Stakeholder Views of Clinical Trials in Low- and Middle-Income … · of conducting clinical trials...
Transcript of Stakeholder Views of Clinical Trials in Low- and Middle-Income … · of conducting clinical trials...
REVIEW ARTICLEPEDIATRICS Volume 137 , number 2 , February 2016 :e 20152800
Stakeholder Views of Clinical Trials in Low- and Middle-Income Countries: A Systematic ReviewPathma D. Joseph, BPharm, MPharm,a,b,c Patrina H.Y. Caldwell, BMed, FRACP, PhD,a,b Allison Tong, BMedSc, MPH (Hons), MM, PhD,a,d Camilla S. Hanson, BPsych (Hons),a,d Jonathan C. Craig, MBCh, FRACP, PhDa,d
abstractCONTEXT: Clinical trials are necessary to improve the health care of children, but only one-
quarter are conducted in the low- to middle-income countries (LMICs) in which 98% of the
global burden of disease resides.
OBJECTIVE: To describe stakeholder beliefs and experiences of conducting trials in children in
LMICs.
DATA SOURCES: Electronic databases were searched to August 2014.
STUDY SELECTION: Qualitative studies of stakeholder perspectives on conducting clinical trials
among children in LMICs.
DATA EXTRACTION: Findingswere analyzed by using thematic synthesis.
RESULTS: Thirty-nine studies involving 3110 participants (children [n = 290], parents or
caregivers [n = 1609], community representatives [n = 621], clinical or research team
members [n = 376], regulators [n = 18], or sponsors [n = 15]) across 22 countries were
included. Five themes were identified: centrality of community engagement (mobilizing
community, representatives’ pivotal role, managing expectations, and retaining
involvement); cognizance of vulnerability and poverty (therapeutic opportunity and
medical mistrust); contending with power differentials (exploitation, stigmatization, and
disempowerment); translating research to local context (cultural beliefs, impoverishment
constraints, and ethical pluralism); and advocating fair distribution of benefits (health care,
sponsor obligation, and collateral community benefits).
LIMITATIONS: Studies not published in English were excluded.
CONCLUSIONS: Conducting trials in children in LMICs is complex due to social disadvantage,
economic scarcity, idiosyncratic cultural beliefs, and historical disempowerment, all of
which contribute to inequity, mistrust, and fears of exploitation. Effective community
engagement in recruiting, building research capacities, and designing trials that are
pragmatic, ethical, and relevant to the health care needs of children in LMICs may help to
improve the equity and health outcomes of this vulnerable population.
aCentre for Kidney Research, The Children’s Hospital at Westmead, Sydney, Australia; bDiscipline of Paediatrics and Child Health, and dSydney School of Public Health, The University of
Sydney, Sydney, Australia; and cThe Pharmacy Department, The Children’s Hospital at Westmead, Sydney, Australia
Ms Joseph contributed to study conception and design, data acquisition, comprehensiveness of reporting appraisal, analysis and interpretation of the data,
and drafting and revising the manuscript; Ms Hanson contributed to study conception and design, comprehensiveness of reporting appraisal, review of the
To cite: Joseph PD, Caldwell PH, Tong A, et al. Stakeholder Views of Clinical Trials in Low- and Middle-Income Countries: A Systematic Review. Pediatrics.
2016;137(2):e20152800
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JOSEPH et al
Globally, the 2000 Millennium
Development Goals and other
initiatives have seen progressive
improvements in child health.1,2
Although research has contributed
positively by promoting therapeutic
advances in health care of children,
inequities are still evident across
different income settings.3 The
“10/90 gap” suggests that only 10%
of global health research funds are
invested into medical conditions that
account for 90% of the global disease
burden, which resides mainly in the
low- and middle-income countries
(LMICs).4,5 Although 89% of children
live in LMICs and contribute 98% to
the global burden of disease, only
one-quarter of trials are conducted in
this setting.,6,7
Conducting clinical trials in children
in LMICs is reportedly more complex
and may be of lower methodologic
quality than trials conducted in
high-income countries.6 Specific
challenges include the risk of
exploitation, scarce resources,
deficient ethical and regulatory
frameworks, and logistical
constraints.8 Qualitative research can
help to explain social phenomena
and provides an understanding
of people’s values, beliefs, and
attitudes.9 Thematic synthesis of
multiple qualitative studies can
generate more comprehensive
insight across different stakeholder
groups and settings.
The aim of the present systematic
review was to describe the
perspectives and experiences
of conducting clinical trials in
children in LMICs among key
stakeholders (including children,
parents or caregivers, community
representatives, clinical and research
teams, regulators, and sponsors) to
inform strategies to improve locally
relevant research in children from
these countries.9
METHODS
We followed the Enhancing
Transparency of Reporting the
Synthesis of Qualitative Research
reporting guidelines for systematic
review of qualitative studies.10,
Data Sources and Searches
The searches were conducted
in Medline and Embase from
inception to August 3, 2014. The
search strategies are provided
in Supplemental Table 4. Google
Scholar and reference lists of
relevant articles and reviews were
also searched. One of the authors
(P.D.J.) screened the titles and
obtained full texts of potentially
relevant studies, which were
assessed for eligibility. Another
author (C.S.H.) independently
reviewed the search results to
ensure that all studies which met the
inclusion criteria were included.
Study Selection Criteria
Qualitative studies on stakeholders
(ie, children, parents or caregivers,
community representatives,
clinical or research team members,
regulators, sponsors) (Fig 1) and
their experiences and perspectives
on conducting trials in children
(aged 0–18 years) in LMICs (as
classified by the World Bank) were
included. Articles were excluded
if they were quantitative surveys,
reviews, or commentaries or if they
only reported on trials conducted in
the adult population. Non-English
articles were excluded to prevent
potential misinterpretation of the
information.
Quality of Reporting Appraisal
For each study, the
comprehensiveness of reporting
was independently appraised by
2 reviewers (P.D.J. and C.S.H.)
using the Consolidated Criteria
for Reporting Qualitative Health
Research framework, which
included criteria relating to
the research team, methods,
study context, analysis, and
interpretations.11 These criteria
provide contextual details for
readers to evaluate the credibility,
dependability, and transferability of
the study findings to other settings.
Any differences in assessment were
discussed and resolved.
Data Extraction and Synthesis
Thematic synthesis was used to
inductively generate analytical
themes from the findings of the
included studies.9 All text under the
‘‘results or findings’’ or ‘‘conclusion
or discussion’’ section of each article
were extracted. The text was entered
verbatim into HyperRESEARCH
version 3.0.3 (ResearchWare, Inc,
Randolph, Massachusetts) software
for coding textual data. One author
(P.D.J.) performed line-by-line coding
of all relevant text and data. Similar
concepts were categorized into
themes, and the themes were revised
as new concepts were identified.
To ensure that coding captured all
relevant issues and reflected the
primary data, 2 reviewers (C.S.H. and
P.H.Y.C.) independently reviewed the
preliminary themes and analytical
framework and discussed the
addition or revision of themes with
2 other authors (P.D.J. and A.T.). This
form of investigator triangulation
2
FIGURE 1Clinical trials in children stakeholders.
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PEDIATRICS Volume 137 , number 2 , February 2016
ensured that the coding framework
and themes reflect the full breadth
of data. Conceptual relationships
between the themes were mapped
to develop an overarching analytical
thematic schema.
RESULTS
Literature Search and Study Characteristics
Overall, 39 studies involving >3110
participants wereincluded (Fig
2). Participants were children (n
= 290), parents or caregivers (n =
1609), community representatives
(n = 621), clinical or research team
members (n = 376), regulators
(n = 18), or sponsors (n = 15).
One study did not report the
number of participants. Study
characteristics are provided
in Table 1. The studies were
conducted across 22 countries,
with the majority in Africa. The
perspectives were predominantly
focused on trials within the
specialty of infectious diseases,
particularly HIV, tuberculosis, and
malaria. Data were collected by
using in-depth,semi-structured
interviews, focus groups, open-
ended surveys, and observations.
Comprehensiveness of Reporting
Reporting was variable, with studies
providing details on 3 to 21 of
the 31 items of the Consolidated
Criteria for Reporting Qualitative
Health Research framework (Table
2). All studies included participant
quotations; 30 of 39 studies
described the participant selection
strategy, 27 of 39 provided the
questions or topic guides, and 27
of 39 reported recording of the
interview. Researcher triangulation
(multiple researchers involved in
coding and analysis) was described
in 24 studies. Theoretical saturation
(when few or no new concepts
are identified in subsequent data
collection) was described in only 7
studies. Member checking (obtaining
feedback from participants on the
preliminary findings) was reported
in 1 study.
Descriptive Synthesis
Five major themes were identified:
centrality of community engagement,
cognizance of vulnerability and
poverty, contending with power
differentials, translating research
to local context, and advocating fair
distribution of benefits. Selected
quotations for each theme are
provided in Table 3. Conceptual links
among themes are depicted in Fig 3.
Centrality of Community Engagement
Mobilizing Community: The need
for community engagement to
build trust and foster acceptance
of trials was emphasized by all
stakeholders.16,19,20,22 They believed
that culturally appropriate strategies
were necessary to educate the
community about new interventions
and encourage active participation
in research. Community leaders in
Ghana suggested using traditional
community gatherings, which
included cultural activities such
as drumming and dancing.16
Many desired “genuine, fair, and
effective”24 dialogue with community
members to improve trial design
and conduct, strengthen ethical
practice, and demonstrate respect for
community values.
