Patient-oriented Clinical Research Research Articles

Research Bronchoscopies in Critically Ill Research Participants: An Official American Thoracic Society Workshop Report.

Bronchoscopy for research purposes is a valuable tool to understand lung-specific biology in human participants. Despite published reports and active research protocols using this procedure in critically ill patients, no recent document encapsulates the important safety considerations and downstream applications of this procedure in this setting. The objectives were to identify safe practices for patient selection and protection of hospital staff, provide recommendations for sample procurement to standardize studies, and give guidance on sample preparation for novel research technologies. Seventeen international experts in the management of critically ill patients, bronchoscopy in clinical and research settings, and experience in patient-oriented clinical or translational research convened for a workshop. Review of relevant literature, expert presentations, and discussion generated the findings presented herein. The committee concludes that research bronchoscopy with bronchoalveolar lavage in critically ill patients on mechanical ventilation is valuable and safe in appropriately selected patients. This report includes recommendations on standardization of this procedure and prioritizes the reporting of sample management to produce more reproducible results between laboratories. This document serves as a resource to the community of researchers who endeavor to include bronchoscopy as part of their research protocols and highlights key considerations for the inclusion and safety of research participants.

Safety Planning for Suicidality in Autism: Obstacles, Potential Solutions, and Future Directions.

Safety Planning for Suicidality in Autism: Obstacles, Potential Solutions, and Future Directions.

Promoting inclusive, patient-oriented research: A rare disease patient perspective

Patients and members of the public contribute valuable information and perspectives to research projects because they have experienced a disease themselves or are close to someone affected by an illness. Patients with rare diseases are incredibly motivated to participate in research projects. Any advancement of scientific or medical knowledge or favourable political decisions can increase the possibility of a cure – or at least a treatment – that can stop or slow the progression of their disease and improve their quality of life. Patients’ lived experience may help researchers fill gaps in understanding conditions that they know mainly from theory. In this article, the authors address the need for more focus on patient-oriented clinical and public health research, the importance of bringing patients’ perspectives into research, issues around patient involvement, and areas for future research on the topic.

Defining Patient-Oriented Natural Language Processing: A New Paradigm for Research and Development to Facilitate Adoption and Use by Medical Experts.

The capabilities of natural language processing (NLP) methods have expanded significantly in recent years, and progress has been particularly driven by advances in data science and machine learning. However, NLP is still largely underused in patient-oriented clinical research and care (POCRC). A key reason behind this is that clinical NLP methods are typically developed, optimized, and evaluated with narrowly focused data sets and tasks (eg, those for the detection of specific symptoms in free texts). Such research and development (R&D) approaches may be described as problem oriented, and the developed systems perform specialized tasks well. As standalone systems, however, they generally do not comprehensively meet the needs of POCRC. Thus, there is often a gap between the capabilities of clinical NLP methods and the needs of patient-facing medical experts. We believe that to increase the practical use of biomedical NLP, future R&D efforts need to be broadened to a new research paradigm—one that explicitly incorporates characteristics that are crucial for POCRC. We present our viewpoint about 4 such interrelated characteristics that can increase NLP systems’ suitability for POCRC (3 that represent NLP system properties and 1 associated with the R&D process)—(1) interpretability (the ability to explain system decisions), (2) patient centeredness (the capability to characterize diverse patients), (3) customizability (the flexibility for adapting to distinct settings, problems, and cohorts), and (4) multitask evaluation (the validation of system performance based on multiple tasks involving heterogeneous data sets). By using the NLP task of clinical concept detection as an example, we detail these characteristics and discuss how they may result in the increased uptake of NLP systems for POCRC.

The impact of clinical trial units on the value of clinical research in Switzerland.

