<p>Spontaneous reporting systems (SRSs) for adverse drug reactions (ADRs) have been developed as a result of the thalidomide disaster, whereby thousands of children world-wide were born with birth defects. The Swedish Adverse Drug Reactions Advisory Committee was established in 1965. Since 1975, reporting has been compulsory for all suspected serious or new ADRs. International collaboration started in 1968 with countries contributing their ADR reports to an international database set up by the World Health Organization. </p><p>ADRs represent the negative side of the benefit-to-risk balance that in theory needs to be counteracted by perceived or established positive drug effects. All drugs are subject to preclinical and clinical testing prior to marketing authorization. However, these studies are insufficient to detect rare ADRs, ADRs that occur after long-term administration or with latency, ADRs that occur in special patient groups such as children, the elderly, patients with renal or hepatic insufficiency or patients on concomitant drug treatment, and ADRs that represent a modest increase in the risk of diseases (including mortality) that are prevalent in the study population. Postmarketing surveillance of drugs is therefore essential, and regulatory action may be needed on the basis of new ADR information. </p><p>SRSs are important sources of ADR information as exemplified here by the evaluation of peripheral sensory disturbances with fluoroquinolones, hyponatremia with antidepressants, blood dyscrasias with dipyrone, glucose intolerance with atypical antipsychotics, pulmonary embolism with combined oral contraceptives and extrapyramidal symptoms with selective serotonin reuptake inhibitors. SRSs can be used to study clinical manifestations of ADRs (that can give insights into potential ADR mechanisms), risk factors for the ADR or for specific outcomes of the ADR, and ADR reporting incidences when combined with sales data. Signals from SRSs may need to be studied further e.g., by use of large-scale epidemiologic studies based on record linkage between drug prescription databases and health databases. Owing to the rapid availability of information, however, SRSs are likely to remain of major importance for the post-marketing surveillance of drugs.</p>

Spontaneous reporting systems (SRSs) for adverse drug reactions (ADRs) have been developed as a result of the thalidomide disaster, whereby thousands of children world-wide were born with birth defects. The Swedish Adverse Drug Reactions Advisory Committee was established in 1965. Since 1975, reporting has been compulsory for all suspected serious or new ADRs. International collaboration started in 1968 with countries contributing their ADR reports to an international database set up by the World Health Organization. ADRs represent the negative side of the benefit-to-risk balance that in theory needs to be counteracted by perceived or established positive drug effects. All drugs are subject to preclinical and clinical testing prior to marketing authorization. However, these studies are insufficient to detect rare ADRs, ADRs that occur after long-term administration or with latency, ADRs that occur in special patient groups such as children, the elderly, patients with renal or hepatic insufficiency or patients on concomitant drug treatment, and ADRs that represent a modest increase in the risk of diseases (including mortality) that are prevalent in the study population. Postmarketing surveillance of drugs is therefore essential, and regulatory action may be needed on the basis of new ADR information. SRSs are important sources of ADR information as exemplified here by the evaluation of peripheral sensory disturbances with fluoroquinolones, hyponatremia with antidepressants, blood dyscrasias with dipyrone, glucose intolerance with atypical antipsychotics, pulmonary embolism with combined oral contraceptives and extrapyramidal symptoms with selective serotonin reuptake inhibitors. SRSs can be used to study clinical manifestations of ADRs (that can give insights into potential ADR mechanisms), risk factors for the ADR or for specific outcomes of the ADR, and ADR reporting incidences when combined with sales data. Signals from SRSs may need to be studied further e.g., by use of large-scale epidemiologic studies based on record linkage between drug prescription databases and health databases. Owing to the rapid availability of information, however, SRSs are likely to remain of major importance for the post-marketing surveillance of drugs.

