Management of quality assurance in clinical trials

Good Clinical Practices (GCP) were first established by the FDA and are now actively implemented by different countries. This becomes necessary as multinational large clinical programs are more complex, involving a large diversity of personnel and locations, with different practices of medicine and local regulatory requirements.

The responsibility of an independent Quality Assurance (QA) organization is to oversee the quality and integrity of research activities, and to assure compliance with company's regulatory requirements, and ethical considerations in order to facilitate worldwide registration of new compounds. The goal of a Clinical QA group is to provide continuous assistance to monitoring teams and investigators to ascertain authentic and reliable clinical trials. The Clinical QA programs must be flexible, calling for active communication and good understanding of quality requirements.

Clinical auditing is one of the instruments of Clinical QA. Study audit activities begin with the protocol, encompass all facets of the clinical trial and end with the final study report.

The focus of the presentation is geared towards auditing activities at investigator's site, purpose of which is to ensure that data gathered in the final clinical study report reflects the raw data collected at the source.     

Culturalising the Abject: Islam,Law and Moral Panic in the West

This paper explores the construction of Islam as abject and the symbolic positioning of Muslims as being outside secular modernity in Australia through an analysis of the way the criminal legal process and perceptions of criminality are culturalised. The empirical focus is gang rape and the trials of Muslim youth on gang rape charges in Sydney between 2000–2003 which quickly became culturally inflected as ‘Muslim’ and ‘Lebanese’ by media reporting of the criminal trials and moral panic about them as source of social menace. Three dimensions of culturalisation of crime and the criminalisation of culture are identified in the criminal legal process and media reporting of it; firstly the cultural inflection of new laws against gang rape by their association with particular events and trials; secondly the introduction of ‘cultural defence’ by the accused as a mitigating factor in the criminal legal process; thirdly, media reporting and commentary on criminal cases which emphasize cultural explanations for individual criminal behaviour.     

跨国公司的北京化与北京的国际化

吸引跨国公司投资现已成为中国政府和包括北京在内的地方政府制定外资政策的主要目标。入世以来,跨国公司在首都经济中扮演了愈发重要的角色。北京与世界跨国公司具有合作的基础和需要,长期合作的关键在于跨国公司的本地化。北京应积极推动跨国公司的北京化,最终实现北京的真正国际化。     

Job‐related stress,social support,and work–family conflict among Mexican workers in a multinational company: A case study of a Korean‐owned,US‐branded former “sweatshop” in Mexico

Due to globalization and outsourcing of commodity production, an estimated 60 million workers are employed in the garment industry by multinational corporations, yet relatively little is known about the work–family tensions experienced by these workers. Building on role stress and job demands–resources theories, this study employed mixed methods to examine job stressors, support, and work–family conflict (WFC) in a sample of 168 Mexican workers in a multinational factory, a rarely studied and underserved population. As hypothesized, results of hierarchical regression analyses indicated that workers experienced high job stress and WFC. Social support from spouses, family, and friends increased the positive association between job stress and WFC, suggesting that culturally relevant obligations increased WFC. This study highlights the need for multinational corporations to implement culturally adaptive, family‐friendly policies. Implications for social workers in multinational work organizations and for future research are discussed.     

