!i". 3. Locations o# a$ric$lar ac$%$nct$re %oints. &ne ear 'as needled d$rin" each treat(ent) alternatin" ears at consec$ti*e *isits. Control %oints are indicated +, #illed trian"les) ) and are la+eled in italics (t'o needles). -tandardi.ed %oints are indicated +, +$ll/0s e,es) (t'o needles). 1atients in the indi*id$ali.ed treat(ent "ro$% 'ere needled in t'o locations selected #ro( a(on" the indi*id$ali.ed (#illed circles) ) and/or standardi.ed (+$ll/0s e,es) ) %oints. -ee &leson 2553 ) 4$an" 2563 and Ta+le 5 #or %recise descri%tions o# anato(ic locations. 5a,#air 5edical) 4on" Kon"). 6e are not a'are o# relia+ilit, or *alidit, st$dies o# this instr$(ent. 4o'e*er) i t i s i n 'ides%read $se a(on" %ractitioners o# a$ric$lar ac$%$nct$re. The t'o (ost acti*e %oints constit$ted the /7/7%rescri%tion/0/0 #or indi*id$ali.ed a$ric$lar ac$%$nct$re. 6.6. Ac$%$nct$re needlin" 1atients 'ere "i*en an o%%ort$nit, to as8 the ac$%$nct$rists 9$estions related to the %lace(ent o# needles onl,. :isc$ssion a+o$t the %atient/0s +lood %ress$re) treat(ent "ro$%) or the location o# %oints 'as %rohi+ited. All st$d, ac$%$nct$re occ$rred in %ri*ate treat(ent roo(s. The %atients re(o*ed their o$ter clothin" incl$din" shoes and stoc8in"s. A clean sheet 'as %ro*ided to co*er the %atient and s$%%orti*e rolls or %illo's 'ere $sed #or %atient co(#ort. The s8in 'as cleaned 'ith an alcohol 'i%e o*er the needlin" locations +e#ore the ac$%$nct$re needle 'as inserted. :$rin" the #irst ac$%$nct$re *isit) the ac$%$nct$rist de(onstrated the %oint locator on his/her o'n hand +e#ore $sin" it on the %atient/0s ear. T' o t,%es o# needles 'ere $sed) needles 'ith and 'itho$t "$ide t$+es (-eirin Kasei) -hi(i.$) ;a%an< Car+o) -$.ho$) China). The choice 'as le#t $% to the treatin" ac$%$nct$rist. All needles 'ere sterile) dis%osa+le (one ti(e $se onl,)) and (ade o# s$r"ical="rade stainless steel. -i.es $tili.ed are sho'n in Ta+le 4 (#ootnote a). 1atients in all three treat(ent "ro$%s recei*ed a$ric$lar ac$%$nct$re in t'o locations at e*er, treat(ent session. A$ric$lar ac$%$nct$re 'as $nilateral at each *isit) 'ith the side alternatin" +et'ee n L.A. Kalish et al. / Controlled Clinical Trials 25 (2004) 76C103 1 le#t and ri"ht ears at consec$ti*e treat(ent *isits. The startin" ear 'as chosen rando(l,. > # i t 'as not %ossi+le to alternate ears (#or e?a(%le in the case o# local in#la((ation or other irritation)) the sa(e ear 'as $sed as d$rin" the %re*io$s treat(ent *isit. 6.6.1. >ndi*id$ali.ed ac$%$nct$re The indi*id$ali.ed ac$%$nct$re "ro$% recei*ed cor%oreal ac$%$nct$re treat(ent accordin" to the %rescri%tion (locations and (ethods o# sti($lation) (ade +, the dia"nosin" ac$%$nct$rist. ># the %rescri%tion incl$ded onl, anterior cor%oreal %oints) the %atient 'as needled in the s$%ine %osition. @eedles 'ere retained #or 30 (in and sti($lated accordin" to the %rescri%tion at the ti(e o# initial insertion) and a"ain at 10 and 20 (in. ># +oth anterior and %osterior %oints 'ere %rescri+ed) anterior %oints 'ere needled #irst (s$%ine %osition) and retained #or 20 (in 'ith the %rescri+ed needle sti($lation at the ti(e o# initial insertion and at 10 (in. The needles 'ere then re(o*ed and the %atient %laced in the %rone %osition. The %osterior %oints 'ere then needled and retained #or 10 (in) 'ith the %rescri+ed needle sti($lation at the ti(e o# insertion. -ee Ta+le 4 and !i". 