos y Dispositivos Médicos para la realización de ensayos clínicos(AU)

The developed world with its increasing competitiveness imposes even greater demands in meeting the medical product registration standards and certification. According to this, it has begun the certification of the clinical centers conducting clinical trials, which gives more credibility to the results from research carried out there and therefore greater prestige and competitiveness to the product. The objective of this paper was to show the implementation of a Good Clinical Practice system in the performance of clinical trials in order to attain the Certification. A descriptive study was made in Dr Juan Bruno Zayas Alfonso general hospital from June 2010 and August 2011 in Santiago de Cuba province. The research consisted of three stages and included all the actions taken during the implementation. Finally, a Good Clinical Practice system was put in place that allowed the Certification of Good Clinical Practices for conduction of clinical trials to be given to the hospital by the Regulatory Center of State Control of Drugs and Medical Equipment and Devices(AU)

Análisis comparativo entre la normativa de buenas prácticas clínicas de Venezuela y las de Argentina, Perú y España / Comparative analysis between the regulations of good clinical practices of Venezuela and those of Argentina, Peru and Spain

La Farmacología Clínica es la disciplina científica que estudia la utilidad profiláctica, terapéutica o de diagnóstico de principios activos y medicamentos en el hombre, así como también el mecanismo de acción, los parámetros farmacológicos que determinan su efectividad, los riesgos y sus efectos adversos. El propósito de este trabajo es realizar una revisión de la Normativa sobre Buenas Prácticas Clínicas (Reglamento de Investigación en Farmacología Clínica), utilizada para evaluar y aprobar las investigaciones clínicas de productos farmacéuticos por el Instituto Nacional de Higiene "Rafael Rangel" de Venezuela, y comparar los preceptos éticos, legales y científicos en ella establecidas, contra las Normativas similares utilizadas en Argentina, Perú y España. Se llevo a cabo una investigación de tipo documental la cual comprendió etapas de revisión, comparación y análisis, obteniéndose como resultado que las Normativas Éticas y Legales de los países en estudio (Argentina, Perú y España) están en concordancia con las Normativas de Venezuela constatándose de esta forma la armonización de las mismas.

Clinical Pharmacology is the scientific discipline that studies the usefulness prophylactic, therapeutic or diagnostic of active substances and drugs in man as well as the mechanism of action, pharmacological parameters that determine its effectiveness, risks and adverse effects. The purpose of this paper is to review the Regulations on Good Clinical Practice (Regulation of Clinical Pharmacology Research), used to evaluate and approve clinical investigations of pharmaceutical products by the National Institute of Hygiene "Rafael Rangel" in Venezuela and compare the ethical, legal and scientific stated therein, against related standards used in Argentina, Peru and Spain. Was carried out documentary research which comprised stages of review, comparison and analysis result indicate that the Ethical and Legal Standards of the countries studied (Argentina, Peru and Spain) are in accordance with the Regulations of Venezuela being stated in this way harmonizing them.

A Survey of Physicians' Understanding of the Regulatory Systems for Clinical Trials in Japan / General Medicine

<b>Background:</b> Re-revision of the Ethical Guidelines for Clinical Study (EGCS) in Japan is planned in 2013. It is important to ascertain the current situation of physicians' understanding to conduct clinical trials. It seems that the difference in regulatory processes between commercial and non-commercial clinical trials has caused significant confusion for physicians in conducting clinical trials in Japan.<br>This survey was undertaken in order to improve awareness of the differences between both types of clinical trials. Furthermore, this survey examined whether it was effective to promote about clinical trials under newly introduced regulatory guidelines and to examine the subsequent willingness of physicians to conduct such clinical trials.<br><b>Methods:</b> From 24^th March to 24^th April 2009 inclusive, a questionnaire survey was conducted targeting 286 physicians working at Shiga University of Medical Science Hospital. A follow-up survey was conducted among 109 participants at a lecture about clinical trials on 8^th July 2009.<br><b>Results:</b> Physicians who had prior knowledge of the regulations, purposes, or support systems for commercial and non-commercial clinical trials responded positively that they were more likely to conduct clinical trials, while physicians who had no prior knowledge of them responded negatively. Both groups reported that their daily working pressures and cumbersome regulatory processes prevented them from conducting clinical trials.<br><b>Conclusion:</b> Japanese physicians lack knowledge and information about clinical trials, leading to negative perceptions and reduced willingness to conduct such studies. Thus, the introduction of any strict and complex regulations should be approached carefully when the environment for clinical trials has not yet been established.

