Parallel-Group, Randomized-Controlled Trial of Navigation Vs Usual Care for The Management of Delays and Racial Disparities Starting Adjuvant Therapy in Adults With Surgically-Managed, Locally Advanced HNSCC (NDURE 2.0)
Phase: NA
Conditions: Squamous Cell Carcinoma of Head and Neck
Sponsor: Medical University of South Carolina

N D U R E 2. 0  
 
Versi o n 7 . 0  
Pr ot oc ol # 1 0 3 1 6 1  
 
3 0  Dece m ber  2 0 2 3  
 
A Si n gle -Site, P ar allel -Gr o u p, R a n d o mize d -C o ntr olle d 
Tri al of N a vi g ati o n Vers us Us u al C are f or T he 
M a n a ge me nt of Del a ys a n d R aci al Dis p arities St arti n g 
P ost o per ati ve R a di ati o n T her a p y i n A d ults wit h 
S ur gic all y -M a n a ge d, L oc all y A d v a nce d He a d a n d 
Nec k S q u a m o us Cell C arci n o m a ( N D U R E 2. 0)  
 
 
Pr ot oc ol N u m ber: 1 0 3 1 6 1  
 
N ati o n al Cli nic al Tri al ( N C T) I de ntifi e d N u m ber s:  N C T 0 4 0 9 8 4 5 8  ( Si n gle-
Ar m N D U R E Feasi bilit y St u d y) a n d N C T 0 4 0 3 0 1 3 0  ( R C T of N D U R E vs U C) 
 
Pri nci p al I n vesti g at or:  E va n Gra b o yes, M D , M P H 
 
S p o ns or: H olli n gs Ca ncer Ce nt er  
 
Gr a nt Title: I m pr o vi n g t he Ti m eli ness a n d E q uit y of A dj u va nt T her a p y F oll o wi n g 
S ur ger y f or Hea d a n d Nec k Ca ncer  
 
G r a nt N u m ber: K 0 8  C A 2 3 7 8 5 8  
 
F u n de d b y: N CI  
 
V ersi o n N u m ber:  v. 7 . 0  (3 0  Dece m ber 2 0 2 3 )  
 
 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
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Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
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C O N F I D E N TI A LI T Y S T A T E M E N T  
T his  d oc u me nt is c o nfi de ntial c o m m u nic ati o n. Ac c e pta nce of t his d oc u me nt c o nstit utes a gre e me nt b y t he 
r e ci pie nt t hat n o u n p u blis he d i nf or mati o n c o ntai ne d herei n will be p u blis he d or discl ose d wit h o ut pri or 
a p pr o val of t he Pri nci pal I n vesti gat or or ot her partici pati n g st u d y le a ders hi p a n d as c o nsiste nt wit h t he NI H 
ter ms of a war d. 
 
 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
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Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
3  
T A B L E O F C O N T E N T S  
Ta ble of C o nte nts  
C O N FI D E N TI A LI T Y S T A T E M E N T  ........................................................................................................... 2  
T A B L E O F C O N T E N T S  .............................................................................................................................. 3  
S T A T E M E N T O F C O M P LI A N C E  .............................................................................................................. 6  
I N V E S TI G A T O R’ S SI G N A T U R E ............................................................................................................... 7  
1  
P R O T O C O L S U M M A R Y  ................................................................................................................. 8  
1. 1  
S y n o psis  .................................................................................................................................... 8  
1. 2  
S c he ma  ................................................................................................................................... 1 0  
1. 2. 1  
N D U R E Fe asi bilit y St u d y  
1 0  
1. 2. 2  
R C T of N D U R E Vers us Us ual Care  
1 0  
1. 3  
S c he d ule of Acti vities ............................................................................................................. 1 1  
2  
I N T R O D U C TI O N ............................................................................................................................ 1 4  
2. 1  
St u d y Rati o nale  ...................................................................................................................... 1 4  
2. 2  
Ba c k gr o u n d ............................................................................................................................. 1 4  
2. 2. 1  
He a d a n d Nec k S q ua m o us Cell Carci n o ma  
1 4  
2. 2. 2  
Dela ys i n Ca ncer Care Deli ver y f or Patie nts wit h H N S C C  
1 4  
2. 2. 3  
Barriers t o Ti mel y, E q uita ble P O R T After S ur ger y f or H N S C C  
1 5  
2. 2. 4  
I nter ve nti o ns t o I m pr o ve Ti mel y, E q uita ble P O R T f or Patie nts wit h H N S C C 1 5  
2. 2. 5  
Rati o nale f or Patie nt Na vi gati o n t o I m pr o ve Ti mel y, E q uita ble P O R T  
1 5  
2. 3  
Ris k/ Be nefit Assess me nt  ........................................................................................................ 1 5  
2. 3. 1  
K n o w n P ote ntial Ris ks  
1 5  
2. 3. 2  
K n o w n P ote ntial Be nefits  
1 6  
2. 3. 3  
Assess me nt of P ote ntial Ris ks a n d Be nefits  
1 6  
3  
O BJ E C TI V E S A N D E N D P OI N T S  ................................................................................................. 1 8  
4  
S T U D Y D E SI G N  ............................................................................................................................. 2 0  
4. 1  
N D U R E Fe asi bilit y St u d y  ...................................................................................................... 2 0  
4. 1. 1  
O verall Desi g n  
2 0  
4. 1. 2  
S cie ntific Rati o nale f or St u d y Desi g n  
2 0  
4. 1. 3  
E n d -of -St u d y Defi niti o n  
2 0  
4. 2  
R C T of N D U R E Vers us Us ual Care  ...................................................................................... 2 0  
4. 2. 1  
O verall Desi g n  
2 0  
4. 2. 2  
S cie ntific Rati o nale f or St u d y Desi g n  
2 0  
4. 2. 3  
J ustific ati o n f or I nter ve nti o n 
2 1  
4. 2. 4  
E n d -of -St u d y Defi niti o n  
2 2  
5  
S T U D Y P O P U L A TI O N  .................................................................................................................. 2 2  
5. 1  
I ncl usi o n Criteria .................................................................................................................... 2 2  
5. 2  
E xcl usi o n Criteria  ................................................................................................................... 2 3  
1.  
S elf -i de ntifie d His pa nic et h nicit y..................................................................................................... 2 3  
5. 3  
Lifest yle C o nsi derati o ns  ......................................................................................................... 2 3  
5. 4  
S cre e n Fail ures  ....................................................................................................................... 2 3  
5. 5  
Strate gies f or Recr uit me nt a n d Rete nti o n ............................................................................... 2 3  
6  
S T U D Y I N T E R V E N TI O N  .............................................................................................................. 2 5  
6. 1  
St u d y I nter ve nti o n A d mi nistrati o n  ......................................................................................... 2 5  
6. 1. 1  
St u d y I nter ve nti o n Descri pti o n  
2 5  
6. 1. 2  
A d mi nistrati o n a n d/ or D osi n g  
3 1  
6. 2  
Fi delit y  .................................................................................................................................... 3 1  
6. 2. 1  
I nter ve nti o nist Tr ai ni n g a n d Tr ac ki n g 
3 1  
6. 3  
Meas ures t o Mi ni mize Bias: Ra n d o mizati o n a n d Bli n di n g  .................................................... 3 2  

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6. 4  
St u d y I nter ve nti o n/ E x peri me ntal Ma ni p ulati o n A d here nce  ................................................... 3 2  
6. 5  
C o nc o mita nt T hera p y  ............................................................................................................. 3 2  
6. 5. 1  
Resc ue T hera p y  
3 2  
7  
S T U D Y I N T E R V E N TI O N DI S C O N TI N U A TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L  ................................................................................................... 3 2  
7. 1  
Disc o nti n uati o n of St u d y I nter ve nti o n/ E x peri me ntal Ma ni p ulati o n  ...................................... 3 2  
7. 2  
Partici pa nt Disc o nti n uati o n/ Wit h dra wal fr o m t he St u d y  ....................................................... 3 2  
7. 3  
L ost t o F oll o w -U p  .................................................................................................................. 3 3  
8  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  ........................................................................... 3 3  
8. 1  
S cre e ni n g Pr oce d ures  ............................................................................................................. 3 3  
8. 2  
Baseli ne Assess me nts  ............................................................................................................. 3 3  
8. 2. 1  
De m o gra p hic  
3 3  
8. 2. 2  
Cli nic al a n d O nc ol o gic  
3 4  
8. 2. 3  
Ris k of P O R T Dela y  
3 4  
8. 2. 4  
C ult ural Assess me nt  
3 4  
8. 3  
N o n -Baseli ne Cli nic al C hara cteristics  .................................................................................... 3 4  
8. 4  
E n d p oi nt a n d Ot her N o n -Saf et y Assess me nts  ........................................................................ 3 4  
8. 4. 1  
Fe asi bilit y Assess me nts  
3 4  
8. 4. 2  
Ac ce pta bilit y Assess me nts  
3 5  
8. 4. 3  
Na vi gat or Casel oa d  
3 5  
8. 4. 4  
Effica c y Assess me nts  
3 5  
8. 4. 5  
Barrier t o Ti mel y P O R T Assess me nts  
3 6  
8. 4. 6  
Ca nc er Care Deli ver y Pr oc ess Assess me nts  
3 6  
8. 4. 7  
He alt h Be ha vi or C o nstr uct Assess me nts  
3 7  
8. 5  
A d verse E ve nts a n d S eri o us A d verse E ve nts  ......................................................................... 3 8  
8. 5. 1  
Defi niti o n of A d verse E ve nts  
3 8  
8. 5. 2  
Defi niti o n of S eri o us A d verse E ve nts  
3 8  
8. 5. 3  
Classific ati o n of a n A d verse E ve nt  
3 9  
8. 6  
U na ntici pate d Pr o ble ms .......................................................................................................... 4 0  
8. 6. 1  
Defi niti o n of U na ntici pate d Pr o ble ms  
4 0  
8. 6. 2  
U na ntici pate d Pr o ble ms Re p orti n g  
4 0  
9  
S T A TI S TI C A L C O N SI D E R A TI O N S  ............................................................................................. 4 1  
9. 1  
Statistic al H y p ot heses  ............................................................................................................. 4 1  
9. 1. 1  
Si n gle Ar m Fe asi bilit y St u d y  
4 1  
9. 1. 2  
R C T of N D U R E vers us Us ual Care  
4 1  
9. 2  
S a m ple Size Deter mi nati o n  .................................................................................................... 4 2  
9. 2. 1  
N D U R E Fe asi bilit y St u d y  
4 2  
9. 2. 2  
R C T of N D U R E Vers us Us ual Care  
4 2  
9. 3  
P o p ulati o ns f or A nal yses  ........................................................................................................ 4 3  
9. 4  
Statistic al A nal yses  ................................................................................................................. 4 4  
9. 4. 1  
Ge neral A p pr oa c h  
4 4  
9. 4. 2  
Missi n g Data  
4 4  
9. 4. 3  
A nal ysis of t he Pri mar y E n d p oi nt  
4 5  
9. 4. 4  
A nal ysis of t he Se c o n dar y E n d p oi nts  
4 5  
9. 4. 5  
Baseli ne Descri pti ve Statistics  
4 7  
9. 4. 6  
Pla n ne d I nteri m A nal yses  
4 7  
9. 4. 7  
S u b -Gr o u p A nal yses  
4 7  
9. 4. 8  
Ta b ulati o n of I n di vi d ual Partici pa nt Data  
4 7  
9. 4. 9  
E x pl orat or y A nal yses  
4 7  
1 0  
S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L C O N SI D E R A TI O N S  ................... 4 8  
1 0. 1  
Re g ulat or y, Et hic al, a n d St u d y O versi g ht C o nsi derati o ns  ..................................................... 4 8  

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1 0. 1. 1  
I nf or me d C o nse nt Pr oc ess 
4 8  
1 0. 1. 2  
St u d y Disc o nti n uati o n a n d Cl os ure  
4 8  
1 0. 1. 3  
C o nfi de ntialit y a n d Pri va c y  
4 9  
1 0. 1. 4  
F ut ure Use of St ore d S peci me ns a n d Data  
5 0  
1 0. 1. 5  
Ke y R oles a n d St u d y G o ver na nce  
5 0  
1 0. 1. 6  
S afet y O versi g ht  
5 0  
1 0. 1. 7  
Cli nic al M o nit ori n g  
5 0  
1 0. 1. 8  
Q ualit y Ass ura nce ( Q A) a n d Q ualit y C o ntr ol ( Q C)  
5 0  
1 0. 1. 9  
Data Ha n dli n g a n d Re c or d Kee pi n g  
5 1  
1 0. 1. 1 0  
Pr ot oc ol De viati o ns  
5 1  
1 0. 1. 1 1  
P u blic ati o n a n d Data S hari n g P olic y  
5 1  
1 0. 1. 1 2  
C o nflict of I nterest P olic y  
5 2  
1 0. 2  
A d diti o nal C o nsi derati o ns  ...................................................................................................... 5 2  
1 0. 3  
A b bre viati o ns a n d S pecial Ter ms  ........................................................................................... 5 2  
1 0. 4  
Pr ot oc ol A me n d me nt Hist or y  ................................................................................................. 5 4  
1 1  
R E F E R E N C E S  ................................................................................................................................. 5 7  
 
 
 

N D U R E 2. 0  
 
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Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
6  
S T A T E M E N T O F C O M P LI A N C E  
T he trial will be c o n d ucte d i n a c c or da nc e wit h I nter nati o nal C o u ncil o n Har m o nisati o n G o o d Cli nic al 
Pr a ctic e (I C H G C P), a p plic a ble U nite d States ( U S) C o de of Fe deral Re g ulati o ns ( C F R), a n d t he Nati o nal 
Ca nc er I nstit ute ( N CI) Ter ms a n d C o n diti o ns of A war d. T he Pri nci pal I n vesti gat or ( PI) will ass ure t hat n o 
de viati o n fr o m, or c ha n ges t o t he pr ot oc ol will ta ke plac e wit h o ut pri or a gree me nt fr o m t he f u n di n g a ge nc y 
a n d d oc u me nte d a p pr o val fr o m t he I nstit uti o nal Re vie w B oar d (I R B),  a n d t he I n vesti gati o nal Ne w Dr u g 
(I N D) or I n vesti gati o nal De vice E xe m pti o n (I D E) s p o ns or, if a p plic a ble, e xc e pt w here ne cessar y t o 
eli mi nate a n i m me diate ha zar d(s) t o t he trial partici pa nts. All pers o n nel i n v ol ve d i n t he c o n d uct of t his 
st u d y ha ve c o m plete d H u ma n S u bje cts Pr ote cti o n a n d I C H G C P Tr ai ni n g.  
 
T he pr ot oc ol, Inf or me d c o nse nt f or m(s), recr uit me nt materials, a n d all partici pa nt materials will be 
s u b mitte d t o t he I R B f or re vie w a n d a p pr o val. A p pr o val of b ot h t he pr ot oc ol a n d t he c o nse nt f or m (s) m ust 
be o btai ne d bef ore a n y partici pa nt is c o nse nte d . A n y a me n d me nt t o t he pr ot oc ol will re q uire re vie w a n d 
a p pr o val b y t he I R B bef ore t he c ha n ges are i m ple me nte d t o t he st u d y. All c ha n ges t o t he c o nse nt f or m (s) 
will be I R B a p pr o ve d; a deter mi nati o n will be ma de re gar di n g w het her a ne w c o nse nt ne e ds t o be o btai ne d 
fr o m partici pa nts w h o pr o vi de d c o nse nt, usi n g a pre vi o usl y a p pr o ve d c o nse nt f or m. 
 
 

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I N V E S TI G A T O R’ S S I G N A T U R E  
T he si g nat ur e bel o w c o nstit utes t he a p pr o val of t his pr ot oc ol a n d pr o vi des t he ne cessar y ass ura nc es t hat 
t his st u d y will be c o n d ucte d a cc or di n g t o all sti p ulati o ns of t he pr ot oc ol, i ncl u di n g all state me nts 
r e gar di n g c o nfi de ntialit y, a n d a cc or di n g t o l oc al le gal a n d re g ulat or y re q uire me nts a n d a p plica ble U S 
f e der al re g ulati o ns a n d I C H g ui deli nes, as descri be d i n t he St ate me nt of C o m pli a nc e  a b o ve . 
 
Pri nci pal I n vesti gat or:  
 
Si g ne d:  
 
Date:  
5 /1 3 / 2 02 2  
 
Na me : E va n Gra b o yes 
 
Title : A Si n gle-Site, Parallel -Gr o u p, Ra n d o mize d -C o ntr olle d Trial of Na vi gati o n Vers us 
Us ual Care f or T he Ma na ge me nt of Dela ys a n d Ra cial Dis parities Starti n g P ost o perati ve 
Ra diati o n T hera p y i n A d ults wit h S ur gic all y -Ma na ge d, L oc all y A d va nc e d He a d a n d Nec k 
S q ua m o us Cell Carci n o ma ( N D U R E 2. 0)  
 
I n vesti gat or C o nta ct I nf or mati o n 
Affiliati o n: Me dic al U ni versit y of S o ut h Car oli na  
A d dr ess: 1 3 5 R utle d ge A ve n ue, M S C 5 5 0, C harlest o n, S C 2 9 4 2 5  
Tele p h o ne: ( 8 4 3) -7 9 2 -0 7 1 9  
E mail: gr a b oyes @ m usc.e d u  
 
 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
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Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
8  
1  
P R O T O C O L S U M M A R Y  
1. 1  
S Y N O P SI S  
 
Title:  
A Si n gle -Site, Parallel -Gr o u p, Ra n d o mize d -C o ntr olle d Trial of Na vi gati o n Vers us 
Us ual Care f or T he Ma na ge me nt of Dela ys a n d Ra cial Dis parities Starti n g 
P ost o perati ve Ra diati o n T hera p y i n A d ults wit h S ur gicall y -Ma na ge d, L ocall y 
A d va nce d Hea d a n d Ne c k S q ua m o us Cell Carci n o ma ( N D U R E 2. 0)  
Gr a nt # : 
K 0 8  C A 2 3 7 8 5 8  
St u d y 
Descri pti o n:  
I n t his st u d y, we e val uate t he fe asi bilit y, a cc e pta bilit y, preli mi nar y cli nic al i m pact, a n d 
preli mi nar y be ha vi oral i m pact of N D U R E ( Na vi gati o n f or Dis parities a n d U nti mel y 
Ra diati o n t h Er a p y), a  na vi gati o n -base d, 
m ultile vel i nter ve nti o n ( M L I) tar geti n g 
barriers t o ti mel y, g ui deli ne -a d here nt P O R T at t he pati e nt -, he alt hcare tea m-, a n d 
or ga nizati o n -le vels t o i m pr o ve ti mel y, e q uita ble p ost-o perati ve ra diati o n treat me nt 
( P O R T) a m o n g patie nts wit h He a d a n d Nec k S q ua m o us Cell Carci n o ma  ( H NS C C). 
W e h y p ot hesize t hat N D U R E will be fe asi ble, a cc e pta ble, i m pr o ve t he ti meli ness of 
P O R T f or w hite a n d A frica n A meric a n  ( A A) H NS C C patie nts a n d decrease dis parities 
i n dela y bet wee n t he t w o gr o u ps b y i m pr o vi n g m ulti -le vel he alt h be ha vi or c o nstr ucts. 
O bj ecti ves:  
 
Pri mar y O bje cti ve ( N D U R E fe asi bilit y st u d y):  
T o assess t he fe asi bilit y of N D U R E a m o n g w hite a n d A A H N S C C patie nts  wit h res pe ct 
t o a c cr ual. 
 
S e c o n dar y O bje cti ves ( N D U R E fe asi bilit y st u d y):  
1. T o assess t he fe asi bilit y of N D U R E a m o n g w hite a n d A A H N S C C patie nts wit h 
res pect t o N D U R E c o m pleti o n. 
2 . T o assess t he ac ce pta bilit y of N D U R E a m o n g H N S C C patie nts a n d pr o vi ders  
3 . T o c haracterize na vi gat or casel oa d a n d ti me all oc ati o n deli veri n g t he N D U R E 
i nter ve nti o n. 
4 . T o descri be t he preli mi nar y cli nical effic ac y of N D U R E o n dela ys starti n g P O R T 
a m o n g w hite a n d A A patie nts wit h H N S C C . 
 
Pri mar y O bje cti ve ( R C T of N D U R E vs Us ual Care):  
T o e val uate t he preli mi nar y cli nic al i m pact of N D U R E c o m pare d wit h us ual c are ( U C) 
o n dela ys starti n g P O R T a m o n g w hite a n d A A H N S C C patie nts . 
 
S e lect S ec o n dar y O bjecti ves ( R C T of N D U R E vs Us ual Care):  
1. T o e val uate t he preli mi nar y cli nic al i m pact of N D U R E c o m pare d wit h U C o n ti me-
t o-P O R T a m o n g w hite a n d A A H N S C C patie nts.  
2. T o e val uate t he preli mi nar y cli nic al i m pa ct of N D U R E c o m pare d wit h U C o n ra cial 
dis parities i n dela ys starti n g P O R T a m o n g w hite a n d A A H N S C C patie nts  
3 . T o e val uate t he preli mi nar y i m pa ct of N D U R E c o m pare d wit h U C o n c a nc er car e 
deli ver y pr oc esses.  
 
E x pl orat or y O bjecti ves ( R C T of N D U R E vs Us ual Care):  
1. T o e x pl ore t he preli mi nar y cli nic al i m pa ct of N D U R E c o m pare d wit h U C o n 
de cre asi n g barriers t o ti mel y P O R T. 
2 . T o e x pl ore t he preli mi nar y be ha vi oral me c ha nis m of a cti o n of N D U R E. 

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E n d p oi nt s: 
Pri mar y E n d p oi nt  ( N D U R E fe asi bilit y st u d y): 
N D U R E Accr ual Rate  
 
S e c o n dar y E n d p oi nt s ( N D U R E f easi bilit y st u d y): 
Na vi gat or Casel oa d  
Na vi gat or Ti me All ocati o n ( Dire ct)  
Na vi gat or Ti me All ocati o n (I n dire ct)  
Patie nt S atisfacti o n wit h t he I nter pers o nal Relati o ns hi p wit h t he Na vi gat or Sc ale  
P O R T dela y  
 
Pri mar y E n d p oi nt ( R C T of N D U R E vs Us ual Care) : 
P O R T d ela y 
 
S elect S ec o n dar y E n d p oi nts  ( R C T of N D U R E vs Us ual Care): 
Ti me -t o-P O R T I nitiati o n  
Tr e at me nt Pac ka ge Ti me  
 
Pre -S ur gic al ra diati o n c o ns ultati o n  
Pre -Ra diati o n thera p y d e ntal e xtracti o ns  
Ti me fr o m sur ger y t o P O R T referral 
Ti me fr o m s ur ger y t o p ost o perati ve a p p oi nt me nt wit h ra diati o n o nc ol o g y  
St u d y 
P o p ul ati o n:  
T he st u d y p o p ulati o n will c o nsist of patie nts 1 8 years of a ge or ol der, male a n d 
fe male se x, a n d self-i de ntifie d w hite a n d A A rac e, wit h l oc all y a d va nc e d H N S C C  
u n der g oi n g c urati ve i nte nt s ur ger y f oll o we d b y P O R T  wit h or wit h o ut c o nc urre nt 
c he m ot hera p y . 
P h ase /St a ge:  
N/ A  
Descri pti o n of 
Sit es:  
T he st u d y will be c o n d ucte d, a n d partici pa nts e nr olle d, at t he Me dic al U ni versit y of 
S o ut h Car oli na ( M U S C) H olli n gs Ca nc er Ce nter ( H C C) He a d a n d Ne c k T u m or Ce nter.  
Descri pti o n of 
St u d y 
I nt er ve nti o n: 
N D U R E is a na vi gati o n -base d, M LI tar geti n g barriers t o ti mel y, g ui deli ne -a d her e nt 
P O R T at t he patie nt -, he alt hcare te a m-, a n d or ga nizati o n -le vels t o de cre ase dela ys a n d 
ra cial dis parities starti n g g ui deli ne-a d here nt P O R T. N D U R E will be deli vere d fr o m 
s ur gic al c o ns ultati o n t o P O R T i nitiati o n ( ~ 3 m o nt hs). T he t hre e N D U R E na vi gati o n 
sessi o ns, w hic h are e x pe cte d t o ta ke 3 0-6 0 mi n utes  ea c h, will c oi nci de wit h t he 
pres ur gical c o ns ult, h os pital disc har ge, a n d 1 st p ost o perati ve cli nic visit, ti me p oi nts 
c h ose n t o facilitate case i de ntificati o n a n d c o or di nati o n a cr oss ke y care tra nsiti o ns.  
St u d y 
D u r ati o n:  
N D U R E F e asi bilit y: 7 m o nt hs  
N D U R E vs Us ual Care R C T: 4 2 m o nt hs  
P artici p a nt 
D u r ati o n:  
3 m o nt hs  
 
 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
1 0  
1. 2  
S C H E M A  
1. 2. 1  N D U R E  F E A SI BI LI T Y S T U D Y  
 
Fi g u r e 1. Fe asi bilit y St u d y S c h e m a.  F oll o wi n g c o m pleti o n of baseli ne q uesti o n naires, partici pa nts ( n = 1 5) 
will be e nr olle d i nt o N D U R E. Meas ures of feasi bilit y will be assesse d d uri n g i nter ve nti o n deli ver y. 
F oll o wi n g c o m pleti o n of t he N D U R E i nter ve nti o n, a c ce pta bilit y will be assesse d via val i date d me as ur es 
satisfa cti o n wit h patie nt na vi gati o n, a st u d y-s pecific pr o gra m e val uati o n, a n d se mi-str uct ure d i nter vie ws 
wit h patie nts a n d pr o vi ders. Preli mi nar y cli nic al effica c y of N D U R E o n dela ys starti n g P O R T will be 
descri be d.  
 
1. 2. 2  R C T  O F N D U R E  V E R S U S U S U A L C A R E  
 
 
 
Fi g u r e 2 . R C T  Sc he m a.  H N S C C  patie nts u n der g oi n g s ur ger y a n d P O R T will be e nr olle d i nt o a pil ot R C T 
c o m pari n g N D U R E t o us ual care t o e val uate t he preli mi nar y cli nical i m pa ct of N D U R E o n dela ys a n d 
r a cial dis parities starti n g P O R T after H N S C C  s ur ger y. 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
1 1  
 
1. 3  
S C H E D U L E O F A C TI VI TI E S  
 
T a ble 1. S c h e d ule of Acti vities f or N D U R E a n d Us u al C ar e: Sc r ee ni n g, Tr e at me nt, a n d F oll o w -
u p  
St u d y Peri o d  
Sc r e e ni n g  
All oc ati o n  
Tr e at me nt  
F oll o w -
U p  
 Visit L a bel  
Pr e
-O p  
Pr e
-
D/
C  
P ost
-
D/ C  
St art 
of 
P O R T  
E n d of 
P O R T  
 Visit #  
1  
-- 
2  
3 a , b 
4 c 
5 d 
6 e 
 St u d y Acti vit y  
 
 
 E nr oll me nt  
Eli gi bilit y Scree n  
X  
 
 
 
 
 
 
I nf or me d C o nse nt 
X  
 
 
 
 
 
 
 All oc ati o n  
All ocati o n  
 
X  
 
 
 
 
 
 St u d y  
I nter ve nti o n 
N D U R E  
 
 
X  
X  
X  
X  
 
Us ual Care  
 
 
X  
X  
X  
X  
 
 St u d y Assess me nts  
 
 B aseli ne  
De m o gra p hics  
X  
 
 
 
 
 
 
Baseli ne O nc ol o gic 
C haracteristics  
X  
 
 
 
 
 
 
C harls o n -De y o C o m or bi dit y 
I n de x 
X  
 
 
 
 
 
 
P O R T Dela y N o m o gra m  
X  
 
 
 
 
 
 
L u k wa g o C ult ural 
Q uesti o n naire  
X   
 
 
 
 
 
 S afet y  
A d verse E ve nts  
 
 
--------------------------------------
→ 
 
 Effic ac y  
S ur g ical Details 
 
 
 
X  
 
 
 
P O R T Start Date  
 
 
 
 
 
 
X  
 Fi d elit y  
N D U R E Fi delit y  
 
 
 
 
 
X  
 
 Fe asi bilit y  
N D U R E Accr ual  
X  
 
 
 
 
 
 
N D U R E C o m pleti o n  
 
 
X  
X  
X  
X  
 
Na vi gat or Casel oa d  
 
 
--------------------------------------
→ 
 
Na vi gat or Ti me All ocati o n  
 
 
X  
X  
X  
X  
 
 Ac ce pt a bilit y  
P S N -I Q uesti o n naire 
 
 
 
 
 
X  
 
S e mi -Str uct ure d I nter vie w  
 
 
 
 
 
X  
 
Pr o gra m E val uati o n 
Q uesti o n naire  
 
 
 
 
 
X  
 
B ar rie rs  
t o 
Ti m el y P O R T  
P B Q -Patie nt Q uesti o n naire  
 
 
X  
X  
X  
X  
 
P B Q -Na vi gat or  
 
 
X  
X  
X  
X  
 
Pres ur gic al R T C o ns ult  
 
 
 
 
 
 
X  
Pre -R T De ntal E xtra cti o ns  
 
 
 
 
 
 
X  

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
1 2  
T a ble 1. S c h e d ule of Acti vities f or N D U R E a n d Us u al C ar e: Sc r ee ni n g, Tr e at me nt, a n d F oll o w -
u p  
St u d y Peri o d  
Sc r e e ni n g  
All oc ati o n  
Tr e at me nt  
F oll o w -
U p  
 Visit L a bel  
Pr e
-O p  
Pr e
-
D/
C  
P ost
-
D/ C  
St art 
of 
P O R T  
E n d of 
P O R T  
 Visit #  
1  
-- 
2  
3 a , b 
4 c 
5 d 
6 e 
 St u d y Acti vit y  
 
 
C a n ce r C ar e 
Deli ve r y 
Pr ocesses  
Date Pat h ol o g y Re p ort 
Ret ur ne d  
 
 
 
 
 
 
X  
Date of P ost o perati ve Referral 
t o Ra diati o n O nc ol o g y 
 
 
 
 
 
 
X  
Date of P ost o p A p p p oi nt me nt  
wit h Ra diati o n O nc ol o g y  
 
 
 
 
 
 
X  
Date of C T Si m ulati o n  
 
 
 
 
 
 
X  
A dj u v a nt 
T h e r a p y 
Det ails  
T y pe of A dj u va nt T hera p y  
 
 
 
 
 
 
X  
P O R T C o m pleti o n Date  
 
 
 
 
 
 
X  
Ra diati o n a n d Me dic al 
O nc ol o g y Fa cilit y  
 
 
 
 
 
 
X  
He alt h 
Be h a vi or   
C o nstr u cts  
C T M -1 5  Q uesti o n naire  
 
 
 
X  
X  
 
 
I S E L-1 2 Q uesti o n naire  
X  
 
 
 
 
 
X  
P S Q Q uesti o n naire  
X  
 
 
X  
X  
 
 
I P Q-R C o nse q ue nces 
Q uesti o n naire  
X  
 
 
X  
X  
 
 
C A S E -Ca ncer  Q uesti o n naire  
X  
 
 
 
 
 
X  
A b br e vi ati o ns ; C A S E : C o m m u nic ati o n & Attit u di nal S elf-Effic a c y S cale; C T : C o m p ute d T o m o gra p h y; 
C T M -1 5 : Care Tr a nsiti o n Meas ures-1 5;  d : da ys; I P Q-R : Ill ness Perc e pti o n Q uesti o n naire-Re vise d; 
I S E L-1 2 : I nter pers o nal S u p p ort E val uati o n List-1 2; N D U R E : Na vi gati o n f or Dis parities a n d U nti mel y 
Ra diati o n T h Era p y;  P B Q : Perc ei ve d Barriers Q uesti o n naire; P O R T : P ost o perati ve Ra diati o n T hera p y; 
P S N -I: Patie nt Satisfa cti o n wit h t he I nter pers o nal Relati o ns hi p wit h t he Na vi gat or Sc ale; P S Q : Percei ve d 
S usc e pti bilit y; Q uesti o n naire;   R a d O n c : Ra diati o n t hera p y R T : Ra diati o n t hera p y 
a If t he disc har ge date is e x pecte d t o be > 2 1 da ys after s ur ger y, t he n c o m plete all St u d y Visit 3 
assess me nts (e xc e pt C T M -1 5) o n p ost o perati ve da y 2 1. If t he patie nt is u na ble t o c o m plete t he 
assess me nts o n p ost o perati ve da y 2 1 ( d ue t o me ntal stat us), t he n c o m plete o n t he 1 st da y after 
p ost o per ati ve da y 2 1 i n w hic h t he me ntal stat us all o ws c o m pleti o n of t he assess me nts.  If t he patie nt is 
s u bse q ue ntl y disc har ge d after p ost o p erati ve  da y 2 1, t he n t he C T M -1 5 c a n be c o m plete d o n t he ti me of 
disc har ge. If t he patie nt is ne ver disc har ge d pri or t o P O R T, t he n t he C T M -1 5 is o mitte d.  
 
b F or  patie nts u n der g oi n g tra ns oral r o b otic s ur ger y a n d sta ge d ne c k dissecti o n, St u d y Visit 3 assess me nts 
s h o ul d be c o m plete d after t he sec o n d h os pitalizati o n (re gar dless of t he or der of tra ns oral r o b otic s ur ger y 
a n d t he nec k disse cti o n). 
 
c If t he partici pa nt is ne ver disc har ge d fr o m t he h os pital p ost o perati vel y pri or t o starti n g P O R T , S t u d y 
V isit 4 i nter ve nti o n a n d assess me nts are o mitte d.  
 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
1 3  
T a ble 1. S c h e d ule of Acti vities f or N D U R E a n d Us u al C ar e: Sc r ee ni n g, Tr e at me nt, a n d F oll o w -
u p  
St u d y Peri o d  
Sc r e e ni n g  
All oc ati o n  
Tr e at me nt  
F oll o w -
U p  
 Visit L a bel  
Pr e
-O p  
Pr e
-
D/
C  
P ost
-
D/ C  
St art 
of 
P O R T  
E n d of 
P O R T  
 Visit #  
1  
-- 
2  
3 a , b 
4 c 
5 d 
6 e 
 St u d y Acti vit y  
 
 
d S t u d y Visit 5 assess me nts  are t o be a d mi nistere d after t he start of P O R T. F or t he p ur p oses of 
deter mi ni n g w he n t o a d mi nister St u d y Visit 5 assess me nts, t he  st u d y c o or di nat or will deter mi ne t hat a 
patie nt has starte d P O R T eit her b y verif yi n g i n t he E M R (f or patie nts u n der g oi n g P O R T at M U S C) or b y 
c o nta cti n g t he patie nt n o s o o ner t ha n 8 we e ks after s ur ger y (f or patie nts u n der g oi n g P O R T o utsi de of 
M U S C).   If P O R T is i n dic ate d b ut ne ver i nitiate d, St u d y Visit 5 assess me nts are t o be c o m plete d 1 2 
we e ks after s ur ger y.  
 
e F oll o wi n g c o m pleti o n of P O R T, t he st u d y c o or di nat or will gat her all of t he re q uire d s o urce 
d oc u me ntati o n t o ascertai n effica c y a n d ca ncer care deli ver y e n d p oi nts as well as a dj u va nt t hera p y details  

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
1 4  
 
2  
 
I N T R O D U C TI O N  
2. 1  
S T U D Y R A TI O N A L E  
H e a d a n d nec k s q ua m o us c ell c arci n o ma ( HN S C C ) is res p o nsi ble f or 1 4, 0 0 0 deat hs a n n uall y i n t he U S  a n d 
has p o or s ur vi val ( 5 0 % at 5 ye ars) des pite i nte nse tre at me nt i ncl u di n g s ur ger y, ra diati o n, a n d 
c he m ot hera p y 1. H N S C C  is als o a disease wit h si g nific a nt ra cial dis parities i n m ortalit y; Africa n A meric a ns 
( AA s) ha ve a 5 1 % relati ve decre ase i n s ur vi val c o m pare d wit h  w hites 2. Dela ys starti n g p ost o per ati ve 
r a diati o n t hera p y (P O R T ) after H N S C C  s ur ger y are a ke y dri ver of hi g h m ortalit y f or all H N S C C  patie nts 
a n d r acial dis parities i n s ur vi val f or A A s. As s uc h, t he deli ver y of ti mel y P O R T is a n a p pe ali n g t hera pe utic 
tar get t o a d dress b ot h iss ues3, 4. W e ha ve s h o w n t hat dela ye d, n o n-g ui deli ne -a d here nt P O R T i nitiati o n  ( > 6 
we e ks after s ur ger y 5) affects 5 6 % of H N S C C  patie nts 6, is 3 1 % m ore c o m m o n i n A A H N S C C  patie nts t ha n 
w hites 6, is ass ociate d wit h a n 1 1 % a bs ol ute de crease i n 5-ye ar s ur vi val 7, a n d is a ke y dri ver of ra cial 
diff ere nces i n m ortalit y 3. O ur pil ot q ualitati ve data s u g gest t hat tre at me nt t o xicit y, tra vel dista nce, c ar e 
c o or di nati o n, fi na nc es, s u p p ort, k n o wle d ge, a n d c o m m u nic ati o n are barriers t o ti mel y, e q uita ble P O R T. 
Deli veri n g ti mel y P O R T t o all H N S C C  patie nts is critic al t o pre ve nt e xcess m ortalit y a n d racial dis parities 
i n s ur vi val. U nf ort u natel y, effecti ve i nter ve nti o ns t o de cre ase dela ys a n d racial dis parities starti n g P O R T 
ar e u n k n o w n 8, 9, d ue i n part t o t he la c k of u n dersta n di n g of t he rele va nt barriers i n t his cli nic al setti n g. O ne 
p ote ntial str ate g y t o i m pr o ve ti mel y, e q uita ble P O R T is patie nt na vi gati o n ( P N), a barrier-f oc use d 
i nter ve nti o n t hat i m pr o ves t he ti meli ness a n d ra cial e q uit y of i nitial c a nc er c are (scre e ni n g, treat me nt 
i nitiati o n)1 0, 1 1. H o we ver, t he i m pa ct of P N o n dela ys a n d ra cial dis parities starti n g P O R T, a differe nt p oi nt 
o n t he c a nc er care c o nti n u u m t ha n scree ni n g a n d tre at me nt i nitiati o n, is u n k n o w n 1 2. I n t his pr o p osal, we 
e xte n d o ur w or k t o de vel o p a n d e val uate t he fe asi bilit y, a c ce pta bilit y, a n d preli mi nar y cli nic al i m pact of 
N D U R E  (N a vi gati o n f or D is parities a n d U nti mel y R a diati o n t h E ra p y), o ur m ulti-le vel, t he or y-base d P N 
i nter ve nti o n t o i m pr o ve ti mel y, e q uita ble P O R T a m o n g H N S C C  patie nts.  
 
