Fisher information matrix for nonlinear mixed effects multiple response models: Evaluation of the appropriateness of the first order linearization using a pharmacokinetic/pharmacodynamic model

We focus on the Fisher information matrix used for design evaluation and optimization in nonlinear mixed effects multiple response models. We evaluate the appropriateness of its expression computed by linearization as proposed for a single response model. Using a pharmacokinetic–pharmacodynamic (PKPD) example, we first compare the computation of the Fisher information matrix with approximation to one derived from the observed matrix on a large simulation using the stochastic approximation expectation–maximization algorithm (SAEM). The expression of the Fisher information matrix for multiple responses is also evaluated by comparison with the empirical information obtained through a replicated simulation study using the first‐order linearization estimation methods implemented in the NONMEM software (first‐order (FO), first‐order conditional estimate (FOCE)) and the SAEM algorithm in the MONOLIX software. The predicted errors given by the approximated information matrix are close to those given by the information matrix obtained without linearization using SAEM and to the empirical ones obtained with FOCE and SAEM. The simulation study also illustrates the accuracy of both FOCE and SAEM estimation algorithms when jointly modelling multiple responses and the major limitations of the FO method. This study highlights the appropriateness of the approximated Fisher information matrix for multiple responses, which is implemented in PFIM 3.0, an extension of the R function PFIM dedicated to design evaluation and optimization. It also emphasizes the use of this computing tool for designing population multiple response studies, as for instance in PKPD studies or in PK studies including the modelling of the PK of a drug and its active metabolite. Copyright © 2009 John Wiley & Sons, Ltd.     

One‐ and two‐stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint

Phase II clinical trials are performed to investigate whether a novel treatment shows sufficient promise of efficacy to justify its evaluation in a subsequent definitive phase III trial, and they are often also used to select the dose to take forward. In this paper we discuss different design proposals for a phase II trial in which three active treatment doses and a placebo control are to be compared in terms of a single‐ordered categorical endpoint. The sample size requirements for one‐stage and two‐stage designs are derived, based on an approach similar to that of Dunnett. Detailed computations are prepared for an illustrative example concerning a study in stroke. Allowance for early stopping for futility is made. Simulations are used to verify that the specified type I error and power requirements are valid, despite certain approximations used in the derivation of sample size. The advantages and disadvantages of the different designs are discussed, and the scope for extending the approach to different forms of endpoint is considered. Copyright © 2008 John Wiley & Sons, Ltd.     

学生课堂教学质量评价问题浅析

综合分析河南中医学院近三年以来学生课堂教学质量评价反馈的信息，认为引发课堂教学评价偏差的人为因素有评价者的能力水平、责任心、情感倾向。其对策为：改变教师的被动地位，进一步修订评价体系，加强对组织评价者的培训，强化临床课的教学，进一步提高学生的认识，跟踪调查课堂教学质量评价。     

化学实验进行开放式教学的研究

通过与传统的化学实验教学模式的比较，详述了开放式教学模式的特点，并且针对实施过程中所遇到的问题提出了详尽的解决方案。     

关于护理院校日语教学的探讨

在护理专业院校教学中以护理专业知识为重点，如何遵循教学宗旨，培养个性化人才，使日话教学从普通的公共学科中脱颖而出，是护理院校日语教师教学工作的重中之重。     

Guidelines for Trials of Behavioral Treatments for Recurrent Headache, First Edition: American Headache Society Behavioral Clinical Trials Workgroup

Guidelines for design of clinical trials evaluating behavioral headache treatments were developed to facilitate production of quality research evaluating behavioral therapies for management of primary headache disorders. These guidelines were produced by a Workgroup of headache researchers under auspices of the American Headache Society. The guidelines are complementary to and modeled after guidelines for pharmacological trials published by the International Headache Society, but they address methodologic considerations unique to behavioral and other nonpharmacological treatments. Explicit guidelines for evaluating behavioral headache therapies are needed as the optimal methodology for behavioral (and other nonpharmacologic) trials necessarily differs from the preferred methodology for drug trials. In addition, trials comparing and integrating drug and behavioral therapies present methodological challenges not addressed by guidelines for pharmacologic research. These guidelines address patient selection, trial design for behavioral treatments and for comparisons across multiple treatment modalities (eg, behavioral vs pharmacologic), evaluation of results, and research ethics. Although developed specifically for behavioral therapies, the guidelines may apply to the design of clinical trials evaluating many forms of nonpharmacologic therapies for headache.     

Some practical perspectives for educating gifted children

This article identifies common characteristics of educationally related programs that form a common basis for understanding and working with gifted programs. Special approaches and programs for educational enrichment as well as specific activities that have been successful are discussed.     

The short-term stability of student ratings of instruction in medical school

The purpose of this study was to assess the degree of consistency in student ratings of teacher effectiveness during the first year of medical school. Student ratings of teaching effectiveness represent a commonly used source of information that enters into the academic decision-making process. In medical school, student evaluations often represent a major source of information that is used in promotion and tenure decisions. It is essential that the precision of such ratings be ascertained so that decision-makers will know how much confidence to place in this source of information on teaching effectiveness. In this study, each member of a first-year medical school class was randomly assigned a two-digit identification number at the beginning of the spring semester, 1986. As the semester progressed students were asked to evaluate each full-time teacher in three major courses. Multiple instructors were utilized in each course (n = 10). Each teacher was evaluated immediately after lectures during the first (T1) and second (T2) halves of the course. Students evaluated the teacher a third time (T3) as part of the end-of-semester overall course evaluation. The teachers were evaluated on a short eight-item Likert-type scale that identified several key indicators of effective teaching. Students attached their anonymous identification numbers to individual ratings so that their responses could be matched in the analysis. The results indicate that medical students are only moderately consistent in the extent to which they evaluate teachers. This inconsistency varied by course and by instructors within courses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Local health services: some lessons from their evolution in Bolivia

Summary For a decade, numerous projects in Bolivia have tried to put in practice the concept of local health systems. But, so far, no significant changes have been made and local health services still are the 'poor relation' of the system. The main components of the project—expansion of health facilities, training of health personnel and institutional decentralization—were not designed to respond to the complexity of the problems encountered. Decentralization was implemented at the level of health districts but not accompanied by redefinition of functions at the central level, and challenged by civil servants' attempts to save their jobs. While training activities did introduce new methods and subjects, they were too often reduced to short workshops or seminars. Health facilities were built without regard for their significance beyond health care. A strategic approach is needed to adapt the planning process to the degree of liberty allowed by society.     

Medical student abuse: perceptions and experience

Summary. A questionnaire containing 18 vignettes of common clinical educational situations with potentially abusive treatment of medical students and a 10-item attitude assessment about abusive behaviour were administered to the first-and fourth-year medical students at a mid-west US university medical school. The first- and fourth-year groups did not differ significantly on perceived abusiveness of most of the vignettes, although several of the individual vignettes were perceived significantly differently by the two groups. As hypothesized, the fourth-year students had experienced such situations more frequently. Attitudes towards abusive behaviour did not differ between the two groups. The authors contrast teaching interactions perceived as educationally useful and not abusive with those seen as abusive and not useful and offer explanations for the differences observed. Finally, the possible implications of the results for medical education are discussed.