美国国立卫生研究院概况

美国国立卫生研究院(the National Institutes of Health,NIH)是美国主要的医学与行为学(medical and behavioral research)研究机构,拥有27个研究所及研究中心和1个院长办公室(office of the director,OD),任务是探索生命本质和行为学方面的基础知识,并充分运用这些知识延长人类寿命,以及预防、诊断和治疗各种疾病和残障。NIH不仅拥有自己的实验室从事医学研究,还通过各种资助方式和研究基金全力支持各大学、医学院校、医院等的非政府科学家及其他国内外研究机构的研究工作,并协助进行研究人员培训,促进医学信息交流。世界一流的科学家在NIH的支持下,自由探索科学问题,取得了辉煌的成就,极大地改善了人类的健康和生存状况。本文旨在介绍NIH的概况、基金管理模式、经费预算等,希望对我国的医学研究事业有所借鉴。     

To Apply or Not to Apply: A Survey Analysis of Grant Writing Costs and Benefits

We surveyed 113 astronomers and 82 psychologists active in applying for federally funded research on their grant-writing history between January, 2009 and November, 2012. We collected demographic data, effort levels, success rates, and perceived non-financial benefits from writing grant proposals. We find that the average proposal takes 116 PI hours and 55 CI hours to write; although time spent writing was not related to whether the grant was funded. Effort did translate into success, however, as academics who wrote more grants received more funding. Participants indicated modest non-monetary benefits from grant writing, with psychologists reporting a somewhat greater benefit overall than astronomers. These perceptions of non-financial benefits were unrelated to how many grants investigators applied for, the number of grants they received, or the amount of time they devoted to writing their proposals. We also explored the number of years an investigator can afford to apply unsuccessfully for research grants and our analyses suggest that funding rates below approximately 20%, commensurate with current NIH and NSF funding, are likely to drive at least half of the active researchers away from federally funded research. We conclude with recommendations and suggestions for individual investigators and for department heads.     

Two strikes: limited NIH R55 and R56 retooling funds and abolishment of the A2 grant mechanism

The U.S. National Institutes of Health (NIH) are facing significant budgetary challenges as a result of the current economic climate. The recent sunset of investigator-initiated R01-type research grants after one revised submission, coupled with the present lack of an NIH retooling funding mechanism for such grant applicants, creates a concerning risk that talented and well-trained investigators may be forced to give up their research careers. Existing NIH retooling mechanisms include the R55 Shannon Award, which was established in 1991 and was essentially replaced in 2005 by the R56 award. There is an urgent need to either significantly expand the R55/R56 mechanisms and definition of NIH grant bridging/retooling support for unfunded meritorious proposals or introduce a new mechanism that provides specific support to investigators with competitive but unfunded R01 revised grants. An expanded retooling funding mechanism deserves implementation during continuing assessment of whether allowance of only one revision of research proposals has achieved its initial intended goals.     

New Insights into an Old Organelle: Meeting Report on Biology of Cilia and Flagella

The rising interest of the scientific community in cilia biology was evident from the fact that registration for the third FASEB conference on ‘The Biology of Cilia and Flagella’ closed out before the early bird deadline. Cilia and flagella are organelles of profound medical importance; defects in their structure or function result in a plethora of human diseases called ciliopathies. 240 clinicians and basic scientists from around the world gathered from 23 June 2013 to 28 June 2013 at Sheraton at the Falls, Niagara Falls, NY to present and discuss their research on this intensely studied subcellular structure. The meeting was organized by Gregory Pazour (University of Massachusetts Medical School), Bradley Yoder (University of Alabama‐Birmingham), and Maureen Barr (Rutgers University) and was sponsored by the Federation of American Societies for Experimental Biology (FASEB). Here, we report highlights, points of discussion, and emerging themes from this exciting meeting.     

Predictors of Negotiated NIH Indirect Rates at US Institutions

Background

The United States (US) Department of Health and Human Services and the Office of Naval Research negotiate institutional rates for payments of overhead costs associated with administration and space usage, commonly known as indirect rates. Such payments account for a large proportion of spending by the National Institutes of Health (NIH). Little has been published about differences in rates and their predictors.