2. 2  
B A C K G R O U N D  
2. 2. 1  H E A D A N D N E C K S Q U A M O U S C E L L C A R CI N O M A  
H N S C C, w hic h affects t he t o n g ue, p har y n x, lar y n x, a n d ne c k, is dia g n ose d i n 6 5, 0 0 0 patie nts i n t he U S 
a n n uall y a n d ca uses 1 4, 0 0 0 deat hs per year 1. N o scree ni n g tests e xist f or H N S C C, a n d as a res ult, m or e 
t ha n t w o-t hir ds of patie nts prese nt wit h l oc all y a d va nce d disease1. Des pite a g gressi ve m ulti m o dal t her a p y 
c o nsisti n g of s ur ger y f oll o we d b y  P O R T a n d c o nc urre nt c he m ot hera p y 5, o utc o mes re mai n p o or wit h o nl y 
5 0 % of patie nts wit h l ocall y -a d va nce d H N S C C s ur vi vi n g 5 ye ars 1. H N S C C is als o a disease wit h si g nific a nt 
r a cial dis parities i n m ortalit y; AA s wit h H N S C C ha ve a 1 9 % a bs ol ute decre ase i n 5 -year s ur vi val relati ve 
t o w hite H N S C C patie nts1 3 a n d a 5 1 % relati ve decre ase i n s ur vi val 2.  
 
2. 2. 2  D E L A Y S I N C A N C E R C A R E D E LI V E R Y F O R P A TI E N T S WI T H H N S C C  
Dela ys starti n g P O R T c o ntri b ute t o hi g h m ortalit y i n H N S C C a n d ra cial dis parities i n s ur vi val.  Dela ys i n 
c a ncer car e deli ver y are a ke y dri ver of m ortalit y f or H N S C C patie nts 1 4 a n d a s o urc e of racial dis parities i n 
s ur vi val f or AA s3. T he critic al ti me peri o d f or H N S C C patie nts is t he ti me fr o m s ur ger y t o t he start of 
P O R T 8, 1 5, t he o nl y as pect of ti mel y H N S C C c are i nc or p orate d i n Nati o nal C o m pre he nsi ve Ca nc er Net w or k 
( N C C N) G ui deli nes (<  6 we e ks after s ur ger y) 5. Dela ys starti n g P O R T are ass ociate d wit h i ncr ease d 
r e c urr e nc e a n d de cre ase d s ur vi val7, 1 6, 1 7. T he 1 1 % i m pr o ve d 5 -ye ar s ur vi val see n wit h ti mel y P O R T 7 is lar ge, 
c o m para ble i n ma g nit u de t o t he be nefit see n  fr o m a d di n g Cis plati n t o P O R T i n la n d mar k H N S C C trials1 8, 1 9. 
U nf ort u natel y, dela ys starti n g P O R T affe ct 5 6 % of H N S C C patie nts 6. Dela ys starti n g P O R T als o 
dis pr o p orti o natel y affe ct A A s, w h o are 3 1 % m ore li kel y t o e x perie nce dela ys t ha n w hites after a dj usti n g 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
1 5  
f or i ns ura nc e, i nc o me, e d uc ati o n, a n d sta ge6. T he hi g h rate of dela ye d P O R T a m o n g A A H N S C C patie nts 
is a s o urc e of pre ve nta ble m ortalit y a n d c o ntri b utes t o ra cial dis parities i n s ur vi val7. 
 
2. 2. 3  B A R RI E R S T O TI M E L Y, E Q UI T A B L E P O R T A F T E R S U R G E R Y F O R H N S C C  
T he barriers t hat c o ntri b ute t o dela ys a n d racial dis parities starti n g P O R T after H N S C C s ur ger y are 
u n k n o w n.  A A ra ce, i ns ura nce stat us, pr ol o n ge d tra vel dista nc e, a n d c are fra g me ntati o n are ass ociate d wit h 
dela ye d P O R T 6, 2 0 -2 2. H o we ver, t he barriers t o ti mel y care deli ver y at t he patie nt-, pr o vi der-, a n d s yste m-
le vel r e mai n u n k n o w n. As a res ult, t he de vel o p me nt of tar gete d, m ulti-le vel i nter ve nti o ns t o a d dress barriers 
a n d i m pr o ve t he deli ver y of ti mel y, e q uita ble P O R T f or H N S C C patie nts has bee n i m pe de d. T o pr e ve nt 
c o nti n ue d tr e at me nt dela ys, it is critic all y i m p orta nt t o i d e ntif y t he barriers t o deli veri n g ti mel y, e q uita ble 
P O R T.  
 
2. 2. 4  I N T E R V E N TI O N S T O I M P R O V E TI M E L Y, E Q UI T A B L E P O R T  F O R P A TI E N T S 
WI T H H N S C C  
T he c ar e deli ver y pat h wa y f or P O R T, w hic h is p ote ntiall y m o difia ble t hr o u g h a m ulti -le vel i nter ve nti o n, 
r e prese nts a n a p peali n g tar get t o de crease m ortalit y a n d ra cial dis parities i n s ur vi val f or H N S C C 
patie nts 3, 4, 8. U nf ort u natel y, des pite t he lar ge cli nical i m pa ct of dela ye d P O R T o n m ortalit y a n d r acial 
dis parities i n s ur vi val, n o effe cti ve i nter ve nti o ns ha ve be e n descri be d 8, 9, 2 3. A pri or st u d y usi n g a n 
at he oretic al, pr o vi der -c e ntric a p pr oa c h di d n ot fi n d a de cre ase i n t he rate of P O R T dela y 2 4. I m pr o vi n g t he 
ti meli ness of P O R T f or w hite a n d A A H N S C C patie nts is cr ucial t o i m pr o vi n g s ur vi val f or all H N S C C 
patie nts a n d decreasi n g racial dis parities i n m ortalit y.  
 
2. 2. 5  R A TI O N A L E F O R P A TI E N T N A VI G A TI O N  T O I M P R O V E TI M E L Y, 
E Q UI T A B L E P O R T  
P N is a patie nt -c e ntere d i nter ve nti o n t hat a d dresses barriers t o c a ncer care, t here b y i m pr o vi n g t he deli ver y 
of ti mel y, e q uita ble ca ncer scre e ni n g, de cr easi n g racial differe nces i n p ost -scre e ni n g dia g n ostic res ol uti o n, 
a n d de cre asi n g c are fra g me ntati o n 1 0, 1 1, 2 5 -2 7. H o we ver, t he effic ac y of P N i n t he se q ue ntial m ulti m o dal c a nc er 
c are setti n g (e. g. s ur ger y t he n P O R T) is u n k n o w n 1 2; c are tra nsiti o ns f oll o wi n g s ur ger y i n v ol ve u ni q ue c ar e 
barriers a n d care c o or di nati o n c halle n ges 2 8. T o a d dress t he la c k of effecti ve i nter ve nti o ns t o de crease dela ys 
a n d ra cial dis parities starti n g P O R T after H N S C C  s ur ger y 8, we will de vel o p a n d test N D U R E , o ur m ulti -
le vel, t he or y-base d P N i nter ve nti o n t o i m pr o ve ti mel y, e q uita ble P O R T a m o n g H N S C C  patie nts. T he 
u n derl yi n g scie ntific pre mise is t hat o ur N D U R E P N i nter ve nti o n has t he p ote ntial t o de crease dela ys 
starti n g P O R T a m o n g H N S C C  patie nts beca use P N is m ost effe cti ve i n 1)  p o p ulati o ns wit h l o w a d here nce 
r ates1 0 (ti mel y P O R T a d here nce is < 5 0 % o verall a n d < 4 0 % a m o n g 
AA s6); 2) ra cial 
mi n orit y 
p o p ulati o ns 1 0, 2 9 ( dela ys starti n g P O R T are 3 1 % m ore c o m m o n i n AA s6); a n d 3) t he setti n g of fra g me nte d 
c are 1 0, 2 7 ( P O R T deli ver y i n v ol ves c o or di nati n g c o ns ults wit h se ve n me dical s pecialties 2 3, care tra nsiti o ns 
fr o m i n patie nt t o o ut patie nt, a n d care tra nsiti o ns acr oss healt hc are s yste ms [i n 5 1 % of c ases 6]). 
 
2. 3  
RI S K/ B E N E FI T A S S E S S M E N T  
2. 3. 1  K N O W N  P O T E N TI A L RI S K S  
O verall, t his researc h st u d y p oses n o m ore t ha n mi ni m al ris ks t o partici pa nts. T here are n o p h ysic al, 
fi na ncial, le gal, s ocial, or c ult ural, ris ks t o t he st u d y partici pa nts b y j oi ni n g t his st u d y. T here are sli g ht 
ps yc h ol o gic al ris ks, as descri be d bel o w. T h ere is a sli g ht ris k t hat s u bje cts ma y e x perie nce a d verse 

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ps yc h ol o gic al re a cti o ns s uc h as a n xiet y or stress as a res ult of disc ussi n g iss ues relate d t o c a nc er or barriers 
t o c a ncer care. We belie ve t hat t his ris k is mi ni mal. We are usi n g s ur ve y ite ms t hat are c o m m o nl y use d i n 
cli nic al setti n gs a n d s u bjects are li kel y t o ha ve ha d pri or e x p os ure t o si milar t y pes of q uesti o ns as part of 
t heir me dic al care. F urt her m ore, i n o ur past st u dies wit h w hite a n d A A me n a n d w o me n wit h H N S C C, t he 
o ver w hel mi n g maj orit y of res p o n de nts ha ve sai d t he y f o u n d t he q uesti o ns t hat we ha ve as ke d relate d t o 
c are ha ve n ot be e n u psetti n g.  
 
T her e is als o a sli g ht ris k t hat c o nfi de ntial i nf or mati o n a b o ut t he partici pa nt ma y be a cci de ntall y discl ose d 
as st u d y partici pa nts ma y be as ke d t o pr o vi de i nf or mati o n c o nsi dere d c o nfi de ntial or pri vate d uri n g st u d y 
i nter vie ws. T he li keli h o o d of t his ris k is l o w as all t he i n vesti gat ors ha ve be e n i n v ol ve d i n si milar rese ar c h 
i n t he past a n d ha ve n ot e x perie nce d t his pr o ble m bef ore d ue t o a de q uate safe g uar ds. 
 
T he de cisi o n t o partici pate i n t his researc h will be v ol u ntar y a n d i n di vi d uals ma y ref use t o ta ke part or 
c h o ose t o st o p ta ki n g part at a n y ti me. Partici pa nts will als o be e nc o ura ge d t o ta ke t heir ti me w he n 
a ns weri n g q uesti o ns a n d ma y de cli ne t o a ns wer a n y  q uesti o n at a n y ti me. If patie nts bec o me u pset tal ki n g 
a b o ut t heir c a nc er a n d t he barriers t hat t he y fa ce d, t he y will be offere d a referral t o t he H olli n gs Ca nc er 
Ce nter ( H C C ) Be ha vi oral Me dici ne pr o gra m ( w hic h is c o vere d b y m ost he alt h i ns ura nc e pr o gra ms ) or t he 
H C C S ocial W or ker w h o will offer li n ks t o ot her H C C a n d c o m m u nit y res o urces.  
 
2. 3. 2  K N O W N P O T E N TI A L B E N E FI T S  
E xtra p olati n g fr o m data a b o ut P N i n ot her setti n gs, N D U R E ma y i m pr o ve t he ti meli ness of P O R T after 
H N S C C s ur ger y a n d decre ase ra cial dis parities i n ti mel y H N S C C c are. H o we ver, alt h o u g h we h y p ot hesize 
a dir ect be nefit t o partici pa nts i n t he N D U R E st u d y (i n ter ms of ti mel y H N S C C c are), it is u n k n o w n w het her 
patie nts will e x perie nce a direct be nefit.  Data ge nerate d fr o m t his st u d y are e x pe cte d t o pr o vi de be nefits t o 
s ociet y b y pr o vi di n g ne w k n o wle d ge a b o ut a practic al a n d scala ble strate g y f or a d dressi n g racia l dis parities 
i n t he ti meli ness of P O R T i n H N S C C patie nts. Be c a use ti mel y P O R T is ass ociate d wit h decrease d r ates of 
r e c urr e nc e a n d i m pr o ve d s ur vi val, it is e x pecte d t hat if we decre ase racial dis parities i n dela ys starti n g 
P O R T, w e will i m pr o ve s ur vi val a n d ra cial e q uit y i n o utc o mes.  
 
2. 3. 3  A S S E S S M E N T O F P O T E N TI A L RI S K S A N D B E N E FI T S  
T he decisi o n t o partici pate i n t his researc h will be v ol u ntar y. Partici pa nts will be i nf or me d t hat t he y c a n 
st o p partici pati n g at a n y ti me a n d/ or refrai n fr o m a ns weri n g a n y q uesti o ns t hat ma ke t he m u nc o mf orta ble. 
T he i nter vie wers are trai ne d rese arc hers wi t h e x perie nce c o n d ucti n g i nter vie ws relate d t o c a nc er. B y usi n g 
s ur ve y ite ms t hat are c o m m o nl y use d i n cli nic al setti n gs (t o w hic h s u bje cts ha ve li kel y ha d pri or e x p os ure 
as part of t heir me dical c are) we will mi ni mi ze ps yc h ol o gic al ris k. If a partici pa nt has a ps yc h ol o gic al 
a d verse e ve nt ( A E) tal ki n g a b o ut his/ her ca ncer a n d/ or t he barriers t hat he/s he fa c e d d uri n g treat me nt, t he 
partici pa nt will be offere d a referral t o t he H C C Be ha vi oral Me dici ne pr o gra m ( w hic h is c o vere d b y m ost 
he alt h i ns ura nce pr o gra m s) or t he H C C S ocial W or ker w h o will offer li n ks t o ot her H C C a n d c o m m u nit y 
r es o urc es as detaile d i n t he Data a n d S afet y M o nit ori n g Pla n. I m me diate ba c k u p a n d s u p p ort will be 
a vaila ble.   
 
T o hel p e ns ure a n d pr ote ct pri va c y of partici pa nts a n d c o nfi de ntialit y of researc h data f or t he st u d y, we will 
assi g n a u ni q ue st u d y I D n u m ber t o e ac h s u bje ct’s i nf or mati o n i n pla c e of his/ her na me a n d will la bel data 
c olle cti o n f or ms wit h t he I D n u m ber. All har d c o p y a n d el e ctr o nic files will be st ore d a p pr o priatel y usi n g 
d o u ble -l oc ke d met h o ds a n d pass w or d-pr otecti o n. O nl y t he st u d y te a m me m bers will ha ve a c cess t o st u d y 
r e c or ds. Partici pa nt data will be c olle cte d a n d rec or de d o n eit her a pass w or d-pr otecte d electr o nic data 
c a pt ure f or mat ( R E D Ca p) or pa per -base d f or ms de pe n di n g u p o n patie nt prefere nce. F or t he pa per c olle cti o n 
data met h o d, t he data c ollecti o n f or m will be la bele d o nl y wit h t he partici pa nt ’s u ni q ue st u d y I D n u m ber, 
a n d t he n st or e d wit hi n l oc ke d dra wers i n a l oc ke d office.  

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T he Inf or mati o n o n t hese pa per f or ms will be tra nsferre d t o a pass w or d -pr ote cte d R E D Ca p data base. A n y 
e x p orte d data f or a nal ysis will be de -i de ntifie d wit h all pri vatel y i de ntifia ble i nf or mati o n a ut o maticall y 
r e m o ve d. T he ke y li n ki n g s u bje ct I D n u m ber t o a n i n di vi d ual will be st ore d i n t he pass w or d pr otecte d 
R E D Ca p data base. T he a u di o re c or di n gs fr o m t he q ualitati ve i nter vie ws will be la bele d o nl y wit h t he 
patie nt’s u ni q ue st u d y I D a n d st ore d usi n g pass w or d -pr ote cte d files o nl y a cc essi ble b y t he st u d y tea m 
t hr o u g h pass w or d-pr otecte d ser vers. O nc e data ha ve bee n c olle cte d, o nl y de -i de ntifie d data will be e x p orte d 
f or a nal ysis. All st u d y pers o n nel will partici pate i n trai ni n g o n pr otecti n g t he pri va c y of st u d y partici pa nts 
a n d pers o nal i nf or mati o n will n ot be discl ose d t o a n y o ne o utsi de of t he researc h tea m. O nl y t he pri nci pal 
i n vesti gat or a n d st u d y staff partici pati n g i n data c olle cti o n or a nal ysis will ha ve a cc ess t o t he data. We ha ve 
n o pla n t o use la pt o ps, j u m p dri ves, C Ds/ D V Ds t o tra ns p ort data.  
 
O n t he w h ole, gi ve n t he mi ni mal ris ks t o t he st u d y partici pa nts a n d t he p ote ntial be nefit of t he researc h t o 
partici pa nts a n d s ociet y, we belie ve t hat t he p ote ntial re war d t o partici pa nts a n d s ociet y s u bsta ntiall y 
o ut wei g hs t he ris ks t o t he partici pa nts.

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3  
O B J E C TI V E S A N D E N D P OI N T S   
T a ble 2 . St u d y O bjecti ves a n d E n d p oi nts 
O BJ E C TI V E  
E N D P OI N T  
N D U R E F E A SI BI LI T Y S T U D Y  
Pri mar y  
T o assess t he fe asi bilit y of N D U R E a m o n g w hite a n d A A 
H N S C C patie nts wit h res pect t o a ccr ual . 
Perc e nt of eli gi ble partici pa nts w h o a ccr ue t o N D U R E ( Pri mar y E n d p oi nt)  
S e c o n dar y  
T o assess t he feasi bilit y of N D U R E a m o n g w hite a n d A A H N S C C 
patie nts wit h res pect t o N D U R E c o m pleti o n . 
Perc e nt of a ccr ue d partici pa nts w h o c o m plete N D U R E  
Perc e nt of a ccr ue d partici pa nts w h o c o m plete N D U R E st u d y assess me nts  
T o assess t he a c ce pta bilit y of N D U R E t o w hite a n d A A H N S C C 
patie nts a n d H N S C C pr o vi ders . 
P S N -I sc ale  sc ore 
N D U R E Pr o gra m E val uati o n sc ale sc ore 
T o c hara cterize na vi gat or c asel oa d a n d ti me all oc ati o n deli veri n g 
t he N D U R E i nter ve nti o n. 
Na vi gat or c asel oa d  
Na vi gat or ti me all ocati o n ( d irect) 
Na vi gat or ti me all ocati o n ( in dir ect)  
Na vi gat or ti me all ocati o n (total)  
T o descri be t he preli mi nar y cli nic al effic ac y of N D U R E o n dela ys 
starti n g P O R T a m o n g w hite a n d A A  patie nts wit h H N S C C . 
P O R T d ela y 
Ra cial differe nc es i n P O R T dela y  
R C T of N D U R E V E R S U S U S U A L C A R E  
Pri mar y  
T o e val uate t he preli mi nar y cli nical i m pa ct of N D U R E c o m pare d 
wit h U C o n dela ys starti n g P O R T a m o n g w hite a n d A A H N S C C 
patie nts . 
P O R T dela y , defi ne d per 
Nati o nal 
C o m pr e he nsi ve 
Ca nc er 
Net w or k 
G ui deli nes as t he i nitiati o n of P O R T > 6 we e ks ( 4 2 da ys) f oll o wi n g defi niti ve 
s ur ger y f or H N S C C. 
S e c o n dar y  
T o e val uate t he preli mi nar y cli nic al i m pact of N D U R E c o m pare d 
wit h U C o n ti me-t o-P O R T  a m o n g w hite a n d A A H N S C C 
patie nts.  
Ti me -t o-P O R T i nitiati o n , defi ne d as t he n u m ber of da ys fr o m t he date of 
defi niti ve s ur ger y f or H N S C C t o t he date of i nitiati o n of P O R T . 
Tr e at me nt pa c ka ge ti me, defi ne d as t he n u m ber of da ys fr o m t he date of 
defi niti ve s ur ger y f or H N S C C t o t he date of P O R T c o m pleti o n.  
T o e val uate t he preli mi nar y cli nic al i m pact of N D U R E c o m pare d 
wit h U C o n ra cial dis parities i n dela ys starti n g P O R T a m o n g 
w hite a n d A A H N S C C patie nts.  
P O R T dela y , defi ne d per Nati o nal C o m pr e he nsi ve Ca ncer Net w or k 
G ui deli nes as t he i nitiati o n of P O R T > 6 we e ks ( 4 2 da ys) f oll o wi n g 
defi niti ve s ur ger y f or H N S C C . 
Ti me -t o-P O R T i nitiati o n , defi ne d as t he n u m ber of da ys fr o m t he date of 
defi niti ve s ur ger y f or H N S C C t o t he date of i nitiati o n of P O R T . 

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T a ble 2 . St u d y O bjecti ves a n d E n d p oi nts 
O BJ E C TI V E  
E N D P OI N T  
Tr e at me nt pa c ka ge ti me, defi ne d as t he n u m ber of da ys fr o m t he date of 
defi niti ve s ur ger y f or H N S C C t o t he date of P O R T c o m pleti o n.  
T o e val uate t he preli mi nar y i m pa ct of N D U R E c o m pare d wit h 
U C o n c a ncer c are deli ver y pr oc esses.  
Pre -s ur gical ra diati o n c o ns ultati o n, defi ne d as t he atte n da nc e b y t he patie nt 
at a c o ns ultati o n wit h t he treati n g r a diati o n o nc ol o gist pri or t o s ur ger y t o 
disc uss ra diati o n t hera p y i n t he defi niti ve or a dj u va nt setti n g. 
Pre -R T de ntal e xtra cti o ns , defi ne d as t he e xtra cti o n of i n dic ate d 
c ari o us/ n o n -rest ora ble te et h pri or t o or d uri n g defi niti ve s ur ger y. 
Ti me fr o m s ur ger y t o P O R T referral, defi ne d as t he ti me, i n da ys, fr o m t he 
date of t he defi niti ve s ur gical pr oce d ure t o t he date t he r eferral ( or 
p ost o perati ve a p p oi nt me nt) is plac e d t o disc uss a dj u va nt t her a p y wit h t he 
tre ati n g ra diati o n o nc ol o gist. 
Ti me fr o m s ur ger y t o p ost o per ati ve a p p oi nt me nt wit h r a diati o n o nc ol o g y, 
defi ne d as t he ti me, i n da ys, fr o m t he date of t he defi niti ve s ur gic al 
pr oc e d ure t o t he date t hat the patie nt atte n ds a p ost o per ati ve a p p oi nt me nt 
wit h ra diati o n o nc ol o g y  
E x pl orat or y  
T o e x pl or e t he preli mi nar y i m pact of N D U R E c o m pare d wit h U C 
o n c o m pleti o n of a dj u va nt t hera p y  
P O R T d ur ati o n, defi ne d as t he n u m ber of da ys fr o m t he i nitiati o n of P O R T 
t o t he c o m pleti o n of P O R T a m o n g patie nts w h o c o m plete t he i nte n de d 
c o urse of a dj u va nt t hera p y. 
C o m pleti o n of i nte n de d c o urse of P O R T, defi ne d as rec ei pt of t he pla n ne d 
P O R T d ose (t otal G y)  
T o e x pl or e t he preli mi nar y cli nic al i m pa ct of N D U R E c o m pare d 
wit h U C o n de creasi n g barriers t o ti mel y P O R T.  
Perc e nt of t otal barriers o n P B Q t hat are r es ol ve d  
N u m ber of u nres ol ve d barriers o n P B Q  
Re as o n f or P O R T dela y  
T o e x pl or e t he preli mi nar y be ha vi oral me c ha nis m of a cti o n of 
N D U R E.  
 
C T M -1 5 scale sc ore  
C ha n ge fr o m baseli ne i n  
•  
I S E L-1 2 scale sc ore  
•  
Perc ei ve d S usce pti bilit y sc ale sc ore  
•  
I P Q-R C o nse q ue nc es sc ale sc ore  
•  
C A S E -Ca ncer sc ale sc ore  

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4  
S T U D Y D E S I G N  
4. 1  
N D U R E F E A SI BI LI T Y S T U D Y  
4. 1. 1  O V E R A L L D E SI G N  
W e will c o n d uct a si n gle -site, si n gle-ar m, n o n -bli n de d trial of N D U R E t o assess its fe asi bilit y , e val uate its 
a c ce pta bilit y a n d c haracterize t he preli mi nar y cli nic al effic a c y of N D U R E as a n i nter ve nti o n t o decre ase 
dela ys a n d r acial dis parities starti n g P O R T i n a d ults wit h s ur gic all y -ma na ge d, l oc all y a d va nce d H N S C C  
( n = 1 5; A A n = 5; w hite n = 1 0). 
4. 1. 2  S CI E N TI FI C R A TI O N A L E F O R S T U D Y D E SI G N  
T he si n gle -ar m st u d y desi g n was c h ose n t o e val uate t he fe asi bilit y a n d a cc e pta bilit y of t he N D U R E 
i nter ve nti o n. Q uesti o n naires t o be use d i n t he R C T will be c olle cte d as descri be d i n t he S c he d ule of 
Acti vities ( S O A ; S ecti o n 1. 3 ) t o assess t he feasi bilit y of d ata c olle cti o n pr oce d ures a n d m o nit or c o m pleti o n 
r ates. P ost-i nter ve nti o n, patie nts will c o m plete vali date d me as ures of P N a cc e pta bilit y. Q ualitati ve w or k 
wit h patie nts a n d pr o vi ders will hel p refi ne N D U R E. O ur i nter disci pli na r y te a m will c o ns ult wit h our 
scie ntific a d vis or y b oar d a n d c o m m u nit y a d v oc ac y gr o u p t o i nter pret t he data a b o ut t he fe asi bilit y a n d 
a c ce pta bilit y of N D U R E t o refi ne recr uit me nt, rete nti o n, a n d t he c o nte nt, f or mat, ti mi n g, a n d deli ver y of 
N D U R E f or t he pla n ne d R C T. We c o nsi dere d ot h er st u d y desi g ns t hat i n v ol ve ra n d o mizati o n. Alt h o u g h 
s uc h a st u d y desi g n w o ul d all o w us t o e val uate feasi bilit y of e nr oll me nt w he n t here is a c o ntr ol gr o u p o pti o n 
( a n d t h us r e as o ns f or st u d y decli ne), it w o ul d dil ute t he sa m ple size t here b y mi ni mizi n g t he a m o u nt of 
i nf or mati o n gai ne d a b o ut fe asi bilit y of a c cr ual t o t he i nter ve nti o n ne c essar y bef ore pr oce e di n g t o t he R C T. 
I n a d diti o n, si nc e t he c o ntr ol gr o u p i n t he R C T is U C , ra n d o mizi n g patie nts t o U C i n t he fe asi bilit y a n d 
a c ce pta bilit y st u d y w o ul d n ot a d d usef ul i nf or mati o n a b o ut t he ac ce pta bilit y of t he c o ntr ol t o t he c o ntr ol 
gr o u p be y o n d w hat is alre a d y k n o w n fr o m re ce nt cli nic al e x perie nc e i n t his setti n g.  
 
4. 1. 3  E N D -O F -S T U D Y D E FI NI TI O N  
T he e n d of t he st u d y is defi ne d relati ve t o c o m pleti o n of t he e n d of st u d y assess me nts f oll o wi n g t he start of 
P O R T as  s h o w n i n t he S o A (S ecti o n 1. 3 ). 
 
4. 2  
R C T O F N D U R E V E R S U S U S U A L C A R E  
4. 2. 1  O V E R A L L  D E SI G N  
W e will c o n d uct a si n gle -site, n o n -bli n de d, parallel -gr o u p, R C T of N D U R E v ers us us ual c are  f or t he 
ma na ge me nt of dela ys a n d racial dis parities starti n g P O R T i n a d ults wit h s ur gic all y -ma na ge d, l oc all y 
a d va nce d H N S C C . T he st u d y is desi g ne d t o test t he f oll o wi n g h y p ot heses: 1) N D U R E will res ult i n a l o wer 
r ate of dela ye d P O R T relati ve t o us ual c are  ( pri mar y o bje cti ve) a n d 2) N D U R E will res ult i n a s maller 
diff ere nce i n P O R T dela y bet we e n A A a n d w hites relati ve t o us ual c are  (sec o n dar y o bjecti ve). T he 
statistic al pla n f or t his bet wee n-gr o u p desi g n a nal yzes t he s u peri orit y of N D U R E relati ve t o us ual c are , 
alt h o u g h o u r p o wer a nal ysis is c alc ulate d wit h α = 0. 1 a n d 1 –  β = 0. 8 base d o n t he desire t o e m p hasize 
p o wer o ver t y pe I err or at t his e arl y sta ge of de vel o p me nt (si n gle-site pil ot R C T ) t o e ns ure f oll o w-u p o n 
pr o misi n g i nter ve nti o ns.   
 
4. 2. 2  S CI E N TI FI C R A TI O N A L E F O R S T U D Y D E SI G N  

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
2 1  
W e c o nsi der e d alter nati ve st u d y desi g ns s uc h as a si n gle -ar m pil ot st u d y wit h c o m paris o n t o l oc al a n d 
nati o nal hist oric al c o ntr ol data. H o we ver, we c o nsi der t he R C T a s u peri or a p pr oa c h t o a si n gle -ar m trial 
c o m pari n g t o hist oric al c o ntr ol 3 0 bec a use t he R C T will all o w us t o de m o nstrate a n d pre cisel y me as ure t he 
c o ntr ol gr o u p, t here b y a v oi di n g sa m ple err or a n d case -mi x differe nces bet wee n t he si n gle -ar m a n d 
hist oric al c o ntr ol 3 1. As a res ult, t he R C T desi g n will pr o vi de us wit h m ore pre cise esti mates of t he eff ect 
size a n d sa m ple size of t he N D U R E i nter ve nti o n relati ve t o us ual c are  i n pre parati o n f or t he defi niti ve p hase 
III R C T3 2. Alt h o u g h met h o d ol o gic al c halle n ges (e. g. c o nta mi nati o n)3 3, will e xist fr o m r u n ni n g a si n gle-site 
R C T ( be c a use pr o vi ders will ha ve patie nts i n b ot h N D U R E a n d  us ual c are  c o nc urre ntl y), o ur gr o u p has 
e x perie nc e s uc cessf ull y c o n d ucti n g si n gle -site pil ot R C Ts 3 4, 3 5. Ot her gr o u ps testi n g P N ha ve si milarl y 
r e p orte d s uc cessf ul st u d y c o m pleti o n a n d a v oi da nce of si g nific a nt c o nta mi nati o n w he n st u d yi n g P N i n t he 
si n gle-ar m setti n g 1 0. 
 
