Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders
Phase: NA
Conditions: Autism Spectrum Disorder, Neurodevelopmental Disorders
Sponsor: University of North Carolina, Chapel Hill

CLINICAL STUDY PROTOCOL
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18 -unH 2021
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Protocol Number 
18 June 2021 - version DRAFT
6WXG\3HUVRQQHO
3rinFipDl ,nvHstiJDtor
/inGD
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linGDBwDtson#mHG.unF.HGu
'r. *rDFH 7. %DrDnHk, 3h'
8nivHrsity oI 6outhHrn &DliIorniD
8nitHG 6tDtHs
7Hl: 323-442-3875
(mDil: EDrDnHk#FhDn.usF.HGu
,nvHstiJDtor
'r. -ohn  6iGHris, 3h'
8nivHrsity oI 6outhHrn &DliIorniD
8nitHG 6tDtHs
7Hl: 323-442-2723
(mDil: siGHris#FhDn.usF.HGu
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8nivHrsity oI 1orth &DrolinD Dt &hDpHl
+ill
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8nivHrsity oI 1orth &DrolinD Dt &hDpHl
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2
 
  
 

Protocol Number 
18 June 2021 - version DRAFT
6\QRSVLV
6WXG\3XUSRVH
7his stuGy HntDils D "prooI oI FonFHpt" HvDluDtion oI D novHl intHrvHntion, 3DrHnts DnG
,nIDnts (nJDJHG (3,(), Ior proGromDl inIDnts Dt-risk Ior nHuroGHvHlopmHntDl GisorGHrs
(1's). 7hH oEjHFtivHs oI thH FurrHnt stuGy DrH to HxDminH whHthHr thH 3,( intHrvHntion (D)
trDnsIorms pDrHnt-inIDnt trDnsDFtions ovHr timH Ds intHnGHG, thHrHEy IDFilitDtinJ inFrHDsHs
in thH timH inIDnts spHnG in joint HnJDJHmHnt with thHir pDrHnts, DnG (E) is DssoFiDtHG
with improvHG soFiDl-FommuniFDtion IunFtioninJ DnG positivH FhDnJHs in inGiFHs oI
DutonomiF sHlI-rHJulDtion in inIDnts Dt-risk Ior 1's.
3ULPDU\2EMHFWLYH
7hH positivH DssoFiDtion EHtwHHn pDrHnt rHsponsivHnHss DnG EHttHr soFiDl-FommuniFDtion
outFomHs in FhilGrHn in JHnHrDl, DnG FhilGrHn with nHuroGHvHlopmHntDl GisorGHrs (1's) in
pDrtiFulDr, hDs GrivHn thH GHvHlopmHnt oI HDrly intHrvHntions promotinJ pDrHnt
rHsponsivHnHss Ior thHsH populDtions. 6uFh intHrvHntion moGHls DssumH thDt inFrHDsHs in
pDrHnt rHsponsivHnHss will improvH FhilG outFomHs. +owHvHr, Ior intHrvHntions tDrJHtinJ
inIDnts DnG toGGlHrs Dt HlHvDtHG likHlihooG oI or GiDJnosHG with 1's, suFh Ds Dutism
spHFtrum GisorGHr ($6'), thH HIIHFts oI pDrHnt rHsponsivHnHss intHrvHntions hDvH EHHn
moGHst in sizH DnG hiJhly vDriDElH, rHnGHrinJ thH HviGHnFH inFonFlusivH Ior pDrHnt
rHsponsivHnHss Ds D mHGiDtor oI inIDnt/toGGlHr outFomHs.
:H proposH thDt HnsurinJ D morH HIIHFtivH pDrHnt-mHGiDtHG intHrvHntion Ior this
populDtion GHpHnGs on thH JuiGDnFH oI D rHIinHG thHory oI FhDnJH—onH HxpliFitly
DFknowlHGJinJ thDt inIDnt EHhDviors inIluHnFH pDrHnt rHsponsivHnHss. 'HvHlopmHntDl
stuGiHs inGiFDtH thDt inIDnts Dt HlHvDtHG likHlihooG oI 1's DrH likHly to HxhiEit EHhDviors
thDt HithHr IDil to HliFit pDrHnt rHsponsHs or HliFit pDrHnt rHsponsHs thDt Go not HIIHFtivHly
support thH inIDnt's HnJDJHmHnt DnG lHDrninJ. ,n DGGition, optimDl IHDturHs oI pDrHnt
rHsponsivHnHss DppHDr to vDry Ds D IunFtion oI FhilGrHn's GHvHlopmHntDl lHvHls DnG othHr
GynDmiF vDriDElHs. 7o GDtH, stuGiHs oI pDrHnt-mHGiDtHG intHrvHntions hDvH not DGGrHssHG
thHsH FomplHxitiHs. +owHvHr, rHFHnt rHsHDrFh points to kHy "FhilG" vDriDElHs likHly to plDy
trDnsDFtionDl rolHs in FommuniFDtion GHvHlopmHnt DmonJ inIDnts DnG toGGlHrs with or Dt-
risk Ior 1's. 7hHsH inFluGH DspHFts oI FhilGrHn's prHlinJuistiF FommuniFDtion
FhDrDFtHristiFs (H.J., intHntionDl FommuniFDtion, GivHrsity oI FonsonDnts) thDt DrH rHlDtHG
to Eoth pDrHnt rHsponsivHnHss DnG FhilGrHn's lDtHr FommuniFDtion skills. $lso, prHliminDry
GDtD Irom our tHDm inGiFDtH inIDnts' sHnsory rHDFtivity (hypo- DnG hypHr-rHDFtivity)
prHGiFts not only pDrHnt rHsponsivHnHss Eut Dlso soFiDl-FommuniFDtion outFomHs oI
inIDnts Dt-risk Ior 1's. $rJuDEly, inFrHDsHs in pDrHnt rHsponsivHnHss lHDG to improvHG
pDrHnt-inIDnt GyDGiF HnJDJHmHnt, whiFh in turn mHGiDtHs inIDnts' FommuniFDtion
outFomHs. )inDlly, physioloJiFDl sHlI-rHJulDtion impDFts soFiDl DnG FommuniFDtion
outFomHs in FhilGrHn, Eut mDy EH GisruptHG in inIDnts Dt-risk Ior 1's, DssoFiDtHG with
thHir GiIIiFultiHs moGulDtinJ sHnsory rHDFtivity.
3
 

Protocol Number 
18 June 2021 - version DRAFT
,n rH-FonFHptuDlizinJ intHrvHntion Ior inIDnts Dt-risk Ior 1's, wH hDvH intHJrDtHG thHsH
vDriDElHs into D nHw moGHl, 3DrHnts DnG ,nIDnts (nJDJHG (3,(), with two kHy FontHnt
GomDins: 6Hnsory 5HDFtivity DnG 3rHlinJuistiF &ommuniFDtion.
2EjHFtivH 1: 7hH primDry oEjHFtivH oI this stuGy is to HxDminH whHthHr thH novHl 3,(
intHrvHntion trDnsIorms pDrHnt-inIDnt trDnsDFtions ovHr timH Ds intHnGHG, thHrHEy
IDFilitDtinJ inFrHDsHs in thH timH inIDnts spHnG in GyDGiF HnJDJHmHnt with thHir pDrHnts.
:H will Dlso HvDluDtH whHthHr GyDGiF HnJDJHmHnt outFomHs GiIIHr EDsHG on whHthHr
pDrHnts DrH FoDFhHG Iirst in thH sHnsory rHDFtivity GomDin IollowHG Ey FoDFhinJ in thH
prHlinJuistiF FommuniFDtion GomDin, or DrH FoDFhHG in thH oppositH orGHr. 
6HFRQGDU\2EMHFWLYHV
2ur sHFonGDry oEjHFtivHs will proviGH IurthHr insiJhts into whHthHr thH 3,( intHrvHntion is
IunFtioninJ Ds intHnGHG. 6pHFiIiFDlly, our sHFonGDry oEjHFtivHs DrH to:
2EjHFtivH 2: (stimDtH thH sHpDrDtH DnG FomEinHG HIIHFts oI thH two 3,( intHrvHntion
GomDins on inIDnt intHntion FommuniFDtion.
2EjHFtivH 3: (vDluDtH thH GiIIHrHntiDl FhDnJHs in pDrHnt rHsponsivHnHss IollowinJ
FoDFhinJ on two inGiviGuDl 3DrHnts DnG ,nIDnts (nJDJHG (3,() intHrvHntion GomDins —
rHsponsHs to vDriDElH inIDnt (D) sHnsory rHDFtivity or (E) prHlinJuistiF FommuniFDtion
— Ds wHll Ds FumulDtivH FhDnJHs in pDrHnt rHsponsivHnHss IollowinJ FoDFhinJ on Eoth
3,( GomDins.
2EjHFtivH 4: 'HtHrminH thH HxtHnt to whiFh (D) DutonomiF inGiFHs oI inIDnt sHlI-
rHJulDtion, DnG (E) lDnJuDJH, sHnsory rHDFtivity pDttHrns, rHsponsH to joint DttHntion,
DnG soFiDl-FommuniFDtion skills FhDnJH ovHr thH FoursH oI thH 3,( intHrvHntion.
*HQHUDO'HVLJQ'HVFULSWLRQ
7hH intHrvHntion phDsHs oI thH stuGy will usH D rDnGomizHG FompDrDtivH triDl GHsiJn, with
two phDsHs. )or 6tuGy 3hDsH 1, GyDGs will pDrtiFipDtH in EDsHlinH DssHssmHnts; thHn
HliJiElH pDrHnt-inIDnt GyDGs will EH rDnGomizHG, strDtiIyinJ Ey FhilG DJH, to onH oI two
trHDtmHnt Drms. $rm 1 IDmiliHs will pDrtiFipDtH in initiDl FoDFhinJ on thH 3,( sHnsory
rHDFtivity (65) GomDin, DnG $rm 2 IDmiliHs will pDrtiFipDtH in initiDl FoDFhinJ on thH 3,(
prHlinJuistiF FommuniFDtion (3&) GomDin. )DmiliHs will pDrtiFipDtH in 6 wHHkly FoDFhinJ
sHssions in thHir rHspHFtivH trHDtmHnt Drms, DnG rHturn Ior 3osttHst-1. )or 6tuGy 3hDsH 2,
GyDGs in $rm 1 will rHFHivH 6 wHHkly FoDFhinJ sHssions on thH 3& GomDin, DnG GyDGs in
$rm 2 will rHFHivH 6 wHHkly FoDFhinJ sHssions on thH 65 GomDin. 7hHn IDmiliHs will rHturn
Ior 3osttHst-2.
4
 

Protocol Number 
18 June 2021 - version DRAFT
6WXG\'DWH5DQJHDQG'XUDWLRQ
7hH stuGy will stDrt $uJust 1, 2017, with GDtD FollHFtion FontinuinJ Ior 22 months. 
1XPEHURI6WXG\6LWHV
7hHrH is onH stuGy sitH Ior GDtD FollHFtion, Dt thH 8nivHrsity oI 1orth &DrolinD Dt &hDpHl
+ill, &hDpHl +ill, 1&.
'DtD proFHssinJ, viGHo FoGinJ, DnG stDtistiFDl DnDlysHs will oFFur Dt two sitHs, thH
8nivHrsity oI 1orth &DrolinD Dt &hDpHl +ill DnG thH 8nivHrsity oI 6outhHrn &DliIorniD, /os
$nJHlHs, &$.  
3ULPDU\2XWFRPH9DULDEOHV
7hH primDry outFomH vDriDElH is pDrHnt-inIDnt GyDGiF HnJDJHmHnt. :H GHIinH GyDGiF
HnJDJHmHnt Ds Dn oEsHrvDElH pDttHrn oI mutuDl IoFus, DFtivH pDrtiFipDtion, DnG rHFiproFDl
HxFhDnJHs within D pDrHnt DnG FhilG intHrDFtion.
:H will FollHFt GDtD on this outFomH Dt EDsHlinH, posttHst 1 (DItHr IDmiliHs hDvH EHHn
rDnGomly DssiJnHG to Dn intHrvHntion Drm DnG FoDFhHG in onH oI thH two 3,( intHrvHntion
GomDins), DnG posttHst 2 (DItHr IDmiliHs hDvH EHHn FoDFhHG in Eoth oI thH 3,( intHrvHntion
GomDins). 
7hH rDtionDlH Ior FhoosinJ GyDGiF HnJDJHmHnt Ds thH primDry outFomH is thDt pDrHnt
FoDFhinJ in HDFh GomDin is GHsiJnHG to Dssist pDrHnts in HnJDJinJ thHir FhilG in positivH
intHrDFtions with thHm DnG inFrHDsinJ thH lHnJth oI thHsH pHrioGs oI HnJDJHmHnt throuJh
supportinJ thH inIDnts in rHJulDtinJ thHir rHsponsHs to sHnsory stimuli DnG/or rHsponGinJ
sHnsitivHly to inIDnts' prHlinJuistiF FommuniFDtion FuHs.
7his outFomH will EH HvDluDtHG usinJ Dn DGDptHG vHrsion oI D pDrHnt-FhilG HnJDJHmHnt
stDtH FoGinJ systHm oriJinDlly GHvHlopHG Ey $GDmson Ht Dl. (2009) DnG DGDptHG Ey
%ottHmD-%HutHl Ht Dl., (2018).
6HFRQGDU\DQG([SORUDWRU\2XWFRPH9DULDEOHV
6HFonGDry outFomH vDriDElHs:
7hH Iirst thrHH sHFonGDry outFomH mHDsurHs will EH DssHssHG Dt thrHH timHpoints:
%DsHlinH, 3osttHst 1 (DItHr IDmiliHs hDvH EHHn rDnGomly DssiJnHG to Dn intHrvHntion Drm
DnG FoDFhHG in onH oI thH two 3,( intHrvHntion GomDins), DnG 3osttHst 2 (DItHr IDmiliHs
hDvH EHHn FoDFhHG in Eoth oI thH 3,( intHrvHntion GomDins). )or thHsH mHDsurHs, wH DrH
pDrtiFulDrly intHrHstHG in whHthHr thHrH DrH HIIHFts spHFiIiF to thH initiDl 3,( FoDFhinJ
GomDin (sHnsory rHDFtivity or prHlinJuistiF FommuniFDtion) Dt 3osttHst 1, DnG whHthHr
5
 
 

Protocol Number 
18 June 2021 - version DRAFT
thHrH DrH orGHr HIIHFts (GiIIHrHnFHs EHtwHHn stuGy Drms) Dt 3osttHst 2. 
1. &hDnJHs in pDrHnt rHsponsivHnHss to inIDnt sHnsory rHDFtivity FuHs. >0HDsurHG viD D
projHFt-GHvHlopHG rDtinJ tool.@ 7his sHFonGDry mHDsurH is inFluGHG to GHtHrminH whHthHr
FoDFhinJ in thH sHnsory rHDFtivity GomDin yiHlGs thH HxpHFtHG spHFiIiF HIIHFts on pDrHnts'
rHsponsHs to inIDnt sHnsory rHDFtivity FuHs.
2. &hDnJHs in pDrHnt rHsponsivHnHss to inIDnt prHlinJuistiF FommuniFDtion
FuHs.  >0HDsurHG viD D projHFt-GHvHlopHG rDtinJ tool.@ 7his sHFonGDry mHDsurH is inFluGHG
to GHtHrminH whHthHr FoDFhinJ in thH prHlinJuistiF FommuniFDtion GomDin yiHlGs thH
HxpHFtHG spHFiIiF HIIHFts on pDrHnts' rHsponsHs to inIDnt prHlinJuistiF FommuniFDtion
FuHs.
3. &hDnJHs in inIDnt intHntionDl FommuniFDtion. >0HDsurHG viD D projHFt-GHvHlopHG
FoGinJ systHm.@ 7hH rDtionDlH Ior inFluGinJ this outFomH mHDsurH is thDt pDrHntDl
rHsponsivH support oI inIDnt HnJDJHmHnt will promotH inIDnts' inFrHDsHG usH oI
intHntionDl FommuniFDtion, prHviously IounG to prHGiFt lDtHr rHFHptivH DnG HxprHssivH
lDnJuDJH outFomHs Ior prHsFhoolHrs DlrHDGy GiDJnosHG with Dutism (<oGHr Ht Dl., 2015). 
7hH IollowinJ 8 sHFonGDry outFomH vDriDElHs will EH mHDsurHG Dt two timHpoints:
%DsHlinH DnG 3osttHst 2. )or thHsH mHDsurHs, wH DrH pDrtiFulDrly intHrHstHG in HxDmininJ
thH mDJnituGH oI FhDnJH ovHr thH FoursH oI thH Iull intHrvHntion, Ds wHll Ds whHthHr thHrH
DrH orGHr HIIHFts (GiIIHrHnFHs EHtwHHn stuGy Drms) Dt 3osttHst 2. 
4. &hDnJHs in inIDnt rHspirDtory sinus DrrhythmiD (56$). 7his mHDsurH wDs FhosHn Ds Dn
inGHx oI pDrDsympDthHtiF systHm IunFtioninJ, DnG will EH mHDsurHG within D pDrDGiJm in
whiFh thH inIDnts DrH pDssivHly oEsHrvinJ viJnHttHs oI inIDnt-GirHFtHG spHHFh, Ds Dn
intHnGHG HxpHrimHntDl DnDloJ oI thH livH pDrHnt-inIDnt intHrDFtions wH DrH viGHorHForGinJ
to GHrivH othHr outFomH mHDsurHs. :H hypothHsizH wH will sHH inFrHDsHG 56$ lHvHls
GurinJ inIDnt-GirHFtHG spHHFh, rHIlHFtinJ JrHDtHr pDrDsympDthHtiF Fontrol, Ey 3osttHst 2. 
5. &hDnJHs in inIDnt skin FonGuFtDnFH lHvHl (6&/). 7his mHDsurH wDs FhosHn Ds Dn inGHx
oI sympDthHtiF systHm IunFtioninJ, DnG will EH mHDsurHG within thH DEovH GHsFriEHG
inIDnt-GirHFtHG spHHFh pDrDGiJm. :H hypothHsizH wH will sHH GHFrHDsHG 6&/ lHvHls GurinJ
inIDnt-GirHFtHG spHHFh, rHIlHFtinJ lHss HlHvDtion oI sympDthHtiF DFtivity whHn oEsHrvinJ
inIDnt-GirHFtHG spHHFh viJnHttHs, Ey 3osttHst 2. 
6 &hDnJHs in inIDnts' rHFHptivH lDnJuDJH. >0HDsurHG viD thH 0ullHn 6FDlHs oI (Drly
/HDrninJ (06(/) 5HFHptivH /DnJuDJH sFDlH, 0ullHn, 1995.@ 7his mHDsurH is D morH GistDl
outFomH mHDsurH thDt wH hypothHsizH will improvH in DssoFiDtion with improvHmHnts in
pDrHnt-inIDnt GyDGiF HnJDJHmHnt DnG inIDnt intHntionDl FommuniFDtion. 
7. &hDnJHs in inIDnts' HxprHssivH lDnJuDJH. >0HDsurHG viD thH 06(/ 5HFHptivH /DnJuDJH
sFDlH, 0ullHn, 1995.@ 7his mHDsurH Dlso is D morH GistDl outFomH mHDsurH thDt wH
hypothHsizH will improvH in DssoFiDtion with improvHmHnts in pDrHnt-inIDnt GyDGiF
HnJDJHmHnt DnG inIDnt intHntionDl FommuniFDtion. 
8. &hDnJHs in inIDnts' rHsponsHs to DGults' EiGs to GirHFt thHir DttHntion to Dn nHw oEjHFt
(i.H., rHsponsH to joint DttHntion). >0HDsurHG viD D suEsHt oI 6 $ttHntion )ollowinJ triDls
Irom thH -oint $ttHntion 3rotoFol, :Dtson Ht Dl., 2003.@ 2nH IrHquHnt EHhDviorDl
6
 

Protocol Number 
18 June 2021 - version DRAFT
FhDrDFtHristiF oI inIDnts Dt HlHvDtHG likHlihooG oI lDtHr 1's is thDt thHy hDvH GiIIiFulty in
rHsponGinJ to joint DttHntion EiGs thDt rHquirH thHm to rHGirHFt thHir DttHntion DwDy Irom
thHir FurrHnt IoFus to D nHw oEjHFt. 3otHntiDlly, improvHmHnts in pDrHnt-inIDnt GyDGiF
HnJDJHmHnt will, ovHr timH, yiHlG improvHmHnts in rHsponsH to joint DttHntion Ds pDrHnts
lHDrn to usH nHw strDtHJiHs to HIIHFtivHly HnJDJH thHir inIDnt, DnG inIDnts hDvH morH
HxpHriHnFHs in rHFiproFDl intHrDFtions with thHir FDrHJivHrs. 6uFh FhDnJHs FoulG siJnDl
inIDnts' GHFrHDsHG GHpHnGHnFy on pDrHnts oEsHrvinJ DnG rHsponGinJ to thHir immHGiDtH
IoFus oI DttHntion, DnG proviGH D lDrJHr vDriHty oI lHDrninJ opportunitiHs. 
9. &hDnJHs in inIDnts' soFiDl-FommuniFDtion skills. >0HDsurHG viD thH %riHI 2EsHrvDtion oI
6oFiDl-&ommuniFDtion &hDnJH, %26&&, /orG, *rzDGzinski Ht Dl., 2017.@ ,n DnDlysHs with
othHr sDmplHs sFrHHnHG with thH )<,v3.1, our tHDm hDs GoFumHntHG thDt thH positivH
prHGiFtivH vDluH oI thH tool spHFiIiFDlly Ior Dutism is DrounG 30-40%, vDryinJ with thH DJH
Dt sFrHHninJ (unpuElishHG GDtD). 'uH to thH nDturH oI thH itHms on thH )<,v3.1, inIDnts
mHHtinJ thH thrHsholG Ior EHinJ Dt HlHvDtHG likHlihooG Ior 1's on thH )<,v.3.1 will hDvH
pDrHnt-rHportHG soFiDl-FommuniFDtion EHhDviors DssoFiDtHG with Dutism. 7hH %26&& wDs
GHsiJnHG to DssHss improvHmHnts in HDrly soFiDl-FommuniFDtion skills thDt DrH usuDlly
impDirHG in younJ FhilGrHn with Dutism Eut Dlso DrH known to FhDnJH/improvH ovHr timH.
7hus, wH DrH usinJ thH %26&& to HxDminH whHthHr thHsH skills FhDnJH siJniIiFDntly ovHr
thH FoursH oI thH Iull 3,( intHrvHntion.
10. &hDnJHs in oEsHrvHG inIDnt sHnsory rHDFtivity pDttHrns. >0HDsurHG viD thH 6Hnsory
3roFHssinJ $ssHssmHnt Ior <ounJ &hilGrHn, 63$, %DrDnHk, 1999D.@ ,n FoDFhinJ pDrHnts to
EH sHnsitivH to thHir inIDnts' FuHs rHlDtHG to sHnsory rHDFtivity DnG to rHsponG in wDys thDt
support thHir inIDnts' rHJulDtion oI thHsH rHsponsHs, DnothHr potHntiDl GistDl outFomH oI
thH 3,( intHrvHntion woulG EH improvHmHnts in HxtrHmH pDttHrns oI sHnsory rHDFtivity
(i.H., GiminishHG hypo- DnG/or hypHr-rHDFtivity). 8sH oI thH 63$ Ds Dn oEsHrvDtionDl
mHDsurH will proviGH us with thH opportunity to DssHss whHthHr Dny FhDnJHs DrH oEsHrvHG
Ey DssHssors who DrH ElinGHG to thH Drm oI thH stuGy to whiFh IDmiliHs DrH DssiJnHG. 
11. &hDnJHs in pDrHnt-rHportHG inIDnt sHnsory rHDFtivity pDttHrns. >0HDsurHG viD thH
6Hnsory (xpHriHnFHs 4uHstionnDirH v. 2.1, 6(4, %DrDnHk, 1999E.@ $s D FomplHmHnt to thH
63$, wH DrH usinJ thH 6(4 to GHtHrminH whHthHr pDrHnts pHrFHivH improvHmHnts in thHir
FhilGrHn's sHnsory rHDFtivity pDttHrns ovHr thH FoursH oI thH Iull 3,( intHrvHntion. 
6WXG\3RSXODWLRQ
7hH stuGy populDtion is inIDnts EHtwHHn thH DJHs oI 11-16 months who DrH iGHntiIiHG Ds
EHinJ Dt HlHvDtHG likHlihooG oI D lDtHr nHuroGHvHlopmHntDl GisDEility GiDJnosis (H.J.,
Dutism spHFtrum, DttHntion-GHIiFit hypHrDFtivity GisorGHr, lDnJuDJH GHlDy/GisorGHr,
sHnsory proFHssinJ GisorGHr), DlonJ with D pDrHnt (or othHr primDry IDmily FDrHJivHr H.J.,
JrDnGpDrHnt) Ior HDFh FhilG. ,nIDnts will EH rHFruitHG Irom 6 FHntrDl 1orth &DrolinD
FountiHs thDt inFluGH rurDl DnG urEDn DrHDs rHprHsHntinJ wiGH GHmoJrDphiFs. 3DrHnts
initiDlly will EH DskHG to FomplHtH D sFrHHninJ quHstionnDirH, 7hH )irst <HDrs ,nvHntory,
v.3.1E ()<,v3.1E; %DrDnHk Ht Dl., 2014).. 6tuGy HliJiEility will EH IurthHr HvDluDtHG Ior
inIDnts whosH sFrHHninJ sForHs on thH )<,v3.1E mHHt HmpiriFDlly GHtHrminHG thrHsholGs
Ior EHinJ Dt HlHvDtHG likHlihooG Ior D lDtHr GiDJnosHG nHuroGHvHlopmHntDl GisorGHr (1'),
7

Protocol Number 
18 June 2021 - version DRAFT
Ds wHll Ds pDrHnt HliJiEility. $t EDsHlinH DssHssmHnts, inIDnts must hDvH D sForH oI Dt lHDst
1 stDnGDrG GHviDtion EHlow thH mHDn on thH 5HFHptivH or (xprHssivH /DnJuDJH sFDlH (or
Eoth) oI thH 0ullHn 6FDlHs oI (Drly /HDrninJ, Ds wHll Ds mHHtinJ FliniFDl-GHtHrminHG
FritHriD Ior HlHvDtHG pDttHrns oI hypo-rHDFtivity or hypHr-rHDFtivity (or Eoth) on thH
6Hnsory 3roFHssinJ $ssHssmHnt to EH HliJiElH Ior HnrollmHnt in thH intHrvHntion triDl.
,nIDnts will inFluGH Eoth sHxHs, DlthouJh JivHn prHvious stuGiHs wH HxpHFt D 2:1
(mDlH:IHmDlH) rDtio, JivHn thDt Eoys DrH morH likHly to sForH Dt HlHvDtHG likHlihooG Ior
nHuroGHvHlopmHntDl GisorGHrs (H.J., $6') tDrJHtHG Ey thH )<,.  
Exclusion criteria: Infants with known genetic conditions (e.g., Down syndrome), and those with
significant uncorrected vision/hearing/physical impairments will be excluded. We exclude infants with
known genetic disorders due to our focus on testing PIE with infants at elevated likelihood of
neurodevelopmental disorders based on behavioral markers, but whose eventual diagnosis remains
unclear. We will exclude infants with significant uncorrected vision/hearing/physical impairments
because they likely would not be able to fully participate in the assessment procedures, and the
assessment results would be of questionable validity. Families who do not speak English as their
primary language in the home (>50% of the time) will be excluded, because screening tools,
assessments, and interventions are not available uniformly in other languages. 
1XPEHURI3DUWLFLSDQWV
:H plDn to Hnroll 44 inIDnts Dt HlHvDtHG likHlihooG oI D lDtHr 1' DnG D primDry FDrHJivHr oI
HDFh inIDnt. %DsHG on prior stuGiHs with similDr populDtions, wH DntiFipDtH DpproximDtHly
1% oI FomplHtHG )<,s will yiHlG D pDrHnt-inIDnt GyDG thDt mHHts Dll HliJiEility FritHriD DnG
FonsHnts to Hnroll in thH intHrvHntion triDl. 7hus, sFrHHninJ oI ~4400 inIDnts on thH
)<,v3.1 likHly will EH rHquirHG to rHFruit this sDmplH. $ll rHFruitmHnt will tDkH plDFH Dt thH
8nivHrsity oI 1orth &DrolinD Dt &hDpHl +ill stuGy sitH. 
9LVLW6FKHGXOH7DEOHSWLRQDO
6HH DttDFhHG tDElH.
6WXG\)ORZ&KDUWRSWLRQDO
6HH DttDFhHG FhDrt. 
8
 

Protocol Number 
18 June 2021 - version DRAFT
$EEUHYLDWLRQV
$EEUHYLDWLRQ
([SODQDWLRQ
9

Protocol Number 
18 June 2021 - version DRAFT
*ORVVDU\RI7HUPV
*ORVVDU\
([SODQDWLRQ
10

Protocol Number 
18 June 2021 - version DRAFT
7DEOH2I&RQWHQWV
6\QRSVLV................................................................................................................................ 3
6tuGy 3urposH ..................................................................................................................... 3
3rimDry 2EjHFtivH ................................................................................................................ 3
6HFonGDry 2EjHFtivHs  ........................................................................................................ 3
*HnHrDl 'HsiJn 'HsFription ................................................................................................ 3
6tuGy 'DtH 5DnJH DnG 'urDtion ......................................................................................... 3
1umEHr oI 6tuGy 6itHs ........................................................................................................ 3
3rimDry 2utFomH 9DriDElHs ................................................................................................ 3
6HFonGDry DnG (xplorDtory 2utFomH 9DriDElHs  ............................................................... 3
6tuGy 3opulDtion ................................................................................................................. 3
1umEHr oI 3DrtiFipDnts ....................................................................................................... 3
9isit 6FhHGulH 7DElH (0ptionDl) ........................................................................................... 3
$EErHviDtions ....................................................................................................................... 9
*lossDry oI 7Hrms ............................................................................................................. 10
1.1 6tDtHmHnt oI &ompliDnFH ........................................................................................... 13
2.1 %DFkJrounG ................................................................................................................. 13
3.1 3roElHm 6tDtHmHnt ..................................................................................................... 14
3.2 3urposH oI 6tuGy/3otHntiDl ,mpDFt ............................................................................. 14
3.3.1 3otHntiDl 5isks ........................................................................................................ 15
3.3.2 3otHntiDl %HnHIits .................................................................................................... 16
4.1 +ypothHsis ................................................................................................................... 16
4.2 3rimDry 2EjHFtivH ........................................................................................................ 17
4.3 6HFonGDry 2EjHFtivHs  ................................................................................................ 18
5.1 *HnHrDl 'HsiJn 'HsFription ........................................................................................ 18
5.1.1 6tuGy 'DtH 5DnJH DnG 'urDtion .............................................................................. 19
5.1.2 1umEHr oI 6tuGy 6itHs ............................................................................................. 19
5.2 2utFomH 9DriDElHs ...................................................................................................... 19
5.2.1 3rimDry 2utFomH 9DriDElHs ..................................................................................... 19
5.2.2 6HFonGDry DnG (xplorDtory 2utFomH 9DriDElHs  ....................................................... 20
5.3 6tuGy 3opulDtion ......................................................................................................... 23
5.3.1 1umEHr oI 3DrtiFipDnts ............................................................................................ 25
5.3.2 (liJiEility &ritHriD/9ulnHrDElH 3opulDtions ................................................................. 25
6.1 ,ntHrvHntion ................................................................................................................. 27
6.1.1 'HsFription oI ,ntHrvHntion ...................................................................................... 27
6.1.2 0HthoG oI $ssiJnmHnt/5DnGomizDtion ..................................................................... 28
6.1.3 6HlHFtion oI ,nstrumHnts/2utFomH 0HDsurHs ............................................................ 29
6.1.4 ,ntHrvHntion $GministrDtion ..................................................................................... 34
6.1.5 5HDFtion 0DnDJHmHnt ............................................................................................ 36
6.2 $ssHssmHnts ................................................................................................................ 36
6.2.1 (IIiFDFy ................................................................................................................... 36
6.2.2 6DIHty/3rHJnDnFy-rHlDtHG 3roFHGurH ........................................................................ 37
6.2.3 $GvHrsH (vHnts 'HIinition DnG 5HportinJ ................................................................. 37
6.2.4 3hDrmDFokinHtiFs  ................................................................................................... 38
11

Protocol Number 
18 June 2021 - version DRAFT
6.2.5 %iomDrkHrs  ............................................................................................................ 38
6.3 6tuGy 3roFHGurHs ........................................................................................................ 38
6.3.1 6tuGy 6FhHGulH ....................................................................................................... 38
6.3.2 ,nIormHG &onsHnt ................................................................................................... 40
6.3.3 6FrHHninJ ............................................................................................................... 41
6.3.4 5HFruitmHnt, (nrollmHnt DnG 5HtHntion ................................................................... 42
6.3.5 6tuGy 9isits ............................................................................................................. 45
6.3.6 (nG oI 6tuGy DnG )ollow 8p ..................................................................................... 47
6.3.7 5HmovDl oI 6uEjHFts ................................................................................................ 47
6.4 6tDtistiFDl 0HthoG ....................................................................................................... 48
6.4.1 6tDtistiFDl 'HsiJn .................................................................................................... 48
6.4.2 6DmplH 6izH &onsiGHrDtions ..................................................................................... 48
6.4.3 3lDnnHG $nDlysHs .................................................................................................... 49
6.4.3.1 3rimDry $nDlysHs ................................................................................................. 50
6.4.3.2 6HFonGDry 2EjHFtivHs $nDlysHs, iI DppliFDElH ........................................................ 50
6.4.3.3 $nDlysis oI 6uEjHFt &hDrDFtHristiFs ........................................................................ 52
6.4.3.4 ,ntHrim $nDlysis  .................................................................................................. 52
6.4.3.5 +HDlth HFonomiF HvDluDtion, iI DppliFDElH ............................................................. 52
6.4.3.6 2thHr ..................................................................................................................... 52
6.4.4 6uEsHts DnG &ovDriDtHs ........................................................................................... 52
6.4.5 +DnGlinJ oI 0issinJ 'DtD ......................................................................................... 53
7.1 (thiFDl &onsiGHrDtions: ,nIormHG &onsHnt/$ssHnt DnG +,3$$ $uthorizDtion ........... 53
7.2 ,nstitutionDl 5HviHw %oDrG (,5%) 5HviHw .................................................................... 55
7.3 6uEjHFt 3rivDFy, &onIiGHntiDlity & 'DtD 0DnDJHmHnt .............................................. 56
7.4 'HviDtions/8nDntiFipDtHG 3roElHms ........................................................................... 56
7.5 'DtD &ollHFtion ............................................................................................................ 57
7.6 'DtD 4uDlity $ssurDnFH .............................................................................................. 57
7.7 6tuGy 5HForGs ............................................................................................................. 58
7.8 $FFHss to 6ourFH ......................................................................................................... 59
7.9 'DtD or 6pHFimHn 6torDJH/6HFurity ........................................................................... 60
7.10 5HtHntion oI 5HForGs ................................................................................................ 60
7.11 6tuGy 0onitorinJ ....................................................................................................... 61
7.12 'DtD 6DIHty 0onitorinJ 3lDn ..................................................................................... 61
7.13 6tuGy 0oGiIiFDtion .................................................................................................... 61
7.14 6tuGy 'isFontinuDtion ............................................................................................... 62
7.15 6tuGy &omplHtion ..................................................................................................... 62
7.16 &onIliFt oI ,ntHrHst 0DnDJHmHnt 3lDn ...................................................................... 62
7.17 )unGinJ 6ourFH ......................................................................................................... 62
7.18 3uEliFDtion 3lDn ......................................................................................................... 62
$ppHnGiFHs ........................................................................................................................ 63
/ist oI 7DElHs ...................................................................................................................... 65
5HIHrHnFHs ......................................................................................................................... 66
12

