In 1991, the ANRS began conducting phase-1 trials for HIV vaccines, a pioneering research project that was to unfold in the context of an epidemic crisis of HIV/AIDS and the fight against this pandemic.1 All of a sudden, the first attempts to recruit volunteers with the usual methods, ie, nursing schools, participants in a health insurance cohort, priests, etc., were hampered by the refusal of the supervisory authorities of the organizations in which these people were to be found and sometimes by these people themselves. It was then that, taking into account the political, psychological, social, and ethical dimensions of the recruitment of healthy volunteers for these trials, did Professor Jean-Paul Lévy (director of the ANRS) and Yves Souteyrand (head of the Human and Social Sciences Unit of the ANRS) decide to create a multidisciplinary working group to evaluate the implementation of these initial vaccine trials. These experiments were very sensitive because of the complex context of the AIDS epidemic and highly innovative (internationally, the United States was the only country pursuing the same objectives at that time). The objectives of this working group include the organization and execution of phase-1 trials, from the phases of recruitment, selection, and support of volunteers to the end of the trial and the eventual departure of the volunteers from the protocol. All the investigators (doctors, somatic physicians and psychiatrists, psychologist-sociologists, and administrators) believe that it is necessary to consider the physical, psychological, and social consequences of participating in such a trial.
This article, which covers the period from 1991 to 1996, a period in which the authors were involved in this project, and concerns phase-1 trials, aims to describe, first of all, how the protocol for the recruitment and selection of healthy volunteers came about and how the latter was created and functioned. In the second part, the ethical and scientific questions that the clinicians and researchers were faced with are described and discussed. An article published by Olivier Fillieule in this work provides a detailed analysis of the cover letters and profiles of volunteers (1992–2001) using another methodology and different concepts that lead to remarkably similar results as the works that we conducted at the time over a shorter period.2
The social and medical context of the creation of the vaccines in 1991 is dramatic in several respects: severely ill patients, few therapeutic perspectives, and strong stigmatization of these people, including on the part of medical staff.3 This situation gave the vaccine trials an urgency tempered by the principle of the protection of people, which had been laid down in the Huriet-Sérusclat Act (1988).
The Huriet-Sérusclat Act introduced a requirement to protect individuals who make themselves available for clinical research studies as well as, in particular, a duty to inform these people in writing, a requirement to obtain their written consent, and an obligation to cover the risks associated with the research by means of a specific insurance contract. This act provides for the insurance coverage of people as well as the framework for their decision-making, which must be as fully informed as possible. This requires investigators not to use volunteers who are at “serious, foreseeable risk.” However, it specifies “that no biomedical research may be conducted on human beings […] is the foreseeable risk incurred by the people who lend themselves to the research is out of proportion with the benefit expected for these people or the interest of the research.” This wording leaves sufficient space for different interpretations and enables everyone to prioritize the interest of the individual or of the group and the research. This ambiguity in the law can also be found in the amendments that were made to it in July 1994 regarding pregnant women: the legislator added the word “serious” in the phrase “the research […] is only permissible if it does not present any serious, foreseeable risk,” thereby restricting the risks considered to be “unacceptable,” but this research is no longer considered legitimate unless “it cannot be done in any other way,” which considerably restricts the legitimacy of certain experiments.
The authors of the present work took part in the process since the time of the first meetings, which were held in 1991 at the ANRS until 1996. This a is based on various sources, particularly the following:
- The archives of the Inserm-CESP team (A.G.) and of F.L. and P. Stoessel, which include documents and personal notes, minutes of meetings, letters, and files.
- The publications of the group: lectures given during international conferences, articles published in scientific journals and association journals.4–6
This abundant production allows us to trace with precision the scientific and ethical path that prevailed in the implementation of these initial phase-1 vaccine trials.