W e als o c o nsi dere d alter nati ve c o m paris o n gr o u ps, i ncl u di n g a f or m of 
a cti ve c o ntr ol  a gai nst w hic h t o 
c o m pare N D U R E.  Us ual c are  is a m ore a p pr o priate c o m paris o n gr o u p t ha n acti ve c o ntr ol  be c a use  us ual 
c are  r e prese nts t he c urre nt sta n dar d f or t he ma na ge me nt of t his cli nic al sce nari o i n p o p ulati o n u n der st u d y. 
Li mitati o ns of c o m pari n g N D U R E t o  us ual c are  (i nstea d of a cti ve c o ntr ol ) i ncl u de t he p ote ntial t hat 
i m pr o ve me nts see n wit h N D U R E (relati ve t o us ual c are ) are d ue t o n o ns pecific effe cts i nste a d of ke y ‘ acti ve 
i n gr e die nts’ wit hi n t he N D U R E i nter ve nti o n. H o we ver, a sec o n dar y o bje cti ve of t he trial is t o e val uate t he 
pr eli mi nar y be ha vi oral mec ha nis m of acti o n of N D U R E. As s uc h, t he data t hat we will a nal yze re gar di n g 
u n derl yi n g be ha vi oral me c ha nis ms will hel p t o li mit t he c o nc er n a b o ut n o n -s pecific effe cts of t he N D U R E 
i nter ve nti o n. I n a d diti o n, gi ve n t he pil ot nat ure of t his trial, o ur g oal is t o ac hie ve s u peri or o utc o mes f or 
patie nts o ver a n d a b o ve sta n dar d of care; t heref ore,  us ual c are  is a re as o na ble a n d a p pr o priate c o m paris o n 
c o n diti o n 3 6. I n t he f ut ure, as we c o nti n ue t o assess a n d esta blis h t he effica c y of N D U R E i n lar ger trials, we 
will e x pl or e t he ‘a cti ve i n gre die nts’ relati ve t o a cti ve c o ntr ol t o better is olate t he mec ha nis ms u n derl yi n g 
its effic ac y. 
 
4. 2. 3  J U S TI FI C A TI O N F O R I N T E R V E N TI O N  
4. 2. 3. 1  J U S TI FI C A TI O N F O R T H E M O D E O F D E LI V E R Y  
P N is a patie nt -c e ntere d i nter ve nti o n t hat a d dresses barriers t o c a ncer care, t here b y i m pr o vi n g t he deli ver y 
of ti mel y, e q uita ble ca ncer scre e ni n g, de cr easi n g racial differe nces i n p ost -scre e ni n g dia g n ostic res ol uti o n, 
a n d decre asi n g c are fra g me ntati o n 1 0, 2 5 -2 7. Alt h o u g h te c h n ol o g y-e n ha nc e d i nter ve nti o ns are i ncreasi n gl y 
c o m m o n t o f acilitate care c o or di nati o n, P N at its he art is still a patie nt -c e ntere d i nter ve nti o n a n d is deli ver e d 
i n pers o n via fa ce t o fa ce i ntera cti o ns. Fa c e t o fac e i ntera cti o ns c a n u n d ul y b ur de n patie nts a n d res ult i n 
de cre ase d i nter ve nti o n a d here nc e. I n a d diti o n, fa c e t o fac e i ntera cti o ns are bei n g mi ni mize d t o pr o m ote 
patie nt a n d healt hc are w or ker safet y d uri n g  t he C O VI D-1 9 pa n de mic . 
 
T he preferre d met h o d f or deli veri n g N D U R E is fa ce t o fa ce. H o we ver, d ue t o c ha n ges i n he alt hc are deli ver y 
ne c essitate d b y C O VI D -1 9 pa n de mic, it is per missi ble f or t he N D U R E na vi gat or t o use a tele me dici ne 
vi de oc o nfer e nci n g platf or m f or N D U R E sessi o ns 1 or 3 (s t u d y visit 2 or 4). T he n u m ber, fre q ue nc y, a n d 
ti mi n g of i nter ve nti o n c o nta cts (see details i n S e cti o n 4. 2. 3. 2, J ustific ati o n f or N u m be r, Fre q u e n c y, a n d 
Ti mi n g of I nter ve nti o n C o nt acts ) were caref ull y c h ose n t o mi ni mize p ote ntial c o nc er ns t hat ma y arise 
fro m f ac e t o fa ce i nteracti o ns . I n a d diti o n, s u p ple me ntal c o nta ct be y o n d t he t hree prescri be d sessi o ns will 
oc c ur wit h a fre q ue nc y a n d m o dalit y (e. g. te xt messa ge, e mail, etc.) dictate d b y patie nt a n d na vi gat or ne e d.  
 
4. 2. 3. 2  J U S TI FI C A TI O N F O R N U M B E R , F R E Q U E N C Y , A N D TI MI N G O F 
I N T E R V E N TI O N C O N T A C T S 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
2 2  
T he t hr ee N D U R E sessi o ns, w hic h are e x pecte d t o ta ke 3 0 -6 0 mi n utes e ac h, will c oi nci de wit h t he 
pr es ur gical c o ns ult, h os pital disc har ge, a n d 1 st p ost o perati ve cli nic visit. T hese ti me p oi nts were c h ose n t o 
f a cilitate c ase i de ntific ati o n ( pre o perati vel y; Visit 2) a n d c o or di nati o n acr oss ke y c are tra nsiti o ns  fr o m 
i n patie nt t o o ut patie nt stat us at t he ti me of h os pital dis c har ge (i n patie nt; Visit 3) a n d fr o m s ur gical t o 
r a diati o n a n d me dical o nc ol o g y s pecialties ( p ost-disc har ge; Visit 4) . T hese ti me p oi nts als o pr o m ote t he 
f e asi bilit y of N D U R E deli ver y as ne arl y 1 0 0 % of patie nts atte n d t hese t hre e visits ( des pite tra vel dista nc e-
r elate d barriers3 7) si nce patie nts 1) c a n n ot ha ve s ur ger y wit h o ut t heir pres ur gical c o ns ult; 2) are h os pitalize d 
p ost o per ati vel y; a n d 3) ret ur n f or t he 1 st p ost o perati ve visit f or drai n/t u be re m o val.  T he n u m ber of 
i nter ve nti o n c o ntacts is j ustifie d b y t he ne e d t o f oc us t he i nter ve nti o n t o ke y tra nsiti o ns of c are as descri be d 
a b o ve. 
 
4. 2. 4  E N D -O F -S T U D Y D E FI NI TI O N  
Patie nts will be f oll o we d f or c olle cti o n of pri mar y ( P O R T dela y) a n d sec o n dar y (e. g., T T P, P O R T d urati o n, 
a n d tr eat me nt pa c ka ge ti me) f or o ne ye ar ( 3 6 5 da ys) fr o m t he date of s ur ger y.  
 
5  
S T U D Y P O P U L A TI O N  
5. 1  
I N C L U SI O N C RI T E RI A  
I n or der t o be eli gi ble t o partici pate i n t his st u d y, a n i n di vi d ual m ust me et all of t he f oll o wi n g criteria: 
 
Patie nt a n d disease c hara cteristics  
1.  A ge >  1 8 years  at t he ti me of scre e ni n g 
2.  S elf -i de ntifie d w hite or A A ra ce  
3.  C yt ol o gic all y or pat h ol o gic all y c o nfir me d  S C C ( or hist ol o gic varia nt)  of t he oral ca vit y, 
or o p har y n x  ( p 1 6 p ositi ve, ne gati ve, or u n k n o w n), h y p o p har y n x, lar y n x, u n k n o w n pri mar y, 
par a nasal si n uses, or  nasal ca vit y . 
a. I n sit uati o ns i n w hic h t he patie nt f ulfills all ot her i ncl usi o n criteria, b ut t he bi o ps y s h o ws 
S C C i n -sit u or m o derate/se vere d ys plasia ( wit h o ut defi niti ve e vi de nc e of i n vasi ve S C C), 
b ut t he patie nt is sc he d ule d t o u n der g o c urati ve i nte nt s ur ger y  b y t he tre ati n g o nc ol o gic 
s ur ge o n d ue t o cli nic al s us pici o n of i n vasi ve S C C, t he dia g n osis of S C C -i n sit u or 
m o derate/se vere d ys plasia is s ufficie nt t o f ull t he pat h ol o gi c dia g n osis e nr oll me nt criteri o n.  
4.  A merica n J oi nt C o m mitte e o n Ca nc er ( AJ C C) cli nic al sta ge gr o u pi n g III -I V ( 8t h e diti o n) f or 
patie nts wit h S C C of  t he oral ca vit y, p 1 6-ne gati ve or o p har y n x, h y p o p har y n x, lar y n x, para nasal 
si n uses, a n d nasal ca vit y; or AJ C C cli nic al sta ge gr o u pi n g III-I V ( 7t h e diti o n) f or patie nts wit h p 1 6 -
p ositi ve S C C  of t he or o p har y n x or u n k n o w n pri mar y . 
a. At scree ni n g, AJ C C cli nic al sta ge gr o u pi n g s h o ul d be deter mi ne d base d o n a c o m bi nati o n 
of p h ysic al e xa m, dia g n ostic e val uati o n wit h cr oss se cti o nal i ma gi n g of t he ne c k 
(c o m p uterize d t o m o gra p h y ( C T ) a n d/ or ma g netic res o na nc e i ma gi n g ( M RI )) a n d/ or 1 8-F -
fl u or o-de o x y gl uc ose p ositr o n e missi o n t o m o gra p h y ( F D G P E T) C T wit hi n 6 0 da ys  
b.  I n sit uati o ns i n w hic h t he patie nt f ulfills all ot her i ncl usi o n criteria b ut t he bi o ps y s h o ws 
S C C i n -sit u or m o derate/se vere d ys plasia ( wit h o ut defi niti ve e vi de nc e of i n vasi ve S C C), 
b ut w o ul d ot her wise ha ve a n a p pr o priate cli nical sta ge gr o u pi n g as defi ne d  i n criteri o n 5, 
t he dia g n osis of S C C-i n sit u or m o derate/se vere d ys plasia is s ufficie nt t o f ull t he sta gi n g 
e nr oll me nt criteri o n.  
5.  N o pri or e x p os ure t o ra diati o n t hera p y, wit h or wit h o ut c o nc urre nt c he m ot hera p y, f or treat me nt of 
H N S C C i n t he defi niti ve or a dj u va nt t hera p y setti n gs  
 
S ur ger y a n d a dj u va nt t hera p y  e li gi bilit y 
6.  Pla n f or c urati ve i nte nt s ur ger y at M U S C  

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
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Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
2 3  
a. At scre e ni n g, pla n f or c urati ve i nte nt s ur gic al resecti o n of t he H N S C C at M U S C m ust be 
de e me d li kel y b y t he treati n g s ur ge o n a n d/ or m ulti disci pli nar y t u m or b oar d, w hic h m ust 
i ncl u de a fell o ws hi p-trai ne d he a d a n d nec k o nc ol o gic s ur ge o n. 
7.  Pla n f or P O R T (at M U S C or n o n -M U S C) wit h or wit h o ut c o nc urre nt c he m ot hera p y f oll o wi n g 
c ur ati ve i nte nt s ur ger y 
a. At scre e ni n g, pla n f or a dj u va nt t hera p y f oll o wi n g c urati ve i nte nt s ur gic al resecti o n of t he 
H N S C C at M U S C m ust be dee me d li kel y b y t he treati n g s ur ge o n a n d/ or m ulti disci pli nar y 
t u m or b oar d, w hic h m ust i ncl u de a fell o ws hi p-trai ne d hea d a n d nec k o nc ol o gic s ur ge o n, 
base d o n t he cli nical e x pectati o n of at le ast o ne of t he f oll o wi n g a d verse feat ures o n fi nal 
pat h ol o gic e val uati o n: e xtra n o dal e xte nsi o n ( E N E), p T 3 or p T 4 pri mar y, N 1 or gr e ater 
n o dal disease, n o dal disease i n le vels I V or 
V, peri ne ural i n vasi o n ( P NI), or 
l y m p h o vasc ular i n vasi o n ( L VI). 
 
5. 2  
E X C L U SI O N C RI T E RI A  
A n i n di vi d ual w h o me ets a n y of t he f oll o wi n g criteria will be e xcl u de d fr o m partici pati o n i n t his st u d y:  
1.  S elf -i de ntifie d His pa nic et h nicit y 
2.  Pr ese nce of c o g niti ve i m pair me nt t hat precl u des partici pati o n  
3.  S y nc hr o n o us u ntre ate d mali g na nc y  
a. Patie nts wit h  k n o w n u ntre ate d i n d ole nt 
mali g na ncies (e. g. n o n -mela n o ma s ki n c a ncer , 
u ntre ate d C L L, micr o P T C, u ntre ate d pr ostate c a nc er ) at t he ti me of dia g n osis or t hat de vel o p 
d uri n g t he st u d y peri o d w o ul d n ot e xcl u de a patie nt fr o m t he st u d y  
 
 
5. 3  
LI F E S T Y L E C O N SI D E R A TI O N S  
N/ A  
 
5. 4  
S C R E E N F AI L U R E S  
S cre e n f ail ures are defi ne d as partici pa nts w h o c o nse nt t o partici pate i n t his st u d y b u t are n ot s u bse q ue ntl y 
assi g ne d t o t he st u d y i nter ve nti o n or e ntere d i n t he st u d y. I n di vi d uals w h o d o n ot me et t he criteria f or 
partici pati o n i n t his trial (scree n fail ure) be ca use of meeti n g o ne or m ore e xcl usi o n criteria will n ot be  
r escr e e ne d. 
 
5. 5  
S T R A T E GI E S F O R R E C R UI T M E N T A N D R E T E N TI O N  
Re cr uit me nt f or t he N D U R E 2. 0 trial will oc c ur usi n g a cli nic -base d a p pr oac h fr o m t he M U S C Hea d a n d 
Ne c k T u m or Ce nter, a hi g h -v ol u me ac a de mic H N S C C  pr o gra m at t he N CI -desi g nate d H olli n gs Ca nc er 
Ce nter. Rese arc h staff will use c a ncer c e nter re gistr y data, disc ussi o n wit h t he H N S C C  cli nic al te a m, a n d 
the ele ctr o nic me dical rec or d ( E M R) t o i de ntif y patie nts w h o me et st u d y i ncl usi o n criteria. Researc h staff 
will t he n r e vie w cli nic r osters t o i de ntif y eli gi ble patie nts w h o are sc he d ule d f or a n a p p oi nt me nt i n t he  He a d 
a n d Ne c k T u m or Ce nter. St u d y re cr uit me nt will be fa cilitate d t hr o u g h t he use of teste d, str uct ure d pr ot oc ols. 
C ha nita H u g hes -Hal bert, P h D has e vi de nc e d -base d strate gies t hat ha ve be e n s uccessf ull y e m pl o ye d t o 
r e cr uit A A c a nc er patie nts t o t hera pe utic trials. W e will als o use str uct ure d pr ot oc ols fr o m t he pri nci pal 
i n vesti gat or ( E va n Gra b o yes, M D, M P H) a n d c o-me nt or Kat heri ne Ster ba, P h D, M P H. T hese pr ot oc ols 
ha ve be e n s uccessf ull y e m pl o ye d a n d refi ne d f or cli nic -base d recr uit me nt of patie nts wit h H N S C C  t o 
partici pate i n be ha vi oral researc h d uri n g treat me nt peri o d s. Re cr uit me nt is e x pe cte d t o be e n ha nc e d b y t he 
a cti ve cli nical practic e of t he PI.  T he st u d y partici pa nts ma y i ncl u de patie nts of t he PI’s, b ut will n ot be 
e xcl usi vel y patie nts of t he PI. F or p ote ntial partici pa nts w here t he PI is n ot t he atte n di n g p h ysicia n a n d t he 
p ote ntial partici pa nt has n ot c o nse nte d t o partici pate i n researc h per E PI C, t he atte n di n g p h ysicia n f or t he 
patie nt will i ntr o d uc e t he st u d y t o t he p ote ntial partici pa nt. Ot her t h a n t he n otific ati o n of t he st u d y b y t he 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
2 4  
atte n di n g p h ysicia n f or p ote ntial trial partici pa nts, t he researc h tea m will n ot as k ot her cli nicia ns t o be 
i n v ol ve d i n re cr uit me nt. All of t he recr uit me nt will be ha n dle d b y t he st u d y c o or di nat or a n d tea m. 
 
F or t he f e asi bilit y st u d y, we pr o p ose t o a c cr ue 1 5 patie nts ( w hite, n = 1 0 a n d A A, n = 5) t o t he st u d y o ver 4 
m o nt hs. Base d o n data fr o m M U S C/ H C C f or 2 0 1 8, it is e x pe cte d t hat 1 2 5 patie nts/ year will be eli gi ble f or 
t he st u d y, of w h o m 2 2 % are e x pe cte d t o be A A  a n d 7 8 % are e x pecte d t o be w hite. D uri n g t he 4 -m o nt h 
a c cr ual peri o d, we w o ul d e x pect t o scre e n 4 1 patie nts, of w h o m 9 w o ul d be A A  a n d 3 2 w o ul d be w hite. 
Base d o n t he PI a n d st u d y te a m’s pri or e x perie nce re cr uiti n g a n d e nr olli n g f or si milar st u dies e m be d de d 
i nt o cli nic al c are, we a ntici pate t hat 6 0 % of eli gi ble patie nts will a c cr ue t o t his st u d y. Base d o n t his 6 0 % 
e x pe cte d a ccr ual rate, o ver t he c o urse of 4  m o nt hs, we w o ul d e x pe ct t o a c cr ue o ur tar get of n = 5 A A  patie nts 
( a n d o ver-a ccr ue w hite patie nts, n = 2 0). T h us, b y c o nser vati ve esti mates wit h o ver -sa m pli n g of AA , o ur 
a c cr ual tar get f or t he A A  s u b gr o u p ( n = 5) a n d o verall ( n = 1 5) a p pear hi g hl y feasi ble. 
 
F or t he R C T c o m pari n g N D U R E t o  us ual care , we n ote t hat o ur ac cr ual rate tar get of 6 0 %, b y w hic h we 
esta blis h t he fe asi bilit y of re cr uit me nt f or t his R C T, will h a ve be e n teste d i n t he pil ot si n gle -ar m fe asi bilit y 
st u d y. Refi ne me nts t o t he re cr uit me nt strate gies a n d st u d y ti meli ne, as descri be d bel o w, will oc c ur as 
ne e de d t o e ns ure t hat we a c hie ve o ur ac cr ual tar gets descri be d bel o w.  W e pr o p ose t o ac cr ue 7 5 patie nts t o 
e a c h ar m ( w hite, n = 5 0 a n d A A , n = 2 5) t o t he st u d y o ver 3 6 m o nt hs. Base d o n data fr o m M U S C/ HC C f or 
2 0 1 8, it is e x pe cte d t hat 1 2 5 patie nts/ ye ar will be eli gi ble f or t he st u d y, of w h o m 2 8 ( 2 2 %) are e x pe cte d t o 
be A A  a n d 9 7 ( 7 8 %) are e x pecte d t o be w hite. D uri n g t he 3 6 -m o nt h a ccr ual peri o d, we w o ul d e x pect t o 
scr ee n 3 7 5 patie nts, of w h o m 8 3 w o ul d be A A  a n d 2 9 2 w o ul d be w hite. Base d o n t he PI a n d st u d y te a m’s 
pri or e x perie nc e re cr uiti n g a n d e nr olli n g f or si milar st u dies e m be d de d i nt o cli nic al c are a n d t he feasi bilit y 
data gat here d fr o m t he si n gle -ar m pil ot of N D U R E , we a ntici pate t hat 6 0 % of eli gi ble patie nts will a c cr ue 
t o t his st u d y. Base d o n t his 6 0 % a c cr ual rate, o ver t he c o urse of 3 6 m o nt hs, we w o ul d e x pe ct t o a c cr ue 2 2 5 
patie nts ( 5 0 A A s a n d 1 7 5 w hite). T h us, b y c o nser vati ve esti mates wit h a p pr o priate o ver-sa m pli n g of A A s, 
o ur o verall a c cr ual tar ge t ( n = 1 5 0) a n d f or t he A A  ra cial s u b gr o u p ( n = 5 0) a p pe ar hi g hl y fe asi ble. If 
c o nti n ue d o pti mizati o n of e nr oll me nt a n d re cr uit me nt strate gies fails t o yiel d a n a ccr ual rate of 6 0 %, we 
will e xte n d t he d urati o n of t he st u d y a c cr ual be y o n d t he pla n ne d 3 6 m o nt hs b y a n a d diti o nal 6 m o nt hs ( a n d 
r e mai n wit hi n t he gra nt f u n di n g peri o d). If we e xte n d t he st u d y ti meli ne f or a c cr ual b y 6 m o nt hs t o 4 2 
m o nt hs i nste a d of 3 6 m o nt hs (a n d t h us scre e n 4 3 7 patie nts  [ 9 6 A A s] i nste a d of 3 7 5 [ 8 3 A A s]), we w o ul d 
o nl y ne e d a n ac cr ua l rate of 5 2 % a m o n g A A s t o a c hie ve o ur ra cial s u b gr o u p distri b uti o n of n = 5 0 (a n d a n 
a c cr ual r ate of 2 9 % a m o n g w hite H N S C C  patie nts). F or all of t he a b o ve reas o ns ( PI a n d tea m e x perie nce, 
f e asi bilit y testi n g, refi ne me nt of re cr uit me nt pr ot oc ols, a n d e xte nsi o n of re cr uit me nt peri o d), we are hi g hl y 
c o nfi de nt t hat we c a n a ccr ue o ur o verall a n d racial s u b gr o u p tar gets f or t he R C T . 
 
Be c a use we pla n t o e nr oll c o nsec uti ve patie nts f or t his cli nic -base d i nter ve nti o n, o ne p ote ntial c o nc er n 
r elates t o s yste matic, n o n-ra n d o m differe nc es bet we e n patie nts w h o partici pate i n N D U R E a n d patie nts 
w h o de cli ne t o partici pate. E nt h usiastic, he alt h -m oti vate d patie nts ma y e nr oll w hile mar gi nalize d, b ur de ne d 
patie nts w h o distr ust t he me dic al s yste m ma y prefere ntiall y de cli ne. Alter nati vel y, patie nts wit h fe w/ n o 
per cei ve d barriers ma y dis pr o p orti o natel y decli ne t he i nter ve nti o n d ue t o percei ve d la c k of n e e d w hile 
b ur de ne d patie nts partici pate be ca use of t he percei ve d ne e d. 
W hic he ver, if a n y, sit uati o n oc c urs, o ur 
a p pr oac h e ns ure t hat we will still be well p ositi o ne d be c a use we will c ollect i nf or mati o n a b o ut w hic h 
patie nts e nr oll/ de cli ne a n d t heir reas o ns f or e nr olli n g/ de cli ni n g t o hel p refi ne N D U R E f or f ut ur e 
disse mi nati o n.  
 
T hr e e str ate gies will be use d t o e ns ure rete nti o n of e nr olle d patie nts i n t he st u d y. First, s u p p orti ve a n d 
fr e q ue nt i nteracti o ns bet wee n t he partici pa nt a n d na vi gat or are e x pecte d t o occ ur t hr o u g h o ut N D U R E, 
w hic h s h o ul d hel p miti gate a gai nst rete nti o n pr o b le ms (f or t h ose i n t he N D U R E ar m). S e c o n d, we ha ve 
a c c o u nte d f or t he b ur de n of s ur ve ys/ q uesti o n naires w hile patie nts are o n tre at me nt t o e ns ure t hat t he 
e x pe cte d ti me c o m mit me nt fr o m s ur ve ys is reas o na ble a n d t hat t he st u d y i ntera cti o ns will be sc he d ule d a t 
a c o n ve nie nt ti me f or patie nts ( us uall y w hile at M U S C f or cli nic al care alrea d y). Fi nall y, re m u nerati o n will 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
2 5  
als o oc c ur o n a sc he d ule t hat is wei g hte d t o war ds pr o vi di n g t he maj orit y of t he c o m pe nsati o n at t he e n d of 
t he st u d y ti me peri o d. 
 
As a r es ult of t he af ore me nti o ne d t hree strate gies, r ete nti o n of s u bjects is e x pe cte d t o be hi g hl y fe asi ble. 
T he sc he d ule d ti me p oi nts of na vi gat or -partici pa nt i ntera cti o n (i nitial s ur gic al c o ns ultati o n, pri or t o h os pital 
disc har ge, first cli nic visit after h os pital disc har ge) were c h ose n be ca use t hese are sit uati o ns i n w hic h t he 
li keli h o o d of c o nta ct is ~ 1 0 0 %. Alt h o u g h c halle n ges wit h rete nti o n f or c a ncer st u dies d ue t o m ortalit y 
( o verall a n d disease-s pecific) a n d tre at me nt t o xicit y are p ote ntiall y pr o ble ma tic, we d o n ot t hi n k t hat t he y 
will li mit r ete nti o n i n t his fe asi bilit y st u d y of N D U R E. T he rate of o n -treat me nt m ortalit y ( d uri n g s ur ger y 
or a dj u va nt t hera p y) is q uite l o w ( < 5 %) a n d t he st u d y f oll o w -u p d oes n ot e xte n d past t he c o m pleti o n of 
t her a p y. T h us, la c k of rete nti o n d ue t o m ortalit y is n ot e x pe cte d t o be si g nific a nt. Tr e at me nt t o xicit y is 
p ote ntiall y a pr o ble m, as patie nts ma y n ot wa nt t o a ns wer s ur ve ys w hile u n der g oi n g treat me nt or c h o ose t o 
wit h dr a w d ue t o c o m peti n g treat me nt de ma n ds. We d o n ot e x pe ct t his t o be a pr o ble m, h o we ver, bec a use 
N D U R E will be i nte grate d i nt o r o uti ne cli nic al c are a n d t h us s h o ul d n ot cre ate a n e xcess ti me b ur de n f or 
patie nts. I n fa ct, it is li kel y t hat partici pati o n i n t he i nter ve nti o n, w hic h is e x pe cte d t o i m pr o ve c ar e 
c o or di nati o n a n d decrease barriers t o c are, will ma ke t his p ote ntial s o urc e of dr o p o ut less li kel y t ha n ot her 
i nter ve nti o n trials. Usi n g N D U R E t o a d dress i n di vi d ualize d barriers t o ti mel y H N S C C  tre at me nt is a 
si g nific a nt stre n gt h a n d i n n o vati o n of t he st u d y  a n d will li kel y als o i m pr o ve rete nti o n relati ve t o hist oric al 
r ates. 
 
6  
S T U D Y I N T E R V E N TI O N  
6. 1  
S T U D Y I N T E R V E N TI O N A D MI NI S T R A TI O N  
6. 1. 1  S T U D Y IN T E R V E N TI O N  D E S C RI P TI O N  
6. 1. 1. 1  N D U R E  
N D U R E is a na vi gati o n -base d, M LI tar geti n g barriers t o ti mel y, g ui deli ne -a d here nt P O R T at t he patie nt -, 
he alt hc ar e tea m -, a n d or ga nizati o n-le vels (Fi g u re 3 ). C o nsiste nt wit h best pra ctic es f or t he d e vel o p me nt 
a n d e val uati o n of c o m ple x i nter ve nti o ns, 3 8, 3 9 ke y N D U R E f u ncti o ns (t he i nter ve nti o n’s basic p ur p oses; i n 
b ol d) a n d sele cte d f or ms (s pecific i nter ve nti o n c o m p o ne nts/strate gies c ust o mize d t o l ocal c o nte xt ne cessar y 
t o c arr y o ut e ac h f u ncti o n) are descri be d bel o w. 
 
F u ncti o n 1 : N a vi g ate al o n g t h e c a nc er c are c o nti n u u m.  
P O R T -f oc use d n avi g ati o n e nc o u nters li nk e d t o c are tr a nsiti o ns. T here are t h ree ma n ualize d na vi gati o n 
e nc o u nters wit h t he N D U R E na vi gat or. E nc o u nters occ ur al o n g t he c a ncer c are c o nti n u u m a n d are li n ke d 
t o ke y c ar e tra nsiti o ns ( pres ur gic al c o ns ult, h os pital dis c har ge, p ost o perati ve cli nic visit). D uri n g e a c h 
e nc o u nter, t he N D U R E na vi gat or deli vers patie nt e d ucati o n a b o ut ti mel y P O R T, a d dresses c halle n ges wit h 
tr a ns p ortati o n, assesses barriers t o ti mel y P O R T, a n d creates or u p dates a n d i m ple me nts t he P O R T Care 
Pla n.  Dir e ct c o ntact bet we e n t he N D U R E na vi gat or a n d patie nt occ urs via t hree cli nic/ h os pital -base d, f ac e -
t o-f a ce N D U R E na vi gati o n e nc o u nters lasti n g 3 0-6 0 mi n utes eac h.  
 
F u ncti o n 2 : I m p r o ve p atie nt k n o wle d ge a b o ut G ui deli n es f or ti mel y P O R T a n d ass oci ate d c are 
p r ocesses.  
F or m: N D U R E P atie nt Res o urc e G ui de.  D uri n g e a c h of t he t hre e N D U R E na vi gati o n e nc o u nters, t he 
N D U R E na vi gat or  uses t he N D U R E Patie nt Res o urce G ui de t o (a) e d ucate patie nts +/ - care gi vers a b o ut 
N C C N G ui deli nes f or ti mel y P O R T; ( b) pr o vi de a pers o nalize d ris k -esti mate of P O R T dela y usi n g a 
vali date d n o m o gra m 4 0; (c) e x plai n t he o nc ol o gic c o nse q ue nc es of P O R T dela y; a n d ( d) descri be t he 
he alt hc ar e utilizati o n ste ps ne cessar y t o start P O R T (e. g. de ntal e val uati o n +/ - e xtracti o ns, C T si m ulati o n, 
etc). 4 1 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
2 6  
 
F u ncti o n 3 : Mi ni mize t he b u r d e n of tr a vel f or H N S C C c are.  
F or m: Tr av el S u p p ort Al o n g t he C o nti n u u m. T he na vi gat or pr o vi des patie nts +/ - c are gi vers wit h 
i nf or mati o n a b o ut tra vel res o urc es, offers tra vel assista nc e t hr o u g h c o m m u nit y-base d pr o gra ms, a n d 
pr o vi des tr a vel -ass ociate d fi na ncial s u p p ort.  Tra vel assista nc e ma y als o ta ke t he f or m of pr o visi o n of 
te m p or ar y h o usi n g (e. g. A meric a n Ca nc er S ociet y H o pe L o d ge) f or patie nts desiri n g c are at M U S C w h o 
c a n n ot tr a vel ba c k a n d f ort h dail y f or 6 we e ks of ra diati o n t hera p y.  
 
F u ncti o n 4 : I m pr o ve c o m m u nic ati o n b et we e n p atie nt a n d p r o vi d ers re g ar di n g i nte nti o ns a n d g o als 
f or ti mel y, g ui deli n e-a d h er e nt P O R T . 
F or m: St a n d ar dize d disc ussi o n of e x pe cte d i n dic ati o n f or P O R T a n d c h oice of r a di ati o n f acility at i niti al 
c o ns ult ati o n.  At t he i nitial s ur gical c o ns ultati o n, t he cli nicia n i nf or ms t he patie nt t hat base d o n his/ her 
cli nic al sta ge, it is e x pe cte d t hat treat me nt will i ncl u de a pac ka ge of s ur ger y a n d P O R T. At t his sa me cli nic al 
e nc o u nter, t he N D U R E na vi gat or fa cilitates a disc u ssi o n wit h t he patie nt a n d cli nicia n t o hel p t he patie nt 
de ci de at w hic h fa cilit y he/s he will rec ei ve P O R T . 
 
F u ncti o n 5 : E n h a n ce c o or di n ati o n of c are bet we e n h e alt h c ar e te a ms d u ri n g c ar e tr a nsiti o ns a n d 
a b o ut t re at me nt se q uel ae.  
F or m: N D U R E P O R T C are Pl a n. At e ac h na vi gati o n e nc o u nter, t he N D U R E na vi gat or me ets wit h t he 
patie nt, c ar e gi ver, a n d cli nicia ns t o ge ner ate (a n d u p date) a P O R T Care Pla n. T he N D U R E P O R T Care 
Pla n is a n E M R -base d d oc u me nt t hat (a) c a pt ures cli nic al fa ct ors a n d t he c are deli ver y pr oc es ses ne cessar y 
t o start P O R T; ( b) descri bes t he patie nt’s barriers t o ti mel y P O R T; a n d (c) d oc u me nts t he patie nt’s 
pers o nalize d Barrier Re d ucti o n Pla n.  
 
F u ncti o n 6 : Restr u ct ur e t h e or g a niz ati o n t o cl arif y r oles a n d res p o nsi bilities f or c ar e p r oc esses 
ass oci at e d wit h P O R T d eli ve r y t o a v oi d d u plic ati o n a n d g a ps i n c are.  
F or m: N D U R E N avi g at or  m ak es referr als a n d  sc he d ules a p p oi nt me nts t o o pti mize a d here nc e wit h k e y 
P O R T c are deliv ery pr ocess. T he N D U R E na vi gat or is assi g ne d s ole res p o nsi bilit y f or ma ki n g all P O R T -
r elate d ref errals (a n d sc he d uli n g a p p oi nt me nts) wit h  ra diati o n a n d me dic al o nc ol o g y, de ntistr y, a n d or al 
s ur ger y i n a ma n ner t hat o pti mizes a d here nc e t o t he f oll o wi n g c are deli ver y pr oc esses ass ociate d wit h 
ti mel y P O R T. 
( 1) Pri or t o s ur gic al resecti o n, t he patie nt has c o ns ultati o n wit h a ra diati o n o nc ol o gist at t he fa cilit y 
w here t he patie nt i nte n ds t o re c ei ve P O R T.  
 
( 2) Pri or t o s ur gic al rese cti o n, t he patie nt has a c o ns ultati o n wit h a de ntist a n d oral s ur ge o n (if 
i n dic ate d) a n d s u bse q ue ntl y u n der g oes e xtracti o n of i n dic ate d te et h at t he ti me of s ur gic al rese cti o n. 
 
(3 ) E n ga gi n g wit h t he pat h ol o gist if t he pat h ol o g y re p ort is n ot iss ue d b y p ost o perati ve da y 8 . U p o n 
r e cei pt of t he pat h ol o g y re p ort, pr o m ptl y c o m m u nic ati n g ke y pat h ol o gic fi n di n gs t o t he H N te a m 
t o f a cilitate f or mati o n of a pla n f or pat h ol o g y-directe d a dj u va nt t hera p y.  
 
( 4) Sc he d uli n g a p p oi nt me nts wit h ra diati o n o nc ol o g y +/- me dic al o nc ol o g y wit hi n 1 0 da ys of 
s ur ger y as dire cte d b y t he H N te a m. 
 