Recognizing the Pivotal Role of
Leaders and Representatives:
Stakeholders believed that
investigators need to navigate and
respect hierarchical decision-making
structures in the community.20,31
Endorsement by “chiefs” and
understanding their role as
“gatekeepers and mediators” was
considered necessary to “allay
suspicion, to nurture trust, and
to establish the researchers’
credibility.”16 Involving trusted
“grassroot”19 intermediaries such
as community workers was deemed
vital in “opening the way”21 for
researchers. Employing fieldworkers
with knowledge of local customs was
supported to facilitate recruitment
of participants.16 Researchers
recognized that community
3
FIGURE 2Flowchart of review of qualitative studies on the conduct of trials in children in LMICs.
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JOSEPH et al 4
TABL
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2013
31
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01232
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enta
l mot
ivat
ion
for
par
tici
pat
ion
Mal
awi
C
orn
eli e
t al
,
2007
34
HIV
Gov
ern
men
t13
30
100
330
00
Form
ativ
eS
emi-s
tru
ctu
red
inte
rvie
ws,
focu
s gr
oup
,
obse
rvat
ion
s
Con
ten
t
anal
ysis
Com
mu
nit
y en
gage
men
t
info
rmin
g d
esig
n o
f
pro
toco
ls
M
asiy
e et
al,
2008
35
Mal
aria
Gov
ern
men
t81
081
00
00
Qu
alit
ativ
e
des
ign
Focu
s gr
oup
s−
Mot
ivat
ion
for
par
tici
pat
ion
an
d
role
of
rela
tive
s in
dec
isio
n-m
akin
g
P
iwoz
et
al
2006
36
HIV
Gov
ern
men
t19
00
019
00
Form
ativ
eIn
-dep
th in
terv
iew
sC
onte
nt
anal
ysis
Feas
ibili
ty o
f in
terv
enti
on
to in
form
tri
al d
esig
n
Mu
ltin
atio
nal
H
yder
an
d
Wal
i,
2006
37b
Non
spec
ifi c
Gov
ern
men
t78
00
078
00
Qu
alit
ativ
e
des
ign
Focu
s gr
oup
s,
in-d
epth
inte
rvie
ws;
open
-en
ded
qu
esti
ons
in
surv
ey
−D
evel
opin
g co
un
trie
s’
rese
arch
per
spec
tive
s
of in
form
ed c
onse
nt
and
col
lab
orat
ive
rese
arch
Ka
ss e
t al
,
2005
38c
Infe
ctio
us
dis
ease
Gov
ern
men
t26
026
00
00
Qu
alit
ativ
e
des
ign
In-d
epth
inte
rvie
ws
Them
atic
anal
ysis
Par
tici
pan
t m
otiv
atio
ns,
un
der
stan
din
g an
d
volu
nta
rin
ess
Pu
erto
Ric
o
P
érez
-Gu
erra
et a
l,
2012
39
Den
gue
Ind
ust
ry31
311
114
539
180
0G
rou
nd
ed
theo
ry
Inte
rvie
ws,
foc
us
grou
ps
Con
ten
t
anal
ysis
Com
mu
nit
y vi
ews
of
pla
ceb
o-co
ntr
olle
d
den
gue
vacc
ine
tria
l
TABL
E 1
Con
tin
ued
by guest on November 15, 2020www.aappublications.org/newsDownloaded from
PEDIATRICS Volume 137 , number 2 , February 2016 7
Stu
dy
by
Cou
ntr
y
Med
ical
Con
dit
ion
Foc
us
of T
rial
(s)
Sp
onso
r of
Qu
alit
ativ
e S
tud
y
nP
arti
cip
ants
Met
hod
olog
ic
Fram
ewor
k
Dat
a C
olle
ctio
nAn
alys
isTo
pic
Ch
ildre
nP
aren
tsC
omm
un
ity
Clin
ical
/
Res
earc
h
Team
Reg
ula
tors
Sp
onso
rs
Sou
th A
fric
a
Es
sack
et
al,
2010
40
HIV
Gov
ern
men
t31
00
167
35
Qu
alit
ativ
e
des
ign
Sem
i-str
uct
ure
d in
-
dep
th in
terv
iew
−Et
hic
al c
hal
len
ges
in H
IV
vacc
ine
tria
ls
Ja
span
et
al,
2008
41
HIV
Gov
ern
men
t20
057
5192
00
0Q
ual
itat
ive
des
ign
Focu
s gr
oup
Them
atic
anal
ysis
Eth
ical
issu
es
of a
dol
esce
nt
invo
lvem
ent
in H
IV
vacc
ine
tria
ls
Ja
span
et
al,
2010
42a
HIV
Col
lab
orat
ive
grou
p,
gove
rnm
ent
200
5751
920
00
Qu
alit
ativ
e
des
ign
Focu
s gr
oup
sTh
emat
ic
anal
ysis
Atti
tud
es t
owar
d
the
incl
usi
on o
f
adol
esce
nts
in H
IV
vacc
ine
tria
ls
M
ahom
ed e
t
al, 2
00843
Tub
ercu
losi
sFo
un
dat
ion
/
char
ity/
soci
ety,
gove
rnm
ent,
ind
ust
ry
7240
320
00
0Q
ual
itat
ive
des
ign
Focu
s gr
oup
; sel
f-
adm
inis
tere
d
surv
ey
Con
ten
t
anal
ysis
Know
led
ge a
nd
att
itu
des
of a
dol
esce
nts
to
tub
ercu
losi
s tr
ials
Tan
zan
ia
Lih
elu
ka e
t al
2013
44
Mal
aria
Ind
ust
ry55
049
60
00
Qu
alit
ativ
e
des
ign
In-d
epth
inte
rvie
ws,
focu
s gr
oup
Them
atic
anal
ysis
Sec
ond
ary
hea
lth
ben
efi t
s of
mal
aria
vacc
ine
tria
ls
The
Gam
bia
Fa
irh
ead
et
al, 2
00645
Pn
eum
onia
,
men
ingi
tis
Gov
ern
men
t>
600
−−
100
0Et
hn
ogra
ph
yO
bse
rvat
ion
s,
nar
rati
ve a
nd
sem
i-str
uct
ure
d
inte
rvie
ws
Them
atic
anal
ysis
Enga
gem
ent
of p
aren
ts
in v
acci
ne
tria
l
G
eiss
ler
et a
l,
2008
46
Mal
aria
Fou
nd
atio
n/
char
ity/
soci
ety
930
800
130
0Q
ual
itat
ive
des
ign
Sem
i-str
uct
ure
d
inte
rvie
ws
−R
elat
ion
al e
thic
s an
d
mat
eria
l exc
han
ges
Le
ach
et
al,
1999
47
Infl
uen
zaG
over
nm
ent
189
018
90
00
0Q
ual
itat
ive
des
ign
Sem
i-str
uct
ure
d
inte
rvie
w
−In
form
ed c
onse
nt
pro
ced
ure
Uga
nd
a
C
ran
e, 2
01048
HIV
Fou
nd
atio
n/
char
ity/
soci
ety
50
00
50
0Q
ual
itat
ive
des
ign
Sem
i-str
uct
ure
d
inte
rvie
ws
−S
cien
ce a
nd
eth
ics
in
HIV
tra
nsn
atio
nal
rese
arch
in A
fric
a
Zam
bia
Ki
ngo
ri e
t al
,
2010
49
Mal
nu
trit
ion
Un
iver
sity
>30
0>
250
50
0Q
ual
itat
ive
des
ign
Face
-to-
face
in-d
epth
inte
rvie
ws,
focu
s gr
oup
−M
isco
nce
pti
on o
f cl
inic
al
tria
ls
Zim
bab
we
P
ower
et
al,
2004
50d
Sex
ual
hea
lth
−−
−−
−−
Qu
alit
ativ
e
des
ign
Ob
serv
atio
n,
in-d
epth
inte
rvie
ws,
focu
s gr
oup
s
Them
atic
anal
ysis
Feas
ibili
ty s
tud
y
targ
etin
g ad
oles
cen
t
sexu
al h
ealt
h
TABL
E 1
Con
tin
ued
by guest on November 15, 2020www.aappublications.org/newsDownloaded from
JOSEPH et al 8
representatives could potentially
enable or undermine the trial
goals.22
Managing Different Expectations:
The transfer of material benefits
such as health care resources was
expected by the community and was
believed to encourage participation,
but this approach could undermine
intrinsic motivation.28,31 Tensions
arose because volunteer community
workers were dissatisfied with their
poor incentives compared with
the payment of the fieldworkers
employed on the trial.19,21 The
expectations of community workers
to enroll participants for payment
differed from the expectations of
researchers, who believed that
community workers should not
be directly involved in consenting
participants to avoid conflict of
interest.24,31 Some recommended
having mediators (eg, community
TABLE 2 Comprehensiveness of Reporting in the Included Studies
Item Studies Reporting on the Item, Ref. No. N (%)
Personal characteristics
Interviewer/facilitator identifi ed 14, 16–18, 20, 23, 27–37, 39–44, 61, 71, 73–75 27 (69)
Credentials 14, 17, 18, 20, 28, 29, 35, 37, 39–44, 71, 74 16 (41)
Occupation of interview/facilitator 14–18, 20, 26, 28, 30, 35, 39–44, 71, 73, 74 19 (49)
Gender 16–18, 20, 32, 33, 35, 36, 39, 40, 42, 44, 71,73 14 (36)
Experience/training in qualitative research 14,15, 17, 18, 23, 29–31, 35–37, 43, 44, 61, 71, 73–75 18 (46)
