1The case of rare disorders [1] raises a classic question: how did an ensemble of heterogeneous and almost invisible associations become a clearly identified coalition occupying a key position within priorities for public health? Seeking to answer this question leads to another consideration: in what ways can the actions of public authorities contribute to this type of mobilization? The process that leads to a regulatory definition of rare diseases can in fact be considered as much the result of public health policy as the fruit of collective mobilization. In this respect, a tension runs through these illnesses that transcends their specificities and structures two distinct theoretical and methodological perspectives that are nonetheless familiar: [2] one perspective tends to “accord a preeminent role to the state, to officials in the organization and steering of society” and its reasoning is “top-down to demonstrate centralized decisions and their effects”; the other is concerned with “factors of change, interest groups and social movements that are powerful actors for change in public policies and for contesting the political order” and “privileges bottom-up reasoning, starting with the ways in which individual and collective actors interact and come together”. [3]

2The manner in which political institutions, on the one hand, and protest movements and groups on the other, interact has aroused growing interest. [4] Different conceptual tools have been developed to address this question. The one most used is political opportunity structure. [5] Introduced in order to designate the elements of the political environment and context that exert an influence on engagement in collective protest, it has been increasingly criticized: according to the critiques, it tends to describe social movements as determined by political structures; [6] it has reinforced divisions, which it was supposed to address, between specialists of mobilization and specialists of public policy; [7] and it masks the fact that there may be sectoral specificities within public policies, thus overshadowing the characteristics of the national political structure. [8] In the same vein, certain authors have demonstrated that the boundaries between protest actors and institutional actors can be remodeled when alliances are formed which transgress them; [9] when protest becomes institutionalized or when the state adapts to the protestors; [10] or when sites are developed where these actors can interact in specific ways, such as in networks [11] or forums. [12] Other perspectives concentrate on the stage before or after these interactions by considering the framing of demands [13] or the mobilizations’ capacity to influence public policy. [14] These approaches remain, however, dependent on an underlying distinction between the actors who protest against public policy and the actors who decide on that public policy. Another approach therefore consists in paying attention to the process of defining and addressing a public problem, while including the possibility of back and forth exchanges between these two sets of actors. [15] But although there are a growing number of works taking this approach, [16] habitual ways of thinking, in particular the themes of opposition, rivalry, and figures of the ‘challenger’ or the ‘outsider’ persist, to the detriment, it would seem, of a closer analysis focusing on the perspective of public authorities, both when faced with mobilizations, but also when engaged in a dynamic interaction with them.

3The research presented here falls within this latter approach. While many studies analyze the capacity of organizations and mobilizations centered on patients and their loved ones to influence health policies, [17] the case of rare disorders obliges us to keep these two perspectives together in order to grasp how a cause and a public policy are elaborated together. [18] It thus allows us to make an accurate assessment of the reciprocal action of public authorities and protesters and interest groups. This general interrogation raises two secondary, more factual, questions: how does this action operate? How does it develop over time? I am proposing a new type of analysis that differs from the approaches previously mentioned, which are dichotomous in their vision of the actor (the public opposed to the private, decision-makers against protesters) and unidirectional in their study of action (be that public policy operating on private actors who protest against it or, inversely, a mobilization leading public authorities to accept its demands). The analysis of the role of public authorities in the mobilization around rare diseases uncovers two distinct temporal sequences in three stages in which the reciprocal action of the actors takes on different forms.

4In the United States, a legislative measure intended to reinforce the safety of medicines had the unanticipated effect of depriving certain patients of their treatment. As a result, these patients mobilized in order to regain their medication, first individually, then collectively thanks to the action of public authorities, who brought them together in order to find a way to rectify the unintended side-effect they had caused. Finally, in a third phase, the public administration devoted a part of its own role to creating a coalition of associations and used the confrontation between the various parties to come up with an instrument for resolving the initial problem. Key within this sequence of events, which effectively describes the reciprocal dependence of the actors, is the notion of “a public” as defined by John Dewey: that is as “[t]he ensemble of all those who are so affected by the indirect consequences of transactions that it is judged necessary to systematically monitor these consequences”. [19] This concept therefore allows us to understand clearly how an extraordinarily heterogeneous and fortuitous mobilization succeeded in taking shape, as a result of a public policy and with subsequent effects on that policy. The second sequence of events, in Europe, is rather different, while still being in three stages. Public authorities here were approached by the pharmaceutical industry. This approach led the authorities concerned to reformulate the problem that had been put to them and to turn toward the patients who were potentially affected, so that they would support and thus legitimize their policy. Finally, the patients and the French administration pooled their efforts to bring what had become their common cause to the European arena. The function of making collective action coherent, a role undertaken by notion of “a public” in the American sequence, was here undertaken by the public authorities themselves, as they turned themselves into “protest entrepreneurs”. [20] The two institutional contexts strongly diverged on one point. While, in the American example, the intervention of the public administration was considered a necessary evil during the time it took to reach arbitration of the conflict, it was seen in France and in Europe as legitimate and inherent to the proper functioning of the health system as a whole.

