Motives for participating in a clinical research trial: a pilot study in Brazil.

0.23 MB·English

by  Nappo, Solange A

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RESEARCH ARTICLE Open Access
Motives for participating in a clinical research
trial: a pilot study in Brazil
Solange A Nappo*, Giovanna B Iafrate and Zila M Sanchez
Abstract
Background: Inthe past, clinical study participants have suffered from theexperimentsthat theywere subjected
to.Study subjects may not understand thestudy process or may participate inclinical studies because they do not
have access to medical care. The objectives ofthe present study were 1. to analyze the motives that might cause a
volunteer to participate as a study subject; 2. to identify the social-demographicprofile of this study subjects; and 3.
to determine whether the motives to volunteer as a study subject are in accordancewith theestablishedlegal and
ethical principlesfor research inBrazil.
Methods: Mixed-methods research was used (a qualitative-quantitativeapproach). A sampleof 80 volunteers
underwent a semi-structured interview, which was based on a survey script that was elaborated from discussions
withkey informants. The sample was randomly selected from a database of clinical study volunteers that was
provided by Brazilian clinical study centers. The interviews were recorded and transcribed. Descriptive statisticswere
used for content analysis, including contingencytableswith hypothesis testing.
Results: The motivations for clinical study participation were linked to types of benefit. The most frequently
encountered motivations were financial gain and therapeutic alternative. Altruismwas not a common motivator,
and when altruism was present, it was observed as a secondary motivator. All participants reported that they
understood the Informed Consent Statement (ICS). However, onlytwo partsof theform were remembered by allof
thevolunteers:thesection onbeing able to leave the study atany point and the section that stated that there
would be some responsible professional attheirdisposal for the entirety ofthe study.
Conclusions: The present study shows that study participants are primarily motivated by personal benefit when
volunteering to participate in clinical studies. Whetherthesestudy participants had an integral understanding of the
ICS is notclear.
Background In the past, study participants have suffered from the
A clinical study is an investigation that uses human sub- experiments that they were subjected to. One example is
jects to contribute to knowledge that can be applied to the experiments that were performed on prisoners dur-
benefit society. Clinical studies typically evaluate an ing World War II [4], which generated a series of
intervention that is applied to study subjects. The inter- tragedies that are still remembered today. Those experi-
ventionmightbe adrug,vaccine or therapeuticor surgi- ments violated the ethical rules that are currently ap-
cal procedure [1]. Clinical studies are indispensable for plied toclinical studies[5,6].
the progress of medicine, especially for the discovery of Past violations have contributed to the development of
new pharmaceuticals [2]. However, the use of human mechanisms to protect human subjects [7]. The scien-
subjects in these studies as a unit of analysis introduces tific community was made aware of these violations, and
certainchallenges[3]. various regulations have been elaborated to protect
human rights and the integrity and dignity of individuals
participatinginbiomedicalresearch[8].
However, the unethical studies of the past have left a
*Correspondence:[email protected]
BrazilianCenterofInformationofPsychotropicDrugs(CEBRID),Department strong impression and are still referenced in developing
ofPreventiveMedicine,UniversidadeFederaldeSaoPaulo,04038-034,Sao countries. In Brazil, the general perception is that the
Paulo,Brazil
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CommonsAttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,and
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risks to study subjects are greater than the benefits, and to identify the motivations for study participation, focus-
the term “human guinea pig” is commonly used to de- ing on interviewees perception and behaviors [18].
scribe clinical studyparticipants[9]. Quantitative analyzes were used to compare the motiva-
The basic principles of bioethics (autonomy, benefi- tors for research participation between groups and the
cence, non-maleficence and justice) [10] may be violated variablesthatareassociatedwith thismotivation.
in clinical studies on human subjects in such developing
countriesasBrazilandmaybeasourceof biaswithinthe Recruitmentoftheparticipants
study [11]. The characteristics of study populations from A convenience sample was used. Three clinical research
these countries, such as poverty, illiteracy, lack of educa- centers that conduct Phase I (bioequivalence) and Phase
tionandlackofavailability/accesstohealthcare,maycre- III (therapeutic) studies provided the records of subject
ate inherent bias. In addition, several authors warn that participants. One center was in São Paulo, another was
populations in developing countries require special pro- in Campinas and the third was in Goiania. In Brazil,
tection, due to these factors [12]. These study subjects there are few Phase I studies. Therefore, we considered
may not understand the study process or may participate bioequivalence studies, which use healthy volunteers to
inclinicalstudiesbecausetheydonothaveaccesstomed- compare the bioavailability of a generic medicine to a
icalcare.Otherauthorshavenotedthatthesestudyparti- reference medicine, to be Phase I studies. The partici-
cipants are more susceptible to coercion and may more pants were selected from 10 lists with a total of 500
easilybecomevolunteersinclinicalstudies[13]. volunteers each and were contacted by telephone for a
Fortunately, it is clear that there has been increased personalinterview inthe FederalUniversity ofSão Paulo
emphasis on bioethics in Brazil in relationship to clinical (Universidade Federal de São Paulo, UNIFESP). These
studiesof humansubjects.TheClinicalStudyRegulation lists were composed of volunteers who participated in
was created under Resolution 196/96 of the National previous studies when they left permission to be con-
Health Council (Conselho Nacional de Saúde-CNS) of tacted for future studies. They included the names of
the Health Ministry. As a result, the ethical evaluation participants of studies conducted by the centers for the
process that a clinical study must pass is sufficiently two years previously. The participation rate was 89%. In
rigorous and is in accordance with national laws [14]. In total, 90 participants were contacted (30 from each
addition to the bioethics evaluation performed by the center), and 80 agreed to participate. The 10 refusals to
Ethics in Research Committee (Comitê de Ética em participate included 4 men and 6 women, from the 3
Pesquisa - CEP) of the study institution, international centers.
