# Presentation: 892721

## Grant Writing [101] WorkshopScott E. Lukas, Ph.D.

*Director, Behavioral Psychopharmacology Research Laboratory and Sleep Research Program, McLean Hospital*
*Professor of Psychiatry (Pharmacology) Harvard Medical School*

- Supported by NIDA Grant KO5 DA00343

## Pathways to a Research Career

- 2 Steps Towards a Career in Research

**2. LONG & SUCCESSFUL RESEARCH CAREER WITH FULL NIH FUNDING FOR LIFE!!!**

- 1.

## Pathways to a Research Career

- Training Paths Towards a Career in Research

- Finish
- College

**Supported on Mentor’s**
**Grant**

**Submit F31 Pre-Doctoral**
**for thesis only**

**Submit F31 prior to graduation**

**F31 supports coursework & thesis**

**Medical School**

**M.D. Awarded--Internship**

**Residency**

**POSTDOCTORAL**

**T32 Institutional Training**

**F32**

**Ph.D. Awarded**

**RO1**

## Pathways to a Research Career

- Paths to that first RO1...

**1st **
**RO1 Grant!**

-  CEBRA

*or*

*or*

**1st **
**RO1 Grant!**

**+**

**1st **
**RO1 Grant!**

**POSTDOCTORAL**

**F32**

## Pathways to a Research Career

- Training mechanisms

- http://grants1.nih.gov/training/careerdevelopmentawards.htm

## Pathways to a Research Career

- Training mechanisms--F series

- •  F31 Pre-doctoral: designed to provide salary 	support and limited research funds during 	the various phases of graduate school, 		leading to a doctorate degree.
- •  F30 Pre-doctoral/M.D.: is similar to F31 		except that clinical training is 			incorporated as candidate works toward 	a M.D./Ph.D. degree.

## Pathways to a Research Career

- Training mechanisms--F series

- •  F32 Postdoctoral: designed to provide salary 	support and limited research funds during 	postdoctoral training in a relatively new 	direction for the candidate.
- •  T32 Institutional Training Programs: 			Supports an institution to train pre and 		postdoctoral fellows.

## Pathways to a Research Career

- Training mechanisms--K series

- •  KO1 Mentored Research Scientist 			Development Award: For *most* basic 		scientists in a new area of research.
- •  KO8 Mentored Clinical Scientist Research 	Career Development Award: For clinical 	research scientists in non patient-related 	research.

## Pathways to a Research Career

- Training mechanisms--K series

- •  K23 Mentored Patient-Oriented Research 			Career Development Award: For clinical 		research scientists in patient-related research.
- •  K25 Mentored Quantitative Research 			Development Award: Fosters 				interdisciplinary collaboration for 				scientists with engineering, mathematical 		or statistical backgrounds.

## Pathways to a Research Career

- Training mechanisms--K series

- •  K24 Midcareer Investigator Award in Patient-		Oriented Research: For clinical mentors 		conducting funded research.
- •  KO2 Independent Scientist Award: Develops 		the career of funded scientists.
- •  KO5 Senior Scientist Award: For outstanding 		scientists with a sustained level of high 			productivity and mentoring.

## Pathways to a Research Career

- {relatively} New mechanism (K99/R00)

- •  NIH Pathway to Independence (PI) Award
- •  PA-06-133
- •  Provides up to 5 years of support in 2 phases:
- 	• Phase I: 1-2 years mentored support for 		promising postdoctoral scientists
- 	• Phase II: Up to 3 years of independent 		support, contingent upon securing an 		independent research position.

## Pathways to a Research Career

- New mechanism (K99/R00)

- •  Applicants may submit only one PI award 		application.
- •  May not simultaneously submit applications 	or have awards pending for any other PHS 	career development award (K-series) or 	research award (R-series).
- •  Up to two amended applications may be 		submitted.

## General Principles

- Science2 + Marketing
- Resources x (pilot data + good idea)

- =  Grantsmanship

- Your *end product *must survive the
- question “So What?” In addition, it must:
- 	*be important*
- 	*be unique*
- 	*contribute significantly to the field*

## Review Criteria

- •  SIGNIFICANCE
- •  APPROACH
- •  INNOVATION
- •  INVESTIGATOR
- •  ENVIRONMENT

**Hot **“TIP” # 1:  Reviewers are asked to identify the STRENGTHS and WEAKNESSES of your proposal---USE those words in your application to help guide the reviewer!