Protocol Number 
18 June 2021 - version DRAFT
6WDWHPHQWRI&RPSOLDQFH
7hH triDl will EH FDrriHG out in DFForGDnFH with ,ntHrnDtionDl &ounFil on +DrmonisDtion
*ooG &liniFDl 3rDFtiFH (,&+ *&3) DnG thH IollowinJ:
8nitHG 6tDtHs (86) &oGH oI )HGHrDl 5HJulDtions (&)5) DppliFDElH to FliniFDl stuGiHs (45
&)5 3Drt 46, 21 &)5 3Drt 50, 21 &)5 3Drt 56, 21 &)5 3Drt 312, DnG/or 21 &)5 3Drt 812).
1DtionDl ,nstitutHs oI +HDlth (1,+)-IunGHG invHstiJDtors DnG FliniFDl triDl sitH stDII who DrH
rHsponsiElH Ior thH FonGuFt, mDnDJHmHnt, or ovHrsiJht oI 1,+-IunGHG FliniFDl triDls hDvH
FomplHtHG +umDn 6uEjHFts 3rotHFtion DnG ,&+ *&3 7rDininJ.
7hH protoFol, inIormHG FonsHnt Iorm(s), rHFruitmHnt mDtHriDls, DnG Dll pDrtiFipDnt mDtHriDls
will EH suEmittHG to thH ,5% Ior rHviHw DnG DpprovDl. $pprovDl oI Eoth thH protoFol DnG thH
FonsHnt Iorm(s) must EH oEtDinHG EHIorH Dny pDrtiFipDnt is FonsHntHG. $ny DmHnGmHnt to
thH protoFol will rHquirH rHviHw DnG DpprovDl Ey thH ,5% EHIorH thH FhDnJHs DrH
implHmHntHG to thH stuGy. $ll FhDnJHs to thH FonsHnt Iorm(s) will EH ,5% DpprovHG; D
GHtHrminDtion will EH mDGH rHJDrGinJ whHthHr D nHw FonsHnt nHHGs to EH oEtDinHG Irom
pDrtiFipDnts who proviGHG FonsHnt, usinJ D prHviously DpprovHG FonsHnt Iorm
%DFNJURXQG
7hH positivH DssoFiDtion EHtwHHn pDrHnt rHsponsivHnHss DnG EHttHr soFiDl-FommuniFDtion
outFomHs in FhilGrHn in JHnHrDl (%ornstHin, 1995, +uGson Ht Dl., 2015; 7Dmis-/H0onGD Ht
Dl., 2014), DnG FhilGrHn with nHuroGHvHlopmHntDl GisorGHrs (1's) in pDrtiFulDr (%rDGy Ht Dl.,
2014; 'imitrovD Ht Dl., 2016; <oGHr Ht Dl., 2015), hDs GrivHn thH GHvHlopmHnt oI HDrly
intHrvHntions promotinJ pDrHnt rHsponsivHnHss Ior thHsH populDtions ($lGrHG Ht Dl., 2004;
.onJ & &DrtD, 2011; 6illHr Ht Dl., 2014). 6uFh intHrvHntion moGHls DssumH thDt inFrHDsHs in
pDrHnt rHsponsivHnHss will improvH FhilG outFomHs. +owHvHr, Ior intHrvHntions tDrJHtinJ 
LQIDQWVDQGWRGGOHUVDWULVNIRURUGLDJQRVHGZLWK1'V, suFh Ds Dutism spHFtrum GisorGHr
($6'), thH HIIHFts oI pDrHnt rHsponsivHnHss intHrvHntions hDvH EHHn moGHst in sizH DnG
hiJhly vDriDElH (%DrDnHk Ht Dl., 2015; &DrtHr Ht Dl., 2011; *rHHn Ht Dl., 2015; .DsDri Ht Dl.,
2014), rHnGHrinJ thH HviGHnFH inFonFlusivH Ior pDrHnt rHsponsivHnHss Ds D mHGiDtor oI
inIDnt/toGGlHr outFomHs (.onJ & &DrtD, 2011).
:H proposH thDt HnsurinJ D morH HIIHFtivH pDrHnt-mHGiDtHG intHrvHntion Ior this populDtion
GHpHnGs on thH JuiGDnFH oI D rHIinHG thHory oI FhDnJH—onH HxpliFitly DFknowlHGJinJ thDt
inIDnt EHhDviors inIluHnFH pDrHnt rHsponsivHnHss. 'HvHlopmHntDl stuGiHs inGiFDtH thDt
inIDnts Dt-risk Ior 1's DrH likHly to HxhiEit EHhDviors thDt HithHr IDil to HliFit pDrHnt
rHsponsHs or HliFit pDrHnt rHsponsHs thDt Go not HIIHFtivHly support thH inIDnt's
HnJDJHmHnt DnG lHDrninJ (+uGry Ht Dl., 2015; 1orthrup & ,vHrson, 2015; /HHzHnEDum Ht
Dl., 2014; :DrlDumont Ht Dl., 2014). ,n DGGition, optimDl IHDturHs oI pDrHnt rHsponsivHnHss
DppHDr to vDry Ds D IunFtion oI FhilGrHn's GHvHlopmHntDl lHvHls DnG othHr GynDmiF vDriDElHs
(+DHEiJ Ht Dl., 2013). 7o GDtH, stuGiHs oI pDrHnt-mHGiDtHG intHrvHntions hDvH not DGGrHssHG
thHsH FomplHxitiHs. +owHvHr, rHFHnt rHsHDrFh points to kHy "FhilG" vDriDElHs likHly to plDy
trDnsDFtionDl rolHs in FommuniFDtion GHvHlopmHnt DmonJ inIDnts DnG toGGlHrs with or Dt-
13

Protocol Number 
18 June 2021 - version DRAFT
risk Ior 1's. 7hHsH inFluGH DspHFts oI FhilGrHn's prHlinJuistiF FommuniFDtion FhDrDFtHristiFs
(H.J., intHntionDl FommuniFDtion, GivHrsity oI FonsonDnts) thDt DrH rHlDtHG to Eoth pDrHnt
rHsponsivHnHss DnG FhilGrHn's lDtHr FommuniFDtion skills (<oGHr Ht Dl., 2015). $lso,
prHliminDry GDtD Irom our tHDm inGiFDtH inIDnts' sHnsory rHDFtivity (hypo- DnG hypHr-
rHDFtivity) prHGiFts not only pDrHnt rHsponsivHnHss Eut Dlso soFiDl-FommuniFDtion outFomHs
oI inIDnts Dt-risk Ior 1's. $rJuDEly, inFrHDsHs in pDrHnt rHsponsivHnHss lHDG to improvHG
pDrHnt-inIDnt joint HnJDJHmHnt, whiFh in turn mHGiDtHs inIDnts' FommuniFDtion outFomHs.
)inDlly, physioloJiFDl sHlI-rHJulDtion impDFts soFiDl DnG FommuniFDtion outFomHs in
FhilGrHn (&Dlkins & .HDnH, 2004; 'oussDrG-5oosHvHlt Ht Dl., 2001; :Dtson Ht Dl., 2010), Eut
mDy EH GisruptHG in inIDnts Dt-risk Ior 1's ('DlH Ht Dl., 2011; )HlGmDn, 2007), DssoFiDtHG
with thHir GiIIiFultiHs moGulDtinJ sHnsory rHDFtivity (6FhDDI Ht Dl., 2010).  
,n rH-FonFHptuDlizinJ intHrvHntion Ior inIDnts Dt-risk Ior 1's, wH hDvH intHJrDtHG thHsH
vDriDElHs into D nHw moGHl, 3DrHnts DnG ,nIDnts (nJDJHG (3,(), with two kHy FontHnt
GomDins: 6Hnsory 5HDFtivity DnG 3rHlinJuistiF &ommuniFDtion. ,n thH 3,( intHrvHntion,
FoDFhHs will JuiGH pDrHnts in oEsHrvinJ DnG GHsFriEinJ thHir FhilGrHn's sHnsory rHDFtivity
DnG prHlinJuistiF FommuniFDtion FuHs, oEsHrvinJ thHir own rHsponsHs to GiIIHrHnt FuHs DnG
whHthHr thHsH rHsponsHs sHrvH to promotH GyDGiF HnJDJHmHnt EHtwHHn thH pDrHnt DnG
inIDnt, DnG intHntionDlly FontinuinJ thHir usH oI rHsponsivH strDtHJiHs thDt promotH
HnJDJHmHnt whilH Dlso iGHntiIyinJ DnG usinJ nHw strDtHJiHs to promotH HnJDJHmHnt. 
3UREOHP6WDWHPHQW
7hH mDin HIIHFts oI pDrHnt-mHGiDtHG intHrvHntions on outFomHs oI inIDnts Dt HlHvDtHG
likHlihooG oI lDtHr GiDJnosHs oI Dutism DnG othHr nHuroGHvHlopmHntDl GisorGHrs (1's) hDvH
EHHn moGHst in sizH Dt EHst, DnG null Ior most mHDsurHG outFomHs. +owHvHr, D prHvious
triDl oI D pDrHnt-mHGiDtHG intHrvHntion Ey our tHDm (:Dtson Ht Dl., 2017) IounG thDt thH
intHrvHntion ($GDptHG 5HsponsivH 7HDFhinJ) hDG moGHrDtHly lDrJH HIIHFts on pDrHnts' usH
oI rHsponsivH intHrDFtion strDtHJiHs tDrJHtHG Ey thH intHrvHntion, DnG thDt thHsH inFrHDsHs
mHGiDtHG thH rHlDtion EHtwHHn Jroup DssiJnmHnt (intHrvHntion vs. Fontrol) DnG mutliplH
inIDnt outFomHs oI intHrHst (H.J., Dutism symptom sHvHrity, lDnJuDJH, soFiDl DnG
FommuniFDtion DGDptivH skills) in thH DEsHnFH oI mDin HIIHFts on inIDnt outFomHs. :H
proposH thDt wH FDn DFhiHvH EHttHr outFomHs Irom Dn intHrvHntion IounGHG on D rHIinHG
thHory oI FhDnJH, i.H., HxpliFitly DFknowlHGJinJ thDt inIDnts' DnG pDrHnts' EHhDviors hDvH
trDnsDFtionDl impDFts on onH DnothHr, DnG thDt thHsH impDFts mDy not DlwDys opHrDtH in
wDys thDt support optimDl DGDptivH GHvHlopmHnt oI thH inIDnt. :H GHvHlopHG 3DrHnts DnG
,nIDnts (nJDJHG (3,() Ds Dn intHrvHntion thDt HxpliFitly DGGrHssHs thH GynDmiF,
trDnsDFtionDl nDturH oI pDrHnt-inIDnt intHrDFtions in GyDGs thDt inFluGH inIDnts Dt HlHvDtHG
likHlihooG oI 1's. 
3XUSRVHRI6WXG\3RWHQWLDO,PSDFW
7his stuGy HntDils D "prooI oI FonFHpt" HvDluDtion oI D novHl intHrvHntion, 3DrHnts DnG
,nIDnts (nJDJHG (3,(), Ior proGromDl inIDnts Dt-risk Ior nHuroGHvHlopmHntDl GisorGHrs (1's).
7hH oEjHFtivHs oI thH FurrHnt stuGy DrH to HxDminH whHthHr thH 3,( intHrvHntion (D)
trDnsIorms pDrHnt-inIDnt trDnsDFtions ovHr timH Ds intHnGHG, thHrHEy IDFilitDtinJ inFrHDsHs
14

Protocol Number 
18 June 2021 - version DRAFT
in thH timH inIDnts spHnG in joint HnJDJHmHnt with thHir pDrHnts, DnG (E) is DssoFiDtHG with
improvHG soFiDl-FommuniFDtion IunFtioninJ, EHttHr rHJulDtion oI sHnsory rHDFtivity, DnG
positivH FhDnJHs in inGiFHs oI DutonomiF sHlI-rHJulDtion in inIDnts Dt-risk Ior 1's. 2ur stuGy
GHsiJn Dlso pHrmits us to HxDminH whHthHr GyDGiF HnJDJHmHnt (primDry outFomH) DnG our
sHFonGDry outFomHs DrH vDriDElH EDsHG on thH orGHr in whiFh pDrHnts DrH FoDFhHG on thH
two 3,( GomDins; DlthouJh wH hypothHsizH thDt thHrH will EH orGHr HIIHFts on outFomHs
DItHr Dll IDmiliHs hDvH EHHn FoDFhHG in Eoth 3,( GomDins, IinGinJ orGHr HIIHFts woulG
prompt us to rHIinH our thHory oI FhDnJH IurthHr, thHrHEy inIorminJ rHGHsiJn oI thH
intHrvHntion. 
7HstinJ this novHl intHrvHntion moGHl, 3,(, will promotH D rHIinHG thHory oI FhDnJH Ior
EuilGinJ morH HIIHFtivH pDrHnt-mHGiDtHG intHrvHntions Ior inIDnts Dt-risk Ior
nHuroGHvHlopmHntDl GisorGHrs, suFh Ds Dutism. 5Hsults Irom this stuGy will proviGH spHFiIiF
HviGHnFH rHJDrGinJ whHthHr FoDFhinJ pDrHnts on rHsponGinJ to two GomDins oI inIDnt
EHhDvior, sHnsory rHDFtivity DnG prHlinJuistiF FommuniFDtion, FDn impDFt pDrHnt-inIDnt
GyDGiF HnJDJHmHnt DnG inIDnt soFiDl-FommuniFDtion DnG sHlI-rHJulDtion. 7hHsH thrHH
vDriDElHs DrH linkHG FonFHptuDlly DnG HmpiriFDlly to lonJ-tHrm outFomHs in FhilGrHn with
1's. 'HsFriptivH FhDrDFtHrizDtions oI trHDtmHnt HIIHFts DnG HstimDtHG HIIHFt sizHs rHsultinJ
Irom this stuGy will JuiGH IuturH lDrJH-sFDlHG HIIiFDFy triDls.  
3RWHQWLDO5LVNV
$ntiFipDtHG risks to FhilGrHn or IDmiliHs DrH minimDl. $lthouJh thH likHlihooG oI D
FonIiGHntiDlity ErHDFh is vHry low, thH GDtD FollHFtHG (viD pDrHnt survHy, EHhDviorDl
DssHssmHnt/viGHo FoGinJ, DnG physioloJy) yiHlG inIormDtion DEout pDrtiFipDnts' EHhDviors
DnG GHmoJrDphiFs thDt FoulG FDusH HmotionDl GistrHss iI FonIiGHntiDlity wDs ErHDFhHG. :H
will tDkH prHFDutions to DssurH FonIiGHntiDlity oI GDtD (H.J., suEstitutinJ FoGHs Ior
iGHntiIiHrs, limitinJ DFFHss to iGHntiIiHG GDtD, imprHssinJ on thH rHsHDrFh stDII thH
importDnFH oI FonIiGHntiDlity, DnG storinJ rHsHDrFh rHForGs/viGHos in loFkHG IilH FDEinHts
DnG HlHFtroniF IilHs on sHFurH sHrvHrs). 7hHrH DrH only minimDl risks involvHG in thH
FollHFtion oI oEsHrvDtionDl GDtD on thH FhilGrHn. ,nIDnts oFFDsionDlly mDy EHFomH tirHG,
IrustrDtHG or strHssHG Ey FomplHtinJ D GHvHlopmHntDl DssHssmHnt. +owHvHr, Dll oI our
tDsks DrH plDy-EDsHG in nDturH, DnG wH ErHDk up tDsks DnG proviGH rHst/snDFks Ds nHHGHG,
DnG DFFHss to FDrHJivHrs Dt Dll timHs. )Hw inIDnts in our prHvious stuGiHs hDvH hDG GiIIiFulty
in FomplHtinJ similDr DssHssmHnt EDttHriHs. $s Dn DGGitionDl protHFtion, pDrHnts DrH DElH to
HnG thH DssHssmHnt proFHGurHs Dt Dny timH, DnG stDII Dlso Iollow writtHn JuiGHlinHs on
whHn to GisFontinuH Dn DssHssmHnt in thH HvHnt oI inIDnt siJnDls oI GistrHss.
7hH 3,( FoDFhinJ intHrvHntion is implHmHntHG in thH homHs oI IDmiliHs who hDvH DJrHHG to
pDrtiFipDtH. 0inimDl risks to thH inIDnts DnG pDrHnts mDy involvH IDtiJuH, IrustrDtion or
strHss. $ll intHrvHntionists will EH wHll-trDinHG in intHrvHntion strDtHJiHs DnG JHnHrDl
EHhDviorDl mDnDJHmHnt tHFhniquHs Ey thH stuGy 3rinFipDl ,nvHstiJDtors (:Dtson DnG
%DrDnHk), DnG will usH IDmily-IriHnGly FoDFhinJ DpproDFhHs DnG mDtHriDls.  :H will
inGiviGuDlizH strDtHJiHs to Iit thH IDmily FulturH DnG nHHGs.  
$lthouJh unlikHly to oFFur, invHstiJDtors/rHsHDrFh stDII DrH rHquirHG HthiFDlly DnG lHJDlly to
rHport instDnFHs oI suspHFtHG FhilG DEusH or nHJlHFt or instDnFHs in whiFh D rHsHDrFh
suEjHFt is in GDnJHr oI hDrminJ himsHlI/hHrsHlI or othHrs. 7hHsH FirFumstDnFHs unGHr whiFh
15

Protocol Number 
18 June 2021 - version DRAFT
FonIiGHntiDlity woulG EH ErokHn will EH FonvHyHG to Dll pDrtiFipDnts in thH FonsHnt Iorm(s).
3RWHQWLDO%HQHILWV
5isks to pDrtiFipDnts in this stuGy DrH minimDl, Ds outlinHG DEovH, whilH potHntiDl EHnHIits
Eoth to thH pDrtiFipDnts DnG othHrs DrH suEstDntiDl. 7hH primDry EHnHIit oI this stuGy is thH
GHvHlopmHnt oI D nHw intHrvHntion to EHnHIit IDmiliHs who hDvH Dn inIDnt Dt HlHvDtHG
likHlihooG Ior lDtHr nHuroGHvHlopmHntDl GisorGHrs (1's). 7hH intHrvHntion usHs D pDrHnt
FoDFhinJ moGHl intHnGHG to lHDG to improvHmHnts in inIDnt outFomHs in HnJDJHmHnt,
intHntionDl FommuniFDtion DnG EioEHhDviorDl rHJulDtion. 5HJDrGlHss oI Jroup DssiJnmHnt or
thH prHsHnFH or DEsHnFH oI HIIHFts on mHDsurHG outFomHs in two prHvious stuGiHs wH hDvH
FonGuFtHG involvinJ pDrHnt-mHGiDtHG intHrvHntion Ior inIDnts Dt HlHvDtHG likHlihooG oI 1's,
mDny pDrHnt pDrtiFipDnts in thosH stuGiHs hDvH HxprHssHG thDt thHy IHlt supportHG Ey thH
projHFt in lHDrninJ morH DEout thHir FhilG's GHvHlopmHnt DnG in nDviJDtinJ HDrly
intHrvHntion sHrviFHs DvDilDElH in thHir FommunitiHs. :H DntiFipDtH thDt mDny pDrtiFipDnts
in thH FurrHnt stuGy will Dlso HxpHriHnFH thosH EHnHIits. $t thH FonFlusion oI this projHFt, wH
will hDvH prHliminDry HviGHnFH DGGrHssinJ whHthHr D novHl intHrvHntion moGHl thDt tDkHs
into DFFount inIDnt sHnsory rHDFtivity DnG prHlinJuistiF FommuniFDtion FDn impDFt pDrHnt-
inIDnt trDnsDFtions DnG improvH GyDGiF HnJDJHmHnt, soFiDl-FommuniFDtion IunFtioninJ,
DnG physioloJiFDl inGiFHs oI sHlI-rHJulDtion Ior inIDnts Dt HlHvDtHG likHlihooG oI 1's. ,n
DGGition, this projHFt will yiHlG GHsFriptivH FhDrDFtHrizDtions oI trHDtmHnt HIIHFts DnG
HstimDtHG HIIHFt sizHs, thHrHEy proviGinJ D IounGDtion Ior D lDrJHr sFDlH HIIiFDFy triDl oI thH
3,( intHrvHntion.
+\SRWKHVLV
7his stuGy hDs Iour spHFiIiF oEjHFtivHs, with hypothHsHs DssoFiDtHG with HDFh oEjHFtivH.
8nGHrstDnGinJ thH stuGy GHsiJn will proviGH FontHxt Ior intHrprHtinJ thH hypothHsHs. 3DrHnt-
FhilG GyDGs will EH rDnGomizHG to onH oI two stuGy Drms. $ll GyDGs will rHFHivH thH Iull
3DrHnts DnG ,nIDnts (nJDJHG (3,() intHrvHntion, Eut thHy will EH FoDFhHG on thH two 3,(
GomDins (prHlinJuistiF FommuniFDtion DnG sHnsory rHDFtivity) in GiIIHrHnt orGHrs. ,n $rm1,
pDrHnts will Iirst EH FoDFhHG in rHsponGinJ to thHir inIDnts' prHlinJuistiF FommuniFDtion
FuHs. ,n $rm2, pDrHnts will Iirst EH FoDFhHG on rHsponGinJ to thHir inIDnts' prHlinJuistiF
FommuniFDtion FuHs. 3osttHst-1 DssHssmHnts will Iollow thH Iirst GomDin oI FoDFhinJ Ior Dll
pDrtiFipDnts. 7hHn pDrHnts will EH FoDFhHG in thH sHFonG GomDin oI 3,(, DItHr whiFh GyDGs
will pDrtiFipDtH in 3osttHst-2 DssHssmHnts.    
1. (stimDtH thH sHpDrDtH DnG FomEinHG HIIHFts oI thH two 3,( intHrvHntion GomDins on
GyDGiF HnJDJHmHnt (primDry outFomH).
+D: $t 3osttHst-1, GyDGs FoDFhHG in HithHr 3,( GomDin will HxhiEit moGHrDtHly
morH GyDGiF HnJDJHmHnt FompDrHG to %DsHlinH (&ohHn's G ≥ .40).
+E: $t 3osttHst-2, GyDGs in Eoth stuGy Drms will show DGGitionDl smDll to moGHrDtH
inFrHDsHs in GyDGiF HnJDJHmHnt FompDrHG to 3osttHst-1 (&ohHn's G ≥ .25).
2. (stimDtH thH sHpDrDtH DnG FomEinHG HIIHFts oI thH two 3,( intHrvHntion GomDins on
inIDnt intHntionDl FommuniFDtion. 
+D: $t 3osttHst-1, inIDnts in Eoth Jroups will show no morH thDn moGHst JDins in
16

Protocol Number 
18 June 2021 - version DRAFT
intHntionDl FommuniFDtion (&ohHn's G < .25).
+E: $t 3osttHst-2, inIDnts in Eoth Jroups will show moGHrDtH inFrHDsHs in
intHntionDl FommuniFDtion FompDrHG to %DsHlinH (&ohHn's G ≥ .40).
3. (vDluDtH thH GLIIHUHQWLDO FhDnJHs in pDrHnt rHsponsivHnHss IollowinJ FoDFhinJ on two
inGiviGuDl 3DrHnts DnG ,nIDnts (nJDJHG (3,() intHrvHntion GomDins — rHsponsHs to
vDriDElH inIDnt (D) sHnsory rHDFtivity or (E) prHlinJuistiF FommuniFDtion — Ds wHll Ds 
FXPXODWLYHFhDnJHs in pDrHnt rHsponsivHnHss IollowinJ FoDFhinJ on Eoth 3,( GomDins. 
+D: $t 3osttHst-1, pDrHnts in Eoth intHrvHntion Drm will show inFrHDsHs in
rHsponsHs DttunHG to thHir inIDnts' EHhDviors FompDrHG to %DsHlinH, with pDrHnts
FoDFhHG in thH sHnsory rHDFtivity GomDin showinJ morH rHsponsHs DttunHG to
inIDnts' sHnsory rHDFtivity, DnG pDrHnts FoDFhHG in thH prHlinJuistiF FommuniFDtion
GomDin showinJ morH rHsponsHs DttunHG to inIDnts' siJnDls oI DttHntion IoFus DnG
FommuniFDtivH intHnt. 
+E $t 3osttHst-2 (DItHr FoDFhinJ in Eoth 3,( GomDins), thHrH will EH no EHtwHHn-
Drm GiIIHrHnFHs in pDrHnt rHsponsHs DttunHG to inIDnt sHnsory rHDFtions or
prHlinJuistiF FommuniFDtion lHDGs, GuH to inFrHDsHs in pDrHnt rHsponsivHnHss to
thH nHwly FoDFhHG GomDin oI inIDnt EHhDviors. 
4. 'HtHrminH thH HxtHnt to whiFh (D) DutonomiF inGiFHs oI inIDnt sHlI-rHJulDtion DnG (E)
lDnJuDJH, sHnsory rHDFtivity pDttHrns, rHsponsH to joint DttHntion, DnG soFiDl-
FommuniFDtion skills FhDnJH ovHr thH FoursH oI thH 3,( intHrvHntion. .
+EFrom Pretest to Posttest-2, infants will show limited changes in autonomic indices during
exposure to nonsocial stimuli (Cohen's d <.25), but will show moderate-sized increases in
respiratory sinus arrhythmia (RSA) and decreases in skin conductance levels (SCL) during
exposure to child-directed speech (Cohen's d ? .40).
H4b: Infants will demonstrate small improvements in language, sensory reactivity patterns,
response to joint attention, and social-communication skills over the course of the PIE
intervention. 
3ULPDU\2EMHFWLYH
7hH positivH DssoFiDtion EHtwHHn pDrHnt rHsponsivHnHss DnG EHttHr soFiDl-FommuniFDtion
outFomHs in FhilGrHn in JHnHrDl, DnG FhilGrHn with nHuroGHvHlopmHntDl GisorGHrs (1's) in
pDrtiFulDr, hDs GrivHn thH GHvHlopmHnt oI HDrly intHrvHntions promotinJ pDrHnt
rHsponsivHnHss Ior thHsH populDtions. 6uFh intHrvHntion moGHls DssumH thDt inFrHDsHs in
pDrHnt rHsponsivHnHss will improvH FhilG outFomHs. +owHvHr, Ior intHrvHntions tDrJHtinJ
inIDnts DnG toGGlHrs Dt HlHvDtHG likHlihooG oI or GiDJnosHG with 1's, suFh Ds Dutism
spHFtrum GisorGHr ($6'), thH HIIHFts oI pDrHnt rHsponsivHnHss intHrvHntions hDvH EHHn
moGHst in sizH DnG hiJhly vDriDElH, rHnGHrinJ thH HviGHnFH inFonFlusivH Ior pDrHnt
rHsponsivHnHss Ds D mHGiDtor oI inIDnt/toGGlHr outFomHs.
:H proposH thDt HnsurinJ D morH HIIHFtivH pDrHnt-mHGiDtHG intHrvHntion Ior this populDtion
GHpHnGs on thH JuiGDnFH oI D rHIinHG thHory oI FhDnJH—onH HxpliFitly DFknowlHGJinJ thDt
inIDnt EHhDviors inIluHnFH pDrHnt rHsponsivHnHss. 'HvHlopmHntDl stuGiHs inGiFDtH thDt
inIDnts Dt HlHvDtHG likHlihooG oI 1's DrH likHly to HxhiEit EHhDviors thDt HithHr IDil to HliFit
pDrHnt rHsponsHs or HliFit pDrHnt rHsponsHs thDt Go not HIIHFtivHly support thH inIDnt's
HnJDJHmHnt DnG lHDrninJ. ,n DGGition, optimDl IHDturHs oI pDrHnt rHsponsivHnHss DppHDr to
17

Protocol Number 
18 June 2021 - version DRAFT
vDry Ds D IunFtion oI FhilGrHn's GHvHlopmHntDl lHvHls DnG othHr GynDmiF vDriDElHs. 7o GDtH,
stuGiHs oI pDrHnt-mHGiDtHG intHrvHntions hDvH not DGGrHssHG thHsH FomplHxitiHs. +owHvHr,
rHFHnt rHsHDrFh points to kHy "FhilG" vDriDElHs likHly to plDy trDnsDFtionDl rolHs in
FommuniFDtion GHvHlopmHnt DmonJ inIDnts DnG toGGlHrs with or Dt-risk Ior 1's. 7hHsH
inFluGH DspHFts oI FhilGrHn's prHlinJuistiF FommuniFDtion FhDrDFtHristiFs (H.J., intHntionDl
FommuniFDtion, GivHrsity oI FonsonDnts) thDt DrH rHlDtHG to Eoth pDrHnt rHsponsivHnHss DnG
FhilGrHn's lDtHr FommuniFDtion skills. $lso, prHliminDry GDtD Irom our tHDm inGiFDtH inIDnts'
sHnsory rHDFtivity (hypo- DnG hypHr-rHDFtivity) prHGiFts not only pDrHnt rHsponsivHnHss Eut
Dlso soFiDl-FommuniFDtion outFomHs oI inIDnts Dt-risk Ior 1's. $rJuDEly, inFrHDsHs in
pDrHnt rHsponsivHnHss lHDG to improvHG pDrHnt-inIDnt GyDGiF HnJDJHmHnt, whiFh in turn
mHGiDtHs inIDnts' FommuniFDtion outFomHs. )inDlly, physioloJiFDl sHlI-rHJulDtion impDFts
soFiDl DnG FommuniFDtion outFomHs in FhilGrHn, Eut mDy EH GisruptHG in inIDnts Dt-risk Ior
1's, DssoFiDtHG with thHir GiIIiFultiHs moGulDtinJ sHnsory rHDFtivity.
,n rH-FonFHptuDlizinJ intHrvHntion Ior inIDnts Dt-risk Ior 1's, wH hDvH intHJrDtHG thHsH
vDriDElHs into D nHw moGHl, 3DrHnts DnG ,nIDnts (nJDJHG (3,(), with two kHy FontHnt
GomDins: 6Hnsory 5HDFtivity DnG 3rHlinJuistiF &ommuniFDtion.
2EjHFtivH 1: 7hH primDry oEjHFtivH oI this stuGy is to HxDminH whHthHr thH novHl 3,(
intHrvHntion trDnsIorms pDrHnt-inIDnt trDnsDFtions ovHr timH Ds intHnGHG, thHrHEy
IDFilitDtinJ inFrHDsHs in thH timH inIDnts spHnG in GyDGiF HnJDJHmHnt with thHir pDrHnts. :H
will Dlso HvDluDtH whHthHr GyDGiF HnJDJHmHnt outFomHs GiIIHr EDsHG on whHthHr pDrHnts
DrH FoDFhHG Iirst in thH sHnsory rHDFtivity GomDin IollowHG Ey FoDFhinJ in thH prHlinJuistiF
FommuniFDtion GomDin, or DrH FoDFhHG in thH oppositH orGHr. 
6HFRQGDU\2EMHFWLYHV
2ur sHFonGDry oEjHFtivHs will proviGH IurthHr insiJhts into whHthHr thH 3,( intHrvHntion is
IunFtioninJ Ds intHnGHG. 6pHFiIiFDlly, our sHFonGDry oEjHFtivHs DrH to:
2EjHFtivH 2: (stimDtH thH sHpDrDtH DnG FomEinHG HIIHFts oI thH two 3,( intHrvHntion
GomDins on inIDnt intHntion FommuniFDtion.
2EjHFtivH 3: (vDluDtH thH GiIIHrHntiDl FhDnJHs in pDrHnt rHsponsivHnHss IollowinJ
FoDFhinJ on two inGiviGuDl 3DrHnts DnG ,nIDnts (nJDJHG (3,() intHrvHntion GomDins —
rHsponsHs to vDriDElH inIDnt (D) sHnsory rHDFtivity or (E) prHlinJuistiF FommuniFDtion —
Ds wHll Ds FumulDtivH FhDnJHs in pDrHnt rHsponsivHnHss IollowinJ FoDFhinJ on Eoth 3,(
GomDins.
2EjHFtivH 4: 'HtHrminH thH HxtHnt to whiFh (D) DutonomiF inGiFHs oI inIDnt sHlI-
rHJulDtion, DnG (E) lDnJuDJH, sHnsory rHDFtivity pDttHrns, rHsponsH to joint DttHntion,
DnG soFiDl-FommuniFDtion skills FhDnJH ovHr thH FoursH oI thH 3,( intHrvHntion.
18

