國科會計畫撰寫實務

1. 國科會計畫撰寫實務 吳明賢 台大醫院內科部主治醫師 台大醫學院一般醫學科教授

2. Publish or Perish

3. Why Individuals Write Grants • Career development & progression • Personal objectives • Employer or other expectations • Fame and financial rewards

4. 知彼知己，百戰不殆 孫子兵法謀攻篇

5. Background Information on Grants • Type of grants • Funding sources • Understand the reviewer’s perspective

6. Type of Grants • Project vs. Career development grants • Basic vs. Clinical Research • Hypothesis-driven vs. Hypothesis-generating research

7. Four Major Types of Funding Source • Government 政府 • Private foundations 私人基金會 • Industry 藥廠 • Philanthropic 慈善團體

8. Why National Science Council • More prestigious than others and obtaining these types of grants may be more important for your career whether judged by you or your peers • Current approval rate: variable, depending on PI, institution, type of grants etc.

9. Anesthesiology 1988; 88:1660-6

10. Successful Grant Applications • Critical to success in academic society • Both ends of the process: writing & reviewing

11. 慎始(壹) • 先上國科會生物處網頁及最新消息公告事項或特別規劃之公開徵求計畫案件 • 參加國科會業務及計畫撰寫說明暨座談會 • 國科會生物處長給學界的信要詳讀 • 確定所用的計畫書是最新版本

12. 慎始(貳) • 參考過去成功得到經費的研究案子(Review Successful Grant Applications) • 尋求資深或有經驗人員的意見(Get Advice and Input from Mentor or Senior Investigator) • 了解你的reviewer (Know your Audience)

13. 國科會計畫審查作業 • 由二位專家初審評分並給予意見(計畫本身60%及研究者過去表現40%) • 由二位複審委員根據初審意見再予以評分 • 學門召集人召開複審會議決定通過標準 • 最後通過經費及案子由各學門召集人會議共同決定

14. Stamp of Approval • Significance • Approach • Innovation • Investigator • Environment Science 1997; 278(5314):888-9

15. SIGNIFICANCE • Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field?

16. APPROACH • Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

17. INNOVATION • Does the project employ novel concepts, approaches, or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies?

18. INVESTIGATOR • Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)?

19. ENVIRONMENT • Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support?

20. Major Review Issues in National Institutes ofHealth Grant Proposals (n=66) Area* Grants,n (%) Specific aims/hypothesis 30 (45) Goals overstated, overly ambitious or unrealistic 12 (18) Poorly focused or inadequately conceptualized 10 (15) Hypotheses not clearly articulated 8 (12) Inouye Sk et al. Ann Intern Med 2005; 142:274-82

21. Major Review Issues in National Institutes ofHealth Grant Proposals (n=66) Area* Grants,n (%) Background/significance 24 (36) Need for study not well justified 19 (29) Too much background, insufficient room for methods, 3 (5) extraneous information Overstatement of significance of study 2 (3)

22. Major Review Issues in National Institutes ofHealth Grant Proposals (n=66) Area* Grants,n (%) Preliminary/pilot studies 33 (50) More pilot work needed 27 (41) Studies cited with no clear link to proposed study 4 (6) Inadequate description of preliminary studies 2 (3)

23. Major Review Issues in National Institutes ofHealth Grant Proposals (n=66) Area* Grants,n (%) General issues 24 (36) Layout poor (editing/typographical/grammatical errors, 13 (20) inconsistencies, too-small font, omitted lines or tables, poor photocopy, difficult to read) Use of jargon, abbreviations, undefined terms 3 (5) Information presented in wrong sections 3 (5) Limitations not adequately discussed 2 (3) (For revision) Inadequately responsive to previous 5 (8) reviewers’ comments

24. Major Review Issues in National Institutes ofHealth Grant Proposals (n=66) Area* Grants,n (%) Methods 66 (100) Generally underdeveloped 10 (15) Study sample 46 (70) Inclusion criteria 36 (54) Flawed sample (nonrepresentative, potential bias) 24 (36) Poorly described 12 (18) Exclusion criteria 23 (35) Reasons for exclusion not well justified 12 (18) Important exclusions overlooked 7 (11) Postenrollment exclusions (potential bias) 4 (6) Availability of study participants not assured 4 (6)