( 5) E ns uri n g t hat t he p ost o perati ve a p p oi nt me nt wit h ra diati o n o nc ol o g y is sc he d ule d wit hi n 1 0 
da ys of w he n t he referral was plac e d.   
 
F u ncti o n 7 : Tr ac k r efe rr als t o e ns ur e ti mel y sc he d uli n g of a p p oi nt me nts a n d p atie nt atte n d a nc e 
ac r oss fr a g me nte d h e alt h c ar e s yste ms . 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
2 7  
F or m: Referr al a n d a p p oi nt me nt tr acki n g t o e ns ure ti mely sc he d uli n g of a p p oi nt me nts a n d p atie nt 
atte n d a nc e.   T he N D U R E na vi gat or s yste matic all y tra c ks referrals or a p p oi nt me nts t o e ns ure t hat cli nic al 
e nc o u nters nec essar y f or P O R T are sc he d ule d i n a ti mel y fas hi o n b y pr o vi ders a n d atte n de d b y patie nts. 
T he N D U R E na vi gat or will atte m pt t o a dj ust a p p oi nt me nts t o e n ha nc e ti mel y P O R T a n d resc he d ule 
a p p oi nt me nts t hat are misse d b y patie nts or ne e d t o be alt ere d t o refle ct c ha n ges i n t he tre at me nt ti meli ne 
( e. g. h os pital rea d missi on). Referral tra c ki n g is d oc u me nte d i n a n E M R -base d patie nt ti meli ne.  
 
Fi g u r e 3:  N D U R E is a na vi gati o n -base d, m ultile vel i nter ve nti o n tar geti n g deter mi na nts of ti mel y, 
g ui deli ne -a d here nt P O R T f oll o wi n g s ur ger y f or he a d a n d ne c k s q ua m o us cell c arci n o ma wit h i nter ve nti o n 
c o m p o ne nts at t he patie nt (li g ht gre e n), he alt hcare te a m (li g ht bl ue), a n d or ga nizati o nal -le vels ( dar k bl ue) 
 
T he N D U R E i nter ve nti o n c o m p o ne nts descri be d  a b o ve are s u m marize d a n d c o ntraste d wit h Us ual Care i n 
T a ble 3. N D U R E is deli vere d b y a si n gle de dic ate d na vi gat or ac c or di n g t o t he N D U R E Ma n ual, w hic h 
o utli nes t he d uties ne c essar y f or o pti mal deli ver y. F oll o wi n g str uct ure d, e vi de nce -base d trai ni n g 4 2, 4 3, t he 
N D U R E na vi gat or is e m be d de d wit hi n t he H NS C C  s ur ger y tea m, partici pates i n we e kl y m ulti disci pli nar y 
t u m or b oar d, a n d c o or di nates wit h ot her te a ms i n v ol ve d i n P O R T deli ver y.  
6. 1. 1. 2  U S U A L C A R E  
T he pr ocesses of c are t hat defi ne us ual care f or t he i nitiati o n of P O R T are descri be d (a n d c o ntraste d wit h 
N D U R E) i n T a ble 3. U s ual care c o nsists of cli nic -base d, cli nicia n-le d disc ussi o n a b o ut t he healt hc are 
utilizati o n ste ps ne c essar y t o start P O R T. Us ual care  is n ot f or mall y t he or y-base d. T he H N S C C  n urse 
na vi gat or, a pers o n disti nct fr o m t he de dicate d N D U R E na vi gat or, pla ys a r ole i n deli veri n g us ual care (see 
T a ble 3 ). As part of us ual care, t he hea d a n d nec k  n urse na vi gat or i de ntifies a n d a d dress tre at me nt barriers 
pri or t o/ u p t o t he i nitial s ur gic al c o ns ultati o n. F oll o wi n g t he i nitial s ur gic al c o ns ultati o n, t he he a d a n d ne c k  
n urse na vi gat or d oes n ot c o nti n ue pr o vi di n g na vi gati o n ser vic es al o n g t he treat me nt c o nti n u u m. Si milar t o 
t he N D U R E na vi gat or, t he he a d a n d nec k  n urse na vi gat or is e m be d de d wi t hi n t he he a d a n d nec k  s ur ger y 
te a m a n d partici pates i n we e kl y m ulti disci pli nar y t u m or b oar d. Direct c o nta ct bet wee n t he hea d a n d ne c k  
N D U R E i s a N a vi g ati o n- B a se d, M ultil e v el I nt er v e nti o n T ar g eti n g B arri er s t o T i m el y, G ui d eli n e-A d h er e nt  
P o st o p er ati v e R a di ati o n T h er a p y F oll o wi n g S ur g er y f or H e a d a n d N e ck S q u a m o u s C ell C ar ci n o m a
D et er mi n a nt of T i m el y, G ui d eli n e-A d h er e nt P O R T
N D U R E I nt er v e nti o n C o m p o n e nt
P a tie n t e d u ca tio n  u sin g  
N D U R E  P a tie n t R e so u rce  
G u id e
N D U R E  P O R T  C a re  P la n
U n cle a r co m m u n ica tio n  b e tw e e n  
p a tie n t a n d  p ro v id e rs re g a rd in g  
in te n tio n s a n d  g o a ls fo r  tim e ly, 
g u id e lin e -a d h e re n t P O R T
In su f cie n t ca re  co o rd in a tio n  
b e tw e e n  h e a lth c a re  te a m s 
d u rin g  ca re  tra n sitio n s a n d  a b o u t 
tre a tm e n t se q u e la
E n v iro n m e n ta l R e stru ctu rin g
R e fe rra l tra ck in g  a n d  fo llo w -u p
T ra v e l b u rd e n  fo r ca n c e r ca re
A m b ig u ity  a b o u t p ro fe ssio n a l ro le  
a n d  id e n tity
T ra v e l su p p o rt
F ra g m e n ta tio n  o f ca re  a cro ss 
h e a lth ca re  o rg a n iza tio n s
L a ck  o f p a tie n t k n o w le d g e  a b o u t 
tim e ly, g u id e lin e -a d h e re n t P O R T  
a n d  a sso cia te d  ca re  p ro ce sse s; 
b e lie fs a b o u t P O R T  d e la y
S ta n d a rd ize d  p ro ce ss fo r in itia tin g  
d iscu ssio n  o f e x p e cta tio n  fo r P O R T
T e a m  
O rg a n iza tio n
P a tie n t
L e v e l
D e te rm in a n t o f T im e ly, G u id e lin e -A d h e re n t P O R T  
N D U R E  In te re n tio n  C o m p o n e n t

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n urse na vi gat or a n d t he patie nt oc c urs o nl y at t he ti me of i nitial i nta ke/ pre -s ur gic al c o ns ultati o n at t he 
M U S C Hea d a n d Nec k O nc ol o g y  cli nic. T hese c o nta cts ma y be o n t he tele p h o ne pri or t o (a n d i n pre parati o n 
f or t he i nitial c o ns ultati o n) a n d/ or fa ce-t o-fac e at t he ti me of t he i nitial s ur gic al c o ns ultati o n. T he ti me f or 
t hese na vi gati o n e nc o u nters is n ot pr oscri be d b ut is n ote d is ge nerall y re c or de d i n t he E M R. D uri n g t he 
i nta ke he a d a n d ne c k n urse na vi gat or  c o n d ucts a detaile d a n d c o m pre he nsi ve assess me nt of patie nt barriers 
u p o n r eferral t o t he M U S C cli nic.

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
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T a ble 3. N D U R E vs Us ual C are  
C o m p o ne nt                                         
N D U R E  
Us u al C are  
Cli nic al T o ol  
Na vi gati o n 
E nc o u nters  
P O R T -f oc us e d n a vi g ati o n e nc o u nters li n ke d t o c are tr a nsiti o ns. 
T here are t h ree ma n ualize d na vi gati o n e nc o u nters wit h t he N D U R E 
na vi gat or. E nc o u nters occ ur al o n g t he ca ncer care c o nti n u u m a n d are 
li n ke d t o ke y care tra nsiti o ns ( pres ur gical c o ns ult, h os pital dis c har ge, 
p ost o perati ve cli nic visit). D uri n g eac h e nc o u nter, t he N D U R E n a vi gat or 
deli vers patie nt e d ucati o n a b o ut ti mel y P O R T, a d dress es c halle n ges wit h 
tra ns p ortati o n, ass ess es barriers t o ti mel y P O R T, a n d creates or u p dates 
a n d i m ple me nts t he P O R T C are Pla n.  
O ne ge neric e nc o u nter u p o n i nt a ke. T here is o ne na vi gati o n 
e nc o u nter wit h t he hea d a n d nec k  n urs e na vi gat or. T he e nc o u nter 
occ urs u p o n referral t o t he M U S C Hea d a n d Nec k Cli nic. D uri n g 
t he na vi gati o n e nc o u nter, t he hea d a n d nec k  n urs e na vi gat or 
ass ess es barriers t o treat me nt a n d ma kes a p pr o priate referrals.  
Patie nt 
E d ucati o n   
N D U R E P atie nt Res o urce G ui de.  D uri n g eac h of t he t hree N D U R E 
na vi gati o n e nc o u nters, t he N D U R E na vi gat or  us es t he N D U R E Patie nt 
R es o urce G ui de t o (a) e d ucate patie nts +/ - care gi vers a b o ut N C C N 
G ui deli nes f or ti mel y P O R T; ( b) pr o vi de a pers o nalize d ris k -esti mate of 
P O R T dela y usi n g a vali date d n o m o gra m 4 0; (c) e x plai n t he o nc ol o gic 
c o ns e q ue nces of P O R T dela y; a n d ( d) des cri be t he healt hcare utilizati o n 
ste ps necess ar y t o start P O R T (e. g. de ntal e val uati o n +/- e xtracti o ns, C T 
si m ulati o n, etc). 4 1 
N/ A. T hr o u g h o ut t he c o urs e of treat me nt, t he hea d a n d nec k  n urs e 
na vi gat or d oes n ot pr o vi de a n y s pecific e d ucati o n a b o ut (a) N C C N 
G ui deli nes f or ti mel y P O R T; ( b) t he pre vale nce of P O R T dela ys; 
(c) t he o nc ol o gic c o ns e q ue nces of P O R T dela y; or ( d) t he 
healt hcare utilizati o n ste ps necessar y t o start P O R T (e. g. de nta l 
e val uati o n +/ - e xtracti o ns, C T si m ulati o n). Hea d a n d 
Nec k  
cli nicia ns (s ur ge o ns, ra diati o n o nc ol o gists, me dical o nc ol o gists, 
etc) 
ma y a d dress (a) t hr o u g h ( d) per t heir pers o nal practice 
patter ns.  
Tra vel S u p p ort  
T r a vel s u p p ort al o n g t he c o nti n u u m. Fr o m i nitial s ur gical c o ns ultati o n 
t hr o u g h i nitiati o n of P O R T (a n d at eac h care tra nsiti o n), t he N D U R E 
na vi gat or pr o vi des patie nts +/ - care gi vers wit h i nf or mati o n a b o ut tra vel 
res o urces, offers tra vel assista nce t hr o u g h c o m m u nit y-bas e d pr o gra ms, 
a n d pr o vi des tra vel -ass ociate d fi na ncial s u p p ort. Tra vel assista nce ma y 
als o ta ke t he f or m of pr o visi o n of te m p orar y h o usi n g (e. g. A merica n 
C a ncer S ociet y H o pe L o d ge) f or patie nts desiri n g care at M U S C w h o 
ca n n ot tra vel bac k a n d f ort h dail y f or 6 wee ks of ra diati o n t hera p y.  
T r a vel s u p p ort at i nt a ke f or t he s ur gic al c o ns ult ati o n. D uri n g 
t he i nta ke na vi gati o n e nc o u nter, t he hea d a n d nec k  n urs e na vi gat or 
pr o vi des patie nts +/ - care gi vers wit h i nf or mati o n a b o ut tra vel 
res o urces, offers tra vel assista nce t hr o u g h c o m m u nit y-base d 
pr o gra ms, a n d pr o vi des tra vel -ass ociate d fi na ncial s u p p ort 
s pecificall y t o facilitate atte n da nce at t he i nitial s ur gical 
c o ns ultati o n.  
Pr ocess  
f or 
Dis c ussi n g 
Nee d  
f or 
P O R T  
St a n d ar di ze d dis c ussi o n of e x pecte d i n dic ati o n f or P O R T a n d c h oice 
of r a di ati o n f acilit y at i niti al c o ns ult ati o n. At t he i nitial s ur gi cal 
c o ns ultati o n, t he cli nicia n i nf or ms t he patie nt t hat base d o n his/ her 
cli nical sta ge, it is e x pecte d t hat treat me nt will i ncl u de a pac ka ge of 
s ur ger y a n d P O R T. At t his s a me cli nical e nc o u nter, t he N D U R E 
na vi gat or facilitates a dis c u ssi o n wit h t he patie nt a n d cli nicia n t o hel p t he 
patie nt deci de at w hic h facilit y he/s he will recei ve P O R T.  
V ari a ble dis c ussi o n of e x pecte d i n dic ati o n f or P O R T wit h o ut 
dis c ussi o n of c h oice of r a di ati o n f acilit y at i niti al c o ns ult ati o n. 
At t he i nitial s ur gical c o ns ultati o n, t he cli nicia n ma y i nf or m t he 
patie nt t hat bas e d o n his/ her cli nical sta ge, it is e x pecte d t hat 
treat me nt will i ncl u de a pac ka ge of s ur ger y a n d P O R T. T he hea d 
a n d nec k  tea m d oes n ot dis c uss wit h t he patie nt t he c h oice of t he 
facilit y at w hic h t he patie nt will recei ve P O R T pri or t o s ur ger y. 
E M R 
d oc u me ntati o n  
N D U R E P O R T C are Pl a n.  At eac h na vi gati o n e nc o u nter, t he N D U R E 
na vi gat or meets wit h t he patie nt, care gi ver, a n d cli nicia ns t o ge nerate (a n d 
u p date) a P O R T C are Pla n. T he N D U R E P O R T C are Pla n is a n E M R -
N/ A . T hr o u g h o ut t he c o urs e of treat me nt, t here is n o de dicate d  
d oc u me ntati o n i n t he E M R a b o ut (a) cli nical fact ors a n d c are 

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bas e d d oc u me nt t hat (a) ca pt ures cli nical fact ors a n d t he car e deli ver y 
pr ocess es necess ar y t o start P O R T; ( b) des cri bes t he patie nt’s barriers t o 
ti mel y P O R T; a n d (c) d oc u me nts t he patie nt’s pers o nalize d B arrier 
R e d ucti o n Pla n.  
deli ver y pr ocess es necess ar y t o start P O R T; ( b) barriers t o ti m el y 
P O R T; or (c) pla ns t o a d dress barriers t o ti mel y P O R T.  
C are 
deli ver y 
pr oces ses 
N D U R E N a vi g at or is assi g ne d s ole res p o nsi bilit y f or m a ki n g ref err als 
a n d s c he d uli n g a p p oi nt m e nts t o o pti mi ze a d here nce 
wit h c are 
deli ver y pr ocess es ass oci ate d 
wit h ti m el y P O R T.   T he 
N D U R E 
na vi gat or is assi g ne d s ole res p o nsi bilit y f or ma ki n g all P O R T -relate d 
referrals (a n d s c he d uli n g a p p oi nt me nts) wit h  ra diati o n a n d me dical 
o nc ol o g y, de ntistr y, a n d oral s ur ger y i n a ma n ner t hat o pti mizes a d here nce 
t o t he f oll o wi n g care deli ver y pr ocess es ass ociate d wit h ti mel y P O R T.  
( 1) Pri or t o s ur ger y, t he patie nt has c o ns ultati o n wit h a ra diati o n 
o nc ol o gist at t he facilit y w here t he patie nt i nte n ds t o recei ve P O R T.  
 
( 2) Pri or t o s ur gical res ecti o n, t he patie nt has a c o ns ultati o n wit h a de ntist 
a n d oral s ur ge o n (if i n dicate d) a n d s u bs e q ue ntl y u n der g oes e xtracti o n of 
i n dicate d teet h at t he ti me of s ur gical res ecti o n. 
 
( 3) E n ga gi n g wit h t he pat h ol o gist if t he pat h ol o g y re p ort is n ot iss ue d b y 
p ost o perati ve da y 8. U p o n recei pt of t he pat h ol o g y re p ort, pr o m ptl y 
c o m m u nicati n g ke y pat h ol o gic fi n di n gs t o t he H N tea m t o facilitate 
f or mati o n of a pla n f or pat h ol o g y-directe d a dj u va nt t hera p y.  
 
( 4) Sc he d uli n g a p p oi nt me nts wit h ra diati o n o nc ol o g y +/- me dical 
o nc ol o g y wit hi n 1 0 da ys of s ur ger y as directe d b y t he H N tea m.  
 
( 5) E ns uri n g t hat t he p ost o perati ve a p p oi nt me nt wit h ra diati o n o nc ol o g y 
is s c he d ule d wit hi n 1 0 da ys of w he n t he referral was place d. 
V ari a ble r oles a n d res p o nsi bilities of He a d a n d Nec k  c are te a m 
m e m bers t o o pti mize a d here nce wit h c are deli ver y pr ocesses 
ass oci ate d 
wit h ti m el y P O R T.  A varia ble c o m bi nati o n of 
resi de nts o n t he i n patie nt hea d a n d nec k  s er vice a n d o ut patie nt 
a d va nce d practice pr o vi ders a n d n urs es ( b ut n ot t he hea d a n d nec k  
n urs e na vi gat or) are res p o nsi ble f or 
ma ki n g referrals a n d 
s c he d uli n g 
a p p oi nt me nts f or ra diati o n 
o nc ol o g y, 
me di cal 
o nc ol o g y, de ntal o nc ol o g y, a n d oral s ur ger y wit h o ut s pecific 
atte nti o n t o o pti mizi n g  a d here nce t o t he f oll o wi n g care deli ver y 
pr ocess es ass ociate d wit h ti mel y P O R T.  
R eferral  
a n d 
A p p oi nt me nt 
Trac ki n g  
Ref err al a n d a p p oi nt m e nt tr ac ki n g t o e ns ure ti m el y s c he d uli n g of 
a p p oi nt m e nts a n d p atie nt atte n d a nce .   T he N D U R E na vi gat or 
s yste maticall y trac ks referrals or a p p oi nt me nts t o e ns ure t hat cli nical 
e nc o u nters necessar y f or P O R T (e. g. ra diati o n a n d me dical o nc ol o g y, 
de ntistr y, a n d oral s ur ger y) are s c he d ule d i n a ti mel y fas hi o n b y 
pr o vi ders a n d atte n de d b y patie nts. T he N D U R E na vi gat or c o ntacts 
patie nts pri or t o P O R T -relate d a p p oi nt me nts t o pr o m ote atte n da nce, 
c o nfir ms atte n da nce at P O R T -relate d a p p oi nt me nts, a dj usts t he ti mi n g of 
a p poi nt me nts t o e n ha nce ti mel y P O R T, a n d resc he d ules a p p oi nt me nts 
t hat are miss e d b y patie nts or nee d t o be altere d t o reflect c ha n ges i n t he 
treat me nt ti meli ne (e. g. h os pital rea d missi o n). R eferral trac ki n g is 
d oc u me nte d i n a n E M R -base d patie nt ti meli ne.  
N/ A.  M e m bers of t he hea d a n d nec k o nc ol o g y  tea m (i ncl u di n g t he 
n urs e na vi gat or) d o n ot s yste maticall y trac k referrals or 
a p p oi nt me nts t o e ns ure t hat t he cli nical e nc o u nters necess ar y f or 
P O R T are s c he d ule d i n a ti mel y fas hi o n b y pr o vi ders, atte n de d b y 
patie nts, a dj uste d t o e n ha nce ti mel y P O R T, or re -sc he d ule d t o 
reflect c ha n ges i n t he treat me nt ti meli ne. 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
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3 1  
 
6. 1. 2  A D MI NI S T R A TI O N  A N D/ O R D O SI N G  
6. 1. 2. 1  N D U R E  
N D U R E will be deli vere d i n o ne -o n -o ne, fa ce -t o-fa ce sessi o ns bet we e n t he na vi gat or a n d t he partici pa nt i n 
a cli nic - or h os pital -base d setti n g. T he N D U R E i nter ve nti o n c o nsists of t hre e na vi gati o n e nc o u nters  ( St u d y 
Visits 2 -4) , w hic h are e x pe cte d t o ta ke 3 0-6 0 mi n utes ea c h. T he N D U R E na vi gati o n e nc o u nters  ( St u d y 
Visits 2 -4)  will c oi nci de wit h t he pres ur gic al c o ns ult, h os pital disc har ge, a n d 1 st p ost o perati ve cli nic visit  
(se e S ecti o n 1. 3, Sc he d ule of Acti vities ). T hese ti me p oi nts were  c h ose n t o fa cilitate c ase i de ntific ati o n 
a n d c o or di nati o n a cr oss ke y c are tra nsiti o ns. C o nta ct be y o n d t he t hree prescri be d sessi o ns will occ ur wit h 
a fre q ue nc y a n d m o dalit y (e. g. te xt messa ge, e mail, etc.) dictate d b y patie nt a n d na vi gat or ne e d. T he 
N D U R E i nter ve nti o n will deli vere d i n t he f oll o wi n g setti n gs: t he M U S C He a d a n d Ne c k T u m or Ce nter a n d 
M U S C h os pital.  A si n gle de dic ate d na vi gat or wit h n o c o m peti n g cli nic al or a d mi nistrati ve res p o nsi bilities 
o utsi de of t his trial will deli ver t he N D U R E  i nter ve nti o n. F ull d ose of t he N D U R E i nter ve nti o n will c o nsist 
of c o m pleti n g all t hree na vi gati o n sessi o ns.  Be ca use t he a d mi nistrati o n sc he d ule a n d d ose of  us ual care  is 
hi g hl y varia ble, t he N D U R E i nter ve nti o n will n ot be d ose -matc he d t o  us ual c are  o n i nte nsit y, d ur ati o n, 
a n d/ or fre q ue nc y. Partici pa nts i n t he trial are per mitte d t o i ntera ct 
wit h ot her partici pa nts after 
r a n d o mizati o n, re gar dless of tre at me nt all oc ati o n. S uc h e nc o u nters ma y occ ur i n waiti n g r o o ms bef or e or 
after cli nic a p p oi nt me nts g i ve n t he si n gle-site desi g n of t he trial. 
 
6. 1. 2. 2  U S U A L C A R E  
U C c o nsists of disc ussi o ns a b o ut t he i n dic ati o ns, ris ks/ be nefits/alter nati ve, G ui deli nes, ti mi n g, a n d 
l o gistic al details of a dj u va nt t hera p y. T hese disc ussi o ns will be a d mi n istere d a cc or di n g t o pra ctic e patter ns 
of t he i n v ol ve d pr o vi ders. As s uc h,  us ual c are  is e x pe cte d t o be varia ble i n t he n u m ber, fre q ue nc y, i nte nsit y, 
a n d d urati o n of visits a n d disc ussi o ns de dic ate d t o pla n ni n g a dj u va nt t hera p y, de pe n di n g u p o n t he patie nt, 
pr o vi der, c are gi ver, t u m or b oar d, a n d cli nical sce nari o. Us ual care  will be deli vere d  i n t he f oll o wi n g 
setti n gs: t he M U S C He a d a n d Ne c k T u m or Ce nter a n d M U S C h os pital.  N o de dic ate d i nter ve nti o nist will 
deli ver  us ual c are ; i nste a d a c o m bi nati o n of p h ysicia ns (atte n di n gs a n d resi de nts), n urse practiti o ners, a n d 
n urses fr o m t he rele va nt m ulti disci pli nar y s pecialties (s ur gic al, me dical, ra diati o n o nc ol o g y) at M U S C or 
a n o utsi de fa cilit y will all c o ntri b ute t o t hese disc ussi o n s. A d mi nistrati o n of  us ual care  will c o nsist of dir ect 
f a ce-t o-f ac e c o m m u nic ati o n a n d ot her met h o ds (e. g. tele p h o ne c all, e -mail c orres p o n de nce). T he fa ce -t o-
f a ce c o n versati o ns ca n occ ur d uri n g a str uct ure d cli nic al setti n g (e. g. cli nic visit) or m ore i nf or mal, n o n-
a p p oi nt me nt-base d ma n ner (e. g. i n patie nt r o u n ds).  Gi ve n t he varia bilit y i n e x pe cte d deli ver y of  us ual car e , 
t her e is n o n u m ber of sessi o ns t hat c o nstit ute “f ull-d ose ”. Be c a use t he a d mi nistrati o n sc he d ule a n d d ose of  
us ual c ar e  is hi g hl y varia ble, us ual care  will n ot be d ose -matc he d t o N D U R E o n i nte nsit y, d urati o n, a n d/ or 
fr e q ue nc y. H o we ver, t he t hre e cli nic al e nc ou nters at w hic h N D U R E will be deli vere d are cli nic al i n nat ure 
a n d t h us will li kel y c orrelate hi g hl y wit h  us ual c are . Partici pa nts i n t he trial are per mitte d t o i ntera ct wit h 
ot her partici pa nts after ra n d o mizati o n, re gar dless of tre at me nt all oc ati o n. S uc h e nc o u nters ma y oc c ur i n 
waiti n g r o o ms bef ore or after cli nic a p p oi nt me nts gi ve n t he si n gle -site desi g n of t he trial. 
 
6. 2  
FI D E LI T Y  
6. 2. 1  I N T E R V E N TI O NI S T T R AI NI N G A N D T R A C KI N G  
Be c a use t he o bje cti ves of t he pr ot oc ol de pe n d u p o n c o nsiste nt a d mi nistrati o n of t he N D U R E i nter ve nti o n, 
t he fi delit y of deli ver y will be m o nit ore d cl osel y. T he s pecific d uties ne cessar y t o e ns ure o pti mal 
a d mi nistr ati o n of N D U R E are detaile d i n t he N D U R E Na vi gat or Sta n dar d O perati n g Pr oc e d ure ( S O P ). T he 
na vi gat or, s u per vise d b y Dr. Gra b o yes, will ke e p a trac ki n g l o g wit h e nc o u nters ( n u m ber, m o dalit y of e a c h 

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sessi o n), ti me ( dire ct wit h patie nt, i n dire ct t o c o m plete t he B arrier R e d ucti o n P la n), barriers ( n u m ber, t y pe), 
a n d Barrier R e d ucti o n P la n a cti vit y (a cti o n, o utc o me) 4 4. N D U R E sessi o ns will be a u di o-re c or de d a n d 
r a n d o ml y sele cte d sessi o ns ( 2 0 %) will be re vie we d b y Dr. Gra b o yes t o e ns ure fi delit y. Bi-m o nt hl y c ase 
c o nf er e nc es wit h t he na vi gat or, Dr. Gra b o yes, a n d Dr. H u g hes -Hal bert will f urt her e ns ure c o nti n ue d hi g h -
q ualit y P N.  
 
6. 3  
M E A S U R E S T O MI NI MI Z E BI A S: R A N D O MI Z A TI O N  A N D B LI N DI N G  
Bias will be mi ni mi ze d t hr o u g h stratifie d sa m pli n g a n d a stratifie d ra n d o mize d per m ute d bl oc k desi g n. W e 
will use a str atifie d sa m pli n g a p pr oa c h t o ac hie ve a fi xe d sa m ple size f or A A patie nts ( n = 2 5 i n e a c h ar m) 
t o e ns ure t hat we 1) a c hie ve ra cial bala nc e bet we e n t he N D U R E a n d U C ar ms, a n d 2) o versa m ple A A 
r elati ve t o t heir fre q ue nc y i n t he st u d y p o p ulati o n. O versa m pli n g A As is ke y f or t he st u d y desi g n be ca use 
of t he pr o g n ostic si g nific a nce of A A ra ce wi t h dela ye d P O R T i nitiati o n6, 4 5.  W e will t he n use a str atifie d 
ra n d o mizati o n  sc he me, wit h ra n d o mizati o n at t he i n di vi d ual patie nt le vel  usi n g  a 1: 1 all oc ati o n rati o . Str ata 
will be defi ne d b y pre dicte d l oc ati o n of ra diati o n facilit y ( M U S C, n o n-M U S C) be ca use of t he k n o w n 
ass ociati o n of t h is varia ble wit h P O R T dela y 6, 4 5.  As s uc h, o ur desi g n bala nc es b y ke y p ote ntial c o nf o u n ders 
a cr oss trial ar ms. Patie nts will be ra n d o mize d 1: 1 t o N D U R E or us ual care usi n g a per m ute d bl oc k 
r a n d o mizati o n met h o d, wit h ra n d o ml y sele cte d bl oc k sizes of 2 or 4. Gi ve n t he i m p ossi bilit y of deli veri n g 
t he N D U R E i nter ve nti o n i n a n o n-bli n de d fas hi o n, all oc ati o n c o nc eal me nt will be n o n -bli n de d. T he st u d y 
statisticia n will ge nerate a n d i m ple me nt t he ra n d o mizati o n sc he ma a n d ra n d o mizati o n list. T he st u d y 
c o or di nat or will i m ple me nt t he ra n d o mizati o n.  
 
6. 4  
S T U D Y IN T E R V E N TI O N / E X P E RI M E N T A L M A NI P U L A TI O N A D H E R E N C E  
Partici pa nts’ a d here nc e wit h st u d y pr oc e d ures will be trac ke d b y atte n da nce at i nter ve nti o n visits.   All st u d y 
visits ar e ma n dat or y t o re mai n a n acti ve partici pa nt. A d here nc e t o atte n da nce at Visits 2 -4 will be 
asc ertai ne d fr o m t he N D U R E visit n ote a ut h ore d b y t he na vi gat or t hat is a vaila ble i n t he E M R. A d her e nc e 
t o atte n da nce at Visits 1 a n d 5 will be ascertai ne d fr o m t he R E D Ca p data c olle cti o n f or m. A d here nc e t o 
atte n da nce at visits 1 -5 will be d oc u me nte d i n t he e lectr o nic C ase R e p ort F or m ( e C R F) . 
 
6. 5  
C O N C O MI T A N T T H E R A P Y  
N/ A  
 
6. 5. 1  R E S C U E T H E R A P Y  
N/ A  
 
7  
S T U D Y I N T E R V E N TI O N  D I S C O N TI N U A TI O N  A N D P A R TI C I P A N T  
D I S C O N TI N U A TI O N /W I T H D R A W A L  
7. 1  
DI S C O N TI N U A TI O N  
O F  
S T U D Y  
I N T E R V E N TI O N / E X P E RI M E N T A L 
M A NI P U L A TI O N  
At s u bje ct, PI, or st u d y te a m me m ber re q uest.  
 
7. 2  
P A R TI CI P A N T  D I S C O N TI N U A TI O N/W I T H D R A W A L F R O M T H E S T U D Y  
Partici pa nts are fre e t o wit h dra w fr o m partici pati o n i n t he st u d y at a n y ti me u p o n re q uest.  T he i n vesti gat ors 
will se e k t o mi ni mi ze partici pa nt disc o nti n uati o n/ wit h dr a wal fr o m t he st u d y (see S ecti o n 7. 3 , L ost t o 
F oll o w -U p ) e xce pt f or safet y re as o ns.  
 
T he  i n vesti gat or ma y disc o nti n ue a partici pa nt fr o m  t he st u d y f or t he f oll o wi n g re as o ns: 
•  
Si g nific a nt st u d y i nter ve nti o n n o n -c o m plia nce 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
3 3  
•  
L ost -t o-f oll o w u p; u na ble t o c o ntact s u bje ct (se e S ecti o n 7. 3 , L ost t o F oll o w -U p ) 
•  
A n y e ve nt or me dic al c o n diti o n or sit uati o n oc c urs s uc h t hat c o nti n ue d c olle cti o n of f oll o w -u p  
st u d y data w o ul d n ot be i n t he best i nterest of t he partici pa nt  or mi g ht re q uire a n a d diti o nal 
tr e at me nt t hat w o ul d c o nf o u n d t he i nter pretati o n of t he st u d y 
•  
T he partici pa nt is e x pecte d t o ha ve s ur ger y a n d t he n de ci des t o p urs ue ( 1) n o ns ur gic al tre at me nt 
or ( 2) s ur gic al treat me nt at a site n ot partici pati n g i n t he cli nic al trial 
•  
P O R T is e x pe cte d base d o n t he cli nical T N M classificati o n, b ut a nal ysis of t he pat h ol o g y 
s pe ci me n after s ur ger y de m o nstrates n o i n dicati o n f or P O R T per N C C N G ui deli nes (i.e., all of 
t he f oll o wi n g a d verse fe at ures are a bse nt: e xtra n o dal e xte nsi o n , p ositi ve mar gi n, p T 3 or p T 4 
pri mar y, N 2 or N 3 n o dal disease, n o dal disease i n le vels I V or V, P NI, a n d L VI)  
 
T he date a n d re as o n f or partici pa nt disc o nti n uati o n or wit h dra wal fr o m t he st u d y will be rec or de d i n t he  
e C R F.  
 
T he r eas o n f or partici pa nt disc o nti n uati o n or wit h dra wal fr o m t he st u d y will be re c or de d o n t he e C R F.   
 
7. 3  
L O S T T O F O L L O W -U P  
A partici pa nt will be c o nsi dere d l ost t o f oll o w -u p if he or s he fails t o ret ur n f or t w o sc he d ule d visits a n d 
st u d y staff are u na ble t o c o nta ct t he partici pa nt after at least 3 atte m pts.  
 
T he f oll o wi n g a cti o ns m ust be ta ke n if a partici pa nt fails t o ret ur n t o t he cli nic f or a re q uire d st u d y visit: 
•  
T he site will atte m pt t o c o nta ct t he partici pa nt, resc he d ule t he misse d visit wit hi n 2 we e ks, c o u nsel 
t he partici pa nt o n t he i m p orta nc e of mai ntai ni n g t he assi g ne d visit sc he d ule a n d asc ertai n if t he 
partici pa nt wis hes t o a n d/ or s h o ul d c o nti n ue i n t he st u d y  
•  
Bef ore a partici pa nt is de e me d l ost t o f oll o w -u p, t he i n vesti gat or or desi g ne e will ma ke e ver y eff ort 
t o r e gai n c o ntact wit h t he partici pa nt ( w here p ossi ble, 3 tele p h o ne calls a n d, if nec essar y, a certifie d 
letter t o t he partici pa nt’s last k n o w n maili n g a ddress or l oc al e q ui vale nt met h o ds). T hese c o nta ct 
atte m pts will be d oc u me nte d i n t he partici pa nt’s me dic al re c or d or st u d y file.  
•  
S h o ul d t he partici pa nt c o nti n ue t o be u nre ac ha ble, he or s he will be c o nsi dere d t o ha ve wit h dr a w n 
fr o m t he st u d y wit h a pri mar y reas o n of l ost t o f oll o w-u p.  
 
