Acute myocardial infarction (AMI) is one of the leading causes of death and disability worldwide. The European Society of Cardiology Guidelines have established a new definition of myocardial infarction and have strengthened the central role of cardiac troponins in cardiology diagnostics for rule-in and rule-out of non ST-elevation myocardial infarction (NSTEMI). High-sensitivity cardiac troponin I assays (hsTnI) should increase diagnostic sensitivity, and a shorter interval for ruling-in and ruling-out AMI. This analysis aims to provide an overview of the clinical, economic, organizational and ethical impact of the use of hsTnI in clinical practice of Emergency Departments (ED) in Italy.

HsTnl for rule-in and rule-out of AMI in the ED is being evaluated using the EUnetHTA Core Model® framework for health technology assessment. The hsTnI HTA assessment will be completed with real-world evidence derived from a multicenter observational study which has been designed to be conducted in 12 Italian EDs, enrolling 6000 patients with chest pain of suspected cardiac origin, aiming to provide data from the Italian context on clinical, organizational and economic aspects of the use of the test in the ED. Endpoints of the study include: time lapses related to diagnosis, admission, treatment and discharge of patients; number of tests performed; and number of patients diagnosed with AMI.

Initial results from a literature review confirm the usefulness of the hsTnI assay in diagnosing AMI. Generated real-world data will be collected, analyzed and integrated to existing evidence to assess the utility of the test in real contexts, providing details relevant for organizational aspects of the use of the test in the ED.

The use of hsTnl could improve diagnosis of AMI by allowing a faster ruling-in or ruling-out, and reducing inappropriate hospitalizations. Furthermore, this technology could represent an opportunity to reduce overall costs for the healthcare system.

New therapeutic strategies have been established in chronic wound healing procedures, such as the use of platelet-rich plasma (PRP). There is currently still uncertainty about the effectiveness, cost-effectiveness and real safety of PRP in promoting chronic wound healing and what specific types of chronic wounds can benefit most from its use.

We conducted a systematic review of available scientific literature on the effectiveness, safety and cost-effectiveness of PRP compared to placebo, standard care or alternative topical therapies for the treatment of chronic wounds in adults. Overall effect size was estimated through a meta-analysis. A cost-effectiveness analysis was conducted using a Markov model which simulates the costs and health outcomes of individuals for a 5-year horizon, from the perspective of the Spanish National Health Service (NHS) for the PRP versus standard treatment in patients with diabetic foot ulcers. The effectiveness measure was quality-adjusted life years (QALYs). We ran extensive sensitivity analyses, including a probabilistic sensitivity analysis.

Sixteen RCTs and four observational studies were included for the effectiveness and safety meta-analysis. The primary outcome was the proportion of chronic wounds completely healed: 143 patients out of 334 (42.8 percent) were cured in the standard treatment arm and 251 patients out of 375 (66.9 percent) in the PRP arm, relative risk (RR) 1.68 (95% CI: 1.22–2.31). It was unclear whether there was a difference in the risk of infection (RR 0.53, 95% CI: 0.10–2.71) or adverse events (RR 1.05, 95% CI: 0.29–3.88) between PRP and standard care. Three studies were considered for the cost-effectiveness analysis. In the base case analysis, PRP led to higher QALYs and healthcare costs with an estimated incremental cost-effectiveness ratio (ICER) of EUR 41,767 (USD 48,323)/QALY.

PRP treatment is more expensive and more effective than standard treatment. The estimated ICER is above the acceptability threshold in Spain.

In Italy, the central government sets the health benefit package (denominated “Livelli Essenziali di Assistenza” - LEAs) of the National Health System (NHS), which must be provided to all residents. In 2004, the Italian Ministry of Health established a new technical body, the National LEA Commission, responsible for updating LEAs.

Recently, the Ministry has commissioned to the National Institute of Health (NIH) the development of a new value-based procedure for updating the health benefit package for the Italian NHS, supporting the National LEA Commission. A review and comparison of value frameworks and decisional models was performed in order to select a framework and a model that can be applied to the Italian context, design an administrative process for the update procedure, and propose approaches for: (i) the assessment of services currently included in the health benefit basket and of those planned to be incorporated, (ii) the process of appraisal and decision-making to be adopted by the Commission.

