The grant portfolio of the National Center for Medical Rehabilitation Research: the first five years.

OBJECTIVE: To relate grant funding activities of the National Center for Medical Rehabilitation Research (NCMRR) with the Center's mission, priorities, and terminology for disability classification. STUDY DESIGN: Retrospective review by the National Advisory Board on Medical Rehabilitation Research (NABMRR). DATA: Abstracts of 153 research proposals and one contract funded by the NCMRR from 1992 through 1996. METHOD: A six-member research group participated in the development of a rating form and related instructions used to evaluate each abstract. The form was piloted and revised, and interrater agreement was monitored. RESULTS: Funded proposals reflected each of the NCMRR priorities evaluated, with the highest proportion in the areas of assistive technology and whole body system, and the lowest in the area of behavioral adaptation. Although some proposals were funded in each of the domains of the disability classification system, proportionately fewer addressed the domains of disability and societal limitations. Findings also indicated that few funded proposals addressed more than one domain in the disability classification system and that most abstracts did not address consumers' perspectives on quality of life. RECOMMENDATIONS: The NABMRR recommended that the NCMRR (1) encourage more research in the areas of disability and societal limitations and in behavioral adaptation, (2) examine funded proposals in light of a recent Institute of Medicine report, and (3) explore quality-of-life measurements. Further, members of the rehabilitation community are encouraged to e-mail their responses to this review to NCMRR staff at (1q2n@nih.govA) and to suggest areas of research emphasis.     

Functional Limitation and Disability Associated with Congestive Heart Failure

Congestive heart failure (CHF) is a common and increasing problem among older persons. Symptoms associated with CHF include edema, fatigue, dyspnea, limited exercise tolerance, and significant activity limitation. Using a comprehensive review of literature, this article describes the public health burden arising out of CHF in the United States. It describes CHF in terms of functional limitation and disability in the elderly following the National Center for Medical Rehabilitation and Research (NCMRR) disability model. The use of home based interventions (HBI) to assist people with CHF is discussed.     

Advancing integrated research in psychological health and traumatic brain injury: common data elements

Thurmond VA, Hicks R, Gleason T, Miller AC, Szuflita N, Orman J, Schwab K. Advancing integrated research in psychological health and traumatic brain injury: common data elements.In civilian, military, and veteran populations, there is increased recognition of the interrelationship between traumatic brain injury (TBI) and some psychological health (PH) disorders and the need to better understand the relationships by integrating research for these topics. The use of different measures to assess similar study variables and/or assess outcomes may limit important advances in PH and TBI research. Without a set of common data elements (CDEs; to include variable definitions and recommended measures for the purpose of this discussion), comparison of findings across studies is challenging. The federal agencies involved in PH and TBI research, the National Institute of Neurological Disorders and Stroke, Department of Veterans Affairs, National Institute on Disability and Rehabilitation Research, Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury, and Defense and Veterans Brain Injury Center, therefore cosponsored a scientific initiative to develop CDEs for PH and TBI research. Scientific experts were invited to participate in 1 of 8 working groups to develop recommendations for specific topic-driven CDEs. Draft recommendations were presented and discussed in the workshop “Advancing Integrated Research in Psychological Health and Traumatic Brain Injury: Common Data Elements (CDE)” held on March 23-24, 2009, in Silver Spring, MD. The overall process leading to the workshop and subsequent recommendations by the working groups are presented in this article. Topic-driven recommendations for CDEs are presented in individual reports in this edition.     