5These two sequences, in which public authorities were, in turn, creators of a public and entrepreneurs of protest, enable me to contribute – in an integrated perspective – elements of an original response to the two sides of the question of reciprocal dependence between public authorities and mobilization: not only “in what ways does the action of public authorities contribute to a mobilization movement?” but also “how is this action impacted in return?”

How the American administration created a public

6Rare disorders did not initially constitute an autonomous cause, but took on a public protest identity following convergent actions by the Food and Drug Administration on the one hand, and by the subsequently mobilized patients on the other. More specifically, it was the result of the creation, by public authorities in the United States, of another category – orphan drugs – that led to patients being suddenly deprived of medical treatment, forming what John Dewey calls a public. The case of rare diseases should be understood on the basis of this completely new situation: it is important to grasp how the action of public authorities caused unanticipated effects that overwhelmed them and impacted them in return.

7To situate the first part of this sequence – the creation of a public – we need to retrace through American health history [21] a long chain of rulings and semantic slippages until we reach the problem posed by so-called ‘orphan drugs’, that were themselves an unforeseen consequence of the Kefauver-Harris Amendments of 1962 which modified the Food, Drug and Cosmetic Act of 1938. The original text from 1938 required, for the sale of a medication to be authorized, that the company that proposed selling it prove that it did not present a danger to patients. Later, in the early 1960s, the birth of children with deformities caused by thalidomide again brought consumer protection to the fore, and the 1938 text was amended. From then on, for a medication to be approved for sale in the United States, the manufacturer had to prove through recognized experimental protocols that the product was both effective and harmless. This public policy decision had many consequences. The condition applied in fact not only to new drugs but also retroactively to all those that had gone on sale in the country since 1938. That meant, concretely, that either a given drug was tested in an appropriate manner and its fate depended on the evaluation of its effectiveness, or it was not tested and had to be pulled from the market, potentially to wait for the outcome of further studies. [22] Certain drugs escaped this framework, however, and were neither evaluated nor withdrawn. Qualified as “homeless” or “orphaned”, they stayed in circulation in hospital pharmacies, sometimes in large quantities because each pharmacy could have around 60 of these products. This situation was quickly judged untenable by hospital pharmacies that, through the intermediary of the American Society of Hospital Pharmacists, turned to the Food and Drug Administration in 1968 to get these drugs an appropriate legal status. [23]

8Subsequently, the label of ‘homeless’ drugs was supplanted by the much less precise name of ‘orphan’ drugs, a qualifier subsequently broadened to all categories of medications in which the pharmaceutical industry seemed to have very little interest. In the middle of the 1970s, medications with just one use were considered orphans (this label in particular included vaccines, for which the drug manufacturer was responsible and to which a large number of people were exposed, while representing a market that was in the end of not a very high value); as were drugs intended for the treatment of chronic illnesses (because the extended length of time during which patients were exposed to these drugs required in-depth studies on the long-term effects of active substances and their accumulation); drugs which could potentially create problems of legal responsibility (typically, when they might damage the development of a fetus); drugs designated for the treatment of diseases endemic in underdeveloped countries (for patients who are in general not financially creditworthy); drugs that could not be patented; and finally drugs for rare diseases (the argument put forward being the small scale of the market). [24] However, the main effect of extending the reach of the orphan definition this far was to give a name to the difficulties faced by doctors and patients, while the initial problem, that of the future of products that were available but without an adequate legal status, was left hanging.

9The obligation in the Kefauver-Harris Amendments to evaluate therapeutic products, then the refusal of certain pharmaceutical companies to engage in this process for existing drugs whose economic value did not justify it for them, were thus at the root of a completely new situation, in which American patients suddenly found it impossible to get their treatment, which had either been pulled from the market; had only been available because it was in development, which was subsequently interrupted; or had been classified as “homeless” and required meticulous preparation that was difficult to guarantee reliably and continuously. [25] Those people who presented the two characteristics of, on the one hand having a rare disease, and then on the other hand of being deprived of treatment, represented a public as defined by John Dewey: they were impacted by an external issue in such a way that it seemed necessary to rectify its consequences, which became a task for public authorities.

10In a short second phase, the patients who were affected reacted in completely individual ways as consumers. Some obtained illegal sources in Canada and told their elected officials – most notably the democratic representative Henry Waxman, who was very involved in health-related questions – and the American federal administration of their troubles, spontaneously or after having been stopped at customs. [26] They then sought to arrange for this situation, which had clearly not been anticipated when the amendments were adopted in 1962, to be resolved in a way that would allow them to resume taking their medications. Attracting the attention of the federal administration and challenging the pharmaceutical companies involved became their goal, even though, at the same time, the Food and Drug Administration had been seeking for years to end this situation.