Protocol Number 
18 June 2021 - version DRAFT
*HQHUDO'HVLJQ'HVFULSWLRQ
7his intHrvHntion triDl will usH D rDnGomizHG FompDrDtivH triDl GHsiJn. :H will rHFruit
pDrtiFipDnts Ey mDilinJ thH )irst <HDrs ,nvHntory v3.1 ()<,v3.1) to IDmiliHs oI 11- 16-month-
olG inIDnts EDsHG on puEliF Eirth rHForGs Ior our FDtFhmHnt DrHD (Ds in our prior stuGiHs), Ds
wHll Ds GistriEutinJ hDrG FopiHs DnG links to Dn onlinH vHrsion oI thH )<,v3.1 throuJh DrHD
pHGiDtriF prDFtiFHs DnG puEliF hHDlth FliniFs. 3rojHFt stDII will FontDFt pDrHnts oI inIDnts who
sForH Dt or DEovH thH thrHsholG inGiFDtinJ Dn HlHvDtHG likHlihooG oI D IuturH
nHuroGHvHlopmHntDl GisorGHr (1') GiDJnosis Ey phonH to shDrH thH sFrHHninJ rHsults DnG
IurthHr sFrHHn Ior stuGy HxFlusion FritHriD. ,I no HxFlusionDry IDFtors DrH iGHntiIiHG, IDmiliHs
will EH inIormHG DEout thH ovHrDll stuGy DnG spHFiIiFDlly thH EDsHlinH DssHssmHnt. )DmiliHs
who proviGH FonsHnt Ior thH EDsHlinH DssHssmHnt will EH DssHssHG Dt our rHsHDrFh oIIiFHs,
whiFh inFluGH D FhilG-IriHnGly DssHssmHnt suitH. )inDl stuGy HliJiEility will EH GHtHrminHG Ey
thH EDsHlinH DssHssmHnts (i.H., thH inIDnt must GHmonstrDtH rHFHptivH DnG/or HxprHssivH
lDnJuDJH sForHs onH 6' EHlow thH mHDn DnG mHHt FliniFDlly GHtHrminHG FritHriD suJJHstinJ
HxtrHmH hypo- DnG/or hypHr-rHDFtivity). 3DrHnts oI HliJiElH inIDnts will thHn EH DskHG to
FonsHnt to HnrollmHnt in thH intHrvHntion triDl. 7hH projHFt mHthoGoloJist will rDnGomizH
IDmiliHs oI HliJiElH inIDnts (strDtiIiHG Ior DJH < 14 months DnG ≥ 14 months) to EH initiDlly
FoDFhHG on HithHr thH prHlinJuistiF FommuniFDtion GomDin ($rm1) or thH sHnsory rHDFtivity
GomDin ($rm2) oI 3,(. )DmiliHs will pDrtiFipDtH in 6 wHHkly in-homH FoDFhinJ sHssions in
thHir rHspHFtivH trHDtmHnt Drms EHIorH rHturninJ to our rHsHDrFh oIIiFHs Ior 3osttHst-1
DssHssmHnts. $ItHr 3osttHst-1, $rm1 GyDGs will rHFHivH 6 wHHks oI FoDFhinJ on thH sHnsory
rHDFtivity GomDin, DnG $rm2 GyDGs will rHFHivH 6 wHHks oI FoDFhinJ on thH prHlinJuistiF
FommuniFDtion GomDin; FoDFhinJ Ior HDFh Jroup will Dlso inFluGH rHviHw oI thH rHspHFtivH
FontHnt GomDin FoDFhHG in 6tuGy 3hDsH 1. 7hHn IDmiliHs will rHturn Ior 3osttHst-2. 
6WXG\'DWH5DQJHDQG'XUDWLRQ
7hH stuGy will stDrt $uJust 1, 2017, with GDtD FollHFtion FontinuinJ Ior 22 months. 
1XPEHURI6WXG\6LWHV
7hHrH is onH stuGy sitH Ior GDtD FollHFtion, Dt thH 8nivHrsity oI 1orth &DrolinD Dt &hDpHl +ill,
&hDpHl +ill, 1&.
'DtD proFHssinJ, viGHo FoGinJ, DnG stDtistiFDl DnDlysHs will oFFur Dt two sitHs, thH 8nivHrsity
oI 1orth &DrolinD Dt &hDpHl +ill DnG thH 8nivHrsity oI 6outhHrn &DliIorniD, /os $nJHlHs, &$.  
2XWFRPH9DULDEOHV
3ULPDU\2XWFRPH9DULDEOHV
19

Protocol Number 
18 June 2021 - version DRAFT
7hH primDry outFomH vDriDElH is pDrHnt-inIDnt GyDGiF HnJDJHmHnt. :H GHIinH GyDGiF
HnJDJHmHnt Ds Dn oEsHrvDElH pDttHrn oI mutuDl IoFus, DFtivH pDrtiFipDtion, DnG rHFiproFDl
HxFhDnJHs within D pDrHnt DnG FhilG intHrDFtion.
:H will FollHFt GDtD on this outFomH Dt EDsHlinH, posttHst 1 (DItHr IDmiliHs hDvH EHHn
rDnGomly DssiJnHG to Dn intHrvHntion Drm DnG FoDFhHG in onH oI thH two 3,( intHrvHntion
GomDins), DnG posttHst 2 (DItHr IDmiliHs hDvH EHHn FoDFhHG in Eoth oI thH 3,( intHrvHntion
GomDins). 
7hH rDtionDlH Ior FhoosinJ GyDGiF HnJDJHmHnt Ds thH primDry outFomH is thDt pDrHnt
FoDFhinJ in HDFh GomDin is GHsiJnHG to Dssist pDrHnts in HnJDJinJ thHir FhilG in positivH
intHrDFtions with thHm DnG inFrHDsinJ thH lHnJth oI thHsH pHrioGs oI HnJDJHmHnt throuJh
supportinJ thH inIDnts in rHJulDtinJ thHir rHsponsHs to sHnsory stimuli DnG/or rHsponGinJ
sHnsitivHly to inIDnts' prHlinJuistiF FommuniFDtion FuHs. 'yDGiF HnJDJHmHnt is D
FonFHptuDlly importDnt outFomH vDriDElH, Ds suJJHstHG Ey prior HviGHnFH thDt rHsponsivH
pDrHnt lDnJuDJH (i.H., lDnJuDJH thDt Iollows-in to thH FhilG's IoFus oI DttHntion) is DssoFiDtHG
with IuturH lDnJuDJH DnG soFiDl-FommuniFDtion GHvHlopmHnt in younJ FhilGrHn with Dutism,
,) this lDnJuDJH oFFurs GurinJ Dn HnJDJHmHnt stDtH in whiFh thH FhilG DnG pDrHnt DrH
rHsponGinJ rHFiproFDlly to onH DnothHr, Eut not whHn pDrHntDl Iollow-in lDnJuDJH rHsponsHs
DrH JivHn in thH HnJDJHmHnt stDtHs whHrH thH FhilG GoHs not proviGH Dny rHFiproFDl
rHsponsHs to thH pDrHnt (%ottHmD-%HutHl Ht Dl., 2014). 5HFiproFity EHtwHHn thH inIDnt DnG
pDrHnt is D kHy FomponHnt oI our GHIinition oI GyDGiF HnJDJHmHnt. 7hus, HstDElishinJ DnG
mDintDininJ GyDGiF HnJDJHmHnt stDtHs mDy EH FruFiDl to inIDnts Dt HlHvDtHG likHlihooG oI
1's in proviGinJ thHm with optimDl FontHxts Ior lHDrninJ soFiDl-FommuniFDtion DnG
lDnJuDJH skills. 
7his outFomH will EH HvDluDtHG usinJ Dn DGDptHG vHrsion oI D pDrHnt-FhilG HnJDJHmHnt
stDtH FoGinJ systHm oriJinDlly GHvHlopHG Ey $GDmson Ht Dl. (2009) DnG DGDptHG Ey
%ottHmD-%HutHl Ht Dl., (2018). 9DriDtions oI thH $GDmson Ht Dl. HnJDJHmHnt stDtH FoGinJ
hDvH EHHn 5HsHDrFh DssistDnts will EH trDinHG to rHliDEility on FoGinJ GyDGiF HnJDJHmHnt
on viGHos thDt hDvH EHHn FonsHnsus FoGHG Ey projHFt stDII ovHrsHHinJ FoGinJ oI this
vDriDElH. 9iGHos Ior thH stuGy will FomprisH D ~20-minutH viGHo oI pDrHnt-inIDnt intHrDFtions
thDt inFluGHs IrHH-plDy, D sHmit-struFturHG ":hDt's in thH Eox"" DFtivity, snDFk timH, DnG
FlHDninJ up DItHr thH snDFk. )ollowinJ FoGinJ trDininJ, onH out oI HvHry IivH FoGHG viGHos
will EH rDnGomly sHlHFtHG Ior inGHpHnGHnt FoGinJ, in orGHr to DssHss thH rHliDEility oI our
mHDsurH oI GyDGiF HnJDJHmHnt GDtD Ior thH triDl. &oGHrs will not EH DwDrH oI whiFh viGHos
DrH EHinJ FoGHG Ior rHliDEility purposHs. 3HrioGiF EoostHr trDininJ Ior rHsHDrFh DssistDnts
FoGinJ GyDGiF HnJDJHmHnt will oFFur to limit thH risk oI oEsHrvHr GriIt. 
6HFRQGDU\DQG([SORUDWRU\2XWFRPH9DULDEOHV
6HFonGDry outFomH vDriDElHs:
7hH Iirst thrHH sHFonGDry outFomH mHDsurHs will EH DssHssHG Dt thrHH timHpoints: %DsHlinH,
3osttHst 1 (DItHr IDmiliHs hDvH EHHn rDnGomly DssiJnHG to Dn intHrvHntion Drm DnG FoDFhHG
in onH oI thH two 3,( intHrvHntion GomDins), DnG 3osttHst 2 (DItHr IDmiliHs hDvH EHHn
FoDFhHG in Eoth oI thH 3,( intHrvHntion GomDins). )or thHsH mHDsurHs, wH DrH pDrtiFulDrly
intHrHstHG in whHthHr thHrH DrH HIIHFts spHFiIiF to thH initiDl 3,( FoDFhinJ GomDin (sHnsory
20

Protocol Number 
18 June 2021 - version DRAFT
rHDFtivity or prHlinJuistiF FommuniFDtion) Dt 3osttHst 1, DnG whHthHr thHrH DrH orGHr HIIHFts
(GiIIHrHnFHs EHtwHHn stuGy Drms) Dt 3osttHst 2. 
1. &hDnJHs in pDrHnt rHsponsivHnHss to inIDnt sHnsory rHDFtivity FuHs. >0HDsurHG viD D
projHFt-GHvHlopHG rDtinJ tool.@ 7his sHFonGDry mHDsurH is inFluGHG to GHtHrminH whHthHr
FoDFhinJ in thH sHnsory rHDFtivity GomDin yiHlGs thH HxpHFtHG spHFiIiF HIIHFts on pDrHnts'
rHsponsHs to inIDnt sHnsory rHDFtivity FuHs. 3DrHnts will EH rDtHG on D 1-7 sFDlH Ior thHir
rHsponsivHnHss to sHnsory rHDFtivity Ior HDFh oI thH 4 DFtivitiHs inFluGHG in thH pDrHnt-
inIDnt intHrDFtion sHssion, usinJ viGHorHForGinJs oI thHsH sHssions. $ mDnuDl will EH
GHvHlopHG to GHsFriEH thH rDtinJ systHm DnG thH lHvHl oI rHsponsivity DssoFiDtHG with HDFh
oI thH 7 points on thH sFDlH. 5HsHDrFh DssistDnts will EH trDinHG to rHliDEility Ey supHrvisinJ
stDII. 'urinJ rDtinJ oI thH projHFt viGHos, onH oI 5 rDtHG viGHos will EH inGHpHnGHntly rDtHG
Ior rHliDEility. 5DtHrs will EH ElinG to stuGy Drm DnG timHpoint oI pDrtiFipDnts. 
2. &hDnJHs in pDrHnt rHsponsivHnHss to inIDnt prHlinJuistiF FommuniFDtion
FuHs.  >0HDsurHG viD D projHFt-GHvHlopHG rDtinJ tool.@ 7his sHFonGDry mHDsurH is inFluGHG
to GHtHrminH whHthHr FoDFhinJ in thH prHlinJuistiF FommuniFDtion GomDin yiHlGs thH
HxpHFtHG spHFiIiF HIIHFts on pDrHnts' rHsponsHs to inIDnt prHlinJuistiF FommuniFDtion FuHs.
0DnuDlizDtion, trDininJ DnG rHliDEility proFHGurHs DrH iGHntiFDl to thosH GHsFriEHG Ior thH
pDrHnt rHsponsivHnHss to sHnsory rHDFtivity mHDsurH. 
3. &hDnJHs in inIDnt intHntionDl FommuniFDtion. >0HDsurHG viD D projHFt-GHvHlopHG FoGinJ
systHm.@ 7hH rDtionDlH Ior inFluGinJ this outFomH mHDsurH is thDt pDrHntDl rHsponsivH
support oI inIDnt HnJDJHmHnt will promotH inIDnts' inFrHDsHG usH oI intHntionDl
FommuniFDtion, prHviously IounG to prHGiFt lDtHr rHFHptivH DnG HxprHssivH lDnJuDJH
outFomHs Ior prHsFhoolHrs DlrHDGy GiDJnosHG with Dutism (<oGHr Ht Dl., 2015). ,ntHntionDl
FommuniFDtion DFts DrH GHIinHG Ds DFts thDt DrH GirHFtHG towDrG D FommuniFDtion pDrtnHr
(in this FDsH, thH pDrHnt or othHr primDry IDmily FDrHJivHr prHsHnt GurinJ thH pDrHnt-inIDnt
intHrDFtion sHssion) to FonvHy D mHssDJH, DnG inFluGH (D) voFDlizDtions, (E) JHsturHs, or (F)
FomEinDtions oI Eoth voFDlizDtions DnG JHsturHs. $ FoGinJ mDnuDl will EH GHvHlopHG to
GHsFriEH thH FoGinJ systHm DnG proviGH HxDmplHs DnG nonHxDmplHs oI ,nIDnt intHntionDl
FommuniFDtion DFts. 7his mHDsurH will EH FoGHG Irom viGHos oI thH pDrHnt-inIDnt
intHrDFtion sHssions. 5HsHDrFh DssistDnts will EH trDinHG to rHliDEility Ey supHrvisinJ projHFt
stDII. 2nH oI HvHry IivH FoGHG viGHos will EH rDnGomly sHlHFtHG Ior inGHpHnGHnt FoGinJ Ey
DnothHr rHsHDrFh DssistDnt. &oGHrs will EH ElinG to DssiJnHG Drm oI thH intHrvHntion DnG to
timHpoint oI thH DssHssmHnt. 
7hH IollowinJ 8 sHFonGDry outFomH vDriDElHs will EH mHDsurHs Dt two timHpoints: %DsHlinH
DnG 3osttHst 2. )or thHsH mHDsurHs, wH DrH pDrtiFulDrly intHrHstHG in HxDmininJ thH
mDJnituGH oI FhDnJH ovHr thH FoursH oI thH Iull intHrvHntion, Ds wHll Ds whHthHr thHrH DrH
orGHr HIIHFts (GiIIHrHnFHs EHtwHHn stuGy Drms) Dt 3osttHst 2.
4. &hDnJHs in inIDnt rHspirDtory sinus DrrhythmiD (56$). 7his mHDsurH wDs FhosHn Ds Dn
inGHx oI pDrDsympDthHtiF systHm IunFtioninJ, DnG will EH mHDsurHG within D pDrDGiJm in
whiFh thH inIDnts DrH pDssivHly oEsHrvinJ (D) Dn instrumHntDl musiF viGHo without soFiDl
imDJHs, DnG (E) thrHH on-minutH viJnHttHs oI inIDnt-GirHFtHG spHHFh, Ds Dn HxpHrimHntDl
DnDloJ oI pDrHnt-inIDnt intHrDFtions. :H hypothHsizH wH will sHH inFrHDsHG 56$ lHvHls
GurinJ inIDnt-GirHFtHG spHHFh, rHIlHFtinJ JrHDtHr pDrDsympDthHtiF Fontrol DnG improvHG
21

Protocol Number 
18 June 2021 - version DRAFT
sHnsory rHsponsH rHJulDtion, Ey 3osttHst 2. 'DtD will EH FollHFtHG with thH )irstEHDt GHviFH,
with 2 HlHFtroGHs plDFHG on thH inIDnt's FhHst, DnG FovHrHG with thH inIDnt's FlothinJ.
5HForGs oI intHrEHDt intHrvDls will EH DliJnHG with thH viGHo sHJmHnts thH inIDnts viHwHG,
HGitHG usinJ &DrGio(Git (%rDin-%oGy &HntHr, 2007) Ey D rHsHDrFh DssistDnt trDinHG to
rHliDEility, DnG proFHssHG usinJ &DrGio%DtFh (%rDin-%oGy &HntHr, 2007) to GHrivH 56$. 
5. &hDnJHs in inIDnt skin FonGuFtDnFH lHvHl (6&/). 7his mHDsurH wDs FhosHn Ds Dn inGHx oI
sympDthHtiF systHm IunFtioninJ, DnG will EH mHDsurHG within thH DEovH GHsFriEHG inIDnt-
GirHFtHG spHHFh pDrDGiJm. :H hypothHsizH wH will sHH GHFrHDsHG 6&/ lHvHls GurinJ inIDnt-
GirHFtHG spHHFh, rHIlHFtinJ lHss HlHvDtion oI sympDthHtiF DFtivity DnG improvHG sHnsory
rHJulDtion whHn oEsHrvinJ inIDnt-GirHFtHG spHHFh viJnHttHs, Ey 3osttHst 2. 'DtD will EH
FollHFtHG usinJ thH 6himmHr GHviFH; rHForGs oI 6&/ will DliJnHG with thH viGHo sHJmHnts
thH inIDnts viHwHG, DnG proFHssHG usinJ .uEios. 
6 &hDnJHs in inIDnts' rHFHptivH lDnJuDJH. >0HDsurHG viD thH 0ullHn 6FDlHs oI (Drly /HDrninJ
(06(/) 5HFHptivH /DnJuDJH sFDlH, 0ullHn, 1995.@ 3rior rHsHDrFh inGiFDtHs thDt rHFHptivH
lDnJuDJH mDy EH improvHG GistDl to with improvHmHnts in pDrHnt-inIDnt GyDGiF
HnJDJHmHnt DnG inIDnt intHntionDl FommuniFDtion. 7hH 5HFHptivH /DnJuDJH 6FDlH is onH oI
5 06(/ sFDlHs DssHssinJ GHvHlopmHnt Ior FhilGrHn Eirth-68 months. (DFh sFDlH (*ross
0otor, )inH 0otor, 9isuDl 5HFHption, 5HFHptivH /DnJuDJH, (xprHssivH /DnJuDJH) yiHlGs D 7-
sForH, pHrFHntilH DnG DJH HquivDlHnt. 7hH 06(/ hDs EHHn usHG Ds D stDnGDrGizHG mHDsurH
oI GHvHlopmHnt DFross GomDins in mDny trHDtmHnt stuGiHs oI younJ FhilGrHn with 1's.
7. &hDnJHs in inIDnts' HxprHssivH lDnJuDJH. >0HDsurHG viD thH 06(/ 5HFHptivH /DnJuDJH
sFDlH, 0ullHn, 1995.@ %DsHG on prior rHsHDrFh, wH mDy Dlso sHH improvHmHnts in HxprHssivH
lDnJuDJH GistDl to improvHmHnts in pDrHnt-inIDnt GyDGiF HnJDJHmHnt DnG inIDnt intHntionDl
FommuniFDtion. 6HH IurthHr GHtDils on thH 06(/ in itHm #6 DEovH. 
8. &hDnJHs in inIDnts' rHsponsHs to DGults' EiGs to GirHFt thHir DttHntion to Dn nHw oEjHFt
(i.H., rHsponsH to joint DttHntion). >0HDsurHG viD D suEsHt oI 6 $ttHntion )ollowinJ triDls Irom
thH -oint $ttHntion 3rotoFol, :Dtson Ht Dl., 2003.@ 2nH IrHquHnt EHhDviorDl FhDrDFtHristiF oI
inIDnts Dt HlHvDtHG likHlihooG oI lDtHr 1' is thDt thHy hDvH GiIIiFulty in rHsponGinJ to joint
DttHntion EiGs thDt rHquirH thHm to rHGirHFt thHir DttHntion DwDy Irom thHir FurrHnt IoFus to
D nHw oEjHFt. 3otHntiDlly, improvHmHnts in pDrHnt-inIDnt GyDGiF HnJDJHmHnt will, ovHr timH,
yiHlG improvHmHnts in rHsponsH to joint DttHntion Ds pDrHnts lHDrn to usH nHw strDtHJiHs to
HIIHFtivHly HnJDJH thHir inIDnt, DnG inIDnts hDvH morH HxpHriHnFHs in rHFiproFDl intHrDFtions
with thHir FDrHJivHrs. 6uFh FhDnJHs FoulG siJnDl inIDnts' GHFrHDsHG GHpHnGHnFy on pDrHnts
oEsHrvinJ DnG rHsponGinJ to thHir immHGiDtH IoFus oI DttHntion, DnG proviGH D lDrJHr
vDriHty oI lHDrninJ opportunitiHs. 7hH -oint $ttHntion 3rotoFol wDs GHvHlopHG in FonjunFtion
with Dn HDrliHr stuGy Ey our tHDm Ds D mHDsurH thDt FoulG EH sForHG rHliDEly GurinJ
DGministrDtion, DnG hDs GHmonstrDtHG sounG rHliDEility DnG vDliGity Ior usH with younJ
FhilGrHn with Dutism (1owHll Ht Dl., 2018).
9. &hDnJHs in inIDnts' soFiDl-FommuniFDtion skills. >0HDsurHG viD thH %riHI 2EsHrvDtion oI
6oFiDl-&ommuniFDtion &hDnJH, %26&&, /orG, *rzDGzinski Ht Dl., 2017.@ ,n DnDlysHs with
othHr sDmplHs sFrHHnHG with thH )<,v3.1, our tHDm hDs GoFumHntHG thDt thH positivH
prHGiFtivH vDluH oI thH tool spHFiIiFDlly Ior Dutism is DrounG 30-40%, vDryinJ with thH DJH Dt
sFrHHninJ (unpuElishHG GDtD). 'uH to thH nDturH oI thH itHms on thH )<,v3.1, inIDnts
mHHtinJ thH thrHsholG Ior EHinJ Dt HlHvDtHG likHlihooG Ior 1' on thH )<,v.3.1 will hDvH
pDrHnt-rHportHG soFiDl-FommuniFDtion EHhDviors DssoFiDtHG with Dutism. 7hH %26&& wDs
22

Protocol Number 
18 June 2021 - version DRAFT
GHsiJnHG to DssHss improvHmHnts in HDrly soFiDl-FommuniFDtion skills thDt DrH usuDlly
impDirHG in younJ FhilGrHn with Dutism Eut Dlso DrH known to FhDnJH/improvH ovHr timH.
7hus, wH DrH usinJ thH %26&& to HxDminH whHthHr thHsH skills FhDnJH siJniIiFDntly ovHr thH
FoursH oI thH Iull 3,( intHrvHntion. )or this stuGy, wH will usH thH 12-minutH %26&&
intHrDFtion protoFol GurinJ whiFh Dn HxDminHr intHrDFts with thH FhilG, whiFh will EH
viGHorHForGHG DnG sForHG lDtHr Ey trDinHG rHsHDrFh DssistDnts ElinG to DssiJnmHnt Drm DnG
timHpoint. $s with othHr mHDsurHs Irom viGHos, onH oI 5 sForHG viGHos will EH rDnGomly
sHlHFtHG Ior inGHpHnGHnt sForinJ Ior rHliDEility purposHs. 7hH rHsHDrFh DssistDnts workinJ
on this mHDsurH will mHHt rHJulDrly with thH supHrvisinJ stDII to rHviHw sForinJ GHFisions to
DttHntuDtH thH risk oI oEsHrvHr GriIt. 
10. &hDnJHs in oEsHrvHG inIDnt sHnsory rHDFtivity pDttHrns. >0HDsurHG viD thH 6Hnsory
3roFHssinJ $ssHssmHnt Ior <ounJ &hilGrHn, 63$, %DrDnHk, 1999D.@ ,n FoDFhinJ pDrHnts to EH
sHnsitivH to thHir inIDnts' FuHs rHlDtHG to sHnsory rHDFtivity DnG to rHsponG in wDys thDt
support thHir inIDnts' rHJulDtion oI thHsH rHsponsHs, DnothHr potHntiDl GistDl outFomH oI thH
3,( intHrvHntion woulG EH improvHmHnts in HxtrHmH pDttHrns oI sHnsory rHDFtivity (i.H.,
GiminishHG hypo- DnG/or hypHr-rHDFtivity). 8sH oI thH 63$ Ds Dn oEsHrvDtionDl mHDsurH will
proviGH us with thH opportunity to DssHss whHthHr Dny FhDnJHs DrH oEsHrvHG Ey DssHssors
who DrH ElinGHG to thH Drm oI thH stuGy to whiFh IDmiliHs DrH DssiJnHG. 7hH 63$ is D plDy-
EDsHG DssHssmHnt thDt mHDsurHs DpproDFh-DvoiGDnFH to novHl sHnsory toys, sHnsory
sHHkinJ EHhDviors, DnG oriHntinJ rHsponsHs DFross thrHH sHnsory moGDlitiHs, DnG is
sHnsitivH to mDturDtionDl FhDnJHs. ,t hDs JooG intHr-rDtHr rHliDEility (,&&   .91 to .99 Ior
GiIIHrHnt sFDlHs), DnG GisFriminDtHs GiIIHrHnt pDttHrns oI sHnsory rHsponsH EHtwHHn FhilGrHn
with Dutism DnG FhilGrHn with othHr GHvHlopmHntDl GisDEilitiHs (%DrDnHk Ht Dl., 2007). 
11. &hDnJHs in pDrHnt-rHportHG inIDnt sHnsory rHDFtivity pDttHrns. >0HDsurHG viD thH
6Hnsory (xpHriHnFHs 4uHstionnDirH v. 2.1, 6(4, %DrDnHk, 1999E.@ $s D FomplHmHnt to thH
63$, wH DrH usinJ thH 6(4 to GHtHrminH whHthHr pDrHnts pHrFHivH improvHmHnts in thHir
FhilGrHn's sHnsory rHDFtivity pDttHrns ovHr thH FoursH oI thH Iull 3,( intHrvHntion. 7hH 6(4 is
D 43-itHm quHstionnDirH Ior FhilGrHn 6 months to 6 yHDrs thDt mHDsurHs rHsponsHs to
vDrious sHnsory stimuli in thH FontHxt oI GDily DFtivitiHs. )DFtor sForHs Ior hypo- & hypHr-
rHsponsivHnHss DnG sHnsory sHHkinJ DrH FompDtiElH with thH FonFHptuDl moGHl oI thH 63$.
7hH intHrnDl FonsistHnFy is DFFHptDElH (&ronEDFh's α  ,80). ,t GisFriminDtHs pDttHrns uniquH
to $6' DnG is sHnsitivH to mDturDtionDl FhDnJHs (%DrDnHk Ht Dl., 2006).
6WXG\3RSXODWLRQ
7hH stuGy populDtion is inIDnts EHtwHHn thH DJHs oI 11-16 months who DrH iGHntiIiHG Ds
EHinJ Dt HlHvDtHG likHlihooG oI D lDtHr nHuroGHvHlopmHntDl GisDEility GiDJnosis (H.J., Dutism
spHFtrum, DttHntion-GHIiFit hypHrDFtivity GisorGHr, lDnJuDJH GHlDy/GisorGHr, sHnsory
proFHssinJ GisorGHr), DlonJ with D pDrHnt (or othHr primDry IDmily FDrHJivHr H.J.,
JrDnGpDrHnt) Ior HDFh FhilG. ,nIDnts will EH rHFruitHG Irom 6 FHntrDl 1orth &DrolinD FountiHs
whosH IDr EounGDriHs DrH within 90 milHs oI &hDpHl +ill, thH loFDtion oI thH rHsHDrFh oIIiFHs
Ior this stuGy. 7hH two primDry sourFHs oI rHFruitmHnt will EH: (D) stDtH Eirth rHJistriHs (1&
9itDl rHForGs; 6 FountiHs within 90 milHs oI &hDpHl +ill inFluGinJ 2rDnJH, 'urhDm, &hDthDm,
$lDmDnFH, *uilIorG, DnG :DkH), DnG (E) primDry FDrH wHll-EDEy FliniFs — HithHr throuJh
loFDl pHGiDtriF prDFtiFHs or Founty hHDlth FliniFs, in rurDl DnG urEDn DrHDs thDt rHprHsHnt
wiGH GHmoJrDphiFs. )urthHr, wH will hDvH Eooths Dt IDmiliy-oriHntHG IDirs/HvHnts in our
23

Protocol Number 
18 June 2021 - version DRAFT
FDtFhmHnt DrHD oIIHrinJ FhilG-IriHnGly DFtivitiHs (H.J., EuEElH mDFhinHs) DnG stuGy
inIormDtion Ior pDrHnts, DnG GissHminDtH inIormDtion DEout thH stuGy inFluGinJ D link to Dn
onlinH vHrsion oI our pDrHnt rHport sFrHHnHr throuJh soFiDl mHGiD, FDrGs GistriEutHG throuJh
FhilG FDrH FHntHrs, HtF.
3DrHnts initiDlly will EH DskHG to FomplHtH D sFrHHninJ quHstionnDirH, 7hH )irst <HDrs
,nvHntory, v.3.1E ()<,v3.1E; %DrDnHk Ht Dl., 2014), GHvHlopHG to iGHntiIy inIDnts to HlHvDtHG
likHlihooG Ior lDtHr GiDJnosis oI Dutism DnG othHr GHvHlopmHntDl FonGitions (H.J., DttHntion
GHIiFit hypHrDFtivity GisorGHr; lDnJuDJH GHlDys/GisorGHrs; sHnsory proFHssinJ GisorGHrs;
JloEDl GHvHlopmHntDl GHlDys). 7hH sFrHHninJ Fut-points on thH )<,v3.1E wHrH sHt in
FonjunFtion with D prHvious stuGy Ior whiFh wH hDG DFFHss to GiDJnostiF outFomH
inIormDtion suFh thDt wH FDpturH DEout 1/3 oI thH inIDnts who woulG Jo on to EH FonIirmHG
Ds hDvinJ D Dutism spHFtrum GiDJnosis whilH misFlDssiIyinJ lHss thDn 5% oI thH typiFDlly
GHvHlopinJ (7') sDmplH Ds Dt-risk. :H know Irom prHvious stuGiHs usinJ Dn HDrliHr vHrsion
oI thH )<, thDt mDny inIDnts lDtHr GiDJnosHG with othHr 1's Dlso will hDvH sForHs HxFHHGinJ
thH thrHsholG on thH )<, (7urnHr-%rown Ht Dl., 2013).
)or inIDnts whosH sFrHHninJ sForHs on thH )<,v3.1E mHHt thH thrHsholG Ior EHinJ Dt
HlHvDtHG likHlihooG Ior D lDtHr GiDJnosis oI Dn 1', thH rHsHDrFh FoorGinDtor will FDll thH
pDrHnts to IurthHr sFrHHn Ior inIDnt DnG pDrHnt HliJiEility, oIIHr inIormDtion DEout thH stuGy,
DnG invitH IDmiliHs with no HxFlusionDry IDFtors to pDrtiFipDtH in D EDsHlinH DssHssmHnt
(with inIormHG FonsHnt).
$t EDsHlinH DssHssmHnts, HliJiElH inIDnts will hDvH D sForH oI Dt lHDst 1 stDnGDrG GHviDtion
EHlow thH mHDn on thH 5HFHptivH or (xprHssivH /DnJuDJH sFDlH (or Eoth) oI thH 0ullHn
6FDlHs oI (Drly /HDrninJ, Ds wHll Ds mHHtinJ FliniFDlly-GHtHrminHG FritHriD Ior HlHvDtHG
pDttHrns oI hypo-rHDFtivity or hypHr-rHDFtivity (or Eoth) on thH 6Hnsory 3roFHssinJ
$ssHssmHnt: "+<32": &ut-point (HquDl or JrHDtHr thDn) oI 1.69 Ior 0HDn oI thH rDw oriHntinJ
sForH DFross 7 itHms, HDFh with thH rDnJH oI 1 to 4 possiElH points). "+<3(5": &ut-point
(HquDl or JrHDtHr thDn) oI .333 Ior 0HDn oI thH rDw DpproDFh/DvoiG novHl toys sForH DFross
9 itHms, HDFh with thH rDnJH oI 0 to 2 possiElH points) 25 $ny FlHDr "GHIHnsivH" rHsponsH
on oriHntinJ itHms or "<Hs" to FovHrinJ HDrs to sounG (in stHrHotypiHs FhHFklist). 7hHsH
inFlusion FritHriD will HnsurH thDt inIDnts DrH GHmonstrDtinJ GHlDys or GiIIHrHnFHs in DrHDs oI
GHvHlopmHnt thDt DrH tDrJHtHG Ey thH 3,( intHrvHntion (sHnsory rHDFtivity DnG
FommuniFDtion).
,nIDnts will inFluGH Eoth sHxHs, DlthouJh EDsHG on prHvious stuGiHs, wH HxpHFt D 2:1
(mDlH:IHmDlH) rDtio, JivHn thDt Eoys DrH morH likHly to sForH Dt HlHvDtHG likHlihooG Ior 1's
(H.J., Dutism) tDrJHtHG Ey thH )<,.
(xFlusion FritHriD: ,nIDnts with known JHnHtiF FonGitions (H.J., 'own synGromH), DnG thosH
with siJniIiFDnt unForrHFtHG vision/hHDrinJ/physiFDl impDirmHnts will EH HxFluGHG. :H
HxFluGH inIDnts with known JHnHtiF GisorGHrs GuH to our IoFus on tHstinJ 3,( with inIDnts Dt
HlHvDtHG likHlihooG oI nHuroGHvHlopmHntDl GisorGHrs EDsHG on EHhDviorDl mDrkHrs, Eut
whosH HvHntuDl GiDJnosis rHmDins unFlHDr. :H will HxFluGH inIDnts with siJniIiFDnt
unForrHFtHG vision/hHDrinJ/physiFDl impDirmHnts EHFDusH thHy likHly woulG not EH DElH to
Iully pDrtiFipDtH in thH DssHssmHnt proFHGurHs, DnG thH DssHssmHnt rHsults woulG EH oI
quHstionDElH vDliGity. )DmiliHs who Go not spHDk (nJlish Ds thHir primDry lDnJuDJH in thH
homH (!50% oI thH timH) will EH HxFluGHG, EHFDusH sFrHHninJ tools, DssHssmHnts, DnG
intHrvHntions DrH not DvDilDElH uniIormly in othHr lDnJuDJHs.
24