The NIH outlined an evidence and value-based three-step (i.e. priority setting, assessment and appraisal) administrative process that integrates roles and responsibilities of the different Italian healthcare institutions involved in LEA updating and HTA.

The NIH is proposing to the Ministry of Health and to the National LEA Commission a new evidence and value-based procedure for updating the health benefit package for the Italian NHS. This procedure is entering a pilot phase in which potential gaps can be identified and minimized for its subsequent implementation.

Current practice in cost-effectiveness analysis (CEA) involves the estimation of the incremental cost-effectiveness ratio (ICER) between a new intervention and one alternative comparator reflecting the standard of care. As this focuses on pairwise comparisons, rather than considering the whole range of available alternatives at any given time, this method fails to capture the full impact of bringing the new intervention to market.

A multi-comparator ICER (MC-ICER) evaluating the impact of the new technology on patients treated with all comparators used in clinical practice, rather than a theoretical ‘second-best’ alternative only, was estimated. This can be achieved by weighting the incremental costs and benefits for each comparator by its change in market share to generate an MC-ICER. This is shown using a stylized example with three comparators.

The traditional ICER against the second-best alternative was USD 200,000 per QALY, while the estimated multi-comparator ICER is USD 133,548 per QALY, corresponding to a 33 percent decrease. This reflects the fact that patients who switch to the new intervention are not only those who had been previously treated with one particular comparator, as is assumed in a traditional CEA. The difference between the traditional ICER and the MC-ICER depends on how the new intervention impacts on the uptake of each comparator.

Results show that, when comparator selection was made excluding dominated and extendedly-dominated alternatives, the MC-ICER, produced using the method described above, is lower than the traditional ICER comparing the new intervention to the second-best comparator. This captures the fact that patients may switch to the new intervention not only from the second-best comparator, but from the whole range of alternative treatments. Such patient movements determine the real impact, or opportunity cost, of the new intervention on the healthcare system and, therefore, should be captured in CEA alongside traditional one-way ICERs.

The hypoglossal nerve stimulation (HNS) produces a tongue protrusion for the treatment of mod-severe obstructive sleep apnea (OSA). It is one of the emerging health technologies prioritized to assess its possible inclusion on the Spanish National Health System. The objective of this study is to evaluate the efficacy and safety of this system in the treatment of OSA.

An early assessment (horizon scanning) was performed. The searched databases were: PubMed, WOS, Tripdatabase, Dynamed, Cochrane Library and ICTRP. Clinical studies of OSA patients treated with HNS published until 01 March 2017 were reviewed. Outcomes considered were: AHI (Apnea Hypopnea Index) ODI (Oxygen Desaturation Index) ESS (Epworth sleepiness scale) and AE (adverse events).

Four devices of HNS were founded: Inspire™, HGNS®, Aura6000™, and Nixoah™. We found two randomized controlled trials (RCT). The Inspire™ RCT showed significant results on mean differences on AHI (−16.9, 95% CI −24.7 to −9.0); ODI (−15.1, 95% CI −22.7 to −7.5) and ESS (−4.5, 95% CI −7.5 to −1.4) in 46 patients, after one week of follow-up. The HGNS® RCT showed non-significant differences on AHI (device active 22.1 ± 5.2 vs control 29.7 ± 6.2), ODI (11.4 ± 4.1 vs 19.5 ± 5.2) and ESS (9.8 ± 1.0 vs 14.1 ± 2.5) in 21 patients at 6 months. A systematic review that included 6 cases series (3 with HGNS®, 2 with Inspire™ and 1 with Aura6000™) without device subgroup analysis and 7 cohorts studies (6 with Inspire™ and one with Aura6000™) showed significant differences comparing AHI, ODI and ESS results to before treatment values. Major AE reported from the studies varied from 4 to 4.5%. No study with Nixoah™ was found.

Inspire™ seems to be an effective option for OSA patients although the evidence is scarce and of low quality for all HNS devices. It would be necessary further well-designed studies.