Le médicament est un produit de consommation particulier ayant une multiple vocation.Biens spécifiques porteurs de risques par essence, sa répartition ne peut être laissée au seul jeudu marché. Ils doivent être évalués aussi bien à priori qu’à postéri et durant toute leur viecommerciale. Produit actif nécessaire à la santé, ils comportent de nombreux risques. Latotalité du cycle (production, dispensation, récupération) de tout produit de santé doit être trèsétroitement encadrée et confiée à la responsabilité de professionnels. Leur prise en chargerequiert donc l’attention de toute la collectivité, et doit faire l’objet d’une réglementationrigoureuse en raison des problèmes de santé publique résultant d’une mauvaise utilisation.Ces particularités du médicament entraînent un certain nombre de codification. Descontraintes réglementaires régissent la mise sur le marché et l’utilisation de ces biens, afind’assurer leur qualité, leur efficacité et leur innocuité. Les événements indésirables graves nesont pas toujours bien encadrés dans les pays, milieux médical et hospitalier africain. Et encas de dommages à la santé résultant d’une mauvaise utilisation, il importe de s’interroger surles droits et les responsabilités des différents acteurs (professionnels de santé, patient, Etat).On ne peut espérer prévenir les erreurs médicamenteuses si on n’implante pas dans les espritsla culture du risque et de la responsabilité, préalable indispensable à la réorganisation ducircuit des produits de santé. / Drugs are a particular consumer product having a multiple purposes. Specific goods carryrisks in themselves, and shouldn’t be distributed solely to the mainstream market. Rather, theymust be evaluated before, during and after their commercial life. Active products arenecessary for healthcare, but contain numerous risks. The entire cycle (production, delivery,recovery) of all health products must be very strictly supervised and entrusted to aprofessional’s responsibility. Their supervision therefore requires the attention of the wholehealth care community, and must be strictly regulated because health problems can resultfrom misuse. These features of the drug involve a certain codification system. Regulatoryrequirements govern the place on the market and use of these assets to ensure their quality,effectiveness and safety. Medical malpractice is not always well supervised in the medicaland hospital atmosphere of Africa. And in case of damage to health resulting from misuse, itis important to consider the rights and responsibilities of the various people involved(healthcare professionals, patients, government). Medical errors cannot be prevented if theculture of risk and responsibility is not instilled in the minds of the public. This is aprerequisite for the reorganisation of the distribution of health products.

Dans les sociétés anciennes et modernes, la santé a été et est aujourd'hui encore une préoccupation capitale. Elle est le signe du niveau de bien être de la collectivité et de la personne. Dans le cadre de l’accès à la santé qui constitue un droit pour tous, le médicament occupe une place importante en France et au Japon, deux pays où l’espérance de vie et le niveau de vie sont élevés et ne cessent d’augmenter. C’est au vu de ces considérations que nous nous interrogeons à travers cette thèse sur la véritable place de l'usager dans la régulation du médicament en France et au Japon qui sont deux pays différents par leur culture mais qui convergent à certains moments dans le droit. L'on pourrait valablement soutenir qu’un bon système de santé se reconnaît par le niveau de protection qu'il accorde à l'usager du médicament. Cela n'est pas aussi simple car divers intérêts sont en jeu. Il est aussi important de savoir comment se solde le traitement des conflits d'intérêts dans la régulation du médicament : protection de l'être humain ou protection de la science? S'il est soutenable que la protection d'un "humain scientifique" existe, il nous appartient de rechercher la réalité de l'existence d'un ensemble de règles permettant d'assurer une "Science plus Humaine". Nous savons et il a été reconnu que le monde de la santé, émotionnel, individualiste, structuré en groupes de pressions très forts et souvent très capitaliste, est difficile à appréhender. / In former and modern societies, health has been and still is a crucial concern. It is the sign of the community’s and the individual’s well-being. In the setting of access to health that is a right for all, the drug has an important place in France and in Japan, which are countries where life expectancy and level of life are high and keeps on increasing. It is in consideration of this, that we are asking ourselves, through this thesis, about the drug user's right place in drug regulation in France and Japan which are countries different by their culture but sometimes converging in law.We can validly hold up that a good health system can be recognized by the level of protection given to the drug user. But this is not so easy because various interests are at stake. It is important to know how these kinds of conflicts are solved in drug law: is it human or science which is protected? If we can hold up that the protection of the "scientific human" exists, we have to research the reality of the existence of rules insuring a “more human” science. We know and it has been said that the field of health, emotional, individualistic, structured in strong lobbies and often capitalistic, is very difficult to comprehend.

