AIM:To present statistical tools to model and optimize the cost of a randomized clinical trial as a function of the stringency of patient inclusion criteria.METHODS: We consider a two treatment, dichotomous outcome tr...AIM:To present statistical tools to model and optimize the cost of a randomized clinical trial as a function of the stringency of patient inclusion criteria.METHODS: We consider a two treatment, dichotomous outcome trial that includes a proportion of patients who are strong responders to the tested intervention. Patients are screened for inclusion using an arbitrary number of test results that are combined into an aggregate suitability score. The screening score is regarded as a diagnostic test for the responsive phenotype, having a specific cutoff value for inclusion and a particular sensitivity and specificity. The cutoff is a measure of stringency of inclusion criteria. Total cost is modeled as a function of the cutoff value, number of patients screened, the number of patients included, the case occurrence rate, response probabilities for control and experimental treatments, and the trial duration required to produce a statistically significant result with a specified power. Regression methods are developed to estimate relevant model parameters from pilot data in an adaptive trial design. RESULTS: The patient numbers and total cost are strongly related to the choice of the cutoff for inclusion. Clear cost minimums exist between 5.6 and 6.1 on arepresentative 10-point scale of exclusiveness. Potential cost savings for typical trial scenarios range in millions of dollars. As the response rate for controls approaches 50%, the proper choice of inclusion criteria can mean the difference between a successful trial and a failed trial. CONCLUSION: Early formal estimation of optimal inclusion criteria allows planning of clinical trials to avoid high costs, excessive delays, and moral hazards of Type II errors.展开更多
Macular edema is one of the most common visionthreatening complications of uveitis noted in one third of patients with uveitis. The release of a number of inflammatory mediators induces retinal vascular hyperpermeabil...Macular edema is one of the most common visionthreatening complications of uveitis noted in one third of patients with uveitis. The release of a number of inflammatory mediators induces retinal vascular hyperpermeability leading to uveitic macular edema(UME)which most commonly is of cystoid shape. Fluorescein angiography and non-invasive spectral-domain optical coherence tomography are standard procedures for diagnosis and follow-up of UME with some innovations such as scanning laser ophthalmoscope retro-mode imaging. Effective management of UME requires thorough understanding of the individual case. Proper control of intraocular inflammation is mandatory before targeting macular edema itself. Mainstay of treatment is immunosuppressive therapy with various drug delivery routes including topical, local subconjunctival, peribulbar and sub-Tenon's, intravitreal and systemic. Clinical trials with biologics are under way to study the efficacy of these agents in suppressing intraocular inflammation and resolution of UME. Visual prognosis in UME depends on numerous factors. Younger age and better visual acuity at baseline are associated with more favorable visual outcome in most展开更多
文摘AIM:To present statistical tools to model and optimize the cost of a randomized clinical trial as a function of the stringency of patient inclusion criteria.METHODS: We consider a two treatment, dichotomous outcome trial that includes a proportion of patients who are strong responders to the tested intervention. Patients are screened for inclusion using an arbitrary number of test results that are combined into an aggregate suitability score. The screening score is regarded as a diagnostic test for the responsive phenotype, having a specific cutoff value for inclusion and a particular sensitivity and specificity. The cutoff is a measure of stringency of inclusion criteria. Total cost is modeled as a function of the cutoff value, number of patients screened, the number of patients included, the case occurrence rate, response probabilities for control and experimental treatments, and the trial duration required to produce a statistically significant result with a specified power. Regression methods are developed to estimate relevant model parameters from pilot data in an adaptive trial design. RESULTS: The patient numbers and total cost are strongly related to the choice of the cutoff for inclusion. Clear cost minimums exist between 5.6 and 6.1 on arepresentative 10-point scale of exclusiveness. Potential cost savings for typical trial scenarios range in millions of dollars. As the response rate for controls approaches 50%, the proper choice of inclusion criteria can mean the difference between a successful trial and a failed trial. CONCLUSION: Early formal estimation of optimal inclusion criteria allows planning of clinical trials to avoid high costs, excessive delays, and moral hazards of Type II errors.
文摘Macular edema is one of the most common visionthreatening complications of uveitis noted in one third of patients with uveitis. The release of a number of inflammatory mediators induces retinal vascular hyperpermeability leading to uveitic macular edema(UME)which most commonly is of cystoid shape. Fluorescein angiography and non-invasive spectral-domain optical coherence tomography are standard procedures for diagnosis and follow-up of UME with some innovations such as scanning laser ophthalmoscope retro-mode imaging. Effective management of UME requires thorough understanding of the individual case. Proper control of intraocular inflammation is mandatory before targeting macular edema itself. Mainstay of treatment is immunosuppressive therapy with various drug delivery routes including topical, local subconjunctival, peribulbar and sub-Tenon's, intravitreal and systemic. Clinical trials with biologics are under way to study the efficacy of these agents in suppressing intraocular inflammation and resolution of UME. Visual prognosis in UME depends on numerous factors. Younger age and better visual acuity at baseline are associated with more favorable visual outcome in most