Relationships with participants
Established relationships before study 17, 36, 40, 71 4 (10)
Participant knowledge of interviewer 36 1 (3)
Participant selection
Selection method (eg, snowball, purposive, convenience) 14–18, 20, 22, 23, 25, 28–35, 39–44, 61, 70–75 30 (77)
Method of approach/ recruitment 15–17, 19, 21, 22, 25, 26, 29, 30, 32, 34, 35, 38–41, 43, 44, 61, 70–75 26 (67)
Sample size 14–44, 61, 70–75 38 (97)
No./reasons for nonparticipation 23, 25, 30, 33, 34, 41, 70, 74, 75 9 (23)
Setting
Venue of data collection 21, 25, 26, 30, 31, 34, 36, 39–42, 61, 70, 72, 73, 75 17 (44)
Presence of nonparticipants (eg, clinical staff) 27, 30, 41 3 (8)
Description of the sample 14–17, 19–26, 28–35, 37–44, 61, 63, 70–72, 74, 75 35 (90)
Data collection
Questions, prompts, or topic guide 14–16, 22, 23, 25–27, 29, 30, 33–35, 37–44, 70–75 27 (69)
Repeat interviews/observations 14, 29, 72, 75 4 (10)
Audio/visual recording 14–17, 22, 23, 25, 26, 28–32, 34, 35, 37–40, 43, 44, 61, 63, 70, 71, 73, 74 27 (69)
Field notes 14, 16, 20, 22, 23, 29, 31, 32, 35, 37, 40, 41, 44, 61, 75 15 (38)
Duration of data collection (interview or focus group) 16, 22, 26, 31, 34, 38, 39, 61, 72, 75 10 (26)
Data (or theoretical) saturation 15, 22, 35, 44, 72, 73, 75 7 (18)
Participants received transcripts 32 1 (3)
Methodologic theory identifi ed 14–17, 20, 22, 23, 25, 26, 28, 29, 31, 32, 34, 35, 39, 40, 43, 44, 61, 63, 70, 71, 73–75 26 (67)
Data analysis
No. of data coders 14–17, 20, 22, 23, 26, 28, 29, 31, 32, 35, 38–40, 44, 61, 71, 74, 75 21 (54)
Researcher/expert triangulation (multiple researchers
involved in coding and analysis)
14–16, 18, 20, 22, 23, 25, 26, 28, 29, 31, 32, 34, 37, 38, 40, 42, 44, 61, 71, 72, 74, 75 24 (62)
Derivation of themes or fi ndings (eg, inductive, constant
comparison)
14–17, 20, 22, 23, 25–29, 31, 32, 34–41, 44, 61, 63, 70–75 31 (79)
Protocol for translation 14–17, 20, 22, 25, 26, 28–31, 35, 38, 39, 41, 44, 61, 63, 70, 71, 74 22 (56)
Protocol for data preparation/ transcription 14–17, 20, 22, 23, 25, 26, 28, 29, 31–35, 37–40, 43, 44, 61, 63, 70, 71, 73–75 29 (74)
Use of software (eg, NVivo [QSR International, Melbourne,
Australia])
14, 16, 17, 20, 22, 25, 28–30, 39, 41, 43, 61, 70, 75 15 (38)
Member checking (participant feedback on fi ndings) 32 1 (3)
Reporting
Participant quotations provided or raw data provided
(picture, diary entries)
14–44, 61, 63, 70–75 39 (100)
Range and depth of insight into participant perspectives on
clinical trials in child issues in LMICs
14–44, 61, 63, 70–75 39 (100)
− not stated, unclear, or unable to ascertain.a Excluded from the total number of participants because they have the same participants as another study in this review by same author.b Countries of study: China, India, Thailand, the Philippines, South Africa, Tanzania, Kenya, Brazil, Colombia, and Mexico.c Countries of study: Africa and Caribbean.d Number of participants not reported and thus not included in the total number of participants.
TABLE 1 Continued
by guest on November 15, 2020www.aappublications.org/newsDownloaded from
PEDIATRICS Volume 137 , number 2 , February 2016 9
TABL
E 3
Them
es a
nd
Sel
ecte
d Il
lust
rati
ve Q
uot
atio
ns
Su
bth
emes
Par
tici
pan
ts’ Q
uot
atio
ns
and
/or
Auth
ors’
Exp
lan
atio
ns
Con
trib
uti
ng
Ref
eren
ces
Cen
tral
ity
of c
omm
un
ity
enga
gem
ent
As
sist
ing
in m
obili
zin
g co
mm
un
ity
“If
you
don
't g
et t
hem
invo
lved
, you
may
in t
he
end
imp
lem
ent
som
eth
ing
that
will
be
stra
nge
or
som
eth
ing
that
th
ey w
ill n
ot
emb
race
at
all.
So
it is
bet
ter
to g
et t
hem
invo
lved
to
be
able
to
sou
rce
som
e in
form
atio
n f
rom
th
em, t
o b
e ab
le t
o ge
t th
eir
view
ab
out
the
pro
ject
to
mov
e to
th
e n
ext
stag
e, b
ecau
se t
hey
alw
ays
hav
e im
por
tan
t co
ntr
ibu
tion
s to
mak
e to
th
e p
roje
ct, t
o
imp
rove
on
wh
at y
ou h
ave.
” (N
HR
C r
esea
rch
offi
cer
)16
14–
16, 1
8–21
, 24,
26,
31,
32,
34,
36, 3
7, 4
3, 6
1, 7
3
“Tak
ing
adva
nta
ge o
f th
e st
ruct
ure
s th
at a
re a
lrea
dy
ther
e is
wh
at m
akes
it s
ucc
essf
ul.
It d
oesn
't h
ave
to b
e ca
pit
al-in
ten
sive
or
anyt
hin
g.”
(NH
RC
res
earc
h o
ffi c
er)16
R
ecog
niz
ing
the
piv
otal
rol
e of
rep
rese
nta
tive
s an
d le
ader
s
“If
one
had
n't
gon
e th
rou
gh t
he
righ
t p
roce
du
re…
th
at is
, see
ing
the
dis
tric
t au
thor
itie
s an
d t
he
par
amou
nt
chie
fs a
nd
th
e
sub
sect
ion
ch
iefs
an
d s
o fo
rth
, th
ere
mig
ht
hav
e b
een
a lo
t m
ore
susp
icio
n a
bou
t w
hat
was
goi
ng
on, w
hy
we
wer
e d
oin
g th
is,
wh
o w
e w
ere,
do
we
hav
e p
erm
issi
on t
o d
o th
is. E
ssen
tial
ly, t
his
stu
dy
wou
ld n
ot h
ave
bee
n a
ccep
ted
.” (
Exte
rnal
res
earc
her
)16
14–
16, 1
8–20
, 27,
32
“… w
e w
ent
to t
he
mee
tin
g an
d t
he
assi
stan
t ch
ief
said
he
doe
sn’t
wan
t to
hea
r an
y ru
mor
s fr
om a
nyb
ody.
He
said
he
was
an
assi
stan
t ch
ief
and
he
had
a c
hild
wh
o w
as in
th
e KE
MR
I stu
dy.
He
told
peo
ple
if t
hey
won
’t e
nro
ll in
th
e st
ud
y th
ey s
hou
ld ju
st
keep
qu
iet
and
an
ybod
y w
ho
will
be
hea
rd s
pre
adin
g ru
mou
rs w
ill b
e ar
rest
ed …
Aft
er t
he
assi
stan
t ch
ief
calle
d t
he
mee
tin
g,
rum
ours
sto
pp
ed a
nd
for
us
wh
o h
ad a
lrea
dy
join
ed, w
e fe
lt a
bit
bet
ter
bec
ause
ru
mou
rs h
ad s
top
ped
.” (
Fem
ale
par
ent,
late
con
sen
ter)
20
‘‘It
was
not
dif
fi cu
lt a
t al
l; it
was
dif
fi cu
lt t
o co
nvi
nce
th
em t
o jo
in t
he
pro
gram
, bu
t th
rou
gh t
he
lon
g ti
me
I sta
yed
wit
h t
hem
I got
a s
pec
ial r
elat
ion
, an
ind
epen
den
t ra
pp
ort
wit
h t
hem
, so
that
eve
n if
th
ey d
o n
ot w
ant
to jo
in, t
hey
cou
ldn
’t s
ay n
o..”
(Fie
ldw
orke
r)46
M
anag
ing
com
mu
nit
y an
d r
esea
rch
exp
ecta
tion
s
“So
as w
e w
ent
rou
nd
he
[CH
W]
use
d t
o sa
y ‘y
ou m
y co
lleag
ues
ear
n b
ut
for
me
I go
rou
nd
an
d g
et n
oth
ing.
You
hav
e b
icyc
les
and
we
hav
e n
oth
ing
bu
t w
hen
we
go, w
e go
tog
eth
er. I
t’s
like
I am
hel
pin
g yo
u in
you
r w
ork
yet
no
one
look
s af
ter
us.
’ So
that
is o
ne
of t
he
chal
len
ges.
Bu
t h
ones
tly
if I
look
at
it f
airl
y it
s tr
ue;
. . .
if h
e h
ad g
one
to w
ork
[he
wou
ld h
ave]
ear
ned
som
eth
ing
for
a
livin
g . .
. so
it b
ecom
es h
ard
bec
ause
he
wan
ts s
omet
hin
g fr
om t
her
e an
d y
ou s
ee I
can
’t h
elp
th
em.”
(Fi
eld
wor
ker)
19
14–
22, 2
6, 2
7, 3
4–36
, 40,
42,
61, 7
3
“....
..you
sh
ould
not
say
I th
ink
this
is f
or r
esea
rch
, wh
en a
not
her
per
son
is d
yin
g an
d y
ou h
ave
the
med
icin
es, I
th
ink
it’s
not
fai
r.
