Grant ReviewResearch Advocacy Training and Support Program 

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• Speaker(s): Wells Messersmith, MD, FACP

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Today’s Webinar:

What is a RESEARCH ADVOCATE? A research advocate brings the patient viewpoint to the research process and communicates a collective patient perspective.

Fight CRC’s Research Advocacy Training and Support (RATS) Program:

Goal: to improve the ability of research advocates to effectively participate in the research process. This is done by hosting person meetings, online trainings, and webinars, in addition to ongoing support.

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Assessing Grant Proposals

Wells Messersmith, MD, FACP Professor

Director, Gastrointestinal Medical Oncology ProgramCo-Leader, Developmental TherapeuticsUniversity of Colorado Cancer Center

November 2016

Abbreviations and other jargonAACR = Amer Assoc Cancer Research ASCO = Amer Society of Clinical OncologyBiosketch = brief academic summaryDOD = Department of DefenseNCI = National Cancer InstitutePI= principle investigator (leader of grant)RFP = request for proposalSRO = Scientific Review Officer

Scenario #1:

Soon after participating in a patient advocacy training program, you are invited to review grant proposals on colorectal cancer as a “patient advocate”.

Your initial reaction to this invitation is:

a) yes, I am comfortable with grant proposals and look forward to the discussion

b) maybe, I took a few science classes in high school and I can wing it

c) No, I am not a grant reviewer, and this work should be done by scientists only

The first step in reviewing grant proposals is:

a) Read the RFP (request for proposals)b) Look at the background of the principle

investigatorc) Google the institution where the grant proposal is coming fromd) Have a glass of good wine and find your reading glasses

The National Cancer Institute (NCI) Exploratory/Developmental Grant (R21) funding opportunity supports the development of new research activities in all areas of cancer research. The R21 mechanism is intended to encourage exploratory and developmental research projects by providing support for the early and conceptual stages of these projects.

These studies may involve considerable risk but may lead to a breakthrough in a particular area, or to the development of novel techniques, agents, methodologies, models, or applications that could have a major impact on a field of cancer research (biomedical, behavioral, or clinical).

Reviewer Instructions

You will provide criterion scores (1-9 range) for each of the following criteria: significance, investigators, innovation, approach, and environment. And you will provide preliminary overall impact score (1-9 range).

Reviewer Instructions

Reviewer Instructions

Reviewer Instructions

Reviewer Instructions

Reviewer Instructions

Reviewer Instructions

Reviewer Procedures

Scenario #2:You are serving as a patient advocate for a

grant review committee where the RFP states the goal is to “encourage exploratory and developmental research projects”. There is a proposal to do a clinical trial substituting TAS-102 (just approved) for capecitabine as maintenance therapy for colorectal cancer. Both drugs are oral forms of 5-FU.

11 Drugs for Colorectal Cancer“Cytotoxics” Mechanism1. 5-Fluorouracil (5-FU) -> pyrimidine analog2. capecitabine -> oral 5-FU pro-drug3. TAS-102 -> 5-FU drug with metabolism

inhibitor4. irinotecan -> topoisomerase I inhibitor5. oxaliplatin -> 3rd generation platinum

“Biologics/Targeted” Mechanism1. cetuximab -> antibody against EGFR2. panitumumab -> antibody against EGFR 3. bevacizumab -> antibody against VEGF4. ziv-aflibercept -> dummy VEGF receptor5. regorafenib -> tyrosine kinase inhibitor6. ramucirumab -> antibody against VEGFR2

VEGF= Vascular Endothelial Growth Factor; EGFR= Epidermal Growth Factor Receptor

TAS102: BackgroundCombination of two agents:- Trifluridine (FTD), a nucleoside analog activated by thymidine

kinase- Tipiracil hydrochloride (TPI), a thymidine phosphorylase inhibitor

RECOURSE trial- global phase III trial conducted in 13 countries at 114 centres- mCRC refractory to all standard therapies (including EGFR-

targeting mAb for KRAS WT patients)- Randomized 2:1 to TAS-102 (534 patients), 35 mg/m2 BID on

Days 1- 5 and 8-12 of each 28-day cycle, or placebo (266 patients)

- The primary endpoint was overall survival.Yoshino, ESMO 2014, #0022

which inhibits metabolism of trifluridine; also has anti-angiogenic properties via PDGF inhibition.

TAS-102 RECOURSE: OS

Mayer, NEJM 2015

HR = 0.68, p<0.001

How well does this proposal fit the RFP?

a) Very wellb)c)d) Not well

Scenario #3:You are serving as a patient advocate for a

grant review committee. What a small world! The PI of the next grant to be reviewed is married to your brother. You knew she was a scientist but did not know she would be applying beforehand. You are confident you can act in an unbiased manner in reviewing the grant.

You next best course of action is:a) Speak glowingly of the proposal so you

brag at the next family gatheringb) Inform the review officer and recuse

yourself from review of this grantc) Trash the proposal so your sister-in-law learns some humility for onced) Try not to say much, to avoid swaying the review

Conflicts of Interest

Conflicts of Interest

Scenario #4:A grant proposal is reviewed where the PI

proposes to study the direct effects of a drug on tumor cells. The science is excellent and the other reviewers, all PhD’s, speak highly of the proposal. To replicate the results seen in mice, study subjects will need to undergo three successive tumor biopsies.

You next best course of action is:a) Not say much, since the scientists all liked

the proposalb) Send an email to the program officer after

the meeting, expressing your concernsc) Point out that three tumor biopsies can be difficult for colorectal cancer patients, and thus limits your enthusiasm for this grant

Scenario #5:You are reviewing proposals for a “career

development award” (CDA) grant mechanism. There is one proposal where you love the idea, but the PI does not seem especially strong. There is another proposal where the PI seems incredibly talented, but you are not sure about the project.

For your evaluation of a “Career Development Award,” you should:

a) Put more weight on the proposalb) Put more weight on the PIc) Weigh them equally

Questions?

GI & Phase I TeamMy email: Wells.Messersmith@ucdenver.edu

Question & Answer:

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