Purpose: Determine the needed volume and durability of organ replacement technologies

Background: More people register for transplant each year than the available supply of cadaveric organs.  One solution is to manufacture or cultivate organ replacements (ORT) to meet this demand.  One technology expected to reach market soon are tissue-engineered organs, where liver cells are grown on organic scaffold.

Methods:  A discrete-event simulation model of the liver allocation system was constructed.  This was calibrated against waiting list length (WL), deaths, lost organ and other data published by UNOS from 1992 through 2002.  The model was then run assuming ORTs were introduced in year 10 of the model.  Sensitivity analysis was performed on the durability from 1 month to 5 years and production volume of these ORTs.  For this analysis, ORT production volume was assumed to grow at 10%/year from their introduction. This is approximately the same growth rate of transplant center since their introduction.  Patients made no distinction between offered cadaveric organs or ORTs.  If either organ type failed the patient reregistered on the WL.  There were no limits in these scenarios on the number of times this may occur.  The WL length was then compared to the projected WL assuming patient and cadaveric organ procurement remain constant starting model year 10.

Results:  Volume: For an initial volume of 1000 ORT/year significant reduction in the WL is seen between year 3 and 4 after their introduction (p<.05).  For initial volumes > 2500 ORT/year significant reduction is between 1-2 years (p<.05).  Durability: Assuming an initial volume of 1000 ORT/year, durability of 3- 6 months results in a significant WL reduction between years 3-4; for durability > 1 year WL reduction is seen in <  3 years.   At volumes of 500 ORT/year no significant reductions are seen until durability > 5 yrs > 6yrs have passed. For durability < 3 months at volumes < 500 ORT/Year temporary increases in the WL may occur as patients temporarily feedback into the system faster  than they are removed (p=ns).

Conclusion:  This study helps parameterize the durability and manufacturing volume needed for ORTs to significantly reduce the WL.  Volume appears more important than durability; however, at low volumes durability may significantly influence when reductions may be seen.