Even
if y
ou h
ave
the
equ
ipm
ent
for
rese
arch
, it
can
be
use
d f
or d
iagn
osti
cs if
it’s
so
nee
ded
.” (
Res
earc
her
)25
R
etai
nin
g p
arti
cip
atio
n o
f co
mm
un
ity
inte
rmed
iari
es
“Th
ose
wh
o st
opp
ed c
omp
lain
ed o
f m
oney
say
ing
they
are
su
ffer
ing
for
not
hin
g . .
.’ ‘.
. . d
uri
ng
the
du
rbar
th
e co
mm
un
ity
agre
ed
to g
ive
us
(CH
Ws)
som
e in
cen
tive
bu
t u
p t
o n
ow n
oth
ing.
. .’:
‘Th
e B
ible
say
s w
e sh
ould
love
ou
r n
eigh
bou
r lik
e . .
. w
e lo
ve
ours
elve
s, s
o w
het
her
th
e ch
ildre
n v
omit
on
me
or n
ot o
r I’m
bei
ng
pai
d o
r n
ot I
will
sti
ll co
nti
nu
e. .
.’. ‘I
hav
e b
ecom
e so
pop
ula
r
and
res
pec
ted
by
the
peo
ple
in t
he
com
mu
nit
y. .’
…. ‘
I hav
e b
ecom
e a
frie
nd
to
all c
hild
ren
an
d m
oth
ers
in t
he
villa
ge. T
hat
is
my
ben
efi t
fro
m t
his
wor
k.’”
(C
HW
)13
17, 2
0, 2
3, 2
4, 2
7, 3
4
“Th
e tr
ial c
omm
un
ity
bec
ame
a w
eb o
f ev
eryd
ay r
elat
ion
s w
ell b
eyon
d t
he
nec
essi
ties
of
the
tria
l. “W
e ar
e th
ere
day
tim
e, n
igh
t
tim
e, a
fter
noo
n t
ime,
an
y ti
me
you
th
ink
of. A
fter
th
e fi
rst
tria
l, w
e d
o n
ot le
ave
bu
t st
ay…
we
hav
e go
od f
rien
ds.
We
still
vis
it
them
, an
d t
hey
com
e to
us.
” “B
y th
e en
d y
ou b
ecom
e p
art
of t
he
com
mu
nit
y; y
ou d
o ev
eryt
hin
g to
geth
er. I
t w
as s
ad…
to le
ave.
”
(Fie
ldw
orke
r)46
“My
fath
er is
th
e su
ffer
er...
He
use
d t
o b
e th
e al
tern
ate
imam
of
the
villa
ge. N
ow h
alf
of t
he
peo
ple
do
not
wan
t to
sta
nd
beh
ind
him
in t
he
pra
yers
. Th
ey s
ay h
is d
augh
ters
wor
k fo
r N
GO
s, w
hic
h is
not
rig
ht
for
a re
ligio
us
per
son
.” (
CH
W)12
Cog
niz
ance
of
vuln
erab
ility
an
d p
over
ty
Th
erap
euti
c op
por
tun
ity
“Wh
at a
ttra
cted
us
[was
th
at]
we
knew
ou
r ch
ildre
n w
ill r
ecei
ve t
reat
men
t fo
r a
wh
ole
year
in e
very
dis
ease
th
ey s
uff
er. I
f yo
u h
ave
a p
rob
lem
an
d v
isit
th
e p
eop
le c
once
rned
, a c
all i
s m
ade
to t
he
… [
PI]
he
bri
ngs
a v
ehic
le a
nd
[th
e si
ck p
erso
n]
is c
arri
ed a
way
[to
hos
pit
al].
In f
act
it’s
som
eth
ing
we
shou
ld b
e h
app
y ab
out
bec
ause
nob
ody
can
bri
ng
you
a v
ehic
le t
hat
eas
ily.”
(P
aren
t)22
14, 1
5, 2
1, 2
2, 2
5–27
, 29–
32, 3
4,
36, 3
7, 3
9, 4
1, 7
0, 7
3
“On
e go
od t
hin
g ab
out
it is
th
at, t
her
e is
no
mon
ey in
volv
ed. T
he
par
ents
wou
ld a
lso
ben
efi t
fro
m t
he
trea
tmen
t gi
ven
. Dru
gs a
re s
o
exp
ensi
ve a
nd
are
not
ava
ilab
le in
gov
ern
men
t h
osp
ital
s.”
(Mot
her
)18
“I d
on’t
see
an
yth
ing
wro
ng
wit
h t
esti
ng
the
vacc
ine
on u
s . .
. it
’s u
s w
ho
are
dyi
ng
of A
IDS
.” (
Fem
ale
adol
esce
nt)
42
‘‘Doc
tors
will
not
giv
e u
s an
yth
ing
that
is h
arm
ful.”
An
oth
er s
ub
ject
sai
d, ‘
‘Doc
tors
are
in a
way
god
ly. W
ho
wou
ld k
now
bet
ter
than
them
?”18
by guest on November 15, 2020www.aappublications.org/newsDownloaded from
JOSEPH et al 10
Su
bth
emes
Par
tici
pan
ts’ Q
uot
atio
ns
and
/or
Auth
ors’
Exp
lan
atio
ns
Con
trib
uti
ng
Ref
eren
ces
M
edic
al m
istr
ust
“I d
on't
tru
st e
xper
imen
tal v
acci
nes
an
d m
oreo
ver
thes
e va
ccin
es b
rou
ght
her
e to
Afr
ica
by
scie
nti
sts
can
not
be
tru
sted
. Bec
ause
thes
e Eu
rop
ean
s kn
ow w
e ar
e p
oor
peo
ple
an
d s
o ac
cep
t an
y te
rms
and
con
dit
ion
s, t
hey
are
usi
ng
Afri
can
s lik
e gu
inea
-pig
s an
d
Afri
ca a
s a
du
mp
ing
pla
ce f
or s
o m
uch
was
te. I
kn
ow it
's t
rue
that
exp
erim
ents
hav
e to
be
carr
ied
ou
t b
y re
sear
cher
s on
hu
man
bei
ngs
, bu
t I d
on't
wan
t m
y ch
ild t
o b
e in
volv
ed.”
(P
aren
t)47
14, 1
5, 2
1, 2
2, 2
5–27
, 29–
34, 3
6,
37, 4
1, 7
0, 7
3, 7
5
“Th
e si
ckn
ess
alre
ady
red
uce
s th
e b
lood
so
wh
at if
mor
e is
tak
en?”
“W
on’t
th
at fi
nis
h o
f th
e ch
ild?”
27
“If
I giv
e th
em m
y ch
ild a
nd
th
e ch
ild d
ies,
th
en t
hey
giv
e m
oney
, th
at w
ill n
ot b
rin
g m
y ch
ild b
ack.
We
had
to
exp
lain
to
her
un
til
she
un
der
stoo
d. A
nd
in f
act,
som
e re
fuse
d a
t th
at s
tage
wh
en t
hey
hea
rd o
f KE
MR
I giv
ing
‘fi d
ia’ [
com
pen
sati
on],
th
ey s
aid
‘we
don
’t w
ant
our
child
ren
in it
. You
wan
t to
tak
e ou
r ch
ild a
nd
giv
e th
at c
hild
to
the
dev
ils’…
” (M
ale,
fi el
dw
orke
r)20
Con
ten
din
g w
ith
pow
er d
iffe
ren
tial
s
C
once
rnin
g p
oten
tial
for
exp
loit
atio
nW
hen
ask
ed, w
hy
the
MR
C h
ad c
ome
to A
fric
a, m
any
said
“to
hel
p.”
“B
ecau
se w
e Af
rica
ns
are
vuln
erab
le t
o d
isea
ses”
an
d “
bec
ause
they
can
’t fi
nd
th
ese
dis
ease
s in
th
e U
K,”
or “
bec
ause
we
are
pow
erle
ss p
eop
le a
nd
th
ey n
eed
to
hel
p u
s to
kn
ow t
he
dis
ease
s.”
“….b
ecau
se B
rita
in h
as m
ore
pow
er t
han
Afr
ica,
” “i
t w
ill b
e ea
sier
her
e th
an t
her
e” o
r ev
en “
in U
K p
eop
le a
re n
ot w
illin
g to
par
tici
pat
e in
tri
als.
”46
14, 2
2, 2
7, 3
5, 4
0, 4
2, 6
1, 6
3
“....
..th
ey m
igh
t b
e d
oin
g so
met
hin
g el
se a
lso
wit
hou
t yo
u k
now
ing.
If t
hey
are
dra
win
g b
lood
sam
ple
s, t
hey
’re
telli
ng
you
we
are
doi
ng
it f
or M
alar
ia, b
ut
do
anyb
ody
hav
e co
ntr
ol o
ver
it, t
hat
th
ose
blo
od s
amp
les
are
not
goi
ng
out
and
th
ey a
re d
oin
g so
me
gen
etic
tes
tin
g or
th
ey a
re d
oin
g so
met
hin
g el
se o
n it
? /.
../ t
hat
is m
y fe
ar a
nd
con
cern
...”