## Preparing to Write that First RO1

- When to write that first RO1...
- •  Plans for your first RO1 should be built into 	your K Award Training Plan.
- •  So, do a reality check--”Am I ready?”
- •  Take care of the one review criterion that is 	not easily fixed by simple editing or 		running a spell checker--> the Investigator!
- •  Just as in real estate, three important items to a 	K Awardee at this point are---

## More Publications!!!

- Preparing to Write that First RO1

- ---Publications!

- ---Publications!

- and

## Preparing to Write that First RO1

- •  Remember why you were awarded a F or K 	in the first place--to protect time so that 	you can gain valuable experience to 		prepare you for a career as an independent 	scientist.
- •  If you complete your training without 		publishing the results, then the reviewers’ 	enthusiasm for your RO1 application will 	be significantly “dampened”.

## Preparing to Write that First RO1

- •  If it has not been published, then you did not do 	it!
- •  Avoid filling your CV with a bunch of abstracts 	or posters in lieu of peer-reviewed 				publications.
- •  This suggests that either you are unfocused or 		cannot finish a project.
- •  Alternatively, if you convert abstracts to papers, 	then you show good promise.

## Preparing to Write that First RO1

- •  Avoid using the words “in preparation”--			the universe is in preparation.
- •  Awards involving clinical or long-term 			studies need to be creative to ensure 			productivity along the way....
- •  Need to identify smaller components that make 	contributions to the field and warrant 			publication.

## Preparing to Write that First RO1

- •  One way to build a career is to collaborate 		on the grants of others--these publications 		count too!
- •  Use early awards to travel to other labs and 		meet with potential colleagues, both within 		and outside of your institution.

## Preparing to Write that First RO1

- •  Another good reason to publish is that you 	can (and should) use data collected during 	your training as pilot data/preliminary 		studies for your RO1.
- •  Anticipate the need to resubmit, so do not 		wait until the 5th year of your K to send in 	your first application *(end of 3rd year is a **	**good time).*

## Concept Development-RO1

- 	          What should you write about?
- • *Focused *sequence of studies that build on one 		another...
- • Planned studies that:
- 	• have strong theoretical basis
- 	• are hypothesis-driven
- 	• provide useful info regardless of outcome
- 	• info from one study sets stage for others
- 	• have *contingency* plans if they do not work

## Concept Development-RO1

- 	          What should you write about?
- Questions:
- • what is not known about a topic?
- • what new information will be learned?
- • why is it important?
- • how will it be applied?
- • will your project fill any gaps in the literature?
*SPEAK TO NIDA PROGRAM STAFF!*

## Concept Development-RO1

- Focus:
- • Contrary to popular belief, your research focus 		should be narrow, not broad-based.
- • Begin to think about a specific area of research 		within a field.
- • Avoid making grandiose statements about the 		direction of the field and how your proposal 		will change it all...

## Concept Development-RO1

- Focus:
- • Avoid the appearance of a “fishing expedition”.
- • To do this, try to limit your proposal to _**3**_ 			primary hypotheses.
- • Avoid the temptation to get around this by 			adding multiple “secondary hypotheses”.

## Writing Tips

- Title: The title is the FIRST thing that a reviewer 		will 	see so be creative and grab their interest.
- Abstract: This must give an overview of all key 		elements in the proposal. It is a mini 			application and should note the importance, 		background and goals of the research. It is 		archived in NIH databases separate from your 	proposal (CRISP).

- 1

## Writing Tips

- Specific Aims: * *Summary of proposal and goals. 		Typically, complete this in 1 page or less. 		State the hypotheses to be tested and how the 	various phases of the study fit together, 		especially if there are both short- and long-	term goals. If you are responding to an RFA, 	then state the mechanism and how your 		application fits.

- 2

## Writing Tips

- Background & Significance: * A *succinct, scholarly 	and persuasive dialogue that ends with **why** 		the work should be done. Point out the 			theoretical importance of your proposed 		research plan and end with how your research 	will move the field forward. Plan to allocate 		3-5 pages for this section.