2 #or s%eci#ic in#or(ation re"ardin" needle de%th) an"le o# needle insertion and %oint locations. A$ric$lar ac$%$nct$re locations 'ere deter(ined +, the treatin" ac$%$nct$rist as descri+ed a+o*e. A$ric$lar ac$%$nct$re needles 'ere inserted %rior to cor%oreal needles. All a$ric$lar %oints 'ere needled $nilaterall, $sin" 15 (( lon") 0.20 (( dia(eter needles that 'ere inserted 'itho$t sti($lation) %er%endic$lar to the s8in to a de%th o# 1 C 2 (( or dee% eno$"h to +e en"a"ed sec$rel, in s$+c$taneo$s tiss$e and retained 'itho$t sti($lation d$rin" the 30=(in treat(ent %eriod (see !i". 3). 6.6.2. -tandardi.ed ac$%$nct$re -tandardi.ed cor%oreal ac$%$nct$re consisted o# 5 +ilateral cor%oreal %oints (total o# 10 %oints)) needled in the s$%ine %osition $sin" a ne$tral (ethod o# sti($lation (o+tainin" /7/7de 9i/0/0 'itho$t an, #$rther sti($lation). At 10) 20 and 30 (in) the ac$%$nct$rist to$ched each cor%oreal needle +$t did not sti($late the needles. The ac$%$nct$re %oints 'ere L> 11 ) - T 36) AB 20) LC 03 and -1 06. -ee Ta+le 4 and !i". 2 #or s%eci#ic in#or(ation re"ardin" an"le o# needle insertion) de%th and location o# %oints. T' o a$ric$lar needles) 4eart and ;ian" Da Ao$) 'ere inserted %rior to cor%oreal needlin") 'itho$t sti($lation and retained #or 30 (in (see !i". 3 ). 6.6.3. Control ac$%$nct$re 1atients rando(i.ed to the control ac$%$nct$re "ro$% had 5 cor%oreal locations needled +ilaterall, (total o# 10 %oints) and 2 a$ric$lar locations needled $nilaterall, at each *isit. -ee Ta+le 5) !i"s. 2 and 3 #or anato(ic descri%tions o# the locations. &$r (ain o+Eecti*es in desi"nin" the control treat(ent 'ere to choose non=ac$%$nct$re %oints 'e tho$"ht to +e the least reacti*e 'hile (aintainin" (as8in" as +est as %ossi+le. The #ollo'in" criteria "$ided o$r choices o# control %oints F
not +e considered acti*e accordin" to TC5 theor,) in the sa(e *icinit, o# the standardi.ed and (ost co((onl, $sed indi*id$ali.ed %oints) distant #ro( %oints tho$"ht to ha*e an e##ect o n the cardio*asc$lar and s,(%athetic ner*o$s s,ste() %oints on the e?tre(ities sho$ld incl$de locations a+o*e the el+o' and 8nee (considered to +e less reacti*e than %oints +elo' el+o's and 8nees accordin" to TC5 9i circ$lation theor,)) sho$ld +e needled *er, shallo'l, 'ith no sti($lation 'hatsoe*er) and the n$(+ers o# %oints sho$ld (atch the standardi.ed "ro$% . L.A. Kalish et al. / Controlled Clinical Trials 25 (2004) 76C1032 Ta+le 5 Control treat(ent "ro$% %oint s%eci#ications aLe" s$%ine head o# the #i+$la a%%ro?i(atel, 4 in. do'n the le" #ro( the head o# the #i+$la) then hal# the distance #ro( the BL to AB channel on the %osterolateral le" to'ard the +ell, o# the (. "astrocne(i$s !oot s$%ine 3rd and 4th (etatarsals