Enquête de cohorte et analyse multivariée : une analyse épistémologique et historique du rôle fondateur de l'étude de Framingham

International audienceBackground: Begun in 1947 and still ongoing, the epidemiological study of heart disease known as the Framingham study was one of the first prospective studies based on a large cohort and has rapidly been considered as the prototype and model for the cohort study. Nevertheless, an examination of its history reveals that the protocol does not at all correspond to today's standards for this type of study. How, then, can we account for the remarkable reputation of this study? Methods: This paper consists in an epistemological and historical analysis of the Framingham study that provides some of the answers to this question. In my treatment of the study's methodology, I focus on the issue of how the study population was constituted, and the manner in which the multiple factor analyses were conducted, two issues that are now central to cohort studies and more generally to analytic epidemiology. Results: I show how the study population of Framingham and its long-term follow-up have contributed significantly to the interpretation of the cohort as a sort of "population-laboratory". The data generated by this study, which have been very widely used by epidemiologists and other researchers, are unparalleled in terms of the amount of detailed clinical information available for such a long follow-up period. Furthermore, multivariate statistical modelling, which has become a standard statistical tool for clinical as well as epidemiological studies was introduced in the context of this study to improve the identification of significant factors in the simultaneous analysis of multiple correlations. Multivariate analysis has since proved crucial in shaping the epidemiological concept of "risk factor" and in analysing multifactorial diseases. Indeed, I suggest that the modern idea of multifactorial diseases depends on the adaptation of this statistical method. Conclusion: Thus, the Framingham study played a leading role not only in remodelling epidemiology after Second World War, in particular because of its contribution to the establishment of the cohort study as a standard method of investigation in etiological research, but also in constituting the "risk factor approach" to disease.Position du problème : Commencée en 1947, l'enquête épidémiologique dite " de Framingham " sur les maladies coronariennes dure encore aujourd'hui. Elle est habituellement considérée comme l'une des premières grandes enquêtes prospectives de cohorte et comme constituant son prototype. Pourtant, si l'on se penche sur son histoire, son protocole d'étude est bien loin de correspondre aux exigences attribuées aujourd'hui à ce type d'enquête. Comment dès lors expliquer cette renommée ? Méthodes : Cet article de nature épistémologique et historique propose d'apporter quelques éléments de réponse à cette question, principalement à partir de l'analyse de la méthode de l'enquête. Nous nous limitons à deux aspects devenus aujourd'hui fondamentaux pour ce protocole d'étude : la constitution de la cohorte et l'analyse des corrélations multiples. Résultats : Nous montrons que, d'une part, la population d'étude et son suivi ont conduit à faire de la cohorte de Framingham une sorte de " population laboratoire ". Ces données, très sollicitées pour diverses analyses, n'ont pas d'équivalent par leur durée et leur précision clinique. D'autre part, c'est à l'occasion des analyses de corrélations réalisées pour cette étude que les modèles statistiques multivariés furent introduits et adaptés à l'épidémiologie. Ces modèles ont été déterminants pour la constitution de la notion épidémiologique de " facteur de risque " et l'analyse de l'origine multifactorielle des maladies. En effet, il nous semble que la conception moderne de la multifactorialité des maladies est tributaire de l'usage de cette méthode statistique. Conclusion : Ainsi, au milieu du xxe siècle, l'étude de Framingham est bien une enquête fondatrice à cause de sa contribution à l'émergence du rôle nouveau de l'enquête de cohorte dans la recherche étiologique et à la constitution d'une " approche facteurs de risque " de la maladie

Qu’est-ce que la « sante de la population »?

La noción de salud pública parece presuponer la salud de la población. Ahora bien, el concepto de salud está más fácilmente utilizado a nivel de la individualidad orgánica: su aplicación a una población o a un colectivo parece problemática a primera vista. Desde luego, se hace necesario reflexionar sobre este concepto de salud de la población que, sin embargo, nosotros utilizamos. Si el análisis filosófico de los conceptos de salud y enfermedad se ha concentrado sobre los usos de estos a niveles individuales e infra-individuales, aquí queremos mostrar la importancia de una reflexión sobre el nivel supra-individual. A partir de desarrollos recientes de la epidemiología contextual o de la epidemiología social, argumentamos sobre la importancia de dar un contenido al concepto de salud de la población que haga de él algo más que una extensión por analogía del concepto de salud individual o de la suma de todos los casos de salud individual

Putting the exposome into practice: an analysis of the promises, methods and outcomes of the European Human Exposome Network

Objectives Contemporary research on the exposome, i.e. the sum of all the exposures an individual encounters throughout life and that may influence human health, bears the promise of an integrative and policy-relevant research on the effect of environment on health. Critical analyses of the first generation of exposome projects have voiced concerns over their actual breadth of inclusion of environmental factors and a related risk of molecularization of public health issues. The emergence of the European Human Exposome Network (EHEN) provides an opportunity to better situate the ambitions and priorities of the exposome approach on the basis of new and ongoing research. Methods We assess the promises, methods, and limitations of the EHEN, as a case study of the second generation of exposome research. A critical textual analysis of profile articles from each of the projects involved in EHEN, published in Environmental Epidemiology, was carried out to derive common priorities, innovations, methodological and conceptual choices across EHEN and to discuss it. Results EHEN consolidates its integrative outlook by reinforcing the volume and variety of data, its data analysis infrastructure and by diversifying its strategies to deliver actionable knowledge. Yet data-driven limitations severely restrict the geographical and political scope of this knowledge to health issues primarily related to urban setups, which may aggravate some socio-spatial inequalities in health in Europe. Conclusions The second generation of exposome research doubles down on the initial ambition of an integrative study of the environmental effects of health to fuel better public health interventions. This intensification is, however, accompanied by significant epistemological challenges and doesn’t help to overcome severe restrictions in the geographical and political scope of this knowledge. We thus advocate for increased reflexivity over the limitations of this conceptually and methodologically integrative approach to public and environmental health