- 3

**Hot** “TIP” # 2:  Review _only_ most important literature; do not 		cite every paper written on the topic!

## Writing Tips

- Preliminary Studies: * *Present real data (in graphic 	or tabular format) that describes the relevance 	to your application with the aim of showing 		that you have the required expertise to carry 		out the proposed studies. This is where 			PILOT DATA becomes very important as it 		demonstrates the feasibility of the study. 		When possible, try 	to use the same 			instrumentation that you propose to use in the 	application.

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## Writing Tips

- Preliminary Studies: * *Pilot data can be a few 		subjects, and if used properly, can convince 		the reviewers that the proposed studies are 		***feasible***. Often, this section can be filled with 	your prior research findings, but other 			relevant experience or studies conducted by 		your co-investigators can be included.

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## Writing Tips

- A lack of Pilot Data [in an RO1 application] is likely to be a fatal flaw, especially for young investigators.  IF you do not have any Pilot Data, then consider using a different mechanism such as a RO3, R21, B/START, etc.

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## Writing Tips

- Progress Report (Competing Continuation Applications only): * *Very important as it demonstrates what you have been able to accomplish during the *prior* funding period.
- This section is often the *first* of a competing renewal that is read by the reviewer, so spend plenty of time on it.  Refer to published papers and include reprints in Appendix.

- 7

## Writing Tips

- Progress Report (con’t): * *Put Tables and Graphs 		in this section even if you include reprints as 	reviewers are not obligated to look at the 		Appendices.
- •  Do not shrink your figures down to the 			molecular level--they must remain legible!
- Also explain any important developments that had an impact on the rate of progress.

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## Writing Tips

- Progress Report (con’t): * *If you cannot read the graph, then there is no reason to put it in your application.

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## Writing Tips

- Progress Report (con’t): * *In the absence of solid 		progress during the prior funding period, an 		otherwise well-crafted and exciting 			Competing Renewal is doomed to be scored 		lower because of inadequate progress.
- Remember, what you did yesterday is the best predictor of what you will do tomorrow!

- 10

## Writing Tips

- Progress Report (con’t): * *There are no firm page 		limits here, but this section should be longer 		for a competing renewal than for an initial 		submission. A range of 7-8 pages is a good 		starting point and then adjust up or down 		according to your specific needs and the 		scope of the progress.

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## Writing Tips

- Design & Methods:
- 	Introduction-why do the experiment in this 			particular way?
- 	Hypotheses-be clear and concise
- 	Subjects-describe in sufficient detail
- 	Design-use diagrams when possible
- 	Procedures-explain variations, cite standards
- It is also important to explain why you chose a particular method or strategy.

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## Writing Tips

- Design & Methods:
- 	Data analysis-include statistical plan as well 			as a power analyses to justify the N.
- 	Summary-restate the importance of 				experiment and future directions of the 			research should the experiments be 			successful.

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## Writing Tips

- Design & Methods: * *
*•  *Address potential problems and solutions (if 		you have any), but be careful that you do not 	offer up potential problems and no solutions 		or contingency plans or alternatives--the 		reviewers will see this as a weakness in your 	Approach.

- Hot “TIP” # 3: Provide rationales throughout as to why certain
-       methods were selected and why key alternatives were not

- 14

## Writing Tips

- Design & Methods: * *
- •  Let the “artistic” side show with well-			designed headings, emphasis and symmetrical 	organization across studies.
- •  Block diagrams are VERY helpful, especially 		with more complicated research designs.

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## Writing Tips

**Hot** “TIP” # 4:  “Overly Ambitious” is a frequent flaw of most young
-              grant writers

- • Timeline: a realistic and well-planned estimate of 		start/end times for each experiment
- 	DO NOT just stick experiment #1 in year 1 and 			experiment # 2 in year 2, etc...
- 	Make sure that this matches your budget, % effort 		and requested FTEs

- 16

## Writing Tips

- • Human/Animal Subjects: allows you to address 			women, minorities and children/adolescent 			subjects--not included in the 25 page limit.
*Note on distributions*: The % of women/minorities relates to the percent of the population that have the disease or problem being studied, not the % that is available in your home town!

- 17

- Hot “TIP” # 5:  Abide by the page limitation and the minimum font--The new forms are set up to keep these consistent!