a%%ro?i(atel , 1.0 C 1.5 in. a+o*e the 3rd and 4th 'e+ s%ace +et'een the 3rd and 4th (etatarsals+ et'een BL and AB (eridians near AB 41 +et'een AB and -T (eridian s+6ith ar(s #le?ed) %al(s do'n. c@ot a%%lica+le (a$ric$lar needles sho$ld +e in %lace d$rin" +oth s$%ine and %rone %ositions). >n all cor%oreal locations) needles 'ere inserted %er%endic$lar to the s8in 'itho$t sti($lation. -$%ine cor%oreal %oints 'ere to$ched +, the ac$%$nct$rist at 10 (in and 'ithdra'n at 20 (in. The %atient 'as then t$rned o*er to lie %rone and the re(ainder o# the cor%oreal needles inserted. A#ter an additional 10 (i n ( 3 0 (i n tot a l ti (e ) ) th e n e e d l e s ' e re to $c hed an d r e ( o * e d ' i t h o$ t s t i ( $ la ti on. A$ ri c $la r ac$%$nct$re needles 'ere inserted %rior to cor%oreal needlin") 'itho$t sti($lation and 'ere retained 'itho$t sti($lation d$rin" the 30=(in treat(ent %eriod. 7. Blood %ress$re (eas$re(ent >n order to red$ce /7/7'hite coat h,%ertension)/0/0 st$d, n$rses certi#ied +, the @GC> too8 nearl, all o# the st$d, +lood %ress$re (eas$re(ents 2573. -t$d, %h,sicians 'ere allo'ed to ta8e +lood %ress$res #o rThi"h %rone+%o%lite al #ossa a%%ro?i(atel, 4 in. a+o*e the %o%liteal #ossa) then hal# the distance #ro( the BL to the AB channel on the %osterolateral thi"h+et'een BL and AB (eridians Ar( %rone+ !orear( %rone+olecranon and (edial e%icond,le o# the h$(er$s (edial e%icond,le o# the h$(er$sa%%ro?i(atel, 4 in. a+o*e the olecranon %rocess and hal# 'a, to'ard the (edial e%icond,le e?tensor s$r#ace o# the #orear( (id'a, +et'een T4 and -> H+et'een -> and T4 (eridians +et'een -> and T4 (eridian s1oint 1atient %ositionAnato(ic land(ar8 1oint location Celationshi% to (eridians Gar @/Ac Gar @/Ac:ar 'in/0s t$+ercle s$%erior and (edial to :ar'in/ 0s t$+ercle) at the (ost s$%erior %ortion o# the sca%hoi d #ossa) +et'een the heli? and the antiheli? %osterior ear lo+e on the %osterior earlo+e) in the (ost s$%erior and (edial %ortion o# the lo+e< +o$nded s$%eriorl, +, the (ost in#erior %ortion o# the %osterior "roo*ein the a$ric$lar area #or #in"er %oints no na(ed %oints in this are L.A. Kalish et al. / Controlled Clinical Trials 25 (2004) 76C103 3 clinical %$r%oses) s$ch as 'hen (onitorin" a %atient ta%erin" or res$(in" antih,%ertensi*e (edication) +$t 'ere disco$ra"ed #ro( ta8in" other st$d, (eas$re(ents. 1atients 'ere as8ed to +are their ri"ht ar(s #or the +lood %ress$re (eas$re(ent. ># the slee*e 'as ti"ht) the %atient 'as as8ed to re(o*e his or her shirt or %$ll the ar( o$t o# the slee*e. A "o'n 'as (ade a*aila+le i# the %atient #elt (ore co(#orta+le $sin" one. 1$lse and +lood %ress$re (eas$re(ents 'ere (ade a#ter the %atient had +een seated 9$ietl,) 'ith +ac8 s$%%orted and #eet #lat on the #loor) i n an erect +$t co(#orta+le %ost$re #or at least 5 (in. The %atient re(ained seated in this #ashion $ntil all re%licate +lood %ress$re (eas$re(ents 'ere co(%leted) 'aitin" at least 2 (in +et'een re%licate (eas$re(ents. -t$d, (eas$re(ents 'ere (ade $sin" n$(+ered Ba$(ano(eter 'all= (o$nted (erc$r, s%h,"(o(ano(eters (6.A. Ba$( and Co.) Co%ia"$e) @D) that 'ere certi#ied ann$all,. &nce a %atient co(%leted screenin") st$d, n$rses did not disc$ss (eas$re(ents 'ith the %atient or the ac$%$nct$re sta##. At each st$d, *isit) the o##icial +lood %ress$re (eas$re(ents 'ere co(%leted +e#ore other (eas$res) i.e.) %h,sical e?a( and co(%letion o# sel#=ad(inistered 9$estionnaires. 