Reuniting philosophy and science to advance cancer research

Cancers rely on multiple, heterogeneous processes at different scales, pertaining to many biomedical fields. Therefore, understanding cancer is necessarily an interdisciplinary task that requires placing specialised experimental and clinical research into a broader conceptual, theoretical, and methodological framework. Without such a framework, oncology will collect piecemeal results, with scant dialogue between the different scientific communities studying cancer. We argue that one important way forward in service of a more successful dialogue is through greater integration of applied sciences (experimental and clinical) with conceptual and theoretical approaches, informed by philosophical methods. By way of illustration, we explore six central themes: (i) the role of mutations in cancer; (ii) the clonal evolution of cancer cells; (iii) the relationship between cancer and multicellularity; (iv) the tumour microenvironment; (v) the immune system; and (vi) stem cells. In each case, we examine open questions in the scientific literature through a philosophical methodology and show the benefit of such a synergy for the scientific and medical understanding of cancer

Reuniting philosophy and science to advance cancer research

Cancers rely on multiple, heterogeneous processes at different scales, pertaining to many biomedical fields. Therefore, understanding cancer is necessarily an interdisciplinary task that requires placing specialised experimental and clinical research into a broader conceptual, theoretical, and methodological framework. Without such a framework, oncology will collect piecemeal results, with scant dialogue between the different scientific communities studying cancer. We argue that one important way forward in service of a more successful dialogue is through greater integration of applied sciences (experimental and clinical) with conceptual and theoretical approaches, informed by philosophical methods. By way of illustration, we explore six central themes: (i) the role of mutations in cancer; (ii) the clonal evolution of cancer cells; (iii) the relationship between cancer and multicellularity; (iv) the tumour microenvironment; (v) the immune system; and (vi) stem cells. In each case, we examine open questions in the scientific literature through a philosophical methodology and show the benefit of such a synergy for the scientific and medical understanding of cancer

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

La controverse santé-radiofréquences : la science face à l'incertitude et à la partialité

For a decade now, the potential health risks of mobile phone use and more generally, exposure to radiofrequencies have been a very controversial subject. The core of this debate is our uncertainly about the risks entailed by ubiquitous but low-level exposure to the electromagnetic spectrum emitted by telecommunication technologies. The analysis of the health risks from this kind of exposure is very complex; and it divides experts and activists, and even experts among themselves. This paper, which adopts simultaneously a historical and epistemological perspective, shows that this controversy highlights the complexity and ambivalence of how we deal with the uncertainty of environmental risks. The analysis of the institutional and political responses to this debate in France shows the shifts in expert opinion that have followed it. This paper argues that it is essential to reevaluate our view on the links between science and uncertainty if we are to overcome some of the challenges of this kind of controversy.La relation entre la santé et l'usage du téléphone mobile, et plus généralement, les radiofréquences, est depuis une dizaine d'années l'objet d'un très vif débat. Comme souvent, l'incertitude dans laquelle nous sommes sur les risques encourus par une exposition environnementale, dont les niveaux sont faibles mais omniprésents, fait le lit de cette controverse. L'évaluation du risque pour la santé est ici particulièrement complexe. Elle divise les experts scientifiques et les oppose aux associations. Adoptant un double point de vue historique et épistémologique, cet article montre que cette controverse est révélatrice de rapports complexes que nous entretenons avec l'incertitude face au risque environnemental. Il propose une analyse des tentatives de réponses institutionnelles et politiques apportées en France et met en évidence défendons l'importance de renouveler notre regard sur les relations entre science et incertitude pour dépasser certaines impasses de ce genre de débats

Conceptions of the Normal and the Pathological

International audienc

N'y a-t-il de santé que de l'individu ?

Quand on parle de santé ou de maladie, c'est généralement à des individus que l'on se réfère. Pourtant, la notion de "santé publique" pourrait bien impliquer celle de "santé d'une population". Dans cet article, nous proposons d'examiner si la santé peut être la propriété d'autres entités que les individus et, plus précisément, de considérer les arguments pouvant justifier un concept de "santé de la population"

Holisme et réductionnisme en épidémiologie et la question de la continuité entre santé et maladie

L'importance prise par l'épidémiologie dite "quantitative" dans la construction des savoirs sur la maladie conduit à privilégier l'affirmation d'une continuité entre le normal et le pathologique. Qu'en est-il, dès lors, de la thèse vitaliste et holiste de Canguilhem défendant l'existence d'une différence qualitative ? Nous traitons cette question d'une manière quelque peu détournée en partant non pas du couple continuité/discontinuité ni même du couple qualitatif/quantitatif mais de celui tout/parties, ou plus précisément, holisme/réductionnisme. L'épidémiologie, bien que porteuse d'une modélisation continuiste, a une approche de la maladie qui échappe aux critiques de Canguilhem sur le réductionnisme. Dans le contexte d'une médecine des risques, l'alternative entre une conception continuiste ou discontinuiste des relations entre le normal et le pathologique n'est pas dissociable des objectifs pratiques et du niveau d'organisation auquel on cherche à intervenir