Clinical trials integrity: a CRO perspective

When contract research organizations (CROs) were first formed, pharmaceutical companies outsourced to them only certain aspects of the conduct of their clinical trials. At first CROs were highly specialized entities, providing, for example, either biostatistical advice, clinical research associates who monitored investigational sites for regulatory compliance, or regulatory support. Gradually, full service CROs emerged, offering a full range of services for clinical trials, including the selection of investigators and investigational sites, assistance with patient recruitment, safety surveillance and reporting, site audits, and data management and biostatistics. This evolving relationship between CROs and the pharmaceutical and medical device industries has resulted in CROs assuming more and more of the regulatory and ethical risks and responsibilities inherent in the conduct of clinical trials. In this full service role, CROs, unlike sponsors, are not interested in the outcome of study, but like sponsors, are subject to heavy regulation by the federal government, must follow applicable state laws, must respect international guidelines, and are obliged to follow their own operating procedures. Moreover, they are judged by the industry on the basis of the scope and quality of services provided, including the degree of adherence to the research protocol, regulatory requirements, and timelines; the quality of the professional working relationships with investigators and institutions, both academic and community-based; and the validity of the data. Further, CROs are subject to comprehensive audits by sponsoring companies, FDA, and other regulatory authorities. For all these reasons, CROs are being tasked with strict vigilance of all stages of the clinical trial process to ensure that the laws, regulations, and industry standards designed for the protection of human subjects and data integrity are maintained.     

The Meaning of Globalization for Development Policy

The Secretary of State for International Development reviews the Government's development strategy. The core commitment is to help mobilize the international political will to meet the aims of the UN international poverty eradication strategy. This will require resource transfers in the form of aid as investment, if the poorest countries are to be enabled to develop more trade and become part of the global economy. Globalization increases wealth creation, yet there is a danger that some countries could become marginalized from the world economy. To avoid this, developing countries must become full participants on the global economic stage, shaping and influencing the global rules in line with their interests and needs. There are three key challenges at the top of the Government's agenda: (1) the mainstreaming of development issues in the formation of UK and EU policy, (2) encouragement and active support for the efforts of developing countries themselves to become active players on the world economic stage, (3) the building of partnerships to make this happen—with governments, with global economic institutions, with the business sector, with donors and with NGOs. Globalization is characterized by the pace of technological change, the emergence of a more sophisticated system of global economic rules—with the World Trade Organization now at centre stage alongside the IMF and the World Bank—and the increasingly important role of multinational companies. Responding to globalization is not an optional extra. The old models of development need to be rethought. The Department for International Development has a key role to play in this, by ensuring that policy-makers in the UK, within the EU and internationally take full account of development aspects from the outset.     

Under the Influence: The Interplay among Industry,Publishing, and Drug Regulation

The relationships among academe, publishing, and industry can facilitate commercial bias in how drug efficacy and safety data are obtained, interpreted, and presented to regulatory bodies and prescribers. Through a critique of published and unpublished trials submitted to the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for approval of a new antidepressant, vortioxetine, we present a case study of the “ghost management” of the information delivery process. We argue that currently accepted practices undermine regulatory safeguards aimed at protecting the public from unsafe or ineffective medicines. The economies of influence that may intentionally and unintentionally produce evidence-biased—rather than evidence-based—medicine are identified. This is not a simple story of author financial conflicts of interest, but rather a complex tale of ghost management of the entire process of bringing a drug to market. This case study shows how weak regulatory policies allow for design choices and reporting strategies that can make marginal products look novel, more effective, and safer than they are, and how the selective and imbalanced reporting of clinical trial data in medical journals results in the marketing of expensive “me-too” drugs with questionable risk/benefit profiles. We offer solutions for neutralizing these economies of influence.     

中国病人安全立法问题研究

在新医改政策所要达成的长远目标中,病人安全占其首位。解决中国病人安全问题,需要有一个病人安全文化环境。为此,必须重视病人安全立法,创造一个好的制度框架和制度文化环境。本文借鉴丹麦、美国等国家病人安全立法经验,从病人安全事件的定义、建立病人安全事件网络报告制度、病人安全事件自愿报告制度、报告者匿名报告与隐私保护制度、病人安全数据库法律制度、病人安全组织法律制度和政府支持法律制度七个方面,设想了中国病人安全立法的制度安排。     

The inclusion of minority groups in clinical trials: problems of under representation and under reporting of data

