Hurdles and delays in access to anti-cancer drugs in Europe.

Demographic changes in the world population will cause a significant increase in the number of new cases of cancer. To handle this challenge, societies will need to adapt how they approach cancer prevention and treatment, with changes to the development and uptake of innovative anticancer drugs playing an important role. However, there are obstacles to implementing innovative drugs in clinical practice. Prior to being incorporated into daily practice, the drug must obtain regulatory and reimbursement approval, succeed in changing the prescription habits of physicians, and ultimately gain the compliance of individual patients. Developing an anticancer drug and bringing it into clinical practice is, therefore, a lengthy and complex process involving multiple partners in several areas. To optimize patient treatment and increase the likelihood of implementing health innovation, it is essential to have an overview of the full process. This review aims to describe the process and discuss the hurdles arising at each step.

Controversial issues in early-stage breast cancer: a global collaborative survey, supported by the European Society for Medical Oncology (ESMO).

BACKGROUND: To explore the current clinical management of early-stage breast cancer (BC) patients, identify areas of controversy, and interrogate how treating physicians implement latest advances. METHODS: We conducted a 27-item survey, disseminated in two stages: paper distribution at selected BC sessions at the ESMO 2012 Congress, and dedicated mailings to ESMO members. Descriptive statistical analysis and logistic regression analysis were applied to explore potential associations between the demographic characteristics of the participants and replies. RESULTS: A total of 512 physicians from 79 countries participated in the study, accounting for 465 (91%) fully completed questionnaires. The majority of the participants were ESMO members (66%), medical oncologists (86.5%), and working in multidisciplinary teams (91.6%). Heterogeneous results were captured, such as the following: 40.9% of the participants consider no genetic test useful for making adjuvant treatment decisions; 15.3% consider PET-CT a useful imaging modality for staging; 68.8% consider that postmenopausal patients with hormone receptor positive disease should always be offered an aromatase inhibitor as part of their adjuvant therapy; 78.7% prefer to administer trastuzumab concurrently with the taxane component of chemotherapy; and 27% would consider bevacizumab in the neoadjuvant setting. The logistic regression analysis did not identify any strong predictor of the probability of giving a reply fully compatible with evidence in the literature. CONCLUSION: This survey captures clinical practice and whether the latest research advances are implemented in the treatment of early-stage BC by an extended number of physicians. Significant individual differences were found. Areas of controversy were detected, and they deserve further exploration in order to generate 'tailored' educational tools, with the final goal being the standardization of the treatment of early-stage BC patients.

Discrepancies in cancer incidence and mortality and its relationship to health expenditure in the 27 European Union member states.

BACKGROUND: The European Union (EU) is a confederation of 27 member states, the institutions of which work according to negotiated decisions. The EU has implemented similar legislation and a common market, and has adopted the same currency in most of its member states. Although financing health systems is a responsibility of the national governments, the EU has enacted the Charter of Fundamental Rights to standardize public health policies. However, for historical reasons, health policy and health expenditure is not uniform across the 27 EU member states (EU-27). MATERIAL AND METHODS: We hypothesized that increased health expenditure would be associated with better cancer outcome and that this would be most apparent in breast cancer, because of the availability of effective screening methods and treatments. Using publically available data from the World Health Organization, the International Monetary Fund, and the World Bank, we assessed associations between cancer indicators and wealth and health indicators. To do so, we constructed scatter plots and used the Spearman's rank correlation coefficient. RESULTS: A marked difference in wealth and health expenditure indicators was observed between Eastern and Western European countries, with Western European being the higher. Higher wealth and higher health expenditures were associated both with increased cancer incidence and decreased cancer mortality. In breast cancer, the association with incidence was stronger. We created mortality/incidence ratios and observed that the more spent on health, the fewer the deaths after a cancer diagnosis. CONCLUSION: Despite the initiatives to standardize public health policies of the EU-27, health expenditure continues to be higher in Western European countries and this is associated with better cancer outcome in these countries.

[Anticoagulant (AVK) and antibiotic drug interactions in community practice]. / Intéraction médicamenteuse anti-vitamines K/antibiotiques en médecine de ville.

AIM: Anticoagulants (AVK) are frequently responsible for iatrogenic accidents leading to hospitalisation. Antibiotics (ATB) are likely to interact with AVK. The aim of this study was to assess if Loire region practitioners complied with the French agency for the safety of health products (AFSSAPS) recommendations for AVK/ATB association. METHOD: Two strategies were implemented: a retrospective study of the 2007 Loire region general health insurance data on a population exposed to a single AVK split in two groups, exposed or not to antibiotics; a focus-group of practitioners from the Maine et Loire subdivision. RESULTS: Blood tests were not always performed. The proportion of blood tests per month was significantly more frequent in the AVK/ATB group than in the group "not exposed" to antibiotics. GPs did not implement this recommendation, which doesn't correspond to their behaviour, as analysed by a focus-group, and to the low incidence of hospitalisations due to AVK/ATB interaction. CONCLUSION: Loire region practitioners do not follow AFSSAPS recommendations. AVK/ATB interaction must be a GP's constant concern whether responsible or not for initiating AVK.