Ovarian cancer (OC) has the highest mortality rate of all gynecologic malignancies. Completeness of cytoreductive surgery is a key prognostic factor for survival. To differentiate clearly between malignant and healthy tissue is essential for achieving complete cytoreduction. Using current approaches, this differentiation is difficult and can lead to incomplete tumour removal. OTL38 is a folate analogue conjugated to a near-infrared fluorescent dye which has high specificity and affinity for folate receptor alpha (FRα) expressed in OC. OTL38 together with a specific imaging system can help the surgeon to visualize diseased tissue. The objective of this work is to know the effectiveness and safety of OTL38 in of OC surgery.

Early assessment of OTL38 identified through the early-awareness and alert-system, “SINTESIS-new technologies”, of AETS-ISCIII. The searched databases were: PubMed, WOS, Tripdatabase, Dynamed, Cochrane Library and ICTRP. Clinical studies using the OTL38 in cytoreductive surgery in OC published until September 2017 were reviewed.

Only one publication, supported by industry, was retrieved. The study assesses the pharmacokinetics and tolerability of OLT38 in 30 healthy people randomized into 4 groups with different doses and a control group. The study also analyses the percentage of cytoreduction in 12 OC patients. Infusion of 0.025, 0.05, and 0.1 mg/kg OTL38 doses was associated with mild adverse events which did not require intervention. The 0.2 mg/kg dose was associated to adverse events of moderate severity. In OC patients, 0.0125 mg/kg dose was considered the optimal dose with mild adverse events. OTL38 accumulated in FRα-positive tumours and metastases allowed the surgeon to resect an additional 29 percent of malignant lesions which were not detected using standard inspection and palpation methods.

The OTL38 is an emergent health technology, which could help in cytoreductive surgery for ovarian cancer. However, the evidence is scarce and it would be necessary to continue further studies.

It is established that the current cost effectiveness health technology assessment (HTA) paradigm does not appropriately value rare disease technologies. Social willingness-to-pay (SWTP) has been suggested to be higher for rare disease technologies, it's inclusion into existing HTA framework could better reflect social preferences (SP) and enable a more equitable evaluation of rare disease technologies. Our study aims to estimate SP and SWTP for a rare disorder, CLN2 disease.

Relevant attributes for CLN2 disease were developed and validated by literature review and focus groups with patient's primary caregivers. An elicitation survey (discrete choice experiment (DCE) WTP and relative social willingness to pay (RS-WTP)) was developed using the selected attributes and levels of each attribute. The survey instruments and attributes/levels were tested and validated in a pre-pilot survey (n = 103) and a subsequent pilot survey (n = 286) of the United Kingdom (UK) general population. Information about CLN2 disease was provided to respondents and their understanding of the disease was tested including assessment of framing effects. The main survey with the general UK population (n = 4,009) is now complete.

Eight hundred and twenty-six people were contacted, of which 286 completed the DCE, 113 abandoned the survey before the DCE and 92 abandoned after the DCE. There were no significant differences in characteristics of respondents completing the DCE and those starting but not completing the DCE. Median survey completion time was 20 minutes with 90 percent of participants completing in a single sitting. Median score for the understanding test was 3 (Min = 0 and Max = 4). Incoherencies in WTP estimates were analyzed enabling us introduce relevant modifications and select the most appropriate attribute levels.

DCE and RS-WTP potentially are appropriate methods for assessment of social preferences. The selected attributes/levels for the experiment in CLN2 disease have been validated in this pilot.

As part of a national aging and technology network, AGE-WELL, one work group aims to promote the understanding of potential policy and regulatory hurdles among innovators and decision-makers. This study describes the development of resources to help innovators to navigate policy and regulatory systems to have their technologies adopted.

A policy primer was created that highlights considerations for innovators during the innovation process (from development to implementation). The content of the policy primer was developed by identifying resources through the Canadian Agency for Drugs and Technology in Health Grey Matters search tool, and in consultation with legal and regulatory consultants. By surveying AGE-WELL technology-developing projects (n=15) we characterized the technologies being developed within the network. Survey questions included: intended end-user/purchaser of the technology and past/anticipated facilitators/barriers in their innovation process. The policy primer and survey data were combined to create tailored innovation maps with considerations for each technology being developed within the network. These materials were used to develop a beta website where users can receive information relevant to various innovation stages, as it pertains to their technology. We gained feedback about our materials via surveys and interviews with AGE-WELL technology developers.

