阶梯设计试验研究方法及报告规范

阶梯设计是在服务提供和政策评估领域出现的一种新兴的整群随机对照试验设计,近年来逐渐受到医疗卫生领域研究者的重视.阶梯设计试验不需要设置专门的对照组,在资源有限只能分步实施干预的情况下仍保持传统随机对照试验的优势.本文从基本原理、适用情况、特点、设计类型、数据统计分析方法和相关报告规范等方面对阶梯设计试验进行了综述,旨在...     

真实世界研究与随机对照试验、单病例随机对照试验在临床治疗性研究中的关系比较

真实世界研究、随机对照试验及单病例随机对照试验在设计及具体的实施环节上存在明显不同.随机对照试验属于新治疗措施实施前的研究,真实世界研究属于新治疗措施实施后的研究.两者不是对同一个问题的平行论证,而是承启关系.精心设计的随机对照试验是临床上任何干预措施效果评价的基础,其结果需要真实世界研究的进一步验证及拓展补充,综合考虑二者才是最佳的选择.单病例随机对照试验更易在短时间内获得一些特殊病例的信息,是随机对照试验结果的良好补充,也是一定条件下最经济的真实世界研究.临床工作及其研究是十分复杂的过程.不同个体虽患同种疾病,但临床表现互有差异,且临床反应的变化也不尽相同.因此,无法获得同一干预措施下不同个体的相同治疗效果;加之有的治疗措施缺乏真实性和实用价值,从而使得疗效评价成为一个难题.近些年来,普遍采用试验性的研究结果作为证据指导临床实践活动,其中以随机对照试验(RCT)最为受到重视,但由于RCT属于药物面市前研究,对研究对象的选择、治疗措施的应用等均有严格的限定.     

真实世界研究与随机对照试验、单病例随机对照试验在临床治疗性研究中的关系比较

真实世界研究、随机对照试验及单病例随机对照试验在设计及具体的实施环节上存在明显不同.随机对照试验属于新治疗措施实施前的研究,真实世界研究属于新治疗措施实施后的研究.两者不是对同一个问题的平行论证,而是承启关系.精心设计的随机对照试验是临床上任何干预措施效果评价的基础,其结果需要真实世界研究的进一步验证及拓展补充,综合考虑二者才是最佳的选择.单病例随机对照试验更易在短时间内获得一些特殊病例的信息,是随机对照试验结果的良好补充,也是一定条件下最经济的真实世界研究.临床工作及其研究是十分复杂的过程.不同个体虽患同种疾病,但临床表现互有差异,且临床反应的变化也不尽相同.因此,无法获得同一干预措施下不同个体的相同治疗效果;加之有的治疗措施缺乏真实性和实用价值,从而使得疗效评价成为一个难题.近些年来,普遍采用试验性的研究结果作为证据指导临床实践活动,其中以随机对照试验(RCT)最为受到重视,但由于RCT属于药物面市前研究,对研究对象的选择、治疗措施的应用等均有严格的限定.     

疗效比较研究的方法学应用及其实施过程

疗效比较研究(CER)可有效比较诊疗措施的临床效果,为医疗决策提供证据.其设计除采用大规模临床随机对照试验、整群随机对照试验、类试验、数学模型外,以电子病历为基础的观察性研究备受重视.对研究课题的证据生成、综合、传播及应用的每一环节上,采用CER均需相应的统计学方法进行统计分析和质量控制.     

临床真实世界研究中的实验性研究设计

真实世界研究作为解释性随机对照试验在医疗实践中评价干预措施效果的进一步验证和补充已成为医疗卫生领域关注的焦点。但是也存在错误将真实世界研究等同于观察性研究,认为真实世界研究不能实施人为干预,更不能采取随机化。实际上,真实世界研究的基本设计既可以是观察性的,也可以是实验性的。其中真实世界研究的实验性研究设计主要是指实用性随机对照试验和基于注册登记研究的随机对照试验,也可采用非随机对照、自适应设计等其他研究设计方案。     