En décembre 2012, une controverse sur les risques accrus de thrombose veineuse profonde associés aux pilules contraceptives dites de nouvelles générations éclate en France. Cette controverse conduit à l’expression d’une critique à l’égard de la pilule en France, érigée jusqu’alors comme symbole de l’émancipation féminine. Près d’une femme sur cinq abandonne la pilule au profit d’autres méthodes, déstabilisant le modèle contraceptif français centré sur la promotion de ce contraceptif. Malgré son intensité, la controverse est tardive. Dès 1995, les risques associés avaient été identifiés dans de nombreux pays européens, dont le Royaume-Uni.Cette thèse cherche à comprendre le confinement des risques pendant près de vingt années en France. Elle s’appuie sur une enquête par entretiens semi-directifs (n=74) conduits auprès d’acteur·rice·s français·es et européen·ne·s de la contraception, complétée par une analyse des archives du Ministère de la Santé et par une revue de la littérature scientifique et institutionnelle. L’analyse de la controverse britannique de 1995 apporte un éclairage sur les spécificités de la situation française.L’analyse de cette controverse permet de retracer les politiques contraceptives françaises des années 1980 à nos jours. Cette histoire met en évidence la structuration d’un espace de la contraception construit autour d’un schéma hormonal et genré d’appréhension des corps reproducteurs. Il fait apparaître le rôle central des laboratoires pharmaceutiques et l’influence importante de la gynécologie médicale en France. Ces éléments permettent de mieux comprendre la minimisation des risques associés aux contraceptifs hormonaux en France.Outre les stratégies de dissimulation du risque, la trajectoire de cette controverse témoigne aussi d’une division sexuelle du risque, notamment en matière de régulation du médicament. De nombreux travaux ont documenté les effets de la (bio)médicalisation de la contraception sur sa féminisation. Rares sont ceux qui proposent une analyse de la régulation du médicament en général et des contraceptifs en particulier dans une perspective de genre. Les logiques scientifiques, institutionnelles et politiques de définition, mesure et traitement du risque médicamenteux se sont pourtant construites autour d’une appréhension genrée des corps féminin et masculin. La controverse de 2012-2013 met en lumière une distinction et un partage inégal du risque contraceptif entre les sexes, une asymétrie qui repose sur l’essentialisation du travail contraceptif et reproductif. / In December 2012, a controversy broke out in France over the increased risks of deep vein thrombosis associated with new generation contraceptive pills. This controversy led to the expression of an intense criticism of the pill in France, which until then had been a symbol of female emancipation. Nearly one in five women thus dropped the pill in favor of other methods. This has destabilized a French contraceptive model focused on the promotion of the pill. Despite its intensity, this controversy happened in France with quite a delay. As early as 1995, the associated risks had been identified in many other European countries, including the United Kingdom.The aim of this research is to understand the ignorance of these risks in France for nearly twenty years. It is based on interviews (n=74) conducted with French and European actors committed in birth control. An analysis of the Ministry of Health’s archives and a review of the scientific and institutional literature have also been led. The analysis of the 1995 British controversy sheds light on the specificity of the French situation.The analysis of this controversy leads to describe the contraceptive policies from the 1980s to the present days. It reveals how the contraceptive space has been structured around a hormonal and gendered perception of the reproductive bodies. This analysis highlights the central role played by the pharmaceutical companies but also by medical gynecology in France. These first results help to better understand the minimizing of risks associated with hormonal contraceptives in France.The trajectory of this controversy shows more broadly a sexual division of risk, especially in matters of drugs regulation. Many studies have depicted how the (bio)medicalisation of birth control has led to its feminization. But few offer a gender analysis of drugs regulation in general and contraceptives regulation in particular. The scientific, institutional and political logics of definition, evaluation and handling of drugs risks are nevertheless embedded in a gendered perception of female and male bodies. The 2012-2013 controversy reveals the distinction and unequal sharing of contraceptive risks between sexes, an inequality that also relies on an essentialism of contraceptive and reproductive work.

