Influence of site differences between urban and rural American and Central European opioid dependent pregnant women and neonatal characteristics

Background: Multi-center trials enable the recruitment of
larger study samples, although results might be influenced
by site-specific factors. Methods: Site differences of a multicenter
prospective double-blind, double-dummy randomized
controlled trial (7 centers: Central Europe (Vienna)/USA
(3 urban/3 rural centers)) comparing safety and efficacy of
methadone and buprenorphine in pregnant opioid-dependent
women and their neonates. Results: Urban US women
had the highest rate of concomitant opioid (p = 0.050) and
cocaine consumption (p = 0.003), the highest dropout rate
(p = 0.001), and received the lowest voucher sums (p = 0.001).
Viennese neonates had significantly higher Apgar scores
1 min (p = 0.001) and 5 min after birth (p ! 0.001) and were
more often born by cesarean section (p = 0.024). Rural US
newborns had a significantly shorter neonatal abstinence
syndrome treatment duration compared to Viennese and
urban US sites (p = 0.006), in addition to other site-specific
differences, suggesting a more severely affected group of
women in the urban US sites. Conclusion: This clinical trial
represents a role model for pharmacological treatment in
this unique sample of pregnant women and demonstrates
the clinical importance of considering site-specific factors in
research and clinical practice.