## Supporting Material

- • Budget Justification: Allows you to explain how you 	will use the funds as well as define the role of key 	personnel. However, with *Just In Time* guidelines, 	detailed information is not typically requested 		until you pass the initial review (or if you are 		requesting more that $250K per year, direct costs).
- • Biosketches: Make sure that these are current. It is bad 	form to include the biosketch of a senior co-			investigator and his/her last publication is listed as 	1997--CHECK THAT THEY ARE ACCURATE 	AND CURRENT

## Supporting Material

- • Other Support: This section should provide enough 	detail to assess how unique the present proposal is 	and whether there is any scientific or budgetary 	overlap with other projects. If there is overlap, 	simply state it and note what adjustments would 	be made should an award be made. Double check 	the Percent Effort to ensure that key personnel are 	not over committed.

## Supporting Material

- REMEMBER THIS
- Reviewers are only allowed to evaluate the material that is in the application, even if they have first hand information to the contrary! So, be sure to include all pertinent data that helps them review your application.

## Supporting Material

- • Resources & Environment: Allows you to describe the 	key facilities available to you and/or where the 		research is to be conducted. If you are 	collaborating with another scientist, make sure 	that his/her information is also included. Also, 	describe the key instruments that are available to 	you, and which items are not. This is very 	important if you are requesting funds for 	equipment.

## Supporting Material

- • Resources & Environment: Make sure that you have 	letters of commitment from the lab directors or 	service chiefs indicating that you have access to 	the resources that you describe. If you are 	recruiting a clinical population, have the letter 	state how many potential subjects will be made 	available to you and over what time period. This 	will address the issue of feasibility.

## Successful Writing Strategies

- • Look for local support!
- 	Many departments have small startup funds for 		young investigators
- • Start off by writing 5-6 Specific Aims.
- 	(you can delete some later)
- • Enlist in the aid of 2-3 more experienced investigators 	to review your Aims and help you               !
- • Revise your Aims and get additional feedback.

- 1

- FOCUS

## Successful Writing Strategies

- • **Do not try to write your Background & Significance ****	****Section right now! **
- 	Many things could change and you will waste 		time justifying a line of research that you later 		decide is not feasible in this application.
- • As you finalize your aims, an outline of the 			Background & Significance Section will emerge.
- 	The reason for waiting is that these section can 		cause significant “writer’s block.”

- 2

## Successful Writing Strategies

- • Lack of focus is biggest problem for young 			investigators.
- 	There is a tendency to try to “solve the world’s 		problems” in a single RO1 application
- • Once your aims are set, arrange your Preliminary data 		to support these aims.
- 	Sometimes work that you have done in other labs 		can be used to demonstrate feasibility.
- • Write your Methods section next.
- 	Be sure to follow your Specific Aims!

- 3

## Successful Writing Strategies

- • Justify your selection of specific methods if there are 		multiple strategies that could be used.
- 	It is never wise to “trash” another method in favor 	of the one you have selected--you just never know 	what method your *REVIEWER* uses!!!!
- • Write your Background and Significance Section next.
- 	Now that you have your aims and experiments 		finalized, you can focus on setting up the rationale 	for conducting the study. Note that you will have a 	good idea of this section--just not written yet.

- 4

## Successful Writing Strategies

- • Write your Abstract next.
- 	It is wise to use your Specific Aims as a template 		here to avoid any inconsistency. _*Also, the abstract *_*	*_*is the one item that nearly every reviewer in the *__*	*_*	*_*room will read!*_
- • Write your title LAST!
- 	This can be more meaningful now that the entire 		scope of the project is well defined.

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## Successful Writing Strategies

**Hot** “TIP” # 6:  Include basic information where necessary.  Only a 	 	few of the reviewers will be EXPERTS in all aspects of your 	 	application.

- • Audience: remember who is reading your application--	these are VERY busy people, so make it easy for 		them to follow your rationale, logic, planning, 		methods, analysis and thinking.
- • Reviewers: are looking to see if you can THINK 		through a problem and assign *strengths* and 			*weaknesses* to each aspect of the review criteria.

