Beyond Consent: Building Trusting Relationships With Diverse Populations in Precision Medicine Research

With the growth of precision medicine research on health data and biospecimens, research institutions will need to build and maintain long-term, trusting relationships with patient-participants. While trust is important for all research relationships, the longitudinal nature of precision medicine research raises particular challenges for facilitating trust when the specifics of future studies are unknown. Based on focus groups with racially and ethnically diverse patients, we describe several factors that influence patient trust and potential institutional approaches to building trustworthiness. Drawing on these findings, we suggest several considerations for research institutions seeking to cultivate long-term, trusting relationships with patients: (1) Address the role of history and experience on trust, (2) engage concerns about potential group harm, (3) address cultural values and communication barriers, and (4) integrate patient values and expectations into oversight and governance structures.     

对精准医学批评的辨析

首先澄清我国网站上发表的两篇有关精准医学博文中事实上的错误和概念上的混淆。接着讨论了对精准医学提出的批评及对这些批评的分析。指出精准医学术语本身容易引起误解和引起人们过高的期望;对精准医学的论述和实施中存在基因决定论倾向, 即过分夸大基因在健康和疾病中的作用, 而忽视环境、生活方式、社会因素的作用, 这在政策上就会导致在发展高端医学与发展大众医学上不能保持平衡的问题;将巨大的资源投入精准医学研究未进行认真的成本-效果分析, 也未考虑到精准医学研究成果的公平可及, 以避免加深社会不公正问题;最后, 在吸引商家参与精准医学研究计划时未考虑如何力求避免可能引起的利益冲突问题。     

Testing an integrated behavioural and biomedical model of disability in N-of-1 studies with chronic pain

Background: Previous research has supported an integrated biomedical and behavioural model explaining activity limitations. However, further tests of this model are required at the within-person level, because while it proposes that the constructs are related within individuals, it has primarily been tested between individuals in large group studies. We aimed to test the integrated model at the within-person level.

Method: Six correlational N-of-1 studies in participants with arthritis, chronic pain and walking limitations were carried out. Daily measures of theoretical constructs were collected using a hand-held computer (PDA), the activity was assessed by self-report and accelerometer and the data were analysed using time-series analysis.

Results: The biomedical model was not supported as pain impairment did not predict activity, so the integrated model was supported partially. Impairment predicted intention to move around, while perceived behavioural control (PBC) and intention predicted activity. PBC did not predict activity limitation in the expected direction.

Conclusions: The integrated model of disability was partially supported within individuals, especially the behavioural elements. However, results suggest that different elements of the model may drive activity (limitations) for different individuals. The integrated model provides a useful framework for understanding disability and suggests interventions, and the utility of N-of-1 methodology for testing theory is illustrated.     

N-of-1 methods: A practical guide to exploring trajectories of behaviour change and designing precision behaviour change interventions

Objectives(1) To introduce N-of-1 methods and how they can help the researchers identify predictors of behavioural outcomes, (2) to provide examples of studies that test individual theory-based predictions of physical activity and/or exercise; (3) to provide a practical example dataset to illustrate how to design and undertake a basic analysis for an N-of-1 study; and (4) to suggest a future agenda for N-of-1 physical activity and exercise research.DesignFactors for consideration when designing an N-of-1 study include variability of predictors and outcomes, assessment frequency and appropriate analysis methods. Existing literature and piloting can help inform these aspects.MethodsWe use a dataset of 24 individuals who collected data over 28 days to illustrate example analysis procedures. Data, guidance and associated SPSS and R syntax are made available to provide researchers with tools to learn about and practice N-of-1 analysis.ResultsGuidance on dealing with missing data, looking at graphical representations of N-of-1 data, managing autocorrelation using the prewhitening method and analysing N-of-1 datasets is provided. Using the example dataset, we demonstrate how to identify antecedents of physical activity (steps) to assess directionality of associations. We also include an overview of aggregating N-of-1 datasets using multilevel modelling.ConclusionsN-of-1 methodology provides a means of tracking individual patterns of behaviour and identifying potential antecedents of physical activity and exercise to help determine causality. Assisted by mobile technologies, there is great potential to enrich our understanding of movement behaviour using this approach to inform interventions.     

Scientific Forensics: How the Office of Research Integrity can Assist Institutional Investigations of Research Misconduct During Oversight Review

The Division of Investigative Oversight within the U.S. Office of Research Integrity (ORI) is responsible for conducting oversight review of institutional inquiries and investigations of possible research misconduct. It is also responsible for determining whether Public Health Service findings of research misconduct are warranted. Although ORI findings rely primarily on the scope and quality of the institution’s analyses and determinations, ORI often has been able to strengthen the original findings by employing a variety of analytical methods, often computer based. Although ORI does not conduct inquiries or investigations, it has broad authority to provide assistance to institutions at all stages of their reviews of allegations. This assistance can range from providing advice on best practices, to legal assistance, to suggestions for how best to investigate specific allegations. When asked, ORI can also conduct certain forensic analyses, such as a statistical examination of questioned digits or a simple examination of a questioned figure in Photoshop. ORI will not provide opinions or render judgment on such analyses while the institution is still conducting its investigation. Such analyses can be done without knowing much else about the case.     

Increasing walking among older people: A test of behaviour change techniques using factorial randomised N-of-1 trials

Objective: Evaluations of techniques to promote physical activity usually adopt a randomised controlled trial (RCT). Such designs inform how a technique performs on average but cannot be used for treatment of individuals. Our objective was to conduct the first N-of-1 RCTs of behaviour change techniques with older people and test the effectiveness of the techniques for increasing walking within individuals.

