What strategy should France implement for H2020?

The initiation of Horizon 2020--the European Union's 8th Framework Programme for Research and Innovation, allotted a budget of 79 billion euros--provides an opportunity to review France's participation in previous Framework Programmes. Indeed, French participation does not match either its scientific importance or its financial investment. While France contributed 16.5 to 17% of the EU's 7th Framework Programme research budget, its return through the funding of coordinated projects in which French teams are participating stands at around 12.5 to 13%, a shortfall of 600 million euros. Although the situation depends on the type of activity, French participation in clinical research appears to be smaller than that of its neighbours, with fewer responses to European calls for proposals. While France has many assets, which include the assured funding of clinical research, structured thematic networks and the initiation of major national programmes, it suffers from the dilution of resources due to France's regional development policy, the lack of multidisciplinarity and the ignorance of both the medical and scientific community and the institutions to which they belong as to how Horizon 2020 actually works. We propose three types of strategy to encourage proposals for coordinated clinical research projects or projects involving French teams, and to help in the drawing up of applications: Broaden the vision of our children, students and colleagues, helping them to adapt to the globalisation of knowledge throughout their educational and professional lives. Recognise the value of European actions to influence the European landscape and change mentalities. Help and support project initiators by pooling skills within a limited number of expert centres designed to assist them in their funding application. • Broaden the vision of our children, students and colleagues, helping them to adapt to the globalisation of knowledge throughout their educational and professional lives. • Recognise the value of European actions to influence the European landscape and change mentalities. • Help and support project initiators by pooling skills within a limited number of expert centres designed to assist them in their funding application.

Promoting the place of the allied health professions in clinical research.

Clinical research is of major importance to today's society, as scientific evidence is increasingly demanded as a basis for progress, whether this involves developing new healthcare products, improving clinical practice and care protocols or progress in prevention. Clinical research therefore requires professionals who are both experienced and increasingly well trained. Against this background, allied health professionals are becoming involved more and more, both as team members supporting clinical research projects and as managers or coordinators of projects in their own field. Clinical research activities provide an ideal opportunity for continuing professional development. All of this means that the professional skills of the allied health professions and clinical research support professions must be enhanced, their role promoted in the context of lecturer status and in the longer term, their status recognised by the supervisory authorities.

A grading system based on severity of infection to predict mortality in allogeneic stem cell transplant recipients.

BACKGROUND: There is, until now, no prognostic grading system for infections occurring in allogeneic stem cell transplant (SCT) recipients. The aim of this study was to determine the prognostic value of a grading system of infectious complications in predicting death. METHODS: For the purposes of a prospective allogeneic SCT trial, we classified severity of infections in 3 grades according to expected rates of mortality (>or= 60% for grade 3). We prospectively recorded the type and time of occurrence of 440 infectious events in 190 consecutive patients until 6 months after transplant. We used multivariate Cox models with time-dependent covariates to analyze the relationship between the grade of severity of each infectious episode and mortality due or not due to infection, adjusting for possible confounders. RESULTS: Only patients with grade 3 infections had a significantly increased risk of death (P<.0001). The risk was not modified when the occurrence of acute graft-versus-host disease or the dose of IVIg administered were considered. Occurrence of a grade 1 and 2 infection had no additional influence. CONCLUSION: Our grading system identifies the most medically important, life-threatening infections and allow high-risk patients to be identified. We suggest grade 3 infections should be given priority in the evaluation of anti-infectious strategies.

Should immunoglobulin therapy be used in allogeneic stem-cell transplantation? A randomized, double-blind, dose effect, placebo-controlled, multicenter trial.