检测阴性设计在疫苗效果评价中的应用

疫苗在上市之前,通过安慰剂-随机对照试验,疫苗效力/效果可以得到规范的评价。但是,疫苗上市之后,如果采用安慰剂-随机对照试验来评价疫苗的效果,会产生伦理学上的问题。因此,疫苗上市后的效果评价一直是公共卫生领域面临的难题。近年来,检测阴性设计这一研究方法在国际上被广泛用于各类上市之后疫苗的效果评价中,例如流感疫苗、轮状病毒疫苗、霍乱疫苗、肺炎疫苗和EV71疫苗等。但是,目前国内关于检测阴性设计这一研究方法的文献报道很少。为此综述检测阴性设计的基本原理、应用步骤及优缺点,为我国开展检测阴性设计提供理论方法及依据。     

断点回归设计在真实世界疫苗保护效果评价中的应用

疫苗保护效果的真实世界研究是其上市后评价的重要内容,采用断点回归设计进行评价,可以克服随机对照试验的伦理学、现场组织实施等困难,结果更贴近现实,并可提供较高等级的因果推断证据。本文结合实例分析,对断点回归设计的原理、方法、应用场景及未来展望进行介绍与探讨,以期为新型冠状病毒疫苗保护效果的真实世界研究提供思路。     

复杂干预的设计和评价

介绍复杂干预研究的设计及过程,探索其在医学实践中的应用.在经典的干预性研究中,干预措施较为单一且效果评价较为简单.而目前越来越多的研究涉及到多个干预措施的综合,诸如心血管病的社区干预、卒中单元治疗等,此时复杂干预研究设计就较为适用.但复杂干预的设计、实施难度较大,效果评价也较困难.因此,复杂干预研究在设计、实施、评价和报告时,应严格遵守一定的标准,确保干预措施效果和研究的可重复性.     

大型随机对照试验:精准流行病学研究的典范与陷阱

现代流行病学是医学应用型研究的方法论,是在人群中定量地研究有关健康、疾病和医疗服务实践问题一般规律的科学和艺术。流行病学研究结果的准确度主要取决于研究的设计类型,精确度主要取决于样本量大小。大型随机对照试验是最精、最准的流行病学研究设计类型,但是由于伦理的限制,只能用于评估医学干预效果。一项研究需要的设计严谨性和样本量与预期效果的大小成反比：效果越小,所需的研究设计就越严谨,需要的样本量就越大。因此,只有当疗效比较小时,才需要大型随机对照试验,当疗效十分明显时,中小型随机对照试验甚至观察性研究就足以证明其有效性。从研究阶段上看,它是确认性、终结性研究,而不是提出假设的原创性研究。然而,研究的价值最终取决于研究问题的意义和原创性,而不是研究方法和P值的大小。过度推崇大型随机对照试验会引发：①对中、小疗效干预的过度强调;②对确认性研究的过度重视,以及对项目大小和经费多少而不是科学问题的追逐,进而弱化原创性研究工作;③增加研究资源、医学活动和患者利益被制药公司绑架的风险。     

上海市高桥社区糖尿病新型管理模式的效果评估

目的 评价糖尿病的“团队管理群组”模式在高桥社区实施1年的效果,从而探索出符合高桥社区特点的、有效可行的糖尿病新型管理模式.方法 按照以社区为基础的随机对照试验研究设计,以居委会为单位将205名自愿参加该研究的糖尿病患者随机地分为干预组(接受群组看病模式)和对照组(接受常规的糖尿病管理),干预组、对照组各4个居委会,干...     

From "among girl friends" to "among mothers"--baseline research adjusts a health promoting intervention in Nicaragua

PURPOSE: The objective of this study is to show how baseline findings can redefine the design of an intervention. DESIGN: A baseline cross-sectional study. Setting. The study area was a suburban community near the Nicaraguan capital, Managua. SUBJECTS: A sample of 612 girls aged 10 to 14 years was selected, and 592 (97%) participated in the study. MEASURES: Using individual interviews, data were collected on sociodemographics; self-esteem and life prospects; gender; sexuality and human reproduction; knowledge of sexually transmitted diseases, human immunodeficiency virus, and acquired immunodeficiency syndrome; violence; and networking. ANALYSIS: Frequency tables. RESULTS: A high proportion (87.5%) of the girls lived with their mothers, and only 59% had their fathers living with the family. In 51% of the sample, the mothers made the decisions at home. For the majority of the girls, their mothers were their referent persons when they wanted to talk about sexuality and pregnancies, whereas only a few girls said they would talk with friends. CONCLUSION: The mother is the most important significant other, and thus, according to the theory of reasoned action, she would be the most important person to influence the girl. Careful investigations into which groups are forming the norms are essential for an effective intervention program in order to change behavior and enhance self-esteem.     