Common data elements for research on traumatic brain injury and psychological health: current status and future development

Whyte J, Vasterling J, Manley GT. Common data elements for research on traumatic brain injury and psychological health: current status and future development.The National Institute of Neurologic Disorders and Stroke, Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury, National Institute on Disability and Rehabilitation Research, and Defense and Veterans Brain Injury Center jointly supported an effort to develop common data elements (CDEs, ie, consensus-based content domains of importance and recommended ways to measure them) for research on traumatic brain injury and psychological health. The authors served as participants in this effort as well as editors of the resulting articles. This article describes the current status of this multiagency endeavor, the obstacles encountered, and possible directions for future development. Challenges that occurred within the working groups that developed the CDE recommendations and similarities and differences among the articles that describe those recommendations were reviewed. Across all of the working groups, there were challenges in striking a balance between specificity in recommendations to researchers and the need to tailor the selection of variables to specific study aims. The domains addressed by the different working groups varied in the research available to guide the selection of important content areas to be measured and the specific tools for measuring them. The working groups also addressed this challenge in somewhat different ways. The CDE effort must enhance consensus among researchers with similar interests while not stifling innovation and scientific rigor. This will require regular updating of the recommendations and may benefit from more standardized criteria for the selection of important content areas and measurement tools across domains.     

膝骨关节病康复临床路径

卫生部下发《临床路径管理指导原则（试行）》（卫医管发[2009]99号）的通知,希望建立一套既能贯彻医院质量管理标准,又能节约资源的医疗标准化模式。为适应现代医学和康复医学发展的需要,采用康复临床路径对康复治疗进行规范,是非常重要的。四川大学华西医院康复医学科根据临床路径要求,于2011年制定了康复医学科膝骨关节病康复临床路径,希望通过临床试用,对路径的临床实用性、可行性进行探讨,并逐渐完善。     

Evaluation of a Clinical Cancer Trial Research Training Workshop: Helping Nurses Build Capacity in Southwest Virginia

Residents of Southwest Virginia (SWVA) face significant barriers in accessing the most advanced forms of cancer care, cancer risk reduction, and clinical trials involvement. A collaboration between the University of Virginia (UVA) Cancer Center and UVA School of Nursing was forged with oncology caregivers in this region to build community capacity to support Cancer Clinical trials (CCT) by strengthening the workforce, and thus improving health outcomes for this underserved region of Appalachia. The UVA School of Nursing designed an educational workshop focusing on the basics of CCT to facilitate the development of a skilled nursing workforce in the SWVA region that could provide care to patients on protocol and/or to encourage residents to participate in trials. The goal of the workshop was to offer a CCT training session for oncology nurses that fostered the knowledge and skills necessary to facilitate and support CCT infrastructure across this high‐risk region. This evaluation reports the learning outcomes of the CCT training on 32 nurse participants from SWVA. Evaluations of the training program showed high rates of satisfaction, increased comfort level with CCTs, and increased knowledge and attitude toward CCTs. These findings provide information about a curriculum that could be useful in educating other oncology nurses and student nurses how to care for patients who may be enrolled in a clinical trial. Nurses can also be advocates for participation in clinical trials once they have the knowledge and are comfortable in their own understanding of a trial's usefulness. Educating the nursing workforce is an essential component of building capacity and infrastructure to support clinical trials research.     

The European and American Use of Exploratory Approaches for First‐in‐Human Studies

Exploratory approaches for first‐in‐human clinical studies have evolved over the last few years and have stimulated the issuance of national regulatory guidances in some European countries as well as the United States. With the increasing implementation of these approaches and the recent preparation of a multiregional regulatory guidance (ICH M3 rev2), an exchange of experiences on the opportunities and challenges of exploratory clinical trials was desirable; thus, a workshop focusing on the use of this clinical approach was planned and conducted in Lisbon, Portugal, March 18–19, 2009 sponsored by the Portuguese Health Authority (INFARMED) and DIA. The structure of the workshop focused in three main areas. Regulatory representatives from Portugal, Belgium, Germany, the United Kingdom and the United States formally reviewed their experiences. This was followed by a discussion on issues from an ethics review perspective as well as an insight to the opportunities in the area of biologics. The industry perspective was presented by representatives from Merck, Pfizer, J&J, Novartis, Speedel, AstraZeneca, GSK, and Roche. Finally, through break out sessions, issues were identified to be addressed moving forward. It is the purpose of this paper to report on the outcome of this workshop. Clin Trans Sci 2010; Volume #: 1–4     

