1. Ahmet Hoke MD, PhD Johns Hopkins School of Medicine

2. MD or MD/PhD Residency Fellowship K08 Age 22 4-8 years 4 years2-3 years5 years Age 37-42 R01 After college 15-20 years to an independent career!

3.  Pros  Satisfaction of pursuing a challenging area of inquiry  You get to choose what you want to study  Potential for identification of new therapeutic targets  Clinical practice informs your research  Cons  Competition with full time basic researchers  Pressure to see more patients  Lower compensation (salary differential is high, but this is not a critical issue for most clinician-scientists)

4.  Drive to want to make a change  Mentor  Adequate training  Formal (e.g. PhD) or informal (postdoctoral fellowship in a lab, NIH medical student rotations)  Institutional support  Family support

5.  Medical school debt  NIH loan repayment program  Lack of departmental support  Protected time  Space  Access to resources  Pressure to increase clinical practice  Revenue generation (including downstream revenue for the hospital and other departments)  Long wait periods

6.  Identify a mentor early in residency  Choose someone who is willing to spend time with you and campaign for you  Choose an area of research that you like  Enjoy what you are doing, you’ll be doing it for a long time!  Start planning for your independent research program early on  At some point you need to differentiate yourself from your mentor

7.  No need to despair, even in these current economic conditions  Success rate for K-awards is relatively unchanged! (30-40% at NINDS)  First time R01 awards pay at almost at twice the pay-line of senior investigators  Yet the greatest attrition of physician- scientists occur during transition from K to R awards or when renewing first R01 grant.

8. Activity Number Reviewed Number Awarded Success Rate* K0144317239% K027227 38% K078429 35% K08509222 44% K123619 53% K23574216 38% K249749 51% K255024 48% K99795180 23% These are for applications, applicant success rate is higher due to resubmissions 2007 31% 44% 26% 37% 46% 33% 47% 35% 21%

9. These are for applications, applicant success rate is higher due to resubmissions YearSuccess Rate FY0633% FY0726% FY0839% FY0935%

10.  For most people in basic sciences this is the most straightforward path  Pick a lab and mentor early on during training (preferably during residency)  If available take advantage of R25 grants  Use your fellowship time to generate preliminary data for your K08  Take your time for your first grant ▪ It is better to delay than submit a sub-optimal grant (dept and mentor support is critical here)

11.  Proposals that do not appear to have been read by mentor  Proposals that are not good training vehicles and pathways to independence, e.g.:  Methods not yet established  Specific aims 2 and 3 dependent upon success of specific aim 1  Methods that are limited in future applicability  Vague career development plan  Generic chair letter that does not spell out institutional commitment

12.  Remove pressure for rapid submission and resubmission  With only two cycles this will not impact departmental budgets as much as before  Develop an internal review (something that is stressed by NINDS) and make it meaningful.  Allow mentor time for appropriate review  Have candidate reply to reviewers comments  Department or mentor should be able to tell applicant to wait or skip a cycle

13.  Transition to R01 requires adequate productivity from K08 years  Start to differentiate research from that of mentor  Senior authorship  Make sure you have adequate time to prepare the grant and get it vetted by mentor and departmental committee  Pitfalls in the K08 applies to R01  Take advantage of grant writing courses offered

14.  Develop a departmental committee to oversee first R01 applications  Adequate review and feedback  Consider establishing a fund to support junior faculty who is promising but has a funding gap between K08 and R01  Be rigorous in evaluating the potential of the faculty (say no early on – productivity during K years may be a good predictor of future success)

15.  Always on the look for grant opportunities relevant to your area of interest  Non-federal grants (foundations, industry etc)  Cultivate relationships with leaders in your field (they are the ones reading your papers/grants)  Posters at national meetings is better than platform talks  Strike a good balance between quality and quantity of manuscripts