8  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  
8. 1  
S C R E E NI N G P R O C E D U R E S  
O nc e a s u bje ct has si g ne d t he I C F, a n i de ntific ati o n n u m ber will be assi g ne d t o hi m/ her a n d t he st u d y 
r elate d scr ee ni n g pr oc e d ures will start. A s u bje ct will be ra n d o mize d i nt o t he st u d y after he/s he has si g ne d 
t he I C F a n d all eli gi bilit y criteria ha ve be en met . 
 
8. 2  
B A S E LI N E A S S E S S M E N T S  
8. 2. 1  D E M O G R A P HI C  
De m o gr a p hic i nf or mati o n is gat here d as patie nt self -re p ort usi n g t he Be ha vi oral Ris k Fa ct or S ur veilla nc e 
S ur ve y ( B R F S S) De m o gra p hics.  
 
B R F S S  De m o gra p hics  is t he nati o n’s pre mier he alt h-relate d s ur ve y t hat c olle cts data a b o ut he alt h-relate d 
ris k be ha vi ors fr o m U S resi de nts. T he de m o gra p hic secti o n fr o m t he B R F S S will be use d (i n-pers o n) t o 
asc ertai n partici pa nt se x, a ge, rac e, marital stat us, i ns ura nce, e d uc ati o nal attai n me nt, li vi n g sit uati o n, 
zi pc o de, p h o nes f or pers o nal use, e m pl o y me nt, a n d a n n ual h o use h ol d i nc o me 4 6. 
 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
3 4  
8. 2. 2  C LI NI C A L A N D O N C O L O GI C  
Cli nic al a n d o nc ol o gic c hara cteristics are assesse d usi n g cli nic al d oc u me ntati o n wit hi n t he E M R u nless 
ot her wise i n dic ate d . 
 
Baseli ne o nc ol o gic c haracteristics i ncl u de date of dia g n osis,  he a d a n d ne c k t u m or s u bsite, t u m or hist ol o g y, 
p 1 6/ h u ma n pa pill o ma vir us ( H P V) t u m or stat us, AJ C C  8 t h e diti o n cli nic al T N M Class , AJ C C 8 t h e diti o n 
o ver all  cli nic al sta ge gr o u pi n g, a n d pre dicte d fa cilit y deli veri n g a dj u va nt t hera p y . I n s u bje cts wit h O P C or 
c arci n o ma of u n k n o w n pri mar y, H P V stat us will be deter mi ne d b y p 1 6 I H C, as deter mi ne d b y t he 
partici pa nt’s c yt ol o g y or pat h ol o g y re p ort.  T u m or sta gi n g is esta blis he d usi n g t he AJ C C/ T N M Sta gi n g 
s yste m, 8 t h e diti o n base d o n cli nical sta gi n g i nf or mati o n fr o m t he tre ati n g pr o vi der ( w hic h i ncl u des hist or y, 
p h ysic al e xa m, fi ber o ptic e n d osc o p y [as i n dic ate d] a n d ra di ol o gic i ma gi n g (i ncl u di n g C T or M RI a n d 
P E T/ C T). T he p re dicte d P O R T facilit y, a stratific ati o n varia ble f or ra n d o mizati o n, is ascertai ne d b y t he 
pr o gr a m c o or di nat or base d o n disc ussi o ns b y t he pr o gra m c o or di nat or wit h a treati n g cli nicia n  a n d p ote ntial 
partici pa nt.  
 
8. 2. 3  RI S K O F P O R T D E L A Y  
T he ris k of P O R T dela y is assesse d usi n g t he Pres ur gic al N o m o gra ms f or Pre dicti n g Dela ye d P ost o per ati ve 
Ra di ot her a p y I nitiati o n i n He a d a n d Ne c k S q ua m o us Cell Carci n o ma 4 0. T he n o m o gra m is a vali date d ris k -
pr e dicti o n t o ol t o esti mate a pers o nalize d pre -treat me nt ris k of P O R T dela y t hat is c alc ulate d base d o n t he 
f oll o wi n g baseli ne i nf or mati o n a vaila ble i n t he E M R : AJ C C o verall  c li nic al sta ge gr o u pi n g , he a d a n d ne c k 
s u bsite, i ns ura nc e c o vera ge, rac e a n d et h nicit y, a n d C harls o n/ De y o c o m or bi dit y sc ore.  
 
8. 2. 4  C U L T U R A L A S S E S S M E N T  
C ult ur e is  assesse d at baseli ne usi n g t he C ult ural Fa ct or S ur ve y , a vali date d, ps yc h o metric all y s o u n d 
q uesti o n nair e c o nsist i n g of t hree s u bscales : te m p oral orie ntati o n ( 5 ite ms), c olle cti vis m ( 6 ite ms), a n d 
r eli gi osit y ( 9 ite ms)4 7. Pri or P N st u dies ha ve use d t hese sc ales t o me as ure c ult ural fact ors4 8. Ite ms are sc ore d 
o n a 4 -p oi nt Li kert scale fr o m ‘ Str o n gl y Disa gree’ ( 1) t o ‘ Str o n gl y A gree’ ( 4). S c ores o n ea c h s u b -scale 
r a n ge fr o m 5-2 0 (te m p oral orie ntati o n), 6 -2 4 (c olle cti vis m), a n d 9 -3 6 (reli gi osit y). Hi g her sc ores o n e ac h 
s u bsc ale i n dicate greater a m o u nts of ea c h of t he meas ure d c o nstr uct.  S c ores as re p orte d as t he t otal sc ore 
f or ea c h of t he t hree i n di vi d ual s u bsc ales. 
 
8. 3  
N O N -B A S E LI N E C LI NI C A L C H A R A C T E RI S TI C S  
A d diti o nal o nc ol o gic details relate d t o t he c o urse of cli nical c are will be c olle cte d fr o m t he E M R . F or 
patie nts re cei vi n g p orti o ns of t heir care o utsi de of M U S C, a p pr o priate cli nic al re c or ds will ne e d t o be 
c olle cte d.  
 
A d diti o nal n o n -baseli ne o nc ol o gic c haracteristics i ncl u de date of defi niti ve s ur ger y , t y pe of a blati ve 
s ur ger y, t y pe of s ur gical rec o nstr ucti o n, AJ C C 8 t h e diti o n pat h ol o gic T N M Class, AJ C C 8 t h e diti o n o ver all 
pat h ol o gic sta ge gr o u pi n g, a d verse pat h ol o gic fe at ures ( mar gi n stat us, peri ne ural i n vasi o n, e xtra n o dal 
e xte nsi o n),  fa cilit y deli veri n g t he  a dj u va nt t hera p y, pla n ne d ra diati o n d ose ( G y), deli vere d ra diati o n d ose 
( G y), pr ese nc e (a n d t y pe) of c he m ot hera p y , date of c o m pleti o n of ra diati o n t hera p y. 
 
8. 4  
E N D P OI N T A N D O T H E R N O N -S A F E T Y A S S E S S M E N T S  
8. 4. 1  F E A SI BI LI T Y A S S E S S M E N T S  
N D U R E A ccr ual Rate  is defi ne d as t he pr o p orti o n of eli gi ble patie nts w h o e nr oll i n N D U R E 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
3 5  
 
N D U R E C o m pleti o n Rate  is defi ne d as t he pr o p orti o n of e nr olle d patie nts w h o c o m plete t he baseli ne 
assess me nt, at le ast t w o N D U R E i nter ve nti o n sessi o ns, a n d t he fi nal f oll o w -u p assess me nt  
 
8. 4. 2  A C C E P T A BI LI T Y A S S E S S M E N T S  
S atisfacti o n wit h t he I nter pers o nal Relati o ns hi p wit h t he Na vi gat or ( P S N-I) Sc ale : T he P S N -I is a  9 -ite m 
me as ure of t he satisfa cti o n of t he i nter pers o nal relati o ns hi p wit h t he patie nt na vi gat or. T his relia ble a n d 
vali date d me as ure 4 9, 5 0 has bee n wi del y use d i n pri or st u dies of P N. T he t otal sc ore of t he me as ure ra n ges 
fr o m 9 ( mi ni m u m) t o 4 5 ( ma xi m u m); hi g her sc ores re prese nt a better o utc o me ( greater satisfa cti o n wit h 
t he i nter pers o nal relati o ns hi p wit h t he na vi gat or). 
 
8. 4. 3  N A VI G A T O R C A S E L O A D  
I nf or mati o n a b o ut na vi gat or casel oa d is self-re p orte d b y t he Na vi gat or i nt o t he e C R F. 
 
Na vi gat or Casel oa d  is t he n u m ber of si m ulta ne o us c ases ( o n-trial partici pa nts) bei n g na vi gate d b y t he 
N D U R E na vi gat or  
 
Na vi gat or Ti me All ocati o n ( Direct)  is t he ti me (i n mi n utes), t hat t he N D U R E na vi gat or s pe n ds dir ectl y 
i nter a cti n g wit h t he patie nt t o i de ntif y a n d a d dress barriers t o ti mel y, e q uita ble P O R T 
 
Na vi gat or Ti me All oc ati o n (I n direct)  is t he ti me (i n mi n utes), t hat t he na vi gat or s pe n ds ge nerati n g a n d 
d oc u me nti n g t he N D U R E P O R T Care Pla n or perf or mi n g ot her f or ms of d oc u me ntati o n i n t he E M R  
 
Na vi gat or Ti me All ocati o n ( As y nc hr o n o us)  is t he ti me (i n mi n utes), t hat t he N D U R E na vi gat or s pe n ds 
e na cti n g t he N D U R E P O R T Care Pla n t o de cre ase barriers t o c are t hat is neit her fa ce -t o-fac e wit h t he 
patie nt n or ti me d oc u me nti n g i n t he E M R. E xa m ples of as y nc hr o n o us ti me i ncl u de ma ki n g p h o ne c all s t o 
sc he d ule a p p oi nt me nts, fa xi n g referrals, re vie wi n g t he pat h re p ort, a n d ma ki n g p h o ne c alls t o patie nt f or 
r eferral tr ac ki n g. 
 
Na vi gat or Ti me All oc ati o n ( T otal)  is t he s u m of t he ti me, i n mi n utes, of t he dire ct, i n dire ct, a n d 
as y nc hr o n o us na vi gat or ti me. 
 
8. 4. 4  E F FI C A C Y A S S E S S M E N T S  
Data f or t he effic ac y assess me nts descri be d bel o w are gat here d fr o m t he E M R. F or partici pa nts w h o re cei ve 
c are at a n o n -M U S C facilit y (a n d t h us w h ose i nf or mati o n is n ot i n t he M U S C E M R), rec or ds will be 
r e q ueste d f or t he tre ati n g fa cilit y at t he c o ncl usi o n of a dj u va nt t hera p y a n d sca n ne d i nt o M U S C E M R. 
 
P O R T D ela y : T he i nitiati o n of P O R T m ore t ha n 6 we e ks ( 4 2 cale n dar da ys) fr o m t he date of t he defi niti ve 
s ur gic al rese cti o n. 
•  
If t he s ur gic al ma na ge me nt of t he pri mar y t u m or a n d t he ne c k are sta ge d (i.e. occ ur o n t w o diff ere nt 
c ale n dar da ys), t he date of t he defi niti ve s ur ger y f or t he pri mar y t u m or will be use d.  
•  
If a d diti o nal s ur gic al resecti o n is re q uire d (e. g. re -rese cti o n of p ositi ve mar gi ns t o cle ar resi d ual 
dise ase), t he date of t he earlier (i.e. atte m pte d defi niti ve) s ur gical pr oce d ure will be use d t o 
deter mi ne t he date of defi niti ve s ur gical rese cti o n.  
•  
Patie nts w h o s uffer a m ortalit y pri or t o i nitiati n g P O R T a n d > 6 wee ks after s ur ger y will be assesse d 
as ha vi n g a P O R T dela y.  

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
3 6  
•  
Patie nts w h o s uffer a m ortalit y pri or t o i nitiati n g P O R T a n d <  6 we e ks after s ur ger y will be n o n -
e val ua ble f or e val uati o n of t he pri mar y e n d p oi nt of P O R T dela y.  
•  
Patie nts w h o r ec ur pri or t o i nitiati n g P O R T, r e gar dless of t he ti mi n g of t he re c urre nc e relati ve t o 6 
we e ks p ost o perati vel y, will be assesse d e q ui vale ntl y t o p atie nts w h o d o n ot re c ur f or t he p ur p oses 
of t his e n d p oi nt.  
 
Ti me -t o-P O R T ( T T P) : T he ti me, i n da ys, bet wee n t he date of defi niti ve s ur gical resecti o n t o t he i nitiati o n 
of P O R T. All of t he criteria use d t o a dj u dic ate t he date of t he defi niti ve s ur gic al pr oc e d ure descri be d f or 
t he pri mar y o utc o me me as ure will be a p plie d t o t his me as ure. 
•  
F or p atie nts w h o are ali ve a n d ha ve n ot i nitiate d P O R T b y 1 8  we e ks ( 1 2 6 da ys) fr o m s ur ger y , T T P 
will be c e ns ore d at t his ti me p oi nt.  
•  
F or p atie nts w h o s uffer a m ortalit y pri or t o i nitiati n g P O R T a n d < 1 8  wee ks after s ur ger y , T T P will 
be c e ns ore d at t he date of de at h . ( A se nsiti vit y a nal ysis tr e ati n g de at h as a c o m peti n g ris k will be 
perf or me d, as descri be d i n S ecti o n  9. 4 ) 
•  
F or p atie nts w h o r e c ur pri or t o i nitiati n g P O R T, r e gar dless of t he ti mi n g of t he re c urre nc e relati ve 
t o 18  we e ks p ost o perati vel y, T T P will be assesse d e q ui vale ntl y t o patie nts w h o d o n ot re c ur.  
 
8. 4. 5  B A R RI E R T O TI M E L Y P O R T A S S E S S M E N T S  
Per c ei ve d Barrier Q uesti o n naire -Patie nt  ( P B Q-P):  T he P B Q -P is a 1 7 -ite m self-re p ort me as ure of barriers 
t o ti mel y i nitiati o n of P O R T, as assesse d b y t he patie nt. Ea c h ite m is sc ore d as yes/ n o. Versi o ns of t his 
q uesti o n nair e ha ve bee n use d e xte nsi vel y t o assess percei ve d barriers i n pri or P N st u dies 1 1, 4 4, 5 1, 5 2. Ea c h ite m 
is sc or e d as yes/ n o. T he t otal sc ore is c alc ulate d b y s u m mi n g t he i n di vi d ual res p o nses. P B Q-N sc ores ra n ge 
fr o m 0-1 7; hi g her sc ores refle ct gre ater barriers t o ti mel y P O R T.  
 
Per c ei ve d Barriers Q uesti o n naire -Na vi gat or ( P B Q -N): P B Q -N  is a 1 7 -ite m meas ure of barriers t o ti mel y 
i nitiati o n of P O R T, as assesse d b y t he P N. Ea c h ite m is sc ore d as yes/ n o. Versi o ns of t his q uesti o n naire 
ha ve be e n use d e xte nsi vel y t o assess perc ei ve d barriers i n pri or P N st u dies 1 1, 4 4, 5 1, 5 2. Eac h ite m is sc or e d as 
yes/ n o. T he t otal sc ore is calc ulate d b y s u m mi n g t he i n di vi d ual res p o nses. P B Q -P  sc ores ra n ge fr o m 0-1 7; 
hi g her sc ores reflect greater barriers t o ti mel y P O R T.  
 
8. 4. 6  C A N C E R C A R E D E LI V E R Y P R O C E S S A S S E S S M E N T S  
A Ca nc er Care Deli ver y Pr oc ess f or m is i ncl u de d as t he e C R F a n d will be c o m plete d b y t he pr o gra m 
c o or di nat or usi n g i nf or mati o n fr o m t he E M R.  
 
Pr e -S ur gic al Ra diati o n C o ns ultati o n  is defi ne d as t he atte n da nce b y t he patie nt at a c o ns ultati o n wit h t he 
tr e ati n g  ra diati o n o nc ol o gist (at M U S C or else w here) pri or t o s ur ger y t o disc uss R T i n t he defi niti ve or 
a dj u va nt setti n g . Patie nts w h o see a ra diati o n o nc ol o gist at o ne facilit y pri or t o s ur ger y b ut re cei ve P O R T 
at a differ e nt facilit y are e val uate d as ‘ n o’ f or t his me as ure.  
 
Pr e -Ra diati o n T hera p y De ntal E val uati o n  is defi ne d as t he e val uati o n b y a de ntist f or pre-ra diati o n de ntal 
e xtr acti o ns. E de nt ul o us p atie nts are n o n-e val ua ble f or t his me as ure. De nt ul o us p atie nts w h o d o n ot ha ve a 
pr e -s ur gic al de ntal e val uati o n ar e e val uate d  as ‘ n o’. 
 
Pr e -Ra diati o n E xtra cti o ns  of I n dic ate d Teet h wit h Defi niti ve S ur ger y  is defi ne d as t he e xtra cti o n of 
i n dic ate d cari o us/ n o n-rest ora ble te et h eit her  pri or t o or d uri n g defi niti ve s ur ger y. Patie nts w h o ha ve a de ntal 
e val uati o n t hat i n dic ates t he ne e d f or e xtra cti o ns , b ut f or w h o m te et h are n ot e xtra cte d pri or t o or d uri n g 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
3 7  
s ur ger y ar e e val uate d  as ‘ n o’  f or t his me as ure. E de nt ul o us patie nts a n d d e nt ul o us patie nts w h o ha ve a de ntal 
e val uati o n a n d e xtracti o ns are n ot rec o m me n de d are  n ot e val ua ble f or t his me as ure.  
 
Ti me fr o m S ur ger y t o Pat h ol o g y Re p ort is defi ne d as t he pr o d ucti o n of t he pat h ol o g y re p ort fr o m t he 
defi niti ve s ur gical pr oc e d ure wit hi n t he E M R. A d de n da t o t he pat h ol o g y re p ort at t he re q uest of t he H N S C C 
te a m ( e. g. t u m or p 1 6 stat us) are n ot c o u nte d i n t his me as ure. 
 
Ti me fr o m S ur ger y t o P O R T Referral is defi ne d as t he ti me, i n da ys, fr o m t he date of t he defi niti ve 
s ur gic al pr oc e d ure t o t he date t he referral ( or p ost o perati ve a p p oi nt me nt) is pla ce d t o disc uss a dj u va nt 
t her a p y wit h t he tre ati n g ra diati o n o nc ol o gist . F or patie nts w h o ha ve see n a ra diati o n o nc ol o gist pri or t o 
s ur ger y, t his metric refers t o t he sc he d uli n g of t he p ost-o perati ve f oll o w -u p a p p oi nt me nt wit h t he 
r a diati o n o nc ol o gist. I n sit uati o ns i n w hic h a patie nt is re-referre d p ost o perati vel y  (i.e., a patie nt is 
r eferre d t o a  ra diati o n o nc ol o gist  at o ne fa cilit y a n d t he n de ci de s t o get tre at me nt at a differe nt fa cilit y),  
t he me as ure is e val uate d usin g t he ti me t o t he sec o n d referral.  
 
Ti me fr o m S ur ger y  t o P ost o perati ve A p p oi nt me nt  wit h Ra diati o n O nc ol o g y is defi ne d as t he ti me, i n 
da ys, fr o m t he date of defi niti ve  s ur ger y t o t he date t hat t he patie nt atte n ds a p ost o perati ve a p p oi nt me nt 
wit h r a diati o n o nc ol o g y. F or patie nts w h o ha ve see n a ra diati o n o nc ol o gist pri or t o s ur ger y, t his me as ure  
r efers t o t he sc he d uli n g of t he p ost-o perati ve f oll o w -u p a p p oi nt me nt wit h t he ra diati o n o nc ol o gist. I n 
sit uati o ns i n w hic h a patie nt is re-referre d p ost o perati vel y (i.e., a patie nt is referre d t o a  ra diati o n 
o nc ol o gist  at o ne facilit y a n d t he n de ci de s t o get treat me nt at a differe nt fa cilit y),  t he meas ure is e val uate d 
usi n g t he ti m e t o t he sec o n d referral . I n sit uati o ns i n w hic h a n a p p oi nt me nt is sc he d ule d b ut t he patie nt 
d oes n ot atte n d t he a p p oi nt me nt, t he meas ure is e val uate d usi n g t he  date f or w hic h t he a p p oi nt me nt was 
a ct uall y atte n de d. 
 
P O R T D ur ati o n , defi ne d as t he n u m ber of da ys fr o m t he i nitiati o n of P O R T t o t he c o m pleti o n of P O R T 
a m o n g patie nts w h o c o m plete t he i nte n de d c o urse of a dj u va nt t hera p y.  
 
C o m pleti o n of i nte n de d c o urse of P O R T , defi ne d as rec ei pt of t he pla n ne d P O R T d ose (t otal G y) . 
8. 4. 7  H E A L T H B E H A VI O R C O N S T R U C T A S S E S S M E N T S  
He alt h be ha vi or c o nstr uct data will be c ollecte d usi n g vali date d me as ures of e ac h c o nstr uct t o e x pl ore t he 
p ote ntial be ha vi oral me c ha nis ms u n derl yi n g N D U R E.  
 
M o difie d Car e Tra nsiti o n Meas ure -1 5 ( C T M -1 5) : T he C T M -1 5 is a vali date d, ps yc h o metricall y s o u n d 1 5 -
ite m, u ni di me nsi o nal me as ure of care tra nsiti o ns a cr oss t he he alt hc are s yste m t hat is c o nsiste nt wit h t he 
c o nc e pt of patie nt -c e ntere d ness a n d usef ul fr o m a n or ga nizati o n pers pecti ve f or t he p ur p ose of perf or ma nce 
me as ure me nt a n d q ualit y i m pr o ve me nt 5 3. T he C T M -1 5 was m o difie d t o e val uate care tra nsiti o ns ar o u n d 
P O R T dela y. 3 q uesti o ns relate d t o me dic ati o ns at ti me of h os pital disc har ge were re m o ve d t o cre ate a 1 2 -
ite m me as ure.  Ite ms are rate d o n a 4-p oi nt Li kert scale fr o m ‘ Str o n gl y Disa gre e’ ( 1) t o ‘ Str o n gl y A gre e’ 
( 4). T otal sc ore, re p orte d o ut of 1 0 0, is c alc ulate d as t he me a n sc ore (t he s u m me d sc ore fr o m ea c h q uesti o n 
di vi de d b y t he t otal n u m ber of q uesti o ns) wit h a li ne ar tra nsf or mati o n t o 1 0 0 ; hi g her sc ores reflect m ore 
c are i nte grati o n a n d better c are tra nsiti o ns. 
 
I nter pers o nal S u p p ort E val uati o n List-1 2 (I S E L -1 2) : T he I S E L-1 2 is a vali date d, 1 2 -ite m assess me nt of 
i nter pers o nal s u p p ort a cr oss t hre e d o mai ns (a p praisal, bel o n gi n g, a n d ta n gi ble)5 4 t hat has be e n use d t o 
assess s u p p ort i n pri or P N st u dies 5 5. Ite ms are rate d o n a 4-p oi nt Li kert scale fr o m ‘ Defi nitel y False’ ( 1) t o 
‘ Defi nitel y Tr ue’ ( 4). T he sc ore is c alc ulate d b y s u m mi n g sc ores a cr oss all ite ms ( wit h re verse c o di n g f or 
ite ms 1, 2, 7, 8, 1 1, 1 2). S c ores ra n ge fr o m 1 2 -4 8  h i g her sc ores i n dicate  gre ater  i nter pers o nal s u p p ort. 
 

N D U R E 2. 0  
 
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3 8  
Per c ei ve d S usce pti bilit y Q uesti o n naire : T he Percei ve d S usce pti bilit y Q uesti o n naire is a vali date d 3 -ite m 
per cei ve d s usc e pti bilit y s u bsc ale f or ma m m o gra p h y scree ni n g 5 6 t hat has be e n m o difie d t o assess per c ei ve d 
s usc e pti bilit y f or dela ys starti n g P O R T after H N S C C  s ur ger y. It c o nsists of t w o s u bsc ales. T he first s u bsc ale 
c o nsists of t w o q uesti o ns , o ne assessi n g a bs ol ute perc ei ve d s usc e pti bilit y t o dela ys starti n g P O R T  a n d t he 
ot her assessi n g relati ve percei ve d s usc e pti bilit y t o dela ys starti n g P O R T . Ite ms are rate d o n a 5-p oi nt Li kert 
sc ale fr o m ‘ Str o n gl y Disa gree’ ( 1) t o ‘ Str o n gl y A gree’ ( 5). T he sc ore of t he s u bscale is c alc ulate d b y 
s u m mi ng sc ores  acr oss all ite ms. T otal s c ores f or t he s u bscale ra n ge fr o m 2-1 0. H i g her sc ores i n dicate 
gr e ater per c ei ve d s usc e pti bilit y  t o dela ys starti n g P O R T. T he sec o n d s u bscale is a si n gle ite m assessi n g t he 
c o g niti ve e val uati o n of a bs ol ute percei ve d s usce pti bilit y t o P O R T dela y . T he ite m is me as ure d as a 
c o nti n u o us me as ure fr o m 0 ( n o c ha nc e of dela y) t o 1 0 0 ( g uara nte e d dela y). S c ores o n t his s u bsc ale r a n ge 
fr o m 0-1 0 0 wit h hi g her sc ores i n dicati n g a gre ater perc ei ve d s usc e pti bilit y t o P O R T dela ys.  
 
Ill ness Per c e pti o n Q uesti o n naire-Re vise d (I P Q -R) C o nse q ue nces S u bsc ale ( H N S C C  M o dific ati o n) : T he 
I P Q-R is a vali date d assess me nt of a patie nt’s self -re prese ntati o n of t he healt h c o nse q ue nces of t heir ill ness 
t hat c o nsists of 8 se parate s u bsc ales5 7. T he I P Q -R C o nse q ue nces  S u bscale is easil y m o difia ble t o asses 
dise ase -s pe cific percei ve d se verit y 5 8.T he H N S C C 
M o dific ati o n of t he I P Q -R C o nse q ue nc es S u bscale 
c o nsists of 6 q uesti o ns. Ite ms are rate d usi n g a 5 -p oi nt Li kert scale fr o m ‘ Str o n gl y Disa gree’ ( 1) t o ‘ Str o n gl y 
A gr ee’  ( 5). T he  sc ore is c alc ulate d b y s u m mi n g a cr oss all ite ms ( wit h re verse c o di n g f or ite m 3). S c or es 
r a n ge fr o m 5 t o 3 0. H i g her sc ores i n dic ate a greater de gree of  percei ve d se verit y  of t he ill ness . 
 
C o m m u nic ati o n & Attit u di nal S elf -Effica c y S cale ( C A S E) -Ca nc er : T he C A S E -Ca nc er is a vali date d, 
ps yc h o metric all y s o u n d 1 2 -ite m scale t hat a d dresses t hre e d o mai ns of self-effica c y i n ca ncer c are 
( u n dersta n di n g a n d partici pati n g i n c are, mai ntai ni n g a p ositi ve attit u de, a n d see ki n g a n d o btai ni n g 
i nf or mati o n)5 9. T he C A S E-Ca ncer scale has bee n use d e xte nsi vel y i n P N st u dies t o me as ure percei ve d self -
effica c y 1 0, 4 4, 5 2. Res p o nses are o n a 4 -p oi nt Li kert sc ale  fr o m ‘ Str o n gl y disa gre e’ ( 1) t o ‘ Str o n gl y A gre e’ ( 4). 
S c ores ra n ge fr o m 1 2 -4 8; h i g her sc ores i n dicate  gre at er le vels of self -effic ac y  i n c a nc er care. 
 
 
8. 5  
A D V E R S E E V E N T S A N D S E RI O U S A D V E R S E E V E N T S  
8. 5. 1  D E FI NI TI O N O F A D V E R S E E V E N T S  
T his trial is c o nsi dere d t o c arr y a l o w ris k t o s u bje cts (i.e. has a “ n o m ore t ha n mi ni mal ris k” desi g nati o n). 
As s uc h, t his pr ot oc ol defi nes a n a d verse e ve nt ( A E) as a n y u n desira ble si g n, s y m pt o m, me dic al, 
ps yc h ol o gic al, s ocial, or e m oti o nal rea cti o n t hat is defi nitel y, pr o ba bl y, or p ossi bl y relate d t o t he st u d y 
i nter ve nti o n (as descri be d i n 8. 5. 3 ). P ost-s ur gic al tre at me nt t o xicit y ( w o u n d c o m plic ati o ns, h os pital 
r e a d missi o ns, etc) is e x pe cte d f or t he N D U R E a n d U C care gr o u ps a n d k n o w n t o be ass ociate d wit h t he 
pri mar y e n d p oi nt ( P O R T dela y). 6 0 Alt h o u g h it is n ot h y p ot hesize d t hat t he N D U R E i nter ve nti o n will 
de cre ase t he ris k of tre at me nt t o xicit y, it is h y p ot hesiz e d t hat N D U R E will i m pr o ve patie nt -pr o vi der 
c o m m u nic ati o n a n d c are c o or di nati o n a b o ut tre at me nt t o xicit y, t here b y de cre asi n g t he ris k  of P O R T dela y. 
As a r es ult, data a b o ut e x pecte d p ost -s ur gic al treat me nt t o xicit y ( w o u n d-heali n g c o m plic ati o ns, ne e d f or 
a d diti o nal s ur ger y, u n pla n ne d visits t o t he e mer ge nc y r o o m, a n d u n pla n ne d h os pital re a d missi o ns) ar e 
assesse d i n  t he P B Q -P a n d P B Q -N (S ecti o n 8. 4 . 5) t o all o w f or s pe cific c o m paris o n of t hese t y pes of e ve nts 
bet we e n t he N D U R E a n d U C ar ms a n d t heir relati o ns hi p wit h t he pri mar y e n d p oi nt ( P O R T dela y).  
 
8. 5. 2  D E FI NI TI O N O F S E RI O U S A D V E R S E E V E N T S  
A seri o us a d verse e ve nt ( S A E) will be c o nsi dere d a n y u n desira ble si g n, s y m pt o m, or me dical c o n diti o n 
w hic h is f atal, is life -t hreate ni n g, re q uires or pr ol o n gs i n patie nt h os pitalizati o n, res ults i n persiste nt or 
si g nific a nt disa bilit y/i nc a pa cit y, c o nstit utes a c o n ge nital a n o mal y or birt h defect, is me dic all y si g nifica nt 

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3 9  
a n d w hic h t he i n vesti gat or re gar ds as seri o us base d o n a p pr o priate me dic al j u d g me nt. A n i m p orta nt me dical 
e ve nt is a n y A E t hat ma y n ot res ult i n de at h, be life -t hre ate ni n g, or re q uire h os pitalizati o n b ut ma y be 
c o nsi der e d a n S A E w he n, base d u p o n a p pr o priat e me dic al j u d g me nt, it ma y je o par dize t he patie nt a n d ma y 
r e q uir e me dic al or s ur gical i nter ve nti o n t o pre ve nt o ne of t he o utc o mes liste d i n t he defi niti o ns of S A Es.  
As wit h t he defi niti o n of A Es pr o vi de d i n 8. 5. 1, t his pr ot oc ol defi nes a S A E as a n S A E t hat is defi nitel y, 
pr o ba bl y, or p ossi bl y relate d t o t he st u d y i nter ve nti o n (see 8. 5. 3 ). 
 
8. 5. 3  C L A S SI FI C A TI O N O F A N A D V E R S E E V E N T  
8. 5. 3. 1  S E V E RI T Y O F E V E N T  
T he f oll o wi n g g ui deli nes will be use d t o descri be A E se verit y.  
•  
Mil d –  E ve nts re q uire mi ni mal or n o treat me nt a n d d o n ot i nterfere wit h t he partici pa nt’s dail y 
a cti vities.  
•  
M o d er ate –  E ve nts res ult i n a l o w le vel of i nc o n ve nie nce or c o nc er n wit h t he t hera pe utic meas ures. 
M o derate e ve nts ma y c a use s o me i nterfere nce wit h f u ncti o ni n g.  
•  
S e ver e –  E ve nts i nterr u pt a partici pa nt’s us ual dail y a cti vit y a n d ma y re q uire s yste mic dr u g t hera p y 
or ot her treat me nt. S e vere e ve nts are us uall y p ote ntiall y life -t hreate ni n g or i nca pacitati n g.  Of n ote, 
t he ter m “se vere ” d oes n ot ne cessaril y e q uate t o “seri o us”. 
 
8. 5. 3. 2  R E L A TI O N S HI P T O S T U D Y I N T E R V E N TI O N  
All A Es will ha ve t heir relati o ns hi p t o st u d y pr oc e d ures, i ncl u di n g t he i nter ve nti o n, assesse d b y t he PI 
base d o n te m p oral relati o ns hi p a n d his cli nic al j u d g me nt. T he de gre e of certai nt y a b o ut c a usalit y will be 
gr a de d usi n g t he c ate g ories bel o w.  
 
•  
Defi nitel y Rel ate d –  T here is cle ar e vi de nc e t o s u g gest a ca usal relati o ns hi p, a n d ot her p ossi ble 
c o ntri b uti n g fa ct ors c a n be r ule d o ut. T he cli nic al e ve nt, i ncl u di n g a n a b n or mal la b orat or y test 
r es ult, oc c urs i n a pla usi ble ti me relati o ns hi p t o st u d y pr oc e d ures a d mi nistratio n a n d ca n n ot be 
e x plai ne d b y c o nc urre nt disease or ot her dr u gs or c he mic als. T he res p o nse t o wit h dra wal of t he 
st u d y pr oc e d ures s h o ul d be cli nic all y pla usi ble. T he e ve nt 
m ust be p har mac ol o gic all y or 
p he n o me n ol o gic all y defi niti ve.  
•  
Pr o b a bl y Rel ate d –  T here is e vi de nce t o s u g gest a ca usal relati o ns hi p, a n d t he i nfl ue nce of ot her 
f a ct ors is u nli kel y. T he cli nical e ve nt, i ncl u di n g a n a b n or mal la b orat or y test res ult, occ urs wit hi n a 
r e as o na ble ti me after a d mi nistrati o n of t he st u d y pr oce d ures, is u nli kely t o be attri b ute d t o 
c o nc urre nt disease or ot her dr u gs or c he micals, a n d f oll o ws a cli nic all y re as o na ble res p o nse o n 
wit h dra wal.  
•  
P o ssi bl y Rel ate d –  T here is s o me e vi de nc e t o s u g gest a c a usal relati o ns hi p (e. g., t he e ve nt oc c urre d 
wit hi n a re as o na ble ti me after a d mi nistrati o n of st u d y pr oc e d ures). H o we ver, ot her fa ct ors ma y 
ha ve c o ntri b ute d t o t he e ve nt (e. g., t he partici pa nt’s cli nic al c o n diti o n, ot her c o nc o mita nt e ve nts). 
Alt h o u g h a n A E ma y rate o nl y as “ p ossi bl y relate d” s o o n after disc o ver y, it c a n be fla g ge d as 
r e q uiri n g m ore i nf or mati o n a n d later be u p gra de d t o “ pr o ba bl y relate d” or “ defi nitel y relate d”, as 
a p pr o priate. 
 