1atients 'ho ate) s(o8ed) in"ested ca##eine or e?ercised d$rin" the ho$r %rior to a +lood %ress$re (eas$re(ent 'ere as8ed to ret$rn a#ter an ho$r had %assed. -tandardi.ed %roced$res 'ere $sed to deter(ine the (id%oint o# the $%%er ar() (eas$re ar( circ$(#erence at this (id%oint) deter(ine +lood %ress$re c$## si.e) a%%l, the c$##) deter(ine %ea8 in#lation le*el and (eas$re +lood %ress$re 223. &rdinaril,) three re%licate +lood %ress$re (eas$re(ents 'ere ta8en at each *isit) the #irst re%licate readin" dro%%ed) and the +lood %ress$re #or that *isit calc$lated as the a*era"e o# the second and third readin"s. ># the second and third s,stolic or second and third diastolic %ress$res di##ered +, 6 ( ( 4 " o r (ore) t'o additional (eas$res 'ere ta8en) #or a total o# #i*e) and the second thro$"h #i#th (eas$re(ents a*era"ed. Blood %ress$re (eas$re(ent %roced$res 'ere o+ser*ed %eriodicall, +, @GC> sta##) and anal,ses o# #inal di"it %re#erences #or each st$d, n$rse 'ere %er#or(ed %eriodicall, thro$"ho$t the trial in order to (onitor co(%liance 'ith the (eas$re(ent %rotocol. H. Antih,%ertensi*e (edications 1atients 'ith +lood %ress$res .140 (( 4" s,stolic or . 0 (( 4" diastolic at the 'ee8 10 st$d, *isit or later 'ere started on antih,%ertensi*e (edication) ordinaril, an ACG inhi+itor or an"iotensin rece%tor +loc8er. 4o'e*er) the thera%, co$ld +e indi*id$ali.ed +, the st$d, %h,sician +ased on the s$+ Ee ct /0s % r i o r ( e dic at i o n his to r,) +lo o d %re s s$r e r e s %on s e and co nco (i ta n t (e d i c a l %ro +le (s . Antih,%ertensi*e (edications 'ere initiated i((ediatel, i# the +lood %ress$re o# an, rando(i.ed st$d, s$+Eect (eas$red . 1H0 (( 4" s,stolic or . 11 0 ( ( 4 " diastolic. >n addition) antih,%ertensi*es 'ere initiated in the #irst 10 'ee8s #ollo'in" rando(i.ation i# an ad*erse e*ent de*elo%ed that 'o$ld +e a(eliorated +, +lood %ress$re red$ction) or i# t'o consec$ti*e +lood %ress$re (eas$re(ents (at least 7 da,s a%art) o# -B1. 170 or :B1 .105 'ere detected) startin" at the 'ee8 4 *isit or later. 1atients 'ere seen at inter*als o# no "reater than 2 'ee8s $ntil their +lood %ress$re #ell to +elo' 140 (( 4" s,stolic and 0 (( 4" diastolic. 6ith these sa#e"$ards in %lace) 'e #elt that it 'as ethical to 'ithhold (edications #or $% to 3 (onths (incl$din" screenin") 'ith a +lood %ress$re a+o*e 140/0 (( 4" . L.A. Kalish et al. / Controlled Clinical Trials 25 (2004) 76C1034 . Ad*erse e*ents The incidence o# ad*erse e##ects o# ac$%$nct$re in ($lti%le st$dies is lo' 25H)53. 6e (onitored %atients #or ad*erse e*ents o# an, 8ind) incl$din" %ossi+le e##ects o# ac$%$nct$re) o# re(ainin" o## o# antih,%ertensi*e (edications and o# ta8in" antih,%ertensi*es (#or those 'ho 'ent +ac8 on (edication). An, other $ne?