25. Major Review Issues in National Institutes ofHealth Grant Proposals (n=66) Area* Grants,n (%) Data collection/procedures 18 (27) Inadequate description of study instruments or variables 9 (14) Concerns about validity or reliability of data collection methods 5 (8) Important variables omitted 2 (3) Many study variables not used in analyses 2 (3) Outcome 40 (66) Concerns about adequate blinding of outcome assessment 24 (36) Outcome measure inadequately described, defined, or specified 15 (23) Concerns about validity or reliability of outcome measure 9 (14)

26. Major Review Issues in National Institutes ofHealth Grant Proposals (n=66) Area* Grants,n (%) Intervention 16 (24) Inadequate description of how adherence will be monitored 9 (14) or analyzed Method of randomization not described or potential bias 5 (8) in selection process Concerns about potency of intervention 5 (8) Poorly described or unstandardized protocol 4 (6) Unblinded administration of intervention 2 (3) Concerns about unaddressed safety issues 2 (3) Controls 7 (11) Issue of contamination or co-intervention 4 (6) Lack of or inadequate description of control group 3 (5)

27. Major Review Issues in National Institutes ofHealth Grant Proposals (n=66) Area* Grants,n (%) Data analysis 42 (66) Inadequate control for important confounders 21 (32) Insufficient description of analytic approach 16 (24) Intention-to-treat analytic strategy needed 7 (11) Inadequate description of handling missing data or nonresponses 7 (11) Sample size/power 28 (42) Lack of or inadequate description of sample size or power 17 (26) calculations Estimates of attrition rates not provided, too low, or require 13 (20) justification Anticipated attrition or losses to follow-up that threaten 2 (3) validity of study

28. Things to Think About Before YouStart to Write Your Proposal (I) • What is to be done? What is the hypothesis to be tested or question to be answered? Is it easy to collect new data or repeat experiments in the new system. What is the rationale for your project? What is novel/unique about the idea/concept? • If the work is original (and, even more so, if it isn’t), why is it worth doing (significance)? • What are the specific objectives? What is the long-range goal? • Is the methodology ‘state of the art’?

29. Things to Think About Before YouStart to Write Your Proposal (II) • Who will do the work (the reputation of the grantee and her/his team)? • Why should they let you do it? What are your unique qualifications? • How long will the work take? Have you formulated a realistic time-table? • How much will it cost (budget) and why (budget justification)? • What other funds are – or might be – available to support the project? • How will the project be supported in the future after the requested funding is used up?

30. Things to Think About Before YouStart to Write Your Proposal (III) • Where will the work be carried out? • What facilities will the work require? Do you have access to such facilities? • How will the project benefit the granting institution? • How will the project benefit the advancement of science and the work of other scientists? • How will the project benefit society (health-relatedness)?

31. Things to Think About Before YouStart to Write Your Proposal (IV) • For corporation grants: How will the project increase the wealth and/or stature of the corporation? • What are the expected results, and what are your contingency plans if you hit a snag? • Are you and your team aware of what has been done in this and related fields (background)? • Does the agency require a pre-application or letter of inquiry?

32. STEPS FOR CREATING A GOOD GRANT PROPOSAL (I) • Research topic • Formulate ideas/hypotheses for proposal • Plan project • Do preliminary studies • Make an outline of the proposal • Revise outline until all necessary information is included and all is in a logical order

33. STEPS FOR CREATING A GOOD GRANT PROPOSAL (II) • Convert outline to prose document • Proofread and revise document (proposal) • Send to three readers to evaluate content (accuracy), clarity, consistency, brevity and style (emphasis, tone, presentation) • Incorporate appropriate suggestions from readers • Do final revisions, proofread, finalize proposal

34. Minimum timeline for funding of a “perfect” grant applicationto the National Institutes of Health J Pediatric Gastro & Nutr 2002; 35:107-10

35. “The important thing is not to stop questioning” “I have no particular talent, I am merely inquisitive”

36. 研究題目之選擇 • 地區性vs.世界性問題 • 方向性觀念vs.跨域觀念 • 基礎vs.臨床

38. 創新 • 等於借用加連結 • 前提是必須知道別人做了什麼

39. 畢卡索(Picasso)：好的藝術家懂複製。偉大的藝術家則擅偷取畢卡索(Picasso)：好的藝術家懂複製。偉大的藝術家則擅偷取 • If you steal from one person, that’s plagiarism. If you steal from ten, that’s research. If you steal from 100, you are a professor.