The Amphetamine Years is a history of psychostimulant drugs and their clinical applications in post-World War II American medicine. Comprising such well-known substances as the amphetamines (Benzedrine, Dexedrine), methylphenidate (Ritalin), and phenmetrazine (Preludin), this class of pharmaceuticals has been among the most widely consumed in the past half-century. Their therapeutic uses for a variety of indications such as depression, obesity, and attention-deficit/hyperactivity disorder (ADHD) in children, not to mention their relevance for a number of different medical specialties, reveals that psychostimulants have occupied an important, if underappreciated role in the practice of modern medicine. In this dissertation, I illuminate the various ways in which physicians, particularly psychiatrists, put these drugs to work in clinical practice. In short, I contend that physicians exploited the wide range of physiological and psychological effects of psychostimulants and made a place for them in different therapeutic settings, even ones characterized by competing views and theories about the workings of the human body and mind. My dissertation is distinguished by two prominent themes. First, I emphasize the clinician perspective as a vehicle for understanding the history of the psychostimulants, as well as related developments in psychiatry, pharmacotherapy, and the political economy of drugs, in the second half of the twentieth century. Scholars such Nicolas Rasmussen, David Courtwright, and Ilina Singh have elucidated the history of psychostimulants by emphasizing how pharmaceutical companies positioned their products in the medical marketplace. My dissertation takes a different, yet complimentary approach by studying clinicians, themselves, to further historical comprehension of the place of these pharmaceuticals within postwar medicine, society, and culture. Second, I advance the concept of "therapeutic versatility" to explain their historical trajectories. The complex set of psychological and physical effects these drugs produced made them ideal for a diverse range of therapeutic applications, which explains why they were embraced by many different medical specialties, why they were marketed by manufacturers for a variety of indications, and why they have enjoyed an enduring therapeutic lifespan, in spite of increasing efforts since the mid-1960s to regulate their availability and control their consumption. In addition to these two overarching themes, I advance five specific arguments in my dissertation. First, I contend that pharmaceutical markets were simultaneously created by the drug industry and clinicians. Pharmaceutical firms' efforts to develop markets for their products have been well documented by historians, but in my dissertation, I underscore the role also played by clinicians in discerning drugs' applications. Second, I argue that twentieth-century psychiatry's conception of illness and therapeutics may not be served best by strictly dividing its history along lines of institutional and outpatient treatment. Third, I demonstrate how the use of psychostimulants by analytically oriented psychiatrists during the 1950s complicates historical notions of paradigm shift from a psychodynamic to biological orientation. Psychotherapy and psychopharmacology were not competing paradigms; in practice, doctors often employed both. Fourth, I assert that an appreciation of psychiatrists' empirical and eclectic approaches to the use of drugs is necessary to comprehend the rise of psychiatric pharmacotherapy in the postwar era. Finally, I contend that in order to understand the relationship between medical applications of psychostimulants and their extramedical consumption, it is necessary to conceive of a plurality of distinct "amphetamine cultures," each characterized by a unique set of relationships between physician-prescribers, patient-consumers, pharmaceutical firms, and political authorities.

Pharmaceutical drugs are often hailed as the poster child for the proposition that patents foster accelerated rates of innovation. This sentiment stems, in large part, from the significantly high research and development (R&D) costs endemic to the pharmaceutical sector. I argue that if the role of the patent regime is one of fostering higher amounts of investment in the R&D process, it is better served by a direct investment protection regime, where the protection does not depend upon whether or not the underlying idea behind the drug is 'new' and 'inventive', the two central tenets of patent law. Rather, any drug that successfully makes it past the regulatory filter ought to be entitled to protection, since its discovery and development entail significant investment and risk. Owing to the inadequacy of the current patent regime in appropriately protecting intensive pharmaceutical R&D investments from free-riders, I propose a comprehensive investment protection regime that protects all the investment costs incurred during the drug discovery and development process. Though similar to existing data protection regimes in some respects, it differs in others. Firstly, it enables a recovery of all R&D costs, and not only costs associated with clinical trials. Secondly, unlike patents and data exclusivity which offer uniform periods of protection, it rewards investments in a proportionate manner, wherein drug originators are entitled to protection against free-riders only until such time as they recoup their specific investments and earn a rate of return on investment that is dependent on the health value of the drug. Given that a pure market exclusivity based investment protection regime is likely to foster excessive pricing and subject the market to the dictates of a single firm, I advocate a compensatory liability model based on a novel cost sharing methodology, where follow-on entrants are free to manufacture the drug, but must pay a reasonable amount of compensation to the originator.