Yiu-fai Cheung, MD Department of Paediatrics and Adolescent Medicine LKS Faculty of Medicine

1. Sharing in GRF Application Yiu-fai Cheung, MD Department of Paediatrics and Adolescent Medicine LKS Faculty of Medicine The University of Hong Kong Hong Kong, China

2. ‘Pre-Incubation’ Is this an appropriate time to apply? • experience, credentials • track record Should I publish more on ‘focused’ clinical topics first? Discussion with mentor(s)

3. ‘Pre-Incubation’ What reviewers are looking for • scientific merit • potential impact • novelty • solid hypothesis and logical objectives • appropriateness and feasibility of proposed methodology • credentials of investigators (PI and CoIs) • existing facilities

4. Incubation Why am I selecting this clinical problem? • experience and competence • aware of the field’s research directions (‘Blue Ocean’ strategy) and knowledge gaps • competitive edge

5. Incubation Is this an ‘important’ clinical problem to study? What is the clinical impact? • paradigm shift in the understanding of clinical phenomenon and disease mechanism with long-term implications • changes in clinical practice (diagnosis, management) and outcomes • changes in health care policies • ‘correlative or descriptive’ versus ‘mechanistic’

6. Incubation Be careful if the proposal is based solely on the following premises • this clinical problem has not been studied previously (so-what and why not?) • limited data are available (how does your proposal add to the existing literature?) • existing data are extremely controversial (how does your study help to resolve the controversy?) • recent availability of new technologies (method in search of problem versus hypothesis-driven) • personal interest

7. Effect of iron overloading on arterial distensibility and endothelial function in patients with beta-thalassaemia major

8. Developing and Writing Your Research Plan

9. Hypothesis and Objectives Hypothesis-driven clinical studies • define hypothesis before designing the study • Hypothesis (one simple sentence): testable, focused, clearly conceptualized and articulated • Primary and secondary objectives: actionable terms (to determine, compare, correlate …..) • internal peer review

10. Hypothesis and Objectives Beware of • an unfocused hypothesis and hence unclear objectives • just a fishing expedition • being overly ambitious

12. Hypothesis and Objectives With testable hypotheses with achievable objectives, what then is the long-term impact? • possible outcome in terms of local relevance and clinical significance and implications

14. Background Work done by others • a concise updated literature review (what is known) • identify gaps in knowledge (what is unknown) • discuss existing controversies (what is uncertain) • justify the need for this study and describe how the study is innovative • establish links between the background and the proposed hypothesis and objectives • brief recapitulation of the clinical significance (do not overstate the significance)

15. Background Work done by your group • show the expertise (line up collaborators) • demonstrate your track record (PI and CoIs) • summary of promising preliminary data support your hypothesis show the link to the proposed study demonstrate feasibility help to build the confidence of reviewers

16. Research Plan and Methodology Study design • case-control study, randomized control trial, epidemiologic survey, other designs • how to recruit representative subjects from the target population • randomization and blinding procedures • use of flow charts / diagrams may be helpful

17. Research Plan and Methodology Subjects • reassure the reviewer of availability of participants (provide supportive data) • inclusion/exclusion criteria (justify the criteria and address potential biases) • controls (what is meant by ‘normal’ controls?)

18. Research Plan and Methodology Intervention and outcome measures • comprehensive description of intervention strategy and its implementation • potential risks, protective measures, benefits • outcomes definition of primary and secondary outcome measures validity and reliability

19. Research Plan and Methodology Instruments and data collection and procedures • description of the instruments (validity, reliability) • data to be collected (ensure their inclusion in statistical analysis)

20. Research Plan and Methodology Sample size calculation and statistical analysis • discuss with biostatistician • power calculation for primary outcome measure • estimate realistic attrition rate • framework of statistical analysis • address missing data

21. Research Plan and Methodology Other aspects • timetable • awareness of and ways to address potential limitations • contingency plans in case of roadblocks

22. Abstract • the last to complete • the first to be read by reviewers • how to engage and sustain their interest • simple and concise nature of clinical problem need for this research innovation hypothesis, objectives, methodology clinical significance

23. Finally Putting yourself in the shoes of the reviewers • conciseness, clarity • layout and formatting • avoiding jargons and too many abbreviations • self-contained proposal • need to be taught at times • ‘abstract’ and ‘hypothesis and objectives’