Protocol Number 
18 June 2021 - version DRAFT
1XPEHURI3DUWLFLSDQWV
:H plDn to Hnroll 44 inIDnts Dt HlHvDtHG likHlihooG oI D lDtHr 1' DnG D primDry FDrHJivHr oI
HDFh inIDnt. %DsHG on prior stuGiHs with similDr populDtions, wH DntiFipDtH DpproximDtHly
1% oI FomplHtHG )<,s will yiHlG D pDrHnt-inIDnt GyDG thDt mHHts Dll HliJiEility FritHriD DnG
FonsHnts to Hnroll in thH intHrvHntion triDl. 7hus, sFrHHninJ oI ~4400 inIDnts on thH )<,v3.1
likHly will EH rHquirHG to rHFruit this sDmplH. $ll rHFruitmHnt will tDkH plDFH Dt thH 8nivHrsity
oI 1orth &DrolinD Dt &hDpHl +ill stuGy sitH. 
(OLJLELOLW\&ULWHULD9XOQHUDEOH3RSXODWLRQV
(liJiEility
1. ,nIDnt is EHtwHHn 11 DnG 16 months (inFlusivH) Dt thH timH thDt thH pDrHnt FomplHtHs thH
)<,v3.1E.
2. ,nIDnt sForHs Dt or DEovH thrHsholG on thH )<,v3.1E Ior EHinJ Dt HlHvDtHG likHlihooG Ior D
lDtHr 1' GiDJnosis.
3. ,nIDnt sForHs 1 6' EHlow thH mHDn on thH 5HFHptivH /DnJuDJH DnG/or thH (xprHssivH
/DnJuDJH 6FDlH oI thH 0ullHn 6FDlHs oI (Drly /HDrninJ. 
4. ,nIDnt mHHts FliniFDl FritHriD Ior HlHvDtHG hypo- or hypHr-rHDFtivity on thH 6Hnsory
3roFHssinJ $ssHssmHnt Dt thH in-pHrson EDsHlinH DssHssmHnts. 
5. $ pDrHnt or othHr primDry FDrHJivHr oI thH inIDnt is DvDilDElH Ior stuGy pDrtiFipDtion. 
6. )Dmily livHs within thH FDtFhmHnt DrHD Ior thH stuGy. 
(xFlusion FritHriD
1. ,nIDnt hDs D known JHnHtiF FonGitions (H.J., 'own synGromH).
2. ,nIDnt hDs D known siJniIiFDnt unForrHFtHG vision/hHDrinJ/physiFDl impDirmHnts. 
3. )Dmiy who Go not spHDk (nJlish Ds thHir primDry lDnJuDJH in thH homH (!50% oI thH
timH).
9ulnHrDElH populDtions:
7his stuGy will Hnroll pDrtiFipDnts Irom thH vulnHrDElH populDtion oI FhilGrHn. 7his stuGy
Dims to proviGH intHrvHntion GurinJ inIDnFy, EHIorH thH Iull HmHrJHnFH oI EHhDviorDl
symptoms thDt woulG lHDG to D nHuroGHvHlopmHntDl GisorGHr GiDJnosis (H.J., $6',
lDnJuDJH GisorGHr, or DttHntion GHIiFit hypHrDFtivity GisorGHr). 7hH unGHrlyinJ prHmisHs Ior
thH stuGy rHquirH thH pDrtiFipDtion oI FhilGrHn: 1) 7hH Iirst 2 yHDrs oI liIH DrH Dn HspHFiDlly
DFtivH pHrioG oI nHurDl GHvHlopmHnt. 'uH to rDpiG synDptiF proliIHrDtion DnG HxpHriHntiDlly-
25

Protocol Number 
18 June 2021 - version DRAFT
inIluHnFHG shDpinJ oI IunFtionDl FonnHFtivity, intHrvHntions initiDtHG in inIDnFy mDy EH
powHrIul in promotinJ morH typiFDl nHurDl FonnHFtivity. (2) %ioloJiFDlly-EDsHG GiIIHrHnFHs in
inIDnts Dt-risk Ior 1's lHDG to oEsHrvDElH GiIIHrHnFHs in sHnsory rHDFtivity DnG
FommuniFDtion EHhDviors in most inIDnts Ey 11-16 months, prior to thH Iull HmHrJHnFH oI
GiDJnostiF symptoms. (3) 'iIIHrHnFHs in inIDnt EHhDviors inIluHnFH thH quDntity DnG quDlity
oI pDrHnt rHsponsHs. (4) 3DrHnt-FhilG trDnsDFtionDl proFHssHs EHJin HDrly in inIDnFy DnG
impDFt lonJ-tHrm FhilG outFomHs. 
3rotHFtions: 
$ll pDrtiFipDnts will EH DssiJnHG D uniquH iGHntiIiFDtion numEHr DnG Dll mDtHriDls rHlDtHG to
D pDrtiFipDnt will usH this numEHr DnG not D FhilG's or pDrHnt's nDmH. 1DmHs DssoFiDtHG
with ,' numEHrs DrH storHG in D pDssworG-protHFtHG FomputHr IilH. $ll IDmily/FhilG-rHlDtHG
GDtD (pDpHr or HlHFtroniF) DrH storHG in D loFkHG IilH FDEinHt in D loFkHG oIIiFH or on Dn
HnFryptHG FomputHr. $ny sFiHntiIiF rHports, DrtiFlH suEmissions, or summDriHs oI GDtD will
not inFluGH FhilGrHn/IDmily nDmHs. 'DtD will EH prHsHntHG in summDry IormDt thDt will
prHFluGH Dny pHrsonDl iGHntiIiFDtion. 7hH plDnnHG DssHssmHnts DnG intHrvHntion DFtivitiHs
involvH no morH thDn minimDl risks to pDrtiFipDnts. $lthouJh thH FhilGrHn will EH too younJ
to proviGH vHrEDl or writtHn DssHnt, wH will monitor thHir EHhDvior Ior siJns oI unGuH
GistrHss DnG Dsk pDrHnts to inIorm us iI thHy IHHl thHir FhilG is HxpHriHnFinJ unusuDl lHvHls oI
GistrHss or GisFomIort. 5HsHDrFh stDII will HnG DFtivitiHs, whHn EDsHG on HithHr thHir own
juGJmHnt or thH juGJmHnt oI thH FhilG's pDrHnt, thH DFtivitiHs DrH FDusinJ thH FhilG unGuH
strHss. 
3lDns to minimizH risks to FhilGrHn:
7o minimizH thH risk oI Dn inIDnt EHFominJ strHssHG, thH tDsks will EH short DnG plDy EDsHG
to lHnG thHmsHlvHs to thH DttHntion spDn DnG intHrHsts oI inIDnts DnG thHir pDrHnts. 7hH
lDEorDtory spDFH is Dlso GHsiJnHG to EH inIDnt IriHnGly (FDrpHtinJ, FhilG-sizHG IurniturH,
DppropriDtH toys, HtF.) DnG thH inIDnts will EH DllowHG DFFHss to thH pDrHnts DnG snDFks Dt
Dny timH. ,nIDnts will EH JivHn timH to wDrm up to thH spDFH DnG to thH HxDminHrs with
thHir pDrHnts prHsHnt. 6omH unHxpHFtHG stimuli (H.J., sounG stiFk, tDp on thH shoulGHr,
IlDshinJ liJht) will EH GHsiJnHG to EH FonsistHnt with thH typHs oI sHnsory HxpHriHnFHs thDt
DrH nDturDlly oFFurrinJ in thH HnvironmHnt DnG DrH not DvHrsivH in nDturH.
7o minimizH thH risk oI Dn inIDnt EHFominJ strHssHG with DppliFDtion or rHmovDl oI "stiFky"
HlHFtroGHs Ior thH hHDrt rDtH monitors, wH will proviGH sDmplH HlHFtroGHs Ior pDrHnts to usH
Dt homH prior to FominJ to thH tHstinJ sHssion. :H will Dlso HnJDJH thH inIDnt in D JDmH to
GistrDFt thH inIDnt whilH plDFinJ HlHFtroGHs. 7hH HlHFtroGHs will EH FovHrHG DItHr plDFHmHnt
Ey thH inIDnts' FlothinJ (H.J., shirt, soFks) to minimizH thH inIDnt EHFominJ visuDlly
GistrDFtHG Ey thH HlHFtroGHs DnG pullinJ Dt thH HlHFtroGHs. 3HGiDtriF HlHFtroGHs GHsiJnHG Ior
HDsy rHmovDl DnG usinJ nonirritDtinJ mDtHriDls will EH usHG.
,I Dn inIDnt prHsHnts with Dn unusuDlly IHDrIul rHDFtion DnG FDnnot EH HDsily soothHG or
rHGirHFtHG (Ds GHtHrminHG Ey thH HxDminHr or thH pDrHnt) GurinJ thH physioloJiFDl GDtD
FollHFtion, thH GHvHlopmHntDl DssHssmHnts, DnG/or homH intHrvHntion, thH itHm (or tDsk)
will EH GisFontinuHG DnG rHsumHG only onFH thH inIDnt JivHs EHhDviorDl DssHnt DnG no
lonJHr DppHDrs strHssHG. ,I thH inIDnt GoHs not DssHnt or thH pDrHnt or thH HxDminHr IHHls
thDt FontinuinJ woulG strHss thH inIDnt, thH DssHssmHnt/proFHGurH/intHrvHntion will EH
GisFontinuHG.
26

Protocol Number 
18 June 2021 - version DRAFT
3otHntiDl GirHFt EHnHIit to FhilGrHn: 
$ll pDrtiFipDnts will rHFHivH thH EHnHIit oI HDrly iGHntiIiFDtion oI risk Ior GHvHlopmHntDl
GisDEilitiHs. %y FomplHtinJ thH )<,v3.1 whHn thHir FhilG is 11 to 16 months oI DJH, pDrHnts
will EH mDGH DwDrH oI potHntiDl GHvHlopmHntDl proElHms thDt thHy mDy not hDvH notiFHG
until lDtHr. 7his mDy JrDnt thHm HDrliHr DFFHss to intHrvHntion DnG othHr sHrviFHs, whiFh
hDvH EHHn DssoFiDtHG with improvHG GHvHlopmHntDl outFomHs. :H will proviGH DppropriDtH
rHIHrrDl inIormDtion to Dll IDmiliHs whosH FhilGrHn sForH Dt or DEovH thH 95th pHrFHntilH on
thH )<,v3.1E, proviGHG thH pDrHnt proviGHG FontDFt inIormDtion to us. :H will kHHp upGDtHG
FontDFt inIormDtion Ior thH DJHnFiHs thDt mDy EH DppropriDtH (H.J., &hilG 'HvHlopmHnt
6HrviFH $JHnFiHs, 7($&&+, loFDl sHrviFH proviGHrs oI spHHFh thHrDpy or oFFupDtionDl
thHrDpy).
3otHntiDlly, FhilGrHn mDy HxpHriHnFH EHnHIits Irom thH novHl intHrvHntion thDt wH will EH
HvDluDtinJ. 7hH intHrvHntion usHs D pDrHnt FoDFhinJ moGHl intHnGHG to improvH inIDnt
outFomHs in HnJDJHmHnt, intHntionDl FommuniFDtion DnG EioEHhDviorDl rHJulDtion.
$lthouJh Dll pDrtiFipDnts will rHFHivH thH 3,( intHrvHntion, wH Go not yHt know whHthHr thH
FhilGrHn will HxpHriHnFH Dny EHnHIits. 
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3DrHnts DnG ,nIDnts (nJDJHG is D pDrHnt-mHGiDtHG intHrvHntion intHnGHG to improvH
HnJDJHmHnt in pDrHnt-FhilG GyDGs thDt inFluGH inIDnts or younJ toGGlHrs Dt HlHvDtHG
likHlihooG oI D IuturH GiDJnosis oI Dutism spHFtrum GisorGHr ($6') or othHr
nHuroGHvHlopmHntDl GisorGHrs (1's). 3DrHnt-FhilG HnJDJHmHnt is GHIinHG Ds Dn oEsHrvDElH
pDttHrn oI mutuDl IoFus, DFtivH pDrtiFipDtion, DnG rHFiproFity within Dn intHrDFtivH FontHxt.
3,( tDrJHts pDrHnt rHsponsivHnHss to HnhDnFH pDrHnt-FhilG HnJDJHmHnt GurinJ IDmily
routinHs, DnG ultimDtHly improvH FhilGrHn's soFiDl, lDnJuDJH, sHlI-rHJulDtion, DnG FoJnitivH
outFomHs. :ithin 3DrHnts DnG ,nIDnts (nJDJHG, D FoDFh DGGrHssHs two GomDins in whiFh
HDrly siJns oI 1's DrH oItHn sHHn: 6Hnsory 5HDFtivity DnG 5HJulDtion (65) DnG 3rHlinJuistiF
&ommuniFDtion (3&). ,n thH 65 GomDin, thH Dim is to hHlp pDrHnts rHFoJnizH thH sHnsory
HxpHriHnFHs DIIorGHG to thH FhilG, iGHntiIy EHhDviorDl FuHs oI D FhilG's sHnsory HxpHriHnFH,
unGHrstDnG how pDrHnt rHsponsHs to thHsH FuHs FDn promotH thH FhilG's rHJulDtory DEilitiHs
DnG HnJDJHmHnt, DnG thHn prDFtiFH HIIHFtivH rHsponsH strDtHJiHs. 6imilDrly, thH 3& GomDin
Dims to hHlp pDrHnts rHFoJnizH thHir FhilG's prHlinJuistiF FommuniFDtivH DFts, iGHntiIy FuHs
thDt FhilGrHn DrH FommuniFDtinJ LQWHQWLRQDOO\, unGHrstDnG how pDrHnt rHsponsHs FDn
promotH morH intHntionDl FommuniFDtion DnG GyDGiF HnJDJHmHnt, DnG thHn prDFtiFH
HIIHFtivH rHsponsH strDtHJiHs. &oDFhinJ oFFurs within thH homH, DFross vDriHG GDily
routinHs.
)DmiliHs DrH FoDFhHG in HithHr thH 65 or 3& GomDin Ior thHir Iirst 6 sHssions (rDnGomly
DssiJnHG Ior thH purposH oI this triDl), DnG thHn DrH FoDFhHG in thH othHr GomDin Ior Dn
DGGitionDl 6 sHssions. 6tHp onH Ior FoDFhinJ in HDFh GomDin is to IDFilitDtH pDrHntDl
DwDrHnHss DnG intHrprHtDtion oI inIDnt sHnsory rHJulDtory/prHlinJuistiF FommuniFDtion
EHhDviors. 7hH sHFonG stHp shiIts to inForporDtH oEsHrvDtion DnG rHIlHFtion on pDrHnt
27

Protocol Number 
18 June 2021 - version DRAFT
rHsponsHs to FhilG EHhDviors; thH pDrHnt is HnFourDJHG to HxpHrimHnt with DGDptinJ thHir
rHsponsHs EDsHG on whDt thHy know DEout thHir FhilG Ds wHll Ds suJJHstions Irom thH
FoDFh. 7hrouJhout HDFh sHssion, thH FoDFh usHs rHIlHFtivH quHstioninJ DnG othHr strDtHJiHs
to IostHr pDrHnts' FollDEorDtion in iGHntiIyinJ DnG usinJ strDtHJiHs DttunHG to thH FhilG's
uniquH FuHs, DnG HvDluDtinJ whHthHr thH strDtHJiHs improvH pDrHnt-FhilG HnJDJHmHnt. :H
HxpHFt thDt inFrHDsinJ thH pDrHnt's DwDrHnHss oI thH FhilG's EHhDviors DnG thHir
ForrHsponGinJ rHsponsHs throuJh rHIlHFtivH FoDFhinJ will lHDG to inFrHDsHG rHsponsivHnHss
DnG sHnsitivity Ior thH pDrHnt DnG thus D EHttHr FDpDEility to rHFoJnizH thH situDtions in
whiFh to implHmHnt thHir iGHntiIiHG strDtHJiHs. $n DGGitionDl Dim is to HmpowHr pDrHnts to
morH inGHpHnGHntly iGHntiIy DnG implHmHnt strDtHJiHs thDt promotH thHir FhilG's
HnJDJHmHnt in thH IuturH, Ds thHir FhilG's spHFiIiF EHhDviors FhDnJH.
(DFh sHssion hDs Iour mDjor FomponHnts. 'urinJ thH ,QWURGXFWLRQDQG&KHFNLQ, thH
FoDFh GHsFriEHs thH purposH oI thH GDy's sHssion, rHviHws FontHnt GisFussHG in thH prHvious
sHssion, DnG GisFussHs with thH pDrHnt thH strDtHJiHs thHy triHG wHnt. ,n 9LGHR5HYLHZ, thH
FoDFh usHs D viGHo oI thH pDrHnt DnG FhilG (rHForGHG Dt thH prior sHssion) to HnJDJH thH
pDrHnt in rHIlHFtivH oEsHrvDtions oI thHir FhilG DnG thHmsHlvHs Ior DEout 20 minutHs. 7hH
FoDFh hiJhliJhts Dt lHDst 4 viGHo sFHnDrios to support pDrHnts in rHFoJnizinJ thHir FhilG's
FuHs DnG/or oEsHrvinJ how thHy rHsponG to thHir FhilG DnG Dny suEsHquHnt FhDnJHs in
pDrHnt-FhilG HnJDJHmHnt. 7hH IoFus oI thH viGHo rHviHw rHIlHFtions GHpHnGs on thH stHp oI
FoDFhinJ DnG rHlDtHG FoDFhinJ JoDls Ior thH sHssion. ,n 6Hssions 1 DnG 2, HxDmplHs DnG
rHIlHFtions DrH GHsiJnHG to HnhDnFH pDrHnts' unGHrstDnGinJ oI thH FhilG's sHnsory rHDFtivity
or prHlinJuistiF FommuniFDtion FuHs.  ,n 6Hssion 3-6, thH FoDFh promotHs pDrHnts'
unGHrstDnGinJ oI how thHir rHsponsHs to FhilG FuHs impDFt thH FhilG's HnJDJHmHnt. ,n /LYH
&RDFKLQJ, thH FoDFh DnG pDrHnt FollDEorDtivHly ErDinstorm potHntiDl strDtHJiHs Ior
rHsponGinJ to thH FhilG's sHnsory rHDFtivity or prHlinJuistiF FommuniFDtion FuHs to hHlp
mDximizH thHir FhilG's HnJDJHmHnt within thH FurrHnt FoDFhinJ GomDin. 7hHn, thH FoDFh
hHlps thH pDrHnt notiFH thHir FhilG's EHhDviors or rHDFtions DnG opportunitiHs to Dpply
strDtHJiHs, proviGHs IHHGEDFk to thH pDrHnt, DnG IDFilitDtHs rHIlHFtion on HIIHFtivHnHss DnG
moGiIiFDtion oI thH FhosHn strDtHJy. 'urinJ )DPLO\$FWLRQ3ODQQLQJ, thH FoDFh DnG
pDrHnts FollDEorDtivHly GHvHlop D writtHn plDn Ior implHmHntinJ thH strDtHJiHs prDFtiFHG in
livH FoDFhinJ GurinJ thH wHHk DhHDG, inFluGinJ iGHntiIyinJ thH routinHs in whiFh thH
strDtHJiHs will EH triHG, whHn thHsH will oFFur GurinJ thH wHHk, DnG how to DGGrHss EDrriHrs
iI nHHGHG. %HIorH HnGinJ thH sHssion, thH FoDFh viGHos D pDrHnt-FhilG intHrDFtion GurinJ D
routinH iGHntiIiHG Ey thH pDrHnt DnG/or FoDFh, FhoosinJ D GiIIHrHnt routinH HDFh wHHk. 7his
viGHo is rHviHwHG Dt thH IollowinJ sHssion.  
0HWKRGRI$VVLJQPHQW5DQGRPL]DWLRQ
)ollowinJ thH EDsHlinH DssHssmHnt DnG IinDl GHtHrminDtion oI stuGy HliJiEility, Ds wHll Ds
inIormHG FonsHnt Irom HliJiElH GyDGs, thH stuGy FoorGinDtor will FontDFt thH projHFt
mHthoGoloJist with thH ,' numEHr oI GyDG to EH rDnGomizHG to onH oI thH two Drms oI thH
stuGy. 7hH projHFt mHthoGoloJist will rDnGomizH IDmiliHs oI HliJiElH inIDnts (strDtiIiHG Ior
DJH < 14 months DnG ≥ 14 months) on D FontinuinJ EDsis, usinJ thH rDnGomizDtion IunFtion
in 5HG&Dp. 'yDGs will EH rDnGomizHG suFh thDt pDrHnts will EH FoDFhHG on thH 3rHlinJuistiF
&ommuniFDtion GomDin oI thH 3DrHnts DnG ,nIDnts (nJDJHG intHrvHntion Iirst IollowHG Ey
thH 6Hnsory 5HDFtivity GomDin ($rm 1), or to thH 6Hnsory 5HDFtivity GomDin Iirst, IollowHG
Ey thH 3rHlinJuistiF &ommuniFDtion GomDin ($rm 2). 
28

Protocol Number 
18 June 2021 - version DRAFT
7hH projHFt mHthoGoloJist will hDvH no FontDFt with IDmiliHs DnG no knowlHGJH oI EDsHlinH
DssHssmHnt outFomHs prior to rDnGomizDtion. 6imilDrly, thH projHFt FoorGinDtor DnG
DssHssmHnt tHDm will hDvH no knowlHGJH oI thH Drm to whiFh D GyDG will EH DssiJnHG Dt thH
timH oI thH EDsHlinH DssHssmHnt, JivHn thDt rDnGomizDtion GoHs not oFFur until DItHr thH
EDsHlinH DssHssmHnt hDs EHHn FomplHtHG (to HnsurH thH inIDnt mHHts Dll HliJiEility FritHriD
Ior thH triDl). 
$ssHssors will FontinuH to EH ElinGHG to stuGy Drm DssiJnmHnt throuJhout thH triDl.
+owHvHr, thH stuGy FoorGinDtor, pDrHnts, DnG FoDFhHs, D sHlHFtHG Jroup oI rHsHDrFh
DssistDnts, DnG stuGy 3,s will hDvH knowlHGJH oI Drm DssiJnmHnt GuH to thHir involvHmHnt
in implHmHntinJ thH intHrvHntion DnG mHDsurinJ thH IiGHlity oI implHmHntDtion oI thH
intHrvHntion.  
6HOHFWLRQRI,QVWUXPHQWV2XWFRPH0HDVXUHV
35,0$5< 287&20(
1. 3DrHnt-inIDnt GyDGiF HnJDJHmHnt is thH primDry outFomH Ior this stuGy. :H GHIinH GyDGiF
HnJDJHmHnt Ds Dn oEsHrvDElH pDttHrn oI mutuDl IoFus, DFtivH pDrtiFipDtion, DnG rHFiproFDl
HxFhDnJHs within D pDrHnt DnG FhilG intHrDFtion.
:H will FollHFt GDtD on this outFomH Dt EDsHlinH, posttHst 1 (DItHr IDmiliHs hDvH EHHn
rDnGomly DssiJnHG to Dn intHrvHntion Drm DnG FoDFhHG in onH oI thH two 3,( intHrvHntion
GomDins), DnG posttHst 2 (DItHr IDmiliHs hDvH EHHn FoDFhHG in Eoth oI thH 3,( intHrvHntion
GomDins). 
7hH rDtionDlH Ior FhoosinJ GyDGiF HnJDJHmHnt Ds thH primDry outFomH is thDt pDrHnt
FoDFhinJ in HDFh GomDin is GHsiJnHG to Dssist pDrHnts in HnJDJinJ thHir FhilG in positivH
intHrDFtions with thHm DnG inFrHDsinJ thH lHnJth oI thHsH pHrioGs oI HnJDJHmHnt throuJh
supportinJ thH inIDnts in rHJulDtinJ thHir rHsponsHs to sHnsory stimuli DnG/or rHsponGinJ
sHnsitivHly to inIDnts' prHlinJuistiF FommuniFDtion FuHs.
7his outFomH will EH HvDluDtHG usinJ Dn DGDptHG vHrsion oI D pDrHnt-FhilG HnJDJHmHnt
stDtH FoGinJ systHm oriJinDlly GHvHlopHG Ey $GDmson Ht Dl. (2009) DnG DGDptHG Ey
%ottHmD-%HutHl Ht Dl., (2018). 9DriDtions oI thH $GDmson Ht Dl. HnJDJHmHnt stDtH FoGinJ
hDvH EHHn 5HsHDrFh DssistDnts will EH trDinHG to rHliDEility on FoGinJ GyDGiF HnJDJHmHnt
on viGHos thDt hDvH EHHn FonsHnsus FoGHG Ey projHFt stDII ovHrsHHinJ FoGinJ oI this
vDriDElH. 9iGHos Ior thH stuGy will FomprisH D ~20-minutH viGHo oI pDrHnt-inIDnt intHrDFtions
thDt inFluGHs IrHH-plDy, D sHmi-struFturHG ":hDt's in thH Eox"" DFtivity, snDFk timH, DnG
FlHDninJ up DItHr thH snDFk. )ollowinJ FoGinJ trDininJ, onH out oI HvHry IivH FoGHG viGHos
will EH rDnGomly sHlHFtHG Ior inGHpHnGHnt FoGinJ, in orGHr to DssHss thH rHliDEility oI our
mHDsurH oI GyDGiF HnJDJHmHnt GDtD Ior thH triDl. &oGHrs will not EH DwDrH oI whiFh viGHos
DrH EHinJ FoGHG Ior rHliDEility purposHs. 3HrioGiF EoostHr trDininJ Ior rHsHDrFh DssistDnts
FoGinJ GyDGiF HnJDJHmHnt will oFFur to limit thH risk oI oEsHrvHr GriIt. ,n D prHvious stuGy
oI prHsFhoolHrs with Dutism, mHmEHrs oI our rHsHDrFh tHDm mDintDinHG DFFHptDElH to
HxFHllHnt rHliDEility on FoGinJ thH rHlHvDnt HnJDJHmHnt stDtHs DFross timHpoints, with ,&&s
rDnJinJ Irom .72 to .97. 
29

Protocol Number 
18 June 2021 - version DRAFT
7imH rHquirHG Ior stuGy pDrtiFipDnts: 20 minutHs Dt %DsHlinH, 3osttHst-1 DnG 3osttHst-2.
27+(5 ,167580(176 $1' 6(&21'$5< 287&20( 0($685(6
2. 3DrHnt rHsponsivHnHss to inIDnt sHnsory rHDFtivity FuHs. >0HDsurHG viD D projHFt-
GHvHlopHG rDtinJ tool.@ 7his sHFonGDry mHDsurH is inFluGHG to GHtHrminH whHthHr FoDFhinJ
in thH sHnsory rHDFtivity GomDin yiHlGs thH HxpHFtHG spHFiIiF HIIHFts on pDrHnts' rHsponsHs
to inIDnt sHnsory rHDFtivity FuHs. 3DrHnts will EH rDtHG on D 1-7 sFDlH Ior thHir
rHsponsivHnHss to sHnsory rHDFtivity Ior HDFh oI thH 4 DFtivitiHs inFluGHG in thH pDrHnt-
inIDnt intHrDFtion sHssion, usinJ viGHorHForGinJs oI thHsH sHssions. $ mDnuDl will EH
GHvHlopHG to GHsFriEH thH rDtinJ systHm DnG thH lHvHl oI rHsponsivity DssoFiDtHG with HDFh
oI thH 7 points on thH sFDlH. 5HsHDrFh DssistDnts will EH trDinHG to rHliDEility Ey supHrvisinJ
stDII. 'urinJ rDtinJ oI thH projHFt viGHos, onH oI 5 rDtHG viGHos will EH inGHpHnGHntly rDtHG
Ior rHliDEility. 5DtHrs will EH ElinG to stuGy Drm DnG timHpoint oI pDrtiFipDnts. :H will FoGH
thH viGHorHForGHG pDrHnt-inIDnt intHrDFtion sHssions GHsFriEHG Ior our primDry mHDsurH Ior
this mHDsurH Ds wHll Dt %DsHlinH, 3osttHst-1, DnG 3osttHst-2.
1o DGGitionDl timH rHquirHmHnts Ior pDrtiFipDnts.
3. 3DrHnt rHsponsivHnHss to inIDnt prHlinJuistiF FommuniFDtion FuHs.  >0HDsurHG viD D
projHFt-GHvHlopHG rDtinJ tool.@ 7his sHFonGDry mHDsurH is inFluGHG to GHtHrminH whHthHr
FoDFhinJ in thH prHlinJuistiF FommuniFDtion GomDin yiHlGs thH HxpHFtHG spHFiIiF HIIHFts on
pDrHnts' rHsponsHs to inIDnt prHlinJuistiF FommuniFDtion FuHs. 0DnuDlizDtion, trDininJ DnG
rHliDEility proFHGurHs, Ds wHll Ds timHpoints DrH iGHntiFDl to thosH GHsFriEHG Ior thH pDrHnt
rHsponsivHnHss to sHnsory rHDFtivity mHDsurH. 
1o DGGitionDl timH rHquirHmHnts Ior pDrtiFipDnts. 
4. ,nIDnt intHntionDl FommuniFDtion. >0HDsurHG viD D projHFt-GHvHlopHG FoGinJ systHm.@
7hH rDtionDlH Ior inFluGinJ this outFomH mHDsurH is thDt pDrHntDl rHsponsivH support oI
inIDnt HnJDJHmHnt will promotH inIDnts' inFrHDsHG usH oI intHntionDl FommuniFDtion,
prHviously IounG to prHGiFt lDtHr rHFHptivH DnG HxprHssivH lDnJuDJH outFomHs Ior
prHsFhoolHrs DlrHDGy GiDJnosHG with Dutism (<oGHr Ht Dl., 2015). ,ntHntionDl
FommuniFDtion DFts DrH GHIinHG Ds DFts thDt DrH GirHFtHG towDrG D FommuniFDtion pDrtnHr
(in this FDsH, thH pDrHnt or othHr primDry IDmily FDrHJivHr prHsHnt GurinJ thH pDrHnt-inIDnt
intHrDFtion sHssion) to FonvHy D mHssDJH, DnG inFluGH (D) voFDlizDtions, (E) JHsturHs, or (F)
FomEinDtions oI Eoth voFDlizDtions DnG JHsturHs. $ FoGinJ mDnuDl will EH GHvHlopHG to
GHsFriEH thH FoGinJ systHm DnG proviGH HxDmplHs DnG nonHxDmplHs oI ,nIDnt intHntionDl
FommuniFDtion DFts. 7his mHDsurH will EH FoGHG Irom viGHos oI thH pDrHnt-inIDnt
intHrDFtion sHssions. 5HsHDrFh DssistDnts will EH trDinHG to rHliDEility Ey supHrvisinJ projHFt
stDII. 2nH oI HvHry IivH FoGHG viGHos will EH rDnGomly sHlHFtHG Ior inGHpHnGHnt FoGinJ Ey
DnothHr rHsHDrFh DssistDnt. &oGHrs will EH ElinG to DssiJnHG Drm oI thH intHrvHntion DnG to
timHpoint oI thH DssHssmHnt. 0HmEHrs oI our rHsHDrFh tHDm hDvH suFFHssIully FoGHG
intHntionDl FommuniFDtion DFts in prHsFhool FhilGrHn with Dutism with ,&&s rDnJinJ Irom
.84 to .92 DFross thrHH timHpoints. 7his mHDsurH will EH FoGHG Irom thH viGHorHForGHG
pDrHnt-inIDnt intHrDFtion sHssions GHsFriEHG unGHr our primDry outFomH, Dt %DsHlinH,
3osttHst-1, DnG 3osttHst-2.
1o DGGitionDl timH rHquirHG Ior rHsHDrFh pDrtiFipDnts. 
5. ,nIDnt rHspirDtory sinus DrrhythmiD (56$). 7his mHDsurH wDs FhosHn Ds Dn inGHx oI
30

Protocol Number 
18 June 2021 - version DRAFT
pDrDsympDthHtiF systHm IunFtioninJ, DnG will EH mHDsurHG within D pDrDGiJm in whiFh thH
inIDnts DrH pDssivHly oEsHrvinJ (D) Dn instrumHntDl musiF viGHo without soFiDl imDJHs, DnG
(E) thrHH on-minutH viJnHttHs oI inIDnt-GirHFtHG spHHFh, Ds Dn HxpHrimHntDl DnDloJ oI
pDrHnt-inIDnt intHrDFtions. :H hypothHsizH wH will sHH inFrHDsHG 56$ lHvHls GurinJ inIDnt-
GirHFtHG spHHFh, rHIlHFtinJ JrHDtHr pDrDsympDthHtiF Fontrol DnG improvHG sHnsory
rHsponsH rHJulDtion, Ey 3osttHst 2. 'DtD will EH FollHFtHG with thH )irstEHDt GHviFH, with 2
HlHFtroGHs plDFHG on thH inIDnt's FhHst, DnG FovHrHG with thH inIDnt's FlothinJ. 5HForGs oI
intHrEHDt intHrvDls will EH DliJnHG with thH viGHo sHJmHnts thH inIDnts viHwHG, HGitHG usinJ
&DrGio(Git (%rDin-%oGy &HntHr, 2007) Ey D rHsHDrFh DssistDnt trDinHG to rHliDEility, DnG
proFHssHG usinJ &DrGio%DtFh (%rDin-%oGy &HntHr, 2007) to GHrivH 56$. 7hH rHsHDrFh
DssistDnt who HGits DnG proFHssHs thH 56$ GDtD will EH supHrvisHG Ey D rHsHDrFh tHDm
mHmEHr with prior HxpHriHnFH in oEtDininJ DnG proFHssinJ 56$ GDtD. :H hDvH usHG thH
&hilG-'irHFtHG 6pHHFh pDrDGiJm in prHvious stuGiHs with toGGlHr-to-prHsFhool DJH FhilGrHn
with Dutism DnG inIDnt-to-prHsFhool DJH FhilGrHn with no known GHvHlopmHntDl FonFHrns
(:Dtson Ht Dl., 2010, 2012). 7hH intHrnDl FonsistHnFy Ior thH 56$ mHDsurHs GurinJ thH thrHH
FhilG-GirHFtHG spHHFh viJnHttHs (&ronEDFh's DlphD) wDs 0.84 Ior FhilGrHn with Dutism.
7his mHDsurH will EH FollHFtHG Dt %DsHlinH DnG 3osttHst-2, rHquirinJ ~6-10 minutHs oI
pDrtiFipDnts' timH.
5. ,nIDnt skin FonGuFtDnFH lHvHl (6&/). 7his mHDsurH wDs FhosHn Ds Dn inGHx oI
sympDthHtiF systHm IunFtioninJ, DnG will EH mHDsurHG within thH DEovH GHsFriEHG inIDnt-
GirHFtHG spHHFh pDrDGiJm. :H hypothHsizH wH will sHH GHFrHDsHG 6&/ lHvHls GurinJ inIDnt-
GirHFtHG spHHFh, rHIlHFtinJ lHss HlHvDtion oI sympDthHtiF DFtivity DnG improvHG sHnsory
rHJulDtion whHn oEsHrvinJ inIDnt-GirHFtHG spHHFh viJnHttHs, Ey 3osttHst 2. 'DtD will EH
FollHFtHG usinJ thH 6himmHr GHviFH; rHForGs oI 6&/ will DliJnHG with thH viGHo sHJmHnts
thH inIDnts viHwHG, DnG proFHssHG usinJ .uEios. 7hH rHsHDrFh DssistDnt who proFHssHs thH
6&/ GDtD will EH supHrvisHG Ey D rHsHDrFh tHDm mHmEHr with prior HxpHriHnFH with
FollHFtinJ DnG proFHssinJ 6&/ GDtD. 
7his mHDsurH will EH FollHFtHG GurinJ thH sDmH proFHGurH Ds usHG Ior 56$ mHDsurHmHnt, Dt
%DsHlinH DnG 3osttHst-2. 1o DGGitionDl timH rHquirHG Ior pDrtiFipDnts.
6. 7hH 0ullHn 6FDlHs oI (Drly /HDrninJ proviGHs 5 sFDlHs to DssHss GHvHlopmHnt in FhilGrHn
Eirth-68 months . (DFh sFDlH (*ross 0otor, )inH 0otor, 9isuDl 5HFHption, 5HFHptivH
/DnJuDJH, (xprHssivH /DnJuDJH) yiHlGs D 7-sForH, pHrFHntilH DnG DJH HquivDlHnt. 7hH 06(/
sFDlHs hDvH GHmonstrDtHG JooG to stronJ intHrnDl FonsistHnFy, tHst-rHtHst rHliDEility DnG
FonFurrHnt vDliiGity; it hDs EHHn wiGHly usHG Ds D stDnGDrGizHG mHDsurH oI GHvHlopmHnt
DFross GomDins in stuGiHs oI younJ FhilGrHn with 1's, inFluGinJ mDny prHvious stuGiHs Ey
mHmEHrs oI our tHDm. 3rior rHsHDrFh inGiFDtHs thDt rHFHptivH lDnJuDJH mDy EH improvHG
GistDl to with improvHmHnts in pDrHnt-inIDnt GyDGiF HnJDJHmHnt DnG inIDnt intHntionDl
FommuniFDtion. :H will DGministHr thH )inH 0otor, 9isuDl 5HFHption, 5HFHptivH /DnJuDJH,
DnG (xprHssivH /DnJuDJH 6FDlHs Dt %DsHlinH to proviGH GHsFriptivH inIormDtion DFross thHsH
GHvHlopmHntDl GomDin to FhDrDFtHrizH thH GHvHlopmHntDl stDtus oI our sDmplH. $t
3osttHst-2, wH will DGministHr thH 5HFHptivH DnG (xprHssivH /DnJuDJH 6FDlHs only, Ds
sHFonGDry outFomH mHDsurHs to GHtHrminH whHthHr thH 3,( intHrvHntion hDs GistDl HIIHFts
on EroDGHr lDnJuDJH outFomHs oI thH inIDnts. 
,n thH DJH rDnJH Ior our inIDnt pDrtiFipDnts, thH HstimDtHG pDrtiFipDnt timH rHquirHG Ior thH
4 sFDlHs oI thH 06(/ Dt %DsHlinH is 15-20 minutHs. $t 3osttHst-2, thH HstimDtHG timH to
31