Designing intervention programs for infants at risk: Considerations,implementation, and evaluation

There are few syntheses of the burgeoning literature on intervention programs for high risk infants. It is the thesis of the present paper that this problem arises, in part, from lack of a suitable design and evaluative framework. Six intervention programs were selected as representatives of this field and their essential features are summarized. Building on these data, and drawing from human service administration and evaluation literataure, a model which can be used in the design, implementation and evaluation of intervention programs for infants and/or theirfamilies is then presented and discussed. It is suggested that application of this model will aid researchers, service providers and administrators involved with high‐risk infant programs by providing a framework suited to both ongoing and comprehensive evaluations.     

Designing intervention programs for infants at risk: Considerations, implementation, and evaluation

There are few syntheses of the burgeoning literature on intervention programs for high risk infants. It is the thesis of the present paper that this problem arises, in part, from lack of a suitable design and evaluative framework. Six intervention programs were selected as representatives of this field and their essential features are summarized. Building on these data, and drawing from human service administration and evaluation literataure, a model which can be used in the design, implementation and evaluation of intervention programs for infants and/or theirfamilies is then presented and discussed. It is suggested that application of this model will aid researchers, service providers and administrators involved with high-risk infant programs by providing a framework suited to both ongoing and comprehensive evaluations.     

Injury case-control studies using "other injuries" as controls

Studies of event-related (or "event-phase") interventions (such as ski helmets) can address injury at a specific body site (such as the head) by using as controls a group of people who experienced the same event (fall) and suffered injuries at other body sites (other than the head). The research question addressed by this type of study is the effect of an exposure or intervention (helmet) during the event phase (fall) of the causal chain. However, this is a valid case-control design only if the controls (skiers with other injuries) provide a reasonable proxy for the prevalence of exposure (helmet-wearing) in the underlying event-phase source population (skiers who fell). This assumption needs to be carefully assessed. Factors associated with both helmet-wearing and injury given a fall (eg, previous injury history, skiing inexperience, or risk-taking behavior) have considerable potential to create bias.     

Improving the efficiency of individually randomized clinical trials by staggering the introduction of the intervention

In cluster randomized trials, the introduction of the intervention can be staggered in different clusters, leading to a stepped wedge design. This strategy can lead to gains in efficiency, which might also translate to the context of individually randomized trials, though this has been relatively unexplored. Here, we present one illustrative example. We consider trials in which participants start in a control condition such as routine care and can cross over at any stage to the active intervention. We make the assumption that the effect of the intervention is the same however long the delay before a participant crosses over to the intervention condition. We consider designs for a trial with three repeated assessments, including a baseline, and show that a three-sequence design with staggered introduction of the intervention in two of the sequences estimates the treatment effect after one period more efficiently than a parallel groups design.     

Variance formulae for multiphase stepped wedge cluster randomized trial

In a multiphase stepped wedge cluster randomized trial (MSW-CRT), more than one intervention will be initiated on each sequence in a fixed order. Hence, with the MSW-CRT design, the effect of the first intervention can be evaluated when compared to control, as well as the added-on effects of the subsequent interventions. Studies that use MSW-CRT have been proposed, but properties of this design have not been explicitly studied. We derive closed-form variance formulae to test the interventions' effects, which can be readily used for sample size and power calculation. Additionally, we provide relationships between variances to test the interventions' effects and design parameters. Under special conditions, some important properties include: (i) the variances to test different interventions' effects (ie, the first intervention effect and the second intervention effect) may be same; (ii) as the cluster-period mean autocorrelation increases, the variance to test an intervention effect may first increase and then decrease; (iii) as the amount of periods between the initiations of two interventions (ie, lag) increases, the variance to test an intervention effect may remain unchanged. We illustrate the relationships between power and design parameters using the variance formulae. From a few illustrative examples, we observe that the statistical test that uses data only relevant to a specific intervention has inferior power (relative power loss <15%) compared to the test when using all the study data. Also, power is reduced when both the total number of periods and lag are decreased simultaneously (relative power loss <20%).     