40. 摘要(Abstract) • 永遠的第一印象(everlasting first impression) • 很多reviewer只看摘要，因此務必精要但令人想看 • 必須包括hypothesis/specific aim/methodology/significance

41. 好的摘要 • 可從研究者實驗室long-term goal和本次計畫的current goal寫起 • 依序為biologic/biomedical significance, central hypothesis that guide the entire research, the 2-5(一般為3個)specific aims, experimental design/methods, desirable outcomes of the research proposed • 若能簡短提出研究結果對目前領域的影響及衝擊做結尾將更完美

44. 中心假設(Central Hypothesis) • 必須可以驗證(testable)或回答(answerable) • 最好是嶄新(novel)且以現在和主動語氣(present tense and active voice)陳述 • 若能分成幾部分，每部分由-specific aims驗證則更佳

45. HP - dependent MALToma Autocrine Altered Follicular a TNF - /BAFF dendritic cells polymorphism? Immune Signal transduction? T - Cell Delayed Responder HP - independent MALToma MALToma

46. 研究目標(Specific Aims) • 在簡介(通常一段文字)及假設之後帶出研究目標 • 通常可以列出2-5個目標，一般計畫常見為列出3個 • 目標彼此雖有相關，但最好是獨立可驗證，以避免第一個(或第一年)目標無法達成，則往下的目標也無法進行

47. SPECIFIC AIMS (Example) Based on previous studies and our preliminary results, the current research project aims to: 1. Determine alterations of plasma levels of ghrelin and leptin in patients undergoing different bariatric surgery and to investigate possible correlations between these levels and various factors, such as weight loss outcomes, H. pylori infection and duration of surgery. 2. Clarify whether different forms of circulating ghrelin are related to H. pylori infection and postoperative weight loss outcomes.

48. 背景(Background)和意義(Significance) • 簡要(約1/4篇幅)但明白清楚的介紹此研究目的，根據文獻目前此領域已知和未知的部分，這些未知或不清楚部分在此研究達成後，是否可得到解決 • 以簡圖介紹過去模式及本研究提出的模式更能讓reviewer了解此研究之創新性 • 若能符合邏輯地描述此研究計畫為過去的延伸，並且能提供新知識則更理想 • 謹慎使用初步結果並且引用可能reviewer所發表過的文獻

49. 初步資料(Preliminary Data) • 主要目的在讓reviewer相信主持人有能力執行所提出的研究計畫 • 好的初步成果可支持主持人所提出的創新假設 • 也可以圖表陳述 • 若能有系統地配合specific aims表示則更佳 • 整體而言約佔1/4~1/3篇幅

50. PRELIMINARY STUDIES (Example) (1) Effects of obesity surgery on the metabolic syndrome (Arch Surg 2004; 139:1088-92). In this study, we have documented that metabolic syndrome is prevalent in 52.2% of morbidly obese individuals enrolling in an obese surgery program. Significant weight reduction 1 year after surgery markedly improved all aspects of the metabolic syndrome and resulted in a cure rate of 95.6%. Obesity surgery performed by laparoscopic surgery is recommended. In addition, we have enrolled a cohort of patients who have undergone different types of bariatric surgery. (2)The influence of H. pylori infection and corpus gastritis on the postoperative outcomes of laparoscopic vertical banded gastroplasty (Obes Surg, in press) In this prospective cohort of 152 patients, we have demonstrated H. pylori infection and gastric inflammation play a significant role in the amount of weight loss after laparoscopic vertical banded gastroplasty. However, we did not provide relevant data regarding ghrelin and leptin levels in this study. Further prospective studies should examine possible mechanisms and long-term effects on weight loss.