New developments in the conduct and management of multi-center trials: an international review of clinical trial units

Summary— There is an urgent need for the performance of more, better designed, and better managed randomized clinical trials. After visits to 43 leading organizations and units involved in clinical trials in Europe and North America during 1993, the way of conducting randomized clinical trials was analyzed. By using a structured questionnaire, information on recent improvements in the way randomized clinical trials are performed was identified. These developments encompass human aspects (better information, collaboration, and communication) as well as non-human aspects (press button phone randomization and data management systems). By employing such developments, randomized clinical trials can run much more efficiently. This facilitates faster and better answers to the questions addressed by randomized clinical trials, thereby also making them more ethical.     

我国临床试验伦理审查培训现状与对策

目的通过问卷调查,了解和分析中国临床试验伦理审查培训的现状和问题。方法对参加2009年6月开展的首届临床试验伦理审查培训班学员进行问卷调查。结果发放问卷60份,回收34份,回收率56.7%,调查结果显示,78.1%（25/32）的学员表示达到学习目的,12.5%（4/32）由于语言障碍没能达到学习目的。学员们普遍认为培训班各专题内容与质量对其非常有帮助,85.2%（23/27）认为伦理审查工作存在困难为,包括相关法规支持不够（60%,19/32）、方法学欠缺（41%,13/32）、培训缺乏（38%,12/32）等。结论反馈率虽不高,但提示建立我国伦理学培训基地和伦理审查专业人才培训的重要性,可适时考虑将伦理学审查纳入医学生必修课;培训应基于不同对象的需求分层进行,重视教学方法、讲义和教学资料的相关性,授课结合案例分析、讨论和经验交流是一种效果较好的培训方式。     

Research from the Model Spinal Cord Injury Systems: findings from the current 5-year grant cycle

This issue of the Archives of Physical Medicine and Rehabilitation is dedicated to current research findings of the Model Spinal Cord Injury Systems (MSCIS) program. The MSCIS grants were established by the Rehabilitation Services Administration in the 1970s. Now administered by the National Institute on Disability and Rehabilitation Research within the Office of Special Education and Rehabilitation Services in the US Department of Education, the program has included 27 spinal cord injury centers in the United States over the years. In the current 5-year grant cycle (2000-2005), there are 16 designated regional MSCIS centers. In addition to establishing a comprehensive system of care, the grantees contribute patient data to the National Spinal Cord Injury Database (which now contains data on 30,532 subjects with follow-up of up to 30 y). In addition, the MSCIS grants enable the conduct of site-specific and collaborative research projects. To highlight the research findings of the program, the MSCIS have produced a special dissemination effort during each of the previous 5 grant cycles, with this issue of the Archives representing the latest of these endeavors. This article provides a brief history of the MSCIS program and highlights the important findings of the 17 original research articles contained in this issue.     

Sample size calculation in physical medicine and rehabilitation: a systematic review of reporting, characteristics, and results in randomized controlled trials

Abdul Latif L, Daud Amadera JE, Pimentel D, Pimentel T, Fregni F. Sample size calculation in physical medicine and rehabilitation: a systematic review of reporting, characteristics, and results in randomized controlled trials.

Objective

To assess systematically the reporting of sample size calculation in randomized controlled trials (RCTs) in 5 leading journals in the field of physical medicine and rehabilitation (PM&R).

Data Sources

The data source was full reports of RCTs in 5 leading PM&R journals (Journal of Rehabilitation Medicine, Archives of Physical Medicine and Rehabilitation, American Journal of Physical Medicine and Rehabilitation, Clinical Rehabilitation, and Disability and Rehabilitation) between January and December of 1998 and 2008. Articles were identified in Medline.

Study Selection

A total of 111 articles met our inclusion criteria, which include RCTs of human studies in the 5 selected journals.

Data Extraction

Sample size calculation reporting and trial characteristics were collected for each trial by independent investigators.