Objective: To evaluate the representation of minority groups in randomized control trials (RCTs), and the frequency with which this information is reported. Study Design: Reviewers collected data on the racial/ethnic composition of study samples from all RCTs published in six leading medical journals in 1999. Results: Of the 280 RCTs, most (204, 71.3%) provided no information on the race/ethnicity of participants. Of the 89 U.S.-based RCTs, 50 (56.1%) reported their minority distribution. Relative to other trials, those funded by the National Institute of Health (NIH) (n = 52) were more likely to report race/ethnicity data (55.8% vs. 23.7%; x2 = 20.9, p <_0.001) and to include nonwhite participants (13.5 % vs. 12.5%; x2=22.7, p<_0.001). Conclusion: Minority groups are currently under-represented in clinical trials. Information on the race and ethnicity of clinical trial participants is currently underreported in six leading medical journals. Reporting of minority group information was significantly better only in NIH funded trials, which also were more likely to include nonwhite participants. This suggests that mandatory reporting policies may have a positive effect on both reporting and representation.     

Does globalization benefit developing countries? Effects of FDI on local wages

Two different reactions to globalization (either supporting or opposing globalization) are observed throughout the world. Focusing on the effects on the labor market, we examine whether foreign direct investment benefits workers employed by local establishments in a host developing country. The analysis shows that they received wages above the market-based wage that would otherwise prevail in the absence of foreign establishments. Although concerns exist that growing multinational business might have negative impacts on local workers, this paper suggests that those fears might be unwarranted.     

Are antidepressant and antipsychotic drug trials registered? A cross-sectional analysis of registration and reporting of methodologic characteristics

Introduction: In 2005, the International Committee of Medical Journal Editors (ICMJE) proposed that all submitted trials in all 11 member journals must be prospectively registered in order to be considered for publication. Registering drug trials was meant to reduce the likelihood of selective reporting. The aim was to determine the proportion of antipsychotic and antidepressant trials that were registered.

Methods: We searched in Pubmed for all randomized controlled trials of any antidepressant or antipsychotic published between July and December 2014. The primary objective was to determine the proportion of trials that were registered. Secondary objectives included comparing the reporting of methodological details and positive study findings between registered and unregistered trials.

Results: Of the 67 studies identified, 58% were registered. 75% of the antipsychotic trials and 51% of the antidepressant trials were registered, respectively. Registered trials were more likely to report important methodological details associated with risk of bias in RCTs. There was no significant difference in trials reporting positive outcomes for the study intervention between registered and unregistered trials.

Conclusion: Approximately 60% of published antidepressant and antipsychotic drug trials during July to December 2014 were registered. Unregistered trials were less likely to report important methodological details.     

The Inclusion of Minority Groups in Clinical Trials: Problems of Under Representation and Under Reporting of Data

Objective: To evaluate the representation of minority groups in randomized control trials (RCTs), and the frequency with which this information is reported.

Study Design: Reviewers collected data on the racial/ethnic composition of study samples from all RCTs published in six leading medical journals in 1999.

Results: Of the 280 RCTs, most (204, 71.3%) provided no information on the race/ethnicity of participants. Of the 89 U.S.-based RCTs, 50 (56.1%) reported their minority distribution. Relative to other trials, those funded by the National Institute of Health (NIH) (n = 52) were more likely to report race/ethnicity data (55.8% vs. 23.7%; χ² = 20.9, p ≤ 0.001) and to include nonwhite participants (13.5% vs. 12.5%; χ² = 22.7, p ≤ 0.001).

Conclusion: Minority groups are currently under-represented in clinical trials. Information on the race and ethnicity of clinical trial participants is currently underreported in six leading medical journals. Reporting of minority group information was significantly better only in NIH funded trials, which also were more likely to include nonwhite participants. This suggests that mandatory reporting policies may have a positive effect on both reporting and representation.     