Protocol Number 
18 June 2021 - version DRAFT
DGministHr thH 5HFHptivH DnG (xprHssivH /DnJuDJH 6FDlHs is 10 mintuHs. 
7. $ttHntion )ollowinJ triDls Irom thH -oint $ttHntion 3rotoFol (:Dtson Ht Dl., 2003). 2nH
IrHquHnt EHhDviorDl FhDrDFtHristiF oI inIDnts Dt HlHvDtHG likHlihooG oI lDtHr 1' is thDt thHy
hDvH GiIIiFulty in rHsponGinJ to joint DttHntion EiGs thDt rHquirH thHm to rHGirHFt thHir
DttHntion DwDy Irom thHir FurrHnt IoFus to D nHw oEjHFt. 3otHntiDlly, improvHmHnts in
pDrHnt-inIDnt GyDGiF HnJDJHmHnt will, ovHr timH, yiHlG improvHmHnts in rHsponsH to joint
DttHntion Ds pDrHnts lHDrn to usH nHw strDtHJiHs to HIIHFtivHly HnJDJH thHir inIDnt, DnG
inIDnts hDvH morH HxpHriHnFHs in rHFiproFDl intHrDFtions with thHir FDrHJivHrs. 6uFh
FhDnJHs FoulG siJnDl inIDnts' GHFrHDsHG GHpHnGHnFy on pDrHnts oEsHrvinJ DnG rHsponGinJ
to thHir immHGiDtH IoFus oI DttHntion, DnG proviGH D lDrJHr vDriHty oI lHDrninJ opportunitiHs.
7hH -oint $ttHntion 3rotoFol wDs GHvHlopHG DnG usHG in FonjunFtion with Dn HDrliHr stuGy Ey
mHmEHrs oI our tHDm Ds D mHDsurH thDt FoulG EH sForHG rHliDEly GurinJ DGministrDtion, DnG
hDs GHmonstrDtHG sounG intHrnDl rHliDEility, tHst-rHtHst rHliDEility, DnG FonFurrHnt vDliGity
whHn usHG with younJ FhilGrHn with Dutism (1owHll Ht Dl., 2018).
7his mHDsurH will EH FollHFtHG Dt %DsHlinH DnG 3osttHst-2. 7hH HstimDtHG pDrtiFipDnt timH
rHquirHG to DGministHr 6 DttHntion IollowinJ triDls is 2 minutHs. 
8. 7hH %riHI 2EsHrvDtion oI 6oFiDl-&ommuniFDtion &hDnJH (%26&&, /orG, *rzDGzinski Ht Dl.,
2017). ,n DnDlysHs with othHr sDmplHs sFrHHnHG with thH )<,v3.1, our tHDm hDs GoFumHntHG
thDt thH positivH prHGiFtivH vDluH oI thH tool spHFiIiFDlly Ior Dutism is DrounG 30-40%,
vDryinJ with thH DJH Dt sFrHHninJ (unpuElishHG GDtD). 'uH to thH nDturH oI thH itHms on thH
)<,v3.1, inIDnts mHHtinJ thH thrHsholG Ior EHinJ Dt HlHvDtHG likHlihooG Ior 1' on thH
)<,v.3.1 will hDvH pDrHnt-rHportHG soFiDl-FommuniFDtion EHhDviors DssoFiDtHG with Dutism.
7hH %26&& wDs GHsiJnHG to DssHss improvHmHnts in HDrly soFiDl-FommuniFDtion skills thDt
DrH usuDlly impDirHG in younJ FhilGrHn with Dutism Eut Dlso DrH known to FhDnJH/improvH
ovHr timH. 0ultiplH stuGiHs hDvH proviGHG HviGHnFH thDt thH %26&& FDn EH sForHG with
JooG intHrrDtHr rHliDEility DnG hDs JooG tHst-rHtHst rHliDEility DnG FonvHrJHnt vDliGity with
lDnJuDJH DnG FommuniFDtion mHDsurHs (H.J., *HnJoux Ht Dl., 2019; *rzDGzinski Ht Dl.,
2016; .itzHrow Ht Dl., 2016); in DGGition, thH %26&& 6oFiDl-&ommuniFDtion 7otDl 6ForH,
whiFh will EH our mHDsurH, wDs IounG to hDvH JooG intHrnDl FonsistHnFy whHn DppliHG to
viGHoHG intHrDFtions GurinJ Eoth IrHH-plDy (&ronEDFh's DlphD   0.88) DnG snDFk timH
(&ronEDFh's DlphD   .87). 7hus, wH DrH usinJ thH %26&& to HxDminH whHthHr thHsH skills
FhDnJH siJniIiFDntly ovHr thH FoursH oI thH Iull 3,( intHrvHntion. )or this stuGy, wH will usH
thH 12-minutH %26&& intHrDFtion protoFol GurinJ whiFh Dn HxDminHr intHrDFts with thH
FhilG, whiFh will EH viGHorHForGHG DnG sForHG lDtHr Ey trDinHG rHsHDrFh DssistDnts ElinG to
DssiJnmHnt Drm DnG timHpoint. $s with othHr mHDsurHs Irom viGHos, onH oI 5 sForHG viGHos
will EH rDnGomly sHlHFtHG Ior inGHpHnGHnt sForinJ Ior rHliDEility purposHs. 7hH rHsHDrFh
DssistDnts workinJ on this mHDsurH will mHHt rHJulDrly with thH supHrvisinJ stDII (onH oI thH
Duthors oI thH %26&&) to rHviHw sForinJ GHFisions to DttHntuDtH thH risk oI oEsHrvHr GriIt. 
7hH %26&& will EH DGministHrHG Dt %DsHlinH DnG 3osttHst-2. 7hH pDrtiFipDnt timH rHquirHG
Ior this mHDsurH is ~13 minutHs. 
9. 6Hnsory 3roFHssinJ $ssHssmHnt Ior <ounJ &hilGrHn (63$, %DrDnHk, 1999D). ,n FoDFhinJ
pDrHnts to EH sHnsitivH to thHir inIDnts' FuHs rHlDtHG to sHnsory rHDFtivity DnG to rHsponG in
wDys thDt support thHir inIDnts' rHJulDtion oI thHsH rHsponsHs, DnothHr potHntiDl GistDl
outFomH oI thH 3,( intHrvHntion woulG EH improvHmHnts in HxtrHmH pDttHrns oI sHnsory
rHDFtivity (i.H., GiminishHG hypo- DnG/or hypHr-rHDFtivity). 8sH oI thH 63$ Ds Dn
32

Protocol Number 
18 June 2021 - version DRAFT
oEsHrvDtionDl mHDsurH will proviGH us with thH opportunity to DssHss whHthHr Dny FhDnJHs
DrH oEsHrvHG Ey DssHssors who DrH ElinGHG to thH Drm oI thH stuGy to whiFh IDmiliHs DrH
DssiJnHG. 7hH 63$ is D plDy-EDsHG DssHssmHnt thDt mHDsurHs DpproDFh-DvoiGDnFH to novHl
sHnsory toys, sHnsory sHHkinJ EHhDviors, DnG oriHntinJ rHsponsHs DFross thrHH sHnsory
moGDlitiHs, DnG is sHnsitivH to mDturDtionDl FhDnJHs. ,t hDs JooG intHr-rDtHr rHliDEility (,&&
  .91 to .99 Ior GiIIHrHnt sFDlHs), GisFriminDtHs GiIIHrHnt pDttHrns oI sHnsory rHsponsH
EHtwHHn FhilGrHn with Dutism DnG FhilGrHn with othHr GHvHlopmHntDl GisDEilitiHs, DnG shows
sHnsitivity to GHvHlopmHntDl FhDnJHs (%DrDnHk Ht Dl., 2007, 2013). 
7hH 63$ will EH DGministHrHG Dt %DsHlinH DnG 3osttHst-2. 7hH pDrtiFipDnt timH rHquirHG Ior
this mHDsurH is ~15 to 20 minutHs. 
10. 6Hnsory (xpHriHnFHs 4uHstionnDirH v. 2.1, (6(4, %DrDnHk, 1999E). $s D FomplHmHnt to
thH 63$, wH DrH usinJ thH 6(4 to GHtHrminH whHthHr pDrHnts pHrFHivH improvHmHnts in
thHir FhilGrHn's sHnsory rHDFtivity pDttHrns ovHr thH FoursH oI thH Iull 3,( intHrvHntion. 7hH
6(4 is D 43-itHm quHstionnDirH Ior FhilGrHn 6 months to 6 yHDrs thDt mHDsurHs rHsponsHs to
vDrious sHnsory stimuli in thH FontHxt oI GDily DFtivitiHs. )DFtor sForHs Ior hypo- & hypHr-
rHsponsivHnHss DnG sHnsory sHHkinJ DrH FompDtiElH with thH FonFHptuDl moGHl oI thH 63$.
7hH intHrnDl FonsistHnFy is DFFHptDElH (&ronEDFh's α  0.80). ,t GisFriminDtHs pDttHrns
uniquH to $6' DnG is sHnsitivH to mDturDtionDl FhDnJHs (%DrDnHk Ht Dl., 2006).
3DrHnts will EH DskHG to FomplHtH thH 6(4 Dt %DsHlinH, 3osttHst-1, DnG 3osttHst-2, DnG
FomplHtinJ it will rHquirH ~15 minutHs. 
11. 3DrHnts DnG ,nIDnts (nJDJHG ,ntHrvHntion 5DtinJ 3roIilH (3,( ,53; DGDptHG Irom :itt &
0DrtHns, 1983 Ey our tHDm Ior thH 3,( intHrvHntion). 3DrHnts will EH DskHG to FomplHtH thH
3,( ,53 Dt 3osttHst-2 Ds D mHDsurH oI thH soFiDl vDliGity oI 3,( Ds implHmHntHG in this triDl.
7hH mHDsurH FomprisHs 12 stDtHmHnts HDFh rDtHG on D 1-5 /ikHrt sFDlH Ey pDrHnts to
inGiFDtH thHir lHvHl oI DJrHHmHnt with thH stDtHmHnt (H.J., "5HviHwinJ DnG GisFussinJ
viGHos oI mH intHrDFtinJ with my FhilG wDs hHlpIul." ", Dm DElH to rHFoJnizH my FhilG's
sHnsory EHhDviors within routinHs.")
7hH HstimDtHG timH rHquirHG Ior pDrHnts to FomplHtH thH 3,( ,53 is 5 minutHs. 
6ummDry oI DssHssmHnts DnG HstimDtHG pDrtiFipDnt timH Dt HDFh timHpoint:
%DsHlinH: totDl HstimDtHG timH Ior pDrHnt-inIDnt GyDGs is 80 minutHs; Dn DGGitionDl 15
minutHs Ior pDrHnts only.
1. 3DrHnt-inIDnt ,ntHrDFtion sHssion - 20 minutHs (9iGHos oI this sHssion will EH usHG to
mHDsurH 'yDGiF (nJDJHmHnt, 3DrHnt 5HsponsivHnHss to 6Hnsory 5HDFtivity &uHs,
3DrHnt 5HsponsivHnHss to 3rHlinJuistiF &uHs, DnG ,nIDnt ,ntHntionDl &ommuniFDtion)
2. &hilG-'irHFtHG 6pHHFh 3DrDGiJm - 10 minutHs (:ill EH usHG to FollHFt rHspirDtory sinus
DrrhythmiD DnG skin FonGuFtDnFH lHvHl mHDsurHs).
3. 0ullHn 6FDlHs oI (Drly /HDrninJ - 20 minutHs. 9isuDl 5HFHption, )inH 0otor, 5HFHptivH
/DnJuDJH, DnG (xprHssivH /DnJuDJH sFDlHs.
4. $ttHntion )ollowinJ triDls - 2 minutHs
5. %riHI 2EsHrvDtion oI 6oFiDl &ommuniFDtion &hDnJH - 13 minutHs
6. 6Hnsory 3roFHssinJ $ssHssmHnt - 15 minutHs
7. 6Hnsory (xpHriHnFHs 4uHstionnDirH - 15 minutHs (pDrHnts only)
33

Protocol Number 
18 June 2021 - version DRAFT
3osttHst-1: 7otDl HstimDtHG timH Ior GyDGs is 20 minutHs; Dn DGGitionDl 15 minutHs Ior
pDrHnts only.
1. 3DrHnt-inIDnt intHrDFtion sHssion - 20 minutHs
2. 6Hnsory (xpHriHnFHs 4uHstionnDirH - 15 minutHs (pDrHnts only)
3osttHst-2: 7otDl HstimDtHG timH Ior GyDGs is 70 minutHs; Dn DGGitionDl 20 minutHs Ior
pDrHnts only
1. 3DrHnt-inIDnt intHrDFtion sHssion - 20 minutHs
2. &hilG-GirHFtHG spHHFh pDrDGiJm - 10 minutHs
3. 0ullHn 6FDlHs oI (Drly /HDrninJ 5HFHptivH DnG (xprHssivH /DnJuDJH 6FDlHs - 10
minutHs
4. $ttHntion )ollowinJ triDls - 2 minutHs
5. %riHI 2EsHrvDtion oI 6oFiDl-&ommuniFDtion &hDnJH - 13 minutHs
6. 6Hnsory 3roFHssinJ $ssHssmHnt - 15 minutHs
7. 6Hnsory (xpHriHnFHs 4uHstionnDirH - 15 minutHs (pDrHnts only)
8. 3,( ,ntHrvHntion 5DtinJ 3roIilH - 5 minutHs (pDrHnts only)
,QWHUYHQWLRQ$GPLQLVWUDWLRQ
3,( intHrvHntion sFhHGulH:
1.  ,ntroGuFtory visit to mHHt IDmily, outlinH thH 3,( intHrvHntion, rHviHw loJistiFs, DnG
rHForG pDrHnt-FhlG viGHo Ior Iirst FoDFhinJ sHssion
2.  6ix wHHkly FoDFhinJ sHssions oI ~onH hour HDFh in Iirst 3,( GomDin
3. >%rHDk Ior 3osttHst-1@
4. 6ix wHHkly FoDFhinJ sHssions oI ~onH hour HDFh in sHFonG 3,( GomDin
3,( sHttinJ:
&oDFhHs will typiFDlly mHHt with IDmiliHs in thHir homHs, Eut Dlso FoulG mHHt with thHm
in DnothHr Fommunity sHttinJ EDsHG on D pDrHnt rHquHst DnG IHDsiEility (H.J., thH
pDrHnt mDy wDnt FoDFhinJ rHlDtHG to mDnDJinJ D Fommunity outinJ routinH, suFh Ds
JoinJ to thH JroFHry storH DFFompDniHG Ey thHir inIDnt).
3HoplH DGministHrinJ thH intHrvHntion:
7hH FoDFhHs Ior this triDl will hDvH 0DstHr's GHJrHHs in 6pHHFh-/DnJuDJH 3DtholoJy,
2FFupDtionDl 7hHrDpy, (Drly ,ntHrvHntion, or D rHlDtHG IiHlG, DnG prior HxpHriHnFH
workinJ with younJ FhilGrHn with GHvHlopmHntDl GisDEiltiHs DnG thHir pDrHnts.
3,( IiGHlity:
34

Protocol Number 
18 June 2021 - version DRAFT
%HFDusH thH 3,( intHrvHntion is nHwly GHvHlopHG, thHrH is no HxistinJ IiGHlity oI
implHmHntDtion mHDsurH. 7hus, onH proGuFt oI thH projHFt will EH D IiGHlity oI
implHmHntDtion FhHFklist Ior 3,( FoDFhHs. 7hH 3,( intHrvHntion tHDm (lHDG FoDFh,
DGGitionDl FoDFh(Hs), projHFt 3,s, DnG non-FoDFhinJ thHrDpists on thH tHDm) will
FollDEorDtH to GHvHlop this FhHFklist, Ds wHll Ds DGG to thH 3,( intHrvHntion mDnuDl,
throuJh wHHkly mHHtinJs in whiFh 3,( intHrvHntion JoDls DnG FoDFhinJ strDtHJiHs DrH
GisFussHG in thH FontHxt oI rHviHwinJ viGHos oI FoDFhinJ sHssions. ,t is unlikHly thDt thH
IiGHlity oI implHmHntDtion FhHFklist will EH IinDlizHG HDrly HnouJh in thH projHFt to usH it
Ior onJoinJ IiGHlity monitorinJ Irom thH EHJinninJ oI thH triDl. +owHvHr, throuJhout thH
triDl, HDFh FoDFh will viGHo-rHForG two FoDFhinJ sHssions in HDFh oI thH 3,( GomDins Ior
thH purposHs oI (D) potHntiDl rHviHw DnG IHHGEDFk GurinJ thH wHHkly mHHtinJs, DnG (E)
sForinJ Ior IiGHlity oI implHmHntDtion onFH thH IiGHlity FhHFklist is IinDlizHG, DnG
rHliDEility in sForinJ thH IiGHlity FhHFklist hDs EHHn HstDElishHG. 7hHsH proFHGurHs
DllowinJ Ior onJoinJ rHIinHmHnt oI thH 3,( intHrvHntion DnG HlHmHnts FonsiGHrHG to EH
inGiFDtors oI thH IiGHlity oI implHmHntDtion will rHsult in proGuFts (HxpDnGHG 3,( mDnuDl
DnG tHstHG IiGHlity oI implHmHntDtion FhHFklist) thDt will EH HssHntiDl Ior movinJ to Dn
HIIiFDFy stuGy, shoulG thH IinGinJs oI this prooI-oI-FonFHpt stuGy support thDt Ds D nHxt
stHp.
3,( trDininJ: 
7hH lHDG FoDFh DnG D sHFonG FoDFh rHDG thH 3,( intHrvHntion mDnuDl DlonJ with 5ush &
6hHlGon's (2011) Eook on FoDFhinJ in HDrly intHrvHntion. $ItHr rHDGinJ this EDFkJrouG
inIormDtion, thHy will mHHt with thH Iull intHrvHntion tHDm to GisFuss quHstions DnG
FonFHrns. 7hHn thHy will HDFh pilot thH 3,( intHrvHntion with D IDmily oI Dn inIDnt or
toGGlHr with GHvHlopmHntDl FonFHrns who is not HnrollHG in thH triDl, prior to thH
HnrollmHnt oI Dny triDl pDrtiFipDnts. 7hHy will viGHorHForG thHsH sHssions, DnG thH 3,(
intHrvHntion tHDm will rHviHw DnG GisFuss thH viGHos GurinJ wHHkly tHDm mHHtinJs,
IoFusinJ on HIIHFtivH shDrinJ oI EDFkJrounG inIormDtion on HDFh oI thH 3,( GomDins,
rHlDtHG DGGitions nHHGHG to thH 3,( mDnuDl (H.J., hDnGouts Ior pDrHnts), thH proFHss oI
rHIlHFtivH FoDFhinJ spHFiIiF to HDFh GomDin, rHIinHmHnt oI strDtHJiHs usHG Ey thH
FoDFhHs, DnG proElHm-solvinJ rHlDtHG to FhDllHnJHs iGHntiIiHG Ey thH FoDFhHs. 7his
pilotinJ proFHss will FonstitutH thH trDininJ Ior thH lHDG FoDFh DnG thH sHFonG initiDl
FoDFh.
:H DntiFipDtH thDt FoDFhHs will IluFtuDtH DFross thH FoursH oI this stuGy, GuH to our
plDn to rHly on 3h' stuGHnts who hDvH 0DstHr's GHJrHHs DnG DssoFiDtHG FliniFDl/HDrly
intHrvHntion HxpHriHnFH to sHrvH Ds FoDFhHs. 7rDininJ Ior suEsHquHnt FoDFhHs will
inFluGH: (D) rHDGinJ thH 3,( intHrvHntion mDnuDl, Dll FoDFhinJ hDnGouts, thH (Drly
&hilGhooG &oDFhinJ +DnGEook (5ush & 6hHlGon 2011), DnG thH 3,( )iGHlity FhHFklist;
(E) rHviHwinJ D viGHo oI D FoDFhinJ sHssion in thH prHlinJuilstiF FommuniFDtion GomDin
DnG D viGHo oI D FoDFhinJ sHssion in thH sHnsory rHJulDtion GomDin; (F) rolHplDyinJ D
FoDFhinJ sHssion in HDFh GomDin, rHForGinJ D 10-minutH viGHo oI thH rolHplDy Ior
rHviHw Ey thH trDininJ FoDFh; (G) shDGowinJ D prHviously trDinHG FoDFh Ior two
FoDFhinJ sHssions, onH in HDFh FoDFhinJ GomDin; rHviHwinJ proFHGurHs with D trDinHG
FoDFh Ior usinJ tDElHt FomputHr Ior FoDFhinJ, DnG rHForGinJ DnG storinJ FoDFhinJ
viGHos DnG othHr GoFumHnts, with DttHntion to GDtD sHFurity; (G) FonGuFtinJ Dn initiDl
FoDFhinJ sHssion in HDFh 3,( GomDin unGHr thH mHntorship oI D trDinHG FoDFh.
,ntHrvHntion viGHos:
35

Protocol Number 
18 June 2021 - version DRAFT
$ll viGHo IilHs will EH kHpt sHFurHG in thH 3,s lDEorDtoriHs Dt 81&-&hDpHl +ill DnG 86&,
iGHntiIiHG Ey ,' numEHr, DnG DrFhivHG on D sHFurH nHtwork GrivH or on HnFryptHG
HxtHrnDl hDrG GrivHs. 9iGHo IilHs will EH FlHDrly mDrkHG to iGHntiIy whHthHr thH pDrHnt
hDs JivHn pHrmission to usH thHm Ior tHDFhinJ/HGuFDtionDl purposHs. 3ortDElH
FomputinJ GHviFHs, inFluGinJ thH tDElHts usHG Ey thH intHrvHntionists, will EH
HnFryptHG, hDvH D powHr-on pDssworG rHquirHG, DnG Dn DutomDtiF loJ-oII. 9iGHos will EH
storHG on tDElHts usHG Ey FoDFhHs only Ior thH lHnJth oI timH rHquirHG Ior usH in
FoDFhinJ (typiFDlly onH wHHk Ior HDFh viGHo, HxFHpt in FDsHs whHrH D sHssion nHHGs to
EH rHsFhHGulHG to D lDtHr timH). 8pon FomplHtion oI thH stuGy, thH GDtD will EH DrFhivHG
on D sHFurH sHrvHr/in sHFurH IilHs in thH 'HpDrtmHnt oI $lliHG +HDlth 6FiHnFHs Dt 81&
projHFt lDEorDtory oI thH 3, :Dtson DnG/or in thH 0rs. 7.+. &hDn 3roIHssor oI
2FFupDtionDl 6FiHnFH DnG 2FFupDtionDl 7hHrDpy in thH 86& lDEorDtory oI 3, %DrDnHk.
'H-iGHntiIiHG GDtD will EH shDrHG DFForGinJ to thH 5HsourFH 6hDrinJ 3lDn, or othHr
DJrHHmHnts nHJotiDtHG with 1,&+' upon rHFHipt oI thH JrDnt.
5HDFWLRQ0DQDJHPHQW
3roDFtivHly, wH will proviGH DppropriDtH rHIHrrDl inIormDtion Ior DFFHssinJ Fommunity HDrly
intHrvHntion sHrviFHs to Dll IDmiliHs whosH inIDnts' sForHs on thH )<,v3.1E inGiFDtH thHy mDy
EH Dt (/-1'. ,I pDrHnt FhoosH to pursuH thHsH sHrviFHs DnG thH inIDnt is GHtHrminHG to EH
HliJiElH Ior puEliF HDrly intHrvHntion sHrviFHs JovHrnHG Ey IHGHrDl poliFiHs, thH IDmily will EH
DssiJnHG D sHrviFH FoorGinDtor (Ds wHll Ds EHinJ oIIHrHG othHr sHrviFHs EDsHG on thH
,nGiviGuDlizHG )Dmily 6HrviFH 3lDn, or ,)63). %HFDusH Dll oI thH pDrtiFipDnts in this triDl will
EH in wHHkly FontDFt with D projHFt FoDFh or othHr rHsHDrFh stDII mHmEHr (H.J., thH projHFt
FoorGinDtor who is sFhHGulinJ DssHssmHnt DppointmHnts), wH will EH DElH to monitor pDrHnt
DnG inIDnt rHDFtions to thH intHrvHntion or pDrtiFipDtion in thH intHrvHntion triDl. 2n D
sFhHGulHG monthly EDsis, wH will inFluGH Dn itHm on our Iull rHsHDrFh tHDm mHHtinJ DJHnGD
to inquirH DEout Dny sDIHty FonFHrns rHlDtHG to pDrtiFipDnts, inFluGinJ strHss rHDFtions. ,n
DGGition, FoDFhHs will EH DElH to GisFuss Dny FonFHrns thHy mDy hDvH DEout rHDFtions Dt thH
wHHkly intHrvHntion tHDm mHHtinJs (whiFh thH 3,s will DttHnG). $ll stDII intHrDFtinJ with
pDrtiFipDnts will EH inIormHG thDt Dny urJHnt issuHs rHlDtHG to thH hHDlth DnG sDIHty oI
pDrtiFipDnts shoulG EH rHportHG immHGiDtHly to onH oI thH 3,s. :H will mDintDin D list oI
Fommunity rHsourFHs Ior pDrHnt oI younJ FhilGrHn, inFluGinJ FhilGrHn with GHvHlopmHntDl
FonFHrns, Ior our FDtFhmHnt DrHD, DnG shDrH rHsourFHs with pDrHnts Ds DppropriDtH. 
$VVHVVPHQWV
(IILFDF\
7hH Dims oI thH FurrHnt prooI-oI-FonFHpt triDl Go not inFluGH Dn HvDluDtion oI thH HIIiFDFy oI
thH 3,( intHrvHntion, DnG thH GHsiJn oI thH stuGy GoHs not inFluGH thH nHFHssDry Fontrols Ior
Dn HIIiFDFy HvDluDtion. 7hH timinJ DnG proFHGurHs Ior DssHssmHnts DnG thH rDtionDlH Ior
sHlHFtinJ thHm within thH FontHxt oI our stuGy Dims hDvH EHHn GHsFriEHG HlsHwhHrH in this
protoFol (5.2.1 3rimDry outFomH vDriDElHs; 5.2.2 6HFonGDry DnG (xplorDtory vDriDElH; 6.1.3
36

Protocol Number 
18 June 2021 - version DRAFT
6HlHFtion oI ,nstrumHnts/2utFomH 0HDsurHs; 9isit 6FhHGulH 7DElH; 6tuGy )low &hDrt). 
6DIHW\3UHJQDQF\UHODWHG3URFHGXUH
1ot DppliFDElH to our stuGy; DlthouJh it is possiElH somH pDrHnts mDy EH prHJnDnt, thH
stuGy Dims DnG proFHGurHs DrH unrHlDtHG to prHJnDnFy DnG posH no DGGitionDl risks thDn
orGinDry GDily liIH in thH HvHnt thDt D pDrHnt is prHJnDnt. 
$GYHUVH(YHQWV'HILQLWLRQDQG5HSRUWLQJ
$GvHrsH HvHnts DrH GHIinHG EDsHG on 6tDnGDrG 2pHrDtinJ 3roFHGurHs DppliFDElH to
,nvHstiJDtors DnG FliniFDl rHsHDrFh tHDm mHmEHrs FonGuFtinJ humDn suEjHFts rHsHDrFh Dt
thH 8nivHrsity oI 1orth &DrolinD Dt &hDpHl +ill Ds Iollows:
$GvHrsH (vHnt: $ny untowDrG or unIDvorDElH mHGiFDl oFFurrHnFH in D humDn suEjHFt,
inFluGinJ Dny DEnormDl siJn (Ior HxDmplH, DEnormDl physiFDl HxDm or lDEorDtory IinGinJ),
symptom, or GisHDsH, tHmporDlly DssoFiDtHG with thH suEjHFt's pDrtiFipDtion in thH rHsHDrFh,
whHthHr or not FonsiGHrHG rHlDtHG to thH suEjHFt's pDrtiFipDtion in thH rHsHDrFh. $GvHrsH
HvHnts HnFompDss Eoth physiFDl DnG psyFholoJiFDl hDrms DnG oFFur most IrHquHntly in thH
FontHxt oI EiomHGiFDl rHsHDrFh, DlthouJh thHy FDn oFFur in thH FontHxt oI soFiDl DnG
EHhDviorDl rHsHDrFh.
+ospitDlizDtion: DGmission to thH hospitDl Ior lonJHr thDn 24 hours.
6Hrious $GvHrsH (vHnt: 6Hrious DGvHrsH HvHnt mHDns Dny HvHnt tHmporDlly DssoFiDtHG with
thH suEjHFt's pDrtiFipDtion in rHsHDrFh thDt mHHts Dny oI thH IollowinJ FritHriD:
• rHsults in GHDth;
• is liIH thrHDtHninJ (plDFHs thH suEjHFt Dt immHGiDtH risk oI GHDth Irom thH
HvHnt Ds it oFFurrHG);
• rHquirHs inpDtiHnt hospitDlizDtion or prolonJDtion oI HxistinJ hospitDlizDtion;
• rHsults in D pHrsistHnt or siJniIiFDnt GisDEility/inFDpDFity;
• rHsults in D FonJHnitDl DnomDly/Eirth GHIHFt; or
• Dny othHr DGvHrsH HvHnt thDt, EDsHG upon DppropriDtH mHGiFDl juGJmHnt, mDy jHopDrGizH
thH suEjHFt's hHDlth DnG mDy rHquirH mHGiFDl or surJiFDl intHrvHntion to prHvHnt onH oI thH
outFomHs listHG DEovH (HxDmplHs oI suFh HvHnts inFluGH DllHrJiF EronFhospDsm rHquirinJ
intHnsivH trHDtmHnt in thH HmHrJHnFy room or Dt homH, ElooG GysFrDsiDs or Fonvulsions
thDt Go not rHsult in inpDtiHnt hospitDlizDtion, or thH GHvHlopmHnt oI GruJ GHpHnGHnFy or
GruJ DEusH)
5HportinJ:
'r. :Dtson (/HDG 3,) will FonGuFt monthly FDsH rHviHw mHHtinJs whHrH thH stuGy tHDm will
rHport on DFtivH FDsHs involvHG in thH stuGy. $t thH FlosH oI HDFh FDsH rHviHw, stuGy
pHrsonnHl will EH HxFusHG DnG 'rs. :Dtson, %DrDnHk, &rDis, DnG 7urnHr-%rown will GisFuss
Dny GDtD sDIHty issuHs DnG/or Dny DppDrHnt DGvHrsH outFomHs Ior pDrtiFipDnts iGHntiIiHG
GurinJ thH FDsH rHviHw. 'r. :Dtson will rHport unDntiFipDtHG proElHms/DGvHrsH HvHnts in
37

Protocol Number 
18 June 2021 - version DRAFT
DFForGDnFH with 81&-&hDpHl +ill +533 623 # 19.0, DnG will hDlt FontinuDtion oI stuGy
proFHGurHs thDt nHJDtivHly DIIHFt pDrtiFipDnts. 6hH will Dlso rHport unDntiFipDtHG proElHms
or DGvHrsH HvHnts within thH timH IrDmHs stipulDtHG in +533 623 # 19.5 (1 or 2 wHHks,
GHpHnGinJ on thH nDturH oI thH HvHnt) DnG tDkH nHFHssDry ForrHFtivH DFtion. 'r. :Dtson will
GisFuss/prHsHnt Dny FliniFDl/EHhDviorDl tDsk issuHs thDt wHrH iGHntiIiHG with rHsHDrFh
pHrsonnHl to HnsurH thDt HvHryonH is inIormHG DEout HvHnts DnG potHntiDl protoFol
FhDnJHs. 6hH will Dlso DrrDnJH Ior trDininJs Ds nHHGHG. ,I GDtD DnG/or sDIHty issuHs FomH to
thH DttHntion oI 'rs. :Dtson DnG/or %DrDnHk EHtwHHn Eimonthly mHHtinJs, HDFh will
intHrFHGH Ds GHsFriEHG DEovH.
3KDUPDFRNLQHWLFV
1ot DppliFDElH.
%LRPDUNHUV
1ot DppliFDElH. 
6WXG\3URFHGXUHV
6WXG\6FKHGXOH
6HH 9isit 6FhHGulH 7DElH Ior D summDry. 
1. 6FrHHninJ
3DrHnts will FomplHtH thH )<,v3.1E onlinH or in pDpHr Iorm, in thH sHttinJ oI thHir
FhoosinJ. 7his quHstionnDirH will rHquirH 5-10 minutHs.
7hH stuGy FoorGinDtor will FontDFt pDrHnts oI inIDnts whosH sForHs plDFH thHm Dt
HlHvDtHG likHlihooG Ior lDtHr GiDJnosis oI Dn 1' Ey phonH to proviGH sFrHHninJ rHsults,
sFrHHn IurthHr Ior stuGy inFlusion/HxFlusion FritHriD, GHsFriEH thH EDsHlinH DssHssmHnt
in thH FontHxt oI thH lDrJHr stuGy (Ior IDmiliHs who hDvH not mHt Dny HxFlusionDry
FritHriD), DnG rHquHst vHrEDl FonsHnt to pDrtiFipDtH in D EDsHlinH DssHssmHnt with thHir
inIDnt. 7his phonH FDll will tDkH 15-30 minutHs, GHpHnGinJ on quHstions rDisHG Ey thH
pDrHnt.
2. 7hH EDsHlinH DssHssmHnt visit will tDkH plDFH in thH stuGy's oIIiFH in &DrrEoro, 1&, Ds
soon DItHr thH phonH FDll DnG will lDst DpproximDtHly 1 3/4 to 2 hours, DllowinJ Ior
introGuFtions, FomplHtion oI thH writtHn inIormHG FonsHnt proFHss, trDnsitions Irom onH
DssHssmHnt protoFol to thH nHxt, ErHDks Ior thH inIDnt, DnG D EriHI FonvHrsDtion with
pDrHnts rHJDrGinJ thH inIDnt's GHvHlopmHntDl DssHssmHnt rHsults DnG rHFommHnGDtions, iI
DppropriDtH, Ior Fommunity sHrviFHs. 3DrHnts will Dlso FomplHtH Dt quHstionnDirH rHquirinJ
Dn DGGitionDl 15 minutHs, Dt thH loFDtion oI thHir FhoiFH. 7hH IollowinJ DssHssmHnts will EH
38