Methods

Negotiated indirect rates for on-campus research grants were requested from the Council on Governmental Relations for the 100 institutions with greatest NIH funding in 2010. NIH funding, cost of living (ACCRA Index for 2008), public vs. private status, negotiating governmental organization (Department of Health and Human Services or Office of Naval Research), US Census Region, and year were assessed as predictors of institutional indirect rates using generalized estimating equations with all variables included in the model.

Results

Overall, 72 institutions participated, with 207 reported indirect rates for the years 2006, 2008, and 2010. Indirect rates ranged from 36.3% to 78%, with an average of 54.5%. Mean rates increased from 53.6% in 2006 to 55.4% in 2010 (p<0.001). In multivariable models, private institutions had 6.2% (95% CI 3.7%-8.7%; p<0.001) higher indirect rates than public institutions. Rates in the Northeast were highest (Midwest 4.0% lower; West 4.9% lower; South 5.2% lower). Greater NIH funding (p = 0.025) and cost of living (p = 0.034) also predicted indirect rates while negotiating governmental organization did not (p = 0.414).

Conclusions

Negotiated indirect rates for governmental research grants to academic centers vary widely. Although the association between indirect rates and cost of living may be justified, the cause of variation in rates by region, public-private status, and NIH funding levels is unclear.     

Use and importance of the NIH noncompeting continuation application

Each year National Institutes of Health (NIH) grant recipients must submit a noncompeting continuation application before receiving continued federal funding. This paper describes the use and value of the application. Investigators benefit by a yearly self-assessment of the research progress and future plans. The noncompeting continuation application is part of the important communication and interaction that should exist between the investigator and NIH staff. NIH staff members use the application to determine important scientific advances that have resulted from supported grants. Many planning activities and required reports are based on information contained in these applications. NIH staff performs scientific and budgetary review to ensure that research progress is satisfactory and that all budgetary and certification issues are in order. Detailed guidance is provided to help the grantee prepare the application. A separate significance section is suggested as a means to document key findings and their importance.     

Review by a local medical research ethics committee of the conduct of approved research projects,by examination of patients' case notes,consent forms,and research records and by interview.

OBJECTIVE: To monitor the conduct of medical research projects that have already been approved by the local medical research ethics committee. DESIGN: Follow up study of ethically approved studies (randomly selected from all the studies approved in the previous year) by examination of patients'' case notes, consent forms, and research records and by interview of the researchers at their workplace. SETTING: Tayside, Scotland (mixed rural and urban population). SUBJECTS: 30 research projects approved by Tayside local medical research ethics committee. MAIN OUTCOME MEASURES: Adherence to the agreed protocol, particularly for recruitment (obtaining and recording informed consent) and for specific requirements of the ethics committee, including notification of changes to the protocol and of adverse events. RESULTS: In one project only oral consent had been obtained, and in a quarter of the studies one or more consent forms were incorrectly completed. Inadequate filing of case notes in five studies and of consent forms in six made them unavailable for scrutiny. Adverse events were reported, but there was a general failure to report the abandoning or non-starting of projects in two studies the investigators failed to notify a change in the responsible researcher. CONCLUSIONS: Monitoring of medical research by local medical research ethics committees promotes and preserves ethical standards, protects subjects and researchers, discourages fraud, and has the support of investigators. We recommend that 10% of projects should undergo on-site review, with all others monitored by questionnaire. This would require about six person hours of time and a salary bill of 120 pounds per study monitored.     

Biomedical research funding: when the game gets tough, winners start to play

Extramural funding provides major support for biomedical research in academia, and National Institutes of Health (NIH) grants often constitute direct evaluation criteria for promotions and tenure. Therefore, NIH budget trends influence long-term scientific strategies and career decisions, as well as the progress of science itself. Our analysis of the last 37 years of NIH awards, however, reveals that the success rate of grant applications submitted for funding is negatively related to the total yearly amount of (inflation-adjusted) NIH extramural expenditure. Instead, as might be expected, the ratio between available funding and the number of submission directly predicts the probability of winning support in any given year. We purport that the considerable success rate variability can be parsimoniously explained by a proportional but delayed reaction of the number of applications to budget fluctuations. As a counterintuitive consequence, grant proposals conceived during lean periods might stand the best chance of success.     