THE PROCEDURE FOR THE SELECTION AND RECRUITMENT OF HEALTHY VOLUNTEERS
The first meeting of the working group took place on September 13, 1991, in the offices of the director of the ANRS. The composition of the working group demonstrates the multidisciplinary approach taken by the ANRS at the time. Virologists, infectiologists, epidemiologists, a psychiatrist-psychoanalyst, and ethics specialists, including a philosopher and a psychosociologist, participated in this group. Gilles Pialoux (Hospital of the Institut Pasteur) and Yves Souteyrand (ANRS) engaged the following doctors for the first meeting: epidemiologist: Isabelle de Vincenzi, (Centre européen de Surveillance et d'Épidémiologie du Sida, Saint Maurice), a bioethics expert: Christian Hervé (Hôpital Necker), 1 psychiatrist: F.L. (Inserm U158, Bichat Claude Bernard Hospital, Rothschild Hospital), a social psychologist: A.G. (Inserm/Laboratoire de Psychologie clinique individuelle et sociale/Université Paris Diderot), a second epidemiologist: Antoine Messiah (Inserm U 292), 1 sociologist: Serge Karsenty, 1 philosopher: Emmanuel Hirsch (France Culture), 2 virologists: Stanley Plotkine and Marc Girard (Institut Pasteur), Jean Louis Excler from Pasteur Mérieux Sérums et Vaccin. The following doctors were unable to attend: Gustavo Gonzales (Hôpital Pasteur) and Pierre Saliou, bioepidemiologist (Institut Pasteur), Prof. Elisabeth Rouveix, (ANRS and Hôpital Ambroise Paré) and Brigitte Autran (Hôpital de la Pitié). As of the second meeting, the core members of the working group will be EH, A.G., Ide V, GP, GGC, YS, and F.L. Infectiologists from Institute Pasteur and Hôpital Cochin (especially Dominique Salmon and Didier Sicard) and psychiatrists from the Infectious Diseases and Addiction departments (Pascale Beau, Catherine Meut, Catherine Péquart, and Patrick Stoessel) will be taking part in the work of the Selection Committee, as well as Véronique Doré (Project Manager at the ANRS). The main problems connected with selection were addressed: Where should volunteers be recruited? Which methodology should be used? Which inclusion and exclusion criteria should be used? What are the risks associated with participation? Jean-Paul Lévy emphasizes that there are 2 main risks connected with participation: one is psychological, and the other is pharmacological (nosocomial). It is believed that the injected substance (the candidate vaccine) contains the risk of weakening the immune defenses and facilitating actual contamination in the event of exposure to the virus. This is also why volunteers are not recruited solely for the first 2 phase-1 trials but also with the entire scientific program in mind, which still remains to be developed. The notion of a “volunteer network” is still in its infancy.
After the second meeting of the working group, A.G. suggested performing clinical research in social psychology7,8 based on the use of material collected in different phases of the protocol: cover letters, selection interviews, psychological follow-up, and the pooling of the clinical experiments of the investigators and psychiatrists [Chantal Lavigne, psychologist and sociologist, Senior Lecturer at Université Paris Ouest (Nanterre), and Danièle Silvestre, psychoanalyst (Research Associate at Inserm U158), were involved in the execution of the VAX project.]. Research in the human sciences is at the very heart of the biomedical system of vaccine trials and the clinical activity of the selection, recruitment, and support of volunteers. The question of the autonomy and subjectivity of the individual is considered to be of key importance by the entire team for the success of the vaccine trials and the long-term participation of the volunteers as well as for the protection and support of the volunteers (Table 1).
The most original parts of the protocol for the selection of volunteers, compared with other enterprises of this nature, lie in its psychological dimension and the participation of a team of psychiatrists (mostly psychoanalysts) and in the creation of a network of volunteers who will receive information and support as well as assistance should any problems occur at any time during the trial.9
THE ROLE OF PSYCHIATRISTS IN THE PROCEDURE
The psychiatrists participated in the selection protocol by developing the public appeal for volunteers jointly with the other members of the committee and designing the psychological selection interview. Similarly, they were present throughout the selection process, taking part in the evaluation and selection of cover letters, the 2 medical consultations of preselected volunteers, and the final decision to include selected applicants in the volunteer network and their support throughout their participation in the trials.
The selection procedure was not simple for the volunteers: each of them had to examine their deepest personal and sexual motivations. A complete biological examination was offered to every individual, including an HIV serology test. The consequences of this procedure must be anticipated: disappointment or even a loss of self-esteem because of not being selected, discovery of different biological results, the surfacing of depression previously kept under control.
It was also the first time that a network had been set up to recruit healthy volunteers independently of any pharmaceutical company for the purpose of testing vaccines. Absolute financial independence from a public institution such as the ANRS enables a protocol to be developed which is less subject to industry pressure to be profitable.
