1. Protocol Overview Background4-5 pages Question/Objective/Hypothesis4 lines Design4-20 lines Study Population0.5-1 page Measurement3.5-4 pgs. Outcomes Exposures/predictors Confounders Analysis0.5-1 page Other (ethics/procedure/expected contribution) 0.5-1 page

2. Generic Structure of the Write-Up Per Main Exposure/ Outcome Variable Rationale (optional) Conceptual Definition Source of Information Reliability (past) Validity (past) (Feasibility) Operational Definition Precision/Bias Control Plan Type of Variable

3. Conceptual Definition Medication compliance-the extent of adherence to prescribed regimen (options: all, only appropriate, only essential for disease management, dose per day vs. dose and timing) Source of Information Prescription Refills (self-report, pill count, serum level, counter-cap) Reliability (past) Not tested—agreement between what dispensed and what recorded; variation between systems and pharmacists Validity (past) R=0.4-0.8 with clinical outcomes in chronic disease such as HTN (Feasibility) Can retrieve data from public insurer (except in Alberta)—appendix a=letter Operational Definition Number of pills available/number required/month Type of Variable continuous variable=% of days supply Dichotomous=compliant=(80-110%) Bias/Precision Control Subject,observer,procedure,instument Example: Measuring Medication Compliance

4. Managing Sources of Unreliability and Bias in Measurement SourcePossible ReasonsExample Remedies SubjectBiological variation (e.g. blood pressure) Repeated measurements on some subject to estimate true value Increase the number of subjects (sample size) Sampling error (e.g. health beliefs) Increase like number of items used to measure like attributes Subject’s beliefs/ memory influence accuracy of measurement Blind subjects to research question, outcome, exposure Use historical records vs. self-report Triangulate different sources

5. Managing Sources of Unreliability and Bias in Measurement SourcePossible ReasonsExample Remedies ObserverDifferent interpretation/data collection methods Train the observers Standardize the data collection method/the interpretation Blind the observer Balance observers in the design/implementation Remove/revise items where observers can’t agree Get rid of the observers; find a machine

6. Managing Sources of Unreliability and Bias in Measurement SourcePossible ReasonsExample Remedies ProcedureProcedure for data collection varies (e.g. conditions in which data collected) Standardize the data collection methods InstrumentDifferent instruments, instrument variability Standardize the instruments Calibrate the instruments regularly

7. Conceptual Definition Placque rupture risk as reflected by the following histological characteristics that reflect instability++ inflammatory cells, hematoma, thrombosis, lipid content Source of Information Ultrasound: density and texture of the placque; as assessed by multiple measures of placque size, colour, contour, luminescence, heterogeneity Reliability (past)Inter-technician and inter-interpreter agreement Validity + Responsiveness (past) Predictive study==placque rupture—how quickly does placque change and does this measure pick it up Operational Definition 52 measures obtained by US are summarized into 5 placque characteristics, each of which has a continuous score reflecting the extent to which that characteristics is present. Based on the scores in the 5 categories based on an algorith based on factor analysis, the placque is classified into one of 4 mutually exclusive ordinal risk categories (low to high), based on predictive model of rupture Type of Variableordinal Bias/Precision Control Plan Selection criteria, ?training. Establishing the procedures, agreement in producing result with expert, or 2 operators, or with a standard value, interpreters=test with xx standard images, periodically or systematically measure, same machine Hot Placques (Rupture risk) increases the risk of TIA and CVA

8. Conceptual Definition Source of Information Reliability (past) Validity (past) (Feasibility) Operational Definition Type of Variable Bias/Precision Control Plan