studies must also receive consent from the National
Commission of Ethics in Research of the National Procedurefortranslatingthedata
Health Council (Comissão Nacional de Ética em Pesquisa The interviews were conducted in Portuguese being
do Conselho Nacional de Saúde - CONEP) and the recorded and later on transcribed and analyzed. The
National Sanitary Monitoring Agency (Agência Nacional final result wastranslatedinto EnglishbyAJE(American
deVigilânciaSanitária-ANVISA)[5]. Journal Experts) a site of experts from the scientific
All subjects receive an Informed Consent Statement community with expertise in the two languages (English
(ICS). This document explains in accessible language the and Portuguese). The quotes were back translated in
researchdetailstoensurethatthatthesubjectunderstands order to ensure the fidelity of the interviewees’
the procedures, risks, discomforts, benefits and rights statements.
involvedandmakesanautonomousdecision[15,16].
Despite the rigor of these interventions, the idea per- Samplesize
sists that study subjects in Brazil participate in clinical The sample was composed of 80 volunteers who had
studiesforthewrongreasons[9]. participated in at least one Phase I or Phase III clinical
The objective of the present study is to identify the study. The sample size was limited by the qualitative in-
specific motivators that inspire Brazilian volunteers to depth interview. Furthermore, this pilot study was not
participate in clinical studies and to describe the demo- intended to be representative of the entire population of
graphic profile of these study subjects. In addition, we study participants. Rather, this study was designed to
will evaluate whether the motivations are in accordance identify the main motivations that lead to clinical study
with established ethical andlegalprinciples. participation and whether these motivators differ by re-
search phase.
Methods
Rationaleforthechoiceofmethodology Keyinformants(KI)
A multi-methods study [17] with qualitative and quanti- Key informants were people with specific knowledge
tative phases was used. Qualitative methods were used regarding the study population and who were prepared
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to share knowledge about the study. The KI introduced of the respondent. The interviews were approximately
the theme of the research, noting the peculiarities of the 40 minutes in duration, and the participants were com-
participants [19]. A total of ten KIs were interviewed. pensated R$20.00 (twenty reais) upon completion of the
Three were principle investigators from the study cen- interview.
ters, two were clinical study center coordinators, one
was a representative of the Brazilian Society of Clinical Analysisoftheresults
Study Professionals (Sociedade Brasileira de Profissionais Qualitativeanalysisoftheinterviews
de Pesquisa Clinica-SBPPC), one was a representative of After transcription, the interviews were submitted for
the Brazilian Association of Clinical Study Representa- content analysis, as proposed by Taylor and Bogdan [23]
tive Organizations (Associação Brasileira de Organiza- andBardin[24]inaccordancewiththe following steps:
ções Representativas de Pesquisa Clínica-CRO), one was
a regional director of clinical operations of the pharma- Initialreading
ceutical industry and two were doctors responsible for The initial reading allowed for the formation of general
conducting the studies in public and private reference impressions.
hospitals. The interviews with the KIs were unstruc-
tured, conversational interviews [20,21]. They were Preparationofthematerial
recorded, transcribed, analyzed and provided informa- The material was prepared by separating and categoriz-
tion that could be used to develop interview questions ing the responses according to topic. This material gave
for the clinical study subjects and to aid in understand- rise to independent archives for each script item: age,
ingthediscussionsoftheinterviewed individuals[19]. gender, education level, motivation for participation,
These interviews allowed for comparative analysis of study type, number of times the individual participated
the motivations for participation in research studies in clinical studies, method of recruitment, compensation
accordingtosubjectsandKIs. forparticipation, understandingoftheICSandsocioeco-
nomic class. Eachitemincluded80responsesthatcorres-
Datacollectioninstrument pond to each sample constituent. With this information,
The categories that emerged from the discussion with thecategorieswereconstructed.
the KIs were used to describe the study subject volun-
teer profile and topics in the survey script. This survey Treatmentoftheresults
script included sociodemographic data (age, gender and The frequencies were calculated, allowing for interpret-
education), type of clinical study (Phase I or III), the ation. In the present study the triangulation technique
involved pathology and location, the number of times was used [19]. Each interview was coded by more than
that the volunteer participated in clinical studies, the oneresearchertoensuretheconsistencyofinterpretations
motivation for participation, information concerning the andincreasethereliabilityofthecategories.Excerptsfrom
ICS (whether it was introduced correctly and whether theinterviewswithKIsandstudysubjectsappearinitalics
the volunteer could explain the study topic and remem- intheresults.