"Teach to goal": theory and design principles of an intervention to improve heart failure self-management skills of patients with low health literacy

Self-management is vital for achieving optimal health outcomes for patients with heart failure (HF). We sought to develop an intervention to improve self-management skills and behaviors for patients with HF, especially those with low health literacy. Individuals with low health literacy have difficulty reading and understanding written information and comprehending numerical information and performing calculations, and they tend to have worse baseline knowledge, short-term memory, and working memory compared with individuals with higher health literacy. This paper describes theoretical models that suggest methods to improve the design of educational curricula and programs for low literate audiences, including cognitive load theory and learning mastery theory. We also outline the practical guiding principles for designing our intervention, which includes a multisession educational strategy that teaches patients self-care skills until they reach behavioral goals ("Teach to Goal"). Our intervention strategy is being tested in a randomized controlled trial to determine if it is superior to a single-session brief educational intervention for reducing hospitalization and death. If this trial shows that the "Teach to Goal" approach is superior, it would support the value of incorporating these design principles into educational interventions for other diseases.     

"Eat for Health": a supermarket intervention for nutrition and cancer risk reduction.

OBJECTIVES. The results of an evaluation of "Eat for Health," a supermarket nutrition intervention, are presented. The study tested whether such a program could be successfully carried out and whether it could effect changes in knowledge, attitudes, and food purchasing behavior in line with nutrition and cancer risk reduction guidelines. METHODS. The evaluation consisted of an in-store monitoring element, an in-store and telephone consumer survey, and an analysis of sales data on selected foods. A matched-pair design, using a total of 40 stores in the intervention and comparison groups, was used. RESULTS. The intervention was successfully implemented and had limited success in changing some food purchasing behaviors. There appeared to be no effect on knowledge and attitudes except for increased awareness of a link between diet and cancer and of the program itself. CONCLUSIONS. Despite the intervention''s success, limitations of the consumer survey and sales data analyses and the continuing diffusion of nutrition messages throughout society make it difficult to specify the impact of this program on consumer nutrition knowledge and behaviors.     

Bedeutung der Genetik beim Thema "soziale Ungleichheit und Gesundheit"

In Germany it has rarely been assessed in a systematic way, if and how genetic disposition and genetic testing are linked to health inequality. The paper aims to be a contribution towards closing this gap. In a first step, it is pointed out that the discussion about potential links between genetic causes of social inequalities has concentrated on issues such as body height and intelligence. It is stressed that, of course, social status is mainly determined socially and not genetically. In the second step, medical benefits of genetic testing are discussed. It can be assumed that low status groups are using these tests less often than high status groups, and that they are less capable of interpreting the results. Tests that can have a positive effect on health could thus lead to an increase of health inequalities. However, empirical studies for testing these hypotheses are hardly available. In the third step, the question is raised whether genetic information could lead to social discrimination (e.g. concerning health insurance, life insurance or employer). According to the current empirical literature, to date, this risk is (still) rather small. Thus, it is stressed that more research is needed, and that already today there is some need for intervention (e.g. concerning equal access to genetic testing, better information of low status groups).     

In randomization we trust? There are overlooked problems in experimenting with people in behavioral intervention trials

ObjectivesBehavioral intervention trials may be susceptible to poorly understood forms of bias stemming from research participation. This article considers how assessment and other prerandomization research activities may introduce bias that is not fully prevented by randomization.Study Design and SettingThis is a hypothesis-generating discussion article.ResultsAn additivity assumption underlying conventional thinking in trial design and analysis is problematic in behavioral intervention trials. Postrandomization sources of bias are somewhat better known within the clinical epidemiological and trials literatures. Neglect of attention to possible research participation effects means that unintended participant behavior change stemming from artifacts of the research process has unknown potential to bias estimates of behavioral intervention effects.ConclusionStudies are needed to evaluate how research participation effects are introduced, and we make suggestions for how research in this area may be taken forward, including how these issues may be addressed in the design and conduct of trials. It is proposed that attention to possible research participation effects can improve the design of trials evaluating behavioral and other interventions and inform the interpretation of existing evidence.