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91.
More than fifteen years ago, it was noted that the failure rate of antidepressant clinical trials was high, and such negative outcomes were thought to be related to the increasing magnitude of placebo response. However, there is considerable debate regarding this phenomenon and its relationship to outcomes in more recent antidepressant clinical trials. To investigate this, we accessed the US Food and Drug Administration (FDA) reviews for sixteen antidepressants (85 trials, 115 trial arms, 23,109 patients) approved between 1987 and 2013. We calculated the magnitude of placebo and antidepressant responses, antidepressant‐placebo differences, as well as the effect sizes and success rates, and compared these measures over time. Exploratory analysis investigated potential changes in trial design and conduct over time. As expected, the magnitude of placebo response has steadily grown in the past 30 years, increasing since 2000 by 6.4% (r=0.46, p<0.001). Contrary to expectations, a similar increase has occurred in the magnitude of antidepressant response (6.0%, r=0.37, p<0.001). Thus, the effect sizes (0.30 vs. 0.29, p=0.42) and the magnitude of antidepressant‐placebo differences (10.5% vs. 10.3%, p=0.37) have remained statistically equivalent. Furthermore, the frequency of positive trial arms has gone up in the past 15 years (from 47.8% to 63.8%), but this difference in frequency has not reached statistical significance. Trial design features that were previously associated with a possible lower magnitude of placebo response were not implemented, and their relationship to the magnitude of placebo response could not be replicated. Of the 34 recent trials, two implemented enhanced interview techniques, but both of them were unsuccessful. The results of this study suggest that the relationship between the magnitude of placebo response and the outcome of antidepressant clinical trials is weak at best. These data further indicate that antidepressant‐placebo differences are about the same for all of the sixteen antidepressants approved by the FDA in the past thirty years.  相似文献   
92.
Adipose-derived stem cells (ASCs) are mesenchymal stem cells (MSCs) that are obtained from abundant adipose tissue, adherent on plastic culture flasks, can be expanded in vitro, and have the capacity to differentiate into multiple cell lineages. Unlike bone marrow-derived MSCs, ASCs can be obtained from abundant adipose tissue by a minimally invasive procedure, which results in a high number of cells. Therefore, ASCs are promising for regenerating tissues and organs damaged by injury and diseases. This article reviews the implications of ASCs in tissue regeneration.  相似文献   
93.
There is an alleged tension between undue inducement and exploitation in research trials. This paper considers claims that increasing the benefits to research subjects enrolled in international, externally‐sponsored clinical trials should be avoided on the grounds that it may result in the undue inducement of research subjects. It proceeds from the premise that there are good grounds for thinking that, at least some, international research sponsors exploit trial participants because they do not provide the research population with a fair share of the benefits of research. This provides a prima facie argument for increasing the benefits for research participants. Concern over undue inducement is a legitimate moral concern; however, if this concern is to prevent research populations from receiving their fair share of benefits from research there must be sufficient evidence that these benefits will unduly influence patients’ decision‐making regarding trial participation. This article contributes to the debate about exploitation versus undue inducement by introducing an analysis of the available empirical research into research participants’ motivations and the influence of payments on research subjects’ behaviour and risk assessment. Admittedly, the available research in this field is limited, but the research that has been conducted suggests that financial rewards do not distort research subjects’ behaviour or blind them to the risks involved with research. Therefore, I conclude that research sponsors should prioritise the prevention of exploitation in international research by providing greater benefits to research participants.  相似文献   
94.
Both cucumber mosaic virus (CMV) and tobacco mosaic virus (TMV) coat protein (CP) genes have been transferred to chilli pepper (Capsicum annuum var. Longunt) cultivar 8212 by a modified procedure of Agrobacterium tumefaciens-mediated transformation using hypocotyl as the explant. PCR analysis revealed the presence of both CMV and TMV CP genes in at least 11 primary transformants out of 49 kanamycin-resistant chili pepper plants. Ten T1 lines from five independent transformation events were identified as putative homozygous transgenic lines based on the rooting assay of their T2 seedlings on the kanamycin-containing media. Integration and expression of CMV CP and TMV CP transgenes in one of the homozygous line, 16-13, were confirmed bySouthern blot, RT-PCR and western blot analyses. Line 16-13 was highly resistant to infection of homologous CMV and TMV strains in greenhouse conditions when successively challenged with CMV and TMV or challenged with TMV alone.Futhermore, field trials on T2, T3 and T4 progenies of Line 16-13 were performed on scales of 123, 300 and 10,000 plants, respectively, in consecutive years 1996, 1997 and 1998 with the permission of the Chinese government authority. The transgenic plants displayed delayed symptom development and significantly milder disease severity in field conditions when compared to untransformed chili pepper plants, resulting in 47 and 110% increase in pepper fruit yield in surveys conducted in 1997 and 1998 trials, respectively. Finally, quality analysis and biosafety assesment were performed on transgenic chili pepper fruit concurrently with the control fruit, and demonstrated that the transgenic chili pepper fruit is substantially equivalent to the non-transgenic pepper in terms of the quality and biosafety when consumed as a food additive.  相似文献   
95.