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## Successful Writing Strategies

**Hot** “TIP” # 7:  High tech is no substitute for 		solid logical planning.

- • Repetition: repeat significance and what will be 		learned at the end of experiment.
- • KOD*: wonderfully elaborate and detailed 			methods, 	techniques and procedures are 		worthless if you do 	not convince the 			reviewer that the study is worth doing in the 		first place!
- 							* Kiss of Death

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## Successful Writing Strategies

- • Power of suggestion: highlight the strengths of 	your proposal wherever you can.
- • Humility: it is far better to identify weaknesses 	and explain how you will deal with them 	than it is to “hope” that the reviewer will not 	find them--they usually do!

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## Successful Writing Strategies

**Hot** “TIP” # 8:  Use **Bold**, *italics* or _underline_ judiciously to emphasize key points and to help with the organization--BUT do not overdo it!

- 9

## Successful Writing Strategies

- • There are two steps to becoming a millionaire:
- 	The first step is to get a million dollars.
- 	and, the second step is to...
- • The bottom line is that you need to have a good 	idea that is a significant issue, 	preliminary/pilot data, a well crafted 	approach, a solid research team and a 	supporting environment to earn a highly 	meritorious score!

- 10

## Successful Writing Strategies

- • Where do you get good ideas? It is harder to 		come up with one when you are trying to...

- 11

## Common Pitfalls

- • Common problems include:
- 	•  overly ambitious or grandiose (lacks focus)
- 	•  background lacks critical review
- 	•  design flaws
- 		•  missing control groups
- 		•  wrong control groups

- 1

## Common Pitfalls

**Hot** “TIP” # 9:  Try to get accurate measures of effect sizes so that you can predict sample sizes.

- 2

## Common Pitfalls

- •  design flaws
- 	•  insufficient statistical power
- 	•  imprecise measures (dependent variables)
- 	•  cannot recruit the needed population
- 	•  lack of face validity
- •  methods not appropriate for questions posed
- 	•  sampling errors
- 	•  “you picked the wrong technique...”

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## Common Pitfalls

**Hot**  “TIP” # 10: Pay attention to details--organization, spelling and grammatical errors question the care that you used to put the rest of the application together.

## Common Pitfalls

- •  investigator
- 	•  lacks sufficient expertise
- 	•  lacks skilled collaborators
- 	•  lacks demonstrated “track record”
- 	•  mediocre publication record
-         *(your K-Award is supposed to fix these...)**	*

**Hot**    “TIP” # 11:  If you engage in collaboration, then let him/her READ the application before you send it.

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## Common Pitfalls

- •  studies lack cohesiveness
- 	•  sequence of experiments is not logical
- 	•  results of a study lead to a dead end
- 	•  subsequent studies rely too much on 					previous experiment(s)
- 	•  contingency plans either not stated or ill 				conceived and are not feasible

**Hot** “TIP” # 12:  Do your homework and make sure that no one
- 	has already done your study.

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## Common Pitfalls

**Hot** “TIP” # 13:  Discuss your ideas with NIDA Staff as they can help direct your efforts to improve the quality of your proposal.

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## Amended Applications -A1

- •  _*READ *_the review very carefully and then put it 		away for a day or so.
- •  If you did not receive a score, then there will 		not be a summary of the discussion.
- •  An *Unscored* application means that it was in 		the bottom half of that particular round of 		applications.
- •  A low score will have a summary of the most 		important weaknesses that led to the score.

- 1

## Amended Applications -A1

- •  Allows you to address the previous review--use 	these 3 pages *wisely*
- •  Throw out your first response to the reviewers
- •  Be sure to address ALL comments/concerns in 		the Introduction
- •  Use the same terminology as the reviewer[s]
- •  Avoid confrontation
- •  Avoid becoming defensive
- •  Highlight the major changes in the application

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## Amended Applications -A1

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- Here is an example of balanced highlighting...

## Amended Applications -A1

- 4

- _Sleep Disturbances During Drug Withdrawal_. In studies that involved administering known amounts of marihuana, the abrupt termination of access to the drug was associated with sleeplessness associated with an increase in rapid eye movement (REM) sleep. The profile of marihuana withdrawal symptoms reported by Wiesbeck et al. (165) included* *sleep disturbances in 235 out of 1735 (or 13.5%) frequent marihuana users and 204 out of 270 (or 75%) frequent users who experienced multiple symptoms. Jones et al. (34) reported that disturbed sleep (verified by polysomnography) was experienced by 89% of the subjects who were abruptly withdrawn from THC; these subjects also reported nervousness, greater tension and restlessness.

