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

A clinical study is an investigation that uses human subjects to contribute to knowledge that can be applied to benefit society. Clinical studies typically evaluate an intervention that is applied to study subjects. The intervention might be a drug, vaccine or therapeutic or surgical procedure [1]. Clinical studies are indispensable for the progress of medicine, especially for the discovery of new pharmaceuticals [2]. However, the use of human subjects in these studies as a unit of analysis introduces certain challenges [3].

In the past, study participants have suffered from the experiments that they were subjected to. One example is the experiments that were performed on prisoners during World War II [4], which generated a series of tragedies that are still remembered today. Those experiments violated the ethical rules that are currently applied to clinical studies [5, 6].

Past violations have contributed to the development of mechanisms to protect human subjects [7]. The scientific community was made aware of these violations, and various regulations have been elaborated to protect human rights and the integrity and dignity of individuals participating in biomedical research [8].

However, the unethical studies of the past have left a strong impression and are still referenced in developing countries. In Brazil, the general perception is that the risks to study subjects are greater than the benefits, and the term “human guinea pig” is commonly used to describe clinical study participants [9].

The basic principles of bioethics (autonomy, beneficence, non-maleficence and justice) [10] may be violated in clinical studies on human subjects in such developing countries as Brazil and may be a source of bias within the study [11]. The characteristics of study populations from these countries, such as poverty, illiteracy, lack of education and lack of availability/access to health care, may create inherent bias. In addition, several authors warn that populations in developing countries require special protection, due to these factors [12]. These study subjects may not understand the study process or may participate in clinical studies because they do not have access to medical care. Other authors have noted that these study participants are more susceptible to coercion and may more easily become volunteers in clinical studies [13].

Fortunately, it is clear that there has been increased emphasis on bioethics in Brazil in relationship to clinical studies of human subjects. The Clinical Study Regulation was created under Resolution 196/96 of the National Health Council (Conselho Nacional de Saúde-CNS) of the Health Ministry. As a result, the ethical evaluation process that a clinical study must pass is sufficiently rigorous and is in accordance with national laws [14]. In addition to the bioethics evaluation performed by the Ethics in Research Committee (Comitê de Ética em Pesquisa - CEP) of the study institution, international studies must also receive consent from the National Commission of Ethics in Research of the National Health Council (Comissão Nacional de Ética em Pesquisa do Conselho Nacional de Saúde - CONEP) and the National Sanitary Monitoring Agency (Agência Nacional de Vigilância Sanitária - ANVISA) [5].

All subjects receive an Informed Consent Statement (ICS). This document explains in accessible language the research details to ensure that that the subject understands the procedures, risks, discomforts, benefits and rights involved and makes an autonomous decision [15, 16].

Despite the rigor of these interventions, the idea persists that study subjects in Brazil participate in clinical studies for the wrong reasons [9].

The objective of the present study is to identify the specific motivators that inspire Brazilian volunteers to participate in clinical studies and to describe the demographic profile of these study subjects. In addition, we will evaluate whether the motivations are in accordance with established ethical and legal principles.

There was a predominance of women among the respondents (58%). Table 1 shows that the majority completed high school or college (approximately 90%), were less than 50 years of age (72%), were in either socioeconomic class B or C (84%) and had participated in only one clinical study (63%).

Developing nations are participating in multi-center clinical studies at increasing rates. This participation is due to the reduced operational costs, ease of recruiting study subjects, ability to conduct research and regulatory capacity of these countries [26]. According to several authors, this shift is primarily due to economic considerations [20, 27], suggesting that volunteers for clinical studies in developing countries are “guinea pigs” [9]. Therefore, there should be heightened concern for the ethical requirements to conduct a clinical study in these areas [21]. Further innovation in the pharmaceutical field requires these countries to be able to conduct clinical studies ethically. It is essential for international studies to be conducted in Brazil to advance the body of knowledge [2].

Despite advances in legislation and in professional development in this field, Brazil is far from being considered a major research center. The idea that Brazilian research participants are guinea pigs is not justified. Brazil conducts only 1.8% of total global clinical studies (n =1417). In contrast, the United States performs the majority of clinical studies; 54.3% of global clinical studies are conducted in the US (n= 41917) [25]^.

These numbers demonstrate that Brazil is still not an important clinical research center, despite having characteristics that would be conducive for performing studies. Therefore, it is inappropriate to accuse Brazil of being the supplier of guinea pigs for clinical studies [9]. However, this finding should not decrease the focus on ethical concerns for clinical studies. These advances must be made rationally and should avoid unfounded critiques and prejudices of emerging countries.

Altruism should be the main reason for a subject’s decision to participate in a research study²⁸⁾. Ideally, the volunteer is capable of making decisions based on the information provided about the proposed study, and understands the purpose, risks, benefits, alternatives and requirements of the study. After receiving this information, the volunteer is able to decide to participate, free from coercion or improper influences [28]. However, there is concern that the benefits may interfere with the study subject’s evaluation of the risks [21].

The results of the present study, although preliminary, show that health and financial benefits are the primary motivators for respondents to become study subjects. Individuals from higher socioeconomic classes were more likely to cite altruism as a secondary motivator after economic advantage (Phase I) or therapeutic option (Phase III). The same motivations were also identified by the KIs.

