Design of Vaccine Equivalence/Non-Inferiority Trials with Correlated Multiple Binomial Endpoints

Immunogenicity trials that study the immune responses to vaccination are often used in the vaccine development process as alternatives to clinical efficacy trials. The comparisons of immune responses among various treatment groups are conducted in a non-inferiority or equivalence framework. When there exists a level of immune response that correlates with protection against disease, it is of interest to compare the proportion of responders as defined as response above a specific level or as a predefined increase in immune levels for post-vaccination levels above pre-vaccination levels. Since vaccines often contain several antigens, the correlations between the immune responses need to be taken into account in the analysis. In this paper, we describe appropriate testing methods for demonstrating the non-inferiority/equivalence of two treatments on each of the binomial endpoints. We conduct a comprehensive simulation study to shed light on how the Type I error and power are affected and to what extent when correlated multiple binomial endpoints are present in the vaccine trials. We also illustrate the computation of power for assessment of non-inferiority/equivalence in real studies.     

Tensions among siblings in parent care

From a place of “genealogical equivalence” as children of their parents, siblings spend a lifetime developing separate identities. As parents near the end of their lives, issues of sibling equivalence are renegotiated in the face of equal obligations to provide care and equal entitlement to parent assets. In this paper, we hypothesize how unresolved issues of rivalry for parent affection/attention among siblings may be reasserted when parents need care. Data are drawn from a project about how parent care and assets are shared. In-depth interviews with three sibling groups experiencing conflict over sharing parent care and assets along with six Canadian legal case portrayals of disputes among siblings over how parent care and assets were shared are examined. Findings are that disputes occur when siblings perceive others as dominating parent care and assets through tactics such as separating the parent from other siblings and preventing other siblings from being engaged in decisions about care and assets. Discussion is focused on paradoxes faced by siblings given expectations for equity in parent relationships alongside perceived pre-eminence in care and asset decisions. Because the legal cases are part of public record, actual names are used in reporting and referencing these data. Pseudonyms were assigned to siblings from caregiving families who were interviewed.     

Methodological issues in the obsessive–compulsive spectrum

The obsessive–compulsive spectrum is a heterogeneous class of conditions. Recently, expert consensus has emerged regarding possible candidate disorders [Mataix-Cols, D., Petrusa, A., Leckman, J.F., 2007. Issues for DSM-V: How should obsessive–compulsive and related disorders should be classified. American Journal of Psychiatry, 164, 1313–1314]. Further, expert survey data suggest that obsessive-compulsive disorder is composed of overlapping subtypes. However, methodological approaches for testing whether candidate disorders properly belong in the spectrum have varied widely, and do not necessarily differentiate conditions from subtypes. We describe preliminary methodological and statistical recommendations for a systematic approach to determining what constitutes a subtype, how to determine inclusion in the spectrum, and means for ruling out candidate disorders.     

Translation and equivalence: the Profile of Mood States Short Form in English and Chinese

As international research collaborations increase, health care professionals are becoming more aware of the advantages of using common measures to compare outcomes of assessments across cultures. Measuring mood states across diverse cultures is important for understanding the universal aspects of mood and measuring outcomes of nursing interventions. The purpose of this article is to describe the process used to translate the Profile of Mood States Short Form from English to Chinese and to assess the equivalence of this instrument in the two languages. The translated Chinese version of the instrument was found to be as reliable as the original English version and is appropriate for use with Chinese elders who speak either Mandarin or Taiwanese.     

A Model of Equivalence in the Cultural Adaptation of HRQoL Instruments: The Universalist Approach

The health-related quality of life (HRQoL) literature presents a confused picture of what ‘equivalence’ in the cross-cultural use of HRQoL questionnaires means and how it can be assessed. Much of this confusion can be attributed to the ‘absolutist’ approach to the cross-cultural adaptation of HRQoL questionnaires. The purpose of this paper is to provide a model of equivalence from a universalist perspective and to link this to the translation and adaptation of HRQoL questionnaires. The model evolved from reviews of the HRQoL and other literatures, interviews and discussions with researchers working in HRQoL and related areas and practical experience in the adaptation and development of HRQoL instruments. The model incorporates six key types of equivalence. For each type of equivalence the paper provides a definition, proposes various strategies for examining whether and how types of equivalence can be achieved, illustrates the relationships between them and suggests the order in which they should be tested. The principal conclusions are: (1) that a universalist approach to the cross-cultural adaptation of HRQoL instruments requires that six types of equivalence be taken into account; (2) that these are sufficient to describe and explain the nature of the cross-cultural adaptation process; (3) that this approach requires careful qualitative research in target cultures, particularly in the assessment of conceptual equivalence; and (4) that this qualitative work will provide information which will be fundamental in deciding whether to adapt an existing instrument and which instrument to adapt. It should also result in a more sensitive adaptation of existing instruments and provide valuable information for interpreting the results obtained using HRQoL Instruments in the target culture. This revised version was published online in June 2006 with corrections to the Cover Date.     

