Research
Participant adherence: measurement, run-in and effect on the estimateDefinitions of adherence, crossover and withdrawal, the effect of low adherence on power and on the estimate, the run-in period, and methods to measure adherence in clinical trials.Crossover, factorial, withdrawal and cluster designsExplains the variations on the parallel trial: crossover, factorial, withdrawal and group allocation, with the assumptions of each and what they require of the reader.Blinding: single, double, triple and blinded outcome assessmentExplains the levels of blinding in clinical trials, the PROBE design, how blinding is lost, and what a paper should report about who was blinded.Clinical trial phases: the question each phase answersDescribes phases I to IV of clinical development, the question each one answers, typical designs, and the limits of each phase for clinical decisions.Data monitoring committee: structure and functionIndependence, membership, open and closed sessions, blinding and meeting frequency of the data monitoring committee (DMC/DSMB), with examples of stopping decisions.Ethics in clinical trials: equipoise, consent, conflict of interest, and publication biasSummarizes the ethical requirements of a clinical trial, clinical equipoise, placebo use, informed consent, conflict of interest, and publication bias.Assessment and reporting of harm in clinical trialsExplains the difference between adverse event and adverse effect, the limits of trials for detecting harm, how events are collected and classified, and what a paper should report.Health-related quality of life as an outcomeDimensions, instrument selection, timing of assessment and the minimal important difference when health-related quality of life is a clinical trial outcome.Historical controls and non-randomized studiesExplains non-randomized concurrent controls, historical controls and databases, the empirical evidence of bias toward the new intervention, and when these designs have a place.Reporting and interpreting results: CONSORT, plausibility, absolute effect and applicabilityReporting guidelines, publication bias and the questions for interpreting a trial: whether it worked as planned, how it compares with other studies and to whom it applies.Study population: eligibility criteria, enrichment, and generalizationExplains how eligibility criteria define a trial population, how enrichment increases power, and the limits this places on generalizing the results.Surrogate endpoints and biomarkersDefines surrogate endpoints, presents Prentice's criteria, and uses CAST, ILLUMINATE, fluoride, and CD4 to show why an effect on a biomarker does not always predict a clinical effect.Coronary obstruction in TAVI: a decade of CT screeningFive studies on coronary obstruction in TAVI (Ojeda, Ribeiro, Khan, Jabbour, ICARO) and what CT screening still misses.Control arms of 29 trials as the natural history of chronic CAD: what the Mahesh et al. meta-analysis showsMahesh et al. pooled the control arms of 29 trials into one Kaplan-Meier curve. The idea is original, but the curve mixes four decades of therapy and does not support the claim that risk accelerates.DCB in chronic total occlusion: the order of the questionsThe comparison between DCB and DES in CTO is being made before two upstream questions have been answered.IVUS-CHIP and OPTIMAL: optimization rates and the angiography armIVUS-CHIP and OPTIMAL were neutral. Optimization rates are similar to those of the positive trials, and the angiography arm already applies what IVUS taught.Thrombosis after TAVI: frequency, clinical impact and valve designA joint reading of the Jacobsen et al. review and the SAPIEN 3 Ultra RESILIA data from OCEAN-TAVI on leaflet thrombosis after TAVI.