PROTECTION FROM CONTAMINATION RISKS
Two risks were identified very quickly during the selection interviews:
- The feeling of being protected by a candidate vaccine, which could give rise to risk-taking potentially resulting in a seroconversion of the volunteers.
- The other risk is associated with “seropositivity in the absence of the virus,” which results from the inoculation of the product and the psychological repercussions it may cause in individuals, and in particular, the inhibition or disinhibition of sexual activity or the emergence of latent depression linked to the imaginary activity that may develop as a result of this experimental seropositivity. These 2 issues were later explored in the psychosocial research.2,10
The objectives of the selection, apart from strict compliance with the requirements of the Huriet Act, consist in selecting only those people who present with the least possible risks but more importantly are able to comprehend and process the issues and the consequences of such an experiment, especially for themselves. The volunteers taking part in vaccine trials must not only be seronegative for HIV, they must also be sufficiently informed about the methods of transmission, so that they do not become infected during the period of the trial (as well as afterward, of course). This involves 2 methods of evaluation: an evaluation in behavioral terms of the subject's sexual activity by means of a questionnaire (number of partners in the last 6 months, circumstances involving the use of a condom, etc.) as well as an interview to investigate the volunteer's subjective approach to sex, his ability to express his problems with adopting systematically less risky behavior, and his understanding of the nonprotective nature of the test vaccines. This therefore required an evaluation of the social and epidemiological context and the characteristics of the sexual partners of these people as well as their psychological ability to manage the risks taken.
The Risks Associated With Seropositivity Without the Virus
The risks incurred by taking part in an experiment may also be connected with the seropositivity in the Elisa test: stigmatization by other people or social consequences identical to those experienced by people seropositive for HIV, problems to obtain a loan, repeated absences at work because of the medical follow-up, unwillingness by the partner to have sex,11 problems if the seropositivity is discovered during a hospital stay, etc. A personal card certifying participation in vaccine trials was created, so that the volunteers could present it when necessary.
The Psychiatric and Psychopathological Risks
The psychological interview protocol was developed after discussions with a military psychiatrist (Val-de-Grâce) about how to select volunteers for risky tasks as well as on the basis of the literature concerning healthy volunteers, which emphasizes their “openness to risk, taking action, and strong emotions.”12 At the end of the interview, ratings of items (the antecedents and semiology are listed according to the usual criteria of an initial psychiatric interview. Regarding this point, see Ref. 13) and observations and comments about the interview and the presentation of the candidate were developed.
Otherwise, it was decided not to conduct any personality tests. In addition to the difficulty of assessing the reliability of these tests in a population, which is a priori not demanding in terms of therapy and which does not a priori present with psychological pathologies, the use of these tests would have entailed several disadvantages: the subject under examination may feel that the examiner will know everything about him, particularly things that he does not want to discuss. Furthermore, for many people, the use of these tests reminds them of circumstances when they were judged and evaluated (eg, professional recruitment). We do not consider this situation to be akin to a partnership between the volunteers and the investigators while an interview allows for a more open discussion.
During the semistructured interviews, the effects, expected and/or unexpected, of such a participation was discussed with the volunteers as well as the practical consequences of their participation (time, daily routine, and relationships) and the change in their motivations over the course of such a long trial.
The exclusion criteria included a history of psychiatric disorders and regular use of legal or illegal psychoactive substances because of the risks, which may be associated with them, ie, withdrawal from the protocol and drug interactions.
This approach is based on 2 requirements: first, an ethical requirement that recommends not exposing anyone to a very emotional experience who would find it difficult to tolerate or who may even decompensate in the psychiatric sense of the term; second, a methodological requirement that aims to select only those people who can tolerate such an experiment in the long term without suffering any excessive consequences and thereby without withdrawing from the protocol. The objective of these 2 requirements is to detect possible psychological disorders in volunteers, so that psychotic disorders can be excluded, ie, paranoia, schizophrenia and bipolar disorders, and inclusion limited to common neurotic disorders only.14
The injection of a vaccine may be seen as an intrusion by a dangerous foreign body. If this idea cannot be denied, people who do not understand the scientific data explained but wish to take part despite their apprehension and are willing to sacrifice themselves by “giving their bodies to science” should be excluded from such experiments. It was clear that for some people in the selection process, the protocol would present a real danger of psychological decompensation in an anxious and depressive, or even psychotic, mode. Others, aware of the risks of such an experiment sought a form of pleasure connected with risk-taking. It was not acceptable for the experimenters to promote such a quest from an ethical point of view, and as such, a certain number of applications seemed to be inadequate. These included an excessive idealization of science and researchers, an unfounded hope of rapidly discovering a vaccine, unrealistic enthusiasm, and an intense desire for social recognition [Revalorisation narcissique dans la participation aux essais vaccinaux (Narcissistic revaluation in participation in vaccine trials), Danièle Silvestre, 1996, personal document.].