A prominent 2014 series by The Lancet on "Increasing value, reducing waste in biomedical research" provided recommendations on how to optimise precious resources, including in clinical research. Despite being ideally placed to lead the movement in patient-oriented clinical research, academia struggles to take corresponding measures and find ways to evaluate their impact. A decade ago, Swiss stakeholders established constructive initiatives to improve the quality of clinical research, including a national Clinical Trial Unit (CTU) Network, predominantly rooted in university hospitals. At the 10th anniversary of this network (2007-2017), we reflect on the CTUs' trajectory and review whether - and how - they have been successful in improving the value of clinical research conducted in Switzerland. Anonymised surveys with involved clinical research stakeholder institutions and CTU customers at university hospitals suggest that the CTU Network has positively influenced the quality of academic clinical research. Future goals should include standardised education on Good Clinical Practice; the establishing of an audit function; the positioning of the network as an "entrance gate" for international trials; and support for young scientists launching their careers. Although stakeholder feedback has been very positive, praise does not constitute a standardised measure of the actual impact of CTU services. Beyond that, a broad understanding and practical guidance on how to increase value in academic clinical research are still lacking. We conclude with ways forward, including "INcreasing QUality In clinical Research" (INQUIRE), a comprehensive framework for the practical assessment of quality in academia developed by the CTU Basel. INQUIRE, founded on consensus across international and Swiss stakeholders, outlines six key quality dimensions to be fulfilled study-wide and is available for all relevant parties involved. INQUIRE encourages academic institutions to adopt waste-reducing strategies and strives to build an evidence-based clinical research landscape in Switzerland, with national and international influence.

Helping hands: Organizations, institutions work to assist and mentor early career investigators.

Helping hands: Organizations, institutions work to assist and mentor early career investigators.

The effect of an intense mentoring program on junior investigators' preparation for a patient-oriented clinical research career.

There is a recognized need to translate scientific discoveries to patient-oriented clinical research (POCR). Several obstacles interfere with the successful recruitment and retention of physicians for POCR careers. The American Society of Hematology developed a yearlong educational and mentoring experience, the Clinical Research Training Institute (CRTI), for early-career physician-scientists from multiple institutions throughout the United States and Canada pursuing POCR careers. Several academic outcome measures of the 140 participants in the first seven years (2003-2010) of CRTI were evaluated by reviewing former trainee participants' curriculum vitae and survey responses. Ethnic, racial, and gender diversity of CRTI trainees was reflective of the proportions represented across U.S. hematology/oncology fellowship programs. Eighty-six percent (109/126) of trainees reported success establishing a POCR study; nearly half (62/126) had primarily research-focused jobs. Former CRTI trainees received at least 262 external grant awards and published 1,035 peer-reviewed manuscripts, 173 chapters, and 115 review articles. Because mentorship is key to developing a successful career, the CRTI program is being modified to enhance longitudinal mentorship by CRTI faculty mentors and mentors at trainees' home institutions, as well as to encourage the establishment of collaborations and the potential for research project success. Efforts to make the CRTI experience available to more phy sicians, include more CRTI graduates as faculty, and increase participation by hematologists from backgrounds under represented in medicine are under way.

Patientenorientierte chirurgische Forschung im Verbund – Das Chirurgische Studiennetzwerk CHIR-Net

Patient-oriented clinical research in surgery requires prospective randomised multicentre trials (mRCTs) to generate valid evidence. In order to conduct high quality mRCTs, a network of surgical clinical trial centres is necessary. The Surgical Trial Network (CHIR-Net), which is funded by the German Federal Ministry of Education and Research (BMBF), was established as a structure of surgical regional centres. Currently, the CHIR-Net comprises 12 regional surgical centres with their associated clinical partner hospitals. The major aim of this network is to generate patient-relevant surgical questions of high clinical impact and to answer these questions in high-quality prospective randomised multicentre trials with well-trained study personnel. Since 2006 32 mRCTs have been initiated in the CHIR-Net. Twelve surgical regional centres - in cooperation with 333 German and European hospitals - have recruited more than 7,500 patients. More than 80 surgeons have successfully completed the CHIR-Net educational curriculum for young surgeons. The CHIR-Net has successfully established a national clinical trial network to investigate surgical questions in randomised multicentre clinical trials. A nationwide research infrastructure, including university and non-university hospitals as well as the associated clinical coordination centres (KKS), was created to ensure patient-oriented surgical clinical research in a network at the highest methodological level thus implementing evidence-based medicine in daily surgical practice.