NIH ImageJ and Slice-O-Matic computed tomography imaging software to quantify soft tissue

Objective: To compare reliability and limits of agreement of soft tissue cross‐sectional areas obtained using Slice‐O‐Matic and NIH ImageJ medical imaging software packages. Research Methods and Procedures: Abdominal and midthigh images were obtained using single‐slice computed tomography. Two trained investigators analyzed each computed tomography image in duplicate. Adipose tissue and skeletal muscle cross‐sectional areas (centimeters squared) were calculated using standard Hounsfield unit ranges (adipose tissue: ?190 to ?30 and skeletal muscle: ?29 to 150). Regions of interest included abdominal total area, total fat area, subcutaneous fat area, visceral fat area (AVF), and right and left thigh total area, fat area, and skeletal muscle area. Results: For all images, intra‐investigator coefficients of variation ranged from 0.2% to 3.4% and from 0.4% to 5.6% and inter‐investigator coefficients of variation ranged from 0.9% to 4.8% and 0.2% to 2.6% for Slice‐O‐Matic and NIH ImageJ, respectively, with intra‐ and inter‐investigator coefficients of reliability of R² = 0.99. Mean AVF values for investigators A and B ranged from 168 to 170 cm² using Slice‐O‐Matic and NIH ImageJ. Bland‐Altman analyses revealed that Slice‐O‐Matic and NIH ImageJ results were comparable. The mean differences (95% confidence intervals) between the AVF cross‐sectional areas obtained using the Slice‐O‐Matic and NIH ImageJ medical imaging software were +2.5 cm² (?5.7, +10.8 cm²) or +1.4% (?3.4%, +6.4%). Discussion: These findings show that both the Slice‐O‐Matic and NIH ImageJ medical imaging software systems provide reliable measurements of adipose tissue and skeletal muscle cross‐sectional areas.     

Studying de-implementation in health: an analysis of funded research grants

Background

Studying de-implementation—defined herein as reducing or stopping the use of a health service or practice provided to patients by healthcare practitioners and systems—has gained traction in recent years. De-implementing ineffective, unproven, harmful, overused, inappropriate, and/or low-value health services and practices is important for mitigating patient harm, improving processes of care, and reducing healthcare costs. A better understanding of the state-of-the-science is needed to guide future objectives and funding initiatives. To this end, we characterized de-implementation research grants funded by the United States (US) National Institutes of Health (NIH) and the Agency for Healthcare Research and Quality (AHRQ).

Methods

We used systematic methods to search, identify, and describe de-implementation research grants funded across all 27 NIH Institutes and Centers (ICs) and AHRQ from fiscal year 2000 through 2017. Eleven key terms and three funding opportunity announcements were used to search for research grants in the NIH Query, View and Report (QVR) system. Two coders identified eligible grants based on inclusion/exclusion criteria. A codebook was developed, pilot tested, and revised before coding the full grant applications of the final sample.

Results

A total of 1277 grants were identified through the QVR system; 542 remained after removing duplicates. After the multistep eligibility assessment and review process, 20 grant applications were coded. Many grants were funded by NIH (n?=?15), with fewer funded by AHRQ, and a majority were funded between fiscal years 2015 and 2016 (n?=?11). Grant proposals focused on de-implementing a range of health services and practices (e.g., medications, therapies, screening tests) across various health areas (e.g., cancer, cardiovascular disease) and delivery settings (e.g., hospitals, nursing homes, schools). Grants proposed to use a variety of study designs and research methods (e.g., experimental, observational, mixed methods) to accomplish study aims.

Conclusions

Based on the systematic portfolio analysis of NIH- and AHRQ-funded research grants over the past 17 years, relatively few have focused on studying the de-implementation of ineffective, unproven, harmful, overused, inappropriate, and/or low-value health services and practices provided to patients by healthcare practitioners and systems. Strategies for raising the profile and growing the field of research on de-implementation are discussed.