[Evaluation of the attitude towards disabled persons of 3rd and 4th year medical students using the "Attitude towards disabled persons" questionnaire. Effect of courses and rotations in physical medicine and rehabilitation departments]. / Evaluation de l'attitude vis-à-vis des personnes handicapées des étudiants en médecine de 3e et 4e année par le questionnaire "Attitude towards disabled persons". Effets de l'enseignement théorique et de stages dans les services de médecine physique et réadaptation.

UNLABELLED: Modifications of the medical curriculum have included a compulsory course on disability. OBJECTIVE: To determine whether attendance in a course on disability and/or rotations in physical medicine and rehabilitation departments modify the attitude of medical students towards disabled people. METHODS: All third- and fourth-year students completed a translated version of the ATDPb. This questionnaire rates items evaluating attitude towards disabled people on a 6-point scale (minimum 0; maximum 180). Retro-translation was performed to control the translation. During the second year, all students had attended a general course in ethics. Fourth-year students had attended a 17 hours course on disability, and 21 of 78 had spent 9 weeks in the physical medicine and rehabilitation department. The study compares fourth-year students to third-year students, considered as controls, and students having spent a rotation in the physical medicine and rehabilitation department to others. RESULTS: The mean score of all students was 108.86+/-15.84 (73-160) on the ATDP scale. Males and females did not differ significantly, and the score did not change from that before the course on disability (109.95+/-14.98 vs 107.6+/-16.65, P=0.23) nor after a rotation in the physical medicine and rehabilitation department (113.52+/-11.42 vs 108.54+/-16.03, P=0.14). CONCLUSION: Development and validation of scores that would fit better to the European cultural context would be useful. The present method of theoretical courses and rotations do not improve the attitude of students towards disabled people and should be modified if this objective is to be achieved.

[Conservative surgery of the mitral valve. Immediate and late results]. / Chirurgie conservatrice de la valve mitrale. Résultats immédiats et à distance.

A consecutive series of 130 cases of pure or predominant mitral regurgitation underwent conservative mitral valve surgery between January 1975 and January 1982. The mean age of the patients was 30 +/- 17 years; 25 patients were under 15 years of age. The most common aetiology was rheumatic fever (112/130). Fifty nine patients had associated valvular lesions requiring surgical correction. The patients were divided into 4 groups, according to the surgical technique: Group I: valvular mobilisation (35 cases); Group II: reduction of the amplitude of valvular excursion (48 cases); Group III: mixed valvular mobilisation and reduction of amplitude of excursion (45 cases); Group IV: isolated annuloplasty (2 cases). Hospital mortality was 2.3% (3 patients). Five patients (3.8%) were lost to follow-up. The mean follow-up period was 38 +/- 27 months for the 122 patients followed-up. Seven patients needed reoperation. The long term mortality was 3.1% (4 patients). Four late thromboembolic episodes were observed; they were all transient and regressive in patients with atrial fibrillation. The 7 year actuarial survival rate for the whole series, including hospital mortality, was 92% (1.0 +/- 0.5 patients/year). It was 93.7 +/- 4.9% at 7 years for isolated mitral valvuloplasty and 89.9% +/- 5.6% at 5 years for combined mitro-tricuspid procedures. The actuarial percentage of patients without thromboembolic complications was 91.2% at 7 years with a thromboembolic risk of 1.0 +/- 0.5% patients/year. Eighty eight per cent of patients were not reoperated at 7 years and the reoperation rate was 1.7 +/- 0.7% patients/year.(ABSTRACT TRUNCATED AT 250 WORDS)

[Role of peri-operative treatment in the surgery of advanced valvular cardiopathies]. / Rôle du traitement péri-opératoire dans la chirurgie des cardiopathies valvulaires évoluées.

