Abstract
This report provides a brief overview of some relevant ongoing research on critical care and how research priorities are determined by the National Heart, Lung, and Blood Institute. Long-term and patient-centered outcomes have become more prominent research questions for clinical studies in patients who are critically ill. Rehabilitation research would be appropriate in this context, and funding is most likely received through investigator-initiated R01 applications. National Institutes of Health program staff are available for discussion and advice and encourage contact from extramural investigators.
The multidisciplinary nature of critical illness presents an opportunity as well as a challenge for investigators seeking to obtain research funding from the National Institutes of Health (NIH). Because of the complexity of critical illness, its science fits into the missions of many of the individual institutes of NIH, and thus does not have one identified “home.” The critical care research community has been active over the last 2 decades in raising awareness of the needs of both patients and researchers. Critical care medicine is a significant area of research for NIH. The link between effective critical care and adverse outcomes is a newer idea in this field, as it has been only recently that investigators have begun to study longer-term outcomes and quality of life after survival from critical illness.1 Research to test specific remedies to improve long-term outcomes represents a new step in the research enterprise for critical care. Because of the relative novelty of research in rehabilitation for critical illness, this report will provide a more generic overview of NIH funding, include a brief overview of some relevant ongoing research in critical care, and discuss how research priorities are determined and new research areas are recognized and addressed. We will discuss our institute, the National Heart, Lung, and Blood Institute (NHLBI), but most NIH institutes follow a similar method.
The NIH mission “is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce the burdens of illness and disability.”2 In recent years, NIH has increased its emphasis on translational research. Translational research is defined as work that transforms basic research findings into clinical practice and increases knowledge of molecular events underlying pathogenesis of diseases. The explosion of information from decoding the human genome may lead to the ultimate goal of developing personalized treatments based on an individual patient's unique biology. Because the theme of this special issue of PTJ is improving the recovery of patients who are critically ill, the focus of this article is primarily on translational research rather than extensive, ongoing efforts in genomic and molecular research in critical care, which are reviewed elsewhere.3
Setting Priorities
The NHLBI mission4 is to provide “global leadership for a research, training, and education program to promote the prevention and treatment of heart, lung, and blood diseases and enhance the health of all individuals so that they can live longer and more fulfilling lives.” The NHLBI “stimulates basic discoveries about the causes of disease, enables the translation of basic discoveries into clinical practice, [and] fosters training and mentoring of emerging scientists and physicians.”
The scientific priorities of the NHLBI are summarized in the NHLBI Strategic Plan,5 which was developed after an extensive iterative process involving hundreds of individuals representing research, patient advocacy groups, and professional societies. The NHLBI program staff are expected to be knowledgeable in a particular scientific or medical area and to implement and update priorities broadly identified by the Strategic Plan. This work is done by obtaining the widest possible input from the research community. To identify research needs, staff use their broad perspective gained through analysis of currently funded work and will identify specific research areas that are not well represented and may need a “push.” Staff organize workshops to seek the advice of extramural investigators who will meet, review current science, and make specific recommendations to fill scientific and research gaps. Workshop reports generally are published, and summaries are provided on the NHLBI website. Initiatives may be released in research areas that meet 2 minimal criteria: (1) there is a particular opportunity for new research progress and (2) the area of research is not currently well represented (ie, there is a gap) in the research portfolio. These initiative ideas then must be prioritized among the many research areas funded by NHLBI. Ideas for initiatives are presented at regular in-house “Idea Forum” meetings, where NHLBI leadership and staff from all divisions extensively discuss and refine ideas. Following the Idea Forum, ideas are reviewed and prioritized first by the NHLBI Board of Extramural Experts (BEE) and then by the NHLBI Advisory Council (NHLBAC), both of which review the ideas and advise the director about which specific initiatives should be considered. Both the BEE and NHLBAC are composed of distinguished and senior extramural scientists who have extensive research experience and perspective, as well as representatives from patient advocate groups. The NHLBI director makes final decisions based on this input, scientific priorities, and budget.
To encourage a workshop in a particular research area that may require specific attention, extramural scientists should discuss ideas with appropriate NIH program staff.
Examples of NIH-Initiated Research
In 2002, NIH initiated the Roadmap Program, with the purpose of more rapidly and effectively translating research supported by NIH into tangible, positive effects on the health of the US population. The NIH issued a number of initiatives as a part of the Roadmap Program, including the Clinical and Translational Science Awards, which provide support to form collaborative teams of investigators to develop practical solutions to clinical research. For critical care, publication of the NHLBI Report of the Task Force on Research in Cardiopulmonary Dysfunction in Critical Care Medicine in 19946 is arguably one of the milestones for NIH and critical care research, as it laid out in detail the breadth and depth of research opportunities and needs. Despite the detail and breadth of the areas covered in this document, long-term outcomes and rehabilitation were not mentioned at all by this group. In more recent working groups, critical care researchers recognize the importance of longer-term outcomes, as discussed below.7,8
The NHLBI followed many of the recommendations of the task force's report. For example, the Division of Lung Diseases developed a clinical trials network to test new therapies to improve survival of patients who are critically ill with acute lung injury or its more severe form, acute respiratory distress syndrome (ARDS). At that time, it was unknown whether randomized clinical trials could even be conducted in the intensive care unit. A contract solicitation was issued to establish the ARDS Clinical Trials Network (ARDSnet), with clinical sites and a clinical coordinating center awarded based on scientific merit determined by peer review.
