The RedETS horizon scanning (HS) program in Spain is focused on identifying non-pharmaceutical emerging health technologies. HS is organized in three steps: (i) identification using different sources (PubMed, the biomedical press, and others); (ii) screening performed by the HS Working Group and clinicians; and (iii) prioritization using the PriTec tool. This study aimed to evaluate the accuracy of RedETS HS in identifying disruptive emerging technologies for our health system.

Data from brief files and full reports related to the identified emerging technologies were collected. Full health technology assessment (HTA) reports were also reviewed. The period of analysis was from 2016 to 2023. The information collected included the name, type, category, and indication of the emerging technology and the source of identification. An ad hoc Excel spreadsheet was designed to collect the information. The analysis consisted of a description of the variables and an assessment of concordance between the emerging technologies identified and those with full HTA reports.

There were 338 emerging technologies identified. These technologies were mainly therapeutic (52.1%) or diagnostic (25.7%). In addition, about 45 percent were medical devices and 15.7 percent were in vitro diagnostic tests; imaging comprised 7.4 percent. Most of the emerging technologies were identified through the biomedical press (22.2%), PubMed (23.6%) and industry (20.3%). In a preliminary analysis of these main sources, 31 percent of the technologies identified by HS had full HTA reports, with all of these being identified three years before the HTA.

HS systems might help identify the most relevant technologies for healthcare systems, enabling them to be more ready to incorporate the new technologies. Therefore, HS must be able to detect emerging technologies that will have an impact on the health system. Periodic evaluation of the accuracy of HS programs will improve their impact in the HTA process.

Pulsed-field ablation (PFA) is a new non-thermal ablative approach for treating paroxysmal and persistent atrial fibrillation (AF). It provides an alternative to the conventional thermal techniques of radiofrequency ablation and cryoablation. PFA is currently performed with the Farapulse PFA system (Boston Scientific, USA), which recently received CE marking in Europe. In this study, we describe the current evidence on the efficacy, safety, and cost-effectiveness of this new technology.

The Early Awareness and Alert System of the Agencia de Evaluación de Tecnologías Sanitarias-at the Instituto de Salud Carlos III- identified this new ablation approach in June 2021. An early technology assessment was conducted by reviewing relevant literature published to November 2021. The literature was identified by searching PubMed, Embase, the International Clinical Trials Registry Platform, ClinicalTrials.gov, and the Cochrane Library.

Seven relevant publications were identified, including three open-label trials for paroxysmal AF and one for persistent AF. Three studies comparing PFA with conventional thermal ablation techniques were also included. The safety results showed a lower incidence of complications (esophageal injury, pulmonary venous stenosis, pericardial effusion, and aortic injury) after PFA relative to conventional techniques. In terms of efficacy, PFA resulted in lower rates of AF recurrence in the medium and long term, compared with conventional techniques, and there were no differences in the lengths or success rates of the procedures. No cost-effectiveness studies were identified. Seven ongoing trials were identified, but no results have been published.

The current evidence for PFA in the treatment of AF showed good safety and promising efficacy. However, there is a lack of information on its effect on quality of life and the risk of death, disabling stroke, or cardiac arrest. Early evaluation of new and emerging technologies makes it possible to gather the minimum information necessary to support decisions on their inclusion in the healthcare system. In this case, based on current evidence, the widespread use of PFA is not recommended, except under a rigorous research protocol.

Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world. High-intensity focused ultrasound (HIFU) is a new non-invasive therapeutic option for treating the motor symptoms of PD. HIFU is an imaging-guided procedure for therapeutic brain ablation that has been used for patients with essential tremor and neuropathic pain. It is indicated for patients older than 22 years of age who have PD that is refractory to drug treatment and are ineligible for surgery. The objective of this study was to conduct an early assessment of HIFU subthalamotomy for the treatment of motor symptoms in patients with PD.

HIFU was identified by the early awareness and alert system, SINTESIS- nuevas tecnologías, of the Agencia de Evaluación de Tecnologías Sanitarias at the Instituto de Salud Carlos III. Relevant literature published to October 2021 was identified by searching PubMed, EMBASE, ClinicalTrials.gov, and the Cochrane Library.

One prospective study and one randomized controlled trial (RCT) were found that assessed the efficacy and safety of HIFU subthalamotomy for treating the motor symptoms of PD. The Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS III) was used to measure changes in symptoms (>30% change from baseline was considered clinically relevant). Both studies reported a reduction of symptoms in the intervention group. The MDS-UPDRS III score changed from 16.6 to 7.5 six months after treatment in the prospective study and from 19.9 to 9.9 four months after treatment in the RCT (a decrease of 11.6 points was observed after 12 months). The main adverse events reported were dyskinesia, speech and gait disturbances, and weakness, all of which resolved without treatment.

The results regarding the efficacy and safety of HIFU for treating the motor symptoms of PD are promising. HIFU is a non-invasive procedure that eliminates the risks associated with surgery. Although rapid diffusion of this technology is expected, further studies and economic evaluation are needed.