ber the ICS), compensation received for participation
and recruiting vehicles (how the volunteer found out Statisticalanalysis
about the study). Socioeconomic class was measured Hypothesis tests were conducted for each of the script
using the ABEP scale (Brazilian Association of Research variables to compare the characteristics and motivations
Companies - Associação Brasileira de Empresas de Pes- of Phase I and Phase III study subjects. After codifying
quisa), which takes into consideration the education the answers from the qualitative phase, each theme was
level of the head of the household and ownership of analyzed to generate up to 5 response categories. These
assets [22]. This scale was used to sort participants into variables were tested for the homogeneity of the distri-
standardized subgroups labeled from A to E where A bution of responses across categories. The Student’s t-
was the highest economic strata. Mean family income test was used to evaluate average age, study phase and
(MFI) at the E-level of the ABEP index is very low research motivation. The Pearson’s chi-squaretest or the
(below a 'living wage' level considered acceptable for Fisher’s exact test was used for the categorical variables.
families in the US), whereas a D-level family enjoys a A significance levelof5%wasadopted, andStataversion
MFI value roughly 1.5 times the E-level MFI. The C- 11softwarewasusedtoperform theanalyses.
level MFI is roughly 2–3 times the E-level value, A-level
and B-level is approximately 27 times and 9 times the E- Ethics
levelMFI valuerespectively. The protocol was reviewed and approved by the
The anonymous interviews were semi-structured, in- Universidade Federal de São Paulo (UNIFESP) Re-
depth conversationsthatwererecorded with the consent search Ethics Committee (Protocol #0870/10), with
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provisions for participants to participate anonymously, to Analysisoftheinterview
decline to participate, to leave questions unanswered, and Motivationtoparticipate
that they could interrupt their participation at any time, Content analysis of the interviews identified motivating
according to the Declaration of Helsinki. No one of the factors for participation in clinical studies. Figure 1 lists
researchers occupy dual role (they were not clinicians or the main motivation for participation categories that
clinicalresearcher’smanagers). emerged from the discussions with the KIs and study
subjects. Both groups identified the therapeutic option
and financial compensation as key motivators, suggest-
Results ing that the KIs understood the motivations of the
There was a predominance of women among the respon- volunteers.
dents (58%). Table 1 shows that the majority completed
highschoolorcollege(approximately90%),werelessthan Therapeuticoption
50 years of age (72%), were in either socioeconomic class Keyinformants
B or C (84%) and had participated in only one clinical Opinion oftheKIsversusthestudysubjects
study(63%). According to the KIs, the therapeutic option to have
access to a new treatment and the hope that this new
Table1Sociodemographicdataforthe80respondents drug can produce an improvement is a motivator to en-
accordingtoresearchphase gage in clinical studies for potential experimental treat-
ments. The discussions with the KIs in the following
Characteristics PhaseIN(%) PhaseIIIN(%) TOTALN
transcriptsrevealthe opinions oftheseprofessionals.
Gender
Male 19(47.5) 27(67.5) 46
Thegroupofpatients,becausetheyalreadyhave the
Female 21(52.5) 13(32.5) 34
illness,isalwayssearching for something better,anew
Education
treatment.Theysubmitthemselvestothecollateral
Primary 4(10.0) 4(10.0) 8 effectsofthemedicationtotryanewmedication,i.e.,
HighSchool 17(42.5) 18(45.0) 35 forcancer.
College 18(45.0) 18(45.0) 36
NR 1(2.5) 0(0) 1 Othersopttoparticipateinthestudybecausetheydo
Socioeconomicclass1 not haveanothertherapeuticoption.These casesare
more commoninoncology andrareillnesses withfew
A 0(0) 0(0) 0
conventionaltreatment options.
B 11(27.5) 4(10.0) 15
C 28(70.0) 24(60.0) 52
Studysubjects
D 1(2.5) 9(22.5) 10
Motivation for participating in a clinical study according
E 0(0) 3(7.5) 3
tostudy participants:
Numberofstudies According to study subjects, the therapeutic option is
1 24(60.0) 26(65.0) 50 a strong motivator to enroll in a clinical study. The po-
2 1(2.5) 11(27.5) 12 tential benefit of a new medication was the most cited
3 9(22.5) 2(5.0) 11 motivator. However, it is worth noting that this motiv-
4ormore 6(15.0) 1(2.5) 7 ator is restricted to those volunteers with some type of
Age(years) pathology (in this case, Phase III study subjects). The
≤20 1(2.5) 0(0) 1 following excerpt is from an interview with a study par-
ticipant:
21-30 19(47.5) 1(2.5) 20
31-40 11(27.5) 4(10.0) 15
Motivation? Itwasforthebenefititself becauseitwas
41-50 8(20.0) 14(35.0) 22 aproblemthat Ihave.Ithought:let’sdoit!
