Recommendations from the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL)

International audienceAbstractRare diseases are an important public health issue with high unmet need. The introduction of the EU Regulation on orphan medicinal products (OMP) has been successful in stimulating investment in the research and development of OMPs. Despite this advancement, patients do not have universal access to these new medicines. There are many factors that affect OMP uptake, but one of the most important is the difficulty of making pricing and reimbursement (P&R) decisions in rare diseases. Until now, there has been little consensus on the most appropriate assessment criteria, perspective or appraisal process. This paper proposes nine principles to help improve the consistency of OMP P&R assessment in Europe and ensure that value assessment, pricing and funding processes reflect the specificities of rare diseases and contribute to both the sustainability of healthcare systems and the sustainability of innovation in this field. These recommendations are the output of the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL), a collaboration between rare disease experts, patient representatives, academics, health technology assessment (HTA) practitioners, politicians and industry representatives. ORPH-VAL reached its recommendations through careful consideration of existing OMP P&R literature and through a wide consultation with expert stakeholders, including payers, regulators and patients. The principles cover four areas: OMP decision criteria, OMP decision process, OMP sustainable funding systems and European co-ordination. This paper also presents a guide to the core elements of value relevant to OMPs that should be consistently considered in all OMP appraisals. The principles outlined in this paper may be helpful in drawing together an emerging consensus on this topic and identifying areas where consistency in payer approach could be achievable and beneficial. All stakeholders have an obligation to work together to ensure that the promise of OMP’s is realised

Rethinking representation as delegation in the framework of communalist direct democracy

The political theory of communalism as formulated by Murray Bookchin asks anew two correlated questions: that of the main political unit for a people to govern itself, and that of how public power should be exercised. It answers by advocating for the commune to be the main political unit, in order to realize direct democracy. Indeed, communalism sees the municipality as the locus where communities would collectively manage their own affairs through popular assemblies. To decide on issues going beyond the scope of the municipality, these self-governed municipalities would organize in confederations, where each assembly would send delegates with imperative and recallable mandates to administer the policies formulated by them. As such, to enable decision-making across assemblies these delegates endorse a task of representation, in the generic definition of Pitkin of “making present that which is absent”, since they make present the will of the absent popular assembly at the confederal level through the imperative mandate. However, this conception of representation is radically different than the one of representative government. This paper intends to capture how decision-making could happen across assemblies and to rethink what representation would mean in a communalist framework. To this end, I first develop the main concepts of the theory of direct democracy proposed by communalism, that I call communalist direct democracy: the continuous assembly of the people to exercise all public power (political and economic), and the delegation, or direct representation, of such power when it can no longer be assembled. Second, I propose solutions to ease the tension between delegation through imperative mandates and decision-making across assemblies

Key Indexing Terms: POLYARTERITIS NODOSA VISCERAL HEMATOMA Personal, non-commercial use only