Between January 1981 and October 1982, 100 consecutive patients with valvular heart disease (49 p. 100 polyvalvular disease) underwent surgery. All had severe lesions; Class III or IV of the NYHA classification; cardiomegaly with an average cardio-thoracic ratio of 59 +/- 7.7 p. 100; a cardiac index of less than 2.5 1/min/m2 in 70 p. 100 of cases; pulmonary hypertension (mean PAP : 31.93 +/- 12.17 mmHg) in 89 p. 100 of cases. Half the patients were in atrial fibrillation and all had been on chronic digitalo-diuretic therapy before surgery. Thirty of the 41 patients given preoperative venous vasodilator therapy had significant reductions of their cardiothoracic ratios (63 +/- 1.5 p. 100 vs 59.1 +/- 1.6 p. 100, p less than 0.001). Conservative surgical procedures were possible in 58 cases of mitral valvuloplasty and 5 aortic valvuloplasties. Correction of functional tricuspid regurgitation (34 p. 100) was systematic. Tricuspid regurgitation masked by salt and water depletion was detected by digital palpation after clamping the pulmonary artery. In 8 cases the aortic ring had to be enlarged. The low hospital mortality (6 p. 100) and the lack of postoperative complications (assisted ventilation for less than 24 hours in 92 p. 100 of cases) compare favourably with other reported series.

Transposition of posterior leaflet for treatment of ruptured main chordae of the anterior mitral leaflet.

A 13-year-old girl with mitral regurgitation resulting from rupture of multiple chordae of the anterior leaflet had repair by transposition of a part of the posterior leaflet to the free edge of the anterior mitral cusp. Postoperative clinical hemodynamic, and angiographic studies showed perfect function of the mitral valve. This technique seems to be a good solution for mitral repair in the presence of ruptured anterior mitral chordae.

[Aortic valve replacement by bioprosthesis with enlargement of the aortic ring]. / Remplacement valvulaire aortique par bioprothèse avec élargissement de l'anneau aortique.

Small diameter aortic valve bioprostheses are associated with resting ventriculo-aortic pressure gradients of 10 to 35 mmHg. In order to avoid this factor favouring degradation of left ventricular function and early deterioration of the bioprosthesis, we enlarged the aortic ring when the diameter was less than 23 mm in patients considered unsuitable for long-term anticoagulation. The surgical technique involved incising the annulus from the postero-lateral commissure to the anterior mitral leaflet and implanting a Dacron patch lined with pericardium. Nine patients aged from 10 to 70 years (average 22 years) underwent aortic valve replacement with a Carpentier-Edwards bioprosthesis associated with enlargement of the aortic ring, between June 1979 and December 1981. The mean follow-up period is now 18 months (range 9 to 39 months). One patient has been lost to follow-up. Before surgery, 6 patients were in Stage III and 3 patients in Stage IV of the NYHA classification. There were 4 patients with pure aortic regurgitation with valve prolapse, 1 patient with aortic regurgitation due to endocarditis, and 4 patients with mixed aortic valve disease. The underlying disease was rheumatic in 6 cases, congenital in 2 cases and infective endocarditis in 1 case. The mean diameter of the aortic ring before enlargement was 19 mm. After the procedure, it increased to 23,8 mm, so enabling the implantation of no 23 and no 25 bioprostheses. Three patients had associated mitral regurgitation, 3 patients had mixed mitral valve disease, 1 patient had a membranous VSD with infundibular stenosis, and 1 patient had subvalvular aortic stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitral reconstructive operations. A series of 130 consecutive cases.

Between January, 1975, and January, 1982, 130 patients underwent mitral valvuloplasty for pure or predominant mitral insufficiency. Mean age at operation was 30 +/- 17 years. Twenty-five patients were under 15 years of age. Mitral insufficiency was mainly (112/130) due to rheumatic disease. Fifty-nine patients (45.4%) had another diseased valve which necessitated a surgical correction (tricuspid in 36 and aortic in 23). Surgical technique for mitral valvuloplasty varied according to the lesions. Three patients died in the first month after operation (2.3%). Five patients are lost to follow-up. The mean follow-up period for the 122 remaining patients is 38 +/- 27 months. Seven patients required reoperation and three of them died. An additional patient died without reoperation. Therefore, the late mortality was 3.1% (4/122). Almost all (116/118) of the remaining patients are in Class I (105) or II (11) of the New York Heart Association. Mean cardiothoracic ratio decreased from 60.6% +/- 7.7% preoperatively to 53.7% +/- 6.2% postoperatively (p less than 0.001). Thromboembolic episodes were noted in four patients, all of them in atrial fibrillation. Actuarial curves including hospital mortality showed a 92.0% survival rate at 7 years for the overall series (1.0% +/- 0.5%/patient-year), 93.7% +/- 4.9% at 7 years for isolated mitral reconstruction and 89.9% +/- 5.6% for mitral-tricuspid valvuloplasty at 5 years. The embolism-free rate at 7 years was 91.2%, with a rate of thromboembolic episodes of 1.0 +/- 0.5%/patient-year. Eighty-eight percent were free of reoperation at 7 years, with a rate of reoperation of 1.7 +/- 0.7%/patient-year. This system of mitral repair can provide stable functional results, low surgical and late mortality, and an acceptable rate of reoperation.