Protocol Number 
18 June 2021 - version DRAFT
FomplHtHG: 
3DrHnt-inIDnt ,ntHrDFtion sHssion - 20 minutHs (9iGHos oI this sHssion will EH usHG to
mHDsurH 'yDGiF (nJDJHmHnt, 3DrHnt 5HsponsivHnHss to 6Hnsory 5HDFtivity &uHs,
3DrHnt 5HsponsivHnHss to 3rHlinJuistiF &uHs, DnG ,nIDnt ,ntHntionDl &ommuniFDtion)
&hilG-'irHFtHG 6pHHFh 3DrDGiJm - 10 minutHs (:ill EH usHG to FollHFt rHspirDtory sinus
DrrhythmiD DnG skin FonGuFtDnFH lHvHl mHDsurHs).
0ullHn 6FDlHs oI (Drly /HDrninJ - 20 minutHs. 9isuDl 5HFHption, )inH 0otor, 5HFHptivH
/DnJuDJH, DnG (xprHssivH /DnJuDJH sFDlHs.
$ttHntion )ollowinJ triDls - 2 minutHs
%riHI 2EsHrvDtion oI 6oFiDl &ommuniFDtion &hDnJH - 13 minutHs
6Hnsory 3roFHssinJ $ssHssmHnt - 15 minutHs
6Hnsory (xpHriHnFHs 4uHstionnDirH - 15 minutHs (pDrHnts only; FDn EH FomplHtHG
onlinH, or in hDrGFopy Iorm iI pDrHnts prHIHr, Irom loFDtion oI pDrHnt FhoiFH)
)or FhilGrHn who mHHt IinDl stuGy HliJiEility FritHriD Ior thH intHrvHntion triDl EDsHG on
EDsHlinH DssHssmHnt rHsults Ior thH HxprHssivH DnG/or rHFHptivH lDnJuDJH DnG sHnsory
rHDFtivity, thH stuGy FoorGinDtor will FomplHtH thH writtHn inIormHG FonsHnt proFHss Dt thH
HnG oI thH EDsHlinH DssHssmHnt.
3. 7hH DssiJnHG 3,( intHrvHntion FoDFh Ior HDFh HnrollHG IDmily will sFhHGulH Dn initiDl
introGuFtory visit with thH IDmily, whiFh will inFluGH rHForGinJ D 5-10 minutHs viGHo oI
pDrHnt-inIDnt intHrDFtion to usH in thH Iirst FoDFhinJ sHssion. 7his introGuFtory visit will
rHquirH D totDl oI DpproximDtHly 45-60 minutHs.
4. &oDFhinJ in thH Iirst 3,( GomDin Ior thH IDmily (rDnGomly DssiJnHG) will tDkH plDFH in 6
wHHkly visits Dt thH homH oI thH GyDG, lDstinJ DpproximDtHly onH hour HDFh. 
5. 3osttHst-1 will oFFur DItHr thH FonFlusion oI FoDFhinJ in thH Iirst 3,( GomDin Dt thH stuGy's
oIIiFH in &DrrEoro, 1&. 7otDl HstimDtHG timH Ior GyDGs is 25-30 minutHs, DllowinJ Ior timH Ior
introGuFtions DnG thH inIDnt to sHttlH into thH sHttinJ; pDrHnts will spHnG Dn DGGitionDl 15
minutHs FomplHtinJ D quHstionnDirH Dt D loFDtion oI thHir FhoiFH. 7hH IollowinJ DssHssmHnts
will EH FomplHtHG:
3DrHnt-inIDnt intHrDFtion sHssion - 20 minutHs
6Hnsory (xpHriHnFHs 4uHstionnDirH - 15 minutHs (pDrHnts only; FDn EH FomplHtHG
onlinH, or in hDrGFopy Iorm iI pDrHnts prHIHr, Irom loFDtion oI pDrHnt FhoiFH)
6. &oDFhinJ in thH 2nG 3,( GomDin will tDkH plDFH in 6 wHHkly visits Dt thH homH oI thH
GyDGs, lDstinJ DpproximDtHly onH hour HDFh.
7. 3osttHst-2 DssHssmHnts willl tDkH plDFH Dt thH stuGy oIIiFH in &DrrEoro, 1&, DnG will lDst
DpproximDtHly 1.5 to 2 hours, DllowinJ Ior introGuFtions, trDnsitions EHtwHHn DssHssmHnt
DFtivitiHs, ErHDks Ior thH inIDnt, DnG D EriHI FonFluGinJ FonvHrsDtion with pDrHnts rHJDrGinJ
thH inIDnt's GHvHlopmHntDl DssHssmHnt rHsults DnG rHFommHnGDtions, iI DppropriDtH, Ior
Fommunity sHrviFHs. 3DrHnts will Dlso FomplHtH two quHstionnDirHs rHquirinJ Dn DGGitionDl
15-10 minutHs, Dt thH loFDtion oI thHir FhoiFH.
3DrHnt-inIDnt intHrDFtion sHssion - 20 minutHs
&hilG-GirHFtHG spHHFh pDrDGiJm - 10 minutHs
39

Protocol Number 
18 June 2021 - version DRAFT
0ullHn 6FDlHs oI (Drly /HDrninJ 5HFHptivH DnG (xprHssivH /DnJuDJH 6FDlHs - 10
minutHs
$ttHntion )ollowinJ triDls - 2 minutHs
%riHI 2EsHrvDtion oI 6oFiDl-&ommuniFDtion &hDnJH - 13 minutHs
6Hnsory 3roFHssinJ $ssHssmHnt - 15 minutHs
6Hnsory (xpHriHnFHs 4uHstionnDirH - 15 minutHs (pDrHnts only, FDn EH FomplHtHG
onlinH, or in hDrGFopy Iorm iI pDrHnts prHIHr, Irom loFDtion oI pDrHnt FhoiFH)
3,( ,ntHrvHntion 5DtinJ 3roIilH - 5 minutHs (pDrHnts only, FDn EH FomplHtHG onlinH, or in
hDrGFopy Iorm iI pDrHnts prHIHr, Irom loFDtion oI pDrHnt FhoiFH)
)DmiliHs will EH sFhHGulHG Ior EDsHlinH DssHssmHnts Ds quiFkly Ds possiElH DItHr thH initiDl
sFrHHninJ; wH DntiFipDtH thH stuGy tHDm will hDvH thH FDpDFity to sFhHGulH DnG FomplHtH
EDsHlinH DssHssmHnts within 1 to 2 wHHks DItHr rHFHivinJ thH )<,v3.1E; howHvHr, IDmily
sFhHGulH prHIHrHnFHs DnG FonstrDints will EH DFFommoGDtHG DnG mDy lHnJthHn this timH
pHrioG. 7hH totDl lHnJth oI timH Irom thH EDsHlinH DssHssmHnt (whHn thHy woulG FonsHnt to
thH intHrvHntion triDl) throuJh 3osttHst-2 woulG EH D minimum oI 16 wHHks, DssuminJ thDt
no visits woulG EH morH thDn onH-wHHk DpDrt. +owHvHr, Irom our pDst HxpHriHnFH with
similDr intHrvHntion triDls, thHrH will EH somH lHnJthHninJ oI thH pDrtiFipDtion pHrioG Ior
most GyDGs, GuH to nHHGs to DFFommoGDtH sFhHGulinJ FonIliFts Ior Eoth DssHssmHnt DnG
intHrvHntion visits. 7hus, thH totDl DFtuDl lHnJth oI pDrtiFipDtion timH Irom thH )<,v3.1E
FomplHtion throuJh 3osttHst-2 is HstimDtHG to DvHrDJH ~22-25 wHHks.
,QIRUPHG&RQVHQW
1. &onsHnt Ior sFrHHninJ ()<,v3.1E).
%oth thH mDil DnG onlinH vHrsion oI thH )<, will inFluGH D FovHr pDJH thDt is HssHntiDlly D
IDFt shHHt DEout thH )<, DnG lDrJHr stuGy. $ll inIormDtion typiFDlly inFluGHG in Dn inIormHG
FonsHnt Iorm is GHsFriEHG in thH pDJH,inFluGinJ FonIiGHntiDlity, risks, DnG EHnHIits oI thH
stuGy. 7hus, D pDrHnt who rHDGs thH pDJH DnG suEmits thH quHstionnDirHs will hDvH JivHn
us thHir impliHG FonsHnt to usH thHir )<, HliJiEility GDtD. :H hDvH inFluGHG D quHstion:
"woulG you EH willinJ to EH FontDFtHG DEout IuturH rHsHDrFh" Ds D FonsHnt to EH notiIiHG
DEout HliJiEility Ior thH 3,( intHrvHntion stuGy. )DmiliHs who rHturn thH )<, will Dlso hDvH thH
option to FomplHtH D "6uEsHquHnt 3DrtiFipDtion" Iorm with thHir FontDFt inIormDtion,
inFluGinJ tHlHphonH numEHrs.
2. &onsHnt Ior EDsHlinH DssHssmHnts.
7hH stuGy FoorGinDtor will FontDFt IDmiliHs oI inIDnts whosH sForHs on thH )<,v3.1E plDFH
thHm Dt HlHvDtHG likHlihooG Ior Dn HvHntuDl 1' GiDJnosis, to shDrH sFrHHninJ rHsults DnG
Dsk iI thH pDrHnt is intHrHstHG in lHDrninJ morH DEout thH stuGy. ,I thH pDrHnt inGiFDtHs
intHrHst, thH stuGy FoorGinDtor will HxplDin thH ovHrDll stuGy, Ds wHll Ds thH purposH DnG
proFHGurHs Ior thH EDsHlinH DssHssmHnt visit, DnG Dsk iI thH pDrHnt is rHDGy to JivH vHrEDl
FonsHnt Ior D EDsHlinH DssHssmHnt. ,nIDnts who hDvH mHt Dll thH FritHriD to pDrtiFipDtH in
EDsHlinH DssHssmHnts must mHHt FritHriD Ior GHmonstrDtinJ FommuniFDtion GHlDys DnG
HlHvDtHG pDttHrns oI sHnsory rHDFtivity (hypo- DnG/or hypHr-rHDFtivH) GurinJ thH initiDl
EDsHlinH DssHssmHnts in orGHr to mHHt Iully HliJiEility FritHriD Ior thH intHrvHntion phDsH oI
thH stuGy. 7hHrHIorH, FonsHnt Ior thH IDmiliHs will EH oEtDinHG sHpDrDtHly Ior thH EDsHlinH
40

Protocol Number 
18 June 2021 - version DRAFT
DssHssmHnt visit DnG thH intHrvHntion phDsH oI thH stuGy (FontinJHnt on thH inIDnt mHHtinJ
Dll inFlusion FritHriD). 
8pon DrrivDl Dt thH EDsHlinH DssHssmHnt, D trDinHG rHsHDrFh stDII mHmEHr (stuGy
FoorGinDtor or onH oI thH projHFt DssHssors) will rHviHw thH ,nIormHG &onsHnt GoFumHnt Ior
thH EDsHlinH DsssHssmHnt visit with thH pDrHnt, GHsFriEinJ thH initiDl HvDluDtion point-Ey-
point, stoppinJ IrHquHntly to Dsk iI thH pDrHnt hDs Dny quHstions or FonFHrns, DnG to prompt
thH pDrHnt to rHviHw/rHstDtH inIormDtion to HnsurH thHir unGHrstDnGinJ. 7hH Iorms will EH
siJnHG DnG GDtHG Ey Eoth thH pDrHnt DnG thH projHFt stDII rHprHsHntinJ thH stuGy. &opiHs oI
thH siJnHG FonsHnt Iorms will EH JivHn to thH pDrHnt, DlonJ with D list oI FontDFt numEHrs iI
thHy hDvH IuturH FonFHrns or quHstions. 3DrHnts will EH rHminGHG thDt thHy FDn withGrDw
pDrtiFipDtion Irom thH stuGy Dt Dny timH Ey simply FDllinJ onH oI thH FontDFt pHrsons, or
tHllinJ onH oI thH DssHssors iI thHy GHFiGH to withGrDw GurinJ thH DssHssmHnt sHssion. $s
pDrt oI our stuGy, IDmiliHs will EH HnFourDJHG to pursuH Fommunity sHrviFHs Ior thHir FhilG.
:H will proviGH IDmiliHs with rHIHrrDl inIormDtion rHJDrGinJ Fommunity sHrviFH proviGHrs
GHpHnGinJ on thH spHFiIiF nHHGs oI thHir FhilG. $GGitionDlly, somH oI thH FhilGrHn involvHG in
our stuGy mDy DlrHDGy EH rHFHivinJ Fommunity sHrviFHs prior to thHir HnrollmHnt in our
stuGy. $ rHlHDsH oI inIormDtion Iorm will Dllow us to Dssist FonsHntinJ IDmiliHs with thHir
initiDl Fommunity-EDsHG rHIHrrDl Ds wHll Ds to pDss DlonJ our DssHssmHnt/intHrvHntion
inIormDtion to DJHnFiHs with whiFh FonsHntinJ IDmiliHs DrH DlrHDGy workinJ with.7his Iorm
must EH siJnHG EHIorH DssHssmHnts DrH FonGuFtHG. 7hH rHsults oI thH oriJinDl DssHssmHnt
will EH shDrHG with Dll IDmiliHs thDt pDrtiFipDtH in thH initiDl DssHssmHnt. )or HliJiElH
IDmiliHs, thH projHFt FoorGinDtor will rHviHw thH FonsHnt Iorm Ior thH intHrvHntion stuGy DnG
JivH pDrHnts thH opportunity to Hnroll in thH intHrvHntion stuGy. 
3. &onsHnt Ior intHrvHntion stuGy.
,I thH inIDnt mHHts Iull HliJiEility FritHriD GurinJ thH EDsHlinH DssHssmHnt visit, D trDinHG
projHFt stDII mHmEHr (stuGy FoorGinDtor or Dn DssHssor) will rHviHw thH inIormHG FonsHnt
GoFumHnt Ior pDrtiFipDtinJ in thH intHrvHntion phDsH oI thH stuGy Dt thH HnG oI thH EDsHlinH
visit, DJDin stoppinJ IrHquHntly to Dsk iI thH pDrHnt hDs Dny quHstions or FonFHrns, DnG to
prompt thH pDrHnt to rHviHw/rHstDtH inIormDtion to HnsurH thHir unGHrstDnGinJ. ,I D pDrHnt
is rHDGy to proviGH writtHn FonsHnt Ior thH intHrvHntion Dt thH HnG oI thH EDsHlinH visit, thHn
thH Iorm will EH siJnHG DnG GDtHG Ey thH pDrHnt DnG thH projHFt stDII mHmEHr, DnG D Fopy
proviGHG to thH pDrHnt. $ltHrnDtivHly, pDrHnts FDn tDkH thH FonsHnt Iorm homH with thHm
DnG rHturn thH Iorms Ey mDil iI thHy GHFiGH thHy wDnt to pDrtiFipDtH in thH stuGy. 
4. ,n DGGition to thH proFHGurHs HmEHGGHG in thH FonsHnt proFHss GHsFriEHG DEovH,
inFluGinJ DGHquDtH timH Ior pDrHnts' GHFision mDkinJ, wH hDvH FonsiGHrHG thH possiEility oI
FoHrFion with rHIHrHnFH to thH inFHntivHs Ior stuGy pDrtiFipDtion. 7hH inFHntivHs DrH
intHnGHG to oIIsHt thH pDrHnts' timH Ior DssHssmHnt pDrtiFipDtion DnG to FovHr inFiGHntDl
HxpHnsHs. 7hH totDl Dmount oI inFHntivHs is in-linH with whDt Dn DvHrDJH 1& wDJH HDrnHr
woulG JHt Ior 4-5 hours oI timH, HvHn without DFFountinJ Ior trDvHl timH. 1o inFHntivHs DrH
plDnnHG Ior thH in-homH intHrvHntion sHssions. 
6FUHHQLQJ
3DrHnts will FomplHtH thH )<,v3.1E onlinH or in pDpHr Iorm, in thH sHttinJ oI thHir FhoosinJ.
41

Protocol Number 
18 June 2021 - version DRAFT
7his quHstionnDirH will rHquirH 5-10 minutHs. 
7hH )<,v3.1E will EH rHFHivHG Ey thH projHFt stDII viD 5HG&Dp (Ior onlinH Iorms), Ey mDil, or
Ey piFkup Irom hHDlthFDrH proviGHrs' oIIiFHs upon rHquHst, DnG sForHG immHGiDtHly upon
rHFHipt. 
7hH )<,v3.1E wDs GHvHlopHG to iGHntiIy inIDnts to HlHvDtHG likHlihooG Ior lDtHr GiDJnosis oI
Dutism DnG othHr GHvHlopmHntDl FonGitions (H.J., DttHntion GHIiFit hypHrDFtivity GisorGHr;
lDnJuDJH GHlDys/GisorGHrs; sHnsory proFHssinJ GisorGHrs; JloEDl GHvHlopmHntDl GHlDys).
7hH sFrHHninJ Fut-points on thH )<,v3.1E wHrH sHt in FonjunFtion with D prHvious stuGy Ior
whiFh wH hDG DFFHss to GiDJnostiF outFomH inIormDtion suFh thDt wH FDpturH DEout 1/3 oI
thH inIDnts who will Jo on to EH FonIirmHG Ds hDvinJ D Dutism spHFtrum GiDJnosis whilH
misFlDssiIyinJ lHss thDn 5% oI thH typiFDlly GHvHlopinJ (7') sDmplH Ds Dt-risk. :H know
Irom prHvious stuGiHs usinJ Dn HDrliHr vHrsion oI thH )<, thDt mDny inIDnts lDtHr GiDJnosHG
with othHr 1's Dlso will hDvH sForHs HxFHHGinJ thH thrHsholG on thH )<, (7urnHr-%rown Ht
Dl., 2013).
,I pDrHnts hDvH proviGHG FonsHnt Ior IurthHr FontDFt DnG FontDFt inIormDtion in FonjunFtion
with FomplHtinJ thH )<,v3.1E, thH stuGy FoorGinDtor will FontDFt pDrHnts oI inIDnts whosH
sForHs plDFH thHm Dt HlHvDtHG likHlihooG Ior lDtHr GiDJnosis oI Dn 1' Ey phonH to proviGH
sFrHHninJ rHsults, proviGH inIormDtion DEout thH stuGy, DnG sFrHHn IurthHr Ior stuGy
inFlusion/HxFlusion FritHriD. 6pHFiIiFDlly, in this phonH FDll thH stuGy FoorGinDtor will sFrHHn
Ior thH IollowinJ FritHriD:
,nFlusion FritHriD: 
$ pDrHnt or othHr primDry FDrHJivHr oI thH inIDnt is DvDilDElH Ior stuGy pDrtiFipDtion,
DlonJ with thH inIDnt.
)Dmily livHs within thH FDtFhmHnt DrHD Ior thH stuGy.
(xFlusion FritHriD
,nIDnt hDs D known JHnHtiF FonGitions (H.J., 'own synGromH).
,nIDnt hDs D known siJniIiFDnt unForrHFtHG vision/hHDrinJ/physiFDl impDirmHnts. 
)Dmiy who Go not spHDk (nJlish Ds thHir primDry lDnJuDJH in thH homH (!50% oI thH
timH).
5HFUXLWPHQW(QUROOPHQWDQG5HWHQWLRQ
+ow pDrtiFipDnts will EH iGHntiIiHG:
7o iGHntiIy inIDnts Dt-risk Ior nHuroGHvHlopmHntDl GisorGHrs, wH will usH D populDtion-
sFrHHninJ mHthoG EDsHG on Eirth rHForGs in 1orth &DrolinD, mDilinJ postFDrGs to
IDmiliHs oI FhilGrHn in this DJH rDnJH within our FDtFhmHnt DrHD; wH will supplHmHnt
rHFruitmHnt Ey GistriEutinJ postFDrGs/IlyHrs throuJh physiFiDn's oIIiFHs, puEliF hHDlth
FliniFs, DnG FhilGFDrH proJrDms, DnG viD HmDil DnG listsHrv DnnounFHmHnts; wH Dlso will
rHDFh out to IDmiliHs oI younJ FhilGrHn viD soFiDl mHGiD Jroups thDt inFluGH pDrHnts oI
younJ FhilGrHn in our FDtFhmHnt DrHD, DnG viD Eooths Dt IDmily-oriHntHG loFDl
42

Protocol Number 
18 June 2021 - version DRAFT
IDirs/IHstivDls. $ll oI thHsH will EH GirHFtHG Dt proviGinJ pDrHnts with Dn opportunity to
FomplHtH thH )<,v3.1 Ior thHir 11- to 16-month-olG inIDnts.
+ow DnG whHrH pDrtiFipDnts will EH rHFruitHG:
3DrtiFipDnts will EH rHFruitHG throuJhout thH FHntrDl rHJion oI 1orth &DrolinD throuJh
two primDry sourFHs: (D) stDtH Eirth rHJistriHs (1& 9itDl rHForGs; 6 FountiHs within 90
milHs oI &hDpHl +ill inFluGinJ 2rDnJH, 'urhDm, &hDthDm, $lDmDnFH, *uilIorG, DnG
:DkH), DnG (E) primDry FDrH wHll-EDEy FliniFs — HithHr throuJh loFDl pHGiDtriF prDFtiFHs
or Founty hHDlth FliniFs, in rurDl DnG urEDn DrHDs thDt rHprHsHnt wiGH GHmoJrDphiFs.
2ur tHDm hDs HxpHriHnFH DnG suFFHss with thHsH mHthoGs ovHr thH pDst 15 yHDrs
throuJh othHr rHsHDrFh stuGiHs. )DmiliHs iGHntiIiHG throuJh Eirth rHJistriHs will rHFHivH
Dn inIormDtionDl postFDrG (viD postDl mDil) DskinJ thH pDrHnt oI thH inIDnt to FomplHtH
thH survHy ()<,) onlinH or to rHquHst D pDpHr Iorm, DnG rHturn to thH projHFt's 32 %ox.
)DmiliHs iGHntiIiHG throuJh pHGiDtriF prDFtiFHs DnG hHDlth FliniFs will EH JivHn Dn
inIormDtionDl postFDrG Dt thH timH oI thHir wHll-EDEy visits Ey oIIiFH stDII Dt thosH
FliniFs. 7hHy mDy Dlso Iill thH )<, out onlinH or Ds D pDpHr Iorm DnG rHturn to thH
projHFt's 32 %ox. )illinJ out thH Iorm FonstitutHs FonsHnt Ior thH initiDl sFrHHninJ (EDsHG
on our prHvious ,5% DpprovHG proFHGurHs). )or rHFruitmHnt viD listsHrvs, thH listsHrv
mHssDJH will inFluGH D link to thH onlinH )<,v3.1E Ds wHll Ds FontDFt inIormDtion Ior thH
projHFt (HmDil, phonH) throuJh whiFh pDrHnts FDn rHquHst D hDrG Fopy oI thH )<,.
)inDlly, Ior Eooths Dt loFDl IDmily-oriHntHG IDirs DnG IHstivDls,
/ikHlihooG wH will hDvH DFFHss to thH tDrJHtHG numEHr oI pDrtiFipDnts:
%DsHG on prHvious stuGiHs with similDr mHthoGoloJiHs DnG FDtFhmHnt DrHDs, wH
HstimDtH thDt thH IDmilHs oI 32,000 inIDnts will hDvH thH opportunity to FomplHtH thH
)<,v3.1 ovHr thH FoursH oI thH projHFt, with Dn ovHrDll rHturn rDtH oI ~15%, yiHlGinJ
4800 FomplHtHG )<,s. :H DntiFipDtH thDt 5% oI thHsH inIDnts (1 240) will sForH Dt risk
on thH )<, (i.H., risk sForHs ≥ 95th %ilH EDsHG on thH )<,v3.1 normDtivH GDtD). 2I thosH,
35% will EH HliJiElH Ior thH DssHssmHnt phDsH oI thH stuGy DnG DJrHH to thH
GHvHlopmHntDl DssHssmHnt Dt 81& (1 84), DnG 57% oI thHsH will mHHt Iull inFlusion
FritHriD (1 49). 2I thosH, 90% will FonsHnt to rDnGomizDtion, yiHlGinJ DpproximDtHly
44-45 IDmiliHs to rDnGomizH into thH intHrvHntion stuGy. 7hH inFlusion HnrollmHnt tDElH
proviGHs thH ErHDkGown Ey sHx DnG HthniFity JivHn thH 1orth &DrolinD GHmoJrDphiFs,
DGjustHG Ior HxpHFtHG Dttrition Ior non-(nJlish spHDkinJ IDmiliHs (i.H., wH hDvH rHGuFHG
+ispDniF HnrollmHnt Ey 1/3 oI FHnsus IiJurHs). >127(: &urrHnt FHnsus GHmoJrDphiFs
DrH: 64.7% :hitH (not +ispDniF); 22.0% %lDFk/$IriFDn $mHriFDn; 2.5% $siDn; 8.7%
+ispDniF//Dtino*; 2.0% 0orH thDn onH rDFH; 0.1% 1DtivH +DwDiiDn/3DFiIiF ,slDnGHr; 1.5%
$mHriFDn ,nGiDn/$lDskD 1DtivH. %irths in thH 6 Founty FDtFhmHnt DrHD numEHrHG
26,814 in 2014 DnG Eirth rDtHs hDvH inFrHDsHG sinFH thHn. :H will EroDGHn thH
FDtFhmHnt DrHD to DGjDFHnt urEDn DrHDs (H.J., :inston-6DlHm; )DyHttHvillH) Ds nHHGHG
to yiHlG thH tDrJHt sDmplH.@
3rotHFtion oI privDFy oI potHntiDl suEjHFts GurinJ rHFruitmHnt:
3ostFDrGs DEout thH stuGy will EH mDilHG to IDmiliHs on D onH-timH EDsis whHn thH
FhilGrHn DrH EHtwHHn 11 DnG 16 months oI DJH. 7hHsH FDrGs will EH sHnt to IDmiliHs
EDsHG on Eirth rHForGs DlonH, with no prior knowlHGJH oI how thH inIDnts will sForH on
43

Protocol Number 
18 June 2021 - version DRAFT
thH )<,. 7hH postFDrGs will JivH D wHE DGGrHss to whiFh pDrHnts FDn Jo to FomplHtH thH
)<,v3.1; in DGGition, IDmiliHs will EH proviGHG Dn HmDil DGGrHss DnG phonH numEHr,
HithHr oI whiFh FDn EH usHG to rHquHst thDt D hDrG Fopy oI thH )<,v3.1 EH mDilHG to
thHm. 7hH )<,s will EH rHturnHG Ey pDrHnts, unsForHG, in D postDJH-pDiG sHlI-DGGrHssHG
HnvHlopH, or will EH FomplHtHG onlinH. )<,s will Dlso EH DvDilDElH Dt pHGiDtriF prDFtiFHs
DnG hHDlth FliniFs DlonJ with postDJH-pDiG sHlI-DGGrHssHG HnvHlopHs.7hH )<,s will EH
iGHntiIiHG with thH potHntiDl pDrtiFipDnts' DssiJnHG ,' numEHrs rDthHr thDn with nDmHs.
$JrHHmHnt to suEsHquHnt FontDFt DnG FontDFt inIormDtion (nDmHs, DGGrHssHs, phonH
numEHrs) will EH FollHFtHG on D sHpDrDtH Iorm Irom thH )<,. 7his inIormDtion will EH
storHG in D sHpDrDtH IilH Irom thH )<, rHsults, DnG linkHG viD thH pDrtiFipDnt ,' numEHr.
)or Dny )<,s IlDJJHG GuH to D FhilG mHHtinJ thH prHGHIinHG FritHriD (risk sForHs Dt or
DEovH thH 95th %ilH), thH 3rojHFt &oorGinDtor will rHtriHvH thH FontDFt inIormDtion usinJ
thH pDrtiFipDnt ,' DnG initiDtH FontDFt with thH IDmily Ey phonH. ,n thH HvHnt thDt thH
IDmily GoHs not DnswHr DnG thH FDll JoHs to voiFHmDil, thH 3rojHFt &oorGinDtor will lHDvH
D mHssDJH thDt shH hDs FDllHG DlonJ with hHr phonH numEHr, Eut will not lHDvH Dny
inIormDtion pHrtDininJ to thH )<, rHsults.
+ow potHntiDl pDrtiFipDnts will EH FontDFtHG:
&omplHtHG )<,s will EH sForHG DnG sFrHHnHG Ior risk stDtus. ,nIDnts who sForH ≥95th
%ilH risk sForH will EH IlDJJHG, DnG thosH IDmiliHs will rHFHivH D phonH FDll inIorminJ
thHm oI thH rHsults oI thH sFrHHninJ (Ey D quDliIiHG/trDinHG projHFt FoorGinDtor), DnG
sFrHHninJ thH FhilG DnG IDmily Ior DGGtionDl inFlusion DnG HxFlusion FritHriD is thHy DrH
intHrHstHG in potHntiDlly pDrtiFipDtinJ in thH stuGy. 7hosH who hDvH FontinuHG to mHHt
HliJiEility FritHriD thDt FDn EH DssHssHG throuJh thH )<,v3.1E DnG thH phonH FDll will EH
invitHG Ior D morH FomprHhHnsivH EDsHlinH DssHssmHnt. $ mDximum oI 4 DttHmpts will
EH mDGH to FontDFt D IDmily: Dn initiDl phonH FDll, D Iollow-up phonH FDll iI thHrH is no
rHsponsH to thH initiDl FDll DItHr onH wHHk, Dn HmDil (iI thH pDrHnts proviGHG Dn HmDil
DGGrHss in thHir FontDFt inIormDtion), DnG IinDlly D mDilHG lHttHr. 7hH JoDl in thH Iirst
thrHH DttHmpts will EH to hDvH D phonH FonvHrsDtion with onH oI thH FhilG's pDrHnts, to
inIorm thHm DEout thH FhilG's sForH on thH )<,, to oIIHr rHsourFH inIormDtion DEout thH
puEliF HDrly intHrvHntion proJrDm, DnG to GHtHrminH whHthHr thH FhilG/IDmily DrH
HliJiElH to pDrtiFipDtH in thH %DsHlinH DssHssmHnt. ,I wH Go not JHt D rHsponsH to thH
Iirst thrHH DttHmpts, wH will inFluGH inIormDtion DEout thH FhilG's sFrHHninJ rHsults DnG
FontDFt inIormDtion Ior thH rHJionDl &hilG 'HvHlopmHnt 6HrviFH $JHnFy thDt woulG
sHrvH thH IDmily in thH lHttHr, Ds wHll Ds FontDFt inIormDtion Ior thH projHFt shoulG thH
pDrHnts wish to GisFuss thH sFrHHninJ rHsults or potHntiDlly FonsiGHr FonsHntinJ to Dn
initiDl HvDluDtion Dt thDt point. ,I wH JHt no rHsponsH Irom thH pDrHnts DItHr thHsH 4
DttHmpts, wH will DssumH thH pDrHnts hDvH GHFlinHG HnrollmHnt in thH stuGy.
:ho will Go thH rHFruitinJ:
5HFruitmHnt mDtHriDls (IlyHrs, mDilinJs ,HtF.) will EH prHpDrHG Ey stuGy stDII DnG
voluntHHrs, who Dlso will GistriEutH rHFruitmHnt mDtHriDls to hHDlth FDrH IDFilitiHs,
FhilGFDrH proJrDms, on soFiDl mHGiD, DnG Dt loFDl IDirs/IHstivitiHs. $t loFDl IDirs DnG
IHstivDls, stuGy stDII will usH tDElHt FomputHrs to proviGH pDrHnts oI FhilGrHn in thH DJH
rDnJH DFFHss to Dn HlHFtroniF vHrsion oI thH )<,v3.1E. 3honH FontDFts with pDrHnts oI
FhilGrHn who sForH Dt-risk Ior thH )<,v3.1, phonH sFrHHninJ Ior HxFlusion FritHriD,
HxplDnDtion oI thH stuGy, mDilinJ oI stuGy inIormDtion DnG FonsHnt Iorms, DnG thH in-
44

Protocol Number 
18 June 2021 - version DRAFT
pHrson inIormHG FonsHnt proFHss will EH thH rHsponsiEility oI thH 3rojHFt &oorGinDtor.
6WXG\9LVLWV
1. 7hH EDsHlinH DssHssmHnt visit will tDkH plDFH in thH stuGy's oIIiFH in &DrrEoro, 1&, Ds
soon DItHr thH phonH FDll DnG will lDst DpproximDtHly 1 1/2 to 2 hours. 3DrHnts will Dlso
FomplHtH Dt quHstionnDirH rHquirinJ Dn DGGitionDl 15 minutHs, Dt thH loFDtion oI thHir
FhoiFH. 7hH IollowinJ DssHssmHnts will EH FomplHtHG: 
3DrHnt-inIDnt ,ntHrDFtion sHssion - 20 minutHs (9iGHos oI this sHssion will EH usHG to
mHDsurH 'yDGiF (nJDJHmHnt, 3DrHnt 5HsponsivHnHss to 6Hnsory 5HDFtivity &uHs,
3DrHnt 5HsponsivHnHss to 3rHlinJuistiF &uHs, DnG ,nIDnt ,ntHntionDl &ommuniFDtion)
&hilG-'irHFtHG 6pHHFh 3DrDGiJm - 10 minutHs (:ill EH usHG to FollHFt rHspirDtory sinus
DrrhythmiD DnG skin FonGuFtDnFH lHvHl mHDsurHs).
0ullHn 6FDlHs oI (Drly /HDrninJ - 20 minutHs. 9isuDl 5HFHption, )inH 0otor, 5HFHptivH
/DnJuDJH, DnG (xprHssivH /DnJuDJH sFDlHs.
$ttHntion )ollowinJ triDls - 2 minutHs
%riHI 2EsHrvDtion oI 6oFiDl &ommuniFDtion &hDnJH - 13 minutHs
6Hnsory 3roFHssinJ $ssHssmHnt - 15 minutHs
6Hnsory (xpHriHnFHs 4uHstionnDirH - 15 minutHs (pDrHnts only; FDn EH FomplHtHG
onlinH, or in hDrGFopy Iorm iI pDrHnts prHIHr, Irom loFDtion oI pDrHnt FhoiFH)
)or FhilGrHn who mHHt IinDl stuGy HliJiEility FritHriD Ior thH intHrvHntion triDl EDsHG on
EDsHlinH DssHssmHnt rHsults Ior thH HxprHssivH DnG/or rHFHptivH lDnJuDJH DnG sHnsory
rHDFtivity, thH stuGy FoorGinDtor will FomplHtH thH writtHn inIormHG FonsHnt proFHss Dt thH
HnG oI thH EDsHlinH DssHssmHnt.
2. 7hH DssiJnHG 3,( intHrvHntion FoDFh Ior HDFh HnrollHG IDmily will sFhHGulH Dn initiDl
introGuFtory visit with thH IDmily oI 45-60 minutHs. 7opiFs Ior GisFussion will EH:
:hDt Go wH mHDn Ey FoDFhinJ"
:hy DrH wH GoinJ thHsH sHssions"
+ow will FoDFhinJ work"
7hH FoDFh Dlso will FomplHtH thH 3,( 5outinHs 4uHstionnDirH with thH pDrHnt, Ds D EDsis Ior
GisFussinJ whDt thH usuDl IDmily routinHs DrH involvinJ thH inIDnt, DnG whDt JoDls thH
pDrHnt mDy hDvH Ior improvinJ thH inIDnt's pDrtiFipDtion in thHsH routinHs. 
$t thH HnG oI thH sHssion, thH FoDFh will rHForG D ~10-minutH viGHo oI thH pDrHnt
intHrDFtinJ with thH inIDnt Ior usH in thH Iirst FoDFhinJ sHssion. 
4. &oDFhinJ in thH Iirst 3,( GomDin Ior thH IDmily (rDnGomly DssiJnHG) will tDkH plDFH in 6
wHHkly visits Dt thH homH oI thH GyDG, lDstinJ DpproximDtHly onH hour HDFh. 7hH DJHnGD Ior
HDFh visit will inFluGH: 
&hHFk-in DnG introGuFtion to thH sHssion
5HviHw oI sHlHFtHG sFHnDrios in thH viGHo oI pDrHnt-inIDnt intHrDFtion Irom thH prior
sHssion, to support pDrHnts unGHrstDnGinJ oI thHir inIDnt's lHvHl oI HnJDJHmHnt,
45