P e r s o n a l n o n -c o m m e r c i a l u s e o n l y . T h e J o u r n a l o f R h e u m a t o l o g y . C o p y r i g h t © 2 0 0 4 . A l l r i g h t s r e s e r v e d The Paris, Cochin Hospital, Paris, France; and Department of Rheumatology, Bulgarian Medical Academy, Sofia, Bulgaria. Y. Allanore, MD; C. Rosenberg, MD, Department of Rheumatology; O. Vignaux, MD, PhD; P. Legmann, MD, PhD, Department of Radiology, Cochin Hospital; K. Kanev, MD, Rheumatology Clinic, Bulgarian Medical Academy; C.J. Menkes, MD; A. Kahan, MD, PhD, Department of Rheumatology, Cochin Hospital. Address reprint requests to Dr. Y. Allanore, Hôpital Cochin, Service de Rhumatologie A, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France. E-mail: [email protected] Submitted December 29, 2003; revision accepted March 24, 2004. Polyarteritis nodosa (PAN) is a rare disease characterized by necrotizing vasculitis of small and medium size arteries 1 . The clinical symptoms that usually reveal PAN are neuritis, arthralgia, myalgia, cutaneous lesions, orchitis, and abdominal pain 2 . Prompt diagnosis is important because PAN can be life-threatening: severe organ manifestations include congestive heart failure, cerebrovascular events, gastrointestinal (GI) tract hemorrhage, and malignant hypertension. We describe a patient with an unusual presentation of PAN, revealed by successive spontaneous visceral hematomas involving the kidneys, bladder, and liver. CASE REPORT A 28-year-old Bulgarian man was admitted to our department for exploration of repeated spontaneous hematomas. Symptoms began in March 2000, with isolated, violent lumbar pain, and no decline in general health status. Ultrasound and computed tomography (CT) scans revealed a left perinephritic hematoma. Surgery was performed. Pathological analysis confirmed the diagnosis and identified no other abnormality. The pain disappeared with standard analgesic treatment, and he resumed all regular activities. One year later, he suffered the same symptoms, with right kidney involvement, and the same course. In June 2001, he suffered spontaneous bleeding of the bladder, as revealed by macroscopic hematuria, with no renal insufficiency. This bleeding stopped spontaneously within a few days. One year later, he reported spontaneous pain in the right upper abdominal quadrant, and CT scan revealed the presence of a hematoma in the liver. Investigations over this 2-year period revealed no coagulation or immunological abnormalities, but biological examinations showed repeated signs of transient inflammation with increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Histological analysis of a kidney sample removed during surgery revealed no inflammatory disease, specific infiltration, or vessel abnormalities other than hematoma. By the time of admission to our hospital in March 2003, our patient had lost 20 kg over 2 years (weight 58 kg; height 1.75 m); he had had fever and abdominal pain for 4 days. On physical examination, he was pale and sweating. His blood pressure was 130/80 mm Hg, pulse 100/min, and temperature 38.8°C. Diffuse tenderness was noted on abdominal pressure, without palpable abnormality. Neurological and cardiopulmonary examinations were normal. Laboratory investigations gave the following results: white blood cell count 14,000/mm 3 , ESR 74 mm/h, CRP 240 mg/l (normal < 5 mg/l), hemoglobin concentration 12.6 g/dl, aspartate aminotransferase 402 IU/l, alanine aminotransferase 648 IU/l, creatininemia 67 µmol/l, and absence of proteinuria. Hemostasis test results: prothrombin time 104%, activated partial thromboplastin time 40 s (normal = 40 ± 5), lupus anticoagulant absent; and factor VIII, IX, and von Willebrand levels were normal. Blood cultures, urinalysis, and tests for tuberculosis (skin test and gastric culture), human immunodeficiency virus, hepatitis C virus, and hepatitis B virus (last generation ELISA tests) were negative. No autoantibodies, including antinuclear, anti-dsDNA, antiphospholipid, antiextractible nuclear antigens, antineutrophil cytoplasmic antibodies, rheumatoid factor, or cryoglobulinemia were detected. Thoracic and abdominal radiographs, electrocardiogram, and echocardiography results were normal. Thoracoabdominal CT scan showed 2 recent intrahepatic hematomas, visible as spontaneous hyperdensity lesions DISCUSSIO

Evaluation of the usefulness of six commercial agglutination assays for serologic diagnosis of toxoplasmosis.

International audienceSix agglutination tests for detecting Toxoplasma gondii-specific antibodies (immunoglobulin G or M) in serum were performed and compared. In total, 599 sera were examined using direct and indirect agglutination assays. Sensitivity varied from 93.7% to 100% and specificity from 97.1% to 99.2%. In a selected population with interfering diseases, the percentage of false positives ranged from 4.3% to 10.9%. Although an overall agreement of 100% was found for chronic toxoplasmosis, sensitivity for the detection of confirmed acute toxoplasmosis ranged from 86.4% to 97.3%. Regarding the large variability in terms of the performance of the 6 assays, tests based on the hemagglutination principle were found to be better than the other agglutination tests for all the panels evaluated, meaning that they could be used as qualitative or semiquantitative low-cost screening assays