BACKGROUND: The universal use of prophylactic immunoglobulin in stem-cell transplantation has not been supported by strong evidence of benefit. Results of most trials were reported before effective drugs for cytomegalovirus infection and disease were available, and no trial was placebo controlled. OBJECTIVE: To assess the role and the dose-effect relationship of immunoglobulin in the prophylaxis of complications after allogeneic stem-cell transplantation. DESIGN: Multicenter randomized, double-blind, dose effect placebo-controlled study. SETTING: 19 stem-cell transplantation centers in France. PATIENTS: 200 patients who had allogeneic stem-cell transplantation from HLA-identical sibling donors between 1998 and 2000. INTERVENTION: Immunoglobulin at doses of 50 mg/kg of body weight, 250 mg/kg, or 500 mg/kg weekly from day -7 to day 100 after transplantation or placebo. MEASUREMENTS: Cumulative incidence of infection, graft-versus-host disease, veno-occlusive disease, interstitial pneumonia, and transplantation-related mortality at 6 months; overall survival at 2 years after transplantation. RESULTS: Immunoglobulin had no benefit over placebo; 92% of patients in the pooled immunoglobulin group and 90% of patients in the placebo group had one or more infections (difference, 2 percentage points [95% CI, -8 to 12 percentage points]). Cumulative incidences of interstitial pneumonia, graft-versus-host disease, transplantation-related mortality, and overall survival were similar in patients receiving placebo and those receiving immunoglobulin; no dose-effect relationships were evident. Grade 3 (severe) veno-occlusive disease occurred more frequently as the immunoglobulin dose increased (P = 0.01). CONCLUSIONS: Use of prophylactic immunoglobulin in allogeneic recipients of stem-cell transplant from HLA-identical sibling donors is not recommended.

Predicting the costs of allogeneic sibling stem-cell transplantation: results from a prospective, multicenter, French study.

BACKGROUND: Allogeneic hematopoietic stem-cell transplantation is a widely used, cost-intensive procedure. Our purpose was to estimate costs and determine cost predictors. METHODS: We used data from a prospective French study comparing four doses of immunoglobulins. Resource use of hematopoietic stem-cell transplant recipients during the first 6 months posttransplant, both inpatient and ambulatory costs, in 85 patients from five centers were collected prospectively and costed. Baseline data and clinical events were retrieved. Protocol-driven costs were excluded. Multivariable analysis evaluated the association between costs and patient's pretransplant status and transplant-related complications. Because of the absence of differences in outcome among the four randomization groups, cost data for all patients were pooled. RESULTS: Total costs per patient were the following: mean 76,237 Euros; standard deviation 32,565 Euros; median 69,516 Euros; range 183,758 to 14,761Euros. The major cost driver was hospital days. No association was found between costs and baseline status. The "predictors" of higher costs (adding an average 20,000 Euros/patient) were the occurrence of transplant-related complications: graft-versus-host disease and repeated infections that were unpredictable before transplant in this homogeneous group of patients. CONCLUSION: Our data highlight the discrepancy between the Diagnosis Related Group prospective payment system and actual costs. The actual cost of geno-identical stem-cell transplantation results from posttransplant complications that cannot be predicted prospectively and require ex post cost adjustment.

Intravenous immunoglobulin or high-dose methylprednisolone, with or without oral prednisone, for adults with untreated severe autoimmune thrombocytopenic purpura: a randomised, multicentre trial.

BACKGROUND: Treatment of adults with autoimmune thrombocytopenic purpura (AITP) is based more on individual experience than on results of controlled studies. We compared intravenous immunoglobulin with high-dose methylprednisolone in untreated adults with severe AITP and assessed efficacy of subsequent oral steroids compared with placebo. Primary outcome was number of days with platelet count greater than 50 x 10(9)/L within the first 21 days. METHODS: We did a randomised multicentre trial based on a 232 design. 122 adults with severe AITP (platelet count < or =20 x 10(9)/L) were randomly assigned to receive either intravenous immunoglobulin or high-dose methylprednisolone on days 1-3 (randomisation A), and then to receive either oral prednisone or placebo (randomisation B) on days 4-21. Analysis was by intention to treat. FINDINGS: Six patients were excluded from the analysis. The number of days on which platelet counts were above 50 x 10(9)/L was 18 in 56 patients receiving intravenous immunoglobulin and 14 in 60 receiving high-dose methylprednisolone (p=0.02). Percentage of patients who had platelet counts over 50 x 10(9)/L on days 2 and 5 was 7% and 79%, respectively, in the intravenous immunoglobulin group compared with 2% and 60%, respectively, in the high-dose methylprednisolone group (p=0.04). During the second treatment period, prednisone was more effective than placebo for all short-term endpoints. Patients who received intravenous immunoglobulin and prednisone had platelet count greater than 50 x 10(9)/L for 18.5 days (p=0.005), and those treated with high-dose methylprednisolone and prednisone had this count for 17.5 days. INTERPRETATION: Intravenous immunoglobulin and oral prednisone seems to be more effective than high-dose methylprednisolone and oral prednisone in adults with severe AITP, although the latter treatment is effective and well tolerated.