Letters to the editor

This article proposes that an assessment of commercial feasibility should be integrated as a prerequisite for human clinical testing to improve the quality and relevance of materials being investigated, as an ethical aspect for human subject protection, and as a means of improving accountability where clinical development is funded on promises of successful translational research. A commercial feasibility analysis is not currently required to justify human clinical testing, but is assumed to have been conducted by industry participants, and use of public funds for clinical trials should be defensible in the same manner. Plant-made vaccines (PMVs) are offered in this discussion as a model for evaluating the relevance of commercial feasibility before human clinical testing. PMVs have been proposed as a potential solution for global health, based on a vision of immunizing the world against many infectious diseases. Such a vision depends on translating current knowledge in plant science and immunology into a potent vaccine that can be readily manufactured and distributed to those in need. But new biologics such as PMVs may fail to be manufactured due to financial or logistical reasons—particularly for orphan diseases without sufficient revenue incentive for industry investment—regardless of the effectiveness which might be demonstrated in human clinical testing. Moreover, all potential instruments of global health depend on translational agents well beyond the lab in order to reach those in need. A model comprising five criteria for commercial feasibility is suggested for inclusion by regulators and ethics review boards as part of the review process prior to approval of human clinical testing. Use of this model may help to facilitate safe and appropriate translational research and bring more immediate benefits to those in need.     

Adverse events reporting--the tip of an iceberg

NIH data indicate that annually seven million human subjects are enrolled in research sponsored by NIH alone. In addition, there are sixteen federal agencies and numerous departments outside NIH conducting experiments with human subjects. Moreover, the pharmaceutical industry spends $26 billion on research (compared to $16 billion for NIH), thus, the total number of human subjects enrolled in research for both the public and private sectors can be estimated as high as nineteen million. I present data on the potential magnitude of adverse events in the United States among human subjects enrolled in research that appear to be unreported and unaccounted for. We obtained data from the Office for Human Research Protections (OHRP) through the Freedom of Information Act for the years 1990 to August 2000 regarding all Institutional Incident Reports (IRPTs) and a list of Compliance Oversight Branch Investigations (COBIs) involving Multiple Project Assurances (MPAs). In the ten years of reporting for nearly seventy million human subjects, there were only 878 IRPTs and 41 investigations. From the incident reports to OHRP, 44% involved adverse events. Those projects investigated for Multiple Project Assurances violations (41 such investigations) showed that 51% were suspended or terminated. The number of deaths reported to OHRP in ten years for the seventy million human subjects is merely eight. The anticipated number of deaths among the general population in seventy million (assuming subject's duration in trials is one month) is 51,000. The number of suicides and attempted suicides alone among the seventy million expected research subjects can be anticipated to be about 5,000. Therefore, the number of expected deaths should have been between 5,000 and 51,000. These numbers and percentages represent minimal numbers since they are not a result of random audits or investigations, but a result of self-reporting or an exogenous complaint. Despite the fact that these are conservative estimates, they represent a significant problem. The purpose of this paper is to present the potential boundaries and magnitude of the problem in the current use of human subjects in research. This is a call for responsible institutions to undertake a thorough evaluation of the problem in order to obtain accurate information. For the immediate future, strong actions need to be taken to increase the protection of human subjects enrolled in research. This precautionary policy is prudent in light of recent revelations and data from this investigation.     

Assessing commercial feasibility: a practical and ethical prerequisite for human clinical testing

This article proposes that an assessment of commercial feasibility should be integrated as a prerequisite for human clinical testing to improve the quality and relevance of materials being investigated, as an ethical aspect for human subject protection, and as a means of improving accountability where clinical development is funded on promises of successful translational research. A commercial feasibility analysis is not currently required to justify human clinical testing, but is assumed to have been conducted by industry participants, and use of public funds for clinical trials should be defensible in the same manner. Plant-made vaccines (PMVs) are offered in this discussion as a model for evaluating the relevance of commercial feasibility before human clinical testing. PMVs have been proposed as a potential solution for global health, based on a vision of immunizing the world against many infectious diseases. Such a vision depends on translating current knowledge in plant science and immunology into a potent vaccine that can be readily manufactured and distributed to those in need. But new biologics such as PMVs may fail to be manufactured due to financial or logistical reasons--particularly for orphan diseases without sufficient revenue incentive for industry investment--regardless of the effectiveness which might be demonstrated in human clinical testing. Moreover, all potential instruments of global health depend on translational agents well beyond the lab in order to reach those in need. A model compromising five criteria for commercial feasibility is suggested for inclusion by regulators and ethics review boards as part of the review process prior to approval of human clinical testing. Use of this model may help to facilitate safe and appropriate translational research and bring more immediate benefits to those in need.     

