Clinical trials are essential to assessing new therapies and advancing evidence-based treatments. Currently, the vast majority of research about factors that influence participation in clinical trials, as well as interventions to improve it, has been carried out in the field of cancer,1,2 in which only a small percentage of patients consent to participate.3 Results have shown that barriers to participate exist at different levels, related to the patient, the trial, or contextual factors. Among personal factors, cultural and linguistic diversity, lower income, or less trust in the physician or the health system are associated to a lower participation.4 Regarding the trial, uncertainties related to randomization and the benefit/risk balance of the intervention investigated are basic aspects in the decision to participate.5 Finally, contextual factors such as distance to the research centre, the number of required visits or medical tests also play an important role in potential participants’ decision.3

The few existing studies with patients diagnosed with human immunodeficiency virus (HIV) considering participation in clinical trials have focused on issues associated with the informed consent process,6 ethnic minorities recruitment,7,8 or on barriers and motivators to participate in vaccination of people at high risk of infection.9,10 A recent systematic review of qualitative studies in sub-Saharan Africa (including studies of vaccination or treatment) concluded that participation in HIV research is associated with considerable fear and uncertainty.11 Both feelings are influenced by social relationships, socioeconomic and domestic factors, the research clinic context and the relationships with research staff. Although these studies have produced a valuable knowledge about the psychological experience of HIV patients considering trial participation, specific variables related to the decision-making process (e.g., preference and perception of involvement, decisional conflict and regret) remain mostly unexplored. In standard care settings, research on HIV patients’ participation is also very scarce; the few existing studies show that a majority of patients want to be involved in the decision about treatment,12–14 and that this preference is associated to a better adherence to antiretroviral treatment.12 Patients presented more decisional conflict (i.e., uncertainty about treatment uptake) when they did not perceive this desired level of participation.13

This study aims to explore the decisional process of people with HIV currently enrolled in clinical trials about pharmacological treatment. Specifically, we want to describe: 1) patients’ motives for participating in the clinical trial; 2) their perceived decisional role; 3) the level of decisional conflict; 4) their current regret about trial participation; and 5) associations among these variables as well as with sociodemographic and clinical factors.

This cross-sectional retrospective study was conducted from November 2016 to February 2017 in the Fundación Huésped, a not-for-profit organization located in Buenos Aires (Argentina), that offers health and education services to people at risk or diagnosed with transmissible diseases, especially HIV.

Ninety-nine consecutive patients enrolled in clinical trials were invited to participate, and 93 agreed. Mean age was 34.4 and 77.4% were men. Approximately half of the sample had only primary or secondary studies, 58.1% lived alone and almost one-third were immigrants. Most worked (79.6%) but a 52.7% had a salary insufficient to cover basic needs. Seventy-one per cent had the HIV diagnosis within the previous year, and 88.2% were enrolled in their first clinical trial (Tables 1 and 2).

This study explored retrospectively the decisional process of patients with HIV, enrolled in clinical trials evaluating antiretroviral treatments, as well as their current regret. Among the assessed reasons/facilitators for trial participation, those associated with the personal experience with Fundación Huésped (i.e, gratitude towards the institution due to the services it offers to patients, doctor's recommendation, and easy access to treatment through clinical trials) have been more frequent than a desire for modern treatments, altruistic motives or external pressures. The sample recruited had a considerable level of economic deprivation (52% stated having a monthly income which does not cover their basic needs), and although treatment for HIV is covered by the national health system, more than a quarter of participants perceived an easier access in Fundación Huésped (due to excessive bureaucracy and waiting lists in the public system).

These patients’ characteristics could make them more vulnerable to pressures to participate from doctors or their family, but results showed that very few participants perceived this pressure, and most thought that they had decided autonomously or in collaboration with the doctor. Professionals in Fundación Huésped have not specific formation in shared decision making, beyond their personal attitudes and abilities in the interaction with patients. In standard care settings, where shared decision-making is advocated as the gold standard in diagnostic or treatments decisions,18,19 a perception of being included in treatment decisions has been shown to be associated to less decisional conflict, in HIV13 and other conditions20,21 (we could not test this association since only two patients perceived not to be involved in the decision). In the scenario of clinical trials, however, there is usually more uncertainty about treatment's benefits and risks, and the concept of informed (vs. shared) decision-making could be seen more appropriate, due to ethical and legal concerns. However, many patients prefer and/or perceive a collaborative decision process with professionals,22 as it has occurred in our sample.