(In
stit
uti
onal
rev
iew
boa
rd)25
“… v
illag
e el
der
s te
nd
ed t
o b
e co
erci
ve s
omet
imes
… y
ou c
ould
go
wit
h t
hem
[to
hom
es]
and
you
kn
ow t
hat
… [
rese
arch
]
par
tici
pat
ion
is v
olu
nta
ry. B
ut
then
for
a v
illag
e el
der
, bec
ause
he
wan
ts t
he
[res
earc
h]
agen
da
fulfi
lled
th
en h
e sa
ys, ‘
we
wan
t
ever
ybod
y w
ho
has
an
elig
ible
ch
ild t
o jo
in t
he
stu
dy,
or
else
we
will
mak
e su
re y
ou a
re r
emov
ed e
ven
fro
m o
ther
gov
ern
men
t
pro
ject
s th
at a
re b
rou
ght
her
e.’ S
o in
su
ch a
pla
ce y
ou [
fi el
dw
orke
r] h
ave
to c
ome
bac
k ag
ain
an
d t
ry t
o ex
pla
in t
hat
th
is
[res
earc
h]
is n
ot a
mu
st, i
t’s
volu
nta
ry.”
(M
ale,
fi el
dw
orke
r)20
Fe
arin
g d
iscr
imin
atio
n a
nd
sti
gmat
izat
ion
“Th
is m
igh
t h
ave
un
inte
nd
ed o
utc
omes
wh
ere
peo
ple
mig
ht
feel
th
at t
hey
are
use
d, u
nd
erst
and
, . .
. un
fort
un
atel
y w
e h
ave
a lo
ng
his
tory
of
apar
thei
d w
her
e b
lack
s w
ere
exp
loit
ed.”
(M
ale
edu
cato
r)42
15, 2
2, 2
6, 2
8, 2
9, 3
1, 3
3, 3
7,
38, 6
1
“. .
. th
e co
mm
un
ity
will
ask
. . .
‘wh
at is
it t
hat
we
do
not
wan
t it
to
know
if t
her
e is
no
dan
ger
invo
lved
in t
his
res
earc
h?’
You
try
to e
xpla
in t
hat
th
ere
are
thin
gs in
a f
amily
, fam
ily s
itu
atio
n t
hat
. . .
on
ly f
amily
mem
ber
s sh
ould
kn
ow .
. . t
hat
is w
her
e p
eop
le
wou
ld b
egin
to
be
susp
icio
us;
an
d .
. . c
onfi
den
tial
ity
is g
ood
in t
hat
it s
aves
th
e liv
es o
f th
e p
eop
le w
ho
are
par
tici
pat
ing
in
rese
arch
an
d a
t th
e sa
me
tim
e it
is r
etar
din
g in
th
e co
mm
un
ity
that
is b
ein
g en
cou
rage
d t
o p
arti
cip
ate.
” (C
omm
un
ity
advi
sory
boa
rd m
emb
er)40
“Th
e w
ay [
the
FWs]
are
fre
e w
ith
us;
th
ey c
an v
isit
in t
he
mor
nin
g or
eve
nin
g to
ch
eck
on t
he
kid
. [S
o n
on-p
arti
cip
ants
] h
ave
now
star
ted
sp
read
ing
rum
ours
th
at t
hey
are
not
on
ly K
EMR
I bu
t ou
r b
oyfr
ien
ds.
” (M
oth
er)22
D
isem
pow
erm
ent
ham
per
ing
info
rmed
con
sen
t
If t
he
hu
sban
d s
ays
[in
a h
ouse
hol
d v
isit
] ‘o
h y
eah
you
go
liste
n a
nd
join
th
e st
ud
y,’ t
hen
th
ey a
re m
ore
likel
y to
… [
sin
ce]
they
alre
ady
hav
e p
erm
issi
on if
I m
ay s
ay s
o. B
ut
if y
ou ju
st s
pea
k to
th
em [
wom
en]
in a
bar
aza
[pu
blic
mee
tin
g] a
nd
th
en t
hey
go
exp
lain
to
thei
r h
usb
and
s, t
he
resp
onse
is n
ot s
o go
od.”
(Tr
ial s
taff
)20
15, 1
9, 2
2, 2
3, 2
5, 2
9–32
, 34,
36–
39, 4
1, 4
3, 6
1, 7
1–74
“Res
earc
h p
roje
ct?
They
bu
ild h
ouse
s?”
A tr
ansl
ator
for
a w
oman
wh
ose
child
was
in t
he
pla
ceb
o-co
ntr
olle
d m
alar
ia t
rial
exp
lain
ed, “
Sh
e d
oes
not
kn
ow w
hat
res
earc
h is
. Sh
e th
ough
t th
ey h
ave
alre
ady
don
e th
e re
sear
ch, a
nd
th
ey a
re t
ryin
g to
imp
lem
ent
the
resu
lts
of t
he
rese
arch
wit
h t
hes
e ch
ildre
n.”
(S
take
hol
der
)38
“You
r m
ain
con
cern
is t
o ge
t yo
ur
child
tre
ated
. Th
ey c
ould
eve
n a
sk y
ou t
o st
and
by
a fi
re a
ll d
ay, a
nd
you
’d d
o it
!” (
Mot
her
)29
Tran
slat
ing
rese
arch
to
loca
l con
text
TABL
E 3
Con
tin
ued
by guest on November 15, 2020www.aappublications.org/newsDownloaded from
PEDIATRICS Volume 137 , number 2 , February 2016 11
Su
bth
emes
Par
tici
pan
ts’ Q
uot
atio
ns
and
/or
Auth
ors’
Exp
lan
atio
ns
Con
trib
uti
ng
Ref
eren
ces
R
esp
ecti
ng
bel
iefs
an
d c
ult
ura
l pra
ctic
es“…
…..s
omew
her
e in
th
e n
orth
, wh
en a
ch
ild is
bor
n it
is n
ot b
rou
ght
out
un
til a
fter
on
e m
onth
or
so. S
o if
we
are
look
ing
at a
vacc
ine
targ
etin
g ch
ildre
n o
f fo
ur
wee
ks o
r le
ss, t
hat
can
pos
sib
ly b
e a
bar
rier
to
such
ch
ildre
n g
etti
ng
acce
ss t
o th
e va
ccin
e.”
(Rel
igio
us
lead
er)14
16, 2
2, 2
9, 3
1, 3
3, 3
7, 6
3, 7
0, 7
4
“...I
was
un
com
fort
able
dis
cuss
ing
top
ics
like
rep
rod
uct
ive
orga
ns
bec
ause
acc
ord
ing
to o
ur
Sh
ona
cult
ure
it’s
tab
oo.”
(Te
ach
er)50
This
was
illu
stra
ted
in t
he
bre
astf
eed
ing
stu
dy
rega
rdin
g th
e is
sue
of r
and
om a
ssig
nm
ent
of m
oth
er–
infa
nt
dya
ds
to b
reas
t- o
r
bot
tle-
feed
ing
grou
ps.
Alt
hou
gh r
and
omiz
atio
n a
lon
e p
osed
no
eth
ical
pro
ble
ms
(ass
um
ing
pro
per
su
pp
ort
of s
afe
bot
tle-
feed
ing
was
pro
vid
ed),
su
ch a
pro
ced
ure
cle
arly
cla
shed
wit
h p
reva
ilin
g cu
ltu
ral e
xpec
tati
ons
that
par
ents
sh
ould
ch
oose
an
infa
nt’
s fe
edin
g m
eth
od.17
“Tim
e is
su
ch a
big
con
stra
int
bec
ause
som
etim
es y
ou g
o to
info
rm t
he
chie
f an
d h
e sa
ys, ‘
Com
e b
ack
in 2
or
3 d
ays.
’…. y
ou n
eed
to a
dd
ab
out
a m
onth
just
to
com
ple
te t
he
com
mu
nit
y p
roce
ss.”
(N
HR
C s
ocia
l sci
enti
st)
“It
is p
art
of o
ur
cult
ure
; wh
atev
er y
ou a
re d
oin
g, if
th
ere
is n
o to
bac
co, i
t is
not
pro
per
.” (
Eld
er)16
U
nd
erst
and
ing
reso
urc
e co
nst
rain
tsIn
ad
dit
ion
, th
e H
aiti
an c
ust
om o
f sh
arin
g fo
od w
ith
nee
dy
nei
ghb
ors
and
hou
sem
ates
wou
ld h
ave
to b
e re
spec
ted
an
d t
aken
into
acco
un
t; t
hu
s, t
he
pro
visi
on o
f gr
ain
was
rec
omm
end
ed a
s a
mea
sure
to
dis
cou
rage
con
sum
pti
on o
f th
e in
fan
t fo
rmu
la b
y ot
her
fam
ily m
emb
ers.
17
29, 3
1, 3
3, 3
7, 4
2, 6
3, 7
0
“My
child
ren
are
als
o m
aln
ouri
shed
. I w
ould
sh
are
the
sup
ple
men
ts w
ith
th
em s
o th
ey c
an a
lso
hav
e go
od h
ealt
h.”
(M
oth
er)34
The
ped
iatr
ic w
ard
s at
UTH
du
rin
g th
e co
nd
uct
of
this
stu
dy
wer
e of
ten
con
gest
ed. “
Floo
r b
eds,
” w
hic
h w
ere
tem
por
ary
bed
s,
cou
ld b
e fo
un
d o
n t
he
war
ds
du
e to
th
e la
rge
nu
mb
er o
f p
atie
nts
an
d in
suffi
cie
nt
reso
urc
es.49
How
ever
, it
was
ack
now
led
ged
th
at: “
bei
ng
com
ple
tely
alt
ruis
tic
and
par
tici
pat
ing
in r
esea
rch
th
at is
[go
ing
to]
ben
efi t
soc
iety
an
d
futu
re g
ener
atio
ns,
is s
omet
imes
a li
ttle
har
d t
o ex
pec
t fr
om p
eop
le w
ho’
re s
tru
gglin
g to
kee
p t
hei
r fa
mily
fed
.” (
Sit
e st
aff)
40
Et
hic
al p
lura
lism
“Man
y of
th
e p
eop
le in
th
e re
gula
tory
div
isio
ns
in t
he
US
or
the
Wes
t h
ave
real
ly c
ond
uct
ed t
rial
s in
th
e W
est.