BUILDING A NETWORK OF VOLUNTEERS
The concept of a network of volunteers fulfills 2 needs, ie, of partnership and transparency. Partnership is necessary because such an experiment, which is innovative in terms of its concerns and its form, is only possible if investigators and volunteers interact closely and with mutual perspective. The ANRS has therefore highlighted this notion of partnership: mass communication (mass media such as TV, newspapers, etc.), methods of experimentation, results and the creation of a network of volunteers (participating or potentially participating in trials), information for these volunteers (documentation, meetings with researchers in the basic sciences, discussions with the investigating doctor, whom them meet regularly, etc.), and a record of their observations. Transparency is necessary because the important concerns of this type of trial, ie, social, economic, and political as well as with regard to public health, required that all of society be informed about the methodology and results.15
The first meeting of the Volunteer Network will take place on July 8, 1992. It is open to all volunteers, who may also be accompanied by one person of their choosing, and will take place with the participation of members of the initial working group and selection committee. The volunteers submitted many questions concerning HIV and vaccine research as well as the duration of the follow-up and the potential occurrence of adverse events. The network will meet once a year.
Like any medical experiment conducted in humans, the vaccine research protocols must be submitted to various ethics bodies. On this basis, the vaccine trial protocols were submitted to the Consultative Committees for the Protection of People in Biomedical Research (Comités Consultatifs de Protection des Personnes dans la Recherche Biomédicale, CCPPRB). The working group of the ANRS subjected the creation of the volunteers' network to the same procedure. This methodology (collection of motivations in writing, 2 selection interviews, evaluation of risky behavior, and the development of consent at different stages) was also submitted to the French Data Protection Authority (Commission Nationale Informatique et Libertés, CNIL) and the CCPPRB of Cochin Hospital. The latter issued a favorable opinion but also expressed reservation regarding the principle of the “noncompensation” of volunteers apart from the reimbursement of their expenses.
In addition, the opinion of the French National AIDS Council (Conseil National du Sida, CNS) was requested on the more specific topic of recruitment by means of “a call to the public through the media.” After interviewing E. Rouveix and F.L., the CNS stated in an opinion issued on January 13, 1992, that it found the principle to be legitimate. During the interview, a member of the CNS also emphasized the ethical need for “everything concerning the epidemic to be made public.”
WOMEN OF CHILDBEARING AGE: PREVENTING A MEDIUM-TERM RISK
The opinion of the CNS will be requested for a second time regarding the possibility of recruiting women of childbearing age. After interviewing the main officers of the volunteer network, the CNS stated in an opinion of 11 pages, dated May 23, 1996, “that there is no impediment in principle to the participation of women of childbearing age in prevaccine immunization trials.” However, given the impossibility of eliminating all somatic and psychological risk for all volunteers (male and female) and for unborn children, it is recommended that as much information as possible be obtained regarding local vaccine immunity through animal experiments; verifying that as much information as possible has been obtained through a study of women who are already volunteers and have been selected for ongoing vaccine trials; initially recruiting women who are very unlikely to become pregnant; and limiting the recruitment of women of childbearing age from study protocols, which specifically explore female genitalia.” This opinion will make it easier to recruit women and thereby to increase the share of women in the cohort of volunteers.
VAX RESEARCH: MOTIVATION AND RELUCTANCE TO ENGAGE IN TRIALS
As early as October 1991, the idea of research that would question the experimental system was envisaged. The organization of this psychological and sociological research project was the subject of an amendment to this very CCPPRB.