%ected (edical e*ent 'as also recorded. 1atients 'ere as8ed 'hether the, had de*elo%ed an ad*erse e*ent or side e##ect o# treat(ent each ti(e their +lood %ress$re 'as (eas$red. The relationshi% o# the ad*erse e*ent to ac$%$nct$re thera%, and/or antih,%ertensi*e thera%, 'as assessed +, the st$d, %h,sician and n$rses. -erio$s ad*erse e*ents 'ere de#ined and re%orted accordin" to %olicies o# the 4$(an Cesearch Co((ittees o# the @GC>) the 5A4 and the @CCA5. 10. Ac$%$nct$re +elie#s 1atients/0 +elie#s or e?%ectations re"ardin" the e##icac, o# a (edical inter*ention can in#l$ence their treat(ent res%onse 260 C 633. 6e e(%lo,ed a sel#=ad(inistered instr$(ent +ased on the /7/7treat(ent credi+ilit, scale/0/0 o # Bor8o*ec and @a$ 2643 to assess +elie#s and e?%ectations re"ardin" the e##icac, o# ac$%$nct$re #or treatin" h,%ertension. Iario$s *ersions o# this instr$(ent ha*e +een e(%lo,ed in ac$%$nct$re st$dies 2653 . Iincent 2663 #o$nd one *ersion to ha*e "ood internal consistenc, and test C retest relia+ilit,. The three 9$estions e(%lo,ed in -4AC1 'ereF (1) 4o' con#ident are ,o$ that ac$%$nct$re can control ,o$r +lood %ress$reJ< (2) 4o' con#ident 'o$ld ,o$ +e in reco((endin" ac$%$nct$re treat(ents to a #riend 'ith hi"h +lood %ress$reJ< and (3) :oes treatin" hi"h +lood %ress$re 'ith ac$%$nct$re (a8e sense to ,o$J Ces%onses 'ere assessed $sin" a #i*e=%oint Li8ert scale. The instr$(ent 'as ad(inistered d$rin" screenin") at the 'ee8 2 *isit and at the 'ee8 10 *isit. 11 . Assess(ent o# (as8in" The s$ccess o# %atient (as8in" 'as assessed 'ith a sel#=ad(inistered instr$(ent. 1atients 'ere as8ed to indicate 'hich treat(ent "ro$% the, tho$"ht the, 'ere rando(i.ed to) +, circlin" one o# #o$r choicesF the three treat(ent "ro$%s and /7/7don/0t 8no'./0/0 > # the, indicated one o# the three treat(ent "ro$%s) a second 9$estion as8ed ho' con#ident the, 'ere o# their ans'er (on a 5=%oint Li8ert scale) and a list o# 10 ,es/no 9$estions addressed 'hich #actors their assess(ent 'as +ased on. Ce%resentati*e #actors incl$ded chan"e (or lac8 o#) in +lood %ress$re and in o*erall 'ell +ein") sensations d$rin" ac$%$nct$re) chan"es in $se o# (edication) location o# ac$%$nct$re %oints and /7/7E$st "$essin"./0/0 The instr$(ent 'as ad(inistered at the (onths 4 and 12 *isits) i.e.) a#ter the %ri(ar, end%oint 'as assessed. 12. !$nctional health stat$s !$nctional health stat$s 'as (eas$red in -4AC1 %artici%ants $sin" the -!=36) a *alidated sel#=re%ort 9$estionnaire that has +een in 'ide $se #or (ore than a decade 2673 . The -!=36 #oc$ses on ei"ht di(ensions o# health. 1re*io$s st$dies ha*e sho'n that h,%ertensi*e %atients score lo'er on the -!=3 6 L.A. Kalish et al. / Controlled Clinical Trials 25 (2004) 76C103 5 than do nor(otensi*e %atients 26H C 703. > n addition to "eneral health) do(ains (ost consistentl, a##ected are those related to %h,sical s,(%to(s. A linear relationshi% has +een o+ser*ed +et'een the $se o# antih,%ertensi*e (edications and #$nctional health stat$s 26H3. -4AC1 %artici%ants 'ere as8ed to co(%lete the -!