An
d t
hey
’re
very
good
, bu
t in
res
ourc
e-lim
ited
set
tin
gs, t
hey
act
ual
ly s
omet
imes
don
’t u
nd
erst
and
th
e co
nte
xt o
f th
e p
atie
nts
bei
ng
very
sick
, you
as
a re
sear
cher
bei
ng
thei
r p
rim
ary
clin
icia
n s
o yo
u’r
e d
ealin
g n
ot o
nly
wit
h t
he
stu
dy
com
pon
ent,
bu
t yo
u’r
e al
so
pro
vid
ing
care
an
d t
reat
men
t. A
nd
so
ther
e ar
e a
lot
mor
e vi
sits
th
at g
o b
eyon
d t
he
stu
dy
visi
ts t
hat
you
hav
e to
tak
e ca
re o
f
as a
res
earc
her
. So
ther
e ar
e a
lot
of s
ever
e, a
dve
rse
even
ts t
hat
are
not
rel
ated
to
the
dru
g, b
ut
actu
ally
are
sev
ere,
ad
vers
e
even
ts t
hat
are
par
t an
d p
arce
l of
a ch
ild g
row
ing
up
in A
fric
a w
ith
a h
igh
infa
nt
mor
talit
y ra
te, a
lot
of m
alar
ia a
nd
pn
eum
onia
,
dia
rrh
ea. J
ust
th
e co
mm
on il
lnes
ses
that
all
nee
d t
o b
e re
por
ted
as
seri
ous
adve
rse
even
ts. Y
ou k
now
, we’
re n
ot d
enyi
ng
that
they
sh
ould
be
rep
orte
d, b
ut
ther
e is
a h
eavy
load
on
th
e st
aff
that
are
doi
ng
the
stu
die
s.”
(In
vest
igat
or)48
15, 2
2, 2
7, 3
0, 3
5, 3
6, 4
2, 4
3, 7
2
“My
opin
ion
is t
hat
we
shou
ld u
se t
he
stan
dar
d o
f ca
re h
ere.
Bec
ause
it m
akes
mor
e se
nse
if y
ou a
re in
vest
igat
ing
wh
eth
er
som
eth
ing
is u
sefu
l, yo
u s
hou
ld c
omp
are
it w
ith
wh
at is
bei
ng
don
e h
ere
rath
er t
han
wh
at is
bei
ng
don
e in
th
e U
S, w
hic
h w
ill
take
a lo
ng
tim
e ac
tual
ly t
o b
e d
one
her
e.”
(In
vest
igat
or)48
“I s
aid
to
them
, ‘th
is is
ver
y go
od, b
ut
wh
y ar
e yo
u g
ivin
g a
pla
ceb
o to
th
is o
ther
gro
up
? D
o yo
u k
now
th
at t
he
tran
smis
sion
is
obvi
ousl
y p
rove
n. I
t’s
ther
e. S
o, c
an y
ou r
eally
giv
e p
lace
bo
to t
his
gro
up
?’ T
hey
sai
d, ‘
Yeah
. Bu
t yo
u k
now
, in
as
far
as w
e ar
e
con
cern
ed, t
her
e is
no
oth
er s
tud
y re
gard
ing
this
so
we
real
ly w
ant
to g
ive
pla
ceb
o to
pro
ve it
.’ I s
aid
, ‘N
o w
ay!
Ther
e’s
no
way
!
You
kn
ow t
hat
th
ese
mot
her
s ar
e at
a d
isad
van
tage
.
The
child
ren
are
at
a d
isad
van
tage
. How
do
you
say
you
are
goi
ng
to g
ive
pla
ceb
o? Y
ou a
re d
elib
erat
ely
infe
ctin
g th
ose
child
ren
!’
Rig
ht?
So
we
refu
sed
an
d t
hat
gro
up
was
giv
en n
evir
apin
e an
d t
his
oth
er g
rou
p r
ecei
ved
th
e n
ew d
rugs
. So
they
did
th
e st
ud
y…
‘It’s
th
e sc
ien
ce a
nd
th
e et
hic
s. T
ell m
e in
Sw
eden
, in
th
e S
tate
s, in
Can
ada,
in F
ran
ce, w
ould
th
is r
esea
rch
pas
s th
e et
hic
s
com
mit
tee?
Wou
ld A
mer
ican
ch
ildre
n, C
anad
ian
ch
ildre
n, S
wed
ish
ch
ildre
n, F
ren
ch, N
orw
egia
n c
hild
ren
be
del
iber
atel
y ex
pos
ed
to m
ilk t
hat
was
HIV
-infe
cted
an
d b
e gi
ven
pla
ceb
o? A
nd
com
par
ed w
ith
a g
rou
p t
hat
was
rec
eivi
ng
anti
-ret
rovi
ral d
rugs
? W
ould
that
pas
s yo
ur
eth
ics
com
mit
tee?
’” (
Inve
stig
ator
)48
“Som
etim
es p
eop
le d
on’t
eve
n lo
ok a
t th
e is
sues
, you
kn
ow, t
hey
mig
ht
be
inte
rest
ed in
wh
at t
hey
are
goi
ng
to g
et o
ut
of t
he
tria
l
in t
erm
s of
mon
ey”
(Res
earc
h e
thic
s co
mm
itte
e). “
…Th
e p
rob
lem
is, i
f yo
u s
tart
ago
niz
ing
over
ind
uce
men
ts t
hen
you
com
e ou
t
sayi
ng
that
if a
per
son
is p
oor
we
will
giv
e le
ss t
o b
e in
th
e tr
ial t
han
if t
hey
are
ric
h.”
(S
pon
sor)
40
Advo
cati
ng
fair
dis
trib
uti
on o
f b
enefi
ts
TABL
E 3
Con
tin
ued
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advisory boards) to address
expectations of the community and
researchers more effectively.31,40
Retaining Community Intermediaries’
Involvement: Retention of
community workers was deemed
critical for a trial to be successful,
but potential barriers included
dissatisfaction with remuneration,
limited scope of responsibilities,
heavy workload, work-related
travel, familial opposition, and
negative attitudes of parents toward
the workers.12,13 Community
workers were motivated to
participate because of recognition
and appreciation, altruism,
humanitarian, and religious reasons,
but they recommended appropriate
compensation and incentives to
improve retention.13,20
Cognizance of Vulnerability and Poverty
Vital Therapeutic Opportunity: For
parents, the hope for free, quality
medical care for their children and
their family was the driving force for
participation in trials.35 Some parents
feared that refusal to participate
would result in denial of medical
care.40,42 The Gambian community
appreciated having posttrial access
to treatment,46 and mothers in
Malawi valued the clinical testing
provided in the trials.35 Parents had
a “therapeutic misconception”23
that all trial interventions were
beneficial; for example, they believed
that participating in the HIV trials
would prevent their child from
contracting HIV.23,34 Altruism also
motivated participation, with the
goal of contributing to science and
providing hope for new therapies
for future generations and the
underprivileged.43,47
Medical Mistrust: The community’s
mistrust of medical research
was a barrier that researchers
believed needed to be addressed
sensitively.22,40 A major concern in
Africa was the perceived dangers
of gathering blood samples. The
community believed the blood
12
Su
bth
emes
Par
tici
pan
ts’ Q
uot
atio
ns
and
/or
Auth
ors’
Exp
lan
atio
ns
Con
trib
uti
ng
Ref
eren
ces
S
up
por
tin
g h
ealt
h c
are
and
soc
ieta
l nee
ds
“...w
e w
ant
to e
nsu
re t
hat
if y
ou a
re c
arry
ing
rese
arch
wit
hin
a p
arti
cula
r co
mm
un
ity,
you
nee
d t
o gi
ve t
hem
som
eth
ing
bac
k fo
r
inst
ance
a h
osp
ital
or
som
eth
ing,
eve
n if
you
are
doi
ng
clin
ical
res
earc
h. I
t ca
n b
e an
yth
ing
else
th
at c
an b
enefi
t t
he
com
mu
nit
y.
Som
e so
rt o
f in
fras
tru
ctu
re, s
o th
at t
hey
can
at
leas
t se
e th
at t
hey
are
ben
efi t
ing.
On
ce y
ou h
ave
don
e th
at, a
ctu
ally
th
ey w
ill
feel
th
at t
hey
are
par
t of
th
e p
roce
ss...
” (C
ivil
Soc
iety
Org
aniz
atio
n)26
16, 2
7, 4
4, 7
5
“...
he
likes
to
talk
ab
out
‘bra
in g
ain
’ as
opp
osed
to
‘bra
in d
rain
.’ I m
ean
th
e fa
ct is
, we
are
bei
ng
able
to
pro
vid
e in
tere
stin
g
rese
arch
wor
k fo
r lo
ts o
f sc
ien
tist
s....
bu
t th
ere
are
a lo
t of
doc
tors
th
at a
re a
ble
to
do
wh
at t
hey
wan
t to
do
wh
ich
is t
o st
ay in
thei
r ow
n c
oun
try
and
wor
k in
th
eir
own
cou
ntr
y.”
(Pu
blic
pri
vate
par
tner
ship
1)26
The
effe
ctiv
e an
d f
ast
trea
tmen
t of
fere
d t
o tr
ial p
arti
cip
ants
as
wel
l as
non
par
tici
pan
ts…
“Th
e d
eath
of
child
ren
has
bee
n
mas
sive
ly r
edu
ced
in t
he
pae
dia
tric
war
d.”