The tailored innovation maps and website were seen as helpful resources for understanding policy and regulatory processes required for technology adoption. Technology developers expressed interest in gaining further access to these resources. Innovators desired additional resources about demonstrating value and measuring technology effectiveness.

Resources were developed to help guide technology innovators through policy and regulatory processes; preliminary feedback suggests these were valued by innovators. Next steps include refining the website and releasing these resources to innovators beyond the AGE-WELL Network.

Hyperphosphatemia is a most common problem in dialysis patients. Phosphorus imbalance in dialysis patients increases the risk of developing the bone mineral disorder and cardiovascular mortality. Randomized controlled trials (RCTs) presented variable findings concerning the reduction of phosphorous level in nicotinamide user. So, this systematic review is aimed to explore the efficacy and safety of nicotinamide in hemodialysis patients.

This systematic review was conducted by adhering to the PRISMA guidelines. Study for inclusion was identified by running the suitable keywords in databases including PubMed, Embase, and Cochrane central from inception to 31 October 2017. Cochrane risk of bias tool was used to judge the quality of included RCTs. The change in serum phosphorus level was the primary outcome, while the change in other biochemical parameters including serum calcium, calcium-phosphorus product level, iPTH, platelets, lipid profile parameters, and the safety profile was considered under secondary outcomes. Review Manager (RevMan v5.3) was used for statistical analysis.

Finally four articles were qualified for inclusion in this study with a total of 274 participants of which 136 were in the treatment (nicotinamide) group. All the included studies showed statistically significant reduction in mean serum phosphorous, calcium-phosphorus product level in the treatment arm at the end point of the study, while the reduction in the placebo group was not statistically significant in all the studies. Among other biochemical parameters analyzed, only high-density lipoprotein (HDL) was found to be significantly increased from baseline to the endpoint of the study in the nicotinamide group, while the placebo group showed no significant change in all the included studies except the study by Shahbazian et al. Thrombocytopenia was the most commonly reported adverse event in the treatment group followed by diarrhea.

Nicotinamide was found to be effective in the management of hyperphosphatemia in hemodialysis patients. The safety profile was found to be satisfactory.

Renal transplantation is considered a cost-effective treatment compared to dialysis and represents a significant percentage of public health resources. Post-transplant treatment requires the use of three immunosuppressive drugs. The immunosuppressive regimens consists of a corticosteroid, a calcineurin inhibitor (cyclosporine or tacrolimus) and an antiproliferative agent (azathioprine or mycophenolate) and also by sirolimus or everolimus. In Brazil, the Unified Health System (as known as Sistema Único de Saúde - SUS) is responsible for 95 percent of all kidney transplants performed, as well as ensuring access to immunosuppressive drugs. Therefore, there is a huge and growing economic impact caused by the distribution of these drugs in SUS. We evaluated the factors associated with kidney graft loss in patients who received deceased donor organ and used maintenance immunosuppressive regimens in SUS, in fifteen years.

We analyzed a nationwide cohort of kidney transplant recipients from January 2000 to December 2015 developed through deterministic-probabilistic linkage of SUS administrative databases: Hospital Information System (SIH/SUS); Subsystem for High Complexity Procedures (SIA/SUS) and the Mortality Information System (SIM). Graft loss was defined as death or dialysis for more than three months. All regimens included corticosteroid. We used Cox proportional hazards model to evaluate the factors associated with progression to graft loss.

