药物临床试验的伦理审查几个要点

药物临床试验中,为充分保护受试者权益,在伦理审查中要特别重视受试者参加风险和受益,力求风险最小和受益最大,保证受试者充分了解临床试验后知情同意,注意特殊受试人群保护,避免发生利益冲突。     

Proposal for ethical standards in therapeutic trials

Presented here are the conclusions and recommendations of an interdisciplinary French committee which informally considered the ethical issues involved in clinical trials as they are currently designed and conducted. These drug trials were examined in terms of type of trial, selection of subjects, informed consent, population size and composition, risks and benefits, dosage schedules, and randomization. The committee proposed that trials with low success from the start be reduced, that subjects be selected who have a strong probability of benefit, and that the physician's respect for the individual subject be monitored. To assure that clinical trials balance the interests of patients and society, the report urges the establishment of ethics committees, consisting of two physicians, a statistician, a lawyer, and a judge, to evaluate trial proposals.     

Patients' perceptions of information provided in clinical trials

BACKGROUND: According to the Declaration of Helsinki, patients who take part in a clinical trial must be adequately informed about the trial's aims, methods, expected benefits, and potential risks. The declaration does not, however, elaborate on what "adequately informed" might amount to, in practice. Medical researchers and Local Research Ethics Committees attempt to ensure that the information which potential participants are given is pitched at an appropriate level, but few studies have considered whether the patients who take part in such trials feel they have been given adequate information, or whether they feel able to understand that information. OBJECTIVES: To explore trial participants' views (i) on the amount of information provided, and (ii) of their own understanding of that information. DESIGN: Structured interviews of patients participating in clinical trials for the treatment of chronic medical condition. FINDINGS: Patients generally felt they were given an appropriate amount of information, and that they were able to understand all or most of it. They felt they were given adequate time to ask questions before agreeing to take part. In comparison with treatment given out with the research setting, patients generally felt they received more information when participating in a clinical trial. CONCLUSIONS: Researchers sometimes complain that patients are given too much information during clinical trials, and have limited understanding of that information. The present study shows that this perception is not necessarily shared by patients. More research is needed in this area, particularly to gauge whether patient understanding is indeed accurate.     

药物临床试验中受试者权益保护存在的问题及对策

从我国临床试验行政许可、伦理委员会建设和研究者应承担的责任等角度出发,分析临床试验中受试者保护措施现状及在受试者权益保护方面存在的主要问题:不胜任的机构仍在开展临床试验,伦理审查委员会的独立性和能力建设存在问题,知情同意流于形式或在知情同意过程中研究者行为失范。针对这些问题提出了一些建议和改善措施:完善不良反应处理机制和受试者补偿机制,加强伦理审查委员会的能力建设,加强GCP的伦理培训,规范临床试验机构资格认定与复核管理,建立健全行政监督机制。     

某院药物临床试验受试者脱落原因浅析及对策探讨

目的分析药物临床试验中影响受试者脱落的主要因素,探讨提高受试者依从性的策略。方法分析某院2009年1月至2011年10月48项的药物临床试验资料,共954例门诊受试者,其中11项为国际多中心药物临床试验。在对受试者脱落的原因分析基础上探讨提高受试者依从性的多项策略。结果 954例受试者中,66例受试者脱落。3项国际多中心试验无一例脱落。受试者个人因素致脱落的占4.55%;药物和试验方案因素是主要的影响因素,占62.13%;环境因素致脱落的占33.32%。近年药物临床试验的国际化发展,对受试者的依从性要求更高。结论应在药物临床试验的各个阶段实施针对性措施,对受试者充分知情同意、进行依从性教育、建立良好的医患关系、积极处理不良事件,多方面提高受试者依从性,从而提高药物临床试验质量。     

Informed consent and participant perceptions of influenza vaccine trials in South Africa