51-60 0(0) 9(22.5) 9
61ormore 0(0) 12(30.0) 12 Financialcompensation
NR 1(2.5) 0(0) 1 Keyinformants
NR=NoResponse. According to the KIs, financial compensation influences
1Awasthehighesteconomicstrata.Meanfamilyincome(MFI)attheE-level a volunteer’s decision to participate in a clinical study,
oftheABEPindexisverylow(belowa'livingwage'levelconsidered
acceptableforfamiliesintheUS),whereasaD-levelfamilyenjoysaMFIvalue especially among healthy volunteers. Although the
roughly1.5timestheE-levelMFI.TheC-levelMFIisroughly2–3timestheE-
Brazilian legislation only allows for compensation for
levelvalue,A-levelandB-levelisapproximately27timesand9timestheE-
levelMFIvaluerespectively. time spent in the study, this remuneration is often
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Key Informants Study Subjects
Therapeutic option Therapeutic option
Financial compensation Financial compensation
Access to healthcare
Altruism Altruism (secondary motivation)
Other
Figure1PrincipalmotivatorsforparticipationinaclinicalstudyaccordingtoKIsandstudysubjects.
attractivetoaportionoftheparticipants: examinations,theyaretakencareofwith a special
attention bythedoctor...
Ibelievethatthehealthy volunteers,inPhaseIstudies
and insomeother situationsaremotivatedbya The KIs mentioned access to healthcare as one of the
financialcompensation, althoughinaccordancewith main reasons for engaging in a clinical trial. However,
resolution196wecannot payaStudy Subject in the clinical trial participants did not evaluate it the same
Brazil,butinsomewaythiscompensation isthe way. They acknowledge access to healthcare as a benefit
greatestmotivation toparticipateinthe study. but secondarily to other reasons that they consider more
Thereisacamouflaged payment[compensation forthe important for participating in a clinical trial, such as: fi-
work-lossday],butmanytimesitismuch higherthat nancial advantage ortherapeuticoption.
theworkdaycompensation.
Altruism
Studysubjects Keyinformants
Healthy volunteers identified compensation as the prin- The KIs believed that a small portion of the study sub-
cipal motivation for participation in a study. The major- jects altruistically engage in these studies to improve the
ity of volunteers did not want to reveal the amount that lives ofothers.
they received forparticipatinginthese studies.
Ibelievethatthereisanemotionalcomponenttothis
Itisnot thefirsttimethat Ihaveparticipated. They condition thatemerges.Forexample,afather that
paywell, andIhaveconfidenceintheplace anditis volunteersforanAIDSvaccinebecausehelost achild
goodbecausetheydoseveralexaminations,andIa tothedisease.
findout about howmyhealth is.
Studysubjects
Accesstohealthcare Some of the respondents mentioned the possibility of
Keyinformants helping other people as a motivator for participating but
According to KIs, many study subjects enter clinical alwaysassecondarymotivation.
studiesbecausetheybelievethattheywillhaveimproved
access to health care and better quality of care. The sub- Itwastoimprovemy knee and alsotohelpinthe
jects believe that they will be better able to check up on study.
their health and will be able to avoid the time that they First,becauseIhave arthritis,andmyhealthcareplan
would spend in the public health sector. Moreover, the wasverybad....and second,becauseIamhelping the
ability to call a study physician at any time is attractive researcher,andwho knows,maybe humanity.
tothesepatients.
Othermotivations
Ingeneralthepeople,whoparticipateofclinicalstudies, Keyinformants
participateinresearchprojectsbecausetheyreceive The KIs also commented that the possibility for volun-
excellentattentionandahealthcareoptionthatis teers to make friends with people of a similar age and
frequentlybetterthanthehealthcaremedicalplans. health statusmight leadthem toparticipate.
Thepatientfeelstruly takencareof,thisisvery
difficultformetoassume,butitiswhathappens,the (...)Theelderly women created acertaincommunity
easinessinthe attendance,thepatientsundergo then, theymet inthewaitingroom,theyexchanged
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experiences,theytalked andtheystartedtomeet For example, 94.7% of respondents that were motivated
outsideoftheclinic. by financial compensation were Phase I study subjects.
Conversely, 100% of the respondents who were searching
The possibility of receiving the test medication for the foratherapeuticoptionwerePhaseIIIstudysubjects.
entire illness period, even after completing the study, Other motivations such as altruism and access to the
wasanother motivationthatwasmentioned bythe KIs. healthcare were mentioned but were not the main moti-
vators. Only 4% of participants alleged that these were
Studysubjects theprincipalmotivators.
Few study subjects cited motivations other than a new The average age of participants (Table 3) was signifi-
therapeuticoptionandfinancialcompensation.However, cantly different depending on the phase of the clinical
some added additional motivators, such as the recom- study (p <0.0001). Those that participated in Phase I
mendation of their personal physician to participate in studies were younger (average age: 32 years; 95% CI:
thestudy. 28.7-34.8) than participants in Phase III studies (average
age: 53years:95%CI:49.1 -56.0%).
Iwanted totryanother treatment. Theonesthat Ihad The average age varied by study purpose (p < 0.0001).
tried hadnoeffect.Thatwaswhenmydoctor said The bioequivalence and medication studies had the
that theremightbe agoodopportunityformeto youngest average ages (average age: 31.5; SD= 9.3). In
participate ina study foranewarthritis medication. thiscase,allwere phaseIstudysubjects(Table4).
