Multiple Criteria Decision Analysis for HTA across four EU Member States: Piloting the Advance Value Framework.

Multiple Criteria Decision Analysis (MCDA) has emerged as a methodology for Health Technology Assessment (HTA). However, limited empirical evidence is available on its use by decision-makers; where available, it only comes from single-setting exercises, while cross-country comparative studies are unavailable. This study applies the Advance Value Framework (AVF), an MCDA methodology for HTA based on multi-attribute value theory, through a series of case studies with decision-makers in four countries, to explore its feasibility and compare decision-makers' value preferences and results. The AVF was applied in the evaluation of three drugs for metastatic, castrate resistant, prostate cancer (abiraterone, cabazitaxel and enzalutamide) in the post-chemotherapy indication. Decision conferences were organised in four European countries in collaboration with their HTA or health insurance organisations by involving relevant assessors and experts: Sweden (TLV), Andalusia/Spain (AETSA), Poland (AOTMiT) and Belgium (INAMI-RIZIV). Participants' value preferences, including performance scoring and criteria weighting, were elicited through a facilitated decision-analysis modelling approach using the MACBETH technique. Between 6 and 11 criteria were included in each jurisdiction's value model, allocated across four criteria domains; Therapeutic Benefit criteria consistently ranked first in relative importance across all countries. Consistent drug rankings were observed in all settings, with enzalutamide generating the highest overall weighted preference value (WPV) score, followed by abiraterone and cabazitaxel. Dividing drugs' overall WPV scores by their costs produced the lowest "cost per unit of value" for enzalutamide, followed by abiraterone and cabazitaxel. These results come in contrast with the actual country HTA recommendations and pricing decisions. Overall, although some differences in value preferences were observed between countries, drug rankings remained the same. The MCDA methodology employed could act as a decision support tool in HTA, due to the transparency in the construction of value preferences in a collaborative manner.

The relative clinical efficacy of trametinib-dabrafenib and cobimetinib-vemurafenib in advanced melanoma: an indirect comparison.

WHAT IS KNOWN AND OBJECTIVE: Melanoma causes the majority of skin cancer-related deaths. The outcome of melanoma depends on its stage at diagnosis. Currently, for patients with advanced melanoma, two MEK inhibitors (trametinib and cobimetinib) have been authorized by the European Medicines Agency. The main objective of this study was to compare the relative efficacy of trametinib-dabrafenib and cobimetinib-vemurafenib in patients with advanced melanoma through adjusted indirect treatment comparisons (ITCs). METHODS: A search was made up to the 3rd of November 2015. Databases consulted were MEDLINE, the Cochrane Library and the Centre for Reviews and Dissemination. Randomized controlled trials (RCTs) which compared the efficacy of trametinib-dabrafenib or cobimetinib-vemurafenib versus a common treatment comparator, in which outcomes of overall survival, progression-free survival (PFS) and overall response rate (ORR) were considered. ITCs were carried out using the method proposed by Bucher et al. RESULTS AND DISCUSSION: Two RCTs were included (one for each drugs combination). The results of the adjusted ITCs showed that there were no statistically significant differences between the two combinations in terms of PFS and ORR. WHAT IS NEW AND CONCLUSION: The ITCs indicate no difference in efficacy between both treatments. However, there should be an independent, head-to-head trial of both combinations to confirm the results.

Stentoplasty effectiveness and safety for the treatment of osteoporotic vertebral fractures: a systematic review.

UNLABELLED: To assess the effectiveness and safety of stentoplasty in people with osteoporotic vertebral body fractures. A systematic search of databases including MEDLINE, EMBASE and Cochrane library, between others, was conducted to June 9, 2014. Clinical trials and observational studies that included alive adults with osteoporotic vertebral body fractures and the comparators were the intervention himself, vertebroplasty or balloon kyphoplasty were selected. Quality of evidence was graded according to the GRADE approach. Two review authors independently selected studies, assessed risk of bias and extracted data. Forty-two citations were identified during the search. After removing duplicates, five studies were included: two clinical trials and three observational studies. Stentoplasty, showed higher rate of adverse events related to material (P=0.043) and cuff pressure (P=0.014) in comparison to kyphoplasty. There was no difference between two procedures in terms of reduction of kyphosis, time of exposure to radiation or postoperative loss of cement. Stentoplasty in comparison to vertebroplasty, showed an improvement of restoration of vertebral height (P=0.042), kyphosis correction and volume of bone cement. No differences were found between two procedures in terms of loss of vertebral body volume. Based on observational studies, stentoplasty improved vertebral height, pain and functional disability at 6 and 12months follow-up, and corrected the angle vertebral fractures in patients with osteoporotic vertebral body. Stentoplasty was presented as a safe procedure in short-medium term, with a low complication rate, a reduced loss of cement and new vertebral body fractures lower rates. Stentoplasty improves vertebral height, reduces the pain and functional disability and correct the vertebral angle in patients with osteoporotic vertebral body fracture with minimum adverse events. Stentoplasty is comparable to kyphoplasty in terms of correction of kyphosis, time of exposure to radiation and cement postoperative loss, and comparable to vertebroplasty in terms of restoration of vertebral height correction and bone cement volume. LEVEL OF EVIDENCE: Level II systematic review.