Data Synthesis

In 2008, 57.3% of articles reported sample size calculation as compared with only 3.4% in 1998. The parameters that were commonly used were a power of 80% and alpha of 5%. Articles often failed to report effect size or effect estimates for sample size calculation. Studies reporting sample size calculation were more likely to describe the main outcome and to have a sample size greater than 50 subjects. The study outcome (positive vs negative) was not associated with the likelihood of sample size reporting. Trial characteristics of the 2 periods (1998 vs 2008) were similar except that in 1998 there were more negative studies compared with 2008.

Conclusions

Although sample size calculation reporting has improved dramatically in 10 years and is comparable with other fields in medicine, it is still not adequate given current publication guidelines.     

新型冠状病毒肺炎(COVID-19)临床研究的启示与国家临床试验网络构想

新型冠状病毒肺炎(COVID-19)疫情爆发以来,从2020年1月23日至2020年3月5日由中国临床研究人员在中国临床试验注册中心(www.chictr.org.cn)和美国临床试验注册网站(www.clinicaltrials.gov)两个平台上登记注册并已经或将要在中国境内进行的针对新型冠状病毒肺炎的干预性临床试验项目总数已超过200个。这一现象引起了社会各界的关注。本文在对已登记注册的249个在中国开展的COVID-19临床试验项目的主要特征作描述性分析的基础上,借鉴美国国家卫生研究院(National Institutes of Health)组建的专项疾病领域国家临床试验网络的实践,思考在突发流行病情况下提高临床试验质量与效率的对策。     

The state of rehabilitation research: art or science?

Rehabilitation research has been criticized as not standing up enough to the rigors of scientific method to be called "science." The field has been portrayed as slow to promote its scientific achievements and to include them under the rubric of evidence-based rehabilitation. Following in the footsteps of psychology, rehabilitation as a broad-based discipline has faced many similar obstacles in achieving scientific status. Controversy exists about what exactly constitutes rehabilitation science versus its art and its respective multidisciplinary domains. The conception of these domains is directly related to current methods available to assess the state of the discipline and its research accomplishments. I used quantitative methods, such as randomized clinical and/or controlled trials (RCTs) and systematic reviews, to assess the status of rehabilitation research. Findings suggest that, as a field, rehabilitation makes significant contributions to science, measurable by the number and quality of RCTs and systematic reviews conducted so far on topics of critical importance for clinical care. In "artful" complement, qualitative approaches can be used as research tools to aid investigators in seeking knowledge beyond that obtained by quantitative methods, assessing many complexities associated with the various contexts of rehabilitation research. Other requirements to develop a common vision of rehabilitation science are also discussed.     

关节置换与保留关节修复肱骨近端移位3，4部分骨折的Meta分析

背景：目前的肱骨近端骨折治疗方法包括保留关节治疗（保守治疗、切开复位内固定等）和关节置换,如何选择存在争议。目的：收集肱骨近端移位3,4部分骨折保留关节与关节置换治疗的随机对照试验,对两种治疗方法的疗效差异进行Meta分析。方法：检索Medline（1966年1月至2013年12月）、Pubmed（1980年1月至2013年12月）、Embase（1990年1月至2013年12月）、Science（1990年1月至2013年12月）、Springer（1990年1月至2013年12月）、CNKI（1994至2013年）、万方数据库（1982至2013年）等数据库中关于肱骨近端3,4部分骨折保留关节与关节置换治疗的随机对照试验,纳入符合标准的文献,提取相关数据输入 Comprehensive Meta-Analysis Software （CMA）软件进行Meta分析。结果与结论：共7篇文献符合纳入标准,共计320例患者（165例行保留关节治疗,155例行关节置换治疗）,均为英文文献,经改良的Jadad评分判定均为高质量研究。Meta分析结果显示,总Constant平均值为55.9（95%CI：50.7-61.1,P〈0.001）,保留关节治疗组的Constant评分值高于关节置换组（P〈0.01）。研究的异质性显著（I2=88%,Q统计量=107.6,Q=13,P〈0.001）,在Meta分析时肩关节Constant评分值随着男女性别比增长、肱骨结节骨吸收率增加而下降。提示保留关节肱骨近端移位3,4部分骨折患者治疗后期可较关节置换得到较高的Constant评分值。此外年龄、骨折类型、性别比和并发症发生率是影响Constant值的显著因子。鉴于研究的异质性和方差,需要有更多更好的随机对照试验进一步证明。     