(H
ealt
h w
orke
r)44
“Eve
n if
th
e p
aren
ts o
r gu
ard
ian
s d
o n
ot h
ave
mon
ey t
hey
sti
ll ge
t q
ual
ity
hea
lth
ser
vice
, th
is p
roje
ct d
oes
not
seg
rega
te b
etw
een
rich
peo
ple
an
d p
oor
peo
ple
…”
(48-
year
-old
Fem
ale)
44
S
pon
sor
oblig
atio
n“.
..in
th
e p
revi
ous
dec
ade
(th
e in
du
stry
) w
as s
een
to
just
pu
rely
pro
fi t
from
hu
man
su
ffer
ing
and
peo
ple
had
a v
ery
neg
ativ
e vi
ew
of t
he
ph
arm
aceu
tica
l in
du
stry
. An
d in
th
e la
st 1
0 ye
ars,
we
are
sort
of
re-m
odel
ling
our
self
an
d t
ryin
g to
mak
e su
re w
e p
roje
ct
our
self
in a
ver
y re
spon
sib
le m
ann
er...
” (P
har
mac
euti
cal c
omp
any
1)25
16, 2
2, 3
5, 4
0
“...
I th
ink
you
sh
ould
be
real
isti
c, t
hat
nob
ody
is g
oin
g to
com
e b
ack
and
you
may
not
be
ther
e to
en
forc
e th
at s
omeb
ody
shou
ld
give
bac
k to
th
e co
mm
un
ity.
..an
d o
nce
th
ey fi
nd
wh
at t
hey
are
look
ing
for,
th
ey m
ay ju
st t
ake
off..
.” (
Inst
itu
tion
al r
evie
w b
oard
)25
C
olla
tera
l com
mu
nit
y b
enefi
ts
“We
can
not
ser
ve t
he
enti
re c
omm
un
ity,
bu
t n
eith
er c
an w
e on
ly s
erve
vol
un
teer
s an
d le
ave
out
thei
r w
ives
an
d c
hild
ren
… t
hes
e
peo
ple
are
all
rela
ted
—b
ut
wh
ere
wou
ld w
e en
d?”
(Fi
eld
wor
ker)
46
22, 2
7, 2
8, 3
2, 4
0
“We
do
not
acc
ept!
We
do
not
acc
ept
it a
t al
l! A
nd
if y
ou d
o so
, we
will
wit
hd
raw
com
ple
tely
fro
m t
he
stu
dy!
We
wan
t to
be
vacc
inat
ed: u
s, o
ur
child
ren
, ou
r h
usb
and
s an
d e
ven
ou
r d
ogs!
” “M
ayb
e th
ey [
non
par
tici
pan
ts]
are
the
ones
th
at w
ill b
e b
itte
n
by
dog
s an
d w
e w
ill n
ot g
et t
hat
vac
cin
e . .
.” (
Mot
her
s)23
“Eve
n w
ith
far
es; a
stu
dy
will
giv
e ex
act
fare
, an
oth
er o
ne
will
giv
e ex
tra—
like
one
and
a h
alf
the
amou
nt
that
peo
ple
are
ch
arge
d,
so s
omet
imes
it b
rin
gs p
rob
lem
s an
d y
ou k
now
som
etim
es t
hey
are
in o
ne
stu
dy
wh
en t
hey
com
ple
te t
hen
may
be
anot
her
ch
ild
is in
an
oth
er s
tud
y, s
o th
ey a
re li
ke, ‘
wh
y is
it t
hat
I w
as g
iven
dou
ble
far
e an
d n
ow y
ou a
re g
ivin
g m
e on
ly o
ne
way
.’” (
Clin
ical
offi
cer)
30
CH
W, c
omm
un
ity
hea
lth
wor
ker;
FW
, fi e
ldw
orke
r; M
RC
, Med
ical
Res
earc
h C
oun
cil;
NH
RC
, Nav
ron
go H
ealt
h R
esea
rch
Cen
tre;
UTH
, Un
iver
sity
Tea
chin
g H
osp
ital
.
TABL
E 3
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ued
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PEDIATRICS Volume 137 , number 2 , February 2016
was sold “because our blood is of
higher quality than that of the white
people.”45 Parents were anxious that
“the trial was a disguise for witchcraft
or Satanism,”49 “children’s body parts
would be removed and sold,” or the
“white people” would infect them
with HIV or tuberculosis.21 Parents in
Puerto Rico were reluctant to enroll
their children in a placebo-controlled
trial because they “would not trust
what is being injected to their
children.”39 The need to sign consent
forms were regarded with suspicion,
and some perceived that it was a way
to absolve researchers of liability.20,28
Contending With Power Differentials
Potential for Exploitation:
Most stakeholders believed
impoverishment rendered these
communities “powerless” and
vulnerable to exploitation.46
Regulators raised concerns regarding
LMICs being easy recruitment
sites in multinational trials in
which researchers “parachute in,
parachute out.”25,46 There were
concerns of inducement and conflict
of interest because some leaders
and trial staff were perceived
as exercising their authority to
“exert pressure” on the community
to participate.20 Regulators felt
that providing benefits or large
monetary payments to participants
could lead to commodification of
research, but sponsors believed
that participant payments should
be equitable and not based on the
country’s economy.27,40 Researchers
were afraid of being involved with
the media, whom they perceived as
exploitative, “vultures,” and always
“raping their work.”40
Fearing Discrimination and
Stigmatization: In South Africa,
stakeholders advocated for fairness
in community and participant
selection because of the perceived
discrimination in which vulnerable
“black people were targeted as
research participants.”40 Participants
feared stigmatization and
humiliation; they feared that their
participation would be misconstrued
as them having HIV in the context of
the trial.17,41,42 Parents in a malaria
vaccine trial feared becoming a
“laughingstock” by nonparticipants
and desired that results of ineffective
interventions remain confidential.22
Disempowerment Hampering
Informed Consent: Stakeholders
believed that disempowerment,
poor education, and difficulty in
translating scientific concepts were
barriers to informed decision-
making.30,38,39 They recommended
that consent forms be simplified
and presented in a culturally and
linguistically appropriate format
with verification of parental
comprehension.17 Parents’
implicit trust in physicians was a
concern because the physician’s
recommendation of the trial could
be misinterpreted as endorsement
that the intervention is effective.34
In patriarchal African and Indian
societies, women were believed
to have minimal decision-making
power,18,23 although in some
countries, such as Malawi, women
made decisions autonomously.18,23,35
There were conflicting views on
children’s decision-making capacity.
Some reported children being
persuaded to participate.40,41
Translating Research to Local Context
Respecting Beliefs and Cultural
Practices: Cultural beliefs that
conflicted with the trial were a
challenge for researchers. For
example, parents felt that the
requirement for contraception to
prevent pregnancy in the vaccine
trial “will encourage girls to have
sexual intercourse before getting
married” or “could cause infertility.”39
In some communities, illness was
believed to be due to physical or
spiritual occurrences, and herbalists
and religious leaders were trusted
to protect their child’s health,
which discouraged participation in
trials.45 The confidentiality measures
required in trials were perceived by
the community to be a contravention
of their cultural practices and were
misinterpreted that the trial was
unethical or shameful.40 Researchers
also recognized that culturally
13
FIGURE 3Thematic schema.
by guest on November 15, 2020www.aappublications.org/newsDownloaded from
JOSEPH et al
accepted practices could conflict
with ethical principles. For example,
in Ghana, presenting the paramount
chiefs with gifts at the initial trial visit
was customary, but this action could
be seen as an inducement.16
Understanding Constraints of
Impoverishment: Researchers
advocated that international
sponsors need to understand the
severe economic scarcity when
planning trials and to ensure that
interventions are feasible and
sustainable in LMICs.17,48 Parents
reported sharing therapeutic
interventions with nonparticipants.
The community in Malawi
recommended that for the bottle-
feeding intervention in the HIV
trial to be sustained, the “sterilizing
paraphernalia” needed to be
provided because they could not
afford these items.34
Ethical Pluralism: In international
trials, some supported the
“universality of ethics,”40 whereas
others argued that ethical standards
vary across cultures.28,48 Researchers
believed that rigorous international
requirements of documentation
were too ambitious for LMICs.22,37
Some believed that trials needed
to produce locally relevant results
and should not have “an island of
excellent investigation where that’s
not your standard of care.”48 African
researchers were concerned that if
international standards were not
strictly applied locally, their research
quality would be unacceptable in the
global arena. For example, serious
adverse events required all coexisting
medical conditions and symptoms
related to poverty (eg, malnutrition)
to be reported.
Advocating Fair Distribution of Benefi ts
Supporting Health Care and Societal
Needs: Stakeholders encouraged
the “sharing and mutuality”21 of
research-related benefits with
participants to prevent exploitation
and promote the societal value of
international health research.21,25
However, they recognized that the
governance framework regarding
provision and accountability of
these benefits was inadequate.26,40
Stakeholders believed that “tangible
benefits to host communities have
been insufficient and unfairly so.”16
Many stakeholders supported trials
as a means to help address health
care inequities, including poor access
and affordability of therapeutic
products for children, and to promote
social justice.25
Sponsor Obligation: Regulators and
researchers argued that sponsors
had a moral responsibility to
ensure availability of the proven
interventions after trial completion
and to improve research and health
care capacities.40 For example, in
Kenya, the secondary benefits of
a malaria vaccine trial included
improved local health facilities,
provision of medical equipment, and
upskilling of medical personnel.30
Community members perceived
that the primary role of sponsors
was to provide access to treatment
and better quality medical care.26,46
Reimbursement of out-of-pocket trial
expenses and providing ancillary
medical care were considered
distinct to sharing benefits arising
from the research.