Protocol Number 
18 June 2021 - version DRAFT
FommuniFDtivH or sHnsory rHDFtivity FuHs oI thH inIDnt DnG how thHy DrH rHlDtHG to thH
inIDnt's HnJDJHmHnt, DnG how pDrHnt's rHsponsH strDtHJiHs impDFt thH inIDnt's
HnJDJHmHnt
/ivH FoDFhinJ - FoDFh will iGHntiIy with pDrHnt whDt rHsponsH strDtHJiHs thHy will usH to
try to inFrHDsH thH inIDnt's HnJDJHmHnt, proviGH IHHGEDFk to thH pDrHnt GurinJ DnG
DItHr thHir intHrDFtion with thH inIDnt DEout whDt thHy oEsHrvH, DnG HliFit pDrHnt's
rHIlHFtions on thH intHrDFtion DnG how strDtHJiHs miJht EH FhDnJHG, HxpDnGHG or
HnhDnFHG.
)Dmily DFtion plDnninJ - pDrHnt DnG FoDFh FomplHtH D writtHn plDn Ior thH FominJ wHHk
oI rHsponsH strDtHJiHs thH pDrHnt will FonsFiously usH, DnG thH routinHs in whiFh thH
rHsponsH strDtHJiHs will EH usHG.
&oDFh rHForGs D ~10-minutH viGHo oI D pDrHnt-inIDnt intHrDFtion to usH in thH nHxt
FoDFhinJ sHssion.
5. 3osttHst-1 will oFFur DItHr thH FonFlusion oI FoDFhinJ in thH Iirst 3,( GomDin Dt thH stuGy's
oIIiFH in &DrrEoro, 1&. 7otDl HstimDtHG timH Ior GyDGs is 25-30 minutHs; pDrHnts will spHnG
Dn DGGitionDl 15 minutHs FomplHtinJ D quHstionnDirH Dt D loFDtion oI thHir FhoiFH. 7hH
IollowinJ DssHssmHnts will EH FomplHtHG:
3DrHnt-inIDnt intHrDFtion sHssion - 20 minutHs
6Hnsory (xpHriHnFHs 4uHstionnDirH - 15 minutHs (pDrHnts only; FDn EH FomplHtHG
onlinH, or in hDrGFopy Iorm iI pDrHnts prHIHr, Irom loFDtion oI pDrHnt FhoiFH)
6. &oDFhinJ in thH 2nG 3,( GomDin will tDkH plDFH in 6 wHHkly visits Dt thH homH oI thH
GyDGs, lDstinJ DpproximDtHly onH hour HDFh.
&hHFk-in DnG introGuFtion to thH sHssion
5HviHw oI sHlHFtHG sFHnDrios in thH viGHo oI pDrHnt-inIDnt intHrDFtion Irom thH prior
sHssion, to support pDrHnts unGHrstDnGinJ oI thHir inIDnt's lHvHl oI HnJDJHmHnt,
FommuniFDtivH or sHnsory rHDFtivity FuHs oI thH inIDnt DnG how thHy DrH rHlDtHG to thH
inIDnt's HnJDJHmHnt, DnG how pDrHnt's rHsponsH strDtHJiHs impDFt thH inIDnt's
HnJDJHmHnt
/ivH FoDFhinJ - FoDFh will iGHntiIy with pDrHnt whDt rHsponsH strDtHJiHs thHy will usH to
try to inFrHDsH thH inIDnt's HnJDJHmHnt, proviGH IHHGEDFk to thH pDrHnt GurinJ DnG
DItHr thHir intHrDFtion with thH inIDnt DEout whDt thHy oEsHrvH, DnG HliFit pDrHnt's
rHIlHFtions on thH intHrDFtion DnG how strDtHJiHs miJht EH FhDnJHG, HxpDnGHG or
HnhDnFHG.
)Dmily DFtion plDnninJ - pDrHnt DnG FoDFh FomplHtH D writtHn plDn Ior thH FominJ wHHk
oI rHsponsH strDtHJiHs thH pDrHnt will FonsFiously usH, DnG thH routinHs in whiFh thH
rHsponsH strDtHJiHs will EH usHG.
&oDFh rHForGs D ~10-minutH viGHo oI D pDrHnt-inIDnt intHrDFtion to usH in thH nHxt
FoDFhinJ sHssion.
7. 3osttHst-2 DssHssmHnts willl tDkH plDFH Dt thH stuGy oIIiFH in &DrrEoro, 1&, DnG will lDst
DpproximDtHly 1.25 hours. 3DrHnts will Dlso FomplHtH two quHstionnDirHs rHquirinJ Dn
DGGitionDl ~20 minutHs, Dt thH loFDtion oI thHir FhoiFH.
3DrHnt-inIDnt intHrDFtion sHssion - 20 minutHs
&hilG-GirHFtHG spHHFh pDrDGiJm - 10 minutHs
46

Protocol Number 
18 June 2021 - version DRAFT
0ullHn 6FDlHs oI (Drly /HDrninJ 5HFHptivH DnG (xprHssivH /DnJuDJH 6FDlHs - 10
minutHs
$ttHntion )ollowinJ triDls - 2 minutHs
%riHI 2EsHrvDtion oI 6oFiDl-&ommuniFDtion &hDnJH - 13 minutHs
6Hnsory 3roFHssinJ $ssHssmHnt - 15 minutHs
6Hnsory (xpHriHnFHs 4uHstionnDirH - 15 minutHs (pDrHnts only, FDn EH FomplHtHG
onlinH, or in hDrGFopy Iorm iI pDrHnts prHIHr, Irom loFDtion oI pDrHnt FhoiFH)
3,( ,ntHrvHntion 5DtinJ 3roIilH - 5 minutHs (pDrHnts only, FDn EH FomplHtHG onlinH, or in
hDrGFopy Iorm iI pDrHnts prHIHr, Irom loFDtion oI pDrHnt FhoiFH)
Families will be scheduled for baseline assessments as quickly as possible after the initial screening; we
anticipate the study team will have the capacity to schedule and complete baseline assessments within 1
to 2 weeks after receiving the FYIv3.1b; however, family schedule preferences and constraints will be
accommodated and may lengthen this time period. The total length of time from the baseline
assessment (when they would consent to the intervention trial) through Posttest-2 would be a minimum
of 16 weeks, assuming that no visits would be more than one-week apart. However, from our past
experience with similar intervention trials, there will be some lengthening of the participation period for
most dyads, due to needs to accommodate scheduling conflicts for both assessment and intervention
visits. Thus, the total actual length of participation time from the FYIv3.1b completion through Posttest-2
is estimated to average ~22-25 weeks.
(QGRI6WXG\DQG)ROORZ8S
&oDFhHs will FomplHtH Dn Hxit intHrviHw Ior thH intHrvHntion with IDmiliHs Dt thH HnG oI thHir
lDst FoDFhinJ sHssion. 3DrHnts Dlso will EH DskHG to FomplHtH thH ",ntHrvHntion 5DtinJ
3roIilH" Ior thH 3,( intHrvHntion Dt thH timH oI thH 3osttHst-2 DssHssmHnt. 
$t thH HnG oI thH 3osttHst-2 DssHssmHnt, thH DssHssmHnt FoorGinDtor (DnG onH or morH
othHr DssHssors Ds DppropriDtH) will proviGH inIormDtion to thH IDmily on thH FhilG's
GHvHlopmHntDl stDtus EDsHG on thH stDnGDrGizHG DssHssmHnts FonGuFtHG, DnG will proviGH
pDrHnts with D writtHn summDry thDt thHy FDn tDkH homH with thHm.
3DrHnts who wish to GisFontinuH pDrtiFipDtinJ in thH intHrvHntion will EH invitHG to FontinuH
pDrtiFipDtinJ in Dny rHmDininJ sFhHGulHG DssHssmHnts. 7hHir rHDson(s) Ior GisFontinuinJ thH
intHrvHntion will EH rHForGHG iI thH pDrHnts is willinJ to shDrH, DnG iI thH rHDson suJJHsts D
possiElH DGvHrsH HvHnt, thH stuGy FoorGinDtor will ErinJ this to thH DttHntion oI thH 3,s Ior
rHviHw.6imilDrly, iI D pDrHnt wishHs to withGrDw Irom thH HntirH stuGy, thH stuGy FoorGinDtor
will rHForG thH rHDson iI proviGHG, DnG notiIy thH 3,s immHGiDtHly iI thH rHDson inGiFDtHs D
possiElH DGvHrsH HvHnt. 
3DrHnts will EH invitHG to FontDFt thH stuGy FoorGinDtor IollowinJ thH HnG oI thHir stuGy
pDrtiFipDtion iI thHy hDvH quHstions or FonFHrns rHlDtHG to thH stuGy, or iI thHy DrH sHHkinJ
DssistDnFH in IinGinJ Fommunity sHrviFHs Ior thHir FhilG. 
5HPRYDORI6XEMHFWV
47

Protocol Number 
18 June 2021 - version DRAFT
3DrtiFipDnts mDy withGrDw voluntDrily Dt Dny timH; this option will EH FovHrHG in thH FonsHnt
proFHss DnG stuGy stDII will rHminG pDrHnts thDt thHy hDvH thDt option iI thHy HxprHss
rHluFtDnFH to FontinuH thHir stuGy pDrtiFipDtion Dt Dny point. 
:H Go not DntiFipDtH Dny situDtions in whiFh thH stuGy stDII woulG mDkH D GHFision to
rHmovH pDrtiFipDnts Irom thH stuGy, JivHn thH low lHvHl oI risk DssoFiDtHG with thH stuGy
proFHGurHs. 
6WDWLVWLFDO0HWKRG
6WDWLVWLFDO'HVLJQ
7hH stuGy is GHsiJnHG Ds D rDnGomizHG FompDrDtivH triDl with two phDsHs. )or 6tuGy 3hDsH
1, GyDGs will pDrtiFipDtH in EDsHlinH DssHssmHnts; thHn HliJiElH, FonsHntinJ IDmiliHs will EH
rDnGomizHG, strDtiIyinJ Ey FhilG DJH, to onH oI two trHDtmHnt Drms. $rm1 IDmiliHs will
pDrtiFipDtH in initiDl FoDFhinJ on thH 3,( sHnsory rHDFtivity (65) GomDin, DnG $rm2 IDmiliHs
will pDrtiFipDtH in initiDl FoDFhinJ on thH 3,( prHlinJuistiF FommuniFDtion (3&) GomDin.
)DmiliHs will pDrtiFipDtH in 6 wHHkly FoDFhinJ sHssions in thHir rHspHFtivH trHDtmHnt Drms,
DnG rHturn Ior 3osttHst-1. )or 6tuGy 3hDsH 2, GyDGs in $rm1 will rHFHivH 6 wHHkly FoDFhinJ
sHssions on thH 3& GomDin, DnG GyDGs in $rm2 will rHFHivH 6 wHHkly FoDFhinJ sHssions on
thH 65 GomDin. 7hHn IDmiliHs will rHturn Ior 3osttHst-2. 
&ompDrisons oI GyDGs DssiJnHG to $rm1 DnG $rm2 Dt 3osttHst-1 will Dllow us to HstimDtH
thH sHpDrDtH HIIHFts oI thH two GomDins oI 3,( FoDFhinJ, Ds GyDGs will hDvH only EHHn
FoDFhHG in onH GomDin (rHsponGinJ to prHlinJuistiF FommuniFDtion FuHs or sHnsory
rHDFtivity FuHs) prior to 3osttHst-1. $t 3osttHst-2, wH will JHt HstimDtHs oI thH DGGitivH
HIIHFts oI FoDFhinJ in thH sHFonG 3,( GomDin, DnG EH DElH to HvDluDtH whHthHr thHrH DrH
Dny HIIHFts oI thH orGHr oI FoDFhinJ Ey FompDrinJ GyDGs in $rm1 to thosH in $rm2. 
)or DnDlysHs, wH will utilizH rHpHDtHG mHDsurH DnDlysHs within D mixHG moGHlinJ
IrDmHwork, to DssHss timH DnG tx orGHr HIIHFts, whilH DFFommoGDtinJ missinJ GDtD DnG
optimDlly utilizinJ Dll DvDilDElH GDtD. 
6DPSOH6L]H&RQVLGHUDWLRQV
 $ssuminJ rHFruitmHnt oI 44 inIDnt-pDrHnt GyDGs DnG DllowinJ Ior D 9% (n 4) Gropout rDtH,
whiFh is FonsistHnt with hiJh rHtHntion rDtHs (! 95%) in our prior intHrvHntion stuGiHs, 40
GyDGs (20 pHr trHDtmHnt Drm) will hDvH FomplHtH GDtD Ior DnDlysHs. $ssuminJ D
FonvHntionDl typH , Hrror rDtH oI .05, DnG intHrForrHlDtions DmonJ thH rHpHDtHG mHDsurHs
Irom .3 to .7, thH mDJnituGH oI trHDtmHnt Jroup HIIHFts GHtHFtDElH with D .80 stDtistiFDl
powHr will rDnJH Irom I .37 to .42, rHspHFtivHly, whiFh DrH lDrJH stDnGDrGizHG HIIHFts. 7hH
mDJnituGH oI timH HIIHFts DnG timH-Ey-trHDtmHnt Drm intHrDFtion HIIHFts GHtHFtDElH with D
.80 powHr will rDnJH Irom .27 to .18, Dlso rHspHFtivHly, whiFh DrH mHGium-sizHG
stDnGDrGizHG HIIHFts. 7hus, thH stuGy is unGHrpowHrHG to GHtHFt Dny Eut lDrJH GiIIHrHnFHs
48

Protocol Number 
18 June 2021 - version DRAFT
EHtwHHn thH trHDtmHnt Drms DnG mHGium-sizHG or lDrJHr HIIHFts on timH DnG timH-Ey-
trHDtmHnt Drm intHrDFtions. 0orH importDnt thDn thH stDtistiFDl FompDrisons, thouJh, thH
DnDlysHs will yiHlG kHy GHsFriptivH FhDrDFtHrizDtions oI thH trHDtmHnt-Drm HIIHFts Dt thH two
posttHst points (i.H., mHDns, mHGiDns, proportions, DnG vDriDnFHs) on kHy outFomHs, Ds wHll
Ds HIIHFt sizH HstimDtHs thDt FDn EH usHG in plDnninJ D lDrJHr sFDlHG HIIiFDFy triDl oI thH 3,(
intHrvHntion.
3ODQQHG$QDO\VHV
'DtD will EH DnDlyzHG usinJ Dn intHntion-to-trHDt DnDlytiF DpproDFh. 'HpHnGinJ on pDttHrns
oI Dttrition or numEHrs oI GyDGs pDrtiFipDtinJ in IHwHr thDn thH plDnnHG 6 FoDFhinJ sHssions
in HDFh oI thH two 3,( GomDins, wH mDy DGGitionDlly Hmploy somH post-hoF DnDlytiF
DpproDFhHs (H.J., FompDrisons oI trHDtHG pDrtiFipDnts in HDFh Drm; inFluGinJ D FovDriDtH Ior
numEHr oI sHssions) to inIorm our unGHrstDnGinJ oI thH outFomHs in this prooI-oI-FonFHpt
stuGy. 7hH stuGy outFomHs EDsHG on thH plDnnHG intHntion-to-trHDt DnDlysHs will EH
rHportHG, with supplHmHntDl post hoF DnDlysHs rHportHG iI DppropriDtH/inIormDtivH.  
$nDlysHs will DGGrHss onH primDry oEjHFtivH DnG thrHH sHFonGDry oEjHFtivHs:
3rimDry:   
1. (stimDtH thH sHpDrDtH DnG FomEinHG HIIHFts oI thH two 3,( intHrvHntion GomDins on
GyDGiF HnJDJHmHnt (primDry outFomH). 
6HFonGDry
2. (stimDtH thH sHpDrDtH DnG FomEinHG HIIHFts oI thH two 3,( intHrvHntion GomDins on
inIDnt intHntion FommuniFDtion. 
3. (vDluDtH thH GLIIHUHQWLDO FhDnJHs in pDrHnt rHsponsivHnHss IollowinJ FoDFhinJ on two
inGiviGuDl 3DrHnts DnG ,nIDnts (nJDJHG (3,() intHrvHntion GomDins — rHsponsHs to vDriDElH
inIDnt (D) sHnsory rHDFtivity or (E) prHlinJuistiF FommuniFDtion — Ds wHll Ds 
FXPXODWLYHFhDnJHs in pDrHnt rHsponsivHnHss IollowinJ FoDFhinJ on Eoth 3,( GomDins.
4. 'HtHrminH thH HxtHnt to whiFh (D) DutonomiF inGiFHs oI inIDnt sHlI-rHJulDtion DnG (E)
lDnJuDJH, sHnsory rHDFtivity pDttHrns, rHsponsH to joint DttHntion, DnG soFiDl-
FommuniFDtion skills FhDnJH ovHr thH FoursH oI thH 3,( intHrvHntion. .
2vHrDll DnDlytiF proFHGurHs: 
$ll GDtD will EH FlHDnHG DnG inspHFtHG Ior outliHrs, missinJ GDtD DnG GistriEutionDl
irrHJulDritiHs. $lthouJh JHnHrDl linHDr moGHlinJ mHthoGs DrH roEust to minor violDtions oI
GistriEutionDl Dssumptions, DpprHFiDElH GHpDrturHs Irom normDlity FDn FompromisH
stDtistiFDl tHsts DnG HstimDtors. :hHrH Hrror GistriEutions potHntiDlly GHviDtH Irom normDlity
or hHtHrosFHGDstiFity is suspHFtHG, thH tHsts oI thH FontrDsts GHsFriEHG EHlow will EH
FonGuFtHG usinJ HxDFt (rHsDmplinJ-EDsHG) nonpDrDmHtriF mHthoGs. 
:H will FomplHtH plDnnHG DnDlysHs oI stuGy outFomHs usinJ rHpHDtHG mHDsurHs DnDlysHs
within D mixHG moGHlinJ IrDmHwork, to DssHss timH DnG tx orGHr HIIHFts, whilH
49

Protocol Number 
18 June 2021 - version DRAFT
DFFommoGDtinJ missinJ GDtD DnG optimDlly utilizinJ Dll DvDilDElH GDtD. 
$lthouJh wH DrH pHrIorminJ multiplH stDtistiFDl tHsts DFross outFomHs DnG hypothHsHs in
DGGrHssinJ thH thrHH spHFiIiF Dims, in this projHFt is morH importDnt to DvoiG ovHrlookinJ
stDtistiFDl siJnDls oI HIIHFtivHnHss oI thH novHl intHrvHntion DpproDFh (typH ,, Hrrors), thDn
DvoiGinJ IDlsH DssHrtions oI HIIHFtivHnHss (typH , Hrrors). :H EHliHvH it is prHmDturH,
thHrHIorH, to Hmploy FonsHrvDtivH DGjustmHnts to thH typH , Hrror rDtHs in stDtistiFDl tHsts,
whiFh woulG FompromisH thH powHr oI stDtistiFDl tHsts to GHtHFt suFh siJnDls. 
3ULPDU\$QDO\VHV
7hH primDry oEjHFtivH oI this stuGy is to HxDminH whHthHr thH novHl 3,( intHrvHntion
trDnsIorms pDrHnt-inIDnt trDnsDFtions ovHr timH Ds intHnGHG, thHrHEy IDFilitDtinJ inFrHDsHs
in thH timH inIDnts spHnG in GyDGiF HnJDJHmHnt with thHir pDrHnts. :H will Dlso HvDluDtH
whHthHr GyDGiF HnJDJHmHnt outFomHs GiIIHr EDsHG on whHthHr pDrHnts DrH FoDFhHG Iirst in
thH sHnsory rHDFtivity GomDin IollowHG Ey FoDFhinJ in thH prHlinJuistiF FommuniFDtion
GomDin, or DrH FoDFhHG in thH oppositH orGHr.
6pHFiIiFDlly, wH will HstimDtH thH sHpDrDtH DnG FomEinHG HIIHFts oI thH two 3,( intHrvHntion
GomDins on GyDGiF HnJDJHmHnt (primDry outFomH). +1D: $t 3osttHst-1, GyDGs FoDFhHG in
HithHr 3,( GomDin will HxhiEit moGHrDtHly morH GyDGiF HnJDJHmHnt FompDrHG to %DsHlinH
(&ohHn's G ≥ .40). +1E: $t 3osttHst-2, GyDGs in Eoth stuGy Drms will show DGGitionDl smDll
to moGHrDtH inFrHDsHs in GyDGiF HnJDJHmHnt FompDrHG to 3osttHst-1 (&ohHn's G ≥ .25).
2ur primDry DnDlysis will EH FonGuFtHG to HxplorH D priori FontrDsts oI intHrHst within usinJ
rHpHDtHG mHDsurHs within D mixHG moGHlinJ IrDmHwork. 2I kHy intHrHst will EH thH FontrDst
oI %DsHlinH to 3osttHst-1 sForHs DnG thH FontrDst oI %DsHlinH to 3osttHst-2 sForHs (timH
HIIHFt). ,n DGGition, thH moGHl will inFluGH tHrms Ior trHDtmHnt Drm HIIHFts DnG trHDtmHnt
Drm-Ey-timH intHrDFtions. $ timH HIIHFt will inGiFDtHs Jrowth in thH outFomH Irom EDsHlinH
to thH posttHst point, D zHro or nHJliJiElH timH HIIHFt inGiFDtHs stDEility, DnG D nHJDtivH timH
HIIHFt suJJHsts D Grop in sForHs. $ non-nHJliJiElH trHDtmHnt Drm HIIHFt inGiFDtHs thDt thH
two trHDtmHnt Drms GiIIHr on thH outFomH; whilH D non-nHJliJiElH intHrDFtion FoHIIiFiHnt
suJJHsts thDt thH mDJnituGH oI FhDnJH Irom EDsHlinH to thH posttHst point DrH not
HquivDlHnt Ior mHmEHrs oI thH 2 trHDtmHnt Drms. 6inFH thH primDry outFomHs DrH
proportions, DrF sin trDnsIormDtions oI thHsH proportions will EH pHrIormHG EHIorH HntHrinJ
thHm into thH moGHls. 
6HFRQGDU\2EMHFWLYHV$QDO\VHVLIDSSOLFDEOH
6HFonGDry 2EjHFtivH $nDlysHs
2EjHFtivH 2. (stimDtH thH sHpDrDtH DnG FomEinHG HIIHFts oI thH two 3,( intHrvHntion
GomDins on inIDnt intHntion FommuniFDtion.
50

Protocol Number 
18 June 2021 - version DRAFT
+D: $t 3osttHst-1, inIDnts in Eoth Jroups will show no morH thDn moGHst JDins in
intHntionDl FommuniFDtion (&ohHn's G < .25).
+E: $t 3osttHst-2, inIDnts in Eoth Jroups will show moGHrDtH inFrHDsHs in intHntionDl
FommuniFDtion FompDrHG to %DsHlinH (&ohHn's G ≥ .40).
$nDlysHs: 7his outFomH vDriDElH involvHs Founts oI inIDnt intHntionDl FommuniFDtion
DttHmpts. :H HxpHFt thH DvHrDJH numEHr oI Founts to EH suIIiFiHntly lDrJH (HJ. ≥ 8) thDt D
normDl DpproximDtion to D 3oisson Hrror GistriEution will EH DppropriDtH; howHvHr, iI not,
3oisson or nHJDtivH EinomiDl rHJrHssion mHthoGs, or nonpDrDmHtriF DpproDFhHs mDy EH
HmployHG. 7hH DnDlysHs Ior 2EjHFtivHs 2 DnG 3 will usH thH sDmH IrDmHwork Ds Ior our
primDry 2EjHFtivH #1, thDt is, to HvDluDtH D priori FontrDsts oI intHrHst within D rHpHDtHG
mHDsurHs mixHG moGHlinJ IrDmHwork. :H will HxDminH thH FontrDst oI %DsHlinH to
3osttHst-1 sForHs DnG thH FontrDst oI %DsHlinH to 3osttHst-2 sForHs (timH HIIHFt). ,n DGGition,
thH moGHls will inFluGH tHrms Ior trHDtmHnt Drm HIIHFts DnG trHDtmHnt Drm-Ey-timH
intHrDFtions.  
2EjHFtivH 3. (vDluDtH thH GiIIHrHntiDl FhDnJHs in pDrHnt rHsponsivHnHss IollowinJ FoDFhinJ
on two inGiviGuDl 3DrHnts DnG ,nIDnts (nJDJHG (3,() intHrvHntion GomDins — rHsponsHs to
vDriDElH inIDnt (D) sHnsory rHDFtivity or (E) prHlinJuistiF FommuniFDtion — Ds wHll Ds
FumulDtivH FhDnJHs in pDrHnt rHsponsivHnHss IollowinJ FoDFhinJ on Eoth 3,( GomDins.
+D: $t 3osttHst-1, pDrHnts in Eoth intHrvHntion Drm will show inFrHDsHs in rHsponsHs
DttunHG to thHir inIDnts' EHhDviors FompDrHG to %DsHlinH, with pDrHnts FoDFhHG in thH
sHnsory rHDFtivity GomDin showinJ morH rHsponsHs DttunHG to inIDnts' sHnsory rHDFtivity,
DnG pDrHnts FoDFhHG in thH prHlinJuistiF FommuniFDtion GomDin showinJ morH rHsponsHs
DttunHG to inIDnts' siJnDls oI DttHntion IoFus DnG FommuniFDtivH intHnt.
+E: $t 3osttHst-2 (DItHr FoDFhinJ in Eoth 3,( GomDins), thHrH will EH no EHtwHHn-Drm
GiIIHrHnFHs in pDrHnt rHsponsHs DttunHG to inIDnt sHnsory rHDFtions or prHlinJuistiF
FommuniFDtion lHDGs, GuH to inFrHDsHs in pDrHnt rHsponsivHnHss to thH nHwly FoDFhHG
GomDin oI inIDnt EHhDviors.
$nDlysHs: 6HH DnDlysHs Ior 2EjHFtivH 2. 
2EjHFtivH 4. 'HtHrminH thH HxtHnt to whiFh DutonomiF inGiFHs oI inIDnt sHlI-rHJulDtion
FhDnJH ovHr thH FoursH oI thH 3,( intHrvHntion.
+D: )rom 3rHtHst to 3osttHst-2, inIDnts will show limitHG FhDnJHs in DutonomiF inGiFHs
GurinJ HxposurH to nonsoFiDl stimuli (&ohHn's G <.25), Eut will show moGHrDtH-sizHG
inFrHDsHs in rHspirDtory sinus DrrhythmiD (56$) DnG GHFrHDsHs in skin FonGuFtDnFH lHvHls
(6&/) GurinJ HxposurH to FhilG-GirHFtHG spHHFh (&ohHn's G ≥ .40).
+E Infants will demonstrate small improvements in language, sensory reactivity patterns, response to
joint attention, and social-communication skills over the course of the PIE intervention. 
Analyses: The models for these analyses will use the repeated measures mixed modeling framework, as
for Objectives 1, 2 and 3, except that the effects will be examined only at Posttest-2 (given that these
measures will not be taken at Posttest-1). The models will include terms for treatment arm effects and
treatment arm-by-time interactions.  
51

Protocol Number 
18 June 2021 - version DRAFT
$QDO\VLVRI6XEMHFW&KDUDFWHULVWLFV
%DsHlinH FhDrDFtHristiFs will EH DnDlyzHG Ey stuGy Drm Ds Iollows: 
1. &hilG DJH - ForrHFtHG DJH in months - mHDn, 6', rDnJH
2. &hilG sHx - mDlH, IHmDlH - numEHrs in HDFh FDtHJory
3. &hlG rDFH, Ds iGHntiIiHG Ey pDrHnts - :hitH, %lDFk, 0orH thDn onH rDFH, 2thHr - numEHrs
in HDFh FDtHJory
4. 3DrHnt sHlI-iGHntiIiHG rDFH - :hitH, %lDFk, 0orH thDn onH rDFH, 2thHr - numEHrs in HDFh
FDtHJory
5. &hilG HthniFity, Ds iGHntiIiHG Ey pDrHnts - /Dtino/+ispDniF, 1on-/Dtino/1on-+ispDniF -
numEHrs in HDFh FDtHJory
6. 3DrHnt sHlI-iGHntiIiHG HthniFity - /Dtino/+ispDniF, 1on-/Dtino/1on-+ispDniF - numEHrs in
HDFh FDtHJory
7. 3DrHnt HGuFDtion - lHvHl oI HGuFDtion oI pDrHnt HnrollHG in thH stuGy - numEHrs oI
pDrHnts with hiJhHst HGuFDtion lHvHl: < hiJh sFhool: FomplHtHG hiJh sFhool; FomplHtHG
1-2 yHDr post hiJh sFhool FHrtiIiFDtH or GHJrHH proJrDm or somH FollHJH; holG 4-yHDr
FollHJH GHJrHH (%DFhHlor's lHvHl); holG JrDGuDtH or proIHssionDl GHJrHH (0DstHr's, 3h',
0', -').
8. &hilG sForHs on thH 0ullHn 6FDlHs oI (Drly /HDrninJ - 9isuDl 5HFHption DnG )inH 0otor 7-
sForHs - mHDn, 6', rDnJH
9. &hilG sForHs on thH 0DF$rthur &ommuniFDtion 'HvHlopmHnt ,nvHntory - worGs
unGHrstooG, worGs spokHn, JHsturHs - mHDn pHrFHntilH sForH, 6', rDnJH
10. 3DrHnt 6trHss 6FDlH - totDl sFDlH sForH - mHDn, 6', rDnJH
)or HDFh oI thHsH EDsHlinH FhDrDFtHristiFs, FompDrisons will EH mDGH EHtwHHn GyDGs
DssiJnHG to thH two stuGy Drm to HvDluDtH EDsHlinH HquivDlHnFH oI thH Drms on non-
outFomH FhDrDFtHristiFs. 
,QWHULP$QDO\VLV
:H Go not plDn Ior intHrim DnDlysHs. 
+HDOWKHFRQRPLFHYDOXDWLRQLIDSSOLFDEOH
1ot DppliFDElH. 
2WKHU
6XEVHWVDQG&RYDULDWHV
52

Protocol Number 
18 June 2021 - version DRAFT
0oGHls will initiDlly EH run without FovDriDtHs. ,I Dny EDsHlinH FhDrDFtHristiFs GiIIHr
siJniIiFDntly EHtwHHn thH two stuGy Drms, wH will FonsiGHr rHrunninJ moGHls with
FovDriDtHs iI thHrH is D FonFHptuDl EDsis Ior thH FovDriDtH potHntiDlly FonIounGinJ thH stuGy
outFomHs. 
+DQGOLQJRI0LVVLQJ'DWD
8nGHr thH ,77 IrDmHwork, Dll rHsHDrFh IDmiliHs' DvDilDElH GDtD will EH DnDlyzHG, HvHn iI
inFomplHtH. )ull inIormDtion mDximum likHlihooG HstimDtion, whiFh Iully utilizHs Dll DvDilDElH
GDtD HvHn iI inFomplHtH, will EH usHG in DnDlysHs whHrHvHr possiElH. 7his DpproDFh yiHlGs
ForrHFt stDtistiFDl FonFlusions in thH prHsHnFH oI missinJ GDtD, Ds lonJ Ds thH GDtD FDn EH
FonsiGHrHG "missinJ Dt rDnGom (0$5)" (/ittlH & 5uEin, 2019). 7hH 0$5 Dssumption impliHs
thDt missinJ GDtD HlHmHnts FDn EH trHDtHG Ds rDnGomly missinJ Ds lonJ D FovDriDtHs
rHlHvDnt to thH rHDsons (tHFhniFDlly proEDEility oI EHinJ missinJ) DrH inFluGHG in thH
moGHls. $ltHrnDtivHly, iI sDmplH sizHs DrH insuIIiFiHnt to support Iull inIormDtion mDximum
likHlihooG HstimDtion, thHn multiplH imputDtion (0,), whiFh is DsymptotiFDlly HquivDlHnt,
mDy EH HmployHG (/ittlH & 5uEin, 2019; 6hDIHr, 1997).
(WKLFDO&RQVLGHUDWLRQV,QIRUPHG&RQVHQW$VVHQWDQG+,3$$
$XWKRUL]DWLRQ
,nFHntivHs
)DmiliHs pDrtiFipDtinJ in thH stuGy will rHFHivH D smDll monHtDry inFHntivH to
pDrtiFipDtH. :H hDvH EuGJHtHG Ior D 20 GollDr JiIt FHrtiIiFDtH Ior thH Iirst DssHssmHnt
(%DsHlinH), 25 GollDrs Ior thH sHFonG DssHssmHnt (3osttHst-1), DnG 50 GollDrs Ior thH
thirG (3osttHst-2). :H will Dlso proviGH IDmiliHs with D 10 GollDr JDs FDrG Dt HDFh
DssHssmHnt visit.
)DmiliHs will rHFHivH thH spHFiIiHG inFHntivH Dt HDFh DssHssmHnt visit. ,I D IDmily
withGrDws Irom thH stuGy thHy will not rHFHivH thH suEsHquHnt inFHntivH(s).
%oth FhilGrHn DnG thHir pDrHnts will pDrtiFipDtH in our stuGy. 7hH inFHntivH pDymHnts
will EH mDGH to thH pDrHnts.
Potential for coercion: The incentives are intended to cover the parents'/guardians' time for study
participation, incidental expenses and for travel (gas card) for each visit. The incentives increase
slightly to increase retention of the sample to the conclusion of the study. The participants will
receive 95 dollars in incentives for approximately four hours of assessment. According to data
released in 2016 by the NC Department of Commerce, the average hourly wage in NC is 21.24.
Thus the incentive offered for assessment visits, considering travel time, is in-line with what an
average wage-earner would get for this amount of time. No incentives are planned for the in-home
intervention sessions.
Privacy considerations: We will not collect Social Security Number information for the purposes of
offering these incentives. 
Costs to be borne by the participants: The only potential costs to participants related to study
participation will be any missed employment compensation due to their participation in home
intervention sessions and assessment visits. Additionally, the gas cards may not fully compensate
53