11The Food and Drug Administration, in a third phase, transformed these individual protests into a collective mobilization. In 1982 it had established a department specifically dedicated to orphan products (Office of Orphan Drugs Development, whose director, Marion Finkel, had previously been in charge of evaluating new proprietary medicinal products) and organized stakeholder conferences, notably in 1982 and 1984, with the goal of finding a solution to the problem that would satisfy all parties. [27] These events catalyzed the patient movement. In fact, the action – this time collective – by people who did not yet identify themselves as having a rare disease, emerged from their fortuitous gathering as a public, whose identity was still being shaped, subsequently linked with other actors. At meetings, the representatives from the patient associations identified themselves and were identified as consumers, and in particular as consumers who were demanding to have new, legal access in the United States to a given medication, [28] while at the same time expressing a more complex reality: their experience of being unusual took shape for them as a feeling of isolation. From then on, being in contact with other people in the same situation became a fundamental experience, which they wished to prolong and that represented therefore a very strong incentive for collective action. [29] The comments of the only patient representative to speak during the 1982 conference provides an overall view of how people suffering from a rare disease (at the time described as ‘orphan’) saw their situation after having got to know each other because of the question of orphan drugs.

12

“Together, we represented millions of people with orphan diseases, and our one voice was made much louder. Thus, an informal coalition was created to achieve political power as well as share information. Many of us had not known that other orphan disease victims were suffering under a similar fate of hopelessness. As we began to talk with each other, we found many common problems; particularly the massive obstacles faced by researchers into orphan diseases.” [30]

13This is how, although due to chance, the act of coming together through a rare condition, and being understood as individuals and not as numbers, in the end appears “natural” to the patient representatives. [31] Summoned by the Food and Drug Administration, this public of patient-consumers came to see in the rarity of their conditions a way to describe their experience, which constituted a platform for collective action. It allowed for the formulation of a simple demand, issued by the patients toward the other actors: ensure that the situation of people with a rare disease falls in line with that of other patients. Following the conference of 1982, a coalition of associations was officially formed, the National Organization for Rare Disorders.

14The creation of this association simultaneously corresponded to a new development in public policy. In fact, the first duty of the Food and Drug Administration is the protection of consumers and this public created a paradoxical situation in which the organization suddenly found itself responsible for two groups with completely antagonistic needs. On the one hand, it was responsible for watching over the interests of a very large public that brought together people suffering from common diseases. Based on the size of this group, a problem having to do with even a small percentage of the population quickly impacts a large number of individuals. In this case, the goal is to protect consumers from the industry and its products, from the prescribing doctor, and also from themselves, in order to place them in a situation where the risks they run are as minimal as possible. On the other hand, the norms established for this first public creates a second, through the removal of therapies that do not satisfy the new demands but are just as necessary to a very small part of the population. How then to reconcile a mission consisting in protecting these two antagonistic groups? This is where the existence of the coalition had an important impact on public policy. In one sense, we can say that the Food and Drug Administration solved this dilemma by limiting its action to the general population and by delegating responsibility for managing rare diseases to the sufferers themselves (who are, according to Dewey, precisely the people “who watch over and take care of the interests that have thus been affected”. [32]) The Food and Drug Administration explicitly entrusted the coalition of associations of rare diseases with a mission to centralize information and bring together potential medical and industry partners, thus giving patients and their friends and family an influence rarely seen at the time, whilst also allowing public authorities to unburden themselves of the corresponding tasks. [33]

15The Food and Drug Administration could then proceed to the creation of an instrument based on the collective mobilization it had organized. The creation of a coalition of associations in effect left aside the question of the status of orphan drugs. A law passed in 1983, the first version of the Orphan Drug Act, aimed to resolve the problem of orphan drugs, understood as unprofitable medications. The FDA defines them as follows:

16

“The term ‘rare disease or condition’ means any disease or condition which occurs so infrequently in the United States that there is no reasonable expectation that the cost of developing and making available in the United States a drug for such disease or condition will be recovered from sales in the United States of such drug.”

17In addition, this law establishes that a company that develops such a drug can benefit from a tax credit for the period of clinical research, that it can receive technical and administrative help during the evaluation process, and that it enjoys exclusive rights to the sale of the drug for seven years after it becomes available, instead of the twenty years after patenting stipulated by common law.

18This text was amended in 1984 and from then on has clarified what constitutes an infrequent disease; it sets the limits still in use today. But these orphan drugs remain the object of public attention. The change introduced by the 1984 version established that, from then on, a medication for which the statute of orphan is solicited must either 1) be indicated for a condition that impacts fewer than 200,000 people in the United States, or 2) be indicated for a condition that impacts more than 200,000 people in the United States but whose profitability on the American market is highly uncertain. In hindsight, this second condition, which is particularly difficult to verify, has never been put forth in order to obtain the status of orphan drug. [34] The common interpretation of this situation is that orphan drugs are medications for rare diseases. But this conclusion is founded on the subsequent application of the text, not on its precise wording, which does not so much define rare diseases as the circumstances of a drug’s non-profitability on the American market.