In total, 18,333 patients were included; 58.5 percent used tracolimus+mycophenolate, 11.7 percent cyclosporine+mycophenolate, 8.9 percent tacrolimus+azathyoprine, 5.5 percent cyclosporine+azathyoprine and 15.4 percent received other immunosuppressive regimens (sirolimus+mycophenolate, everolimus+mycophenolate, tacrolimus, mycophenolate, cyclosporine, azathyoprine) . Most patients were male with a median age of 46 years. A higher risk of graft loss was associated with the use of tracolimus+mycophenolate (HR = 1.069; 95% CI, 0.999–1.146), sirolimus+mycophenolate (HR1.395;95% CI, 1 .150–1.692), tracolimus (monotherapy) (1.468;1.239–1.739); mycophenolate (monotherapy) (1.297;1.126–1.493), male gender (1.144; 1.072–1.221), an additional year of age (1.010; 1.007–1.013), a median dialysis period greater than 38 months (1.266; 1.182–1.356), a diagnosis of diabetes (1.211; 1.071–1.367) and a diagnosis of arterial hypertension (1.209; 1.134–1.288) (HR=1.468;95% CI,1.239 −1.739); mycophenolate (monotherapy) (HR = 1.297; 95% CI, 1.126–1.493), male gender (HR = 1.144; 95% CI 1.072–1.221), an additional year of age (HR = 1.010; 95% CI, 1.007–1.013), a median dialysis period greater than 38 months (HR = 1.266; 95% CI, 1.182–1.356), a diagnosis of diabetes (HR = 1.211; 95% CI, 1.071–1.367) and a diagnosis of arterial hypertension (HR = 1.209; 95% CI, 1.134–1.288)as the primary cause of chronic kidney disease.

In Brazil, the use of regimens mycophenolate, tacrolimus, tacrolimus+mycophenolate was associated a higher risk of graft loss, among other factors. The choice of drug therapy is one of the few factors that influence survival amenable to direct action by health professionals. Therefore, the results of this study are important and should be disseminated aiming to better outcomes for kidney transplant patients.

Antimicrobial resistance is a serious public health problem at the global level. The sensitivity test in liquid and solid media-based techniques is traditionally used in Brazil for the diagnosis of resistant tuberculosis (TB). However, the time required for the diagnosis of this test is, on average, 60 (sixty) days, a period considered to be very high, especially considering certain vulnerable populations (street dwellers), since the long time to the result of the test makes it difficult to establish a second contact between the health institution and the individual, resulting in people without access to diagnosis and appropriate treatment. The line probe assay (LPA) technique often replaces the use of the sensitivity test in many countries, being considered of low time for the diagnosis, ranging from 24 to 48 hours.

We searched the Medline databases (via Pubmed), Embase, and The Cochrane Library, with the aim of finding systematic reviews with meta-analyses. The articles were screened by titles and abstracts and later the full text reading was carried out, according to the inclusion criteria.

Three systematic reviews with meta-analysis were selected. The interventions evaluated the LPA technique compared to the conventional drug sensitivity test. The evaluated tests showed good performance as rapid screening tests for resistance to rifampicin in high prevalence sites. However, although the test results for resistance to isoniazid showed good specificity, there was a high variability in sensitivity estimates.

This study reinforces the idea that the LPA technique may contribute to the previous diagnosis, and this is a probable strategy to control the disease, especially in vulnerable populations that are more likely to be affected by tuberculosis. For a broader analysis of the benefit of the technique, further studies are suggested.

Dalbavancin is a new innovative long-acting antimicrobial treatment that allows clinicians to endorse an early discharge program for patients suffering from acute bacterial skin and skin structure Infections (ABSSSI). The aim of this study was to develop a spending predictor model for evaluating the direct costs associated with the management of ABSSSI from the National Health Service (NHS) perspective of Italy, Spain, and Romania. The main purpose is to compare the hospitalization and drug costs due to the treatment of ABSSSI patients treated with standard antibiotics therapy or innovative long-acting treatment dalbavancin.

A decision-analytic model was performed to evaluate the diagnostic and clinical pathways of ABSSSI patients in the hospital, based on clinicians’ expert opinion. The standard of care scenario was compared with the dalbavancin scenario. The epidemiological and cost parameters were extrapolated from national administrative databases (hospital information system) and from a systematic literature review for each country. Only direct costs in the national payer's perspective were considered. Probabilistic sensitivity analysis (PSA) and one-way sensitivity analysis (OSA) were performed to check the robustness of the model assumptions.

Overall, the model estimated an average annual number of patients with ABSSSI equal to around 50,000 in Italy, Spain, and Romania. The introduction of dalbavancin reduced the length of stay of, on average, 3.3 days per ABSSSI patient. From the economic point of view, dalbavancin did not incur any additional cost from the NHS perspective with homogenous results between countries. The PSA and OSA demonstrated the robustness of the results.

