Randomized response surface pathway design with skewed starting point and stochastic dose window

Background:The aim was to introduce response surface pathway(RSP)-design with skewed starting value and stochastic dose-window to estimate optimal efficacy dose (OED) of BP-C2 after IL-1? stimulation in Atlantic salmon.Methods:54 healthy smolt of Atlantic salmon between 50 and 100g before habituated to saltwater were included. The study was conducted as a one-dimensional, randomized between-patient three-level RSP designed trial with one interventional-and one response variable and odd outcomes. The interventional variable was intraperitoneal injected BPC2 with skewed starting dose of 0.10 mg/100g related to the initial dose-window <0.02-0.5 mg/100g. The response variable was the Ct-value of mRNA IL-1? expression 24 hours after injection.Results:Skewed starting value of 0.10 mg/100g was chosen in the first design-level with a dose-window of <0.0-0.20].The three smolt obtained a reduction in Ct-value above 15%, and the dose-window adjusted with the lower boundary equals the previous dose. The five smolt at second esign-level received 0.16 mg/100g with a dose-window [0.10-0.22]. Four smolt obtained above 15% and one of 0.5% reduction in cycle threshold (Ct)-value. Six smolt in the third design-level received 0.21 mg/100g and one 0.16 mg/100g. The mean Ct-value was reduced from 30.0 in the nstimulated situation to 25.0, 24.8 and 26.4 after BP-C2 stimulation of 0.10, 0.16 and 0.21mg/100g, respectively. The OED of BP-C2 related to IL-1? was estimated to 0.14 mg/100g.Conclusions: Skewed starting value in the initial dose-window made the K-adjustment factor and dose-window stochastic. The RSP-procedure works in accordance to the expectation and estimated OED of BP-C2 sufficiently.

Randomized two dimensional between patient response surface pathway design with two interventional and one response variable in estimating minimum efficacy dose

Background:The aim of this paper is to introduce and evaluate the RSP design with two interventional and one response variable exemplified by estimating minimum efficacy dose (MED) of osteopathic manual therapy (OMT) in treatment of gastroesophageal reflux disease (GERD).Methods:15 GERD patients, divided in three design-level with three, five and seven patients. The study was performed as a randomized two-dimensional, between-patient RSP designed multicenter study with two interventional–and one response variable. The interventional variables “Number of OMT’s” and “Treatment Interval” with common response variable, formed two independent one-dimensional randomized between-patient RSP studies. The response variable was percent reduction in sum of the five GERD score from baseline. Three GERD patients were allocated on the first design level and given six OMT with five days’ interval. Based on results obtained in the first and second design level, five patients were included to the second design level and seven to the third.Results:The two-dimensional randomized between-patient RSP-design with the combined outcome procedure worked as expected. The percent reduction in GERD score increased with increasing number of OMT’s and time intervals. This increase leveled out after three to five OMT’s and three to four days between treatments. A clinical interaction between the two interventional variables was obtained. The estimated MED of OMT in treatment of GERD was three treatments with two days between treatments.Conclusions: The suggested two-dimensional, randomized between-patient RSP-design worked as expected and estimated MED of OMT in GERD patient sufficiently