19The statistical definition of rare disorders had major effects in terms of collective mobilization and in terms of public policies. This definition supported the potential mobilization of “orphan” patients by giving them a precise and ongoing identity: they were now “rare”. This definition had an equally important effect on public authorities: it reaffirmed the role of the Food and Drug Administration in protecting the health of consumer-citizens and reinforced its neutrality regarding the different demands that are addressed to it. The specific role that actors attribute to public authorities, the role of arbiter, is clearly demonstrated in the demands that they make of them. The demands of the patients were partially taken up – but largely inflected – by doctors, who attributed their own difficulties above all to a division of medical tasks that seemed ineffective to them and in which they perceived an excessive disproportion between the efforts that they would like to be able to undertake for a given disease and the lack of interest that public authorities or industry showed to support these efforts. Doctors thus cited the difficulties caused by the necessity of applying on a small scale technical norms which had been developed for the large scale; [35] their inability to convince the public administration to fund studies on diseases that only impacted a few people; [36] or the refusals of pharmaceutical companies to allow them to take over the development of a drug which looked promising, but which would be of use only to a small number of patients. [37] American doctors wished to modify this division of tasks by asking public authorities to force the pharmaceutical industry to increase its research and development efforts for generally unprofitable treatments. It is however in terms of profitability that representatives of the pharmaceutical industry approach the subject of orphan drugs. Contemporaries and commentators [38] perceived this position as the root of the problems of orphan drugs and focused their complaints on the American Pharmaceutical Manufacturers Association. The representatives of pharmaceutical companies make the size of the potential market for a drug a decisive factor, which is naturally tied to the number of people impacted by the illness for which the medication is indicated. If a disease is rare, the corresponding market is small, and it is probable that it will be difficult to make a profit given the costs of developing a product intended for this market. The category of rare diseases, based on prevalence, allows for the indirect evaluation of the size of a market for a given drug. From this perspective, the category of ‘rare diseases’ represented an acceptable compromise between the wishes expressed by the patients and their doctors that the pharmaceutical industry be forced to take on board their priorities, and the refusal by the industry to be subjected to any form of control.

20While it is true that the pharmaceutical industry was in a position of power, this did not in fact mean that it was the most decisive actor within the emergence of the rare diseases issue. This, despite appearances, was the Food and Drug Administration. In the 1970s, its efforts to convince the representatives of the pharmaceutical industry to participate in working groups on orphan drugs were in vain. [39] Given the FDA’s capacities and the generally uncooperative attitude of the industry, the position taken by its representatives meant that an acceptable solution needed to fulfill three conditions: it could only be regulatory, given the nature of the means of action available to the Food and Drug Administration; it could not be restrictive for companies, nor involve direct intervention from public authorities; finally, it was preferable that it be simple and consistent for all parties involved. The definition of a threshold of prevalence below which a financial incentive would be implemented satisfied these conditions.

21The director of the orphan drug office thus proposed the definition of a very unsophisticated tool, the threshold of prevalence, that allowed for the resolution of what for them was the problem: the existence of orphan drugs. It was necessary first to define these products. They were not, then, medications for rare diseases, but rather:

22

“Orphan products are drugs, devices (including in vitro diagnostics), biological products and foods for special dietary purposes which, despite potential usefulness, remain inadequately tested and/or unavailable to patients because of limited commercial interest. Such products can be useful in uncommon conditions or they may be applicable to common conditions but are not developed or distributed because they are unpatentable, or because impending patent expiration discourages research investment.” [40]

23The next step in their reasoning consisted in finding a way to define the notion of limited commercial interest. Since this was the sense of the pharmaceutical companies’ arguments, then it was proposed that an infrequent disease be considered as one which is of little commercial interest. Then all that was necessary was to define what was meant by “rare”. The observation that pharmaceutical companies refused to produce treatments for those few illnesses which affected only around 200,000 people in the United States finally enabled the determination of a threshold of prevalence associated with a level of profitability judged insufficient by the industry: around 200,000 patients. [41] This policy instrument thus presents many characteristics of policy instruments in general. [42] It rests on a conception of the relationship between politics and society in which politics arbitrates between interests, through weak regulation, privileging incentives. This brought an end to the sequence of interactions initiated by the Kefauver-Harris amendments.