The preliminary results highlight that the introduction of dalbavancin could generate a significant reduction in term of length of stay with no incremental cost from the NHS perspective. This model could represent a good tool for policymakers to provide information on the early discharge approach in the ABSSSI management.

In Brazil, the medicines marketed for acute external otitis are ciprofloxacin and the combination polymyxin B, neomycin, and fluocinolone. The aim of this study was to evaluate the proportion of cure and cost-effectiveness of quinolone versus polymyxin B, neomycin, and steroid combined (PNS) for acute external otitis from the perspective of the Brazilian Public health system.

A systematic review was conducted using Medline, Cochrane Library, CRD and Lilacs databases. Studies evaluating quinolones versus PNS in the treatment of acute external otitis were included. A cost-effectiveness model was made using a decision tree, considering the direct cost of treatment. Univariate sensitivity analysis was conducted, considering the confidence interval of clinical outcomes and a 15 percent variation in cost.

The proportion of cure in up to 10 days was 70.1 percent with quinolone and 60.4 percent with PNS (p = 0.004). The treatment costs were BRL 16.22 (USD 5.02) with quinolone and BRL 3.04 (USD 0.94) with PNS. The incremental cost-effectiveness ratio was BRL 136.25 (USD 42.15) per cure in up to 10 days for quinolone in relation to PNS. This value was more sensitive to clinical outcomes, ranging from BRL 95.48 (USD 29.54) to BRL 254.25 (USD 78.65) for cure with quinolone and from BRL 90.77 (USD 28.08) to BRL 262.57 (USD 81.23) for cure with PNS. These values should be considered with caution because acute external otitis is resolved within a few days and treatment effectiveness is not measured by life years.

There are few studies on therapeutic alternatives available in Brazil. Through the available evidence, there is a lack of results on the effects attributed to each drug. Considering the higher effectiveness, low cost and rational use of antibiotics, quinolone is considered a cost-effective alternative for acute external otitis in Brazil.

The Brazilian public health system (SUS) provides technologies based on the best available scientific evidence. However, there is a large number of lawsuits against the government for access to non-standard technologies, a phenomenon called “judicialization of the right to health”, which disrupts the system's operating logic. The aspect of judicialization that most impacts the health system involves unregistered technologies without scientific evidence of superiority being comparing to the alternatives already offered in the country. The aim of this study is to report experience of the National Committee for Health Technology Incorporation in the Brazilian Health System (CONITEC) to mitigate the effects of the judiciary, with the elaboration of informative documents about technologies directed towards policy-makers, patient, users of system health, professional health and other stakeholders.

The main judicialized technologies in the country were identified and then a meeting with experts was realized to discuss a more appropriate format for these documents. After defining the format, a review of the literature was carried out to identify the best available evidence of those health technologies.

A question-and-answer (QA) format document was drawn. The QA addressed information on the use of the technology for a specific clinical condition. Health registry and price in Brazil, if it has already been evaluated by CONITEC and its respective recommendation, as well as strategies of care and therapeutic alternatives available in the SUS were included. Their content has been adapted to a lay language and all of the documents were made available on the CONITEC website in the “Law and Health Section”.

The availability of QA represents a strong link between evidence and actions in health. For, they enable broad access to quality information by the lay public and stakeholders who seek information to support evidence-based decision-making.

Public consultation is one of the phases provided by the law that rules the health technology incorporation process in Brazilian Public Health System (SUS). In the Brazilian model, anyone can participate as long as he/she identifies her/himself. During the decision-making process these suggestions are analyzed by the National Committee for Health Technology Incorporation (CONITEC) and, sometimes, they are responsible for changing a preliminary recommendation for a technology. This study aims to identify the health technologies for which CONITEC revised the initial negative recommendations due to the contributions received during the public consultation.

A descriptive study using as input data the information on coverage decisions available on the CONITEC website.