     

Medical research; the program of the U.S. Public Health Service

Federal Government expenditures for medical research have increased apace in the last ten years. The increase in federal research funds has stimulated support from private sources; contributions from other than federal sources have doubled. More than half of medical research funds are being used by universities, hospitals, and other nonprofit institutions, and less than one-fourth by laboratories of the Federal Government.Grants-in-aid of research, fellowships and extended training are made on the advice of Advisory Councils made up of leaders in the various research fields. The previous record of research by staffs and faculties of institutions is taken into account. Special attention is given to unknown investigators and small projects. Noninterference with a scientist in the conduct of research is a basic principle of all grants. He may change the direction of his research to pursue promising leads without asking permission. Continuity of grants so that promising projects need not be abandoned at the end of a grant period is given special consideration.     

MEDICAL RESEARCH—The Program of the U. S. Public Health Service

Federal Government expenditures for medical research have increased apace in the last ten years. The increase in federal research funds has stimulated support from private sources; contributions from other than federal sources have doubled.More than half of medical research funds are being used by universities, hospitals, and other nonprofit institutions, and less than one-fourth by laboratories of the Federal Government.Grants-in-aid of research, fellowships and extended training are made on the advice of Advisory Councils made up of leaders in the various research fields. The previous record of research by staffs and faculties of institutions is taken into account. Special attention is given to unknown investigators and small projects.Noninterference with a scientist in the conduct of research is a basic principle of all grants. He may change the direction of his research to pursue promising leads without asking permission.Continuity of grants so that promising projects need not be abandoned at the end of a grant period is given special consideration.     

An investigation of the organization of pigtail monkey groups through the use of challenges

In a sequence of tests challenging pigtail monkey groups through presentation of a variety of stimuli in an openable release box, or by humans directly, it was found that the control male responded to direct challenges to the group and that other males were most active when the challenge was less direct, i.e., contained in a box. Immature males opened the box and were in the vicinity of the stimulus box more than any other group members, regardless of box content. On most trials with group members serving as stimuli, subordinate animals did not approach or release higher status animals. Findings were consistent with other reports of the organization of macaque, baboon, and capuchin social groups.This research was supported by NSF grant GB1167 and in part by NIH grants FR-00165, H-5691, and FR-05325.     

Complex biomedical systems: from basic science to translation

The Department of Biomedical Engineering (BME) of the University of Southern California (BME@USC) has a longstanding tradition of advancing biomedicine through the development and application of novel engineering ideas. More than 80 primary and affiliated faculty members conduct cutting-edge research in a wide variety of areas, such as neuroengineering, biosystems and biosignal analysis, medical devices (including biomicroelectromechanical systems (bioMEMS) and bionanotechnology), biomechanics, bioimaging, and imaging informatics. Currently, the department hosts six internationally recognized research centers: the Biomimetic MicroElectronic Systems Engineering Research Center (funded by the National Science Foundation), the Biomedical Simulations Resource [funded by the National Institutes of Health (NIH)], the Medical Ultrasonic Transducer Center (funded by NIH), the Center for Neural Engineering, the Center for Vision Science and Technology (funded by an NIH Bioengineering Research Partnership Grant), and the Center for Genomic and Phenomic Studies in Autism (funded by NIH). BME@USC ranks in the top tier of all U.S. BME departments in terms of research funding per faculty.     