The French administration becomes a protest entrepreneur

24At the end of the 1990s, the European medical landscape, including that in France, was very different from the state of the American landscape at the time of the adoption of the Orphan Drug Act, nearly twenty years earlier. These differences are important in order to understand in what ways – although the regulations could hardly be more similar – the European ruling nevertheless represented an incredible reversal of the situation. In France, throughout the 1980s and particularly in the 1990s, there was a parallel boom in associative movements and reflections on the rights of patients. The legal framework of medicine noticeably developed, with the creation of the Conseil national d’éthique (National council of ethics) in 1983, the Huriet-Sérusclat law of 1988 on the rights of patients involved in biomedical research, laws on bioethics in 1994, and in a slightly different register, laws in 1989 and 1993 on medications arising from human blood and on the safety of blood transfusions. The activity of the pharmaceutical industry was also the focus of renewed questioning, as a result of specific crises (in particular the contaminated blood affair, then the debates about the availability of treatments for AIDS between 1994 and 1999, which illustrated different ways of asking ethical questions and of attributing responsibilities to the industry) and of technical or scientific advances in biotechnologies that provoked industrial researchers to reflect on their own practices. The division of roles and of power was also modified. Greater powers in medical and ethical terms were gradually granted to patients; it became possible to control more strictly the work of medical researchers; and the pharmaceutical landscape diversified with the emergence of biotechnology companies. This tableau only vaguely resembles the previous American situation, which was characterized by a dominant pharmaceutical industry with public authorities far in the background, and particularly by the existence of “homeless” medications. While, in the United States, ‘orphan drugs’ was the problem to be resolved through the notion of rare diseases, the reverse was true in Europe. For the French administration, rare diseases were a problem of public health that it needed to contribute to resolving by transforming them into a cause for associations representing patients suffering from illnesses – and not necessarily infrequent ones at that. To map this out so as to bring out the relationship between public policy and mobilization, we might say that European history was written almost entirely backwards from American history: 1) the French administration was alerted to the situation by the pharmaceutical industry, 2) identified and formulated a problem different from that with which it had been presented and sought the support of a coalition of associations to bring this cause to the European level, and 3) created a cause that subsequently became autonomous.

25Initially, as the formalization of a European drug market [43] became only a matter of time, the American experience with the Orphan Drug Act attracted the interest of the pharmaceutical industry, which brought the attention of the French administration to the American model. The pharmaceutical industry was keen to benefit from the incentive for innovation which seemed to them to constitute the status of orphan drugs; the French administration saw a way to deal with previously neglected aspects of public health and thus proceeded to reverse the relationship between the ideas at stake. In fact, from the moment the French administration processed the request from the pharmaceutical industry, orphan drugs came to be seen as a response to the difficulties faced by those involved in rare diseases (patients, but also researchers and pharmaceutical companies). This new relationship was reinforced when French public authorities then turned to patient associations.

26The European pharmacy industry thus became interested in the Orphan Drug Act. In 1987, European pharmacy companies organized a conference in Brussels entitled “Health Orphans” [44] under the aegis of a group of pharmaceutical research laboratories, Prospective et santé publique (Forecasting and public health). This conference was motivated by the future reorganization of the pharmaceutical industry in Europe, which had as its goal an improved ability to satisfy new regulatory demands, and to give the industry the means to be more innovative. All eyes were focused on the measures introduced in the US: the European pharmaceutical industry understood the Orphan Drug Act as a mechanism for promotion and innovation. It should be stressed that, on this occasion, profitability did not figure amongst the questions raised. On the contrary, discussions focused on orphan drugs considered as a tool for therapeutic innovation, and not as products intended only for infrequent diseases. Indeed, these illnesses were no longer the primary focus. The conference shed light on the different general directions for future activities being envisaged by pharmaceutical companies in Europe. Their primary concerns could be summed up thus: how to innovate? Was the orphan drug statute an appropriate tool?

27In the middle of the 1990s, the European pharmaceutical industry seemed convinced that it needed to adapt quickly to new demands. [45] But it did not define the infrequence of certain diseases as a specific problem. Priority was given to taking into account existing regulatory norms, which did not distinguish among diseases based on their frequency but tended to promote a standard approach to illness, supported by the desire to offer the same guarantees of quality to all patients. But the pharmaceutical industry was not in a position to modify these norms. In this perspective, it was not the industry that was capable of acting but public health authorities that could define such rules. This point highlights a major difference between the United States and Europe: the intervention of the state was judged disruptive by American industry officials, while their European counterparts believed that this intervention was, on the contrary, necessary. Pharmaceutical enterprises thus turned to public authorities to contribute to the transformation of their activities.

28In 1994, four pharmaceutical companies (Elf Sanofi, Fournier, Rhône-Poulenc Santé and Roussel Uclaf) wrote to the director of the Institut national de la santé et de la recherche médicale (Inserm, National institute of health and medical research) to raise the question of both orphan drugs and orphan diseases – but not rare disorders – a sign that these different categories were far from stable. The companies wanted the relevant public authorities to help them facilitate or improve the development of medications. [46] Inserm responded favorably to this request and carried out a report on the subject. This was delivered in autumn 1994, and was a decisive advance in the introduction of the notion of an orphan drug, and thus of rare diseases, in the European Union.