Since CONITEC's creation until October 2017, CONITEC enacted 241 public consultations. Fifteen cases of change to the preliminary negative recommendation were found and among these eight (53 percent) had the economic studies or proposed technology price reconsidered by the companies. In the other seven decisions, the Board also regarded as important the reasons for changing the initial recommendation: new evidence on efficacy and safety as well as the analysis of different outcomes previously unconsidered in the preliminary assessment.

During the public consultations, besides technical-scientific information, personal experiences and opinion reports on each health technology analyzed, CONITEC received new price offers and economic studies from the applicants. This new material has allowed, in some cases, these technologies to become competitive and to be included as alternatives to those already available, provided there is no clinical impairment. This study reinforces the importance of the public consultation and social participation in the process of health technologies incorporation in Brazil, considering its capacity to add new information to the decision-making process.

The Federal District in Brazil has about 2.9 million inhabitants and the public health system is focused on medical specialties, with one university hospital and twenty regional hospitals. This ecosystem is favorable for fostering health technology assessment (HTA) to improve the efficiency and effectiveness of health care. The objective was to identify institutions that could form a HTA network to support decision-oriented evidence in the public health system.

Stakeholders from the hospitals and training/research institutions in the Federal District were surveyed. An online questionnaire (Google Docs) was developed to identify the potential and capacity of institutions to analyze or produce clinical and economic evidence. Two HTA seminars were held to spread knowledge about HTA and to encourage stakeholders to complete the survey.

The questionnaire response rate was thirty-five percent (25/70). Fifteen institutions were cited by the respondents as having the potential to build a HTA network. Twelve of the institutions produced rapid reviews and clinical guidelines, but only three of these had an organized priority setting process or produced assessments at the request of the hospital manager. The challenges identified were training and willingness of decision makers to organize HTA units in the hospitals.

An executive group was created which defined a strategy to support the implementation of HTA units as part of the HTA National Network (REBRATS). A regulation proposal was also created to encourage decision makers to activate a HTA network in the Federal District.

The use of drugs for clinical conditions that differ from those approved in prescribing information (product labels) is known as off-label use. In Brazil, the Brazilian Health Regulatory Agency (ANVISA) is the official organization that regulates the use of health technologies. For technologies to be incorporated into the Brazilian public health system, registration with ANVISA is mandatory. However, occasionally, it is necessary to evaluate technologies for off-label use in the interests of public health. This study aimed to identify the health technologies recommended by the National Committee for Health Technology Incorporation (CONITEC) with an off-label indication between January 2012 and October 2017.

A descriptive study was undertaken using data available on the CONITEC website.

The study identified seven drugs with a favorable recommendation for off-label use: everolimus, sirolimus, and tacrolimus as immunosuppressants in transplant recipients; clozapine for bipolar affective disorder; pentoxifylline for cutaneous leishmaniosis mucosa; risperidone for adults with autism spectrum disorder, and bevacizumab for age-related macular degeneration and diabetic macular edema. For these decisions the Committee considered the scientific evidence available for the indication proposed, the severity of the disease, and the existence or absence of alternative treatments. This was possible because Brazilian legislation allows ANVISA to authorize the off-label use of health technologies provided that the analysis is supported by scientific evidence regarding effectiveness, accuracy, and safety for the intended purpose.

The off-label use of health technologies is a worldwide practice that can favor vulnerable populations and neglected diseases. This practice should be seen as positive when there is evidence supporting off-label use, and such decisions should not be influenced by political, economic, or marketing considerations.

The conventional drug sensitivity test is traditionally used in Brazil to diagnose drug-resistant tuberculosis. However, the test can take up to 60 days to return a diagnosis, which is considered too long for certain vulnerable populations. Therefore, this study analyzed the available scientific evidence on the accuracy and time to diagnosis of the nitrate reductase assay for diagnosing resistant tuberculosis, compared with the conventional drug sensitivity test.

We searched MEDLINE, Embase, and The Cochrane Library for systematic reviews with meta-analyses. The articles were screened by title and abstract. The full-texts of potentially relevant articles were then screened according to the inclusion criteria.

Three systematic reviews with meta-analyses were selected that compared the nitrate reductase assay with the conventional drug sensitivity test. The accuracy of the nitrate reductase assay was satisfactory in most of the results when compared with the sensitivity test, except for one study that showed low sensitivity for the detection of streptomycin resistance. In addition, the nitrate reductase assay had a shorter time to diagnosis than the drug sensitivity test.