## Amended Applications -A1

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- _Sleep Disturbances During Drug Withdrawal_. In studies that involved administering known amounts of marihuana, the abrupt termination of access to the drug was associated with sleeplessness associated with an increase in rapid eye movement (REM) sleep. _***The profile of marihuana withdrawal symptoms reported by Wiesbeck et al. (165) included sleep disturbances in 235 out of 1735 (or 13.5%) frequent marihuana users and 204 out of 270 (or 75%) frequent users who experienced multiple symptoms. Jones et al. (34) reported that disturbed sleep (verified by polysomnography) was experienced by 89% of the subjects who were abruptly withdrawn from THC;***_ these subjects also reported nervousness, greater tension and restlessness.

- THIS is hard on the eyes...

## Amended Applications -A1

- 	•  attack the Reviewer’s intentions
- 	•  rush to get it out by the next submission cycle
- 	•  add substantial NEW information or new studies
- 	•  over react and take comments personally
- 	•  point out the reviewers’ weaknesses
- 	•  write a rebuttal that is longer than the critique
- 	•  dwell on a reviewer’s error--make the point and 			move on with your response

**Hot** “TIP” # 14:  Ask a colleague to read your application (as a
- 	reviewer, not as a friend)

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## Amended Applications -A1

- Simply have the resolve to send your application back until the Study Section gets it right!

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## Career Planning

- • NOW is the time to develop key collaborations
- 	that will be crucial to the success of the RO1
- 	that you write in the next two years.
- • Begin to think about your career now, not in the 	last 6 months of your K or after F is over.
- • Think about the types of careers that are 			available to you and discuss with your 			mentor(s) and NIDA Program Staff.

## Career Planning

- •  Plan to obtain no more than 50-60% of your salary 		from 	your first RO1--so from where does the 		rest come?
- •  Consider building collaborations now and have small 		percentages of salary on other grants.

## Career Planning

- •  It is never too early to begin to think about such 		collaborations as they will help define you as a 		scientist and increase your chances of receiving an 	outstanding score.
- •  Do not be afraid of jumping on the RO1 treadmill of 		life. It is like buying your first home--start small 		and trade up!

## Career Planning

- •  Clinician scientists have more options in terms of 		splitting careers between clinical practice, 			teaching, consulting and research.
- •  Non clinician scientists have similar issues and can 		balance the teaching and research activities with 		consulting.
- •  Learn how to multitask--it is not what you think it is.
- •  Do not forget family life!!!!

## Some Recommendations

- • Discuss your ideas with NIDA Program Staff.
- • Have a senior colleague critically *read* your 	application.
- • Write clearly and succinctly.
- • Avoid unnecessary complexity.
- • Be open to helpful criticism--learn from your mistakes.
- • Anticipate problems and plan contingencies.
- • Be persistent! Applications often need amending.

## Some Recommendations

- •  Try to keep clinical applications below $249,000 per 		year, direct costs.
- •  However, imaging studies are typically more costly.
- •  Aim for 3 years of support; it is tough for reviewers to 	be convinced that 5 years of support is justified for 	an untested junior scientist. The budget on an RO1  	is scrutinized very carefully.

## Some Recommendations

- •  It is helpful to make out a “duty sheet” to ensure that 		all aspects of the research are covered.
- • Make sure that your research team has seen the 			application and that they have provided you with 		feedback.
- •  This means that you cannot give them the application 		to read on June 30 for a July 5 receipt date...

## Some Recommendations

- • Be persistent in reaching your goal. The success rates 		for first time applications are low.
- • Do not send off your grant and then sit around in the 		lab waiting for the results to come back--find 		other ways to collect the pilot data, foster your 		collaborative relationships and write scientific 		papers.

## Mentoring the Next Generation

- •  Avoid taking on too many students or postdocs too 		soon.
- •  You owe it to yourself (and your future students) to 		become firmly established as a researcher _*before*_ 		you try to support others.
- •  Remember, that next challenge is either getting that 		second RO1 or renewing your first grant--and 		these come up very quickly!!!

## Parting Thought

- Getting to this point is more than half of the battle...