Design: Eight adults aged 60–87 were randomised to a 2 (goal-setting vs. active control) × 2 (self-monitoring vs. active control) factorial RCT over 62 days. The time series data were analysed for each single case using linear regressions.

Main outcome measures: Walking was objectively measured using pedometers.

Results: Compared to control days, goal-setting increased walking in 4 out of 8 individuals and self-monitoring increased walking in 7 out of 8 individuals. While the probability for self-monitoring to be effective in 7 out of 8 participants was beyond chance (p = .03), no intervention effect was significant for individual participants. Two participants had a significant but small linear decrease in walking over time.

Conclusion: We demonstrate the utility of N-of-1 trials for advancing scientific enquiry of behaviour change and in practice for increasing older people’s physical activity.     

N-of-1 study of weight loss maintenance assessing predictors of physical activity,adherence to weight loss plan and weight change

Objective: Behaviour change interventions are effective in supporting individuals to achieve clinically significant weight loss, but weight loss maintenance (WLM) is less often attained. This study examined predictive variables associated with WLM.

Design: N-of-1 study with daily ecological momentary assessment combined with objective measurement of weight and physical activity, collected with wireless devices (Fitbit?) for six months. Eight previously obese adults who had lost over 5% of their body weight in the past year took part. Data were analysed using time series methods.

Main outcomes measures: Predictor variables were based on five theoretical themes: maintenance motives, self-regulation, personal resources, habits, and environmental influences. Dependent variables were: objectively estimated step count and weight, and self-reported WLM plan adherence.

Results: For all participants, daily fluctuations in self-reported adherence to their WLM plan were significantly associated with most of the explanatory variables, including maintenance motivation and satisfaction with outcomes, self-regulation, habit, and stable environment. Personal resources were not a consistent predictor of plan adherence.

Conclusion: This is the first study to assess theoretical predictions of WLM within individuals. WLM is a dynamic process including the interplay of motivation, self-regulation, habit, resources, and perceptions of environmental context. Individuals maintaining their weight have unique psychological profiles which could be accounted for in interventions.     

转化医学——医学基础研究与临床应用间的桥梁

当前医学发展进程中,医学基础研究进展迅速,而临床医学则相对滞后。究其原因,大量基础研究成果不能及时有效地用于临床,使二者间产生了巨大的鸿沟。转化医学搭建了沟通二者的桥梁,为促进医学基础研究向临床的应用,同时为针对临床需要提出基础研究方向提供了有效途径。     

循证医学与临床科研

循证医学 (Ｅｖｉｄｅｎｃｅ -ｂａｓｅｄｍｅｄｉｃｉｎｅ ,ＥＢＭ )是临床流行病学和现代信息学与临床医学结合的典范 ,其含义为 :有目的、正确地运用现有最好的科学依据来指导对每位病人的治疗 ,其核心思想是谨慎、明确、明智地应用当代证据 (资料 ) ,对个体病人医疗作出决策[1] ,而其中最佳证据主要是指随机对照试验 (Ｒａｎｄｏｍｉｚｅｄｃｏｎｔｒｏｌｌｅｄｔｒｉａｌｓ ,ＲＣＴ)及针对特定疾病综合所有ＲＣＴ所作出的系统评价 (ｓｙｓｔｅｍａｔｉｃｒｅ ｖｉｅｗ ,ＳＲ) [2 ] 。循证医学是 2 1世纪的临床医学 ,也为 2 1世纪的临床…     

美国人体研究的监督：科学发展中的伦理与规定

美国保护人体受试者的制度建立在伦理学基础之上,并正式通过相关法律。对人体研究的监督是保护受试者个人的健康和权益,确保研究的有效性,整体性,以及科学与社会更大范围的利益,监督审查机构是联邦卫生部下属的两个机构-食品与药品管理局（FDA）和人体研究保护办公室（OHRP）,大部分人体研究受两机构监督。美国人体受试者保护系统的基础部分是伦理审查委员会（IRB）及知情同意,IRBU电在提供一种机制,以进行客观的审查,同意和研究过程听持续监督;知情同意意在保证个人在了解与实验相关的风险,不适,收益后能自由做出参加与否的决定,美国人体研究保护制度正面临着挑战。美国也为促进人体受试者保护在进行新的努力。     

中西医结合研究未来发展的方法学思考

中医科学化是中西医结合研究的重要任务.然而,50多年试图从物质的角度阐释中医理论的研究,并没有拉近中医和科学的距离.对科学的误读可能是其原因之一.通过不断的实践,实现自我纠错,是科学的核心价值观.因此,运用西医建立的临床论证方法,实现对中医理论的去伪存真,应是中西医结合研究的发展方向.     

人类干细胞之伦理原则与监管政策（上）

本文分两大部分。第一部分从干细胞的功能、来源与社会争议性3种角度划分了人类干细胞的种类,并讨论与人类干细胞研究及临床应用相关的9条伦理原则,特别强调了西方国家对胚胎捐赠在知情同意方面的伦理耍求。第二部分讨论了制定监管人类干细胞研究的3个原则,并简单地介绍了在英美各国监管的情况,其中较详细地评论了英国的种种立法过程、设立的法定机构和执行的种种政策与机制,作为在我国讨论类似政策参考之用。