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

Abstract

<p class="abstract"><strong>Background:</strong> 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).</p><p class="abstract"><strong>Methods:</strong> 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.</p><p class="abstract"><strong>Results:</strong> 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.</p><p class="abstract"><strong>Conclusions: </strong>The suggested two-dimensional, randomized between-patient RSP-design worked as expected and estimated MED of OMT in GERD patient sufficiently.</p><em> </em>

Determination of maintenance Jarlsberg® cheese dose to keep the obtained serum osteocalcin level; a response surface pathway designed de-escalation dose study with individual starting values

“…The dose de-escalation study was conducted as a onedimensional, within-patient 3-level RSP designed trial with individual starting dose. [9][10][11] The daily dose of Jarlsberg® cheese was used as intervention variable and the percent increase in tOC from the run-in period as the outcome variable. If the tOC level decreased >5% from the run-in period after 3 weeks during a given design level, the daily cheese dose was increased.…”

“…Recently, a dose-response study with healthy premenopausal Norwegian women was performed with a 3-level between patient RSP design. [9][10][11] The study was performed on 19 women with daily intake of Jarlsberg® cheese during a period of 5 weeks. 12 This recent study estimated the MED of Jarlsberg® cheese to 57 g/day and resulted in an increase of both the total serum osteocalcin level (tOC) and vitamin K2 levels.…”

“…9 All the previous published RSP designs are based on an equal starting dose with mid-point strategy. 10,11 RSP design with skewed starting point is previously introduced, but will not be able to correct for the expected individual deviations in osteocalcin increase. 12,13 In order to optimize the study, it is necessary to develop a within-patient RSP design with an individual starting dose, which will depend on the individual tOC increase after 6 weeks on MED.…”