Challenges in Implementing Hospice Clinical Trials: Preserving Scientific Integrity While Facing Change

Background/AimsNumerous changes can occur between the original design plans for clinical trials, the submission of funding proposals, and the implementation of the clinical trial. In the hospice setting, environmental changes can present significant obstacles, which require changes to the original plan designs, recruitment, and staffing. The purpose of the study was to share lessons and problem-solving strategies that can assist in future hospice trials.MethodsThis study uses one hospice clinical trial as an exemplar to demonstrate challenges for clinical trial research in this setting. Using preliminary data collected during the first months of a trial, the research team details the many ways their current protocol reflects changes from the originally proposed plans. Experiences are used as an exemplar to address the following questions: 1) How do research environments change between the initial submission of a funding proposal and the eventual award? 2) How can investigators maintain the integrity of the research and accommodate unexpected changes in the research environment?ResultsThe changing environment within the hospice setting required design, sampling, and recruitment changes within the first year. The decision-making process resulted in a stronger design with greater generalization. As a result of necessary protocol changes, the study results are positioned to be translational following the study conclusion.ConclusionResearchers would do well to review their protocol and statistics early in a clinical trial. They should be prepared for adjustments to accommodate market and environmental changes outside their control. Ongoing data monitoring, specifically related to recruitment, is advised.     

Rehabilitation medicine summit: building research capacity. Executive summary

The general objective of the "Rehabilitation Medicine Summit: Building Research Capacity" was to advance and promote research in medical rehabilitation by making recommendations to expand research capacity. The 5 elements of research capacity that guided the discussions were researchers; research culture, environment, and infrastructure; funding; partnerships; and metrics. Participants included representatives of professional organizations, consumer groups, academic departments, researchers, governmental funding agencies, and the private sector. Small group discussions and plenary sessions generated an array of problems, possible solutions, and recommended actions. A post-Summit, multiorganizational initiative is called for to pursue the agendas outlined in this report.     

Addressing the Evidence Gap in Stroke Rehabilitation for Complex Patients: A Preliminary Research Agenda

Evidence suggests that a stroke occurs in isolation (no comorbid conditions) in less than 6% of patients. Multimorbidity, compounded by psychosocial issues, makes treatment and recovery for stroke increasingly complex. Recent research and health policy documents called for a better understanding of the needs of this patient population, and for the development and testing of models of care that meet their needs. A research agenda specific to complexity is required. The primary objective of the think tank was to identify and prioritize research questions that meet the information needs of stakeholders, and to develop a research agenda specific to stroke rehabilitation and patient complexity. A modified Delphi and World Café approach underpinned the think tank meeting, approaches well recognized to foster interaction, dialogue, and collaboration between stakeholders. Forty-three researchers, clinicians, and policymakers attended a 2-day meeting. Initial question-generating activities resulted in 120 potential research questions. Sixteen high-priority research questions were identified, focusing on predetermined complexity characteristics—multimorbidity, social determinants, patient characteristics, social supports, and system factors. The final questions are presented as a prioritized research framework. An emergent result of this activity is the development of a complexity and stroke rehabilitation research network. The research agenda reflects topics of importance to stakeholders working with stroke patients with increasingly complex care needs. This robust process resulted in a preliminary research agenda that could provide policymakers with the evidence needed to make improvements toward better-organized services, better coordination between settings, improved patient outcomes, and lower system costs.     