Recent Trends in TANF Caseloads and the Status of TANF Recipients in West Virginia and Selected States Outside of Appalachia

Abstract

The author examines the trends in TANF caseloads in West Virginia and selected states outside of Appalachia while including national trend data for further comparisons. State administrative data on the reasons for case closures is also reviewed. The major findings indicate that caseload declines accelerated in each state, as well as nationally, after the passage of PRWORA in 1996. National declines are resulting in an increasing concentration of Hispanics and minorities among TANF recipients. Administrative data indicates that one-third or fewer of the selected states' closures were attributed to employment. While states have improved their tracking systems, there is still some uncertainty surrounding the reasons for closures. This suggests the need for further research on data reporting.     

When safety culture backfires: Unintended consequences of half-shared governance in a high tech workplace

This paper applies concepts from the sociology and anthropology of organizations to understand limits to the implementation of a more effective safety culture in the workplace. It highlights unintended consequences of combining bureaucratic control and shared governance and identifies sources of inertia within already existing safety cultures. The data come from focus group interviews with workers in a research and development facility of a multinational corporation in the Western U.S. It is found that safety protocols, rules, and rhetoric, combined with efforts to give workers more responsibility for safety in the workplace, create tendencies toward worker alienation, shame with regard to injuries, complacency, and fear of bureaucratic processes. Therefore it appears that some efforts to create safety culture in the workplace may unintentionally undermine the goal of manufacturing safety.     

Educational Policy, Politics, and Mixed Heritage Students in the United States

This article describes local, state, and federal policies related to collecting, aggregating, and reporting data on student race and ethnicity in U.S. K-12 and postsecondary education. It traces data policy from the 1997 decision by the Office of Management and Budget to change from single-race reporting to a format that permits respondents to choose more than one race, to the October 2007 issuance of final guidance from the Department of Education. Taking a K-20 perspective, I consider how policies for data collection and reporting may affect educational and developmental outcomes for students, as well as local, state, and national education policy environments.     

全球化与场域精神：麦当劳在东亚城市的“文化定制”逻辑

全球化的故事并非文化的同质化。麦当劳在东亚城市的推进过程中,更多的是“文化定制”的结果--麦当劳所传递的不是完全同质化的美国文化,而是美式文化内核与地方文化生境碰撞而产生的特殊的全球地方化经验,其在东亚这个特定的文化场域内遵循着一整套的行动逻辑。地方文化虽然在成长,但总体上被全球文化所裹挟并吞噬。需要关注的是,麦当劳极具技巧地引导地方在参与“文化浅层定制”的过程中,逐步由“文化自觉”转变为“文化不自觉”。要启发地方由“文化不自觉”回归到“文化再自觉”,必须反思以乡村为主体的“文化自觉”类型本身在全球城市化背景下表达的有效性和代表性,城市和城市人的文化自觉应被予以更多的关注。     

代工产业中的劳工团结:以兴达公司员工委员会试验为例

中国沿海地区兴起的出口代工产业存在血汗工厂的现象与这一地区跨国品牌外来资本本地政府外来工人这一独特的产业生态密切相关,全球化力量正在改变传统的劳动保护模式。本文论述的是沿海地区一家代工企业在跨国网络的力量促进下进行的一项工会试验,与中国组合主义的工会模式不同的是,兴达公司的这项企业内部工会试验得到了资本方、跨国品牌、国际倡议网络的有力支持,从而说明这种内部工会模式对于增进工人团结的积极意义和有限性。