The ASH Clinical Research Training Institute (CRTI) Positively Impacts The Success Of Early Career Hematologists In Patient-Oriented Clinical Research

There is a recognized need to translate scientific discoveries to patient-oriented clinical research (POCR) in order to improve human health. To overcome obstacles that interfere with the recruitment and retention of physicians for POCR careers, in 2003 the American Society of Hematology (ASH) developed the Clinical Research Training Institute (CRTI), an enhanced and extensive mentored experience for early career POCR investigators. The ASH CRTI is limited to 20 trainees/year (senior fellows or junior faculty) with an equivalent number of faculty mentors. The year-long Institute includes a 1 week workshop with didactic sessions on a variety of POCR and career development topics, disease-specific small group sessions focusing on research protocol development with biostatistician participation, and one-on-one interactions with faculty and representatives with expertise in career-development awards from the U.S. National Institutes of Health. Trainees have additional interactions with their small groups and CRTI mentors throughout the ensuing year to promote career development and research collaborations. Communications between the trainees' CRTI and home institution mentors are a vital component of the program. Evaluation of the POCR career development successes of the first 7 CRTI classes (140 trainees) was performed by reviewing trainees' curriculum vitaes and their responses to an electronically distributed survey. Gender, racial and ethnic distributions were similar to that of U.S. Hematology/Oncology fellowship programs. The majority (66%) of trainees were senior fellows or graduates of adult hematology/oncology training programs, 31% of pediatric hematology/oncology programs and the remainder of other hematology-related programs. Eighty-six percent of trainees had self-described success establishing a POCR study and 85% considered themselves clinical investigators. Nearly half of trainees had positions that were primarily research focused. CRTI trainees received at least 144 external grant awards plus additional internal awards, and had published 1035 peer-reviewed manuscripts,173 chapters and 115 review articles. Over 95% of trainees were satisfied with their CRTI experience and testimonials supported their impression that CRTI had a significant impact on their career success. Enhancements introduced into the CRTI program, as a result of ongoing program evaluations, include broadening participant eligibility to include up to 5 international trainees per class to enhance global research collaborations and further enhancements to the trainee-mentor interactions. The outcomes of the ASH CRTI support the hypothesis that enhanced mentoring experiences contribute to the successful career development of physicians pursuing POCR careers. Disclosures:Clayton:American Society of Hematology: Employment.

Developing an international network for clinical research in ophthalmology: the European Vision Institute Clinical Research Network (EVICR.net)

There is a well-identified need for patient-oriented clinical research and this can only be achieved by creating active collaboration between academic centers with competence for clinical research, following GCP guidelines and supported by an infrastructure that provides appropriate management of clinical trials at a realistic cost. The European Vision Institute Clinical Research Network (EVICR.net) is a legal entity established as an independent European Economic Interest Grouping in accordance with the Council Regulation (EEC) #2137/85 and was built and developed to function as the necessary structure to perform clinical research in ophthalmology in the EU according to ICH GCP Guidelines and European Directives.

Institutional profile: Integrated center for research and treatment of vertigo, balance and ocular motor disorders