8. 5. 3. 3  TI M E P E RI O D A N D F R E Q U E N C Y F O R E V E N T A S S E S S M E N T A N D F O L L O W -U P  
Re c or di n g/r e p orti n g of A Es will be gi n after t he s u bject si g ns i nf or me d c o nse nt a n d e n d after t he s u bje ct 
c o m pletes t he i nter ve nti o n a n d f oll o w u p peri o d as defi ne d i n t he pr ot oc ol.  
 

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8. 5. 3. 4  A D V E R S E E V E N T R E P O R TI N G  
All A Es, as defi ne d a b o ve, will be c olle cte d a n d re p orte d. Data c ollecti o n will oc c ur via electr o nic 
s pre a ds he et. T he i nf or mati o n will be sa ve d i n R E D Ca p a n d ma na ge d b y t he st u d y tea m. I n c o ns ultati o n 
wit h t he PI, a trai ne d me m ber of t he st u d y te a m will be res p o nsi ble f or c o n d ucti n g a n e val uati o n of a S A E 
a n d s hall r e p ort t he res ults of s uc h e val uati o n t o t he NI H a n d t he re vie wi n g I nstit uti o nal Re vie w B oar d 
(I R B) as s o o n as p ossi ble a n d i n a c c or da nc e wit h t he re vie wi n g I R B p olic y 
 
8. 5. 3. 5  S E RI O U S A D V E R S E E V E N T R E P O R TI N G  
I n c o ns ultati o n wit h t he PI, a trai ne d me m ber of t he st u d y te a m will be res p o nsi ble f or c o n d ucti n g a n 
e val uati o n of a S A E a n d s hall re p ort t he res ults of s uc h e val uati o n t o t he NI H a n d t he re vie wi n g I R B as 
s o o n as p ossi ble a n d i n a cc or da nc e wit h t he re vie wi n g I R B p olic y. 
 
8. 5. 3. 6  R E P O R TI N G E V E N T S T O P A R TI CI P A N T  
N/ A  
8. 5. 3. 7  E V E N T S O F S P E CI A L I N T E R E S T  
N/ A  
8. 5. 3. 8  R E P O R TI N G O F P R E G N A N C Y  
N/ A  
 
8. 6  
U N A N TI CI P A T E D P R O B L E M S  
8. 6. 1  D E FI NI TI O N O F U N A N TI CI P A T E D P R O B L E M S  
T his pr ot oc ol uses t he defi niti o n of U na ntici pate d Pr o ble ms ( U P) as defi ne d b y t he Offic e f or H u ma n 
Rese arc h Pr ote cti o ns ( O H R P). O H R P c o nsi ders u na ntici pate d pr o ble ms i n v ol vi n g ris ks t o partici pa nts or 
ot hers t o i ncl u de, i n ge neral, a n y i nci de nt, e x perie nc e, or o utc o me t hat me ets all  of t he f oll o wi n g criteria:  
 
•  
U ne x pecte d i n ter ms of nat ure, se verit y, or fre q ue nc y gi ve n (a) t he researc h pr oce d ures t hat ar e 
descri be d i n t he pr ot oc ol -relate d d oc u me nts, s uc h as t he I R B-a p pr o ve d researc h pr ot oc ol a n d 
i nf or me d c o nse nt d oc u me nt; a n d ( b) t he c haracteristics of t he partici pa nt p o p ulati o n bei n g st u die d;  
•  
Relate d or p ossi bl y relate d t o partici pati o n i n t he researc h (“ p ossi bl y relate d” mea ns t here is a 
r e as o na ble p ossi bilit y t hat t he i nci de nt, e x perie nc e, or o utc o me ma y ha ve be e n c a use d b y t he 
pr oc e d ures i n v ol ve d i n t he researc h); a n d  
•  
S u g gests t hat t he researc h pla ces partici pa nts or ot hers at a gre ater ris k of har m (i ncl u di n g p h ysic al, 
ps yc h ol o gic al, ec o n o mic, or s ocial har m) t ha n was pre vi o usl y k n o w n or rec o g nize d.  
 
8. 6. 2  U N A N TI CI P A T E D P R O B L E M S R E P O R TI N G  
T he i n vesti gat or  will re p ort U P s t o t he re vie wi n g I R B a n d to t he  le a d PI. T he U P  re p ort will i ncl u de t he 
f oll o wi n g i nf or mati o n: 
 
•  
Pr ot oc ol i de ntif yi n g i nf or mati o n: pr ot oc ol title a n d n u m ber, PI’s n a me, a n d t he I R B pr oje ct n u m ber  
•  
A  detaile d descri pti o n of t he e ve nt, i nci de nt, e x perie nce, or o utc o me   

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
4 1  
•  
A n e x pla nati o n of t he basis f or deter mi ni n g t hat t he e ve nt, i nci de nt, e x perie nc e, or o utc o me 
r e prese nts a n U P  
•  
A  descri pti o n of a n y c ha n ges t o t he pr ot oc ol or ot her c orre cti ve a cti o ns t hat ha ve be e n ta ke n or are 
pr o p ose d i n res p o nse t o t he U P  
 
T o satisf y t he re q uire me nt f or pr o m pt re p orti n g, U P s will be re p orte d usi n g t he f oll o wi n g ti meli ne:  
•  
U p s will be re p orte d t o t he I R B a n d t o t he N CI  i n a c c or da nc e wit h p olic y re gar di n g ti meli ness of 
r e p orti n g 
•  
All U Ps  s h o ul d be re p orte d t o a p pr o priate i nstit uti o nal officials (as re q uire d b y a n i nstit uti o n’s 
writte n re p orti n g pr oce d ures), t he s u p p orti n g a ge nc y he a d ( or desi g ne e), a n d t he O H R P i n 
a c c or da nc e wit h p olic y  re gar di n g ti meli ness 
 
9  
S T A TI S TI C A L C O N S I D E R A TI O N S   
9. 1  
S T A TI S TI C A L H Y P O T H E S E S  
9. 1. 1  SI N G L E A R M F E A SI BI LI T Y S T U D Y  
N D U R E A ccr ual ( Pri mar y E n d p oi nt)  
W e h y p ot hesize t hat at least 6 0 % of eli gi ble s u bjects f or t he N D U R E st u d y will a ccr ue t o t he st u d y. 
Alter nati vel y, o ur n ull h y p ot hesis is t hat less t ha n 6 0 % of eli gi ble s u bje cts f or t he N D U R E st u d y will 
a c cr ue t o t he st u d y . 
 
T he preli mi nar y fe asi bilit y a nal ysis will be calc ulate d f or t he se c o n dar y e n d p oi nt usi n g t he first 2 5 
patie nts eli gi ble t o a c cr ue t o t he st u d y, w hic h is e x pe cte d t o oc c ur o ver 4 m o nt hs.  
 
N D U R E C o m pleti o n ( S e c o n dar y E n d p oi nt)  
W e h y p ot hesize t hat at le ast 8 5 % of s u bje cts w h o e nr oll i n t he N D U R E st u d y (at least 1 3 of 1 5 s u bjects) 
will c o m plete all 3 N D U R E sessi o ns. Alter nati vel y, o ur n ull h y p ot hesis is t hat less t ha n 1 3 of t he 1 5 
s u bje cts w h o e nr oll i n t he N D U R E st u d y will c o m plete all 3 N D U R E sessi o ns 
 
T he preli mi nar y fe asi bilit y a nal ysis will be calc ulate d f or t he se c o n dar y e n d p oi nt usi n g t he first 1 5 
patie nts w h o a ccr ue t o t he st u d y, w hic h is e x pecte d t o occ ur o ver 6 m o nt hs.  
 
9. 1. 2  R C T O F N D U R E V E R S U S  U S U A L C A R E  
 
P O R T D ela y  ( Pri mar y E n d p oi nt) 
W e h y p ot hesize t hat, c o m pare d wit h  patie nts w h o re cei ve us ual care , patie nts w h o re cei ve N D U R E 
will ha ve a de crease d rate of P O R T dela y (i nitiati o n of P O R T > 6 wee ks after s ur ger y). Alter nati vel y, 
o ur n ull h y p ot hesis is t hat t here will be n o differe nce i n t he rate of P O R T dela y bet we e n N D U R E a n d 
us ual c are . 
 
P O R T D ela y  ( Se c o n dar y E n d p oi nt) 
W e h y p ot hesize t hat, c o m pare d wit h  us ual c are, N D U R E will res ult i n a s maller differe nce i n t he r ate 
of P O R T dela y (i nitiati o n of P O R T > 6 we e ks after s ur ger y) bet wee n A A a n d w hite patie nts. 
Alter nati vel y, o ur n ull h y p ot hesis is t hat t here will be n o differe nce i n t he rate of P O R T dela y be t we e n 
A A a n d w hite patie nts bet wee n N D U R E a n d us ual care.  
 
T T P  ( S ec o n dar y E n d p oi nt) 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
4 2  
W e h y p ot hesize t hat, c o m pare d wit h  patie nts w h o re cei ve us ual care, patie nts w h o re cei ve N D U R E 
will ha ve a  s h orter me dia n T T P ( ti me, i n da ys, bet wee n t he date of defi niti ve s ur gical rese cti o n t o t he 
i nitiati o n of P O R T). Alter nati vel y, o ur n ull h y p ot hesis is t hat t here will be n o differe nc e i n me dia n T T P 
bet we e n N D U R E a n d us ual c are.  
 
T T P  ( S ec o n dar y E n d p oi nt) 
W e h y p ot hesize t hat, 
c o m pare d wit h  us ual care, N D U R E will res ult i n a s maller differe nc e i n t he  
me dia n T T P  bet wee n A A a n d w hite patie nts. Alter nati vel y, o ur n ull h y p ot hesis is t hat t here will be n o 
diff ere nce i n t he me dia n T T P  bet we e n A A a n d w hite patie nts bet wee n N D U R E a n d us ual care.  
 
9. 2  
S A M P L E SI Z E  D E T E R MI N A TI O N  
9. 2. 1  N D U R E F E A SI BI LI T Y S T U D Y  
P o wer a n d sa m ple size c alc ulati o ns were perf or me d usi n g t he U ni versit y of I o wa Bi n o mial Distri b uti o n 
a p plet. T he sa m ple size j ustific ati o n f or t his si n gle -ar m st u d y is base d o n t he pri mar y fe asi bilit y e n d p oi nts 
of N D U R E a c cr ual a n d c o m pleti o n. I n t he R C T of N D U R E , we pla n t o e nr oll 6 0 % of eli gi ble patie nts. W e 
e x pe ct si milar a c cr ual i n t his feasi bilit y st u d y . T heref ore, we h y p ot hesize t hat at le ast 6 0 % of eli gi ble 
s u bje cts f or t he N D U R E st u d y will a c cr ue t o t he st u d y. Alter nati vel y, o ur n ull h y p ot hesis is t hat less t ha n 
6 0 % of eli gi ble s u bje cts f or t he N D U R E st u d y will a c cr ue t o t he st u d y.  A c cr ui n g t o N D U R E will be 
c o nsi der e d f easi ble if at le ast 1 5 of 2 5 eli gi ble s u bjects e nr oll.  O ur sa m ple size f or t he fe asi bilit y st u d y was 
sele cte d t o pr o vi de a s mall pr o ba bilit y of ha vi n g a n o bser ve d ac cr ual rate of at le ast 6 0 % w he n t he tr ue 
a c cr ual pr o ba bilit y is a ct uall y less t ha n 6 0 %. F or e xa m ple, if t he tr ue a ccr ual pr o ba bilit y f or o ur pr o p ose d 
desi g n is 4 5 % ( 3 5 %), t he pr o ba bilit y o f e nr olli n g 1 5 or m ore of 2 5 eli gi ble s u bje cts is o nl y 1 0 % ( 1 %). 
A d diti o nall y, w e h y p ot hesize t hat at le ast 8 5 % of s u bje cts w h o e nr oll i n t he N D U R E st u d y will c o m plete 
all 3 N D U R E sessi o ns.  Alter nati vel y, o ur n ull h y p ot hesis is t hat less t ha n 8 5 % of  s u bje cts w h o e nr oll i n t he 
N D U R E st u d y will c o m plete all 3 N D U R E sessi o ns . T hat is t o sa y, N D U R E will be c o nsi dere d fe asi ble if 
at le ast 1 3 of t he 1 5 s u bje cts e nr olle d c o m plete all t hre e N D U R E sessi o ns. Ac c or di n gl y, o ur sa m ple size 
f or t he si n gle-ar m st u d y was sele cte d t o pr o vi de a s mall pr o ba bilit y of ha vi n g a n o bser ve d c o m pleti o n r ate 
of at least 8 5 % w he n t he tr ue c o m pleti o n pr o ba bilit y of t he i nter ve nti o n is a ct uall y less t ha n 8 5 %. F or 
e xa m ple, if t he tr ue c o m pleti o n pr o ba bilit y f or o ur pr o p ose d desi g n is 7 0 % ( 6 0 %), t he pr o ba bilit y t hat 1 3 
or m or e of t he 1 5 e nr olle d patie nts c o m plete all t hre e N D U R E sessi o ns is 1 3 % ( 3 %). T heref ore, t he 
pr o ba bilit y of falsel y declari n g N D U R E fe asi ble is reas o na bl y c o ntr olle d base d o n t his sa m ple size.  
 
9. 2. 2  R C T  O F N D U R E V E R S U S U S U A L C A R E  
P o wer a n d sa m ple size c alc ulati o ns were perf or me d usi n g P A S S v 0 8. 0. 1 3, “I ne q ualit y Tests f or T w o 
I n de pe n de nt Pr o p orti o ns.” T he pri mar y e n d p oi nt f or t his pil ot R C T is t he rate of P O R T dela y, defi ne d as 
starti n g P O R T > 6 we e ks after s ur ger y. O ur pri mar y o bje cti ve is t o c o m pare P O R T dela y rates bet wee n t he 
N D U R E a n d  us ual c are  ar ms. W e h y p ot hesize t hat, c o m pare d wit h  patie nts w h o re c ei ve us ual care, patie nts 
w h o r ec ei ve N D U R E will ha ve a decre ase d rate of P O R T dela y (i nitiati o n of P O R T > 6 we e ks after 
s ur ger y). Alter nati vel y, o ur n ull h y p ot hesis is t hat t here will be n o differe nc e i n t he rate of P O R T dela y 
bet we e n N D U R E a n d us ual c are . We ass u me t he rate of P O R T dela y i n t he  us ual c are  ar m will be 4 5 % 4 5 
a n d tar get a n a bs ol ute re d ucti o n i n P O R T dela y of 2 0 % (rate of P O R T dela y i n t he N D U R E ar m = 2 5 %) 2 4. 
T his effe ct size is cli nicall y si g nific a nt a n d re alistic gi ve n res ults i n si milar ( n o n -ra n d o mize d) 
i nter ve nti o ns2 4. S e ve nt y-fi ve patie nts i n e ac h ar m yiel ds 8 3 % p o wer t o dete ct a 2 0 % re d ucti o n i n P O R T 
dela y ( 4 5 % vers us 2 5 %) base d o n a t w o -si de d Z -test wit h p o ole d varia nc e of t w o i n de pe n de nt pr o p orti o ns 
ass u mi n g a t w o -si de d α = 0. 1. O ur sele cti o n of α = 0. 1 a n d 1 –  β = 0. 8 is base d o n t he desire t o e m p hasize 
p o wer o ver t y pe I err or at t his e arl y sta ge of de vel o p me nt (si n gle -site pil ot R C T ) t o e ns ure f oll o w-u p o n 
pr o misi n g i nter ve nti o ns. F urt her m ore, gi ve n t he trial’s desi g n , c o m paris o n of P O R T dela y rates bet wee n 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
4 3  
trial ar ms will be a nal yze d usi n g a m o del-base d a p pr oa c h ( disc usse d i n S ecti o n 9. 4. 3. 2 ) wit h i ncl usi o n of 
r a n d o mizati o n stratific ati o n varia bles as m o del c o variates, a n a nal ytic a p pr oa c h w hic h preser ves t he t y pe I 
err or r ate at n o mi nal α, a n d i ncre ases p o wer relati ve t o a n u na dj uste d m o del.6 1 T heref ore, o ur p o wer a nal ysis 
base d o n a Z -test is c o nser vati ve, a n d we a ntici pate e ve n gre ater p o wer base d o n o ur a nal ytic pla n. W e 
t her ef or e c o nsi der o ur R C T t o be a p pr o priatel y a n d ri g or o usl y desi g ne d t o dete ct a cli nic all y me a ni n gf ul 
r e d ucti o n i n P O R T dela y. I n or der t o ha ve 1 5 0 patie nts eli gi ble f or t he P O R T dela y a nal ysis set (see Se cti o n 
9. 3, P o p ul ati o n f or A n al yses ), we pla n t o e nr oll 17 0  patie nts. O ur sa m ple size is i nflate d b y 1 7 % base d o n 
hist oric al data.  If at 1 7 0 patie nt a c cr uals we ha ve n ot a c hie ve d  7 5  patie nts e val ua ble f or t he pri mar y 
e n d p oi nt i n e a c h ar m, we will c o nti n ue t o e nr oll u ntil we ha ve ac hie ve d eit her a ccr ual of a mi ni m u m of 7 5 
e val ua ble patie nts i n e ac h ar m or ha ve ac cr ue d a ma xi m u m of 1 8 0 t otal patie nts.  
 
 
9. 3  
P O P U L A TI O N S F O R A N A L Y S E S  
T he s afet y a n al ysis set ( S A S) is c o m p ose d of all patie nts e nr olle d w h o re cei ve a n y part of eit her t he 
N D U R E or U C  i nter ve nti o n. T he S A S will be use d t o c o n d uct all safet y a nal yses. Patie nts will be 
a nal yze d base d o n t he i nter ve nti o n re cei ve d re gar dless of t he assi g n me nt at ra n d o mizati o n.  
 
T he P O R T d el a y a n al ysis set is c o m p ose d of all patie nts e nr olle d i n t he trial w h o are: 
1.  Ra n d o mize d t o N D U R E or U C  
2.  Re c ei ve c urati ve i nte nt s ur ger y at M U S C  
3.  Ha ve a n i n dic ati o n f or P O R T per N C C N G ui deli nes base d o n t he prese nc e of at least o ne of t he 
f oll o wi n g a d verse feat ures o n fi nal pat h ol o gic e val uati o n: E N E, p ositi ve mar gi n, p T 3 or p T 4 
pri mar y, at least p N 1 n o dal disease ( per AJ C C 8 t h e diti o n f or p 1 6 -ve n o n -or o p har y n geal S C C or 
AJ C C 7 t h e diti o n f or p 1 6 + ve or o p har y n geal S C C), n o dal disease i n le vels I V or V, P NI or L VI  
4.  Ar e ali ve f or >  6 wee ks p ost o perati vel y . 
 
A nal ysis will be perf or me d base d o n assi g n me nt at ra n d o mizati o n re gar dless of t he i nter ve nti o n rec ei ve d 
( m o difie d i nte nt t o tre at). T his a nal ysis set will be use d f or a nal ysis of t he pri mar y e n d p oi nt. T he rati o nale 
f or t his defi niti o n of t he P O R T dela y e val ua ble set is t hat eli gi bilit y, ra n d o mizati o n, a n d deli ver y of a 
p orti o n of t he i nter ve nti o n occ ur pri or t o defi niti ve treat me nt of t he H N S C C. H o we ver, t he pri mar y 
e n d p oi nt is e val ua ble o nl y f or patie nts w h o u n der g o s ur ger y f or H N S C C, ha ve a n i n dic ati o n f o r a dj u va nt 
P O R T ( w hic h c a n o nl y be defi niti vel y k n o w n f oll o wi n g s ur gic al resecti o n), a n d are ali ve f or at le ast 6 
we e ks p ost o perati vel y. T heref ore, we e x pe ct t hat a s u bset of patie nts w h o meet all eli gi bilit y criteria will 
be e nr olle d i n t he st u d y, ra n d o mize d t o N D U R E or UC , re c ei ve a p orti o n of t he i nter ve nti o n, b ut 
s u bse q ue ntl y be n o n-e val ua ble f or t he pri mar y e n d p oi nt w he n i nf or mati o n bec o mes a vaila ble later i n t he 
cli nic al c o urse t hat ca n n ot be k n o w n at t he ti me of st u d y e nr oll me nt a n d ra n d o mizati o n (e. g., t he y ( 1) 
ele ct a n o n-s ur gical treat me nt o pti o n; ( 2) ha ve n o i n dicati o n f or P O R T per N C C N G ui deli nes o n fi nal 
pat h ol o gic assess me nt ; ( 3) ha ve a m ortalit y pri or t o 6 wee ks p ost o perati vel y).  
 
Ti m e -t o-P O R T ( T T P) a n al ysis  set is c o m p ose d of all patie nts e nr olle d i n t he trial w h o are:  
1.  Ra n d o mize d t o N D U R E or U C  
2.  Re c ei ve c urati ve i nte nt s ur ger y at M U S C  
3.  Ha ve a n i n dic ati o n f or P O R T per N C C N G ui deli nes base d o n t he prese nc e of at least o ne of t he 
f oll o wi n g a d verse feat ures o n fi nal pat h ol o gic e val uati o n: E N E, p ositi ve mar gi n, p T 3 or p T 4 
pri mar y, at least p N 1 n o dal disease ( per AJ C C 8 t h e diti o n f or p 1 6 -ve n o n -or o p har y n geal S C C or 
AJ C C 7 t h e diti o n f or p 1 6 + ve or o p har y n geal S C C), n o dal disease i n le vels I V or V, P NI or L VI  
A nal ysis will be perf or me d base d o n assi g n me nt at ra n d o mizati o n re gar dless of t he i nter ve nti o n rec ei ve d 
( m o difie d i nte nt t o tre at). T his a nal ysis set will be use d f or a nal ysis of t he se c o n dar y e n d p oi nt  T T P  
 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
4 4  
T he t re at m e nt p ac k a ge ti me ( T P T) a n al ysis set  is t he T T P a nal ysis set restricte d t o patie nts w h o ha ve 
i nitiate d P O R T. 
 
T he f ull a n al ysis set ( F A S) is t he set of all trial partici pa nts w h o e nr oll a n d are eli gi ble f or t he st u d y. 
Patie nts w h o e nr oll b ut s u bse q ue ntl y dr o p o ut pri or t o recei vi n g a n y of t he assi g ne d i nter ve nti o n will be 
r e plac e d. T he F A S will be use d f or e val uati o n of t he pre -s ur gic al ra diati o n c o ns ultati o n, a n d f or 
se c o n dar y a nal yses of b ot h t he pri mar y e n d p oi nt a n d se c o n dar y e n d p oi nts. 
 
T he de nt al e v al u ati o n pri or t o s u r ge r y a n al ysis set  will be t he F A S restricte d t o patie nts w h o rec ei ve 
c ur ati ve i nte nt s ur ger y at M U S C a n d are i n dicate d f or de ntal e val uati o n.  
 
T he e xtr acti o n of i n dic ate d te et h a n al ysis set  is t he s u bset of patie nts i n t he de ntal e val uati o n pri or t o 
s ur ger y a nal ysis set w h o are i n dic ate d f or de ntal e xtra cti o ns pri or t o s ur ger y. 
 
T he ti me f r o m s ur ger y t o P O R T refer r al sc h e d uli n g a n al ysis set a n d ti me fr o m s u r ger y t o 
a p p oi nt me nt wit h r a di ati o n o nc ol o g y a n al ysis set  are  e q ui vale nt t o t he T T P a nal ysis set.  
 
Pe r p r ot oc ol set  is c o m p ose d of all patie nts e nr olle d i n t he trial w h o ha ve c o m plete d all 3 of t he 
E N D U R E i nter ve nti o n sessi o ns as descri be d i n t he pr ot oc ol. T his a nal ysis set will be use d f or sec o n dar y 
a nal yses of b ot h t he pri mar y e n d p oi nt a n d sec o n dar y e n d p oi nts.   
 
9. 4  
S T A TI S TI C A L A N A L Y S E S  
9. 4. 1  G E N E R A L A P P R O A C H  
W e will c o nstr uct gra p hic al dis pla ys a n d calc ulate descri pti ve statistics (e. g. fre q ue ncies 
a n d perc e nt f or 
c ate g oric al varia bles, a n d me a n, me dia n, sta n dar d de viati o n, a n d ra n ge f or c o nti n u o us varia bles) . F or 
i nf er e ntial tests, we will use a p-val ue of 0. 0 5, t w o -si de d, a n d 90 % c o nfi de nc e i nter vals ( CIs) t o assess 
statistic al si g nific a nc e ( T y pe I err or), u nless ot her wise n ote d. C o variates i ncl u de d i n t he a nal ysis pla n will 
be pr e -s pe cifie d as descri be d bel o w. N or malit y of t he data will be assesse d bef ore statistic al pr oc e d ur es 
will be perf or me d. W e will e val uate varia ble tra nsf or mati o ns as ne e de d t o satisf y ass u m pti o ns a n d c o nsi der 
tr a nsf or mati o ns of varia bles t o i n d uc e a p pr o xi mate n or malit y a n d sta bilize variance as nee de d. 
N o n para metric tests will be a p plie d w he n a p pr o priate . 
 
9. 4. 2  MI S SI N G D A T A  
•  
P O R T dela y stat us ( dela y or ti mel y P O R T) will be c o nsi dere d ‘ dela ye d’ f or a n y e val ua ble patie nt 
wit h mi ssi n g P O R T dela y stat us. 
•  
T T P will be ri g ht -c e ns ore d f or e val ua ble patie nts w h o die pri or t o P O R T i nitiati o n, are  l ost t o 
f oll o w-u p pri or t o P O R T i nitiati o n, or w h o ha ve n’t re cei ve d P O R T b y t he e n d of f oll o w -u p ( 1 8  
we e ks p ost o perati vel y).  
•  
T P T will be ri g ht -c e ns ore d f or e val ua ble patie nts w h o die  or are l ost t o f oll o w -u p pri or t o t he 
c o ncl usi o n of P O R T , or w h o pre mat urel y disc o nti n ue t heir i nte n de d c o urse of P O R T. T P T will 
als o be ri g ht -ce ns ore d f or patie nts w h o ha ve n ot c o m plete d P O R T b y t he e n d of f oll o w -u p ( 1 8 
we e ks p ost o perati vel y).  
•  
Ti me fr o m s ur ger y t o P O R T r eferral sc he d uli n g will be ri g ht -c e ns ore d f or e val ua ble patie nts w h o 
die pri or t o P O R T i nitiati o n, are l ost t o f oll o w -u p pri or t o P O R T i nitiati o n, or w h o ha ve n’t 
r e cei ve d P O R T b y t he e n d of f oll o w-u p ( 1 8 wee ks p ost o perati vel y).  
•  
Ti me fr o m s ur ger y t o a p p oi nt me nt wit h ra diati o n o nc ol o g y will be ri g ht -c e ns ore d f or e val ua ble 
patie nts w h o die pri or t o P O R T i nitiati o n, are l ost t o f oll o w -u p pri or t o P O R T i nitiati o n, or w h o 
ha ve n’t re cei ve d P O R T b y t he e n d of f oll o w -u p ( 1 8 wee ks p ost o perati vel y).  

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A nal yses of e x pl orat or y e n d p oi nts will be c o n d ucte d usi n g c o m plete case a nal ysis.  
9. 4. 3  A N A L Y SI S O F T H E P RI M A R Y E N D P OI N T  
9. 4. 3. 1  N D U R E F E A SI BI LI T Y S T U D Y  
F or t he pri mar y e n d p oi nt (N D U R E Ac cr ual  Rate ), we will c alc ulate  t he pr o p orti o n a n d fre q ue nc y of eli gi ble 
patie nts w h o a c cr ue ( o verall, w hite, a n d Afric a n A meric a n). Gi ve n its pil ot nat ure, t he st u d y is n ot desi g ne d 
t o e val uate racial differe nc es i n a ccr ual, alt h o u g h reas o ns f or st u d y decli ne will be c ollecte d, a nal yze d f or 
e a c h r acial s u b gr o u p, a n d use d t o refi ne re cr uit me nt.  
 
9. 4. 3. 2  R C T  O F N D U R E V E R S U S U S U A L C A R E  
F or t he pri mar y e n d p oi nt ( dela ys starti n g P O R T  as defi ne d i n S e cti o n 8. 4 , En d p oi nt a n d Ot he r N o n -
S af et y Assess me nts ), the differe nce i n P O R T dela y c o m pari n g N D U R E t o U C will be e val uate d usi n g a 
m o del -base d a p pr oa c h t o ac c o m m o date a dj ust me nt f or ra n d o mizati o n stratific ati o n varia bles. S pe cific all y, 
we will use a bi nar y re gressi o n ge neralize d li near m o del ( G L M) wit h i de ntit y li n k t o m o del t he pr o ba bilit y 
of P O R T  dela y as a f u ncti o n of tre at me nt ar m a n d ra n d o mizati o n stratific ati o n varia bles  (ra c e a n d pre dicte d 
l oc ati o n of r a diati o n fa cilit y). W e a d o pt t his a p pr oa c h as o p p ose d t o a l o git m o del or Ma ntel -Hae nzel ( M H) 
t y pe a p pr oac h si nc e t he esti ma n d is t he p o p ulati o n a vera ge tre at me nt effect, w hereas t he  o d ds rati o is n ot 
c olla psa ble a n d t heref ore i nfere nce base d o n l o gistic re gressi o n or M H esti mati o n w o ul d be li mite d t o a 
c o n diti o nal tre at me nt effect. (A d diti o nal details c a n be f o u n d i n t he F D A G ui da nc e D oc u me nt o n A dj usti n g 
f or C o variates i n Ra n d o mize d Cli nic al Trials.) T he ris k differe nce ( P O R T dela y rate i n U C –  P O R T dela y 
r ate i n N D U R E) will be esti mate d base d o n t he tre at me nt effect sl o pe para meter. We will re p ort t he  
c orres p o n di n g m o del -base d 9 0 % CI a n d t w o -si de d p-val ue. W e will a d diti o nall y re p ort m o del -base d P O R T 
dela y r ates f or e ac h trial ar m wit h c orres p o n di n g 9 0 % CIs. S h o ul d G L M c o n ver ge nc e be a n iss ue, we will 
a d o pt a n alter nati ve a p pr oac h base d o n s u bje ct-le vel pre dicte d pr o ba bilities of P O R T dela y fr o m a l o gistic 
m o del as o utli ne d b y Fre e d ma n 6 2 a n d b y Stei n gri mss o n .6 3  A nal ysis will be perf or me d usi n g t he P O R T 
dela y a nal ysis set.  
 
9. 4. 4  A N A L Y SI S O F T H E S E C O N D A R Y E N D P OI N T S  
9. 4. 4. 1  N D U R E F E A SI BI LI T Y S T U D Y  
N D U R E c o m pleti o n rate will be a nal yze d as 1) t he perce nta ge of e nr olle d patie nts w h o atte n d all t hr e e 
N D U R E sessi o ns a n d 2) t he pr o p orti o n of t hre e N D U R E sessi o ns t hat are c o m plete d.  F or na vi gat or 
c asel oa d, we will c o nsi der t he fre q ue nc y of si m ulta ne o us c ases na vi gate d. Na vi gat or ti me all oc ati o n f or 
dir e ct a n d i n dire ct ti me, as well as patie nt -re p ort meas ures of satisfacti o n wit h na vi gati o n will be 
s u m marize d as descri be d a b o ve f or c o nti n u o us data. St u d y q uesti o n naire c o m pleti o n rate will be calc ulate d 
as t he pr o p orti o n of pre - a n d p ost-i nter ve nti o n q uesti o n naires ( n = 5 ea c h) c o m plete d. Q ualitati ve data will 
be a nal yze d usi n g esta blis he d te a m c o de b o o ks a n d f oc us o n t he c o nte nt, f or mat, d eli ver y, a n d ti mi n g of 
N D U R E. Q ualitati ve a nal ysis of se mi -str uct ure d i nter vie ws wit h patie nts a n d pr o vi ders f oll o wi n g t he pil ot 
will be a nal yze d usi n g esta blis he d c o de b o o ks fr o m t he st u d y te a m f or e val uati n g t he fe asi bilit y a n d 
a c ce pta bilit y of cli nic -bas e d H N S C C  i nter ve nti o ns wit h a f oc us o n t he c o nte nt, f or mat, deli ver y, a n d ti mi n g 
of N D U R E.  
 
9. 4. 4. 2  R C T  O F N D U R E V E R S U S U S U A L C A R E  
P O R T d el a y dis p arit y ( Bl ac k vs W hite) i n N D U R E vs U C : T he c o m paris o n of P O R T dela y dis parit y 
( P O R T dela y i n Blac k patie nts vs P O R T dela y i n W hite patie nts) i n N D U R E vers us U C will be e val uate d 
usi n g a si milar G L M as descri be d f or t he pri mar y e n d p oi nt, b ut t he m o del will i ncl u de a ra ce -b y -tre at me nt 

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ar m i nter acti o n  ter m. M o del-base d esti mates of P O R T dela y dis parit y will be c o nstr ucte d f or e ac h ar m wit h 
c orres p o n di n g 9 0 % CIs . The m o del -base d differe nc e i n dis parit y bet wee n trial ar ms will be re p orte d al o n g 
wit h c orr es p o n di n g 9 0 % CIs. A nal ysis will be perf or me d usi n g t he P O R T dela y a nal ysis set.  
 
Ti m e -t o-P O R T initi ati o n , N D U R E vs U C: T T P  will be a nal yze d usi n g c u m ulati ve i nci de nc e pl ots  ( 1 –  
Ka pla n -Meier pl ots) wit h Gre e n w o o d varia nce esti mati o n t o c o nstr uct c orres p o n di n g 9 0 % CIs. Tr e at me nt 
gr o u p  c o m paris o ns will be c o n d ucte d usi n g a stratifie d l o g -ra n k test a dj usti n g f or ra n d o mizati o n 
str atific ati o n varia bles. As n ote d, T T P will be ri g ht-c e ns ore d f or e val ua ble patie nts w h o die or are l ost t o 
f oll o w-u p pri or t o P O R T i nitiati o n, or w h o ha ve n’t re ce i ve d P O R T b y t he e n d of f oll o w-u p ( 1 8 we e ks 
p ost -o per ati vel y).  T he h a zar d rati o c o m pari n g t he t w o ar ms will be esti mate d usi n g C o x pr o p orti o nal 
ha zar ds re gr essi o n c o ntr olli n g f or stratificati o n varia bles. A se nsiti vit y a nal ysis will be c o n d ucte d treati n g 
de at hs pri or t o P O R T i nitiati o n as a c o m peti n g ris k  t o e val uate t he bias i nc urre d i n c u m ulati ve i nci de nc e 
esti mati o n b y ri g ht -c e ns ori n g deat hs . A nal yses will be perf or me d usi n g t he T T P a nal ysis set.  
 