Armonización de estándares de calidad para ensayos clínicos: Norma ISO 9001-Guía de Buena Práctica Clínica / Harmonization of quality standards for clinical trials. ISO-9001 standard and Guide of Good Clinical Practice

El proceso de ensayo clínico necesario para autorizar el uso de nuevos medicamentos en humanos es extenso y complejo. Para garantizar la calidad y estandarizar este proceso, la Conferencia Internacional de Armonización ha establecido la Guía E6 para la Buena Práctica Clínica, la cual ha sido asumida y adaptada por las agencias reguladoras nacionales para estandarizar este proceso en sus países. Otra norma que permite garantizar calidad es la ISO 9001:2008, que establece requisitos para implementar Sistema de Gestión de Calidad. El objetivo de este trabajo consistió en establecer elementos comunes que demuestren la armonización entre la Buena Práctica Clínica de la Conferencia Internacional de Armonización, la Buena Práctica Clínica cubana y la ISO 9001:2008 para su implementación en sistemas de calidad para los ensayos clínicos. Para ello se realizó el estudio de estos estándares analizando qué tienen en común en su aplicación para el proceso de ensayo clínico. Se determinó que el cliente, los proveedores, el enfoque de proceso, la documentación, la dirección, las revisiones, la forma de realización de la investigación y la mejora de la calidad son puntos comunes para los cuales se establecen requisitos a cumplir. Esto permitió afirmar que los estándares estudiados al ser usados de conjunto en el proceso de ensayo clínico, contribuyen a elevar la calidad, pues no existe ningún aspecto contemplado en ellos que refleje contradicción sino aspectos comunes que permiten su armonización y uso

A clinical trial is an extensive, complex and necessary process to authorize the use of new medications in humans. For the purpose of assuring the quality and the standardization of this process, the International Conference of Harmonization (ICH) set the Guideline E6 for Good Clinical Practice, which has been adopted and adapted by the national regulatory agencies. There also exists another standard to guarantee quality in the organizations, namely the ISO 9001:2008 that establishes requirements for Quality Management System. The objective of this paper was to determine common elements showing the harmonization among the Good Clinical Practice of the ICH, the Cuban one and the ISO 9001:2008 in order that they can be implemented in the clinical trials. To this end, one study was performed on the Good Clinical Practice of the ICH, the Cuban and the ISO 9001:2008 standards to find out what they had in common in their use for the clinical trials. It was determined that the clients, the suppliers, the process approach, the documentation, the management, the reviews, the style of conducting the research studies and the quality improvement were common aspects for which there are several requirements set by these standards. The aforementioned allowed stating that the joint use of the studied standards in the clinical trial contributes to raise the quality, since there is not a single aspect that reveals any contradiction whatsoever; there are common aspects that make their harmonization and use possible

Clinical Trial for Antidiabetic Drugs: FDA Guidance for Diabetes Mellitus-Evaluation of Cardiovascular Risk in New Antidiabetic Therapies / 임상당뇨병

Type 2 diabetes is rapidly increasing worldwide, and there have been many advances in the care of diabetic patients. Nevertheless, less than half of the patients are achieving the glycemic goal of HbA1c < 7%. This shows that current therapeutic modalities have limitations, and the need for continued development of new antidiabetic drugs is clear. In 2007, a meta-analysis focusing on the thiazolidinedione drug rosiglitazone suggested an unacceptably high cardiovascular risk for this newly approved drug, prompting changes in regulations for antidiabetic drug development. The FDA guidance for Diabetes Mellitus-Evaluation of Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes was released as a draft in Feb 2008, and the final form was published in December 2008. The guidance, though not a regulation, requires developers to demonstrate that all new antidiabetic agents have an acceptable cardiovascular risk. The European Medicine Agency (EMA) also published a draft guideline in January 2010 on the clinical investigation of medicinal products for the treatment of diabetes mellitus which included a cardiovascular safety assessment component. Considering the increased CV risk in type 2 diabetic patients, antidiabetic drugs should not result in an unacceptable increase in cardiovascular risk. The FDA has offered guidelines for the assessment of cardiovascular safety for antidiabetic drugs. Careful prospective planning of clinical trials (choice of study type, subject selection, and meta-analysis) and thorough preclinical safety assessment (choice of cardiovascular endpoints: MACE, endpoint adjudication) are needed to assess possible cardiovascular risk.

Mejoras en el acceso a la información de los ensayos clínicos / Improved access to clinical assay information

El Centro de Inmunología Molecular ha venido desarrollando biomoléculas para el tratamiento del cáncer. En la medida que se avanza en el desarrollo de estos productos, se avanza en las fases I, II, III y IV de los ensayos clínicos, lo que trae aparejado un incremento en el número de pacientes a tratar y en el número de hospitales involucrados. Se cuenta con diez productos diferentes, implicados en más de 50 ensayos clínicos, nacionales y multinacionales, con un pronóstico de inclusión de 2 500 pacientes nuevos por año. En este proceso están incluidos alrededor de 30 hospitales en 13 provincias del país. Para mejorar el acceso a la información de ensayos clínicos por parte de los investigadores comprometidos, se creó un sitio Web formado por cuatro secciones fundamentales, relacionadas con los productos y sus indicaciones, buenas prácticas clínicas, la entrada remota de datos y la gerencia de los ensayos clínicos. Todo lo anterior mejora fundamentalmente la calidad de la información brindada a los investigadores clínicos involucrados y redunda en una mayor organización de la compleja actividad de los ensayos clínicos en Cuba

