Yiu-fai Cheung, MD

Department of Paediatrics and Adolescent Medicine

LKS Faculty of MedicineThe University of Hong Kong

Hong Kong, China

Sharing in GRF Application

Is this an appropriate time to apply?

• experience, credentials• track record

Should I publish more on ‘focused’ clinical topics first?

Discussion with mentor(s)

‘ 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

‘ Pre-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

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’

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

Incubation

Effect of iron overloading on arterial distensibility and endothelial function

in patients with beta-thalassaemia major

Developing and Writing Your Research Plan

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

Hypothesis and Objectives

Beware of

• an unfocused hypothesis and hence unclear objectives

• just a fishing expedition• being overly ambitious

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

Hypothesis and Objectives

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)

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 hypothesisshow the link to the proposed study demonstrate feasibilityhelp to build the confidence of reviewers

Background

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

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?)

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

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)

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

Research Plan and Methodology

Other aspects

• timetable• awareness of and ways to address potential

limitations• contingency plans in case of roadblocks

Research Plan and Methodology

• the last to complete• the first to be read by reviewers• how to engage and sustain their interest• simple and concise

nature of clinical problemneed for this researchinnovationhypothesis, objectives, methodologyclinical significance

Abstract

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’