Le prix, le coût et la valeur de l’insuline David Beran MSc PhD Service de médecine tropicale et humanitaire

Déclarations d’intérêts Aucun financement de l’industrie pharmaceutique Présentation en mon nom Ne représente pas le point de vue des institutions auxquels je suis affilié

La détermination du prix de l’insuline

L’offre: Domination de trois multinationales Identification de 39 autres fabricants d’insuline Valeur du marché de l’insuline (2012): US$ 20.8 milliards Schultz Novo Nordisk 2011; Etude ACCISS 2016

Domination = détermination des produits sur le marché

Domination = détermination des produits sur le marché (rouge: humaine; bleu: analogue; vert: animale) High Income Upper Middle Income Lower Middle Income Low Income Beran et al. 2016

Liste des médicaments essentiels de l’OMS http://www.who.int/selection_medicines/Complete_UNEDITED_TRS_18th.pdf

Cochrane 2005 - 'Human' insulin versus animal insulin in people with diabetes mellitus A comparison of the effects of human and animal insulin as well as of the adverse reaction profile did not show clinically relevant differences. Many patient-oriented outcomes like health-related quality of life or diabetes complications and mortality were never investigated in high-quality randomised clinical trials. The story of the introduction of human insulin might be repeated by contemporary launching campaigns to introduce pharmaceutical and technological innovations that are not backed up by sufficient proof of their advantages and safety. Our analysis suggests only a minor benefit of short acting insulin analogues in the majority of diabetic patients treated with insulin. Until long term efficacy and safety data are available we suggest a cautious response to the vigorous promotion of insulin analogues. For safety purposes, we need a long-term follow-up of large numbers of patients and well designed studies in pregnant women to determine the safety profile for both the mother and the unborn child. Our analysis suggests, if at all only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2 treated with "basal" insulin regarding symptomatic nocturnal hypoglycaemic events. Until long-term efficacy and safety data are available, we suggest a cautious approach to therapy with insulin glargine or detemir.

Cochrane 2006 - Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus A comparison of the effects of human and animal insulin as well as of the adverse reaction profile did not show clinically relevant differences. Many patient-oriented outcomes like health-related quality of life or diabetes complications and mortality were never investigated in high-quality randomised clinical trials. The story of the introduction of human insulin might be repeated by contemporary launching campaigns to introduce pharmaceutical and technological innovations that are not backed up by sufficient proof of their advantages and safety. Our analysis suggests only a minor benefit of short acting insulin analogues in the majority of diabetic patients treated with insulin. Until long term efficacy and safety data are available we suggest a cautious response to the vigorous promotion of insulin analogues. For safety purposes, we need a long-term follow-up of large numbers of patients and well designed studies in pregnant women to determine the safety profile for both the mother and the unborn child. Our analysis suggests, if at all only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2 treated with "basal" insulin regarding symptomatic nocturnal hypoglycaemic events. Until long-term efficacy and safety data are available, we suggest a cautious approach to therapy with insulin glargine or detemir.

Cochrane 2007 - Long acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus A comparison of the effects of human and animal insulin as well as of the adverse reaction profile did not show clinically relevant differences. Many patient-oriented outcomes like health-related quality of life or diabetes complications and mortality were never investigated in high-quality randomised clinical trials. The story of the introduction of human insulin might be repeated by contemporary launching campaigns to introduce pharmaceutical and technological innovations that are not backed up by sufficient proof of their advantages and safety. Our analysis suggests only a minor benefit of short acting insulin analogues in the majority of diabetic patients treated with insulin. Until long term efficacy and safety data are available we suggest a cautious response to the vigorous promotion of insulin analogues. For safety purposes, we need a long-term follow-up of large numbers of patients and well designed studies in pregnant women to determine the safety profile for both the mother and the unborn child. Our analysis suggests, if at all only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2 treated with "basal" insulin regarding symptomatic nocturnal hypoglycaemic events. Until long-term efficacy and safety data are available, we suggest a cautious approach to therapy with insulin glargine or detemir.

Cochrane 2016 - Short-acting insulin analogues versus regular human insulin for type 1 diabetes mellitus A comparison of the effects of human and animal insulin as well as of the adverse reaction profile did not show clinically relevant differences. Many patient-oriented outcomes like health-related quality of life or diabetes complications and mortality were never investigated in high-quality randomised clinical trials. The story of the introduction of human insulin might be repeated by contemporary launching campaigns to introduce pharmaceutical and technological innovations that are not backed up by sufficient proof of their advantages and safety. Our analysis suggests only a minor benefit of short acting insulin analogues in the majority of diabetic patients treated with insulin. Until long term efficacy and safety data are available we suggest a cautious response to the vigorous promotion of insulin analogues. For safety purposes, we need a long-term follow-up of large numbers of patients and well designed studies in pregnant women to determine the safety profile for both the mother and the unborn child. Our analysis suggests, if at all only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2 treated with "basal" insulin regarding symptomatic nocturnal hypoglycaemic events. Until long-term efficacy and safety data are available, we suggest a cautious approach to therapy with insulin glargine or detemir.