This research aimed to explore many questions: What would be the motivations of people who apply for such trials? Are there good (altruistic) and bad (individualistic) motivations? With regard to donation, what are the differences between militant engagement, financial involvement, and the engagement of one's own body in an experiment? What might the psychological and social repercussions of this experience be? What are the imaginary ideas at play in the field of AIDS? The analyses were conducted from 2 different perspectives. On the one hand, we analyzed the “motivations” that the volunteers expressed at the start of their participation in the trial in the form of letters, such as the expression of their representations, and at the end of the trial by means of semistructured interviews to understand the evolution of their representations during their participation.16 On the other hand, with a sample of nonvolunteers (people who did not apply), we tried to understand the reasons for their nonengagement in these trials by identifying their representations of medical research, vaccines, AIDS, and people living with the virus.10 The analyses initially revealed that most applicants have a close social and emotional relationship with people who are living with HIV or who have already died of AIDS. This closeness can take different forms, eg, friendship, a romantic relationship, a relative (parent, sibling or partner), or participation in NGOs, which help and support people with HIV. We observe the presence of another category of volunteers who work in the health care sector, social activism, or education. These people are less personally involved in the world of HIV but want their participation in these trials to contribute to the eradication of the HIV infection and for future generations not to be exposed to it. The motivations expressed by most volunteers were along the lines of altruism, solidarity, compassion, or a form of processing their grief about someone's death. These are the main types of motivations expressed.16
The applicants who were excluded from the trial (based on their cover letter) usually expressed motivations, which were directly connected with participation in the trial itself rather than its end goal. Thus, a large number of them said that they were willing to “put themselves in the hands of science,” to “donate themselves,” “to carry out an act of redemption or sacrifice,” “motivated to take part in a fun and exciting experience to fill an empty existence.” A minority expressed motivation at the potential prospect of compensation. In addition, the members of this group expressed themselves in a much less nuanced and more dramatic and extreme tone and emphasized the exceptional nature of their application. Those whom the selection committee considered to be too emotionally involved were excluded since this posed a risk.
The study of “nonvolunteers”10 revealed that their refusal to participate seemed to be associated with a refusal to be identified with the “world of AIDS”: “We are not like those who try to become infected by any means, so we will not take the risk of becoming infected.” The only way to identify with the “world of AIDS” is to consider the suffering of a patient. This therefore creates a split among those who were unwilling to take part between, on the one hand, the “world of AIDS” represented mainly in terms of sex and risk-taking, and, on the other hand, the suffering attributed to the disease. This split determines whether it is possible to identify with certain categories of people with the disease and not with others. The fear caused by the risk of infection is reinforced by the uncertainties, scientific controversies, and political issues surrounding AIDS. Finally, these fears and uncertainties occur in a climate of a crisis of confidence in medicine and a rejection of the “world of AIDS.”
The phase-I vaccine trials constitute a paradox, which was considered by the committee. The people who were the most exposed to risk were selected less frequently than the people who were less exposed to risk out of a concern to protect people. The first trials were not conducted with the main potential recipients (intravenous drug users and women of childbearing age) but with people who felt concerned without being directly involved in the “fight against AIDS”: partners or parents of people with the disease or people involved in altruistic social action. Gay men, selected based on their attitude to risk-taking, took part in the trials.
The ethical and legal obligation to protect people was an essential principle of the selection and support of volunteers. This approach was apparent throughout the process, which remained based on a form of conscious adherence, expressed and explained at each stage. The partnership established with the volunteers thus intended to act as the framework for their engagement and to clarify the foundations on which it was based.
THE QUESTION OF CONSENT
The signing of written consent forms was required throughout the experiment. The repetition of consent requests (consent at the time of initial HIV testing, consent to join the network, and consent to take part in an actual trial) allows volunteers to reflect and rethink at each stage of participation.
Obviously, this consent is considered to be “free, informed, and express” according to the terminology of the Huriet Act. Although vaccine experiments are performed with high levels of precaution in France, the extreme attention given to these questions gives rise to the following points:
- Providing accurate information is a minimum prerequisite for any experiment. It is a ordinary everyday language that can be easily understood by most volunteers to convey complex technical knowledge. We see that beyond the avatars of communication, the classical hiatus observed in psychoanalysis and anthropology of medicine emerges between the “knowledge” delivered by the experimenters and the “truth” forged by the participant, a singular truth for each one, modeled on elements of reality, certainly, but also by the weight of the imaginary. Far beyond the required changes in behavior, psychoanalysis, through the free speech it allows, leads to reflection on the conscious and unconscious implications of the meaning of the act. This has much more effective consequences than “correcting” behavior. Because it was inevitable that the reasons for the action would be misunderstood, the committee simply tried to reduce this lack of knowledge by encouraging potential volunteers to express themselves freely.