Ti m e -t o-P O R T initi ati o n  ( Bl ac k vs W hite) i n N D U R E vs U C: T T P c u m ulati ve i nci de nce pl ots ( 1 –  
Ka pla n -Meier pl ots) will be c o nstr ucte d f or Bla c k a n d W hite patie nts ra n d o mize d t o N D U R E a n d f or 
Bla c k a n d W hite patie nts ra n d o mize d t o U C as descri be d. Gr o u p c o m paris o ns will be c o n d ucte d usi n g a 
str atifie d l o g-ra n k test, b ut c o ntr olli n g o nl y f or pre dicte d ra diati o n facilit y as a ra n d o mizati o n 
str atific ati o n varia ble si nce a ra ce -b y -trial ar m i nteracti o n ter m is use d t o e val uate t his h y p ot hesis. A C o x 
pr o p orti o nal ha zar ds re gressi o n m o del will be fit as descri be d wit h a p pr o priate ra ce -b y -trial ar m 
i nter a cti o n. Ce ns ori n g  r ules will be as descri be d i n S e cti o n 9. 4. 2. A se nsiti vit y a nal ysis will be perf or me d 
tr e ati n g deat hs pri or t o P O R T i nitiati o n as a c o m peti n g ris k. A nal yses will be c o n d ucte d usi n g t he T T P 
a nal ysis set.  
 
Tr e at me nt p ac k a ge ti me , N D U R E vs U C: T P T is defi ne d as t he n u m ber of da ys bet wee n t he date of 
defi niti ve s ur ger y a n d t he date of P O R T c o m pleti o n. A nal ysis will be c o n d ucte d usi n g c u m ulati ve 
i nci de nc e pl ots ( 1 –  Ka pla n -Meier pl ots) wit h Gree n w o o d varia nc e esti mati o n t o c o nstr uct c orres p o n di n g 
9 0 % CIs. Tr e at me nt gr o u p  c o m paris o ns will be c o n d ucte d usi n g a stratifie d l o g -ra n k test a dj usti n g f or 
r a n d o mizati o n stratific ati o n varia bles. T P T will be ri g ht -ce ns ore d as descri be d i n Se cti o n 9. 4. 2. T he 
h a zar d rati o c o m pari n g t he t w o ar ms will be esti mate d usi n g C o x pr o p orti o nal ha zar ds re gressi o n 
c o ntr olli n g f or stratificati o n varia bles. A se nsiti vit y a nal ysis will be c o n d ucte d treati n g de at hs after P O R T 
i nitiati o n b ut  pri or t o t he c o m pleti o n of P O R T as a c o m peti n g ris k t o e val uate t he bias i nc urre d i n 
c u m ulati ve i nci de nce esti m ati o n b y ri g ht-ce ns ori n g deat hs. A nal yses will be perf or me d usi n g t he T P T 
a nal ysis set.  
 
Tr e at me nt p ac k a ge ti me  ( Bl ac k vs W hite) i n N D U R E vs U C : T P T c u m ulati ve i nci de nce pl ots ( 1 –  
Ka pla n -Meier pl ots) will be c o nstr ucte d f or Bla c k a n d W hite patie nts ra n d o mize d t o N D U R E a n d f or 
Bla c k a n d W hite patie nts ra n d o mize d t o U C as descri be d. Gr o u p c o m paris o ns will be c o n d ucte d usi n g a 
str atifie d l o g-ra n k test, b ut c o ntr olli n g o nl y f or pre dicte d ra diati o n facilit y as a ra n d o mizati o n 
str atific ati o n varia ble si nce a ra ce-b y -trial ar m i nteracti o n ter m is use d t o e val uate t his h y p ot hesis. A C o x 
pr o p orti o nal h a zar ds re gressi o n m o del will be fit as descri be d wit h a p pr o priate ra ce -b y -trial ar m 
i nter a cti o n. Ce ns ori n g r ules will be as descri be d i n S e cti o n 9. 4. 2. A se nsiti vit y a nal ysis will be perf or me d 
tr e ati n g deat hs after  P O R T i nitiati o n b ut pri or t o t he c o m pleti o n of P O R T as a c o m peti n g ris k. A nal yses 
will be c o n d ucte d usi n g t he T P T  a nal ysis set.  
 
Ti m e f r o m s u r ge r y t o P O R T r efer r al sc h e d uli n g , N D U R E vs U C : Ti me fr o m s ur ger y t o P O R T 
r eferral sc he d uli n g will be a nal yze d usi n g t he a p pr oa c h descri be d f or all ti me -t o-e ve nt e n d p oi nts. 
Ce ns ori n g r ules will be as descri be d i n S ecti o n 9. 4. 2. A nal yses will be perf or me d usi n g t he ti me fr o m 
s ur ger y t o P O R T r eferral sc he d uli n g a nal ysis set. 
 

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Ti me fr o m s ur ger y t o a p p oi nt me nt wit h r a di ati o n o nc ol o g y , N D U R E vs U C : Ti me fr o m s ur ger y 
t o a p p oi nt me nt wit h ra diati o n o nc ol o g y  will be a nal yze d usi n g t he a p pr oac h descri be d f or all ti me -t o-
e ve nt e n d p oi nts. Ce ns ori n g r ules will be as descri be d i n Se cti o n 9. 4. 2. A nal yses will be perf or me d usi n g 
t he ti me fr o m s ur ger y t o a p p oi nt me nt wit h ra diati o n o n c ol o g y  a nal ysis set. 
 
Pr e -s u r gic al r a di ati o n c o ns ult ati o n, N D U R E vs U C will be a nal yze d usi n g a bi nar y re gressi o n G L M 
wit h i de ntit y li n k as descri be d. If t he G L M fails t o c o n ver ge, t he n u na dj uste d (e m pirical) rates a n d 
c orres p o n di n g 9 0 % CIs will be c o nstr ucte d, wit h trial -ar m c o m paris o ns c o n d ucte d usi n g a z -test of t w o 
i n de pe n de nt pr o p orti o ns.  A nal yses will be perf or me d usi n g t he F A S.  
 
De nt al e v al u ati o n pri or t o s u r ge r y , N D U R E vs U C  will be a nal yze d usi n g a bi nar y re gressi o n G L M 
wit h i de ntit y li n k as descri be d. If t he G L M fails t o c o n ver ge, t he n u na dj uste d (e m pirical) rates a n d 
c orres p o n di n g 9 0 % CIs will be c o nstr ucte d, wit h trial -ar m c o m paris o ns c o n d ucte d usi n g a z -test of t w o 
i n de pen de nt pr o p orti o ns.  A nal yses will be perf or me d usi n g t he  d e nt al e v al u ati o n p ri or t o s ur ger y 
a n al ysis set . 
 
E xt r acti o n of i n dic ate d teet h , N D U R E vs U C  will be a nal yze d usi n g a bi nar y re gressi o n G L M wit h 
i de ntit y li n k as descri be d. If t he G L M fails t o c o n ver ge, t he n u na dj uste d (e m piric al) rates a n d 
c orres p o n di n g 9 0 % CIs will be c o nstr ucte d, wit h trial -ar m c o m paris o ns c o n d ucte d usi n g a z -test of t w o 
i n de pen de nt pr o p orti o ns.  A nal yses will be perf or me d usi n g t he e xtr acti o n of i n dic ate d teet h a n al ysis 
set. 
 
 
9. 4. 5  B A S E LI N E D E S C RI P TI V E S T A TI S TI C S  
B aseli ne c hara cteristics  ( e.g ., de m o gra p hics , o nc ol o gic details , be ha vi oral c hara cteristics) f or t he N D U R E 
a n d Us ual Care ar ms will be s u m marize d, a n d descri pti ve statistics  c alc ulate d . Me dia n f oll o w -u p o ver all 
a n d b y trial ar m will be c alc ulate d usi n g a re verse Ka pla n -Meier esti mat or.  
 
9. 4. 6  P L A N N E D I N T E RI M A N A L Y S E S  
N/ A  
 
9. 4. 7  S U B -G R O U P A N A L Y S E S  
Pla n ne d s u b -gr o u p a nal yses of t he pri mar y e n d p oi nt will oc c ur base d o n a ge a n d se x t o e val uate t he i m pa ct 
of i ncl usi o n a cr oss t he lifes pa n a n d se x as bi ol o gic varia ble s. Hist oric al data ha ve n ot esta blis he d a n 
ass ociati o n bet wee n eit her a ge or se x wit h t he pri mar y e n d p oi nt 6. Gi ve n t he i m p orta nc e of rac e t o t he st u d y 
o bje cti ves, a nal ysis of t he pri mar y e n d p oi nt b y rac e is e val uate d as a se c o n dar y o bje cti ve i nstea d of pla n ne d 
s u bset a nal ysis. A d diti o nal pla n ne d s u bset a nal yses will e val uate t he i m pa ct of t he N D U R E i nter ve nti o n  o n 
t he pri mar y e n d p oi nt base d o n i ns ura nce stat us a n d fra g me ntati o n of care bet we e n t he s ur gic al fa cilit y a n d 
r a diati o n fa cilit y, b ot h of w hic h ha ve be e n descri be d as ris k fa ct ors f or dela ye d P O R T 6. As s uc h, b ot h of 
t hese varia bles ha ve t he p ote ntial t o c o nf o u n d t he effect of t he i nter ve nti o n were t he y t o be i m bala nce d i n 
a f ut ur e R C T. As s uc h, e val uati n g t heir i m pa ct o n t he pri mar y e n d p oi nt i n t his st u d y w o ul d all o w f or rati o nal 
str atific ati o n i n pla n ne d f ut ure R C Ts. 
 
9. 4. 8  T A B U L A TI O N O F I N DI VI D U A L P A R TI CI P A N T D A T A  
I n di vi d ual partici pa nt data will n ot be liste d b y me as ure a n d ti me p oi nt. 
 
9. 4. 9  E X P L O R A T O R Y A N A L Y S E S  

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F or ot her e x pl orat or y  e n d p oi nts (e. g., he alt h be ha vi or c o nstr ucts), data will be s u m marize d usi n g fre q ue nc y 
a n d per ce nt f or c ate g orical varia bles a n d usi n g me a n, me dia n, sta n dar d de viati o n, I Q R a n d ra n ge f or 
c o nti n u o us varia bles. 
We will c o nstr uct 9 0 % CIs t o pr o vi de a me as ure of u ncertai nt y i n esti mate d 
pr o p orti o ns a n d mea ns. C o m paris o ns bet we e n trial ar ms of ot her e x pl orat or y  e n d p oi nts will be perf or me d 
usi n g t-tests a n d c hi-s q uare tests, or Wilc o x o n ra n k s u m a n d Fis her’s e xact tests as a p pr o priate. Pr e - a n d 
p ost -i nter ve nti o n val ues of varia bles me as uri n g t he t he oretic al c o nstr ucts u n derl yi n g N D U R E (i.e. care 
c o or di nati o n, self -effic ac y i n c a ncer care, s u p p ort, a n d k n o wle d ge) will be c o m pare d usi n g Wilc o x o n si g n 
r a n k tests. C o m paris o ns bet wee n ar ms of t he c ha n ge i n sc ores will be c o n d ucte d usi n g Wilc o x o n ra n k s u m 
tests. 
 
F or t he e x pl orat or y  e n d p oi nts of barrier re d ucti o n a n d u nres ol ve d barriers, we will c alc ulate t he pr o p orti o n 
of u nres ol ve d barriers a n d t he fre q ue nc y of u nres ol ve d barriers (res pecti vel y) at t he e n d of N D U R E, 
c o nsiste nt wit h pri or P N st u dies 5 1. 
W e will use l o gisti c re gressi o n t o assess t he ass ociati o n  bet wee n 
u nr es ol ve d barriers a n d t he rate of P O R T dela y ( pri mar y e n d p oi nt), c o ntr olli n g f or ra n d o mizati o n 
str atific ati o n varia bles. 
 
 
1 0  S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L C O N S I D E R A TI O N S  
1 0. 1  R E G U L A T O R Y, E T HI C A L , A N D S T U D Y O V E R SI G H T C O N SI D E R A TI O N S  
1 0. 1. 1  I N F O R M E D C O N S E N T P R O C E S S 
W e will o btai n f ull writte n I nf or me d c o nse nt fr o m patie nts e nr olli n g i n t he st u d y. I nf or me d c o nse nt will 
oc c ur via fa ce-fa ce disc ussi o n bet we e n o ne of t he st u d y te a m me m bers desi g nate d t o perf or m i nf or me d 
c o nse nt a n d t he p ote ntial st u d y partici pa nt.  After descri bi n g t he st u d y a n d all o wi n g t he p ote ntial 
partici pa nts t o as k a n y q uesti o ns, we will sc he d ule i nter vie ws wit h t h ose w h o are eli gi ble a n d i ntereste d i n 
partici pati n g i n t he st u d y. Partici pa nt will ha ve ti me t o re a d t he i nf or me d c o nse nt f or m a n d HI P A A 
d oc u me nt o n t heir o w n.  C o nse nts will be writte n i n si m ple, e as y -t o-u n dersta n d la n g ua ge a n d o btai ne d o n 
t he da y of e nr oll me nt b y t he trai ne d st u d y c o or di nat or. A st u d y te a m me m ber will a ns wer a n y q uesti o ns 
a b o ut t he st u d y a n d partici pa nts will be as ke d t o si g n t he c o nse nt a n d HI P A A f or ms. All partici pa nts will 
si g n i nf or me d c o nse nt f or ms bef ore t he i nter vie w.  All par tici pa nts will rec ei ve a c o p y of t heir i nf or me d 
c o nse nt a n d HI P A A f or ms f or t heir re c or ds. T he i nf or me d c o nse nt pr oc ess will ta ke pla ce i n a pri vate r o o m 
i n t he R utle d ge T o wer He a d a n d Ne c k Ca ncer Cli nic or i n a pri vate r o o m i n t he H C C. O nl y t he st u d y 
part ici pa nt will pr o vi de i nf or me d c o nse nt. S u bjects will be all o we d u p t o o ne we e k t o deci de w het her t o 
partici pate i n t he st u d y.  
 
1 0. 1. 2  S T U D Y DI S C O N TI N U A TI O N A N D C L O S U R E  
T his st u d y ma y be te m p oraril y s us pe n de d or pre mat urel y ter mi nate d if t here is s ufficie nt reas o na ble ca use. 
Writte n n otific ati o n, d oc u me nti n g t he reas o n f or st u d y s us pe nsi o n or ter mi nati o n, will be pr o vi de d b y t he 
s us pe n di n g or ter mi nati n g part y t o st u d y partici pa nts, i n vesti gat or, f u n di n g a ge nc y, a n d re g ulat or y 
a ut h orities. If t he st u d y is pre mat urel y ter mi nate d or s us pe n de d, t he PI will pr o m ptl y i nf or m st u d y 
partici pa nts, t he I R B, a n d s p o ns or/f u n di n g a ge nc y a n d will pr o vi de t he re as o n(s) f or t he ter mi nati o n or 
s us pe nsi o n. St u d y partici pa nts will be c o nta cte d, as a p plic a ble, a n d be i nf or me d of c ha n ges t o st u d y visit 
sc he d ule. 
 
Cir c u msta nc es t hat ma y warra nt ter mi nati o n or s us pe nsi o n i ncl u de, b ut are n ot li mite d t o:  
•  
Deter mi nati o n of u ne x pecte d, si g nific a nt, or u na cc e pta ble ris k t o partici pa nts  
•  
I ns ufficie nt c o m plia nc e of st u d y staff t o t he pr ot oc ol (e. g. si g nific a nt pr ot oc ol vi olati o ns) 
•  
Data t hat are n ot s ufficie ntl y c o m plete a n d/ or e val ua ble  

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
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4 9  
 
T he st u d y ma y res u me o nce c o nc er ns a b o ut safet y, pr ot oc ol c o m plia nce, a n d data q ualit y are a d dresse d, 
a n d satisf y t he f u n di n g a ge nc y, s p o ns or, I R B, F o o d a n d Dr u g A d mi nistrati o n ( F D A), or ot her rele va nt 
r e g ulat or y or o versi g ht b o dies ( O H R P, D S M B).  
 
1 0. 1. 3  C O N FI D E N TI A LI T Y A N D P RI V A C Y  
Partici pa nt c o nfi de ntialit y a n d pri va c y is strictl y hel d i n tr ust b y t he partici pati n g i n vesti gat ors, t heir staff, 
t he saf et y a n d o versi g ht m o nit or(s), a n d t he s p o ns or(s) a n d f u n di n g a ge nc y. T his c o nfi de ntialit y is e xte n de d 
t o t he data bei n g c olle cte d as part of t his st u d y. Data t hat c o ul d be use d t o i de ntif y a s pecific st u d y 
partici pa nt will be hel d i n strict c o nfi de nce wit hi n t he researc h tea m. N o pers o nall y i de ntifia ble i nf or mati o n 
fr o m t he st u d y will be rele ase d t o a n y u na ut h orize d t hir d part y wit h o ut pri or writte n a p pr o val of t he 
s p o ns or/f u n di n g a ge nc y. T o hel p pr otect partici pa nt c o nfi de ntialit y, we will assi g n a u ni q ue st u d y I D 
n u m ber t o e a c h s u bject’s i nf or mati o n i n pla c e of his/ her na me a n d will la bel data c olle cti o n f or ms o nl y wit h 
t he I D n u m ber. All har d c o p y a n d ele ctr o nic files will be st ore d a p pr o priatel y usi n g d o u ble-l oc ke d met h o ds 
a n d pass w or d -pr ote cti o n. O nl y t he st u d y te a m me m ber will ha ve a c c ess t o st u d y re c or ds. Partici pa nt data 
will be c olle cte d a n d rec or de d o n eit her a pass w or d -pr ote cte d  ele ctr o nic data c a pt ure f or mat ( Researc h 
Ele ctr o nic Data Ca pt ure; R E D Ca p) or pa per -base d f or ms de pe n di n g u p o n patie nt prefere nc e. F or t he pa per 
c olle cti o n data met h o d, t he data c ollecti o n f or m will be la bele d o nl y wit h t he partici pa nt's u ni q ue st u d y I D 
n u m ber, a n d t he n st ore d wit hi n l oc ke d dra wers i n a l oc ke d offic e. T he i nf or mati o n o n t hese pa per f or ms 
will be tr a nsferre d t o a pass w or d -pr ote cte d R E D Ca p data base s uc h t hat all data will be st ore d i n t he 
pass w or d -pr ote cte d R E D Ca p Data base. O nl y me m bers of t h e st u d y te a m will ha ve a cc ess t o t he data. W e 
ha ve n o pla n t o use la pt o ps, j u m p dri ves, C Ds/ D V Ds t o tra ns p ort data.  
All r ese ar c h a cti vities will be c o n d ucte d i n as pri vate a setti n g as p ossi ble.  
 
T he st u d y m o nit or, ot her a ut h orize d re prese ntati ves of t he s p o ns or or f u n di n g a ge nc y, re prese ntati ves of 
t he I R B, r e g ulat or y a ge ncies or re prese ntati ves fr o m c o m pa nies or or ga nizati o ns s u p pl yi n g t he pr o d uct, 
ma y i ns pe ct all d oc u me nts a n d re c or ds re q uire d t o be mai ntai ne d b y t he i n vesti gat or, i ncl u di n g b ut n ot 
li mite d t o, me dic al re c or ds ( offic e, cli nic, or h os pital) a n d p har ma c y re c or ds f or t he partici pa nts i n t his 
st u d y. T he cli nic al st u d y site will per mit a c cess t o s uc h rec or ds.  
 
T he st u d y partici pa nt’s c o nta ct i nf or mati o n will be sec urel y st ore d at ea c h cli nic al site f or i nter nal use 
d uri n g t he st u d y. At t he e n d of t he st u d y, all re c or ds will c o nti n ue t o be ke pt i n a sec ure l oc ati o n f or as l o n g 
a peri o d as dictate d b y t he re vie wi n g I R B, I nstit uti o nal p olicies, or s p o ns or/f u n di n g a ge nc y re q uire me nts.  
 
It is NI H p olic y t hat t he res ults a n d a cc o m plis h me nts of t he acti vities t hat it f u n ds s h o ul d be ma de a vaila ble 
t o t he p u blic (see htt ps:// gr a nts. ni h. g ov/ p olic y/s h ari n g. ht m ). T he PI will e ns ure all me c ha nis ms use d t o 
s har e data will i ncl u de pr o per pla ns a n d safe g uar ds f or t he pr ote cti o n of pri vac y, c o nfi de ntialit y, a n d 
se c urit y f or data disse mi nati o n a n d re use (e. g., all data will be t h or o u g hl y de -i de ntifie d a n d will n ot be 
tr a ce a ble t o a s pecific st u d y partici pa nt). Pla ns f or arc hi vi n g a n d l o n g-ter m preser vati o n of t he data will be 
i m ple me nte d, as a p pr o priate.  
 
T o f urt her pr otect t he pri va c y of st u d y partici pa nts, t he Se cretar y, He alt h a n d H u ma n Ser vices ( H H S), has 
iss ue d a Certificate of C o nfi de ntialit y ( C o C) t o all rese arc hers e n ga ge d i n bi o me dical, be ha vi oral, cli nical 
or ot her h u ma n s u bje cts researc h f u n de d w h oll y or i n part b y t he fe deral g o ver n me nt.   Reci pie nts of NI H 
f u n di n g f or h u ma n s u bje cts researc h are re q uire d t o pr ote ct i de ntifia ble researc h i nf or mati o n fr o m f orc e d 
discl os ure per t he ter ms of t he NI H P olic y (see htt ps:// h u m a ns u bje cts. ni h. g ov/c oc/i n dex ). As set f ort h i n 4 5 
C F R Part 7 5. 3 0 3(a)  a n d NI H G P S C ha pter 8. 3 , reci pie nts c o n d ucti n g NI H-s u p p orte d rese arc h c o ver e d b y 
t his P olic y are re q uire d t o esta blis h a n d mai ntai n effe cti ve i nter nal c o ntr ols (e. g., p olicies a n d pr oc e d ur es) 
t hat pr o vi de reas o na ble ass ura nce t hat t he a war d is ma na ge d i n c o m plia nce wit h Fe deral stat utes, 
r e g ulati o ns, a n d t he ter ms a n d c o n diti o ns of a war d. It is t he NI H p olic y t hat i n vesti gat ors a n d ot hers w h o 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
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Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
5 0  
ha ve ac cess t o rese arc h re c or ds will n ot discl ose i de ntif yi n g i nf or mati o n e xce pt w he n t he partici pa nt 
c o nse nts or i n certai n i nsta nc es w he n fe deral, state, or l oc al la w or re g ulati o n re q uires discl os ure. NI H 
e x pe cts i n vesti gat ors t o i nf or m researc h partici pa nts of t he pr ote cti o ns a n d t he li mits t o pr ote cti o ns pr o vi de d 
b y a Certificate iss ue d b y t his P olic y.  
 
1 0. 1. 4  F U T U R E U S E O F S T O R E D S P E CI M E N S A N D D A T A  
Data c olle cte d f or t his st u d y will be a nal yze d a n d st ore d wit h t he st u d y te a m.  After t he st u d y is c o m plete d, 
t he de-i de ntifie d, arc hi ve d data will be tra ns mitte d t o a n d st ore d wit h t he st u d y te a m , f or use b y ot her 
r esear c hers i ncl u di n g t h ose o utsi de of t he st u d y. 
 
1 0. 1. 5  K E Y R O L E S  A N D S T U D Y G O V E R N A N C E  
Pri n ci p al I n vesti g at or  
E va n Gr a b o yes, M D , M P H, F A C S 
Me dic al U ni versit y of S o ut h Car oli na  
1 3 5 R utle d ge A ve, M S C 5 5 0  
C harlest o n, S C 2 9 4 2 5  
8 4 3 -7 9 2 -0 7 1 9  
gr a b o yes @ m usc.e d u  
 
1 0. 1. 6  S A F E T Y O V E R SI G H T  
S afet y o versi g ht will be u n der t he directi o n of a PI.  A g gre gate re vie ws will oc c ur b y t he PI f or all A Es, 
U Ps, pr ot oc ol vi olati o ns, a u dit res ults, earl y wit h dra wals, w het her t he st u d y ac cr ual patter n warr a nts 
c o nti n uati o n/a cti o n, a n d e n d p oi nt data. A g gre gate re vie ws will oc c ur m o nt hl y.  
 
1 0. 1. 7  C LI NI C A L M O NI T O RI N G  
N/ A  
 
1 0. 1. 8  Q U A LI T Y A S S U R A N C E ( Q A) A N D Q U A LI T Y C O N T R O L  ( Q C) 
Ea c h cli nical site will perf or m i nter nal q ualit y ma na ge me nt of st u d y c o n d uct, data a n d bi ol o gical s peci me n 
c olle cti o n, d oc u me ntati o n a n d c o m pleti o n. 
 
Q ualit y c o ntr ol ( Q C) pr oc e d ures will be i m ple me nte d as f oll o ws:  
 
I nf or m e d c o nse nt --- St u d y staff will re vie w b ot h t he d oc u me ntati o n of t he c o nse nti n g pr oc ess as well as 
a per ce nta ge of t he c o m plete d c o nse nt d oc u me nts.  T his re vie w will e val uate c o m plia nc e wit h G C P, 
a c c ur ac y, a n d c o m plete ness.  Fe e d bac k will be pr o vi de d t o t he st u d y tea m t o  e ns ure pr o per c o nse nti n g 
pr oc e d ur es are f oll o we d .  
 
S o ur c e d oc u me nts a n d t h e ele ctr o nic d at a --- Data will be i nitiall y c a pt ure d o n s o urc e d oc u me nts (se e 
S e cti o n 1 0. 1. 9 , D at a H a n dli n g a n d Re c or d Kee pi n g) a n d will ulti matel y be e ntere d i nt o t he st u d y 
data base.  T o e ns ure ac c ura c y site staff will c o m pare a re prese ntati ve sa m ple of s o urce data a gai nst t he 
data base, tar geti n g ke y data p oi nts i n t hat re vie w.  
 
I nt er ve nti o n Fi d elit y —  C o nsiste nt deli ver y of t he st u d y i nter ve nti o ns will be m o nit ore d t hr o u g h o ut t he 
i nter ve nti o n p hase of t he st u d y. Pr oc e d ur es f or e ns uri n g fi delit y of i nter ve nti o n deli ver y are descri be d i n 
S e cti o n 6. 2. 1 , I nter ve nti o nist Tr ai ni n g a n d Tr ac ki n g.  

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5 1  
 
S h o ul d i n de pe n de nt m o nit ori n g be c o me ne cessar y, t he PI will pr o vi de dire ct ac cess t o all trial relate d sites, 
s o urc e data/ d oc u me nts, a n d re p orts f or t he p ur p ose of m o nit ori n g a n d a u diti n g b y t he s p o ns or/f u n di n g 
a ge nc y, a n d i ns pecti o n b y l ocal a n d re g ulat or y a ut h orities.  
 
1 0. 1. 9  D A T A  H A N D LI N G  A N D R E C O R D  K E E PI N G   
1 0. 1. 9. 1  D A T A C O L L E C TI O N A N D  M A N A G E M E N T R E S P O N SI BI LI TI E S  
Data c olle cti o n will be  t he res p o nsi bilit y of t he cli nic al trial staff at t he site u n der t he s u per visi o n of t he site 
in vesti gat or . T he i n vesti gat or will be  res p o nsi ble f or e ns uri n g t he a c c ura c y, c o m plete ness, le gi bilit y, a n d 
ti meli ness of t he data re p orte d. All s o urc e d oc u me nts will  be c o m plete d i n a neat, le gi ble ma n ner t o e ns ure 
a c c ur ate i nter pretati o n of data.  
 
Har dc o pies of t he st u d y visit w or ks heets will be pr o vi de d f or use as s o urc e d oc u me nt  w or ks heets f or 
r e c or di n g data f or e a c h partici pa nt c o nse nte d/ e nr olle d i n t he st u d y.  Data re c or de d i n t he e C R F deri ve d 
fr o m s o urce d oc u me nts will  be c o nsiste nt wit h t he data rec or de d o n t he s o urce d oc u me nts.  
 
Cli nic al data will be e ntere d i nt o R E D Ca p . T he data s yste m i ncl u des pass w or d pr ote cti o n a n d i nter nal 
q ualit y c he c ks, s uc h as a ut o matic ra n ge c hec ks, t o i de ntif y data t hat a p pear i nc o nsiste nt, i nc o m plete, or 
i na c c ur ate. Cli nic al data will be e ntere d dire ctl y fr o m t he s o urc e d oc u me nts. 
 
1 0. 1. 9. 2  S T U D Y R E C O R D S R E T E N TI O N  
I n a c c or da nce wit h He alt h a n d H u ma n S er vic es re g ulati o n at 4 5 C F R 4 6. 1 1 5( b), we will retai n I R B re c or ds 
f or at le ast t hre e ye ars. At t he e n d of t hree years, rec or ds will be b o xe d, la bele d, a n d se nt t o c e ntral st or a ge 
f or a n ot her t hre e ye ars. Rese arc h rec ords will be retai ne d f or si x ye ars t o all o w e val uati o n a n d re petiti o n 
b y ot hers of t he res ults a n d t o i n vesti gate a n alle gati o n of researc h misc o n d uct.  
 
1 0. 1. 1 0  
P R O T O C O L D E VI A TI O N S   
A pr ot oc ol de viati o n is a n y varia nc e fr o m t he pr ot oc ol i n v ol vi n g a s u bject or s u bje cts t hat is n ot a p pr o ve d 
b y t he I R B pri or t o its i nitiati o n or i m ple me ntati o n, a n d oc c urs w he n a me m ber of t he st u d y te a m de parts 
fr o m t he I R B-a p pr o ve d pr ot oc ol i n a n y wa y w it h o ut t he i n vesti gat or first o btai ni n g I R B a p pr o val ( S ee 
M U S C I R B P olic y H R P P 4. 1 4).  
 
1 0. 1. 1 1  
P U B LI C A TI O N A N D D A T A S H A RI N G P O LI C Y   
T his st u d y will  be  c o n d ucte d i n a cc or da nc e wit h t he f oll o wi n g p u blic ati o n a n d data s hari n g  p olicies a n d 
r e g ulati o ns: 
 
Nati o nal I nstit utes of He alt h ( NI H ) P u blic Ac cess P olic y, w hic h e ns ures t hat t he p u blic has ac cess t o t he 
p u blis he d r es ults of NI H f u n de d researc h. It re q uires scie ntists t o s u b mit fi nal pe er -re vie we d j o ur nal 
ma n uscri pts t hat arise fr o m NI H f u n ds t o t he di gital arc hi ve P u b Me d Ce ntral u p o n a c ce pta nce f or 
p u blic ati o n.  
 
T his st u d y will c o m pl y wit h t he NI H Data S hari n g P olic y a n d P olic y o n t he Disse mi nati o n of NI H -F u n de d 
Cli nic al Trial I nf or mati o n a n d t he Cli nic al Trials Re gistrati o n a n d Res ults I nf or mati o n S u b missi o n r ule . As 
s uc h, this trial will be  re gistere d at Cli nic al Trials. g o v, a n d res ults i nf or mati o n fr o m t his trial will  be 
s u b mitte d t o Cli nic al Trials. g o v. I n a d diti o n, e ver y atte m pt will be ma de t o p u blis h res ults i n pe er-re vie we d 
j o ur nals.  Data fr o m t his st u d y ma y be re q ueste d fr o m ot her researc hers 2  ye ars after t he c o m pleti o n of t he 

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pri mar y e n d p oi nt b y c o nta cti n g E va n Gra b o yes, M D , M P H.  C o nsi derati o ns f or e ns uri n g c o nfi de ntialit y of 
t hese s hare d data are descri be d i n Se cti o n 1 0. 1. 3 . 
 
1 0. 1. 1 2  
C O N F LI C T O F  IN T E R E S T  P O LI C Y  
T he i n de pe n de nce of t his st u d y fr o m a n y act ual or percei ve d i nfl ue nc e  is critical. T heref ore , a n y a ct ual 
c o nflict of i nterest of pers o ns w h o ha ve a r ole i n t he desi g n, c o n d uct, a nal ysis, p u blic ati o n, or a n y as pe ct 
of t his trial will be discl ose d a n d ma na ge d. F urt her m ore, pers o ns w h o ha ve a perc ei ve d c o nflict of i nterest 
will be r e q uire d t o ha ve s u c h c o nflicts ma na ge d i n a wa y t hat is a p pr o priate t o t heir partici pati o n i n t he 
des ig n a n d c o n d uct of t his t rial. T he st u d y lea ders hi p i n c o nj u ncti o n wit h t he N CI  has esta blis he d p olicies 
a n d pr oce d ures f or all st u d y gr o u p me m bers t o discl ose all c o nflicts of i nterest a n d will esta blis h a 
me c ha nis m f or t he ma na ge me nt of all re p orte d d ualities of i nterest.  
 