用传统显著性检验方法进行等效性检验的规律研究

目的:研究传统显著性检验同等效性检验的联系规律,并探讨在传统显著性检验结果为P>α时,依据等效性界值结合本研究结果下等效结论的可能性。方法:在MATLAB软件上编程进行模拟研究。其中,编写程序的正确性均通过了SPSS13.0软件和EquivTestTM2.0软件的验证。结果:得到了各种情形下基于传统显著性检验P值进行等效性判定的标准,以及不同判定标准下作等效性判定的判错率,并以方便查询的表格形式表达出来。判错率与P值间呈三次模型关系。结论:各医药专业研究人员不必专门系统地学习等效性检验的理论,而可据本研究结果直接利用传统显著性检验方法作出是否等效的判断。     

Comparison of Two Methods for Measuring Ultrasound Properties of the Heel in Postmenopausal Women

Combined indices of ultrasound measurements have been proposed, such as "stiffness index" (SI) for the Lunar Achilles+ and 'quantitative ultrasound index' (QUI) for the Hologic Sahara ultrasound devices. We used the Bland and Altman approach and the kappa (kappa) score (classifying women by tertile, independent of age) to compare these methods. We studied 105 postmenopausal women (ages 57 to 88 years). We measured the heel (in duplicate) using both devices. Single lumbar spine (LS) bone mineral density (BMD) measurements were also made using the same two manufacturers' densitometers. QUI values were higher than SI values with a mean difference of 2.4 units (95% CI, 1.5-3.2). This difference in SI and QUI was most marked at higher ultrasound values (r = 0.61, p<0.0001). The kappa score between SI and QUI was 0.69 (95% CI, 0.57-0.80). When we calculated the kappa scores based on the mean of duplicate SI and QUI measurements, the kappa score increased to 0.90 (95% CI, 0.77-0.94). Lunar DPX LS-BMD values were higher than Hologic QDR 1000/W LS-BMD values with a mean difference of 0.18 g/cm2 (95% CI, 0.17-0.19). The difference between the machines was most marked at higher BMD values (r = 0.38, p<0.001). The kappa score between the DPX and QDR 1000/W was good (kappa = 0.79, 95% CI = 0.66-0.88), and was similar to the agreement of SI and QUI. Based on a single measurement, some women would be classified in different tertiles using the two heel ultrasound machines (about 20%). However, this is not significantly greater than the misclassification rate using two machines to measure spinal BMD (about 15%). Although there are significant differences between SI and QUI measurements, the misclassification rates are similar to those observed measuring LS-BMD using two different manufacturers' DXA machines. The misclassification rate using quantitative ultrasound improves when based on duplicate measurements.     

项目反应理论在医学量表测量误差估计中的应用

目的探讨项目反应理论在医学量表测量误差估计中的应用.方法以国际前列腺增生量表为实例,根据项目反应理论的方法,利用信息函数从测量值中分离出测量误差,以其3倍作为量表测量误差的上限.结果获得了治疗前后每个受试者IPSS总分的测量误差,以1.5作为IPSS总分的最大测量误差.结论项目反应理论是提取医学量表测量误差的有效方法,以其3倍作为其测量误差上限是合理的.     

Shorter vs Longer Immobilization After Surgery for Thumb Carpometacarpal Osteoarthritis: A Propensity Score-Matched Study

ObjectiveTo investigate if shorter immobilization is noninferior to longer immobilization after Weilby procedure for thumb carpometacarpal osteoarthritisDesignProspective cohort study with propensity score matching.SettingData collection took place in 16 outpatient clinics for hand surgery and hand therapy.ParticipantsA total of 131 participants with shorter immobilization and 131 participants with longer immobilization (N=262).InterventionShorter immobilization (3-5 days plaster cast followed by a thumb spica orthosis including wrist until 4 weeks postoperatively) was compared with longer immobilization (10-14 days plaster cast followed by a thumb spica orthosis including wrist until 6 weeks postoperatively) after Weilby procedure for first carpometacarpal joint osteoarthritis. Propensity score matching was used to control for confounders.Main Outcome MeasuresOutcomes were pain measured with a visual analog scale and hand function measured with the Michigan Hand Outcomes Questionnaire at 3 and 12 months. Secondary outcomes were complications, range of motion, grip and pinch strength, satisfaction with treatment, and return to work.ResultsNo significant differences were found in visual analog scale pain (effect size, 0.03; 95% confidence interval [CI], −0.21 to 0.27) or the Michigan Hand Outcomes Questionnaire (effect size, 0.01; 95% CI, −0.23 to 0.25) between the groups at 3 months or at 12 months. Furthermore, no differences were found in complication rate or in other secondary outcomes.ConclusionsIn conclusion, shorter immobilization of 3-5 days of a plaster cast after Weilby procedure is equal to longer immobilization for outcomes on pain, hand function, and our secondary outcomes. These results indicate that shorter immobilization is safe and can be recommended, since discomfort of longer immobilization may be prevented and patients may be able to recover sooner, which may lead to reduced loss of productivity. Future studies need to investigate effectiveness of early active and more progressive hand therapy following first carpometacarpal joint arthroplasty.     

安静条件下语句识别表的等价性研究

目的 通过对解放军总医院研制的12张普通话儿童语句测听词表的难度等价性研究,判断该套材料是否符合言语测听材料的标准,以期挑选出具有难度一致性的词表应用于临床.方法 选取36名听力正常青年受试者,采用听说复述的方式,进行12组句表的测试(每组句表有50个关键词),以关键词计分,然后对各表得分进行统计学分析.结果 进行双因素(表号和强度)方差分析和Post-Hoc两两比较,12张测试表无统计学差异.结论 12张语句识别表具有较好的难度等价性,可应用于临床测试和实验研究.