- The illustration of this hiatus concerns preventive behaviors: the message delivered insists on the fact that the candidate vaccines do not provide any protection whatsoever from HIV. This was a preliminary stage in the creation of a vaccine, which is intended, such as any phase I, to verify the safety and tolerance of the drug and to evaluate the immune responses of the volunteer. This information is important because one of the risks of taking part in trials is that volunteers may start to be less careful about preventive measures because they believe they are protected. Despite all the precautions taken, we have observed that this point is still not clear to some volunteers.
- The participants' freedom may consist, beyond good objective information on protocols or simple encouragement to continue their engagement, in benefiting from moments of dialog and reflection with clinicians and psychiatrists, which allow them to clarify their subjective position on their choice. In other words, replacing, even if only minimally, their desire to participate in the whole of their history with an experiment that can last several years.17
The VAX research highlighted 3 types of representation associated with the vaccine substances: some believed that the candidate vaccine was already a vaccine, and that they could therefore achieve a free sex life with the help of this “vaccine”; others based their refusal to participate on a belief that the vaccine was equivalent to the virus (a belief reinforced by the development of antibodies and a “seropositivity without the virus”); finally, some people, who were already seropositive, applied for the trial believing that the vaccine substances were already a remedy that could potentially treat and cure them.10 It was also very difficult for both the team and the volunteers to understand that the vaccine was only a candidate vaccine intended to evaluate the tolerance of a product and which may potentially result in an infection and induce seropositivity in the absence of the virus. This would therefore not be a true seropositivity nor a false one, although seropositivity would be found in the Elisa and Western Blot tests. Confusion about the definition of a candidate vaccine during the interviews with the volunteers and nonvolunteers was shared to a varying extent by the research team, which can be seen in the frequent use of the term “patient” to refer to the volunteers and especially in the expression “false seropositivity,” long used by the research team, or in metaphors that consider the test vaccine to be a form of “poisoning” (The authors observe the use of different notions at different times in the research: it may be a question of “apparent seropositivity,” “false seropositivity,” “pseudoseropositivity,” “seropositivity” in quotation marks, “seropositivity without the virus,” or the acronym “VISP”: vaccine-induced HIV seropositivity after participation in preventive HIV vaccine trials. The multiple terms used reveals that uncertainties were present in the research team.) in parallel with mithridatism: ‘Mithradates, in 63 BC, who initially resisted the poison because, according to Pliny, he “imagined drinking remedies and poison every day to make the poison harmless through habituation.”18
The selection methodology thus attempted to take into account these elements from different registers by focusing on written expression (cover letter) and a good understanding of the information shared by the ANRS to exclude people from the trial whose lifestyle and personality were liable to reinforce risky behaviors. The opportunities for communication developed in the network made it possible to regularly discuss these types of misunderstanding and clarify them.
THE ABSENCE OF COMPENSATION
The phase-I trials give rise in France to the payment of a sum fixed by law. The selection committee decided to reimburse all expenses incurred as a result of participation such as transport, accommodation in Paris if necessary, and lost earnings, but without paying any compensation for the participation itself. The incentive effect of money seemed to cloud the issue of engagement in the trial. The committee made its choice out of a desire to prioritize other motivations.
WITH OR WITHOUT DIRECT BENEFIT? THE MAIN PARADOX OF THIS PHASE-I VACCINE TRIAL
The main potential recipients of the vaccine in the long term are not necessarily eligible to participate in the trial given the rules regarding the protection of people, and that people with the highest exposure to risk should be not become infected: intravenous drug users, women of childbearing age, and men who have sex with men.
The implementation of these phase-I vaccine trials thus contains an opposition between an individual human ethic, as generally formulated by the Huriet Act, and an ethic focused on “the good of society” in the sense of the utilitarianism of Bentham and Mill, for whom people may be endangered if they accept and understand the risk they are incurring and if the results of the experiment aim at what scientists would consider as scientific and social progress for the majority.19,20
However, the medical liability of the experimenters and, more generally, the members of the selection committee is also located at this level. In effect, they are required to evaluate the “risk” to avoid “fault.” This is the legal meaning of “fault.”