Indirect comparison for Anti-TNF drugs in moderate to severe ulcerative colitis.

OBJECTIVE: To compare the relative efficacy of infliximab, adalimumab and golimumab through adjusted indirect treatment comparisons (ITCs). METHODS: An exhaustive search was performed until October 2013. Databases consulted were MEDLINE, EMBASE, the Cochrane Library, the Centre for Reviews and Dissemination and the Web of Science. Randomized control trials (RCTs) comparing the efficacy of infliximab, adalimumab or golimumab versus placebo, in terms of clinical remission, clinical response and mucosal healing, were included. In the case that more than one RCT fulfilled the inclusion criteria for the same drug, a metanalysis was undertaken using a fixed effects model. ITCs were carried out using the method proposed by Bucher et al. RESULTS: 6 RCTs published in 5 papers were included: 2 for infliximab (ACT 1 and ACT 2), 2 for adalimumab (ULTRA 1 y ULTRA 2) and 2 for golimumab (PURSUIT-SC y PURSUIT-M).In these RTCs, each biological agent was superior in efficacy to placebo. The results of the adjusted ITC are the following. In relation to the clinical remission, in the induction and maintenance period, there are no statistically significant differences between the three anti-TNF drugs. In relation to the clinical response and mucosal healing, in the induction period, there are statistically significant differences between infliximab and adalimumab. CONCLUSION: In view of the results obtained, infliximab, adalimumab and golimumab appear to be similarly effective therapeutic alternatives. Therefore, other considerations such as safety, tolerance and cost-effectiveness should be taken into account in order to select the most appropriate treatment.

Objetivo: Comparar la eficacia relativa de infliximab, adalimumab y golimumab mediante comparaciones indirectas (CI) ajustadas. Métodos: Se realizó una búsqueda bibliográfica que abarcó hasta Octubre 2013. Las bases de datos consultadas fueron: MEDLINE, EMBASE, the Cochrane Library, the Centre for Reviews and Dissemination y the Web of Science. Se incluyeron ensayos clínicos aleatorizados (ECA) que compararan la eficacia de infliximab, adalimumab o golimumab frente a placebo en términos de remisión clínica, respuesta clínica y curación de la mucosa. En el caso de que se incluyera más de un ECA para un mismo fármaco se llevó a cabo un metanálisis utilizado el modelo de efectos fijos. Las CI se realizaron utilizando el método de Butcher et al. Resultados: Se incluyeron 6 ECA publicados en 5 artículos: 2 para infliximab (ACT 1 y ACT 2), 2 para adalimumab (ULTRA 1 y ULTRA 2) y 2 para golimumab (PURSUIT-SC y PURSUIT-M). Los tres agentes biológicos presentaron mayor eficacia que placebo. Los resultados de las CI fueron los siguientes: en relación a la remisión clínica, en el período de inducción y en el período de mantenimiento, no hubo diferencias estadísticamente significativas entre los tres fármacos anti-TNF. En relación a la respuesta clínica y a la curación de la mucosa, en el período de inducción hay diferencias estadísticamente significativas entre infliximab y adalimumab. Conclusiones: En base a los resultados obtenidos (eficacia similar), infliximab, adalimumab y golimumab parecen ser alternativas terapéuticas. Así, otras consideraciones como la seguridad, la tolerancia y el coste-efectividad deben considerarse a la hora de seleccionar el tratamiento más adecuado.

Comparison of the accuracy of CT colonography and colonoscopy in the diagnosis of colorectal cancer.

AIM: The available evidence was reviewed to compare the effectiveness of CT colonography with that of colonoscopy for colorectal cancer (CRC) screening. METHOD: An electronic search was conducted using PubMed, EMBASE, the Cochrane Library and Centre for Reviews and Dissemination databases, from inception to July 2009. Studies were included if investigations used CT colonography for CRC screening in asymptomatic populations. Studies were excluded if investigations were conducted for the diagnosis of CRC or in elderly, high-risk or symptomatic populations. RESULTS: Of the 213 references identified, nine studies were included. The specificity of CT colonography in screening for CRC was high, although it decreased with decreasing diameter of polyp to be detected. The sensitivity of CT colonography for the detection of polyps < 6 mm in diameter was low and heterogeneous, although it was higher for polyps > 10 mm. The main factors contributing to a greater sensitivity of CT colonography were the inclusion of only populations with an average CRC risk and colonic insufflation with CO2 . The incidence of adverse effects was very low for both tests. CONCLUSION: CT colonography has high specificity but heterogeneous sensitivity, although in most cases it is not as sensitive or specific as conventional colonoscopy. CT colonography could therefore be useful as a screening test for populations with an average risk of CRC.