=36 d$rin" screenin" and at the 'ee8 10 and (onth 12 *isits. 13. -ched$le o# (eas$re(ent Ta+le 6 sho's the sched$le o# ac$%$nct$re treat(ents and st$d, assess(ents d$rin" the rando(i.ed trial. -ched$lin" o# ac$%$nct$re is descri+ed a+o*e. Blood %ress$re 'as (eas$red e*er, 2 'ee8s $ntil the 'ee8 10 *isit) then at (onths 4) 6) and 12. 5ore #re9$ent +lood %ress$re (eas$re(ents 'ere (ade as clinicall, indicated. Co(%rehensi*e %atient e*al$ations 'ere %er#or(ed at the 'ee8 10 and (onth 12 *isits. The tar"et dates #or all *isits 'ere (eas$red #ro( the #irst da, o# ac$%$nct$re. Iisit 'indo's 'ere esta+lished aro$nd the tar"et dates #or each *isit. !or *isits thro$"h 'ee8 10) each 'indo' e?tended #ro( 6 da,s %rior to 7 da,s a#ter the tar"et date. !or later *isits) each 'indo' e?tended #ro( 1 (onth %rior to 1 (onth a#ter the tar"et date. 14. -tatistical considerations A (ini($( sa(%le si.e o# 1H0 rando(i.ed %atients 'as esta+lished on an ad hoc +asis #or this %ilot st$d,. Altho$"h not desi"ned to e*al$ate e##icac, de#initi*el,) i t i s $se#$l to %roEect the (a"nit$de o# treat(ent e##ects that this and lar"er sa(%le si.es 'o$ld +e a+le to detect 'ith hi"h %ro+a+ilit,. Ta+le 6 -ched$le o# treat(ent and st$d, assess(ents a- c r e e n i n " 6 e e 8 5 o n t h 1 2 3 4 5 6 H 1 0 4 6 1 2 Ac$%$nct$re treat(ent+ccK K K K K K B l o o d % r e s s $ r e K K K K a># the %atient dro%%ed o$t o# the st$d, %rior to (onth 12) the (onth 12 assess(ents 'ere to +e co(%leted at the ti(e o# dro%o$t. +>deall,) t'ice %er 'ee8 #or 6 'ee8s. 4o'e*er) i # this co$ld not +e adhered to) treat(ent co$ld e?tend to H 'ee8s in order to co(%lete as (an, as %ossi+le o# 12 ac$%$nct$re treat(ents. cAt 'ee8s 2 and 6F +oth a standard (%re=ac$%$nct$re) and %ost=ac$%$nct$re +lood %ress$re 'ere (eas$red. dLa+orator, assess(ent incl$ded co(%lete +lood co$nt) $rinal,sis) creatinine) +lood $rea nitro"en) electrol,tes) #astin" +lood s$"ar and li%id %ro#iles . L.A. Kalish et al. / Controlled Clinical Trials 25 (2004) 76C1036 6ith three treat(ent "ro$%s) there are t'o de"rees o# #reedo( #or treat(ent co(%arisons. :enotin" CtlLcontrol) -tdLstandardi.ed and >ndLindi*id$ali.ed) the #ollo'in" t'o ortho"onal contrasts 'ere %res%eci#ied as +ein" o# %ri(ar, i(%ortance F Ctl *ers$s (-tdM>nd)F control *ers$s acti*e (standardi.ed and indi*id$ali.ed co(+ined)) -td *ers$s >ndF standardi.ed *ers$s indi*id$ali.ed .The %o'er calc$lations are +ased on the chan"e in +lood %ress$re #ro( +aseline to 'ee8 10. An esti(ate o# the standard de*iation o# the chan"e in +lood %ress$re is re9$ired to %er#or( the calc$lations. 6e $sed +aseline and 3=(onth +lood %ress$re (eas$re(ents #ro( o*er 4000 %atients in the 5edical Cesearch Co$ncil (5CC) h,%ertension trial #or older %atients 2713 to %ro*ide these esti(ates (-. 1ococ8) %ersonal co(($nication). A#ter re(o*in" the treat(ent e##ects and adE$stin" #or +aseline *al$es +, anal,sis o# co*ariance) the %atient=to=%atient standard de*iations o# chan"e in -B1 and :B1 'ere 16.6 and .H (( 4") res%ecti*el,. Ta+le 7 sho's the e?