Most of the volunteers from both phases belonged to
InformedConsentStatement(ICS) class C. However, the proportion of class D and E sub-
All the interviewed subjects declared that they had read jectsvariedaccordingtostudyphase.Only2.5%ofparti-
and understood the ICS. They also reported that when cipants from Phase I clinical studies belonged to the
theywereunsurethattherewasaprofessionalavailableto classes D and E. None of the respondents belonged to
help them. However, when asked if they could remember classA(Table5).
the principal points of the ICS, a number of participants Nostatisticallysignificantdifferencesintheproportions
did not remember any of the content. Among those that of men to women when stratifying for study purpose or
remembered some parts of the ICS, none mentioned the research phase. In addition, there were no differences in
potentialrisksofthestudyinwhichtheyparticipated. social class or education level when stratified by motiv-
ationforenteringthestudy(datanotshown).
That Icouldquitwhenever Iwantedto,andthat I
could speakwith adoctorat anytime. Discussion
Icould stop whenIwantedto,that Iwouldtake Developing nations are participating in multi-center
laboratorymedicinewith anamethat Ican’t clinical studies at increasing rates. This participation is
remember...Ihadtodotheexercisescorrectly. due to the reduced operational costs, ease of recruiting
Igonethroughtheentireinterview,Idid allthe study subjects,ability toconduct researchandregulatory
examinations,butIdonot remember whatwas capacity of these countries [26]. According to several
written,Ienrolledwiththedesiretoresolve this authors, this shift is primarily due to economic consid-
[health] problem. erations [20,27], suggesting that volunteers for clinical
studies in developing countries are “guinea pigs” [9].
Resultsofthestatisticalanalysis Therefore, there should be heightened concern for the
Table 2 shows that participants in different types of stud- ethical requirements to conduct a clinical study in these
ies have different motivations to participate (p < 0.0001). areas [21]. Further innovation in the pharmaceutical
field requires these countries to be able to conduct clin-
Table2Motivatorsforclinicalstudyparticipation icalstudiesethically.Itisessentialfor internationalstud-
accordingtostudyphase(N=80) ies to be conducted in Brazil to advance the body of
Motivators PhaseI PhaseIII knowledge[2].
(n=40) (n=40)
n(%) n(%) P-value2 Table3Averageagesofthestudysubjects,accordingto
researchphaseandmotivator(N=79)
<0.0001
N Age(average) CI95% P-value1
FinancialCompensation 36(94.7) 2(5.3)
<0.0001
Therapeuticoption 0(0.0) 34(100.0)
PhaseI 39 32 28.7-34.8
Other1 4(50.0) 4(50.0)
1Includingaltruism,knowledge,medicalindicationandaccesstohealthcare;2 PhaseIII 40 53 49.1-56.0
Fisherexacttest. UsingStudent’st-test.
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Table4Averageage,accordingtotypeofstudy(N=79) likely to cite altruism as a secondary motivator after eco-
Typeofstudy N Age(average) Standarddeviation p-value2 nomic advantage (Phase I) or therapeutic option (Phase
III).ThesamemotivationswerealsoidentifiedbytheKIs.
<0.0001
Although several authors insist that these motivators
Arthritis/ 24 56.7 8.4
osteoarthritis are more common in developing countries[21], studies
Bioequivalence 39 31.5 9.3 demonstrate that they are found in study subjects
throughouttheworld [29,30].
Insomnia 10 48.2 12.4
InareviewbyStunkelandGrady[29],12of13studies
Other1 6 43.3 9.9
showed that financial motivation was the main reason to
Includedstudiesofmenopauseandtemporomandibularpain;
ANOVA. participate in studies. One volunteer from these studies
comments, “Nobody is Robin Hood to make the good for
Despite advances in legislation and in professional de- the society.” In the studies where the participants
velopment in this field, Brazil is far from being consid- affirmed that compensation was the main motivator, no
ered a major research center. The idea that Brazilian participantsrefused payment [31].
research participants are guinea pigs is not justified. In a study of the motivations for healthy subjects to
Brazil conducts only 1.8% of total global clinical studies participate in researchVrhovac et al. [32] found that al-
(n =1417). In contrast, the United States performs the most 80% reported compensation as the primary motiv-
majority of clinical studies; 54.3% of global clinical stud- ator. However, in that study, 20.6% of the volunteers
iesare conductedintheUS(n= 41917)[25]. denied that the money was the principal reason and
These numbers demonstrate that Brazil is still not identified humanitarian motivations and the desire to
an important clinical research center, despite having contribute to society. Thekey informants for the present
characteristics that would be conducive for performing study also mentioned altruism; however, it was only
studies. Therefore, it is inappropriate to accuse Brazil of mentionedinexceptionalsituations.
being the supplier of guinea pigs for clinical studies [9]. Alternatively, there are study subjects that believe that
However, this finding should not decrease the focus on compensation should be commensurate with the risks of
ethical concerns for clinical studies. These advances must the studyand that compensation should be increased for
be made rationally and should avoid unfounded critiques invasiveprocedures,suchasdrawingblood [33].
andprejudicesofemergingcountries. Almeida et al. [34] found that volunteers with low
Altruism should be the main reason for a subject’s de- education and low socioeconomic status were more
cision to participate in a research study28). Ideally, the likely to cite financial motivations to participate in a
volunteer is capable of making decisions based on the clinicalstudy.