Impact of a mis-specification of the response rate under standard treatment in sequential clinical trials

Phase III trials are aimed at assessing whether new treatments have superior efficacy than standards. Sequential methods, such as the single triangular test (STT) and the double triangular test (DTT), allow for early stopping of such trials. They use stopping boundaries which depend, for a binary endpoint, on pi(0) and pi(1) (response rates under standard and new treatment, respectively) and alpha and beta (type I and II errors, respectively). Thus, a wrong estimation of pi(0) at planning phase might have an influence on their statistical properties. We assessed the extent of this influence by simulations regarding alpha, 1--beta, and average sample number (ASN) and compared the two methods with the one-sided and two-sided single-stage designs (SSD). There was no influence on alpha for any test and the power achieved by the one-sided or two-sided SSD was moderately affected by a wrong estimation of pi(0). However, important drifts (whose magnitude depended on chosen design) were observed for sequential methods concerning power and ASN in case of moderate under- or overestimation of pi(0) (+/-20% compared with its 'true' value). For example, when 'true' values of pi(0) and pi(1) are 0.30 and 0.40, respectively, using design values of 0.10 and 0.20, the power is 0.57 and 0.50 for the STT and DTT, respectively, instead of 0.95. When 'true' values of pi(0) and pi(1) are 0.10 and 0.20, respectively, using design values of 0.30 and 0.40, the ASN under H(0) is 1,309 and 2,019 for the STT and DTT, respectively, instead of 392 and 601, respectively, using the right design. Using sequential methods in comparative clinical trials with binary responses requires a precise knowledge of the response rate under standard treatment to avoid losses in power or inappropriate increases in sample size.     

Organisation of a clinical trial unit — a proposal

Summary— The urgent need for the performance of more, better designed, and better conducted randomised clinical trials is increasingly recognised. Based on structured interviews with leading persons of 43 outstanding organisations and units involved in clinical trials in Europe and North America during 1993, ways of organising and staffing clinical trial units were investigated. The present proposal is based on this experience from which an attempt to extract a composite set of minimal requirements has been made regarding pertinent objectives and aims, organisational aspects, staffing, and estimated costs of establishing a clinical trial unit. The core staff is suggested to consist of two chief physicians, one statistician, one data manager, one project coordinator, and two secretaries. In order to fulfil the minimal requirements for running such a unit, it is calculated that about GBP 450,000 per year is needed to cover investments, core staff, and running costs, but excluding housing costs and costs of randomised clinical trials that do not originate from trial coordination. In return, such a unit should be able to mount and launch 6–7 multicenter randomised clinical trials during a 5 year period, corresponding to a total cost for coordination per trial of about GBP 340,000. However, with a larger staff more studies may be coordinated possibly reducing the cost per trial depending on greater effectiveness in utilisation of the basic facilities.     

Analysis of the numbers of clinical trials on physical therapy in Japan: comparison with those in the North American register from 2010 to 2019

[Purpose] Information about clinical trials related to physical therapy (CTPT) in Japan, which has the highest aging rate in the world, is essential for physical therapy education, research, and policymaking to change and strengthen the education system and promote research grants. This survey aimed to clarify the proportion of CTPT in the clinical registry and compare the proportion of CTPT in Japan with that in North America. [Participants and Methods] The ClinicalTrials.gov (CTG) and National Institute of Public Health (NIPH) Clinical Trials were used. The number and proportion of CTPT were compared each year. The analyzed data spanned 10 years from 2010 to 2019. [Results] A total of 222,821 trials were registered in CTG during the 10 years. In search of “physical therapy”, 3,001 trials searched. The proportion of CTPT increased from 0.8% to 1.7%. In total 42,194 trials were registered in the NIPH Clinical Trials Search. From the CTPT, 141 trials were obtained. The proportion of CTPT increased from 0.05% to 0.5%. The proportion of CTPT in the NIPH Clinical Trials Search was one-third or less than that in the CTG. The proportion of CTPT in CTG increased yearly, but the proportion of CTPT in NIPH Clinical Trials Search has not increased since 2016. [Conclusion] The proportion of CTPT is relatively low in Japan, compared with that in North America, and it showed no increasing trend. It is important to provide education and support for clinical trials in an aging country such as Japan.