In 2009 the German BMBF (German Ministry of Education and Research) established an Integrated Center for Research and Treatment (IFB(LMU)) of Vertigo, Balance and Ocular Motor Disorders in Munich. After the 10-year period of funding by the BMBF, it is envisioned that the (IFB(LMU)) will continue over the long term with the joint support of the University Hospital, the Medical Faculty, and the Bavarian State. Vertigo is one of the most common complaints in medicine. Despite its high prevalence, patients with vertigo generally receive either inappropriate or inadequate treatment. This deplorable situation is internationally well known and its causes are multiple: insufficient interdisciplinary cooperation, no standardized diagnostics and therapy, the failure to translate findings of basic science into clinical applications, and the scarcity of clinical multicenter studies. The (IFB(LMU)) will constitute a suitable tool with which these structural, clinical, and scientific deficits can be overcome. It will also make possible the establishment of an international interdisciplinary referral center. Munich has become the site of a unique concentration of leading experts on vertigo, balance and ocular motor disorders, both in the clinical and basic sciences. Academic structures have paved the way for the creation of an interdisciplinary horizontal network that also allows structured, vertical academic career paths via the Bachelor's and Master's degree programs in Neuroscience, a Graduate School of Systemic Neurosciences, and the Munich Center for Neurosciences - Brain and Mind. The (IFB(LMU)) has the following objectives as regards structure and content: to create an independent patient-oriented clinical research center under the auspices of the Medical Faculty but with autonomous administration and budget; to overcome existing clinical and academic barriers separating the traditional specializations; to establish a standardized interdisciplinary longitudinal and transversal network at one site for the management of patients. This should professionalize both the management and the international recruitment of patients (integrated care, telemedicine); to organize the study infrastructure for prospective multicenter clinical studies as well as to free clinical scientists from administrative tasks; to promote translational research with a focus on the innovative topics of molecular, functional and structural imaging, experimental and clinical pharmacotherapy, clinical research of vertigo and balance disorders, mathematical modelling, interaction between biological and technical systems (robotics), and research on functionality and the quality of life; to offer new attractive educational paths and career images for medical doctors, students of the natural sciences, and engineers in clinical research in order to overcome traditional hierarchical structures. This should promote the principles of efficiency and self-reliance; to supplement the existing excellence with up to eight groups of young scientists and up to eight professorships (tenure track). This should also be seen as an incentive that will attract the best young scientists; to incorporate (IFB(LMU)) competence into the existing medical and biological graduate schools. The (IFB(LMU)) is a unique center - worldwide.

Integriertes Forschungs- und Behandlungszentrum für Schwindel, Gleichgewichts- und Okulomotorikstörungen

The German BMBF (German Ministry of Education and Research) has decided to establish an Integrated Center for Research and Treatment of Vertigo, Balance and Ocular Motor Disorders (IFB(LMU)) in Munich in 2010. After funding over a 10-year period, the long-term continuation of the IFB(LMU) by the medical faculty and the hospital is envisioned. Vertigo is one of the most common complaints in medicine. Despite its high prevalence patients with vertigo generally receive either inappropriate or inadequate treatment. This deplorable situation is internationally well known and its causes are multiple: insufficient interdisciplinary cooperation, no standardized diagnostics and therapy, the failure to translate findings of basic science into clinical applications and the scarcity of clinical multicenter studies. The IFB(LMU) will constitute a suitable tool with which these structural, clinical, and scientific deficits can be overcome. It will also make possible the establishment of an international interdisciplinary referral center. Munich has become the site of a unique concentration of leading experts on vertigo, balance and ocular motor disorders, both in the clinical and basic sciences. Academic structures have paved the way for the creation of an interdisciplinary horizontal network that also allows structured, vertical academic career paths via the Bachelor's and Master's degree programs in neuroscience, a Graduate School of Systemic Neurosciences, and the Munich Center for Neuroscience "Brain and Mind". The IFB(LMU) has the following objectives with regard to structure and content: to create an independent patient-oriented clinical research center under the auspices of the Medical Faculty but with autonomic administration and budget; to overcome existing clinical and academic barriers separating the traditional specializations, to establish a standardized interdisciplinary longitudinal and transversal network at one site for the management of patients. This should professionalize both the management and the international recruitment of patients (integrated care, telemedicine); to organize the study infrastructure for prospective multicenter clinical studies as well as to free clinical scientists from administrative tasks; to promote translational research with a focus on the innovative topics of molecular functional and structural imaging, experimental and clinical pharmacotherapy, clinical research of vertigo and balance disorders, mathematical modelling, interaction between biological and technical systems (robotics) and research on functionality and the quality of life; to offer new attractive educational paths and career images for medical doctors, students of the natural sciences and engineers in clinical research in order to overcome traditional hierarchical structures. This should promote the principles of efficiency and self-reliance; to supplement the existing excellence with up to eight groups of young scientists and up to eight professorships (tenure track). This should also be seen as an incentive that will attract the best young scientists; to incorporate IFB(LMU) competence into the existing medical and biological graduate schools. The IFB(LMU) is a unique reference center worldwide.

Insights into Inflammation and Influenza

The emergence of highly pathogenic avian influenza H5N1 viruses in Asia and their spread globally have delivered a timely reminder of the public health and clinical challenges an influenza pandemic would pose. It is remarkable how little patient-oriented clinical research has been conducted over the past 30 years on a disease that could cause such extensive loss of life. There is currently a single oral drug for the treatment of influenza (the neuraminidase inhibitor oseltamivir) and no licensed parenteral drugs, although these are being developed. A key therapeutic question recently addressed by Zheng et al.1 in an animal model is whether adjunctive interventions would improve the outcome of infection.