information provided about the proposed study, and In this study, we did not find this association; there
understands the purpose, risks, benefits, alternatives and was no difference in education level between Phase I
requirements of the study. After receiving this informa- and Phase III participants. However, participants in a
tion, the volunteer is able to decide to participate, free higher socioeconomic class were more likely to partici-
from coercion or improper influences [28]. However, pate in Phase I studies (Table 5) (thus, according to
there is concern that the benefits may interfere with the Table 1, they were more likely to be healthy volunteers
study subject’sevaluationoftherisks[21]. participating for financial reasons). These findings are in
The results of the present study, although preliminary, agreement with those of Kass et al. [30], who found that
show that health and financial benefits are the primary Caucasians with a higher education level were more
motivators for respondents to become study subjects. likely to be motivated by financial benefits. These find-
Individuals from higher socioeconomic classes were more ings are in contrast to the beliefs of some authors who
say that compensation attracts low-income volunteers,
resulting in a disproportionate number of poor people
Table5Socioeconomicclass(basedontheABEPscale),
participatinginclinical studies[35].
stratifiedbystudyphase(N=80)
Gelderen [36] found that the youngest volunteers were
Socioeconomicclass PhaseI(n=40) PhaseIII(n=40)
the most likely to mention money as the primary motiv-
n(%) n(%) p-value1
ator to participate, which is a finding that was repro-
A 0(0) 0(0) <0.0005 duced in our study (average age of 32 years in Phase I
B 11[25] 4[10] participants). This result is not surprising, as younger
C 28(70) 24(60) people might not be as financially established and may
D 1(2.5) 9(22.5) be looking for ways to earn money. Moreover, Phase I
E 0(0) 3(7.5) participants are required to be healthy, which is a criter-
1Fisher’sexacttest. ionthatismore commonamongyounger adults.
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Among Phase III participants, the principal motivation volunteers had a good education, and all declared that
for participation in clinical studies was to search for a theyunderstood the ICS. However, when theywereques-
new treatment, a motivator that was also mentioned by tioned about the study details, they only remembered the
the KIs. Grecco and Diniz [37] have noted that clinical possibility of speaking with a doctor and the possibility of
study volunteers in developing countries see participa- leavingthestudy.Noneofthesubjectsmentionedthedis-
tion in clinical studies as an opportunity to receive advantages of the study, such as the risks or potential ad-
better healthcare, easier access to more expensive la- verse reactions to the medicine. These findings may
boratory examinations and novel drugs. According to indicatethatthevolunteersdidnotadequatelyunderstand
Grecco andDiniz,these motivationsconstituteaconflict the ICS. It is worth noting that a portion of the respon-
of interests. It is worth noting that Brazilians have uni- dents did not remember that some items of ICS may be
versal access to the Unified Healthcare System (Sistema limitedtothetimethattheyparticipatedinthestudy.The
Único de Saúde – SUS), which is funded by the federal more “comfortable” situations associated with the study
government [38]. However, access to this system does were remembered, while the situations associated with
not limit the interest in clinical studies, perhaps due to risks were not mentioned. However, the date of last par-
the quality of the services or the degree of individualized ticipationinaclinicaltrialwasnotquestioned,whichmay
attention. constitutealimitationinanalysisofthedata.
Cabral et al. [1] have noted that in the research envir-
onment, the physician-patient relationship is inverted. Conclusion
Classically, the physician satisfies the needs and interests In the present study, study volunteers were motivated by
of the patient. However, in a clinical study, the patient some type of personal benefit from participating in a
satisfies the interests of the study and thus the re- study (especially financial or therapeutic benefits), which
searcher. Lackey [27] adds that the researcher, for the is a finding has been observed in clinical study partici-
advancement of the study, must treat these subjects as pants in other countries. According to several authors,
scientific objects submitted to the laws of cause and ef- this finding is accentuated in emerging countries, such
fect. Thestudysubjectsmay not understand this distinc- as Brazil, due to the limitations of the health care sys-
tion and may continue to participate in the study tems, even despite the universal access provided by the
expecting a cure when, in reality, the medicine may not SUS. Altruism was not a common motivator, and when
haveany effect. it wasmentioned, itwasneverthe primaryreason. Some
Canvin and Jacob [39] observed a group of volunteers have called type of motivation this “conditional altru-
for a study of epilepsy and noted that these volunteers ism”. The ICS was understood by all participants; how-
were happy to help others only when they could also ever, the degree of understanding may have been
help themselves. The authors called this behavior “weak limited. None of the subjects remembered the text refer-
altruism,” and McCann et al. [40] have called this behav- ring to the potential harms of the procedure or medi-
ior “conditional altruism.” According to these authors, cine. The authors hypothesize that this behavior results
the desire to help others or to contribute to the body of because the individuals participate out of self-interest,
knowledge does not lead a volunteer to participate in a rather thanaltruism.