29In a second phase, this report adopted a broader perspective than merely supporting the pharmaceutical industry and proceeded to reformulate the problem raised by its instigators. With this report the idea gained currency that rare disorders were a problem of public health and that orphan drugs constituted a first attempt to respond to one aspect of the difficulties particular to these diseases. This approach to rare disorders, reversing the previously established relationship between problem and solution, put rare diseases at the heart of public authorities’ concerns.

30Also entitled “Health orphans” (Les orphelins de la santé), this report examined the distinction between rare and orphan disorders and suggested that the latter are “dominant pathologies in developing countries, or rare diseases”. [47] The inclusion of rare disorders in a larger category that incorporated other diseases whose treatment was judged insufficient recalls the situation of rare diseases in the United States in the 1970s. However, the reasons that determined these similar categorizations were very different. In France, the argument put forward to consider rare diseases in industrialized countries and pathologies endemic to developing countries as similar was essentially ethical. In both cases, in fact, the report underlined that fundamental therapeutic needs were not satisfied; [48] but from this starting-point, the French report quickly introduced a difference. Those patients with rare disorders whose needs are taken into account live in industrialized countries, and as a result are financially creditworthy. But this is not the case for people with parasitic diseases endemic in developing countries. The report argued on this score that treatments often exist for these diseases and that the problem of their availability is an economic one. It noted that, for rare disorders, the most frequent issue is an absence of any treatment, due to a lack of sufficient knowledge about the disease and how it works. Thus, the situation of people with rare disorders presents two characteristics: their financial solvency, on the one hand, and the insufficiency of scientific knowledge regarding their disease, on the other.

31The recommendations that conclude the report are very similar to the solutions adopted in the United States: there would be a European approval procedure for orphan drugs that would simultaneously be accelerated, would offer a reduction in taxes, and would end with product follow-up after the drugs became available on the market; a legal model that would accord exclusive rights for ten years from authorization to put the drug on the market, all of this based on the model of the Orphan Drug Act. A European observatory would also be created that would go some way to filling gaps in knowledge, on the model of the Food and Drug Administration database; as would a funding program for epidemiology, and clinical trials with European funding. In France, the report proposed taking advantage of the existence of the Pharmacie centrale des hôpitaux (main pharmacy for hospitals), on the condition that its facilities be aligned with requirements for “good manufacturing practices”, to ensure the preparation of certain treatments and to create a national observatory that would play a very similar role to that allocated to the National Organization for Rare Disorders. This report fell within a relatively favorable political calendar. With the rotating presidency of the European Union, there was a real but brief window for making progress on themes connected to pharmaceutical innovation, orphan drugs, and rare disorders. This agenda, which did not allow for the elaboration of another conceptual framework for these questions, probably contributed to the fact that a pre-existing mechanism was retained, in an almost identical form. Moreover, the alignment of concepts and regulations on the international scale was seen as a necessity. Thus, it seems that the wider agreement on the notion of rare disorders, concerning both means of action and the expectations of public authorities, in particular in terms of international harmonization of public health, strongly contributed to the fact that this definition was retained in visibly different institutional, medical, and political contexts. This report led to the creation, in 1995, of a Mission des médicaments orphelins (Mission for orphan drugs) within the Ministry of Social Affairs.

32The French administration subsequently encouraged the mobilization of associations, deciding that it needed their support to push through a European regulation. It suggested the creation of a coalition of associations, whose members hoped to promote what they saw as a solution to a unique problem faced by the diseases they represented. This coalition, created in 1997 and called Eurordis (European Organisation for Rare Diseases) in an explicit reference to the National Organization for Rare Disorders, included four pioneer associations: l’Association française contre les myopathies (French association for muscular dystrophy, which was to be particularly active in this area), l’Association française de lutte contre la mucoviscidose (French association for cystic fibrosis), la Ligue nationale contre le cancer (National league for cancer) and Aides fédération nationale (National federation of AIDS). The participation of these last two organizations may appear surprising. It is partially explained by the existence of personal contacts among the members of the four groups and also by the familiarity of AIDS activists with the notion of orphan drugs, given the existence for this disease of drugs obtaining this status (notably AZT).

33One of the association leaders [49] clearly described the way in which the French administration at that point – here in the person of the author of the report on orphan drugs, Annie Wolf – was clearly fulfilling the role of protest entrepreneur:

34

“She was the head of medications at the Ministry of Research in France. And then, she wanted to change direction, she was hesitating between taking a leadership job in the fight against AIDS in France, or else focusing on orphan drugs, meaning either orphan drugs for rare diseases, or, in her mind, it was more about neglected drugs for countries of the South. So she made her report, she proposed this idea to Simone Veil, who commissioned the report from her, Annie Wolf being originally a high-ranking official at Inserm, she wrote her report. Then afterwards, during the French presidency of the European Union with Simone Veil, what was retained was one of the two facets of the report, namely to develop a policy regarding orphan drugs in Europe. So we, in order to support this move, she was really the high priestess of all this, but when we met, as early as 1994, we quickly saw eye-to-eye. Because we had almost the same trajectories, the same motivations, me, I knew the American regulations on orphan drugs, I knew that AZT had been developed that way, the medications for cystic fibrosis as well… Anyway, I understood the problems for AIDS with drugs in countries of the South, we were beginning to be faced with that…So, we immediately saw eye-to-eye, I told her she could count on me, on us, and when, after, she moved forward, she needed for it not only to be the administration that moved this forward, that she could take care of, but also that the industry move forward, and she needed the involvement of patient associations to say that she was calling for this regulation. […] Eurordis was really at the beginning created only for one reason. The reason Eurordis exists… It’s very simple. The reason Eurordis exists, is to be a collective of associations asking for the adoption of a European policy on orphan drugs, thus, primarily, regulation, and secondarily, and it is secondary, a public health policy on rare diseases. In other words, at the time, and up until two years ago, European policy, the policy of the European Commission of Public Health was thematic, meaning cancer, AIDS, aging… So it was a matter of adding a line about rare diseases. And it stopped there. Of course, when it was subsequently necessary to create statutes, as always, the statutes of the association were wider-ranging. But the goal and the intention, it was clearly that. That the aim of the battle for the AFM and the founders, it was to get this regulation. And what made the start of Eurordis very difficult, because the people who joined the administration of Eurordis as administrators, in particular two British women who had fought for a long time for regulation on orphan drugs in England, using the American model, they’re Leslie Green and Carol Young, they wanted to work on broader things. But, within the dynamics of the creation of Eurordis, what became apparent to them among themselves, was the idea that, ‘here, in fact, we’re together at the European level, but we still need a level at the national level. Because at the European level, we are going to be able to talk about policies in terms of subsidiarity [what can be done at this level specifically], as an EU policy. But everything that happens on the national level, we are isolated into disease pressure groups, we need to regroup.’”

35This move to structure the sphere of associations continued, and also developed its own logic.

36In a third phase, the associations formulated for themselves their perception of the problem, and then the mobilization movement gathered strength and became autonomous. The involvement of the Association française contre les myopathies gave the cause of rare diseases important publicity, through the intermediary of the Téléthon, a televised fundraising operation, again based on an American show created in 1966 and introduced to France in 1987. The telethon was initially intended to collect donations to finance research on muscular dystrophy, but this target was subsequently widened to include genetic diseases (since muscular dystrophy has a genetic origin), then to rare diseases from 1999. This gradual broadening of its scope corresponded with association strategy, which was seeking in this way to reach the largest possible number of people in order to influence the decisions and directions of public health policy. If the association had limited itself to its original goal, muscular dystrophy, which impacted a few hundred families in France, such an ambitious goal would have been extremely difficult to justify. The association thus went about identifying problems it had in common with other patient representative groups, and widened its scope to coincide with developments in these common problems. [50] In this way it succeeded in having rare disorders included on the agenda of the États généraux de la santé ( “General Health Meetings”) in 1999, a series of consultations at national scale intended to improve the system of care. This contributed strongly to reinforcing the cause, by making it known to the relevant people as well as to the general public.

37For the patients present, the physical proximity of different actors at this event, the possibility it represented to discuss their experiences amongst themselves, and the break this represented in comparison with their usual invisibility, were the major revelations of the meeting. In finding themselves together and exchanging their experiences, they came to feel that the word ‘rarity’ effectively described what they had in common. The accounts of the stage that this meeting represented are eloquent.

38

“I was invited as… as an expert. There were different people, important witnesses, experts. The impression I had when I arrived, was of a population… […] We had all sorts of things in common. It was an explosion, the General Health Meetings. Over and above what made us different, we had all sorts of things in common. In our everyday lives, many common things in our battles to be recognized, that our illness be recognized, and that we, we be recognized as citizens and as patient representatives and that our voice was important. And on the other hand, we realized, and this, this was an explosion too, the extent to which we felt isolated, alone in our corners. Why? Because we were numerous and rare at the same time. There. We were numerous and rare at the same time. And that together, we would be stronger. It’s a sentence that seems so obvious, but… we had to get to the point where together we were stronger, and that there was something to do. But it was… it wasn’t said clearly at the mic, it was felt by everyone, it was beneath the skin, it was transmitted like that, from one person to the next, it was just felt”. [51]

39The European regulation was adopted soon after, in December 1999. In what is provisionally the last episode in the story of rare disorders, the instrument invented in the United States was transferred almost without alteration from one context to another. On the one hand, the text that introduced the notion of “rare disorders” in Europe, the Regulation (EC) n. 141/2000 of the European Parliament and Council on December 16, 1999 concerning orphan drugs, is very close to the Orphan Drug Act. This text, like its model and as its title indicates, defines the notion of an orphan drug in the European context. A medication thus obtains the designation of orphan drug if its promoter can establish:

40

“a) that it is intended for the diagnosis, for the prevention or treatment of a disease that threatens life, or chronic disability, and does not impact more than five people per ten thousand in the European Community at the time the request is made, or that it is intended for the diagnosis, for the prevention or treatment, in the European Community, of a disease that puts life in danger, of a very disabling sickness or a serious and chronic disease, and that it is unlikely that, without such incentive measures, the sale of this medication in the European Community will generate sufficient funds to justify the necessary investment, and b) that there is no satisfactory method that has already been authorized in the European Community for diagnosing, preventing, or treating this disease, or, if one does exist, that the medication in question will provide a significant benefit for those with the disease”. [52]

41This text brings to mind its American counterpart. The two scenarios, infrequent diseases and unprofitable diseases, are revisited, with the addition of a more precise characterization of the disorders through the qualification of threat to life and of chronic disability. The overall device remains exactly comparable: technical and administrative support is provided to the drug’s promoter, who benefits from exclusive commercial rights, for ten years this time, and can take advantage of tax credits.

42* * *

43Institutional political authorities thus do not play a determining role in collective mobilization, but rather there is a reciprocal dependence, which is clearly visible in the sequence of actions undertaken either by the state in relation to private actors, or sometimes by private actors on the state (cf. Table 1).

Table 1

Two sequences of successive interactions and of co-construction by actors in the elaboration of a public policy

United States: the public authorities create a public Europe/France: public authorities encourage and make use of a protest movement Action by the state on private actors The 1962 Kefauver-Harris amendments create a public composed of patients without medications / Action by private actors on the state Patients initially protest individually Pharmaceutical companies request an Inserm report on orphan drugs Action by the state on private actors – The Food and Drug Administration organizes meetings between the parties: this leads to collective patient mobilization and the establishment of the National Organization for Rare Disorders in 1982 – The Orphan Drug Act becomes the instrument to remedy the consequences of the Kefauver-Harris amendments – The National Organization for Rare Disorders is delegated particular responsibilities in relation to rare diseases The report carried out by the Inserm widens the problem to include diseases and patients – A coalition of associations, Eurordis, is created at the instigation of the author of the report as a vehicle for the cause of patients at European level Action by private actors on the state / Patients suffering from diseases which are now termed ‘rare’ organize and demand specific public policy measures

Two sequences of successive interactions and of co-construction by actors in the elaboration of a public policy

44Instead of presenting a two-stage process, in the form of an action and a reaction, the sequencing of actors’ interventions in the elaboration of public policy concerning rare diseases shows how the actors’ actions build upon each other and how they co-construct their problems, their assets, and their relationships, through a series of alternating actions that may be initiated by public authorities (as in the case of the United States) or by a private actor (as in the case of Europe). The action of public authorities, in the United States, affected the patients who mobilized to fix the disappearance of their treatments. Their collective action did not take real shape until it had been encouraged by meetings organized by the Food and Drug Administration itself. This organization could then pass on certain responsibilities to its new interlocutor, the National Organization for Rare Disorders, while also obtaining its support in the preparation of a legislative text, the Orphan Drug Act. In France, it was a private actor who launched the process when pharmaceutical companies solicited a report from Inserm. Public authorities reformulated the problem that the companies submitted to them (but without reformulating the solution) and pushed for the creation of a coalition of associations, Eurordis, to legitimize its policy, at the national but particularly European level. Here the integration of so-called non-conventional participation into public life has been taken to an extreme.

45The American and European cases make two distinct models of reciprocal dependence between public authorities and protest movements more visible, which explains how a movement that was otherwise improbable came about: the creation of a public, in one case, and the launching, by a public actor, of a mobilization, in the other. In institutional terms, these two contexts differ markedly in the way in which private actors, and particularly economic actors, perceive the state and the public sphere in general. This observation paves the way for a more nuanced and potentially comparative reflection on the institutional aspects of the observed phenomena. In effect, the American state, generally seen by the actors involved in orphan drugs as a disruptive actor, certainly appeared as such here, at least at the beginning of the sequence described: it adopted a measure whose unforeseen negative effects it then needed to work to correct. Inversely, the French state appeared as a recourse, as much for the pharmaceutical industry which solicited help as for the associations which knew how to exploit it: as demonstrated by the Association française contre les myopathies, which took advantage of the General Health Meetings. This opposition was very clear in the case of orphan drugs, where the essence of public action consisted in one case in resolving an external issue, and in the other in controlling how a public health problem was dealt with. This suggests that this characterization of public authorities – both by the other actors but also by the authorities themselves – could present an interesting alternative to the dominant approach in terms of political opportunity structures, by reintegrating the institutional aspect not structurally, which is too static a mode, but in paying attention to the co-construction of public action and to how, in so doing, actors mutually attribute these responsibilities and the means to tackle them to one another.