BACKGROUND AND OBJECTIVES: There are few insights from sub-Saharan Africa on research participants' experiences of the informed consent process, particularly in the context of randomised controlled trials, where issues of randomisation and the use of placebos may be confusing concepts for participants. This study investigated the knowledge and perceptions of the informed consent process among individuals participating in influenza vaccine trials in two disadvantaged communities in South Africa.Method: Four to 12 months after completion of the trials, participants were contacted to return to participate in the informed consent study. The semistructured questionnaire administered to assess recall of trial procedures and the informed consent process covered key issues including: purpose of the study; awareness that the study was not part of routine treatment; voluntary nature of participation and freedom to withdraw; randomisation; placebos; and remuneration. RESULTS: A total of 334 participants (93% of the original vaccine trial sample; mean age 68 years, median level of education grade 8, 69% women) completed the questionnaire. Only 21% were able to recall that they were allocated randomly to the different treatment arms. Only 19% of those involved in the placebo controlled study had interpreted the concept of placebo as an inactive medication. CONCLUSION: Although a good general recall of trial concepts was demonstrated, only a small proportion of the participants correctly interpreted and recalled the concepts of randomisation and placebos. Informed consent in this and similarly disadvantaged communities may often be inadequate and new ways to improve understanding of the research process should be explored.     

我国COVID-19相关临床试验注册特点及存在的伦理学问题

目的：通过对我国新型冠状病毒感染(COVID-19)相关临床试验注册信息多角度分析,探讨其中存在的伦理学问题,以期为新突发传染病等公共卫生事件临床伦理的规范化提供依据。方法：在美国临床试验注册中心(ClinicalTrials.gov)和中国临床试验注册中心(ChiCTR)使用“新型冠状病毒”“COVID-19”等关键词检索2020年1月1日至2022年11月15日注册的COVID-19相关临床试验,归纳分析其注册的时空分布特点、研究类型、干预措施、研究状态及伦理等信息,发现并探讨相关伦理学问题。结果：共纳入1 560项COVID-19相关的临床试验,其中ClinicalTrials.gov注册481项,ChiCTR注册1 079项。临床试验注册高峰期集中在2020年2-4月;根据省级行政区划分湖北省、上海市、北京市临床试验注册量较多。干预性研究(843/1 560,54.00%)在所有注册类型中占比最高,注册内容涉及疫苗(202/843,23.96%)、化学药品(193/843,22.89%)、中医药(153/843,18.15%)及生物制品(90/843,10.68%)等多个方面;...     

绝经后骨质疏松症中药治疗研究文献的质量评价

目的 了解目前国内中药治疗绝经后骨质疏松症的临床治疗研究的现状。方法 对检索到的50篇有关中药治疗绝经后骨质疏松症的临床研究论文，按照牛津循证医学中心证据水平标准和临床试验的没计原则，从诊断标准、纳入和排除标准、组间基线可比性、随机、对照、双盲、统计学方法、疗效判断、疗程及药物的不良反应、随访等多个方面进行分析评价。结果 50篇相关文献中，按照牛津循证医学中心证据水平标准评价，推荐级别为B级的占44.0％，C级的占56.0％；证据水平为2b级的占40.0％，3b级的占4.0％，4级的占56.0％；随机对照试验文献占44.0％；临床对照试验文献占4.0％；采用随机双盲者占9.1％，随机单盲者占18.2％，说明组间基线可比的占31.8％，有诊断标准的占90.9％，有纳入和排除标准的占86.4％，说明统计方法的占52.4％，有客观疗效评价指标的占90.9％，说明药物不良反应的占9.1％。结论 有关中医药治疗绝经后骨质疏松症的临床研究论文日益增多，但随机对照试验比例偏低，研究设计及论文撰写水平有待进一步提高。     

眼科新药临床试验中安慰剂对照的伦理审查问题探讨

一些研发中的眼科新药在进行临床试验时常常使用安慰剂作为对照。在眼科新药的临床试验中,使用安慰剂必须遵循两条原则,一是安慰剂的使用不能造成受试者视力不可逆或永久性的损害,二是研究者必须做好安慰剂的风险管控并将安慰剂的风险向受试者完全披露。对于安慰剂使用的伦理审查,应该从标准治疗的效果、安慰剂的风险、研究方案中风险的管理和知情同意书中风险的告知这几个方面进行综合评估。     

A cohort study of summary reports of controlled trials

Substantial numbers of clinical trials continue to be reported only in summary reports that present insufficient methodological details to permit informed judgments about the likely validity of the conclusions. Using a cohort of 176 controlled trials reported in summary form, we tested the hypotheses that they would be more likely to be followed by full reports if, on the basis of the information provided in the summary report, (1) the trial was judged to be methodologically sound, (2) the results favored the test treatment, and (3) the sample size was relatively large. The results of univariate and multivariate analyses provided support for only the third of these hypotheses. Investigators, as well as those who fund and sanction the conduct of clinical research, should make greater efforts to ensure that clinical trials are reported properly.     