study unless that volunteer perceives that his participa-
tion inthestudymaybenefithimpersonally. Studylimitations
The Informed Consent Statement (ICS), which is This study was a preliminary study with a qualitative-
required under Resolution 196/96 (CNS/196), is provided quantitative approach. The study sampled 80 partici-
forthevolunteertoinformhimaboutthestudy,including pants and was not representative of the total population
the associated risks and the responsibilities of those of clinical study participants. Another limitation is the
involved. The ICS is indispensable to the ethical conduct fact that those who refused to participate in the research
oftheresearch.Accordingtoanumberofauthors,volun- were not surveyed.
teersdonotalwayspayenoughattentiontotheICS.This
oversightmayoccurbecausethevolunteertruststhedoc- Studystrengths
tor (or at least the role of the doctor) and does not take This study demonstrates that personal benefit is the pri-
into consideration the role of the doctor as a researcher, mary motivation for volunteers to participate in clinical
that is, the doctor is not necessarily focused on meeting research. However, we argue that this motivation seems
the patient’s global health needs [27]. Additionally, the to be universal and is not limited to developing coun-
patient may overestimate the benefit for himself and lose tries. Moreover, the theory that financial compensation
theabilitytoweighthedisadvantagesofthestudy[41].Fi- disproportionately attracts poor volunteers has not been
nally, the volunteer may not understand the ICS because supported. Furthermore, the fact that study participants
ofa low educational level [42].In the present study,most are primarily motivated by personal benefit does not
Nappoetal.BMCPublicHealth2013,13:19 Page9of9
http://www.biomedcentral.com/1471-2458/13/19
suggest that they do not evaluate the risks of participa- 22. ABEP:AssociaçãoBrasileiradeEmpresasdePesquisa-CritériodeClassificação
tion. For further consideration, if we consider altruism EconômicaBrasil].Brazil:BrazilianAssociationofResearchFirms-Criteriafor
EconomicClassificationBrazil;2010.[Internet].Availablefrom:www.
to be the only ethically acceptable motivation for study
abeporg/codigosguias/Criterio_Brasil_2008pdf2008.
participation, must we evaluate whether the principle of 23. TaylorS,BodganR:IntroductiontoQualitativeResearchMethods.NewYork:
autonomyhasbeendisrespected? JohnWiley&SonsInc.;1998.
24. BardinL:AnálisedeConteúdo.3ªthedition.Lisboa:Edições70;2004.
25. NIH–NationalInstituteofHealth,USA:SearchforClinicalTrials;Disponível
Competinginterests em:http://www.clinicaltrials.gov(lastaccessed04/07/2012).
Theauthorsdeclarethattheyhavenocompetinginterests. 26. ThiersFA,SinskeyAJ,BerndtER:Trendsintheglobalizationofclinical
trials.NatRevDrugDiscov(on-line)2007,November,2.
Authors'contributions 27. LackeyDP:CriticalResearchindevelopingcountriesrecentmoral
SANconceivedthestudyandparticipatedinitsdesignandcoordination arguments.CadSaudePublica2002,18(5):1455–1461.
andwrotethefinalversionofthemanuscript.GBIcollecteddataandZMS 28. GradyC:MoneyforResearchParticipation:Doesitjeopardizeinformed
performedthestatisticalanalysisandinterpretedthedataobtained.All consent?AmJBioeth2001,1(2):40–44.
authorsreadandapprovedthefinalmanuscript. 29. StunkelL,GradyC:Morethanthemoney:Areviewoftheliteratureexamining
healthyvolunteermotivations.ContempClinTrials2011,32:342–352.
Received:24April2012Accepted:22December2012 30. KassNE,MyersR,FuchsEJ,CarsonKA,FlexnerC:Balancingjusticeand
Published:10January2013 autonomyinclinicalresearchwithhealthyvolunterers.ClinPharmacol
Ther2007,82(2):219–227.
31. MtunthamaN,MalambaR,FrenchN,MolyneuxME,ZijlstraEE:Malawians
References
permitresearchbronchoscopyduetoperceivedneedforhealthcare.
1. CabralMML,SchindlerHC,AbathFG:Regulamentações,conflitoseética JMedEthics2008,34(4):303–307.
dapesquisamédicaempaísesemdesenvolvimento.RevSaudePublica
32. VrhovacR,FranceticI,RotimK:Drugtrialsonhealthyvolunteersin
2006,40(3):521–527.
Yugoslavia.IntJClinPharmacolTherToxicol1990,28(9):375.
2. QuentalC,SallesFilhoS:EnsaiosClínicos:capacitaçãonacionalpara
33. FergsonPR:Clinicaltrialsandhealthyvolunteers.MedLawRev2008,
avaliaçãodemedicamentosevacinas.RevBrasEpidemiol2006,9(4):408–424. 16(1):23–51.
3. GreccoD,DinizNM:Conflictsofinterestinresearchinvolvinghuman
34. AlmeidaL,AzevedoB,NunesT,Vaz-da-SilvaM,Soares-da-SilvaP:Why
beings.JIntBioethique2008,19(1–2):143–54–61.
healthysubjectsvolunteerforphaseIstudiesandhowtheyperceive
4. GarrafaV,LorenzoC:Moralimperialismandmulti-centricclinicaltrialsin theirparticipation?EurJClinPharmacol2007,63(11):1085–1094.
peripheralcountries.CadSaudePublica2008,24(10):2219–2226.