Collateral Community Benefits:
Although researchers believed that
trial participants, and those who
did not participate (including those
who withdrew), should have access
to the intervention,40 some parents
felt this approach was unfair and
that only participants should benefit
from the trial intervention.23,40,46
Sponsors in The Gambia elected to
treat nonparticipants and siblings
of participants to maintain overall
community goodwill.45 Tensions
emerged when benefits differed
between studies or when there
was poor clarity or disagreements
on eligibility for reimbursement.30
Researchers proposed that direct
collateral community benefits should
be primarily medical rather than
monetary and should be maximized
through engagement of the country’s
ministry of health.
DISCUSSION
Conducting trials in children in
LMICs is regarded as a complex and
arduous process by a broad range
of stakeholders, including children,
parents or caregivers, community
members, clinical or research team
members, regulators, and sponsors.
This complexity is due to the difficult
financial scarcity and cultural
contexts that have been shaped
historically by disadvantage and
exploitation. This disempowerment
also contributes to the communities’
mistrust of trials and fears of
stigmatization. Stakeholders believed
that trials should be adapted to the
local context, with consideration of
the resource constraints, cultural
beliefs, and ethical pluralism. A
perceived opportunity to access
medical care among parents and the
community, engaging the community,
addressing expectations, and fair
distribution of research benefits were
seen to facilitate the conduct of trials.
The primary motivation of parents
to participate in trials across all
income settings is the opportunity
of better medical care for their child;
however, in LMICs, participation in
trials was often the only option to
access treatment.3,51 The parents’
implicit trust in physicians’
recommendations to enroll children
in trials was apparent, which may
contrast to parental reluctance in
high-income countries.51 Although
involving parents and families in
the protocol design is encouraged
universally, this involvement is more
difficult in LMICs in which there are
specific misconceptions regarding
trials.3 Rumors such as “blood and
organ stealing,” as well as belief in
witchcraft as a cause of illness and
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PEDIATRICS Volume 137 , number 2 , February 2016
traditional medicines as a cure, were
often regarded as more important
and relevant than biomedical
risks.22 These rumors and fears
of stigmatization for participation
may be constructively addressed
by contextualization, community
education to improve health
literacy, and engaging community
representatives to help build trust
by fostering mutual understanding,
respect, and equity.28,49,52–54
Community engagement is a dynamic
process and a constantly changing set
of negotiated relationships to address
expectations and challenges tailored
to the local setting.55,56 Stakeholders
recommended ethnographic research
in preparation for commencing a
trial within a community, to improve
feasibility, methodologic rigor, and
acceptability of trial protocol, while
safeguarding the health and interests
of child participants.17,34 Feedback
of the trial findings to the participant
and the community is complex but
was recognized as a key component
of continuing social interactions and
is encouraged in all trials.23,57
The underlying principle of
consent being free, autonomous,
and informed is the cornerstone
of trials universally.58–60 However,
findings from the present literature
review reaffirm observations that
meaningful decision-making is
further compromised in LMICs
by disempowerment, cultural
idiosyncrasies, extensive illiteracy,
and/or decision-making styles.18,38,59
Thus, the Western ethical principles
of informed consent and child
assent, autonomy, and individualism
need to be contextualized.18,45,61
Many of the controversial ethical
issues (eg, the use of placebo, the
appropriate local standard of care,
resource constraints in complying
with the rigorous trial requirements)
we reported in this literature
review are part of the international
agenda.56,60,62,63 Some stakeholders
reported that ethical approval and
oversight of trials in children were
also inadequate.6 The rigid ethical/
legal framework of children’s
participation in trials, arising from
paternalism and poor awareness,
was recognized as a barrier that
unnecessarily excludes children
from trials.40,41 The results of this
systematic review show that there
is scope for a common international
ethical framework to be applied in
LMICs with ethical reasoning of the
moral application of these principles
in these contexts.47,64 Researchers
supported the development of a
pragmatic ethical framework for
children’s involvement in trials that
is appropriate in LMICs.22,65,66
Communities in LMICs place a greater
emphasis on tangible research
benefits and remuneration, which
some stakeholders believe may be
coercive and cloud the objective
assessment of potential risks to
participants.32,67 Many were troubled
that poverty (compounded by lack of
medical care, unawareness of medical
rights, and language barriers)
rendered children and communities
more vulnerable to exploitation in
trials.17,34,50 Stakeholders reported
potential vertical exploitation, in
which community intermediaries
are encouraged by researchers
to take advantage of their social
relationships to coerce participants,
and horizontal exploitation, in
which intermediaries influenced
participation to increase their
remuneration.68 Some were
concerned that the pharmaceutical
industry may exploit LMICs by
conducting trials primarily for the
benefit of wealthy countries.48 Some
stakeholders therefore supported
research that investigates less
expensive ways of using proven
treatments for treating conditions
specific to local child health
priorities.
The results of the present
systematic review reaffirm the
ongoing discourse of children
and communities needing to
benefit from research to promote
justice and equity.25 Although
benefit sharing and defining fair
research–related benefits are
standard ethical concerns in global
health research, we found that
its practical implementation is
complex, with less attention on
the consequences of delivering on
promises of benefits in LMICs.40,62,69
Controversy and contention still
exist internationally concerning the
ethics of monetary compensation
to parents and investigators.40,70
However, findings from this
literature review showed that there
are poorer governance structures
and greater concerns regarding
inducement or coercion in LMICs.
More empirical work is needed
to guide appropriate and ethical
distribution of research benefits in
LMICs.26,30 There is speculation that
the lack of commercial incentives
to the pharmaceutical industry
(the major driver and sponsor of
trials) to conduct trials in children
with diseases specific to LMICs may
have contributed to a much lower
allocation of resources to trials in
LMICs relative to the tremendous
burden of disease. Addressing this
gap is on the global health research
and development agenda.4,71,72
Stakeholders advocated for
communities to receive concrete
benefits to compensate for years of
disadvantage and ostracism, echoing
the international ethics discussions
that encourage sponsor investment
in developing health research
capacities.73
The experiences, as well as the
practical and ethical concerns of
stakeholders, identified in this
literature review can inform the
design and conduct of clinical trials
in children in LMICs. Our synthesis
reflects the diversity and full breadth
of data reported in the primary
studies, and we recognize that the
majority of the findings were focused
on the problems, challenges, and
issues related to research in LMICs.
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JOSEPH et al
Further studies may be conducted to
elicit stakeholder perspectives on the
initiatives, approaches, and positive
developments that exist or would be
effective in encouraging additional,
high-quality trials of clinical
relevance in children in LMICs. Some
studies were conducted in local
languages, and transcripts were
translated into English, which could
be a potential limitation if linguistic
and cultural nuances were not fully
conveyed in the primary study.14 In
addition, some of the interviews in
the primary studies were conducted
by the research institute or trial
staff, rather than by the independent
interviewers, which may have
limited the full range of issues
and experiences that stakeholders
were willing to share. Studies not
published in English were excluded
to avoid misinterpretation of results.
This systematic review focused on
clinical trials in children in LMICs;
however, some issues are common
for high-income countries as well as
in the adult population.
CONCLUSIONS AND FUTURE DIRECTIONS
The clinical trials paradigm is
complex in LMICs because it is
hampered by impoverishment,
disempowerment, inequity, and
idiosyncratic cultural beliefs that
have created mistrust in clinical
research with fears of exploitation.
Key facilitators are engaging the
community in mobilizing and
designing trials that are pragmatic,
ethical, and relevant to the health
care needs of children in these
diverse settings. Fair distribution
of research benefits, including
investment in research infrastructure
and regulatory frameworks, will help
restore trust lost by the past social
injustices and promote additional
high-quality trials to improve
the future of these historically
disadvantaged children.
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ABBREVIATION
LMICs: low- and middle-income
countries
data collected, analysis and interpretation of the data, and review of the manuscript; and Drs Caldwell, Tong, and Craig contributed to study conception and
design, review of the data collected, analysis and interpretation of the data, and critical review of the manuscript. All authors approved the fi nal manuscript as
submitted.
DOI: 10.1542/peds.2015-2800
Accepted for publication Nov 16, 2015
Address correspondence to Pathma D. Joseph, BPharm, MPharm, The Pharmacy Department, The Children’s Hospital at Westmead, Corner of Hawkesbury Rd and
Hainsworth St, Westmead, NSW Australia 2145. E-mail: [email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2016 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no fi nancial relationships relevant to this article to disclose.
FUNDING: Supported by the National Health and Medical Research Council Postgraduate scholarship (1039338).
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential confl icts of interest to disclose.
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DOI: 10.1542/peds.2015-2800 originally published online January 26, 2016; 2016;137;Pediatrics
Jonathan C. CraigPathma D. Joseph, Patrina H.Y. Caldwell, Allison Tong, Camilla S. Hanson and
Systematic ReviewStakeholder Views of Clinical Trials in Low- and Middle-Income Countries: A
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DOI: 10.1542/peds.2015-2800 originally published online January 26, 2016; 2016;137;Pediatrics
Jonathan C. CraigPathma D. Joseph, Patrina H.Y. Caldwell, Allison Tong, Camilla S. Hanson and
Systematic ReviewStakeholder Views of Clinical Trials in Low- and Middle-Income Countries: A
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by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397. the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2016has been published continuously since 1948. Pediatrics is owned, published, and trademarked by Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
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