In the trade-off between motives/psychological needs favoring participation in the trial, and its perceived potential harms or inconveniences, the former clearly prevailed as reflected in the low level of decisional conflict reported. We cannot know the quality of participants’ objective knowledge about the trials’ benefits and risks when making the decision; previous research has shown that less objectively informed participants were more likely to participate.23 Patients in our sample stated being well informed about the potential benefits and harms of the clinical trial (subscale informed), clear about the importance they attribute to those consequences (values) and sure about the decision (uncertainty, effectiveness). The retrospective nature of the measure could influence these results, since the current satisfaction with participation in the trial (reflected in the complete absence of decisional regret) might introduce a positive retrospective bias. The validity tests performed were in the predicted direction (even in a context of a floor effect), but the risk is not disposable. The effectiveness subscale is possibly the most likely to be sensible to retrospective bias, since it can be seen as a reverse measure of regret, and in fact it obtained by far the lowest mean score.

The subscale support was the only one which showed some level of conflict. A majority of participants (58%) lived alone, and this variable significantly related to worse scores on this subscale. On the other hand, previous research has shown that disclosure of HIV status is an important stressor because it may expose people to stigma, discrimination, abandonment, violence and moral challenges.24 Most of our participants had been diagnosed within the previous year and enrolled in the trial a mean of 6.6 months ago. Therefore, it is likely that a number of them still had not shared with many people their fears and uncertainty associated with living with HIV and starting treatment, increasing their feeling of being unsupported.

A lower education level was the only significant predictor of the decisional conflict total score. This association is possibly mediated by a better understanding of doctor's explanations about the trial in more educated patients, since knowledge of the disease and the therapeutic procedures has been shown to be related to less decisional conflict in other medical conditions.25 Other psychological variables like decisional self-efficacy could also mediate this result.26,27 Therefore, a correct understanding of clinical trials’ procedures and outcomes in less educated patients must be enhanced, as occurs with other vulnerable populations such as rural28 or ethnic minorities.29 Educational and decision support interventions (e.g., decision aids) could help to fill these gaps in knowledge, promoting an actual informed decision and also improving attitudes towards clinical trials.30

Patients did not show decisional regret at all. Previous research about trial participation has focused mainly on the phase of invitation and acceptance, but few studies have analyzed participants’ regret.31–33 In standard care settings in other medical conditions, both the decisional conflict when making treatment decisions, and the subsequent occurrence of adverse effects, have been shown to be associated (among other factors) with later regret.34,35 Both variables could be responsible of the complete absence of decisional regret in our sample.

Despite its limitations, this study contributes to the limited evidence on HIV patients’ decision-making regarding participation in clinical trials. In this sample of HIV patients, the decision-making in a clinical trial was perceived retrospectively as respectful with their autonomy and with a very low level of decisional conflict. Participation was mainly driven by a feeling of reciprocity towards a non-profit organization which offers support and education services for patients. Even in this favorable scenario, results highlight the necessity of enhancing the decision support in more vulnerable patients (e.g., less educated, recently diagnosed, or in those with less social support), thus warranting equity in the quality of the decision making process. More research is needed to determine predictors of participation in HIV trials and the quality of the decision process.

Azucena Santillán.

The corresponding author on behalf of the other authors guarantee the accuracy, transparency and honesty of the data and information contained in the study, that no relevant information has been omitted and that all discrepancies between authors have been adequately resolved and described.

All authors made substantial contributions to conception and design of this study. Feijoo-Cid & Sued, worked in the design and conceptin of the work. Feijoo-Cid & Rivero-Santana performed data analysis. All authors contributed to the interpretation of data. Feijoo-Cid, Rivero-Santana & Sued were involved in drafting the manuscript and the rest of the authors revised it critically for important intellectual content. All authors gave final approval of the version to be published.

We thank all participants who generously answered the questionnaire. We also thank Horacio Beylis, Emanuel Fojo, Virginia Salazar and Fernanda Nadir Cardozo for their contributions to the recruitment process, R Paul Kerston for the review and editing of the manuscript. David Moriña acknowledges financial support from the Spanish Ministry of Economy and Competitiveness, through the María de Maeztu Programme for Units of Excellence in R&D (MDM-2014-0445) and from Fundación Santander Universidades.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The authors declare that there is no conflict of interest.