Successful Concepts Study Rationale Literature Review Study Design

Successful Concepts • • Study Rationale Literature Review Study Design Rationale for Intervention Eligibility Criteria Endpoint Measurement Tools

Successful Concepts • Study Rationale – Condition to be studied is common and of great enough severity in the proposed study population to justify an intervention – Focus background rationale on mechanism(s) likely to be relevant – Is Intervention likely to be adopted by patients? (Size of benefit vs. convenience/ side effects)

Successful Concepts • Literature Review – Up-to-date – Relevant to proposed intervention in proposed population – Do not misinterpret results from previous studies – Do not ignore data that do not support the intervention – Make sure that numbers match correct references

Successful Concepts • Study Design – Clear and consistent focus • Background, primary objective, measurements, length of intervention, statistical design, title – Evidence supports anticipated incidence of events necessary for sample size – If noncompliance was an issue in related studies, propose plan to address – Account for other treatments patients might be taking that will affect endpoint – Blinding is important - especially when subjective endpoint – Historic controls problematic

Successful Concepts • Study Design – Power study to detect minimally clinically important difference - provide details (estimate of standard deviation; absolute size of effect in the measurement instrument) – Realistic effect size – Include plans to handle missing data (acknowledge if high mortality will be a problem)

Successful Concepts • Study Design – Phase I Studies • Endpoints – – Toxicity Feasibility Dose Finding; Time to Effect; Duration Evaluate Potential Endpoints and Instruments – Phase II Studies • Endpoints – Evaluate Potential Endpoints and Instruments – Toxicity – Signals of Efficacy • Statistical design • Plans for phase III

Successful Concepts • Rationale for Intervention – Previous studies suggest pathophysiologic mechanism(s) – Rationale for dose and duration of intervention – Proposed dose/intensity of intervention likely to have an effect on the proposed outcomes – Side effect profile – Is intervention likely to be beneficial only in a subset of patients?

Successful Concepts • Eligibility Criteria – Heterogeneous population has possibility of missing clinically meaningful effect – Criteria should reflect target population • If treating condition, population should have condition • If preventing condition, population should not have condition • Limit to part of population likely to benefit

Successful Concepts • Endpoint – Choose the endpoint that is most important to patient’s wellbeing (e. g. anorexia/weight/function; sexual function vs. vaginal length) – Clearly define primary endpoint and how it will be measured – Choose best instrument for measuring endpoint • Are all questions relevant to population and condition being studied? • Can measurements be standardized across sites? – Choose best time for measuring endpoint • consider time needed to see effect • natural history of condition and mechanism of action of intervention • potential for loss to follow-up

Successful Concepts • Endpoint – Make sure study time points are clear • Baseline in relation to diagnosis/treatment • Timing of assessments in relation to fixed point – Patient reported outcomes not always the best or the only relevant outcomes – Problems with CTCAE as primary endpoint • Not sensitive enough to detect all clinically relevant changes • Multibarreled • Not validated – Explain uses for all data collection at all time points

Successful Concepts • Measurement Tools – Explain why proposed tools are the appropriate measures to use in this study – Validated in similar populations - provide details