The Molecular Immunology Center has been developing biomolecules for cancer treatment. As the development of such products continues, phases I, II, III and IV of clinical assays also advance, which leads to an increase of the number of patients to be treated and the number of involved hospitals. There are ten different products involved in over 50 national and multinational clinical assays in which 2 500 patients are predicted to be included every year. Approximately 30 hospitals from 13 provinces are included in this process. For the purpose of improving the access of committed researchers to the clinical assay information, a new Website with four sections was devised. Those sections are related to products and their indications, good clinical practice, remote data entry and clinical assay management. All the above-mentioned improves the quality of the information given to involved clinical researchers and results in better organization of the complex activity of clinical assays in Cuba

Development an original reporting system ; from trial to the clinic / 医薬品情報学

  In this report, we introduce the importance of a system for sharing information about cancer molecular-targeted medicines from trial to the clinic by the department of knowledge education research, department of breast surgical oncology, department of cardiovascular internal medicine and department of dermatology at St. Luke’s International Hospital in Japan.  At present, information regarding the side effect(s) of a study drug does not reach doctors who are not members of the department in charge of the clinical trial.  The reason for this is because clinical trials are conducted under the legal constraints of GCP (Good clinical practice), and while safety information about any adverse events (side effects) is reported, it is limited to the level of an Institutional Review Board.  When there was an enquiry about a known side effect that had occurred to patients taking molecular-target medicine from a doctor who was not a member of the department in charge of the clinical trial, it became clear that information regarding the clinical trial medicine and non-approved medicine was not reaching the clinic.  We developed an original reporting system for such information that would offer the information using the same format as the clinical trial itself, as well as the department in which the side effect was treated, to resolve the problem of access to side effect information outside of the clinical trial itself.  We show that the reporting of such information leads to resolution of this problem.  We believe that this will relieve the patient and contribute to the clinical trial as well as to the department that deals with such side effects.

Good Clinical Practice in Neonatal Clinical Research

Clinical research is a necessity, not an option, for developing better and new medicines and therapeutic modalities. But in the course of clinical research, there are rules and guidelines that should be followed to ensure the due respect for persons, beneficence, and justice for persons who voluntarily participate in the research as described in the Belmont Report. Good Clinical Practice (GCP) is an "international scientific and ethical quality standard for designing, conducting, recording, and reporting" clinical trials. The main purposes of GCP would be to protect rights, safety, and well-being of trial subjects, in compliance with the principles of Declaration of Helsinki, and to assure that the data obtained from clinical trials are credible. In order to achieve these, investigators must be fully aware of the meanings as well as actual procedures involved in the research and should make the best effort to comply with GCP. For those individuals who belong to vulnerable populations, such as neonates, in addition to the general principles of GCP, further measures to ensure added protection should be implemented. It is our duty to develop and provide better care through clinical research even for neonates. But in doing so, we have to make sure that the importance of protecting the rights, safety, and well-being of the subjects supersede the interests of science and society.

Lo universal, lo particular y lo singular más allá del diagnóstico médico: a propósito de la utilización de guías de buenas prácticas clínicas en la toma de decisiones terapéuticas / The Universal, the Particular and The Singular categories going beyond the medical diagnosis: about the use of Good Clinical Practices Guidelines for therapeutic decision-making

Es reconocido el valor de las categorías dialéctico-materialistas para el estudio de los fenómenos de la naturaleza, la sociedad y el pensamiento. En este artículo se realizó, mediante el empleo de las categorías lo universal, lo particular y lo singular, el análisis de un fenómeno de la práctica médica actual: la introducción de guías de buenas prácticas clínicas, para la toma de decisiones terapéuticas. Se insistió en la necesidad de considerar la unidad dialéctica de estas categorías filosóficas en todo el proceso de elaboración de guías, en su empleo por parte de los médicos asistenciales y en la evaluación por las instancias administrativas de la adherencia de los facultativos a estas guías

The value of dialectical-materialistic categories for the study of nature, society and thinking phenomena is well known. By using the Universal, Particular and Singular categories, the article made an analysis of the present medical practice: introduction of good Clinical Practice Guidelines for decision-taking. It insisted on the need of bearing in mind the dialectical unit of these philosophical categories throughout the complete process of drafting the guides, on their use by care delivery physicians and on the evaluation of the medical staff compliance with these guidelines on the part of administrative entities.

Analysis on Common Problems in Clinical Evaluation of New Chinese Medicines and Countermeasures / 中医杂志

The authors discuss the technical problems in clinical evaluation of newly-developed Chinese medicines.For improvement of evaluation quality,this paper puts forward some suggestions for solving the common problems such as unitary intervention pattern,lack of corresponding treatment for the changed syndrome,subjectivity in standards of syndrome-differentiated diagnosis,ill-chosen medicine in control group,and mismanagement of medicine combination.