The results of this study reinforce the idea that the nitrate reductase assay may diagnose drug-resistant tuberculosis earlier than the conventional drug sensitivity test and be a helpful strategy for controlling the disease, especially in vulnerable populations that are more likely to be affected by tuberculosis. For a broader analysis of the benefit of the assay, it is suggested that studies investigate the impact of the shorter time to diagnosis on morbidity and mortality in patients with drug-resistant tuberculosis. In addition, economic analyses comparing the nitrate reductase assay with the sensitivity test are recommended to evaluate the cost-benefit ratio.

Eculizumab is a monoclonal antibody indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) or with atypical hemolytic uremic syndrome (aHUS). In Brazil in recent years eculizumab was the most expensive drug requested through court orders, obliging public health managers to import it from the USA. From 2012 to 2016, approximately BRL 424 million (USD 112 million) was spent on eculizumab. The purpose of this study was to assess the regulatory situation and the scientific evidence on the safety and efficacy of eculizumab.

A literature search was conducted in PubMed, The Cochrane Library, and the Centre for Reviews and Dissemination databases on September 2017. The websites of regulatory agencies were also searched.

In 2007, the use of eculizumab was approved by the United States Food and Drug Administration and the European Medicines Agency. In Brazil, despite the provision of eculizumab through judicial proceedings since 2009, the manufacturer of eculizumab only requested a licence for it in 2017, after several meetings with the government when the company agreed to provide the drug at approximately half the price of the imported product. The efficacy of eculizumab in PNH patients was assessed in one randomized, placebo controlled study, one single arm study, and one long-term extension study. The drug reduced hemolysis and the need for transfusion, although the studies had methodological problems. The efficacy of eculizumab in the treatment of aHUS was assessed in four prospective, controlled open-label studies, two long-term extension studies, and one retrospective study. Eculizumab normalized platelet counts and reduced the need for plasmapheresis, although the studies had no control group. Eculizumab was well tolerated, with no meningococcal infections occurring after patients were immunized.

Some companies have no interest in licensing their products in Brazil because their provision by judicial proceedings is more lucrative. This situation promotes litigation and irrational prescription of drugs, and also obligates the Brazilian government to import expensive health products.

Vemurafenib plus cobimetinib (VC) for the treatment of metastatic melanoma was requested to be included in the National Formulary in Uruguay. The standard of care for metastatic melanoma in Uruguay is dacarbazine. There is no published head-to-head trial assessing the effects of VC versus dacarbazine. The objective of this study was to perform an indirect comparison of the effects of dacarbazine, compared with VC, based on the results of trials that included both treatments versus the same comparator (vemurafenib alone).

We searched Pubmed and The Cochrane Library for trials comparing either VC or dacarbazine with vemurafenib. Trials were assessed in terms of risk of bias, similarity of interventions and inclusion and exclusion criteria, and comparability of characteristics of patients in the vemurafenib arm. We performed an indirect comparison using the Bucher method.

From the literature search we retrieved two studies that met the inclusion criteria: a randomized clinical trial that assessed VC versus vemurafenib or placebo and another assessing dacarbazine versus vemurafenib. Both studies were similar in terms of methodological quality, inclusion and exclusion criteria, and comparability of the vemurafenib arms. However, the comparison of overall survival and progression-free survival curves for the vemurafenib arms were quite different between the two trials. At 9 months, overall survival was eighty-one percent and fifty-five percent and progression-free survival was thirty percent and fifteen percent, respectively. The indirect comparison provided the following hazard ratios: 0.24 (95% confidence interval [CI]: 0.14–0.48) for overall survival; 0.13 (95% CI: 0.09–0.19) for progression-free survival; and 0.15 (95% CI: 0.02–1.29) for grade 4 adverse events.

Treatment with VC increased overall survival and progression-free survival, compared with dacarbazine. Severe adverse events were less frequent with the combined therapy. However, the differences in the vemurafenib survival curves increases doubts about the accuracy of the indirect estimators of overall survival and progression-free survival.