COBRE Grant Writing Workshop Significance and Innovation Dawn Elliott Thanks to Wendy Sanders, M.A. Assistant Dean for Research Career Development U Maryland School of Medicine and the NIH OER

Overall Impact versus Significance Significance: Did you ask an important question Overall Impact includes significance, but also assesses feasibility, investigators and environment Do you have the right team to carry out this research? Did you propose the best approach? Most common criticism in Overall Impact: “Our enthusiasm about the overall impact of the proposal was diminished by concerns about feasibility . . .”

Significance (NIH Directions) Explain the importance of the problem or critical barrier to progress in the field that the proposed project addresses. Explain how the proposed project will improve scientific knowledge, technical capability, and/or clinical practice in one or more broad fields. Describe how the concepts, methods, technologies, treatments, services or preventative interventions that drive this field will be changed if the proposed aims are achieved.

Significance Role of this subsection crucial 1st subsection of Strategy (1st impression) Significance will be read by all reviewers

Writing the significance section NIH doesn’t specify length; suggested length ¾ -1 page Begin: Identify research problem that you propose to address Explain importance of resolving problem link to mission of NIH institute, include public health aspects Briefly identify most important, relevant studies of other researchers –and identify important issues (questions) that have not yet been addressed Specify how your study will differ from previous work; how it will contribute to scientific knowledge/clinical practice Address anticipated impact of your research on your field on public health

Paragraph Structure Organization: Overview first, then details. Overview: topic sentence, keep it short and simple. Details: supporting sentences.

Writing about the Significance of Your Research Can Be Difficult . . . vs

How to Write about Significance: Be Straightforward –and Current Does this study address an important problem? “This research question was identified as a major research focus (cite NIH program announcement or http://www.niams.nih.gov/About_Us/Mission_and_Purpose/long_range.asp) . . .” If the aims of the application are achieved, how will scientific knowledge be advanced? “Our knowledge of . . . will be advanced by . . .” What will be the impact of these studies on the concepts or methods that drive this field? How will your studies speed advances, hasten translation? Keep in mind new NIH focus on public health: identify how your research will improve public health http://www.boneandjointburden.org/

Significance ≠ Illness Total knee arthroplasty (TKA) is one of the most common knee surgeries performed in the United States; 500,000 primary TKA procedures are performed each year with 97% of these procedures being performed in the management of knee osteoarthritis (OA) at a cost of $42,000.00 per patient. The prevalence of TKA is expected to increase to 3.4 million per year by 2030. Don’t argue that a particular illness is significant. Significance: What will you do to help cure the illness/lessen its consequences/prevent sequelae?

Just because it hasn’t been done doesn’t mean it needs to be done

Writing Significance The Significance subsection is where you begin to increase the level of detail that will extend and validate what was written in the Specific Aims section. Provide a critical analysis of the primary literature that describes the existence of a critical gap in knowledge. This is where you include some of the material that used to be in the “Background” section, which substantiates and validates that there is an important problem. Explain why its continued existence represents an important problem that must be resolved.

Writing Significance Describe the positive impact your contribution will have. How will your contribution enable subsequent thinking and research? If applicable, call attention to decreased mortality/morbidity, improvements in the quality of life or medical outcomes, reduction in cost of medical care. Example: “Improved medication adherence through mail order pharmacy use has the potential to decrease CVD-related hospitalizations and deaths in diabetes patients. Through a full assessment of the risks and benefits of mail order pharmacy use, we can gain important knowledge on how to potentially improve and expand the use of mail order pharmacy services.”

Review Instructions on Significance Reviewers are instructed to “evaluate significance within context of a research field” Take home message: include sufficient information about the field so that reviewers can make informed judgment

Critiques “Low impact” research “Incremental changes” –death knell for significance “Confirmatory research, duplicative”

Innovation (NIH Directions) Explain how the application challenges and seeks to shift current research or clinical practice paradigms. Describe any novel theoretical concepts, approaches or methodologies, instrumentation or intervention(s) to be developed or used, and any advantage over existing methodologies, instrumentation or intervention(s). Explain any refinements, improvements, or new applications of theoretical concepts, approaches or methodologies, instrumentation or interventions.

Think Broadly about Innovation A new specific aim, a new MECHANISTIC hypothesis A new combination of expertise (unusual multi-disciplinary team), leading to new perspective A new combination of 2 previously used methods A refinement of existing model, technology  If all previous studies on cartilage using an acute traumatic model, but you develop a model simulating chronic cartilage lesions that’s novel! Unique sample, opportunity provide the novelty “The proposed study is distinctive in our ability to continue to test a cohort of individuals after ACLR and collect clinical, functional and biomechanical data in a longitudinal sample who are also at risk for the development of knee OA :

Make Sure Your Research Question is Unique Search NIH Research Portfolio Online Reporting Tool Expenditures and Results (RePORTER) database to see if anyone else has been funded to carry out similar research http://report.nih.gov

How to Write about Innovation? Be Straightforward! Note: NIH makes no recommendations re: length; suggested length ½ -¾ page Does your research incorporate a new perspective on your subject? Does the proposed research employ novel concepts, approaches or methods? “The proposed research employs a novel method that we developed . . .” Are the aims original and innovative? “These aims are original in that . . . While they build on . . . , they are designed to advance our understanding of . . .”  Does the project challenge existing paradigms or develop new methodologies or technologies?

Remember: Innovation is Necessary, But Not Justification for Research “This model has been tested in rabbits, mice, rats, drosophila, dogs, cats, chickens, zebrafish and hamsters, but no one has looked at it in a frog yet.”

But… is a different story… “This model has been tested in rabbits, mice, rats, drosophila, dogs, cats, chickens, zebrafish and hamsters, but no one has looked at it in humans or better yet patients with the condition of interest.” is a different story…

Too much “innovation” Be careful about arguing you’re “outside the mainstream” Need to balance innovation with: Feasibility (preliminary data, scope of research) Credibility (training, publications)

Writing Innovation Provide the context (with citations from the literature) so reviewers will be able to understand how your project is innovative. For example, if you plan to assert that innovation stems from a new approach that you will take, you need to support that claim with discussion of previous approaches and why they were unsatisfactory. This is another place where you include material that was previously in the “Background” section.

Writing Innovation Write a statement that begins with the phrase, “The proposed research is innovative because…..” Complete this sentence by stating what objectively sets your project apart, such as a different approach you are taking or a different technology you have created, compared to past investigators. Example: “The proposed research is innovative because it addresses the potential of a healthcare system-level factor – in this case, the provision of mail order pharmacy service – rather than patient-level or provider-level factors to improve patient adherence to medications. “

Writing Innovation Describe the positive impact that will result from your innovative approach. Positive impact under Significance stems from concrete benefit that is relevant to NIH’s mission. Positive impact under Innovation stems from advancement that would have been unlikely without substantive – not incremental – departure from the status quo. Example: “Many researchers and policy makers have lamented that the field of medication adherence research is “stuck” with few good options for moving forward. Research that comprehensively assesses the impact of system-level interventions such as mail order pharmacies can significantly advance the field of structural interventions to improve patient health.”