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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PEDIATRICS Volume 137 , number 2 , February 2016 5

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JOSEPH et al 6

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2007

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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

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ued

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JOSEPH et al

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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tin

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.

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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: pathma.joseph@health.nsw.gov.au

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).

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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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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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