1 0. 2  A D DI TI O N A L C O N SI D E R A TI O N S  
N/ A  
 
1 0. 3  A B B R E VI A TI O N S A N D S P E CI A L T E R M S  
 
T a ble 4 . A b b re vi ati o ns a n d S pe ci al Te r ms 
A A  
A A  
A E  
A d verse E ve nt  
AJ C C  
A merica n J oi nt C o m mitte e o n Ca nc er  
B R F S S  
Be ha vi oral Ris k Fa ct or S ur veilla nce S ur ve y  
C A S E  
C o m m u nic ati o n & Attit u di nal S elf -Effica c y  
C F R  
C o de of Fe deral Re g ulati o ns  
CI  
C o nfi de nc e I nter val  
e C R F  
Electr o nic Case Re p ort F or m  
C T  
C o m p ute d  T o m o gra p h y  
C T M -1 5  Care Tra nsiti o n Met h o d -1 5  
D C C  
Data C o or di nati n g Ce nter  
D S M B  
Data Safet y M o nit ori n g B oar d  
e C R F  
Electr o nic Case Re p ort F or ms  
E M R  
Electr o nic Me dic al Rec or d  
E N E  
E xtra n o dal E xte nsi o n  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
F D G  
F l u or o-de o x y gl uc ose  
G C P  
G o o d Cli nic al Pra ctic e  
H B M  
He alt h Belief M o del  
H C C  
H olli n gs Ca nc er Ce nter  
HI P A A  
He alt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act  
H N S C C  
He a d a n d Nec k S q ua m o us Cell Carci n o ma  
I C H 
I nter nati o nal C o u ncil o n Har m o nisati o n  
I D E 
I n vesti gati o nal De vic e E xe m pti o n 
I N D 
I n vesti gati o nal Ne w Dr u g 
I P Q-R  
Ill ness Perc e pti o n Q uesti o n naire -Re vise d  
I R B 
I nstit uti o nal Re vie w B oar d 
I S E L-1 2  
I nter pers o nal S u p p ort E val uati o n List-1 2  
I T T 
I nte nti o n-T o -Tr e at  

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
5 3  
L VI  
L y m p h o vasc ular I n vasi o n  
M O P  
Ma n ual of Pr oce d ures  
M RI  
Ma g netic Res o na nc e I ma gi n g  
M U S C  
Me dic al U ni versit y of S o ut h Car oli na  
N CI  
Nati o nal Ca ncer I nstit ute  
N C C N  
Nati o nal C o m pre he nsi ve Ca nc er Net w or k  
N C T  
Nati o nal Cli nic al Trial  
N D U R E  
Na vi gati o n f or Dis parities a n d U nti mel y Ra diati o n t h Er a p y  
NI H  
Nati o nal I nstit utes of He alt h  
O H R P  
Office f or H u ma n Researc h Pr ote cti o ns  
P E T  
P ositr o n E missi o n T o m o gra p h y  
PI  
Pri nci pal I n vesti gat or  
P N  
Patie nt Na vi gati o n  
P NI  
Peri ne ural I n vasi o n  
P O R T  
P ost o perati ve Ra diati o n T hera p y  
Q A  
Q ualit y Ass ura nce  
Q C  
Q ualit y C o ntr ol  
R C T  
Ra n d o mize d C o ntr olle d Trial  
R E D Ca p  Researc h Electr o nic Data Ca pt ure  
R T  
Ra diati o n T hera p y  
S C C  
S q ua m o us Cell Carci n o ma  
S A E  
S eri o us A d verse E ve nt  
S o A  
S c he d ule of Acti vities  
S O P  
Sta n dar d O perati n g Pr oc e d ure  
T T P  
Ti me -t o-P O R T  
U P  
U na ntici pate d Pr o ble m  
U S  
U nite d States  
 
 
 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
5 4  
1 0. 4  P R O T O C O L  A M E N D M E N T  H I S T O R Y 
 
T a ble 5 . Pr ot oc ol A me n d me nt Hist or y 
Ve rsi o n  
D ate  
Descri pti o n of C h a n ge  
Brief R ati o n ale  
1. 1  
7/ 2 6/ 1 9  
-Re m o ve d 1 0 t h fl o or fr o m l ocati o n of 
I C F pr oc ess 
-re m o ve d la n g ua ge a b o ut a bilit y t o 
pr o vi de i nf or me d c o nse nt a n d a d here 
t o st u d y r e gi me n fr o m i ncl usi o n 
criteria 
-c ha n ges re q ueste d b y M U S C 
I R B 
2. 0  
9/ 2 7/ 1 9  
-u p date d o bjecti ves t o s pecif y 
c o m paris o n of N D U R E wit h U C  
-cre ate d m ore c o m pre he nsi ve a n d 
s pecific S o A 
-re m o ve d ne oa dj u va nt t hera p y; 
a d de d s y nc hr o n o us mali g na nc y t o 
e xcl usi o n criteria 
-re m o ve d M D A SI-H N  
-a d de d NI H c o nfi de ntialit y v oc a b  
-e n ha nc e clarit y of o bjecti ves 
 
-m ore tra ns pare nt S o A  
 
-i m pr o ve cli nic al rele va nce of 
tar get p o p ulati o n 
 
-i m pr o ve cli nic al w or kfl o w 
-NI H c o m plia nc e  
3. 0  
1 2/ 1 6/ 1 9  
-re plac e d Eliza bet h Hill wit h H o n g 
Li o n st u d y te a m  
 
-u p date d S O A  
 
 
 
-a d de d w hite or A A rac e t o i ncl usi o n 
criteria 
 
-clarifie d stratifie d sa m pli n g a n d 
stratifie d ra n d o mizati o n 
 
 
-re na me barrier l oa d s ur ve y 
 
-har m o nize d sta gi n g i nf or mati o n i n 
i ncl usi o n criteria wit h m o d I T T 
p o p ulati o n  
-Eliza bet h Hill left M U S C/ H C C  
 
 
-m ore pre cisi o n; a d dress 
a c ci de ntal o verla p bet we e n visit 
1 a n d 2  
 
-i nter nall y har m o nize pr ot oc ol 
 
 
-pre vi o usl y mis -re p orte d as 
stratifie d ra n d o mizati o n a cr oss 
t w o strata 
 
-clarit y f or st u d y assess me nt 
 
-i nter nall y har m o nize pr ot oc ol 
4. 0  
2/ 2 6/ 2 0  
-all o we d use of tele me dici ne f or 
N D U R E sessi o ns 1 or 3  
 
-a d de d N D U R E n o m o gra m 
 
 
-clarifie d t hat c o m or bi dit y will be 
me as ure d usi n g A C E -2 7  
-C O VI D -1 9  
 
 
-assess pre -tre at me nt ris k of 
P O R T dela y  
 
-pre vi o usl y n ot s pecifie d 
5. 0  
0 6/ 0 9/ 2 2  
-re vise d S O A 
 
 
-i m pr o ve clarit y a n d pr o vi de 
a d diti o nal g ui da nc e 
 
 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
5 5  
-r e-classifie d s o me se c o n dar y 
e n d p oi nts as e x pl orat or y 
 
-pr o vi de d m ore detail o n descri pti o n 
of N D U R E a n d Us ual Care  
 
 
-a d de d s u bse cti o ns a n d details t o 
clarif y st u d y assess me nt  
-err or i n ori gi nal pr ot oc ol 
 
 
-refle ct p u blis he d w or k; e ns ure 
c o nsiste nt deli ver y of Us ual 
Care  
 
-e n ha nc e usa bilit y of pr ot oc ol 
f or pr o gra m c o or di nat or 
6. 0  
1 0/ 1 5/ 2 3  
-A d de d ne w sec o n dar y (treat me nt 
pa c ka ge ti me) a n d e x pl orat or y 
( P O R T d ur ati o n, c o m pleti o n of 
i nte n de d P O R T, r e as o n f or P O R T 
dela y) e n d p oi nts  
 
-A d de d detail a b o ut defi niti o ns of 
sec o n dar y a n d e x pl orat or y e n d p oi nts 
 
-Delete d u n ne cessar y te xt fr o m 
o verall desi g n  
 
 
 
-Clarifie d relati o ns hi p bet wee n 
eli gi bilit y criteria, criteria f or 
partici pa nt disc o nti n uati o n, a n d 
e val ua ble p o p ulati o ns f or a nal ysis  
 
-Clarifie d pri oritizati o n bet wee n 
i nflate d sa m ple size a n d sa m ple size 
f or P O R T dela y a nal ysis set if 
i nflate d sa m ple size was n ot 
s ufficie ntl y c o nser vati ve 
 
-A d de d secti o n o n missi n g data a n d 
c orres p o n di n g a nal yses f or ne w 
sec o n dar y a n d e x pl orat or y e n d p oi nts 
-A d dress c o ncer n t hat s h orter 
ti me-t o-P O R T c o ul d le a d t o 
u ni nte n de d brea ks d uri n g P O R T  
 
 
 
-A d dress a m bi g uit y i n 
defi niti o ns of e n d p oi nts  
 
-Te xt was i n wr o n g secti o n of 
pr ot oc ol a n d d u plic ati ve wit h 
te xt i n pr o per secti o n of 
pr ot oc ol  
 
-A d dress i nc o nsiste ncies 
re gar di n g best wa y t o defi ne 
criteria i n q uesti o n  
 
 
-A d dress a m bi g uit y a b o ut tar get 
sa m ple size 
 
 
 
 
-A d dress deficie ncies i n pri or 
pr ot oc ol a n d har m o nize 
statistic al a nal ysis se cti o n wit h  
pr ot oc ol c ha n ges descri be d 
a b o ve 
7. 0  
1 2/ 1 5/ 3 1  
-Har m o nize d e n d -of -st u d y defi niti o n 
wit h sec o n dar y e n d p oi nt of treat me nt 
pa c ka ge ti me  
 
 
 
U p date d defi niti o n of ti me -t o-P O R T 
t o e ns ure t hat le n gt h y dela ys i n 
i nitiati n g P O R T w o ul d be c a pt ure d 
wit hi n t he data  
 
-Faile d t o har m o nize e n d -of -
st u d y defi niti o n wit h e n d p oi nt 
of tre at me nt pa c ka ge ti me at 
ti me of pri or a me n d me nt a d di n g 
tre at me nt pac ka ge ti me  
 
-Fail ure t o c o nsi der l o n ger ti me -
t o-P O R T o pti o ns i n ori gi nal 
defi niti o n of t he e n d p oi nt  
 
 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
5 6  
-refi ne d ca ncer care deli ver y pr ocess 
assess me nt defi niti o ns  
 
-clarifie d C T M -1 5 is m o difie d  
 
 
 
Pr o vi de d e x plicit details a b o ut 
e val ua ble p o p ulati o ns f or sec o n dar y 
e n d p oi nts t hat were n ot pre vi o usl y 
defi ne d  
 
-Refi ne d missi n g data t o har m o nize 
wit h u p date d defi niti o n of ti me -t o-
P O R T  
 
-Descri be m o del -base d a p pr oac h t o 
a nal yzi n g pri mar y e n d p oi nt 
 
-Pr o vi de e x plicit a n d detaile d 
a nal ysis pla n f or se c o n dar y  
-A d dress a m bi g uit y, fi x t y p os  
 
 
-F ail ure t o e x plicitl y state t hat 
o nl y 1 2 of 1 5 ite ms i n C T M -1 5 
were bei n g use d  
 
-A d dress i nc o nsiste ncies 
re gar di n g best wa y t o defi ne 
criteria i n q uesti o n  
 
 
-Har m o nize wit h ot her c ha n ges  
 
 
 
-A li g n wit h F D A g ui da nc e a n d 
data str uct ure  
 
-H ar m o nize wit h defi niti o ns of 
e val ua ble p o p ulati o ns f or 
sec o n dar y e n d p oi nts 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
5 7  
1 1  R E F E R E N C E S  
1.  
S oci ety A C. C a nc er F acts & Fi g ur es 2 0 1 8. Av ail a bl e at: htt ps:// w w w.c a nc er. or g/c o nt e nt/ d a m/c a nc er -
or g/r es e arc h/c a nc er -f acts-a n d -st atistics/ a n n u al-c a nc er-f acts-a n d -fi g ur es/ 2 0 1 8/c a nc er-f acts-a n d -fi g ur es-
2 0 1 8. p df . Acc ess e d F e br u ar y 2 6 2 0 1 8. 
2.  
M oli n a M A, C h e u n g M C, P er ez E A et al. Afric a n A m eric a n a n d p o or p ati e nts h av e a dr a m atic ally w ors e 
pr o g n osis f or h e a d a n d n ec k c a nc er: a n ex a mi n ati o n of 2 0, 9 1 5 p ati e nts. C a nc er 2 0 0 8; 1 1 3: 2 7 9 7 -2 8 0 6.  
3.  
G utt m a n n D M, K o bi e J, Gr o v er S et al. N ati o n al dis p ariti es i n tr e at m e nt p ac k a g e ti m e f or r es ect e d l oc ally 
a d v a nc e d h e a d a n d n ec k c a nc er a n d i m p act o n ov er all s ur viv al. H e a d N ec k 2 0 1 8; 4 0: 1 1 4 7 -1 1 5 5.  
4.  
H o A S, Ki m S, Ti g hi o u art M et al. Q u a ntit ativ e s ur viv al i m p act of c o m p osit e tr e at m e nt d el ays i n h e a d a n d 
n ec k c a nc er. C a nc er 2 0 1 8; 1 2 4: 3 1 5 4 -3 1 6 2.  
5.  
N et w or k N C C. N C C N Cli nic al Pr actic e G ui d eli n es i n O nc ol o g y ( N C C N G ui d eli n es): H e a d a n d N ec k C a nc ers. 
F ort W as hi n gt o n, P A: N ati o n al C o m pr e h e nsiv e C a nc er N et w or k, 2 0 2 2.  
6.  
Gr a b o y es E M, G arr ett -M a y er E, S h ar m a A K, L e ntsc h EJ, D ay T A. A d h er e nc e t o N ati o n al C o m pr e h e nsiv e 
C a nc er N et w or k g ui d eli n es f or ti m e t o i niti ati o n of p ost o p er ati v e r a di ati o n t h er a p y f or p ati e nts wit h h e a d 
a n d n ec k c a nc er. C a nc er 2 0 1 7; 1 2 3: 2 6 5 1 -2 6 6 0.  
7.  
Gr a b o y es E M, G arr ett -M a y er E, Ellis M A et al. Eff ect of ti m e t o i niti ati o n of p ost o p er ativ e r a di ati o n t h er a p y 
o n s ur viv al i n s ur gic ally m a n a g e d h e a d a n d n ec k c a nc er. C a nc er 2 0 1 7; 1 2 3: 4 8 4 1 -4 8 5 0.  
8.  
Gr a b o y es E, K o m p elli A, N es k e y D et al. Ass oci ati o n of Tr e at m e nt D el ays wit h S ur viv al f or P ati e nts wit h 
H e a d a n d N ec k C a nc er. J A M A ot ol ar y n g ol o g y -- h e a d & n ec k s ur g er y 2 0 1 9; 1 4 5: 1 6 6 -1 7 7.  
9.  
T e n g M S, G u pt a V. Ti m el y A dj u v a nt P ost o p er ativ e R a di ot h er a p y: R aci n g t o a P O R T i n t h e St or m. J A M A 
ot ol ar y n g ol o g y -- h e a d & n ec k s ur g er y 2 0 1 8.  
1 0.  
Fr e u n d K M, B att a gli a T A, C al h o u n E et al. I m p act of p ati e nt n avi g ati o n o n ti m el y c a nc er c ar e: t h e P ati e nt 
N avi g ati o n R es e arc h Pr o gr a m. J N atl C a nc er I nst 2 0 1 4; 1 0 6: dj u 1 1 5.  
1 1.  
P as k ett E D, K atz ML, P ost D M et al. T h e O hi o P ati e nt N a vi g ati o n R es e arc h Pr o gr a m: d o es t h e A m eric a n 
C a nc er S oci ety p ati e nt n avi g ati o n m o d el i m pr o v e ti m e t o r es ol uti o n i n p ati e nts wit h a b n or m al scr e e ni n g 
t ests ? C a nc er E pi d e mi ol Bi o m ar k ers Pr e v 2 0 1 2; 2 1: 16 2 0 -1 6 2 8.  
1 2.  
G u a d a g n ol o B A, D o h a n D, R aic h P. M etrics f or e v al u ati n g p ati e nt n avi g ati o n d uri n g c a nc er di a g n osis a n d 
tr e at m e nt: cr afti n g a p olic y-r el e v a nt r es e arc h a g e n d a f or p ati e nt n avi g ati o n i n c a nc er c ar e. C a nc er 2 0 1 1; 
1 1 7: 3 5 6 5 -3 5 7 4.  
1 3.  
Si e g el RL, Mill er K D, J e m al A. C a nc er St atistics, 2 0 1 7. C A C a nc er J Cli n 2 0 1 7; 6 7: 7 -3 0.  
1 4.  
M ur p h y C T, G all o w ay TJ, H a n d orf E A et al. S ur viv al I m p act of I ncr e asi n g Ti m e t o Tr e at m e nt I niti ati o n f or 
P ati e nts Wit h H e a d a n d N ec k C a nc er i n t h e U nit e d St at es. J Cli n O nc ol 2 0 1 6; 3 4: 1 6 9 -1 7 8.  
1 5.  
Cr a m er J D, S p e e d y S E, F erris RL, R a d e m a k er A W, P at el U A, S a m a nt S. N ati o n al e v al u ati o n of 
m ulti disci pli n ar y q u ality m etrics f or h e a d a n d n ec k c a nc er. C a nc er 2 0 1 7; 1 2 3: 4 3 7 2 -4 3 8 1.  
1 6.  
A n g K K, Tr otti A, Br o w n B W et al. R a n d o miz e d tri al a d dr essi n g ris k f e at ur es a n d ti m e f act ors of s ur g er y 
pl us r a di ot h er a p y i n a d v a nc e d h e a d -a n d -n ec k c a nc er. I nt J R a di at O nc ol Bi ol P h ys 2 0 0 1; 5 1: 5 7 1 -5 7 8.  
1 7.  
H u a n g J, B ar b er a L, Br o u w ers M, Br o w m a n G, M ac kill o p WJ. D o es d el ay i n st arti n g tr e at m e nt aff ect t h e 
o utc o m es of r a di ot h er a p y ? A s yst e m atic r e vi e w. J Cli n O nc ol 2 0 0 3; 2 1: 5 5 5 -5 6 3.  
1 8.  
B er ni er J, D o m e n g e C, Ozs a hi n M et al. P ost o p er ativ e irr a di ati o n wit h or wit h o ut c o nc o mit a nt 
c h e m ot h er a p y f or l oc all y a d v a nc e d h e a d a n d n ec k c a nc er. N E n gl J M e d 2 0 0 4; 3 5 0: 1 9 4 5 -1 9 5 2.  
1 9.  
C o o p er J S, P aj a k T F, F or asti er e A A et al. P ost o p er ati v e c o nc urr e nt r a di ot h er a p y a n d c h e m ot h er a p y f or 
hi g h -ris k s q u a m o us-c ell c arci n o m a of t h e h e a d a n d n ec k. N E n gl J M e d 2 0 0 4; 3 5 0: 1 9 3 7 -1 9 4 4.  
2 0.  
S h e w M, N e w J, B ur A M. M ac hi n e L e ar ni n g t o Pr e dict D el ays i n A dj u v a nt R a di ati o n f oll o wi n g S ur g er y f or 
H e a d a n d N ec k C a nc er. Ot ol ar y n g ol H e a d N ec k S ur g 2 0 1 9: 1 9 4 5 9 9 8 1 8 8 2 3 2 0 0.  
2 1.  
C h e n M M, H arris J P, Or osc o R K, Sirj a ni D, H ar a W, Divi V. Ass oci ati o n of Ti m e b et w e e n S ur g er y a n d 
A dj u v a nt T h er a p y wit h S ur viv al i n Or al C avity C a nc er. Ot ol ar y n g ol H e a d N ec k S ur g 2 0 1 8; 1 5 8: 1 0 5 1 -1 0 5 6.  
2 2.  
A mi ni A, St o k es W A, J o n es BL et al. P ost o p er ativ e r a di ati o n p erf or m e d at t h e s a m e s ur gic al f acility 
ass oci at e d wit h i m pr o v e d o v er all s ur viv al i n or al c avity s q u a m o us c ell c arci n o m a. H e a d N ec k 2 0 1 9.  
2 3.  
H o ult o n JJ. D efi ni n g O pti m al Tr e at m e nt Ti m es i n H e a d a n d N ec k C a nc er C ar e: W h at Ar e W e W aiti n g F or ? 
J A M A ot ol ar y n g ol o g y-- h e a d & n ec k s ur g er y 2 0 1 8.  
2 4.  
Divi V, C h e n M M, H ar a W et al. R e d uci n g t h e Ti m e fr o m S ur g er y t o A dj u v a nt R a di ati o n T h er a p y: A n 
I nstit uti o n al Q u ality I m pr ov e m e nt Pr oj ect. Ot ol ar y n g ol H e a d N ec k S ur g 2 0 1 8; 1 5 9: 1 5 8-1 6 5.  

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
5 8  
2 5.  
B att a gli a T A, B a k S M, H e er e n T et al. B ost o n P ati e nt N a vi g ati o n R es e arc h Pr o gr a m: t h e i m p act of 
n avi g ati o n o n ti m e t o di a g n ostic r es ol uti o n aft er a b n or m al c a nc er scr e e ni n g. C a nc er E pi d e mi ol 
Bi o m ar k ers Pr e v 2 0 1 2; 2 1: 1 6 4 5 -1 6 5 4.  
2 6.  
R o bi ns o n -W hit e S, C o nr oy B, Sl avis h K H, R os e nz w ei g M. P ati e nt n avi g ati o n i n br e ast c a nc er: a s yst e m atic 
r e vi e w. C a nc er N urs 2 0 1 0; 3 3: 1 2 7-1 4 0.  
2 7.  
N at al e -P er eir a A, E n ar d K R, N e v ar ez L, J o n es L A. T h e r ol e of p ati e nt n avi g at ors i n eli mi n ati n g h e alt h 
dis p ariti es. C a nc er 2 0 1 1; 1 1 7: 3 5 4 3 -3 5 5 2.  
2 8.  
Br o o k e B S, Sl a g er SL, S w or ds D S, W eir C R. P ati e nt a n d c ar e giv er p ers p ectiv es o n c ar e c o or di n ati o n d uri n g 
tr a nsiti o ns of s ur gic al c ar e. Tr a nsl B e h a v M e d 2 0 1 8; 8: 4 2 9-4 3 8.  
2 9.  
R o d d ay A M, P ars o ns S K, S n y d er F et al. I m p act of p ati e nt n avi g ati o n i n eli mi n ati n g ec o n o mic dis p ariti es i n 
c a nc er c ar e. C a nc er 2 0 1 5; 1 2 1: 4 0 2 5 -4 0 3 4.  
3 0.  
R u bi nst ei n L, Cr o wl e y J, Iv y P, L e bl a nc M, S ar g e nt D. R a n d o miz e d p h as e II d esi g ns. Cli n C a nc er R es 2 0 0 9; 
1 5: 1 8 8 3 -1 8 9 0.  
3 1.  
Vic k ers AJ, B all e n V, Sc h er HI. S etti n g t h e b ar i n p h as e II tri als: t h e us e of hist oric al d at a f or d et er mi ni n g 
" g o/ n o g o" d ecisi o n f or d efi nitiv e p h as e III t esti n g. Cli n C a nc er R es 2 0 0 7; 1 3: 9 7 2 -9 7 6.  
3 2.  
R at ai n MJ, S ar g e nt DJ. O pti misi n g t h e d esi g n of p h as e II o nc ol o g y tri als: t h e i m p ort a nc e of r a n d o mis ati o n. 
E ur J C a nc er 2 0 0 9; 4 5: 2 7 5 -2 8 0.  
3 3.  
M urr a y D M, P e n n ell M, R h o d a D, H a d e E M, P as k ett E D. D esi g ni n g st u di es t h at w o ul d a d dr ess t h e 
m ultil ay er e d n at ur e of h e alt h c ar e. J N atl C a nc er I nst M o n o gr 2 0 1 0; 2 0 1 0: 9 0 -9 6.  
3 4.  
St er b a K R, Z a p k a J, L a P ell e N et al. D e v el o p m e nt of a s ur viv ors hi p n e e ds ass ess m e nt pl a n ni n g t o ol f or h e a d 
a n d n ec k c a nc er s ur viv ors a n d t h eir c ar e giv ers: a pr eli mi n ar y st u d y. J C a nc er S ur viv 2 0 1 7.  
3 5.  
St er b a K R, Ar m es o n K, Z a p k a J et al. E v al u ati o n of a s ur viv ors hi p n e e ds ass ess m e nt pl a n ni n g t o ol f or h e a d 
a n d n ec k c a nc er s ur viv or -c ar e giv er d y a ds. J C a nc er S ur viv 2 0 1 9; 1 3: 1 1 7 -1 2 9.  
3 6.  
Fr e e dl a n d K E, M o hr D C, D avi ds o n K W, Sc h w artz J E. Us u al a n d u n us u al c ar e: existi n g pr actic e c o ntr ol 
gr o u ps i n r a n d o miz e d c o ntr oll e d tri als of b e h avi or al i nt er v e nti o ns. Ps yc h os o m M e d 2 0 1 1; 7 3: 3 2 3 -3 3 5.  
3 7.  
J a nz T, Ki m J, Hill E et al. Ass oci ati o n of C ar e Pr oc ess es wit h Ti m el y, E q uit a bl e P ost o p er ativ e R a di ot h er a p y 
i n P ati e nts wit h S ur gic ally Tr e at e d H e a d a n d N ec k S q u a m o us C ell C arci n o m a. J A M A ot ol ar y n g ol o g y-- h e a d 
& n ec k s ur g er y 2 0 1 8; 1 4 4: 1 -1 0.  
3 8.  
Cr ai g P, Di e p p e P, M aci ntyr e S et al. D e v el o pi n g a n d e v al u ati n g c o m pl ex i nt er v e nti o ns: t h e n e w M e dic al 
R es e arc h C o u ncil g ui d a nc e. B MJ 2 0 0 8; 3 3 7: a 1 6 5 5.  
3 9.  
I nstit ut e P-C O R. St a n d ar ds f or St u di es of C o m pl ex I nt er v e nti o ns. Av ail a bl e at: 
htt ps:// w w w. pc ori. or g/r es e arc h -r es ults/ a b o ut-o ur -r es e arc h/r es e arc h-m et h o d ol o g y/ pc ori -m et h o d ol o g y -
st a n d ar ds # C o m pl ex. 
4 0.  
L e v y D A, Li H, St er b a K R et al. D e v el o p m e nt a n d V ali d ati o n of N o m o gr a ms f or Pr e dicti n g D el ay e d 
P ost o p er ativ e R a di ot h er a p y I niti ati o n i n H e a d a n d N ec k S q u a m o us C ell C arci n o m a. J A M A ot ol ar y n g ol o g y -- 
h e a d & n ec k s ur g er y 2 0 2 0.  
4 1.  
J a nz T A, Ki m J, Hill E G et al. Ass oci ati o n of C ar e Pr oc ess es Wit h Ti m el y, E q uit a bl e P ost o p er ativ e 
R a di ot h er a p y i n P ati e nts Wit h S ur gic all y Tr e at e d H e a d a n d N ec k S q u a m o us C ell C arci n o m a. J A M A 
ot ol ar y n g ol o g y -- h e a d & n ec k s ur g er y 2 0 1 8; 1 4 4: 1 1 0 5 -1 1 1 4.  
4 2.  
C al h o u n E A, W hitl e y E M, Es p arz a A et al. A n ati o n al p ati e nt n avi g at or tr ai ni n g pr o gr a m. H e alt h Pr o m ot 
Pr act 2 0 1 0; 1 1: 2 0 5 -2 1 5.  
4 3.  
Br y a nt D C, Willi a ms o n D, C art m ell K, J eff ers o n M. A l ay p ati e nt n avi g ati o n tr ai ni n g c urric ul u m t ar g eti n g 
dis p ariti es i n c a nc er cli nic al tri als. J N atl Bl ac k N urs es Ass oc 2 0 1 1; 2 2: 6 8 -7 5.  
4 4.  
Fr e u n d K M, B att a gli a T A, C al h o u n E et al. N ati o n al C a nc er I nstit ut e P ati e nt N a vi g ati o n R es e arc h Pr o gr a m: 
m et h o ds, pr ot oc ol, a n d m e as ur es. C a nc er 2 0 0 8; 1 1 3: 3 3 9 1 -3 3 9 9.  
4 5.  
J a nz T A, Ki m J, Hill E G et al. Ass oci ati o n of C ar e Pr oc ess es Wit h Ti m el y, E q uit a bl e P ost o p er ativ e 
R a di ot h er a p y i n P ati e nts Wit h S ur gic all y Tr e at e d H e a d a n d N ec k S q u a m o us C ell C arci n o m a. J A M A 
ot ol ar y n g ol o g y -- h e a d & n ec k s ur g er y 2 0 1 8.  
4 6.  
( C D C) Cf D C a P. B e h avi or al Ris k F act or S ur v eill a nc e S yst e m S ur v e y Q u esti o n n air e. Atl a nt a, G A.: U. S. 
D e p art m e nt of H e alt h a n d H u m a n S er vic es, 2 0 1 6.  

N D U R E 2. 0  
 
Versi o n 7 . 0  
 
 
3 0  Dece m ber 2 0 2 3  
 
Base d o n t he NI H Pr ot oc ol Te m plate f or Be ha vi oral a n d S ocial S cie nc es Rese arc h  
5 9  
4 7.  
L u k w a g o S N, Kr e ut er M W, B uc h oltz D C, H olt CL, Cl ar k E M. D e v el o p m e nt a n d v ali d ati o n of bri ef sc al es t o 
m e as ur e c oll ectivis m, r eli gi osity, r aci al pri d e, a n d ti m e ori e nt ati o n i n ur b a n Afric a n A m eric a n w o m e n. F a m 
C o m m u nity H e alt h 2 0 0 1; 2 4: 6 3 -7 1.  
4 8.  
H al b ert C H, Bri g gs V, B o w m a n M et al. Acc e pt a nc e of a c o m m u nity -b as e d n avi g at or pr o gr a m f or c a nc er 
c o ntr ol a m o n g ur b a n Afric a n A m eric a ns. H e alt h E d uc R es 2 0 1 4; 2 9: 9 7 -1 0 8.  
4 9.  
J e a n-Pi err e P, Fisc ell a K, Fr e u n d K M et al. Str uct ur al a n d r eli a bility a n alysis of a p ati e nt s atisf acti o n wit h 
c a nc er-r el at e d c ar e m e as ur e: a m ultisit e p ati e nt n avi g ati o n r es e arc h pr o gr a m st u d y. C a nc er 2 0 1 1; 
1 1 7: 8 5 4 -8 6 1.  
5 0.  
J e a n-Pi err e P, Fisc ell a K, Wi nt ers P C et al. Ps yc h o m etric d e v el o p m e nt a n d r eli a bility a n alysis of a p ati e nt 
s atisf acti o n wit h i nt er p ers o n al r el ati o ns hi p wit h n avi g at or m e as ur e: a m ulti -sit e p ati e nt n avi g ati o n 
r es e arc h pr o gr a m st u d y. Ps yc h o o nc ol o g y 2 0 1 2; 2 1: 9 8 6 -9 9 2.  
5 1.  
R a m ac h a n dr a n A, S n y d er F R, K atz ML et al. B arri ers t o h e alt h c ar e c o ntri b ut e t o d el ays i n f oll o w -u p a m o n g 
w o m e n wit h a b n or m al c a nc er scr e e ni n g: D at a fr o m t h e P ati e nt N a vi g ati o n R es e arc h Pr o gr a m. C a nc er 
2 0 1 5; 1 2 1: 4 0 1 6 -4 0 2 4.  
5 2.  
Kr o k -Sc h o e n JL, Br e w er B M, Y o u n g G S et al. P artici p a nts' b arri ers t o di a g n ostic r es ol uti o n a n d f act ors 
ass oci at e d wit h n e e di n g p ati e nt n avi g ati o n. C a nc er 2 0 1 5; 1 2 1: 2 7 5 7 -2 7 6 4.  
5 3.  
C ol e m a n E A, M a h o n e y E, P arr y C. Ass essi n g t h e q u ality of pr e p ar ati o n f or p ost h os pit al c ar e fr o m t h e 
p ati e nt's p ers p ectiv e: t h e c ar e tr a nsiti o ns m e as ur e. M e d C ar e 2 0 0 5; 4 3: 2 4 6 -2 5 5.  
5 4.  
C o h e n S, M er m elst ei n R, K a m arc k T, H o b er m a n H M. M e as uri n g t h e F u ncti o n al C o m p o n e nts of S oci al 
S u p p ort. I n: I. G. S, B. R. S, e ds. S oci al S u p p ort: T h e or y, R es e arc h a n d A p plic ati o ns . T h e H a g u e, H oll a n d: 
M arti n us Nij h off, 1 9 8 5: 7 3 -9 4.  
5 5.  
M a d or e S, Kil b o ur n K, V alv er d e P, B orr ay o E, R aic h P. F e asi bilit y of a ps yc h os oci al a n d p ati e nt n avi g ati o n 
i nt er v e nti o n t o i m pr o v e acc ess t o tr e at m e nt a m o n g u n d ers er v e d br e ast c a nc er p ati e nts. S u p p ort C ar e 
C a nc er 2 0 1 4; 2 2: 2 0 8 5 -2 0 9 3.  
5 6.  
C h a m pi o n VL. R e vis e d s usc e pti bility, b e n efits, a n d b arri ers sc al e f or m a m m o gr a p h y scr e e ni n g. R es N urs 
H e alt h 1 9 9 9; 2 2: 3 4 1 -3 4 8.  
5 7.  
M oss -M orris R, W ei n m a n J, P etri e KJ, H or n e R, C a m er o n L D, B uic k D. T h e R e vis e d Ill n ess P erc e pti o n 
Q u esti o n n air e (I P Q -R). Ps yc h ol H e alt h 2 0 0 2; 1 7: 1 -1 6.  
5 8.  
Mil es A. P erc eiv e d S e v erity. Av ail a bl e at: 
htt ps://c a nc erc o ntr ol.c a nc er. g ov/ br p/r es e arc h/c o nstr ucts/ p erc eiv e d _s ev erity. ht ml . Acc ess e d M arc h 2 1 
2 0 1 9.  
5 9.  
W olf M S, C h a n g C H, D avis T, M a k o ul G. D e v el o p m e nt a n d v ali d ati o n of t h e C o m m u nic ati o n a n d 
Attit u di n al S elf -Effic ac y sc al e f or c a nc er ( C A S E -c a nc er). P ati e nt E d uc C o u ns 2 0 0 5; 5 7: 3 3 3 -3 4 1.  
6 0.  
Gr a b o y es E M, H al b ert C H, Li H et al. B arri ers t o t h e D eliv er y of Ti m el y, G ui d eli n e -A d h er e nt A dj u v a nt 
T h er a p y A m o n g P ati e nts Wit h H e a d a n d N ec k C a nc er. J C O O nc ol Pr act 2 0 2 0: O P 2 0 0 0 2 7 1.  
6 1.  
A dj usti n g f or C o v ari at es i n R a n d o miz e d Cli nic al Tri als f or Dr u gs a n d Bi ol o gic al Pr o d ucts. F D A G ui d a nc e 
D oc u m e nt f or I n d ustr y. I n: U S D e p art m e nt of H e alt h a n d H u m a n S er vic es F a D A, C e nt er f or Dr u g 
E v al u ati o n a n d R es e arc h, C e nt er f or Bi ol o gics E v al u ati o n a n d R es e arc h, e d., 2 0 2 1.  
6 2.  
Fr e e d m a n D A. R a n d o miz ati o n D o es N ot J ustify L o gistic R e gr essi o n. St atistic al Sci e nc e 2 0 0 8; 2 3: 2 3 7 – 2 4 9.  
6 3.  
St ei n gri mss o n J A, H a nl e y D F, R os e n bl u m M. I m pr o vi n g pr ecisi o n b y a dj usti n g f or pr o g n ostic b as eli n e 
v ari a bl es i n r a n d o miz e d tri als wit h bi n ar y o utc o m es, wit h o ut r e gr essi o n m o d el ass u m pti o ns. C o nt e m p 
Cli n Tri als 2 0 1 7; 5 4: 1 8 -2 4.