La demande: accroissement de la prévalence du diabète Fédération Internationale du Diabète 2015

Type 1 versus Type 2 Besoin absolu pour le Type 1 Type 2 - 10-25% des patients utilisent de l’insuline (Etude ACCISS 2016) Comment définir le « besoin » pour les Types 2 Qui définit les besoins?

Les résultats: prix de l’insuline à différents points du système de santé Etude ACCISS 2016

Et les pays riches? Langreth 2015 ? compétition In 13 instances since 2009, prices of Lantus and Levemir -- which dominate the global market for long-acting injectable insulin with $11 billion in combined sales -- have gone up in tandem in the U.S., according to SSR Health, a market researcher in Montclair, New Jersey. Langreth 2015

Le coût ou les coûts de l’insuline Le coût de fabrication? La question… Le coût pour qui? Patient Système de santé Pas seulement le coût mais l’abordabilité – un coût accessible Pour quelqu’un en France Pour quelqu’un au Mali

En France Haute Autorité de Santé

Au Royaume-Uni 2000 2008 Dépenses pour l’insuline 2008: € 360 millions 86.3% de l’insuline humaine; 10.7% insuline analogue 2008 23.2% insuline humaine; 76.1% insuline analogue Dépenses pour l’insuline 2008: € 360 millions 51% du budget total des médicaments pour le diabète 4% budget total

Les prix de remboursement = les coûts pour les systèmes de santé

Les coûts pour les individus 2.2% des dépenses totale de la santé en Suisse (1998), ou € 2,710 par personne avec le diabète (Schmitt-Koopmann et al. 2004) Beran et Yudkin 2010

Les résultats: le coût de l’insuline en comparaison à d’autres médicaments Etude ACCISS 2016

La valeur de l’insuline 1922: L’insuline et Leonard Thompson “A new race of diabetics has come upon the scene” – E. Joslin (1922) “Now modern discoveries, particularly insulin, have completely changed the outlook. There is no reason why a diabetic should not if he can be taught to do so, lead a long normal life.” – R.D. Lawrence (1925)

La valeur d’un miracle Insulin era Pre-insulin era Life expectancy (years) Pre-insulin era At age 10 Overall Gale Lancet 2003; USA Today 2011

Une valeur mais pas pout tous Quelle est la cause plus fréquente de décès chez un enfant avec le diabète? La réponse d’une perspective mondiale est le manque d'accès à l'insuline Lancet novembre 2006

Comparaison Boston (1897-1945), Mozambique (2003) et Nicaragua (2007) Insulin era Life expectancy (years) Pre-insulin era At age 10 0-14 Gale 2003; Beran 2005; Beran 2007

Pas seulement les pays pauvres L’autre côté du scandale In the US, insulin discontinuation was the leading precipitating cause of diabetic ketoacidosis, and was responsible for 68% of admissions in a US inner city setting.20 Among those who stopped taking insulin, 27% reported lack of money to buy it and 5% were making their insulin supplies last longer by taking smaller doses.

Les valeurs de l’insuline 1921: la découverte de l’insuline Pas de brevets Mission de sauver des vies

Les valeurs de l’insuline La société comme un tabouret Société civile Secteur privé Mintzberg 2015 Gouvernement

Le secteur privé Innovation? Responsabilité sociale versus marketing Analogues Stylos Protection intellectuelle (Luo and Kesselheim 2016) Responsabilité sociale versus marketing Pas seulement les 3 grands mais aussi les intermédiaires Les Pharmacy Benefit Management Services Les grossistes

Les gouvernements Couverture universelle Rationalisation de l’utilisation des insulines analogues P.ex. Nouvelle-Zélande, Allemagne Réglementation des biosimilaires Réglementation des prix Taxes et autres hausses de prix Financement pour le diabète National International Rôle de l’Organisation Mondiale de la Santé Une seule personne au niveau global pour le dossier diabète

La société civile Lancet September 2012 http://www.idf.org/partners/meet-our-partners/

Rétablir l’équilibre du tabouret Le rôle du secteur privé au sens large Un « business case » pour les pays / patients pauvres Une segmentation du marché Biosimilaires = / ≠ Génériques Les gouvernements Leurs rôles Leurs responsabilités Manque de société civile indépendante Exemple VIH Equité

Rétablir l’équilibre du tabouret Aussi Le rôle des médecins Vision de mon patient versus du système de santé Les conflits d’intérêts Le rôle des Universitaires Recherche – faire avancer la science / réalité des besoins La voix critique Le rôle des patients / individus Utilisateur du système de santé / médicaments Membre de la société

Questions? David.Beran@unige.ch http://haiweb.org/what-we-do/acciss/ Merci Questions? David.Beran@unige.ch http://haiweb.org/what-we-do/acciss/