▁and ▁are ▁expected ▁to ▁increase ▁with ▁wider ▁use ▁of ▁public ▁subs id ies . ▁ ▁The ▁ 2 0 1 4 ▁Or phan ▁D rug ▁report ▁stated ▁that ▁the ▁percentage ▁of ▁or phan ▁drug ▁sales ▁as ▁part ▁of ▁all ▁pres cription ▁drug ▁sales ▁had ▁been ▁increasing ▁at ▁rapid ▁rate . ▁The ▁report ▁project ed ▁a ▁total ▁of ▁US $ 1 7 6 ▁billion ▁by ▁ 2 0 2 0 . ▁Although ▁or phan ▁disease ▁populations ▁are ▁the ▁smallest , ▁the ▁cost ▁of ▁per - pat ient ▁out l ays ▁among ▁them ▁are ▁the ▁largest ▁and ▁are ▁expected ▁to ▁increase ▁as ▁more ▁people ▁with ▁rare ▁dise ases ▁become ▁el ig ible ▁for ▁subs id ies ▁— ▁in ▁the ▁U . S ., ▁for ▁example , ▁through ▁the ▁Aff ord able ▁Care ▁Act . ▁ ▁Legisl ation ▁Or phan ▁dru gs ▁generally ▁follow ▁the ▁same ▁regul atory ▁development ▁path ▁as ▁any ▁other ▁ph arma ce ut ical ▁product , ▁in ▁which ▁testing ▁focus es ▁on ▁ph arm ac ok inet ics ▁and ▁ph arm ac od ynam ics , ▁dos ing , ▁stability , ▁safety ▁and ▁effic acy . ▁However , ▁some ▁statistical ▁bur dens ▁are ▁less ened ▁to ▁maintain ▁development ▁momentum . ▁For ▁example , ▁or phan ▁drug ▁reg ulations ▁generally ▁acknow ledge ▁the ▁fact ▁that ▁it ▁may ▁not ▁be ▁possible ▁to ▁test ▁ 1 , 0 0 0 ▁patients ▁in ▁a ▁phase ▁III ▁clin ical ▁trial ▁if ▁fewer ▁than ▁that ▁number ▁are ▁aff lic ted ▁with ▁the ▁disease . ▁ ▁Government ▁inter vention