35. StonesM,McMillanJ:Paymentforparticipationinresearch:apursuitfor
5. CNS-ConselhoNacionaldeSaúde:Resolução196deoutubrode1996.1996. thepoor?JMedEthics2010,36(1):34–36.
Disponívelem:http://conselho.saude.gov.br/resolucoes/reso_96.htm(last
36. GelderenCEM,SavelkoultTJF,DokkumW,MeulenbeltTJ:Motivesand
accessed04/07/12).
perceptionofhealthyvolunteerswhoparticipateinexperiments.EurJ
6. WHO:Ethicsininternationalhealthresearch:aperspectivefromthe ClinPharmacol1993,45(1):15–21.
developingworld.BullWorldHealthOrgan2002,80:114–120.
37. GrecoD,DinizNM:Conflictsofinterestinresearchinvolvinghuman
7. Editorial:Ethicalbehaviorinclinicalresearch-alessonfromthepast. beings.JIntBioethique2008,19(1–2):143–54–202–3.
Lancet2011,378(9795):962.
38. VictoraCG,BarretoML,LealMC,MonteiroCA,SchmidtMI,PaimJ,BastosFI,
8. GarrafaV,PradoMM:MudançasnaDeclaraçãodeHelsinki:
AlmeidaC,BahiaL,TravassosC,ReichenheimM,BarrosFC:TheLancetBrazil
fundamentalismoeconômico,imperialismoéticoecontrolesocial.Cad
SeriesWorkingGroup.2011.Disponívelem:http://www.thelancet.com(last
SaudePublica2001,17(6):1489–1496.
accessed04/07/12).
9. LacativaPGS,SzrajbmanM,SilvaDASM,MelazziACC,GregórioLH,Russo
39. CavinK,JacobyA:Duty,desireorindifference?Aqualitativestudyof
LAT:Perfildesujeitosdepesquisaclínicaemumcentroambulatorial
patientdecisionsaboutrecruitmenttoanepilepsytreatmenttrial.Trials
independente.CadSaudePublica2008,13(3):1023–1032.
2006,7:32.
10. BeauchampTL,ChildressJF:PrinciplesofBiomedicalEthics.4athedition.New
40. McCannS,CampbellMK,Entwistle:Reasonsforparticipatingin
York:OxfordUniversityPress;1994.
randomisedcontrolledtrials:conditionalaltruismandconsiderationsfor
11. Zegers-HochschildF:Barrierstoconductingclinicalresearchin self.Trials2010,11–13.
reproductivemedicine:LatinAmerica.FertilSteril2011,96(4):802–804.
41. LynöeN,SandlundM,JacobssonL:InformedconsentintwoSwedish
12. ShamooAE,KatzelLI:UrgentEthicalChallengesinHumanSubjects
prisons:astudyofqualityofinformationandreasonsforparticipatingin
Protection.JClinResBestPract2007,3(3):1–5. aclinicaltrial.MedLaw2001,20(4):519–523.
13. FarrellK:Humanexperimentationindevelopingcountries:improving
42. MeneguinS,ZoboliELCP,DominguesRZL,NobreMR,CesarLAM:
internationalpracticesbyidentifyingvulnerablepopulationsand
EntendimentodoTermodeConsentimentopelospacientespartícipes
allocatingfairbenefits.JHealthCareLawPolicy2006,9(1):136–161.
empesquisascomfármacosdecardiologia.ArqBrasCardiol2010,
14. MarodinG,GoldinJR:Confusõeseambigüidadesnaclassificaçãode 94(1):4–9.
eventosadversosempesquisaclínica.RevEscEnferUSP2009,
43(3):690–696.
doi:10.1186/1471-2458-13-19
15. GoldimJR,PithanCF,OliveiraJG,RaymundoMM:Oprocessode
Citethisarticleas:Nappoetal.:Motivesforparticipatinginaclinical
consentimentolivreeesclarecidoempesquisa:umanovaabordagem.
researchtrial:apilotstudyinBrazil.BMCPublicHealth201313:19.
RevAssocMedBras2003,49(4):372–374.
16. MuellerMR,InstoneS:Beyondtheinformedconsentprocedure:continuing
consentinhumanresearch.CadSaudePublica2008,13(2):381–389.
17. CreswellJW:Researchdesign:Qualitative,quantitativeandmixedmethods
approaches.3rdedition.USA:SagePublications;2009.
18. MinayoMCS:Odesafiodoconhecimento:pesquisaqualitativaemsaúde.São
Paulo:RJ:HUCITEC-ABRASCO;1994.
19. PattonMQ:Qualitativeresearchandevaluationmethods.USA:Sage
Publications;2002.
20. CastilhoEA,KalilJ:Éticaepesquisamédica:princípios,diretrizese
regulamentações.RevSocBrasMedTrop2005,38(4):344–347.
21. ShahJY,PhadtareA,RajgorD,VaghasiaM,PradhanS,ZelkoH,PietrobonR:
WhatLeadsIndianstoParticipateinClinicalTrials?AMeta-Analysisof
QualitativeStudies.PLoSOne2010,5(5):e10730.