Political advocacy by the American Society for Cell Biology and its partners

I trace how the American Society for Cell Biology became a strong political advocate for the scientific community. I celebrate how good leadership and an effective staff enabled its energetic volunteer organization to have an impact, but I also ask how the effort can be made more successful.Many scientists take for granted that their scientific societies advocate for the well being of their individual members and the health of science. However, advocacy is a relatively recent development that emerged over the past two decades. Advocacy is essential in a democracy because science competes for taxpayer dollars with every other activity supported by the federal government. Advocacy is also important to ensure that lawmakers adopt sensible policies. I review how the American Society for Cell Biology (ASCB) and its allies learned how to fulfill this obligation, and I ask the reader to join the effort. The objective of these advocacy efforts is to influence political decisions through education and information, but the efforts by scientific societies are completely nonpartisan. Support from both political parties is essential to meet our goals.During the 1970s and 1980s biomedical scientists discussed federal funding and public policies that affected our science. Each year the public policy staff of the Federation of Societies of Experimental Biology (FASEB) helped member societies reach a consensus recommendation on the level of federal funding for the biosciences. However, we tended to talk to ourselves because we lacked effective ways to communicate with politicians or the outside world. For the most part we relegated the responsibility for advocacy to medical school deans and presidents of research universities. Their professional associations—the American Association of Medical Colleges (AAMC) and the Association of American Universities (AAU)—generally did a reasonable job of representing the interests of the scientists who worked at their schools.     

Perspectives on human microbiome research ethics

study of ethical, legal, and social implications (ELSI) of human microbiome research has been integral to the Human Microbiome Project (HMP). This study explores core ELSI issues that arose during the first phase of the HMP from the perspective of individuals involved in the research. We conducted semi-structured in-depth interviews with investigators and NIH employees ("investigators") involved in the HMP, and with individuals recruited to participate in the HMP Healthy Cohort Study at Baylor College of Medicine ("recruits"). We report findings related to three major ELSI issues: informed consent, data sharing, and return of results. Our findings demonstrate that investigators and recruits were similarly sensitive to these issues yet generally comfortable with study design in light of current knowledge about the microbiome.     

The Chilling Effect: How Do Researchers React to Controversy?

Background

Can political controversy have a “chilling effect” on the production of new science? This is a timely concern, given how often American politicians are accused of undermining science for political purposes. Yet little is known about how scientists react to these kinds of controversies.

Methods and Findings

Drawing on interview (n = 30) and survey data (n = 82), this study examines the reactions of scientists whose National Institutes of Health (NIH)-funded grants were implicated in a highly publicized political controversy. Critics charged that these grants were “a waste of taxpayer money.” The NIH defended each grant and no funding was rescinded. Nevertheless, this study finds that many of the scientists whose grants were criticized now engage in self-censorship. About half of the sample said that they now remove potentially controversial words from their grant and a quarter reported eliminating entire topics from their research agendas. Four researchers reportedly chose to move into more secure positions entirely, either outside academia or in jobs that guaranteed salaries. About 10% of the group reported that this controversy strengthened their commitment to complete their research and disseminate it widely.

Conclusions

These findings provide evidence that political controversies can shape what scientists choose to study. Debates about the politics of science usually focus on the direct suppression, distortion, and manipulation of scientific results. This study suggests that scholars must also examine how scientists may self-censor in response to political events.     

A report on the 3rd Workshop on Heritable Disorders of Connective Tissue.

The 3rd Workshop on Heritable Disorders of Connective Tissue was held at the National Institutes of Health from 16th to 18th November, 2000. The Workshop was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH Office of Rare Diseases, March of Dimes, Coalition for Heritable Disorders of Connective Tissue, and the Foundation for Basic Cutaneous Research. It was supported by specific grants R13 AR46912 (US Public Health Service) and 4-FY00-4511 (March of Dimes Birth Defects Foundation). The Workshop was divided into six sessions, featuring 29 invited presentations. In addition to the invited participants, more than eighty guests (scientists, NIH staff, and members of the Coalition for Heritable Disorders of Connective Tissue) attended.     

Evaluation of the careers of graduates of the University of Manitoba's BSc (Medicine) program.

The careers of graduates who had taken the BSc (Medicine) (BScMed) program at the University of Manitoba, Winnipeg, between 1950 and 1975 were compared with those of matched classmate controls to determine whether the program had any influence on the research careers of the graduates. More BScMed graduates than control subjects chose an academic career (49% v. 21%), achieved specialty certification (83% v. 65%), and obtained grants (51% v. 18%) and personal awards (37% v. 18%). The BScMed graduates also had significantly more publications than the control subjects. Although part of the difference between the two groups may be explained by the tendency of students who were more inclined toward an academic career to enter the BScMed program, it was evident that the program has a substantial effect on promoting the development of clinical investigators.