Five steps from evidence to effect: exercising clinical freedom to implement research findings

Clinicians read medical journals to keep up to date with new evidence.1,2 To do this effectively means getting through many articles every month. Help with assimilating primary research is available from critically appraised syntheses or meta-analyses published in specialty databases,3 the Cochrane Library4 and other secondary journals.5,6 Some research will have implications for their current clinical practice. As clinicians accumulate new information, they must take it forward for implementation into practice. If they do not, the benefits for patients of research evidence will not be realised. There is clear evidence that clinicians lack confidence in implementing research findings.7,8 Simply making research evidence available through publication is not sufficient to improve care. This is what leads to frustration for researchers, research funders, peer-reviewers and journal editors. Transfer of research into clinical practice often takes too long.9,10 On a worldwide scale, effective evidence-based interventions remain underutilised.9 Unless clinicians keep up to date and have skills in appraising and applying valid and potentially valuable published findings, the journey from evidence to effect will not be shortened. Evidence-based medicine (EBM)11 encourages integration of contemporaneous patient-oriented clinical research knowledge into medical decision-making. EBM also integrates concepts of problem based-learning and lifelong learning because evidence changes over time.12,13 Despite the fact that EBM is highly regarded by many healthcare professionals, it is not widely used.14 With local efforts,11,15–17 where clinicians feel empowered to exercise clinical freedom high levels of evidence-based practice are achievable.18 This commentary will provide a brief overview of the journey from evidence to effect and will outline the hurdles that impede and factors that aid in the implementation of evidence. Using the rational approaches that have been shown to work in diffusion of innovations, clinicians will be able to develop a practical strategy for putting evidence into practice realising the benefits of new research for their patients.

Gerald Shulman digests his award

Gerald Shulman digests his award

Structured data entry for narrative data in a broad specialty: patient history and physical examination in pediatrics

BackgroundWhereas an electronic medical record (EMR) system can partly address the limitations, of paper-based documentation, such as fragmentation of patient data, physical paper records missing and poor legibility, structured data entry (SDE, i.e. data entry based on selection of predefined medical concepts) is essential for uniformity of data, easier reporting, decision support, quality assessment, and patient-oriented clinical research. The aim of this project was to explore whether a previously developed generic (i.e. content independent) SDE application to support the structured documentation of narrative data (called OpenSDE) can be used to model data obtained at history taking and physical examination of a broad specialty.MethodsOpenSDE was customized for the broad domain of general pediatrics: medical concepts and its descriptors from history taking and physical examination were modeled into a tree structure.ResultsAn EMR system allowing structured recording (OpenSDE) of pediatric narrative data was developed. Patient history is described by 20 main concepts and physical examination by 11. In total, the thesaurus consists of about 1800 items, used in 8648 nodes in the tree with a maximum depth of 9 levels. Patient history contained 6312 nodes, and physical examination 2336. User-defined entry forms can be composed according to individual needs, without affecting the underlying data representation. The content of the tree can be adjusted easily and sharing records among different disciplines is possible. Data that are relevant in more than one context can be accessed from multiple branches of the tree without duplication or ambiguity of data entry via "shortcuts".ConclusionAn expandable EMR system with structured data entry (OpenSDE) for pediatrics was developed, allowing structured documentation of patient history and physical examination. For further evaluation in other environments, the tree structure for general pediatrics is available at the Erasmus MC Web site (in Dutch, translation into English in progress) [1]. The generic OpenSDE application is available at the OpenSDE Web site [2].

Factors that Influence Successful Training and Faculty Career Development in Hematology/Oncology Patient-Oriented Clinical Research

We wanted to identify what factors promote career development in patient-oriented clinical research (POCR). We used a survey questionnaire covering areas relevant to the training of subspecialty fellows and the career development of POCR faculty. Pursuit of an academic career after fellowship correlated with completion of a clinical project, availability of a clinical research training program, opportunity to earn academic credit, faculty mentorship, and obtaining independent career development funding. Successful faculty career development in POCR was closely correlated with excellent morale and adequate protected time for academic pursuits. Specific academic environmental factors positively influence success in POCR hematology/oncology fellowship training and faculty career development.