%ected di##erences in +lood %ress$re chan"e that 'o$ld +e detected 'ith H5N %o'er) $sin" an anal,sis adE$sted #or +aseline *al$e and a t'o=sided aL0.05 test. Ta+le 7 ill$strates that the %ilot trial 'ill onl, ha*e hi"h statistical %o'er i# there are #airl, lar"e treat(ent e##ects) #or e?a(%le i# the e?%ected -B1 red$ction 'ith acti*e ac$%$nct$re is H.53 (( 4" "reater than 'ith control ac$%$nct$re. A total sa(%le si.e o# 00 'o$ld %ro*ide "ood %o'er i# this treat(ent di##erence is 3.H2 (( 4". The %ri(ar, e##icac, anal,sis 'ill co(%are treat(ent "ro$%s 'ith res%ect to +lood %ress$re chan"e #ro( +aseline to 10 'ee8s. All rando(i.ed %atients 'ith a*aila+le o$tco(e data 'ill +e incl$ded in this anal,sis and %atients 'ill +e classi#ied accordin" to their ori"inal treat(ent assi"n(ent) accordin" to the intention=to=treat %rinci%le 2723. The si(%lest co(%arison is 'ith a t'o=sa(%le t test. 6e e?%ect the distri+$tion o# chan"e scores to +e a%%ro?i(atel, nor(all, distri+$ted. 4o'e*er) non%ara(etric anal,sis 'ill +e $sed to chec8 ro+$stness o# the concl$sions. !$rther anal,ses) adE$stin" #or +aseline co*ariates (incl$din" +aseline +lood %ress$re) 'ill $se anal,sis o# co*ariance. Ta+le 7 Treat(ent "ro$% di##erence ( ,) ( ( 4") detecta+le 'ith H5N %o'er Total sa(%le si.e 1H0 360 540 720 00 -,stolic +lood %ress$re Ctl *ers$s (-tdM>nd) H.53 6.03 4.3 4.27 3.H1 -td *ers$s >nd .H 6.7 5.6 4.3 4.41 :iastolic +lood %ress$re Ctl *ers$s (-tdM>nd) 5.04 3.56 2.1 2.52 2.25 -td *ers$s >nd 5.H7 4.11 3.36 2.1 2.60 CtlLcontrol) -tdLstandardi.ed) >ndLindi*id$ali.ed. 6e ass$(ed standard de*iations #or s,stolic +lood %ress$re and diastolic +lood %ress$re) adE$sted #or +aseline *al$e) o# 16.6 and .H (( 4") res%ecti*el,) and loss o# 15N o# end%oint data d$e to %atient dro%o$t and loss to #ollo'=$%. !or e?a(%le) 'ith 1H0 %atients) and ass$(in" 15N (issin" data (153 e*al$a+le %atients)) i# %atients recei*in" TC5=+ased ac$%$nct$re (-tdM>nd) ha*e an e?%ected H.53 (( 4" "reater decline in s,stolic +lood %ress$re than %atients recei*in" control ac$%$nct$re) there 'ill +e an H5N chance o# declarin" this treat(ent contrast si"ni#icant $sin" a t'o=sided aL0.05 test . L.A. Kalish et al. / Controlled Clinical Trials 25 (2004) 76C103 7 >n addition to e?%lorator, and "ra%hical (ethods) (i?ed e##ects (odels 2733 'ill +e $sed to (odel the traEector, o# +lood %ress$re o*er ti(e. These (odels can incl$de nonlinear traEectories) interaction ter(s +et'een ti(e and treat(ent to allo' di##erent traEectories #or the di##erent treat(ent "ro$%s) +aseline co*ariates to adE$st #or %atient characteristics and ti(e=*ar,in" co*ariates) #or e?a(%le to (odel the e##ects o# introd$cin" con*entional (edications. The "oal is to descri+e the +lood %ress$re traEector, o*er ti(e 'hile adE$stin" a%%ro%riatel, #or #i?ed and ti(e=*ar,in" co*ariates and #or intras$+Eect correlation. A %otential %ro+le( that (a, +e ind$ced +, the introd$ction o# con*entional (edical treat(ent is the %ossi+ilit, that the e##ects