[Efficacy of educational sessions to modify the prescription of new drugs]. / Eficacia de las sesiones educativas para modificar la prescripción de fármacos nuevos.

OBJECTIVE: To evaluate the efficacy of an educational intervention to minimise the prescription of those new medicines whose therapeutic effects are of little benefit. DESIGN: Controlled and randomised experimental study. SETTING: 27 health centres in the province of Sevilla, Spain. PARTICIPANTS: 376 general practitioners. The 264 who worked in the same posts were randomised for the 6 pre-intervention months. 10 of them did not complete the post-intervention period. INTERVENTIONS: Four 45-minute training sessions in a 2-month period, given by health team doctors, with a critical reading of the studies available on recently marketed drugs, plus personal feed-back on prescription and bulletins on therapeutic novelties. The control group received only the feed-back and bulletins. MAIN MEASUREMENTS: Prescription of new medication of little benefit, measured as the number of packages out of the total. Second, the amount of coxib and eprosartan measured as defined daily doses. RESULTS: In the 6 months after the educational sessions, the doctors in the intervention group prescribed proportionately fewer therapeutic novelties of little benefit than those allocated to the control group (1.34% vs 1.62%; P<.001). The coxib and eprosartan prescribed showed only a non-significant trend towards less prescription by the intervention group. CONCLUSIONS: The group educational sessions, run by doctors trained in aspects of evidence-based medicine and prepared jointly with the pharmacy unit, reduced discreetly the prescription of new medicines that were not very innovative.

[Computer-aided prescribing: from utopia to reality]. / Receta electrónica: de la utopía a la realidad.

OBJECTIVE: To determine whether the introduction of computer-aided prescribing helped reduce the administrative burden at primary care centers. DESIGN: Descriptive, cross-sectional design. SETTING: Torreblanca Health Center in the province of Seville, southern Spain. From 29 October 2003 to the present a pilot project involving nine pharmacies in the basic health zone served by this health center has been running to evaluate computer-aided prescribing (the Receta XXI project) with real patients. PARTICIPANTS: All patients on the center's list of patients who came to the center for an administrative consultation to renew prescriptions for medications or supplies for long-term treatment. MEASURES: Total number of administrative visits per patient for patients who came to the center to renew prescriptions for long-term treatment, as recorded by the Diraya system (Historia Clinica Digital del Ciudadano, or Citizen's Digital Medical Record) during the period from February to July 2004. Total number of the same type of administrative visits recorded by the previous system (TASS) during the period from February to July 2003. MAIN RESULTS: The mean number of administrative visits per month during the period from February to July 2003 was 160, compared to a mean number of 64 visits during the period from February to July 2004. The reduction in the number of visits for prescription renewal was 60%. CONCLUSIONS: Introducing a system for computer-aided prescribing significantly reduced the number of administrative visits for prescription renewal for long-term treatment. This could help reduce the administrative burden considerably in primary care if the system were used in all centers.

[Community effectiveness of vaccines against infectious parotiditis (mumps). Report of cases]. / Efectividad comunitaria de las vacunas frente a la parotiditis infecciosa. Estudio de casos.

BACKGROUND: In our country, there are two types of infectious mumps vaccines available. In recent times, doubts have been raised regarding the overall effectiveness of these vaccines and the comparative effectiveness of the two strains (Rubini strain and Jeryl Lynn strain). In the "East Seville" Primary Care district, 245 cases were reported in 1997 (90.1 cases per 100,000 inhabitants). This study is aimed at taking advantage of the outbreak of cases of mumps to evaluate affected populations and comparative incidence according to type of vaccines given during childhood. METHODS: Descriptive analysis of the cases (age, territorial spread, inoculation history') and trend analysis (annual incident rates) within this health care district and the surrounding area. The overall effectiveness of the mumps vaccines. The case incidence rates among those inoculated with Rubini strain and those inoculated with Jeryl Lynn strain are also estimated. RESULTS: The highest rates of incidence are found among children in the 1-4 age range. Overall effectiveness rates for these vaccines have been estimated. A significantly higher rate of infection has been found among the children inoculated with Rubini strain than those inoculated with the Jeryl Lynn strain (relative risk of 6.5 with a Confidence Interval of 95% 3.6-11.8). CONCLUSIONS: The effectiveness which follows from this study does not seem as good as the theoretical effectiveness anticipated for the mumps vaccines. It thus seems advisable for other case studies to be conducted by types of vaccines used. The data to be furnished by means of sero-epidemiological studies are also of major interest.