Protocol Number 
18 June 2021 - version DRAFT
all participants for their travel to the assessment site, depending on the distance they will travel and
the fuel efficiency of their vehicle. 
Alleviating potential costs to participants: A postage paid envelope will be provided with the any
hard copies of the FYI or other assessment materials for families to return the documents at no cost
to them; a similar envelope will be provided to families to return consent for intervention forms if
these are not signed at the study offices.
Informed Consent: 
The informed consent process is described in detail in section 6.3.2 of this protocol. 
Completion of the FYIv3.1b is considered to entail implied consent for use of the data. Both the mail
and online version of the FYI will include a cover page that is a fact sheet about the FYI and larger
study. All information typically included in an informed consent form is described in the page,
including confidentiality, risks, and benefits of the study. It is our understanding that a parent who
reads the page and submits the questionnaires give us their consent to use their data. Only families
who answer "yes" to the question "would you be willing to be contacted about future research" will
be contacted in the event their child scores at-risk on the FYI.
Written informed consent will be obtained for the baseline assessment and for the intervention
(consent to be obtained separately for baseline assessment and intervention, because some infants
will not meet criteria at the baseline assessment for inclusion in the intervention trial).
Consent documents are attached, including (a) the cover letter for the FYIv3.1b; (b) the consent
form for the baseline assessment, and (c) the consent form for intervention. 
The child participants will not provide written assent due to their young age (11-16 months old at
study entry) and related inability to understand the study purpose or procedures.
Collection of identifiers and sensitive information; confidentiality
We will collect names, mailing/street addresses, telephone numbers, and email addresses for the
purposes of contacting families about the study.
We will collect full face video images of parents and children for the purpose of measuring study
outcomes. 
,GHntiIiHrs FoGHG with D linkDJH IilH will EH storHG HlHFtroniFDlly in D GiIIHrHnt IolGHr Irom
thH rHsHDrFh GDtD FollHFtHG on pDrtiFipDnts. $FFHss to thH IolGHr with thH linkDJH IilH
will EH rHstriFtHG (viD HlHFtroniF pHrmission sHttinJs) to thH 03,s DnG thH 6tuGy
&oorGinDtor. 7hH 6tuGy &oorGinDtor will proviGH thH nHFHssDry FontDFt inIormDtion to
thH intHrvHntionists Ior thH rHspHFtivH IDmiliHs DssiJnHG to HDFh intHrvHntionist.
6FrHHninJ mHDsurHs DnG protoFols Irom thH GHvHlopmHntDl DssHssmHnts will EH storHG
in D loFkHG IilH FDEinHt in D loFkHG oIIiFH DnG iGHntiIiHG only Ey GyDG ,' numEHr. $ny
sFiHntiIiF rHports, DrtiFlH suEmissions, or summDriHs oI thH GDtD will not inFluGH nDmHs.
$GGitionDlly, inGiviGuDl GDtD thDt miJht possiEly iGHntiIy Dny onH FhilG or pDrHnt will not
EH prHsHntHG; GDtD will EH prHsHntHG in summDry IormDt thDt will prHFluGH Dny pHrsonDl
iGHntiIiFDtion. ,n somH FDsHs, pDrHnts mDy JivH pHrmission to usH short sHJmHnts oI
viGHo Ior tHDFhinJ/HGuFDtionDl purposHs. $ll viGHos will EH kHpt sHFurHG in thH 3,'s
lDEorDtory, iGHntiIiHG Ey ,' numEHr, DnG DrFhivHG. 9iGHo IilHs will EH FlHDrly mDrkHG to
iGHntiIy whHthHr thH pDrHnt hDs JivHn pHrmission to usH thHm Ior tHDFhinJ/HGuFDtionDl
purposHs. :H will not shDrH iGHntiIiDElH GDtD with Dny othHr pDrty (suFh Ds D FDrH
proviGHr or physiFiDn) without writtHn FonsHnt Irom thH pDrHnt/JuDrGiDn. +owHvHr iI D
pDrHnt/JuDrGiDn FhoosHs to shDrH thH writtHn rHport thDt wH proviGH to thHm, thHy will
54

Protocol Number 
18 June 2021 - version DRAFT
EH mDGH DwDrH thDt this inIormDtion mDy thHn EHFomH pDrt oI thHir FhilG's rHForG with
thDt institution, whiFh mDy proviGH ,nsurDnFH FompDniHs with DFFHss to thDt
inIormDtion.
(lHFtroniF GDtD will EH storHG on D sHFurH DnG HnFryptHG nHtwork (5('&Dp) thDt
rHquirHs pDssworG DFFHss.
3ortDElH FomputinJ GHviFHs will EH HnFryptHG, hDvH D powHr-on pDssworG rHquirHG, DnG
Dn DutomDtiF loJ-oII.
7hH primDry potHntiDl Ior GHGuFtivH GisFlosurH will FomH Irom our viGHotDpinJ oI
rHsHDrFh pDrtiFipDnts, whiFh is HssHntiDl Ior sHvHrDl DspHFts oI thH stuGy protoFol.
%HFDusH thH viGHotDpHs will hDvH Iull IDFH imDJHs oI FhilGrHn DnG thHir pDrHnts, DnG
EHFDusH Iirst nDmHs will EH usHG oItHn in thH FoursH oI intHrDFtions FDpturHG on
viGHotDpHs, thH iGHntity oI pDrtiFipDnts FoulG EH GHGuFHG Ey somHonH wDtFhinJ thH
viGHotDpHs. :H, thHrHIorH, will tDkH FDrHIul mHDsurHs to protHFt thH sHFurity oI thH
viGHotDpHs.
6tuGy pHrsonnHl will hDvH DFFHss to physiFDl GDtD (pDpHr Iorms, '9', HxtHrnDl hDrG
GrivHs) thDt will EH housHG in thH 3,( oIIiFH in loFkHG FDEinHts. 6tDII will EH rHquirHG to
siJn out/in Dny Iorm oI thHsH GDtD (inIormDtion rHForGHG in GyDG's inGiviGuDl pDpHr IilH
or on '9') in D notHEook. $ll HlHFtroniF GDtD will EH DvDilDElH on D sHFurH nHtwork GrivH
thDt is pDssworG protHFtHG DnG HnFryptHG (5('&Dp, 6Fhool oI 0HGiFinH shDrHG GrivH,
81& 2IIiFH 365 suitH oI sHFurH FlouG DppliFDtions). 7hH GHiGHntiIiHG GDtD will EH
DvDilDElH throuJh thH sHFurHG nHtwork DnG thH iGHntiIyinJ mDtFh will EH housHG
sHpDrDtHly. $FFHss to thH GDtD IilHs will EH rHstriFtHG, EDsHG on thH rolH oI thH rHsHDrFh
tHDm mHmEHr. )or HxDmplH, mHmEHrs oI thH DssHssmHnt tHDm will not hDvH DFFHss to
GDtD rHlDtHG to thH intHrvHntion, in orGHr to prHsHrvH thHir "ElinGnHss" to thH
rDnGomizHG Jroup DssiJnmHnt oI stuGy pDrtiFipDnts.
Privacy
3honH intHrviHws in thH 3,( oIIiFH will EH FonGuFtHG EHhinG FlosHG Goors.
$ssHssmHnts will EH FonGuFtHG in D privDtH suitH.
1o mDilHG inIormDtion will inFluGH Dny inGiFDtion oI FhilG/pDrHnt stDtus thDt is visiElH on
thH HxtHrior oI thH HnvHlopH.
&oDFhinJ sHssions will tDkH plDFH in thH IDmily's homH, sFhHGulHG Dt thH FonvHniHnFH oI
thH pDrHnt.
,QVWLWXWLRQDO5HYLHZ%RDUG,5%5HYLHZ
7hH stuGy will unGHrJo rHviHw DnG DpprovDl Ey thH 81&-&+ ,5%, with thH DppliFDtion
suEmittHG throuJh thH onlinH DppliFDtion systHm (,5%,6). 
0oGiIiFDtions will EH suEmittHG Ior 81&-&+ ,5% rHviHw throuJh thH onlinH systHm, DnG ,5%
DpprovDl will EH sHFurHG EHIorH moGiIiFDtions DrH implHmHntHG.
55

Protocol Number 
18 June 2021 - version DRAFT
 5HportDElH HvHnts DnG unDntiFipDtHG proElHms unGHr thH purviHw oI thH ,5% will EH
rHportHG IollowinJ 81&-&+ 6tDnGDrG 2pHrDtinJ 3roFHGurHs. 
6XEMHFW3ULYDF\&RQILGHQWLDOLW\	'DWD0DQDJHPHQW
6HH sHFtion 7.1 Ior thH protoFol rHlDtHG to pDrtiFipDnt privDFy DnG FonIiGHntiDlity DnG GDtD
sHFurity. 
'DtD will EH HntHrHG DnG storHG in 5HG&Dp. 3DrHnt rHport mHDsurHs will EH HntHrHG GirHFtly
into 5HG&Dp Ey pDrtiFipDnts, unlHss thH pDrtiFipDnts rHquHst to FomplHtH hDrG FopiHs oI
thHsH mHDsurHs instHDG.
2thHr GDtD will EH HntHrHG into 5HG&Dp Ey trDinHG rHsHDrFh DssistDnts who will EH JrDntHG
limitHG DFFHss to thH 5HG&Dp sitH FonsistHnt with thHir GDtD Hntry rolH. 2nH rHsHDrFh
DssistDnt will HntHr thH GDtD initiDlly, DnG D sHFonG rHsHDrFh DssistDnt will inGHpHnGHntly
FhHFk thH GDtD Hntry Ior Hrrors.  
$FFHss to nDmHs, homH DGGrHssHs, HmDil DGGrHssHs, DnG phonH numEHrs HntHrHG into
5HG&Dp will EH rHstriFtHG to thH GDtD mDnDJHr, projHFt 3,s, DnG stuGy FoorGinDtor; thH
projHFt 3,s or stuGy FoorGinDtor mDy proviGH tHmporDry DFFHss to this inIormDtion Ior othHr
stuGy stDII iI nHHGHG to FomplHtH Dn DssiJnHG tDsk. 
'DtD Hntry rHForGs will EH iGHntiIiHG Ey HDFh pDrtiFipDtinJ GyDG's uniquH ,' numEHr. 
'HYLDWLRQV8QDQWLFLSDWHG3UREOHPV
$ loJ oI protoFol GHviDtions will EH mDintDinHG throuJh DFtivH GDtD FollHFtion. $ny protoFol
GHviDtion thDt hDrms D pDrtFipDnt or plDFHs othHrs Dt inFrHDsHG risk oI hDrm will EH rHportHG
to thH ,5% pHr 81&-&+ 623 1401. 
5HportDElH GHviDtions or unDntFipDtHG proElHms will EH rHportHG to thH ,5% throuJh thH
onlinH rHportinJ systHm within two wHHks oI thH 3,s EHFominJ DwDrH oI thH proElHm. 
$ny protoFol GHviDtion thDt is mDGH to HliminDtH Dn immHGiDtH hDzDrG to D pDrtiFipDnt
without ,5% DpprovDl will EH suEsHquHntly rHportHG to thH ,5% pHr 81&-&+ 623 1401. 
$ny unDntiFipDtHG HvHnt thDt involvHs risk to D pDrtiFipDnt or othHrs will EH rHportHG to thH
,5% pHr 81&-&+ 623 1401. )or this purposH, unDntiFipDtHG HvHnts DrH GHIinHG Ds Iollows
(Irom 81&-&+ 623 1401):
1. 8nDntiFipDtHG 3roElHm ,nvolvinJ 5isk to 6uEjHFts or 2thHrs (83,562): $ny inFiGHnt,
HxpHriHnFH, or outFomH thDt
1. 4.5.1  is unHxpHFtHG (in tHrms oI nDturH, sHvHrity, or IrHquHnFy) JivHn (D)
thH rHsHDrFh proFHGurHs thDt DrH GHsFriEHG in thH protoFol-rHlDtHG GoFumHnts, suFh
Ds thH ,5%-DpprovHG rHsHDrFh protoFol DnG inIormHG FonsHnt GoFumHnt; DnG (E) thH
FhDrDFtHristiFs oI thH pDrtiFipDnt populDtion EHinJ stuGiHG;
56

Protocol Number 
18 June 2021 - version DRAFT
2. 4.5.2  is rHlDtHG or possiEly rHlDtHG to D pDrtiFipDnt's pDrtiFipDtion in thH rHsHDrFh;
DnG
3. 4.5.3  is sHrious or suJJHsts thDt thH rHsHDrFh plDFHs pDrtiFipDnts or othHrs Dt D
JrHDtHr risk oI hDrm (inFluGinJ physiFDl, psyFholoJiFDl, HFonomiF, or soFiDl hDrm)
thDn wDs prHviously known or rHFoJnizHG.
'DWD&ROOHFWLRQ
'DtD FollHFtion inIormDtion hDs EHHn prHviously GHtDilHG in sHFtions 5.2, 6.1.3, 6.3.5, DnG in
thH 9isit 6FhHGulH 7DElH. 
'DtD will EH sHFurHly DrFhivHG in 5HG&Dp. 
7hH linkDJH IilH will EH mDintDinHG until viGHos oI thH GyDGs hDvH EHHn GHstroyHG. $FFHss
will EH rHstriFtHG to thH stuGy 3,s or othHr rHsHDrFh stDII thHy GHsiJnDtH, EDsHG on nHHG to
DFFHss thH linkDJH IilHs. 
9iGHos oI GyDGs will EH GHstroyHG EHIorH thH FhilG rHDFhHs thH DJH oI 18. 
'DWD4XDOLW\$VVXUDQFH
$ll rHsHDrFh stDII will FomplHtH trDininJ in humDn suEjHFts rHsHDrFh HthiFs. 
(DFh rHsHDrFh stDII mHmEHr will EH trDinHG to FomplHtH DFtivitiHs rHlDtHG to thHir rolH(s) on
thH projHFt Ey D quDliIiHG trDinHr, with onJoinJ ovHrsiJht. ,n DGGition to kHy pHrsonnHl (03,s
DnG &o-,s, inFluGinJ stuGy mHthoGoloJists/stDtistiFiDns), projHFt rolHs will inFluGH D stuGy
FoorGinDtor (with ovHrDll rHsponsiEility Ior rHFruitmHnt, HnrollmHnt, inIormHG FonsHnt,
sFhHGulinJ visits, GDtD storDJH, GDtD Hntry, DnG trDininJ DnG supHrvision oI 5$s involvHG in
thHsH DFtivitiHs), lHDG FoDFh (rHsponsiElH Ior trDininJ DnG ovHrsiJht oI projHFt FoDFhHs), Dn
DssHssmHnt FoorGinDtor DnG DssHssmHnt tHDm lHDGs (rHsponsiElH Ior orJDnizinJ DnG
proviGinJ DssHssor trDininJ DnG lHDGinJ inGiviGuDl DssHssmHnt visits), DnG FoGinJ tHDm
lHDGHrs (rHsponsiElH Ior trDininJ 5$s DnG monitorinJ DnG mDintDininJ thHir rHliDEility Ior
mHDsurHs involvinJ FoGinJ/rDtinJ/sForinJ oI viGHos).
7hH lHDG FoDFh, DssHssmHnt FoorGinDtor, DnG FoGinJ tHDm lHDGHrs will HDFh HnsurH thDt
tHDm mHmEHrs IulIillinJ rolHs unGHr thHir purviHw hDvH FomplHtHG Dll rHquirHG trDininJ
stHps DnG mHt FritHriD Ior IiGHlity in DGministHrinJ DssHssmHnts, implHmHtinJ intHrvHntion,
DnG/or rHliDEility in sForinJ/rDtinJ/FoGinJ Ds rHquirHG Ior thH purposH oI GDtD quDlity. 
7o simpliIy thH proFHss oI rHliDElH FoGinJ/rDtinJ oI mHDsurHs tDkHn Irom viGHos, Dll
DFtivitiHs rHlDtHG to onH mHDsurH will EH IoFusHG HithHr Dt 81&-&+ or Dt 86&, to minimizH
thH nHHG Ior Fross-sitH trDininJ on FoGinJ or rDtinJ thH sDmH mHDsurH. 
)or mHDsurHs thDt DrH not HntHrHG GirHFtly into 5HG&Dp Ey pDrHnts, GDtD will EH HntHrHG Ey
57

Protocol Number 
18 June 2021 - version DRAFT
onH rHsHDrFh DssistDnt DnG inGHpHnGHntly FhHFk Ior DFFurDFy Ey DnothHr rHsHDrFh
DssistDnt. 9HriIiFDtion thDt GDtD HntHrHG Ior D pDrtiFipDnt's mHDsurH hDvH EHHn FhHFkHG will
EH rHForGHG within 5HG&Dp.
3rior to DnDlysis, GDtD will EH FlHDnHG DnG Dny inFonsistHnFiHs will EH DGGrHssHG. 
6WXG\5HFRUGV
6tuGy rHForGs inFluGH:
&omplHtHG )<,3.1E
6hort 'HmoJrDphiF 4uHstionnDirH (FomplHtHG in FonjunFtion with thH )<,3.1E)
&ontDFt inIormDtion Ior pDrHnts who FomplHtH thH )<,3.1E
/onJ 'HmoJrDphiF 4uHstionnDirH (FomplHtHG Ey pDrtiFipDnts who FonsHnt to EDsHlinH
DssHssmHnts)
0DF$rthur &ommuniFDtion 'HvHlopmHnt ,nvHntory (EDsHlinH)
3DrHnt 6trHss 6FDlH (EDsHlinH)
6Hnsory (xpHriHnFHs 4uHstionnDirH (EDsHlinH, 3osttHst-1, 3osttHst-2)
0ullHn 6FDlHs oI (Drly /HDrninJ 
9isuDl 5HFHption 6FDlH (%DsHlinH)
)inH 0otor 6FDlH (%DsHlinH)
5HFHptivH /DnJuDJH 6FDlH (%DsHlinH, 3osttHst-1, 3osttHst-2)
(xprHssivH /DnJuDJH 6FDlH (%DsHlinH, 3osttHst-1, 3osttHst-2)
3DrHnt-&hilG ,ntHrDFtion 6Hssion (%DsHlinH, 3osttHst-1, 3osttHst-2)
9iGHos oI sHssion
'yDGiF (nJDJHmHnt (FoGHG Irom viGHos, usinJ 2EsHrvHr soItwDrH)
3DrHnt 5Hsponsivity to &hilG 6Hnsory 5HDFtivity &uHs (rDtHG Irom viGHos)
3DrHnt 5Hsponsivity to &hilG 3rHlinJuistiF &ommuniFDtion &uHs (rDtHG Irom viGHos)
&hilG ,ntHntionDl &ommuniFDtion (FoGHG Irom viGHos, usinJ 2EsHrvHr soItwDrH)
&hilG-'irHFtHG 6pHHFh 3rotoFol (%DsHlinH, 3osttHst-2)
9iGHos oI sHssion
*DzHpoint rHForGs (HyH-trDFkinJ GurinJ FhilG-GirHFtHG spHHFh protoFol)
)irstEHDt rHForGs (intHrEHDt-intHrvDl)
6himmHr rHForGs (skin FonGuFtDnFH lHvHls)
%riHI 2EsHrvDtion oI 6oFiDl &ommuniFDtion &hDnJH (%DsHlinH, 3osttHst-2)
58

Protocol Number 
18 June 2021 - version DRAFT
9iGHos oI sHssion
6ForinJ protoFols FomplHtHG Irom viGHos
6Hnsory 3roFHssinJ $ssHssmHnt (%DsHlinH, 3osttHst-2)
9iGHos oI sHssion
6ForinJ protoFols
5HsponsH to -oint $ttHntion 6ForinJ protoFols (%DsHlinH, 3osttHst-2)
'HvHlopmHntDl rHports Ior FhilGrHn (%DsHlinH, 3osttHst-2)
3,( &oDFhinJ IiGHlity viGHos
3,( &oDFhinJ IiGHlity sForinJ protoFols
9iGHos oI pDrHnt-inIDnt routinHs usHG Ior FoDFhinJ
3,( &oDFh sHssion plDns
3,( )Dmily DFtion plDns
,ntHrviHw notHs Irom IinDl FoDFhinJ sHssion Hxit intHrviHw
3,( intHrvHntion rDtinJ proIilH
$FFHVVWR6RXUFH
6ourFH GoFumHnts inFluGH: 
'oFumHnts FrHDtHG whHn pDrtiFipDtinJ pDrHnts FomplHtH mHDsurHs within 5HG&Dp
$FFHssiElH in 5HG&Dp to stuGy stDII with rolHs oI stuGy FoorGinDtor, GDtD mDnDJHr,
stDtistiFiDn, 3,, GDtD GownloDGHr (this rolH will only hDvH DFFHss to GHiGHntiIiHG GDtD)
'DtD FrHDtHG GirHFtly in 5HG&Dp upon Hntry
'oFumHnts FrHDtHG whHn pDrtiFipDtinJ pDrHnts FomplHtH hDrG Fopy vHrsions oI pDrHnt-
rHport mHDsurHs
$FFHssiElH to stuGy stDII with rolHs oI stuGy FoorGinDtor, GDtD mDnDJHr, GDtD Hntry (this
rolH will HntHr GDtD EDsHG on GyDG uniquH ,' without DFFHss to GirHFt iGHntiIiHrs),
stDtistiFiDn, 3,, GDtD GownloDGHr (this rolH will only hDvH DFFHss to GHiGHntiIiHG GDtD)
'DtD HntHrHG into 5HG&Dp Irom hDrG FopiHs Ey GDtD Hntry stDII (rHsHDrFh DssistDnts)
6ForinJ protoFols Ior mHDsurHs DGministHrHG GurinJ DssHssmHnt visits
$FFHssiElH to stuGy stDII with rolHs oI DssHssmHnt FoorGinDtor, DssHssmHnt tHDm lHDG,
59

Protocol Number 
18 June 2021 - version DRAFT
DssHssor, stuGy FoorGinDtor, GDtD mDnDJHr, GDtD Hntry (this rolH will HntHr GDtD EDsHG
on GyDG uniquH ,' without DFFHss to GirHFt iGHntiIiHrs), stDtistiFiDn, 3,, GDtD GownloDGHr
(this rolH will only hDvH DFFHss to GHiGHntiIiHG GDtD)
'DtD FrHDtHG Ey DssHssors on hDrG Fopy protoFols usHG GurinJ DssHssmHnt visits
'DtD HntHrHG into 5HG&Dp Ey GDtD Hntry stDII (rHsHDrFh DssistDnts)
9iGHos oI pDrHnt-inIDnt intHrDFtion sHssions
$FFHssiElH to stuGy stDII with rolHs oI DssHssmHnt FoorGinDtor, DssHssmHnt tHDm lHDG,
DssHssor, stuGy FoorGinDtor, viGHo-GownloDGHG/HGitor (rHsHDrFh DssistDnt), FoGinJ tHDm
lHDGHr, FoGHr (rHsHDrFh DssistDnt), 3,
'DtD FrHDtHG Ey FoGinJ/rDtinJ Irom viGHos, in HithHr (xFHl IilHs or usinJ 2EsHrvHr
(JHnHrDtinJ Dn oGI IilH within thH 2EsHrvHr soItwDrH)
'DtD HntHrHG into 5HG&Dp Ey GDtD Hntry stDII (rHsHDrFh DssistDnts) or Ey HxportinJ Irom
2EsHrvHr into (xFHl, uploDGinJ (xFHl IilHs into 5HG&Dp
)iGHlity viGHos oI FoDFhinJ sHssions
$FFHssiElH to stuGy stDII with rolHs oI lHDG FoDFh, FoDFh, FoGinJ tHDm lHDGHr, FoGHr
(rHsHDrFh DssistDnt), 3,
'DtD FrHDtHG Ey sForinJ IiGHlity oI FoDFh usinJ FoDFhinJ IiGHlity protoFol
'DtD HntHrHG into 5HG&Dp Ey GDtD Hntry stDII (rHsHDrFh DssistDnts)
'DWDRU6SHFLPHQ6WRUDJH6HFXULW\
6HH sHFtions 7.1 DnG 7.3
5HWHQWLRQRI5HFRUGV
'DtD will EH sHFurHly DrFhivHG in 5HG&Dp. 
7hH linkDJH IilH will EH mDintDinHG until viGHos oI thH GyDGs hDvH EHHn GHstroyHG. $FFHss
will EH rHstriFtHG to thH stuGy 3,s or othHr rHsHDrFh stDII thHy GHsiJnDtH, EDsHG on nHHG to
DFFHss thH linkDJH IilHs. 
9iGHos oI GyDGs will EH GHstroyHG EHIorH thH FhilG rHDFhHs thH DJH oI 18. 
2nFH viGHo IilHs hDvH EHHn GHstroyHG, thH linkDJH IilH will Dlso EH GHstroyHG, DnG thH
DrFhivHG GDtDsHt will EH rHviHwHG to FonIirm thDt Dll pHrsonDlly iGHntiIiDElH inIormDtion hDs
EHHn rHmovHG.
7hH GHiGHntiIiHG GDtDsHt will EH rHtDinHG inGHIinitHly.
60

Protocol Number 
18 June 2021 - version DRAFT
'HstruFtion oI rHForGs rHquirH DpprovDl Ey onH oI thH projHFt 3,s.
6WXG\0RQLWRULQJ
0onitorinJ oI this stuGy is thH rHsponsiEility oI thH 03,s. (sHH sHFtion 7.12).
'DWD6DIHW\0RQLWRULQJ3ODQ
7hH protoFol in this stuGy prHsHnts minimDl DntiFipDtHG risk to pDrtiFipDtinJ FhilGrHn or
IDmiliHs. 7hH 81& ,5% will mDintDin HthiFDl DnG rHJulDtory ovHrsiJht oI thH stuGy. 'r. /inGD
:Dtson DnG 'r. *rDFH %DrDnHk (03,s) will EH jointly rHsponsiElH Ior thH sDIHty oI
pDrtiFipDnts DnG Ior thH vDliGity DnG intHJrity oI thH GDtD on D GDily EDsis. 7hHy will HnsurH
thDt:
• only suEjHFts who mHHt thH stuGy HliJiEility FritHriD DrH HnrollHG,
• thH inIormHG FonsHnt proFHss will EH FonGuFtHG DppropriDtHly DnG thDt inIormHG FonsHnt
will EH oEtDinHG prior to proFHHGinJ with Dny stuGy proFHGurHs
• GDtD will EH FollHFtHG DnG DnDlyzHG Ds spHFiIiHG in thH protoFol,
• unDntiFipDtHG proElHms DnG DGvHrsH HvHnts will EH rHviHwHG promptly DnG rHportHG to
thH 81& ,5% Ds rHquirHG,
• privDFy DnG FonIiGHntiDlity oI suEjHFts will EH mDintDinHG
• withGrDwDls DrH GoFumHntHG.
'r. :Dtson (/HDG 3,) will FonGuFt monthly FDsH rHviHw mHHtinJs whHrH thH stuGy tHDm will
rHport on DFtivH FDsHs involvHG in thH stuGy. $t thH FlosH oI HDFh FDsH rHviHw, stuGy
pHrsonnHl will EH HxFusHG DnG 'rs. :Dtson, %DrDnHk, &rDis, DnG 7urnHr-%rown will GisFuss
Dny GDtD sDIHty issuHs DnG/or Dny DppDrHnt DGvHrsH outFomHs Ior pDrtiFipDnts iGHntiIiHG
GurinJ thH FDsH rHviHw. 'r. :Dtson will rHport unDntiFipDtHG proElHms/DGvHrsH HvHnts in
DFForGDnFH with 81&-&hDpHl +ill +533 623 # 19.0, DnG will hDlt FontinuDtion oI stuGy
proFHGurHs thDt nHJDtivHly DIIHFt pDrtiFipDnts. 6hH will Dlso rHport unDntiFipDtHG proElHms
or DGvHrsH HvHnts within thH timH IrDmHs stipulDtHG in +533 623 # 19.5 (1 or 2 wHHks,
GHpHnGinJ on thH nDturH oI thH HvHnt) DnG tDkH nHFHssDry ForrHFtivH DFtion. 'r. :Dtson will
GisFuss/prHsHnt Dny FliniFDl/EHhDviorDl tDsk issuHs thDt wHrH iGHntiIiHG with rHsHDrFh
pHrsonnHl to HnsurH thDt HvHryonH is inIormHG DEout HvHnts DnG potHntiDl protoFol
FhDnJHs. 6hH will Dlso DrrDnJH Ior trDininJs Ds nHHGHG. ,I GDtD DnG/or sDIHty issuHs FomH to
thH DttHntion oI 'rs. :Dtson DnG/or %DrDnHk EHtwHHn monthly mHHtinJs, HDFh will
intHrFHGH Ds GHsFriEHG DEovH.
6WXG\0RGLILFDWLRQ
0oGiIiFDtions to thH stuGy will EH suEmittHG to thH ,5% Ior DpprovDl prior to implHmHntinJ
FhDnJHs (HxFHpt in thH FDsH oI Dny unDntiFipDtHG FhDnJHs rHquirHG Ior immHGiDtH sDIHty oI
pDrtiFipDnts or othHrs).
7hH stuGy FoorGinDtor will upGDtH projHFt GoFumHnts DFForGinJly IollowinJ DpprovDl oI thH
61

Protocol Number 
18 June 2021 - version DRAFT
moGiIiFDtion. 
6WXG\'LVFRQWLQXDWLRQ
:H Go not DntiFipDtH Dny FonGitions unGHr whiFh thH stuGy woulG EH GisFontinuHG, in liJht
oI thH limitHG risks it posHs to pDrtiFipDnts. 
6WXG\&RPSOHWLRQ
7hH initiDl IunGinJ pHrioG Ior this stuGy is 2 yHDrs, stDrtinJ $uJust 1, 2017. :H DntiFipDtH
thDt FomplHtion oI thH stuGy will rHquirH D lonJHr pHrioG oI timH, howHvHr, DnG will rHnHw
our ,5% DppliFDtion/DpprovDl throuJhout thH GurDtion oI thH stuGy. :H will notiIy thH ,5%
whHn thH stuGy is FlosHG. 
&RQIOLFWRI,QWHUHVW0DQDJHPHQW3ODQ
6tuGy invHstiJDtors DnG stDII will Fomply with Dll 81&-&+ proFHGurHs Ior mDnDJinJ FonIliFts
oI intHrHst DnG potHntiDl FonIliFts oI intHrHst, inFluGinJ FomplHtinJ rHquirHG FonIliFt oI
intHrHst rHportinJ in FonjunFtion with HDFh DnnuDl rHnHwDl oI our ,5% DpprovDl. 
)XQGLQJ6RXUFH
7his stuGy is IunGHG Ey D JrDnt Irom 1,&+' 521 +'091547.
3XEOLFDWLRQ3ODQ
7hH 03,s holG primDry rHsponsiEility Ior puElishinJ thH rHsults oI this stuGy.
5Hsults will EH rHportHG in FliniFDltriDls.Jov Ds rHquirHG Ey our 1,+ IunGinJ. 
:H plDn to suEmit D mDnusFript Ior pHHr rHviHw rHportinJ thH rHsults Ior primDry DnG
sHFonGDry outFomHs in this stuGy Ds soon Ds possiElH DItHr Dll GDtD proFHssinJ, FoGinJ,
Hntry, FlHDninJ DnG DnDlysis hDvH EHHn FomplHtHG. 
62

Protocol Number 
18 June 2021 - version DRAFT
$SSHQGLFHV
$SSHQGL[
7LWOH
6HFWLRQ
7RSLF
1
)<, pDrHnt lHttHr
onlinH
6 0HthoGs
6.3.4
5HFruitmHnt,
(nrollmHnt DnG
5HtHntion
2
)<, pDrHnt lHttHr
hDrG Fopy
6 0HthoGs
6.3.4
5HFruitmHnt,
(nrollmHnt DnG
5HtHntion
3
3DrHnt IlyHr
6 0HthoGs
6.3.4
5HFruitmHnt,
(nrollmHnt DnG
5HtHntion
4
)lyHr Ior
hHDlthFDrH
proviGHrs
6 0HthoGs
6.3.4
5HFruitmHnt,
(nrollmHnt DnG
5HtHntion
5
,nIormDtion shHHt
6 0HthoGs
6.3.4
5HFruitmHnt,
(nrollmHnt DnG
5HtHntion
6
)<, postFDrG
6 0HthoGs
6.3.4
5HFruitmHnt,
(nrollmHnt DnG
5HtHntion
7
/HttHr tHmplDtH
Ior FhilGrHn who
mHHt )<, FritHriD
Eut unDElH to
FontDFt
6 0HthoGs
6.3.4
5HFruitmHnt,
(nrollmHnt DnG
5HtHntion
63

Protocol Number 
18 June 2021 - version DRAFT
8
3osttHst-2 rHport
tHmplDtH
6 0HthoGs
6.3.6 (nG oI
6tuGy DnG )ollow
8p
9
)<,v3.1E pDrHnt
lHttHr with
FonsHnt
inIormDtion
7 7riDl
$GministrDtion
7.1 (thiFDl
&onsiGHrDtions:
,nIormHG
&onsHnt/$ssHnt
DnG +,3$$
$uthorizDtion
10
%DsHlinH
$ssHssmHnt
&onsHnt
7 7riDl
$GministrDtion
7.1 (thiFDl
&onsiGHrDtions:
,nIormHG
&onsHnt/$ssHnt
DnG +,3$$
$uthorizDtion
11
,ntHrvHntion
6tuGy &onsHnt
7 7riDl
$GministrDtion
7.1 (thiFDl
&onsiGHrDtions:
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&onsHnt/$ssHnt
DnG +,3$$
$uthorizDtion
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6tuGy )low &hDrt
7 7riDl
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3lDn
13
9isits 7DElH
7 7riDl
$GministrDtion
7.18 3uEliFDtion
3lDn
64

Protocol Number 
18 June 2021 - version DRAFT
/LVWRI7DEOHV
65

Protocol Number 
18 June 2021 - version DRAFT
5HIHUHQFHV
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