96.
An ethical analysis of Jordan's Clinical Research Law, which became effective in 2001, was performed. Accordingly, this paper discusses the major components, key strengths and weaknesses of this law. As an initial effort, the Law addresses important aspects of research ethics and, hence, should serve as an example for other Arab Countries in the Middle East. Unique aspects of the Law include the requirement that those conducting any study have insurance that can compensate for research injuries and a system of fines and punishments for noncompliance with the Law. There are, however, some key items missing in the Jordanian Law. For example, the Law does not mention the requirement of a favourable assessment of risks and benefits, the fair selection of subjects, or articles regarding the protection of the rights and welfare of children and other vulnerable subjects participating in research. The paper concludes with the suggestion that new amendments should be considered for future revisions of the Clinical Research Law in Jordan.  相似文献   
97.
This paper reports on a multidisciplinary meeting held to discuss ethical issues in medical research in the developing world. Many studies, including clinical trials, are conducted in developing countries with a high burden of disease. Conditions under which this research is conducted vary because of differences in culture, public health, political, legal and social contexts specific to these countries. Research practices, including standards of care for participants, may vary as a result. It is therefore not surprising that ethical issues emerge. This meeting sought to identify and discuss these issues from the perspectives of the many actors in such research, including community representatives, with a view to finding ethical and pragmatic solutions to these issues. Dialogue between these actors was also promoted, with a view to identifying the need to develop such dialogue in future.
Drawing from the experiences of the speakers, the colloquium attempted to outline some answers to several key questions characterising the field today. Experiences related to epidemiologic research, vaccine trials, drug trials, diagnostic tests and to some fundamental ethical issues in health research. Speakers were from different countries, disciplines and professions. The meeting provided a forum for consultation and debate between different ethics actors. Both encouraging findings and challenges emerged.  相似文献   
98.
Circulating endothelial progenitor cells (EPCs) have been demonstrated to correlate negatively with vascular endothelial dysfunction and cardiovascular risk factors. However, translation of basic research into the clinical practice has been limited by the lack of unambiguous and consistent definitions of EPCs and reduced EPC cell number and function in subjects requiring them for clinical use. This article critically reviews the definition of EPCs based on commonly used protocols, their value as a biomarker of cardiovascular risk factor in subjects with cardiovascular disease, and strategies to enhance EPCs for treatment of ischemic diseases.  相似文献   
99.
Bayesian clinical trial designs offer the possibility of a substantially reduced sample size, increased statistical power, and reductions in cost and ethical hazard. However when prior and current information conflict, Bayesian methods can lead to higher than expected type I error, as well as the possibility of a costlier and lengthier trial. This motivates an investigation of the feasibility of hierarchical Bayesian methods for incorporating historical data that are adaptively robust to prior information that reveals itself to be inconsistent with the accumulating experimental data. In this article, we present several models that allow for the commensurability of the information in the historical and current data to determine how much historical information is used. A primary tool is elaborating the traditional power prior approach based upon a measure of commensurability for Gaussian data. We compare the frequentist performance of several methods using simulations, and close with an example of a colon cancer trial that illustrates a linear models extension of our adaptive borrowing approach. Our proposed methods produce more precise estimates of the model parameters, in particular, conferring statistical significance to the observed reduction in tumor size for the experimental regimen as compared to the control regimen.  相似文献   
100.
Wages NA  Conaway MR  O'Quigley J 《Biometrics》2011,67(4):1555-1563
Summary Much of the statistical methodology underlying the experimental design of phase 1 trials in oncology is intended for studies involving a single cytotoxic agent. The goal of these studies is to estimate the maximally tolerated dose, the highest dose that can be administered with an acceptable level of toxicity. A fundamental assumption of these methods is monotonicity of the dose–toxicity curve. This is a reasonable assumption for single‐agent trials in which the administration of greater doses of the agent can be expected to produce dose‐limiting toxicities in increasing proportions of patients. When studying multiple agents, the assumption may not hold because the ordering of the toxicity probabilities could possibly be unknown for several of the available drug combinations. At the same time, some of the orderings are known and so we describe the whole situation as that of a partial ordering. In this article, we propose a new two‐dimensional dose‐finding method for multiple‐agent trials that simplifies to the continual reassessment method (CRM), introduced by O'Quigley, Pepe, and Fisher (1990, Biometrics 46 , 33–48), when the ordering is fully known. This design enables us to relax the assumption of a monotonic dose–toxicity curve. We compare our approach and some simulation results to a CRM design in which the ordering is known as well as to other suggestions for partial orders.  相似文献   
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