Methodological quality and reporting of ethical requirements in clinical trials

OBJECTIVES: To assess the relationship between the approval of trials by a research ethics committee (REC) and the fact that informed consent from participants (ICP) was obtained, with the quality of study design and methods. DESIGN: Systematic review using a standardised checklist. MAIN MEASURES: Methodological and ethical issues of all trials published between 1993 and 1995 in the New England Journal of Medicine, the Lancet, the Journal of the American Medical Association and the British Medical Journal were studied. In addition, clinical trials conducted in Spain and published by at least one Spanish author during the same period in any other journal were also included. RESULTS: We studied the published articles of 767 trials and found the following indicators of lower methodological quality to be independent predictors for failure to disclose REC approval or ICP: absence of concealment of allocation, lack of justification for unblinded trials, not using a treatment for the patients in the control group, absent information on statistical methods, not including sample size estimation, not establishing the rules to stop the trial, and omitting the presentation of a baseline comparison of groups. CONCLUSION: Trials of higher methodological and scientific quality were more likely to provide information about their ethical aspects.     

Equitable treatment for HIV/AIDS clinical trial participants: a focus group study of patients, clinician researchers, and administrators in Western Kenya

OBJECTIVES: To describe the concerns and priorities of key stakeholders in a developing country regarding ethical obligations held by researchers and perceptions of equity or "what is fair" for study participants in an HIV/AIDS clinical drug trial. DESIGN: Qualitative study with focus groups. SETTING: Teaching and referral hospital and rural health centre in Western Kenya. PARTICIPANTS: Potential HIV/AIDS clinical trial participants, clinician researchers, and administrators. RESULTS: Eighty nine individuals participated in a total of 11 focus groups over a four month period. The desire for continued drug therapy, most often life long, following an HIV/AIDS clinical trial was the most common priority expressed in all focus groups. Patients with and without HIV/AIDS also thought subsidizing of drug therapies and education were critical forms of compensation for clinical trial participation. Financial incentives were considered important primarily for purchasing drug therapy as well as obtaining food. Patients noted a concern for the potential mismanagement of any money offered. Clinician researchers and administrators felt strongly that researchers have a moral obligation to participants following a trial to provide continued drug therapy, adverse event monitoring, and primary care. Finally, clinician researchers and administrators stressed the need for thorough informed consent to avoid coercion of study participants. CONCLUSIONS: Kenyan patients, clinician researchers, and administrators believe that it would be unfair to stop antiretroviral therapy following an HIV/AIDS clinical trial and that researchers have a long term obligation to participants.     

Does informed consent influence therapeutic outcome? A clinical trial of the hypnotic activity of placebo in patients admitted to hospital

To examine whether written informed consent might influence the results of clinical trials the effect of placebo when given with or without informed consent to patients suffering from insomnia was studied. The study was a single blind observer blinded trial, and patients were paired according to sex, age, and hospital environment. Randomisation assigned the first patient of each pair to the control group (without informed consent) or the group to give informed consent. Of the 56 patients, 26 refused to give informed consent, and the age and sex distribution of these differed significantly (p less than 0.02) from the 30 pairs of patients ultimately enrolled into the study. In this "biased" sample, the hypnotic activity of placebo was significantly higher in the control group (p less than 0.05). It is concluded that the informed consent procedure biases the results of clinical trials and might affect their general applicability.     