The ARDSnet is a collaborative network of intensive care units that tests the efficacy of management strategies and novel therapies for acute lung injury and ARDS. Clinical trials completed by ARDSnet have improved treatment of patients with respiratory failure who are critically ill by providing answers to urgent issues about how they are ventilated9,10 and how fluid11 and nutrition support12 are managed. In particular, the network's clinical trial comparing ventilation strategies has led to worldwide changes in clinical practice. Its studies also have provided evidence that a variety of interventions to inhibit inflammation13–15 or to enhance edema clearance16 did not improve outcomes in these patients. The clinical outcomes chosen by the ARDSnet to study have been either mortality or ventilation-free days, a composite endpoint that also includes mortality.17 In recent years, reflecting the increased awareness of long-term effects of treatments in the intensive care unit, the ARDSnet has begun to collect additional data on longer-term outcomes and quality of life for comparison across treatment groups. The NHLBI has funded add-on ancillary studies to assess neuromuscular function in a subset of ARDSnet patients.
Ongoing NHLBI initiatives are providing opportunities for the critical care research community to advance translational research in acute lung injury. These initiatives include a Division of Lung Diseases request for applications for phase II clinical trials of novel interventions for lung and sleep disorders,18 which has resulted in funding of grants investigating the role of stem cells, individualized ventilator management, and treatment of underlying infection to reduce inflammation and improve outcomes in patients with established acute lung injury. A study that included a novel rehabilitation approach or utilized a long-term outcome end point could be responsive to this initiative. A list of current and past initiatives is available,19 and discussions and questions for NIH program staff about current solicitations are always appropriate and encouraged.
Investigator-Initiated Research
Grants from targeted initiatives represent only a small fraction of NHLBI-supported research. Nearly 75% of the NHLBI budget supports investigator-initiated research,20 as many believe that the wider scientific community is the best source for creative and cutting-edge research ideas.
Investigator-initiated applications are sorted, assigned to an institute, and reviewed by study sections organized by the Center of Scientific Review. A detailed description of how study sections operate is available on the center's website,21 but in short, these are independent expert groups that review and prioritize applications based on scientific merit. For NHLBI, applications that receive a meritorious percentile ranking that falls within our publically available pay lines generally will be funded following NHLBI Council review. Other NIH institutes may have other processes for making funding decisions, but generally also follow peer review rankings. The investigator-initiated path represents the best route for new ideas and studies.
A search across all NIH institutes using the NIH Reporter system22 with key words such as “rehabilitation” and “critical care” or “intensive care” reveals very few relevant funded applications. The NIH funds the congressionally mandated National Center for Medical Rehabilitation Research (NCMRR),23 which is located in the National Institute of Child Health and Human Development. Its emphasis has not been on recovery from critical illness, although some pediatric studies are supported. Because this is not an NHLBI program, we cannot comment further on it.
Because so many patients who are critically ill experience lung injury and respiratory failure, the Division of Lung Diseases of NHLBI has more than 200 investigator-initiated research grants in the Critical Care and Acute Lung Injury portfolio. At this time, only one of these grants is centered on rehabilitation, although long-term outcome measurement is a component of many grants.
For rehabilitation sciences to increase their presence in the critical care research portfolio, high-quality investigator-initiated applications are needed. It might be that multidisciplinary teams of investigators will be needed. Similarly, senior investigators could develop research training programs specifically for rehabilitation research in critical care. Investigators interested in developing training programs should contact program staff to determine where their science and idea might best fit.
Future Research Priorities for NHLBI in Critical Care
In planning for future clinical studies in acute lung injury and related critical illnesses, NHLBI organized a workshop to summarize the current state of clinical research on acute lung injury and to identify new research directions.7 This group concluded both proof of concept and efficacy (phase II and phase III) clinical trials for patients with acute lung injury and ARDS should be continued. The group further emphasized that patient-centered outcomes should be utilized wherever possible. Although mortality remains the most important patient-centered outcome for a patient who is critically ill, the group recognized and stated that consideration should be given to longer-term measures of quality of life and functional outcomes. The NHLBI also supported a conference grant to outline research needs and opportunities in critical care. Experts from each of 4 professional societies—the American Thoracic Society (ATS), the American Association of Critical-Care Nurses (AACN), the American College of Chest Physicians (ACCP), and the Society of Critical Care Medicine (SCCM)—joined with the US Critical Illness and Injury Trials Group (USCIITG) to develop a comprehensive agenda for critical care research.8 An important part of the research agenda is technology to conduct, analyze, and report research focused on improving outcomes important to patients and their families.
Thus, there is evidence that the extramural community is beginning to call for rehabilitation research for critical illness. Researchers often look to expert panel reports such as those described above and develop high-quality investigator-initiated applications that fare well in peer review.
Conclusion
In summary, NIH has 27 institutes and centers, many of which support critical care research as it relates to their mission. We represent one institute (NHLBI) with a particular interest in critical care and have described how priorities are set. Translational research remains important for NIH, including research using various approaches to improve outcomes that are important to patients. Through workshops and peer-reviewed publications such as this special edition of PTJ, the research community is learning that an important area for progress in critical care research will be whether and how therapies such as physical therapy, occupational therapy, and others are effective in improving outcomes. Submission of high-quality, investigator-initiated research grant applications with high scientific merit as assessed in peer review is the most effective way to increase support for research on critical care. The NIH program staff are available to assist potential grantees in learning how to navigate the NIH systems and to find appropriate homes for applications.
Footnotes
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Both authors provided writing.
- Received November 28, 2011.
- Accepted July 23, 2012.
- © 2012 American Physical Therapy Association
References
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