On the other hand, if harmful events occur in the volunteer, the “fault” also has a moral meaning because they have a commitment with the people included in the protocols. This raises the question of the “principle of precaution,” which flows from the “principle of responsibility”21 as defined by Hans Jonas. This should be compared with the widely held idea that “zero risk does not exist,” which obviously implies that these trials necessarily involve risks. The ethical question therefore concerns the responsibility that knowledge brings: knowledge to be shared in a democratic manner, and the knowledge of experts, which is difficult to convey due to its complexity, its limits and its subject matter, which give experts the responsibility of making experimental decisions, a responsibility which they must assume.
DISCUSSION AND PERSPECTIVES
The period during which the network of volunteers was set up in the protocols of the phase-I vaccine trials gave rise to many scientific and ethical debates and controversies, which we have attempted to describe here. In the context of a tension between the need to develop effective responses to the development of an epidemic and the equally important need to protect the people who lend themselves to medical experiments (which also involves protecting them from themselves and their desire to engage in a careless way in this sort of adventure), the assessments made by this group contribute to a reformulation of certain ethical questions.
In terms of ethics, 2 positions were identified: one is based on the idea, as required by the law, of protecting people, according to which consent was only considered to be free and autonomous if the decision to participate was made on the basis of the transmission of proven scientific knowledge. The other, which is more based on the idea of “choice of risk,” leaves more room for autonomy to the person concerned. If a volunteer wants to take the risk of engaging in a trial with consequences that are not fully known to him or the researchers, preventing him from doing so may be considered paternalistic and disrespectful of the absolute autonomy of the person, a view that is more prevalent in the English-speaking countries and shared by activist groups involved in the trials.22
The recruitment process and volunteers' network proved to be remarkably long-lived. The efficacy of the selection process was indicated by the absence of any major accidents during the 25 years of vaccine trials in France. The hypothesis and expectation of a possible long-term HIV-positive status without a virus, with all its psychological and social consequences for volunteers, have also proved to be correct.23 In 2014, the team of the ANRS COHVAC cohort explained in an article that “healthy volunteers must be informed of the possible persistence of VISP (vaccine-induced HIV seropositivity after participation in preventive HIV vaccine trials) almost 17 years after vaccination.”24 Although scientific knowledge has increased, it is a fact that problems remain unsolved: persistence is “possible” and not “certain.”
When the initial position of the selection committee concerning women of childbearing age posed a problem for the progress of the vaccine trials, a need for an external opinion arose and the problems were submitted to the CNS, who issued an opinion explaining the tension between the need to make scientific progress and compliance with the principle of precaution to protect people. In fact, the CNS had recommended “initially recruiting women who are very unlikely to become pregnant.” Thus, 2 ways of thinking found themselves in competition: a statistical notion based on the principle of “probability,” which is valid for the group, versus the “desire for a child,” which is valid for the person, and refers to subjectivity.
Finally, the preparation of this text made it possible to recall the importance of the psychological disciplines in the systems for the “fight against AIDS” and, in particular, biomedical research, which emerged in the early 1990s. Indeed, it is at the very heart of the development of biomedical experimentation that the need for psychological and social support for human volunteers has been advocated by principal investigators from these disciplines. In fact, members of these disciplines had already been involved in research on people with the disease or on other aspects of the epidemic such as nurses' attitudes since 1988.3,25 This collaboration, based on different scientific bases but driven by a single ethical concern, worked. It must be noted that the role of the psychological disciplines (clinical psychology, psychoanalysis, and social psychology) has faded in recent years to the benefit of social sciences such as sociology or health economics or community participation in research conducted in France, which leaves little room for the analysis of people's subjectivity in favor of the study of their behavior or their community identifications. At a time when a risk reduction policy advocates for “combined preventive” approaches, including pharmacological approaches and behavioral approaches,26 the experience of setting up the first phase-I HIV vaccine trials can be seen as a preventive approach experiment combining elements of biomedicine, social psychology, and psychoanalysis. Such collaborations should be developed again. All these questions demonstrate the need for ethical debate as has been suggested by Anne Fagot-Largeault27 “ethical decisions are precarious and to a large extent arbitrary because they are the product of negotiations.”
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