Informed consent in an antiretroviral trial in Nigeria

We examined the process of informed consent in an antiretroviral trial in Nigeria. A semi-structured questionnaire was administered to 88 out of 180 people enrolled in the trial. This covered all aspects of the information disclosed in the leaflet of the antiretroviral trial. We found that 75 (85 per cent) of the respondents knew that the purpose of the research was to test a new drug and 13 (14 per cent) believed that they were receiving free treatment for HIV. Participants understood certain aspects of the research, especially the benefits and duration. Their understanding of the trial's risks and their right to refuse to participate and to withdraw was low. Their level of understanding was significantly related to age but not to gender, marriage, education, religion, employment and occupation. Signed informed consent is not a guarantee that participants have understood the information given to them and therefore made a voluntary decision to participate. Researchers should make sure that the process of obtaining informed consent achieves the desired outcome. This is especially important in the developing world where access to health care is limited, potential participants are poor and literacy levels are low.     

The need for randomized controlled trials in podiatric medical research

The randomized controlled trial is the most robust method available to evaluate health-care treatments. If podiatric medical practice is to be based on rigorous evidence, then high-quality randomized controlled trials are needed to inform that practice. In this article, we examine the extent to which randomized controlled trials are used in recent podiatric medical research and appraise the quality of those that are available. Using the Cochrane database of all randomized controlled trials in health care, we found only six relevant trials undertaken in podiatric medicine since 1997. These studies were of variable quality. We also discuss the key features of a rigorous trial design. To date, the clinical practice of podiatric medicine is not adequately informed by the best available evidence. We call for more high-quality randomized controlled trials to be undertaken in podiatric medical research.     

Acupuncture trials and informed consent

Participants are often not informed by investigators who conduct randomised, placebo-controlled acupuncture trials that they may receive a sham acupuncture intervention. Instead, they are told that one or more forms of acupuncture are being compared in the study. This deceptive disclosure practice lacks a compelling methodological rationale and violates the ethical requirement to obtain informed consent. Participants in placebo-controlled acupuncture trials should be provided an accurate disclosure regarding the use of sham acupuncture, consistent with the practice of placebo-controlled drug trials.     

基于区块链的临床试验研究

分析临床试验存在的主要问题,介绍区块链技术特征与功能,阐述以私有链为基础的区块链技术在临床试验数据公开、知情同意签署、隐私保护、试验过程监管等方面的应用模式,总结时间戳和智能合约技术对提高临床试验效能的具体方式。     

COVID-19 trial graph: a linked graph for COVID-19 clinical trials

ObjectiveClinical trials are an essential part of the effort to find safe and effective prevention and treatment for COVID-19. Given the rapid growth of COVID-19 clinical trials, there is an urgent need for a better clinical trial information retrieval tool that supports searching by specifying criteria, including both eligibility criteria and structured trial information.Materials and MethodsWe built a linked graph for registered COVID-19 clinical trials: the COVID-19 Trial Graph, to facilitate retrieval of clinical trials. Natural language processing tools were leveraged to extract and normalize the clinical trial information from both their eligibility criteria free texts and structured information from ClinicalTrials.gov. We linked the extracted data using the COVID-19 Trial Graph and imported it to a graph database, which supports both querying and visualization. We evaluated trial graph using case queries and graph embedding.ResultsThe graph currently (as of October 5, 2020) contains 3392 registered COVID-19 clinical trials, with 17 480 nodes and 65 236 relationships. Manual evaluation of case queries found high precision and recall scores on retrieving relevant clinical trials searching from both eligibility criteria and trial-structured information. We observed clustering in clinical trials via graph embedding, which also showed superiority over the baseline (0.870 vs 0.820) in evaluating whether a trial can complete its recruitment successfully.ConclusionsThe COVID-19 Trial Graph is a novel representation of clinical trials that allows diverse search queries and provides a graph-based visualization of COVID-19 clinical trials. High-dimensional vectors mapped by graph embedding for clinical trials would be potentially beneficial for many downstream applications, such as trial end recruitment status prediction and trial similarity comparison. Our methodology also is generalizable to other clinical trials.     

药物临床试验GCP管理平台构建

介绍临床试验GCP管理平台的研究与实现,阐明系统总体架构,从系统管理、试验管理、机构资源管理等方面分析系统功能,指出该系统的应用可以对药物临床试验实现全方位、规范化的信息管理。