Remembering the "golden years" of patient-oriented clinical research: a collective conversation.

The period from the end of World War II to the early 1960s has been characterized as the "golden years" of patient-oriented clinical research in the United States, a period catalyzed and fostered by advances in biology and medicine, changes in the organization and financing of research units, and strong moral and political convictions growing out of the war about the importance and possibilities of the scientific enterprise. This account of some of the salient themes, phenomena, and issues in clinical research during that era draws primarily on the proceedings of an oral history conference whose core participants were a number of emeritus physician-investigators who had played major roles in shaping patient-oriented research. The topics that they and the other conferees discussed included the factors that had led the emeritus physician-investigators into clinical research; the organizational attributes of the units where they had trained and worked, focusing particularly on Boston's Peter Bent Brigham Hospital; the vital role played by private and federal funding for research and training; and some of the changes in the nature of clinical research, research training, and their relationships to the care of the sick in the decades since the golden years.

The Thoracic Surgery Foundation for Research and Education

The Thoracic Surgery Foundation for Research and Education (TSFRE) supports research and education in cardiothoracic surgery. The primary purpose is to give young investigators opportunities to get started, to be productive, and do the work that will position them to become independent investigators and mentors for the next generation. TSFRE represents The Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery (AATS), the Southern Thoracic Surgical Association (STSA), and the Western Thoracic Surgical Association (WTSA). TSFRE research grants are in several categories. Faculty research grants provide seed support that leads to subsequent major awards. Resident Fellowships encourage young surgeons to develop their skills in cardiothoracic surgery. The Nina Starr Braunwald Awards further the career opportunities of young women in cardiac surgery. The TSFRE, in partnership with the National Heart, Lung and Blood Institute (NHLBI), supports 5-year Mentored Clinical Scientist Development Awards in basic science (K08 Awards) and in patient-oriented clinical research (K23 Awards). This partnership provides extraordinarily favorable leverage for your donations to support the work of young cardiac surgeons; every TSFRE dollar is more than matched by NHLBI. We expect soon to have a partnership with the National Cancer Institute (NCI) to support young general thoracic surgeons in basic science (K08 Awards) or patient-oriented clinical cancer research (K23 Awards). New money will be needed for that purpose. TSFRE’s emphasis and success in public policy education (supported only from funds specifically donated for that purpose) has significantly helped our specialty to understand and to react as effectively as possible to events in health care. TSFRE recently decided to initiate programs in traditional cardiothoracic surgery education when available funds permit. New money will be needed for that purpose. The investigators and students whose work TSFRE has supported appreciate the generosity of those who have given; however, many thoracic surgeons have not given. Our estimate is that there are 5032 members of STS, AATS, WTSA and STSA, after eliminating overlapping memberships. Only 7.4% of the members have made individual contributions to TSFRE. In my own state of California, only about 7% of practicing thoracic surgeons have given to TSFRE. Conversely, more than 90% of cardiothoracic surgeons have given nothing toward the support of research and education in our own specialty. I hope you agree that this is unacceptable and that every one who has benefited from education and research in our specialty must give back. Our patients and our young colleagues need your help. If you have not given, please become a donor and continue to give at least until you become a Life Member. In addition, please consider making a planned gift to TSFRE as part of your estate planning. I close with optimism. Past performance shows that thoracic surgeons do what is right and TSFRE has come far in a relatively short time thanks to the generosity of individual and corporate donors, and to the wisdom and drive of previous leadership.

A guide to planning careers in hematology and oncology.

Numerous opportunities exist for successful careers in the fields of hematology and oncology. Trainees must choose between dedicated training in one or both disciplines, and between careers in private practice or academic medicine. Individuals who favor academic careers must decide between patient-oriented clinical investigation and laboratory research. This article addresses the factors that influence these decisions and inform trainees about critical elements of the training experience that foster successful career development in academic medicine and private practice. Counsel on employment opportunities is provided along with advice on evaluating the merits of employment offers.