o# treat(ent on +lood %ress$re co$ld (as8 an e##ect o # ac$%$nct$re. !or e?a(%le) i# the standardi.ed and indi*id$ali.ed ac$%$nct$re treat(ents tr$l, do control +lood %ress$re +etter than the control ac$%$nct$re treat(ent) +$t (ore %atients in the control "ro$% "o on con*entional thera%,) 'hich itsel# lo'ers +lood %ress$re) 'e co$ld o+ser*e no di##erence +et'een the "ro$%s. &ne a%%roach is to carr, the last (eas$re(ent ta8en +e#ore con*entional thera%, #or'ard to s$+se9$ent *isits. Another a%%roach to +e e?%lored is o$tlined +, 6hite et al. 2743 . Brie#l,) a n ass$(%tion is (ade that) i# %atients on con*entional treat(ents 'ere not treated) their +lood %ress$res 'o$ld +e a+o*e the "ro$% (edian. The (edian is then $sed as a (eas$re o# location (rather than the (ore con*entional (eas$re) the (ean) and anal,.ed 'ith statistical (ethods) 'hich are in*ariant to the sha%e o# the distri+$tion a+o*e the (edian) #or e?a(%le 9$antile re"ression 2753. The n$(+er o# %atients 'ho start antih,%ertensi*e (edications o*er ti(e 'ill +e ta+$lated. 1artic$lar attention 'ill #oc$s on the %ercenta"e o# %atients 'ho (eet %rotocol criteria #or res$(in" antih,%ertensi*e (edications +e#ore or at the 'ee8 10 *isit. >n addition) ti(e=to=e*ent (ethods 'ill +e $sed to descri+e the %ercenta"e 'ho start (edications o*er ti(e. G?%lorator, s$+"ro$% anal,ses 'ill incl$de treat(ent co(%arisons 'ithin s$+"ro$%s #or(ed #ro( +aseline characteristics s$ch as TC5 dia"nostic "ro$%) antih,%ertensi*e (edication histor, and "ender. 15. -creenin" e?%erience -creenin" +e"an in 5arch 2001 and ended in ;$l, 2002. >nitial contact 'as doc$(ented #or 1442 %ros%ecti*e %artici%ants o# 'hich 5 (6N) $nder'ent the #or(al screenin" inter*ie') 424 (2N) "a*e in#or(ed consent and 12 (13N) 'ere $lti(atel, rando(i.ed. 1ros%ecti*e %artici%ants 'ere as8ed ho' the, heard a+o$t the st$d,. A recr$it(ent so$rce 'as o+tained #or H7N. A(on" these) the re%orted so$rces 'ere %rint (edia (35N< (ostl, ad*ertise(ents and an article in the local %ress)) (ailin"s (2HN< (ostl, #ro( a %ostcard (ass=(ailin" ca(%ai"n)) tele*ision ne's re%orts a+o$t the st$d, (14N)) (edical %ractitioner (11N< HN #ro( the -4AC1 4,%ertension Center %h,sician/0s %ractice and 3N #ro( other %ractices)) %osted ad*ertise(ents and #l,ers (6N)) 'ord o# (o$th (6N) and other so$rces (4N). These %ercenta"es add to and O100N +eca$se 4N re%orted (ore than one so$rce. &# the 1442 %otential %artici%ants contacted) 101H (71N) 'ere e?cl$ded d$rin" initial screenin" (2N sel#=re%orted a trial e?cl$sion criterion) 37N $ninterested) 5N closed o$t 'itho$t additional screenin" 'hen recr$it(ent "oals 'ere co(%leted) and 424 (2N) %ro*ided 'ritten in#or(ed consent (14N s$ +s e9$ en tl , e ? c l $ de d + ase d o n t r i a l e l i " i+ il it , c r i t e r i a ) 2N ' i t h d r e ' # o r l ac8 o# int er e s t ) 1 3 N rando(i.ed). A(on" all those $ninterested in the trial) 33N either "a*e no s%eci#ic reason) did not ret$rn %hone calls) or did not sho' $% #or in=%erson screenin" *isits. The (ost co((on other e?cl$sion