Although several authors insist that these motivators are more common in developing countries[21], studies demonstrate that they are found in study subjects throughout the world [29, 30].

In a review by Stunkel and Grady [29], 12 of 13 studies showed that financial motivation was the main reason to participate in studies. One volunteer from these studies comments, “Nobody is Robin Hood to make the good for the society.” In the studies where the participants affirmed that compensation was the main motivator, no participants refused payment [31].

In a study of the motivations for healthy subjects to participate in research Vrhovac et al. [32] found that almost 80% reported compensation as the primary motivator. However, in that study, 20.6% of the volunteers denied that the money was the principal reason and identified humanitarian motivations and the desire to contribute to society. The key informants for the present study also mentioned altruism; however, it was only mentioned in exceptional situations.

Alternatively, there are study subjects that believe that compensation should be commensurate with the risks of the study and that compensation should be increased for invasive procedures, such as drawing blood [33].

Almeida et al. [34] found that volunteers with low education and low socioeconomic status were more likely to cite financial motivations to participate in a clinical study.

In this study, we did not find this association; there was no difference in education level between Phase I and Phase III participants. However, participants in a higher socioeconomic class were more likely to participate in Phase I studies (Table 5) (thus, according to Table 1, they were more likely to be healthy volunteers participating for financial reasons). These findings are in agreement with those of Kass et al. [30], who found that Caucasians with a higher education level were more likely to be motivated by financial benefits. These findings 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 participating in clinical studies [35].

Gelderen [36] found that the youngest volunteers were the most likely to mention money as the primary motivator to participate, which is a finding that was reproduced in our study (average age of 32 years in Phase I participants). This result is not surprising, as younger people might not be as financially established and may be looking for ways to earn money. Moreover, Phase I participants are required to be healthy, which is a criterion that is more common among younger adults.

Among Phase III participants, the principal motivation for participation in clinical studies was to search for a new treatment, a motivator that was also mentioned by the KIs. Grecco and Diniz [37] have noted that clinical study volunteers in developing countries see participation in clinical studies as an opportunity to receive better healthcare, easier access to more expensive laboratory examinations and novel drugs. According to Grecco and Diniz, these motivations constitute a conflict of interests. It is worth noting that Brazilians have universal access to the Unified Healthcare System (Sistema Único de Saúde – SUS), which is funded by the federal government [38]. However, access to this system does not limit the interest in clinical studies, perhaps due to the quality of the services or the degree of individualized attention.

Cabral et al. [1] have noted that in the research environment, the physician-patient relationship is inverted. Classically, the physician satisfies the needs and interests of the patient. However, in a clinical study, the patient satisfies the interests of the study and thus the researcher. Lackey [27] adds that the researcher, for the advancement of the study, must treat these subjects as scientific objects submitted to the laws of cause and effect. The study subjects may not understand this distinction and may continue to participate in the study expecting a cure when, in reality, the medicine may not have any effect.

Canvin and Jacob [39] observed a group of volunteers for a study of epilepsy and noted that these volunteers were happy to help others only when they could also help themselves. The authors called this behavior “weak altruism,” and McCann et al. [40] have called this behavior “conditional altruism.” According to these authors, the desire to help others or to contribute to the body of knowledge does not lead a volunteer to participate in a study unless that volunteer perceives that his participation in the study may benefit him personally.

The Informed Consent Statement (ICS), which is required under Resolution 196/96 (CNS/196), is provided for the volunteer to inform him about the study, including the associated risks and the responsibilities of those involved. The ICS is indispensable to the ethical conduct of the research. According to a number of authors, volunteers do not always pay enough attention to the ICS. This oversight may occur because the volunteer trusts the doctor (or at least the role of the doctor) and does not take into consideration the role of the doctor as a researcher, that is, the doctor is not necessarily focused on meeting the patient’s global health needs [27]. Additionally, the patient may overestimate the benefit for himself and lose the ability to weigh the disadvantages of the study [41]. Finally, the volunteer may not understand the ICS because of a low educational level [42]. In the present study, most volunteers had a good education, and all declared that they understood the ICS. However, when they were questioned about the study details, they only remembered the possibility of speaking with a doctor and the possibility of leaving the study. None of the subjects mentioned the disadvantages of the study, such as the risks or potential adverse reactions to the medicine. These findings may indicate that the volunteers did not adequately understand the ICS. It is worth noting that a portion of the respondents did not remember that some items of ICS may be limited to the time that they participated in the study. The more “comfortable” situations associated with the study were remembered, while the situations associated with risks were not mentioned. However, the date of last participation in a clinical trial was not questioned, which may constitute a limitation in analysis of the data.

In the present study, study volunteers were motivated by some type of personal benefit from participating in a study (especially financial or therapeutic benefits), which is a finding has been observed in clinical study participants in other countries. According to several authors, this finding is accentuated in emerging countries, such as Brazil, due to the limitations of the health care systems, even despite the universal access provided by the SUS. Altruism was not a common motivator, and when it was mentioned, it was never the primary reason. Some have called type of motivation this “conditional altruism”. The ICS was understood by all participants; however, the degree of understanding may have been limited. None of the subjects remembered the text referring to the potential harms of the procedure or medicine. The authors hypothesize that this behavior results because the individuals participate out of self-interest, rather than altruism.