SINTESIS-new technologies is the early warning system for new and emerging technologies of the Agencia de Evaluación de Tecnologías Sanitarias, Instituto de Salud Carlos III. SINTESIS is part of the Action Plan for the Early Detection of New and Emerging Technologies of the Spanish Network of Health Technology Assessment Agencies (RedETS). In RedETS, four agencies are responsible for the identification of innovative technologies. These agencies have been collaborating since 2016 according to the early awareness methods contained in the EuroScan Methods Toolkit. SINTESIS focuses on secondary information sources (i.e., experts and literature). This study describes the experience of SINTESIS in identifying and filtering new technologies in recent years.

Retrospective analysis of all new and emerging technologies notified by SINTESIS to RedETS since 2018. Technologies were analyzed on a year-by-year basis for their source of information, the clinical specialties involved, and whether technologies found in the identification phase were selected for further assessment.

Between 2018–2020, SINTESIS identified 69 emerging and new technologies. Most of the information came from medical press news (35%), and medical web news (22%); other sources included experts (15%), licensing news search (12%), general press (12%), and scientific websites (6%). Almost 37 technologies (54%) were selected for further analysis. Reasons for exclusion included too early identification of technologies/prototypes without enough evidence (52%), technologies already implemented (28%), overlapping technologies between agencies (17%), and not being medical technologies (3%).

Experience suggests that news sections of general and medical journals, websites, and expert consultation are useful sources to identify new and emerging health technologies. The main limitation is that the technologies identified are often at too early a stage of development for further assessment. SINTESIS contributes, within a national horizon scanning system with other agencies, to broaden the information sources and provide useful data on early awareness of innovative technologies. Further studies are needed to assess the impact of emerging technologies detection on healthcare delivery.

Lung cancer is a leading cause of morbidity and mortality, and early diagnosis is essential for patient survival. Epigenetics is an innovative discipline that provides biomarkers to aid in early diagnosis, patient risk classification, or outcome prediction. Each type of tumor may present specific patterns of gene methylation, the analysis of which may be useful as a diagnostic tool. The aim of this study was to conduct an early assessment of novel in vitro diagnostic (IVD) tests based on the identification of DNA hypermethylation epigenetic signatures developed for the early detection of lung cancer.

We identified this technology through the Early Awareness and Alert System “SINTESIS-new technologies” of the Agencia de Evaluación de Tecnologías Sanitarias - Instituto de Salud Carlos III. A literature search of PubMed, the Trip Medical Database, the International Clinical Trials Registry Platform, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials was conducted. Studies published up to November 2019 were reviewed.

Three tests were identified. Epi proLung® analyzes the hypermethylation status of SHOX2/PTGER4 genes in blood samples using polymerase chain reaction (PCR) and showed good discrimination capacity with respect to healthy controls (area under the curve [AUC] = 0.91) and patients with non-malignant lung diseases (AUC = 0.86). The Epi proLung BL Reflex Assay® for determining the hypermethylation state of the SHOX2 gene in bronchoalveolar lavage samples by PCR had modest sensitivity (69%, 95% confidence interval [CI]: 64–75) and high specificity (96%, 95% CI: 97–100). A test in development for determining the hypermethylation state of BCAT1/CDO1/TRIM58/ZNF177 genes in aspirated or bronchoalveolar lavage samples by pyrosequencing yielded a sensitivity of 85 percent and a specificity of 81 percent, with an AUC of 0.91 at the optimal cutoff point.

The evidence for the three tests showed promising results in terms of diagnostic validity. However, although personalized medicine is becoming increasingly widespread in the field of cancer diagnosis, more studies are needed to evaluate the clinical utility of these diagnostic tests, either as a complementary or a screening test, and the economic impact of their use.

Robotic surgery (RS) can offer benefits compared to freehand surgery (FS) in the treatment of patients with spinal diseases. The aim of this study was to assess efficacy and safety of RS versus FS in spinal fusion. The outcomes considered were accuracy in the placement of pedicle screws, surgical times, hospital stay, exposure to radiation, and complications.

A systematic review and meta-analysis were performed by researchers at the Instituto de Salud Carlos III (ISCIII). Studies published until June 2019 in the English, Spanish, or French languages were retrieved. The data analyses and risk of bias assessments were undertaken using RevMan 5.3.

Eight randomized controlled trials including 610 patients (RS: 308, FS: 302) were found. The mean age of the patients ranged from 56 to 68 years in the FS group and from 55 to 68 years in the RS group. The percentage of women included ranged from 46 to 73 percent undergoing FS and from 33 to 70 percent undergoing RS. The main diagnosis was degenerative spine disease. The number of screws implanted ranged from 22 to 584 for FS and 23 to 532 for RS. The robots used were the SpineAssist and Renaissance Guidance System (Mazor Robotics, Ltd) and the TiRobot® Orthopaedic Robotic System (Beijing Tinavi Medical Technologies Co., Ltd). Pedicle screw placement within the safety zone (Grades A and B on the Gertzbein and Robbins scale) ranged from 93 to 100 percent in FS and from 85 to 100 percent in RS (relative risk 1.0, 95% confidence interval [CI] 0.99–1.03; p = 0.36) (I2=75%; p = 0.0005). Regarding intervention time, the meta-analysis showed a mean difference (MD) of 15.2 minutes (95% CI 5.35–25.05; p = 0.002) (I2 = 0%; p = 0.39) in favor of FS. The MD in hospital stay was 0.36 days (95% CI -1.03–0.31; p = 0.30) (I2 = 62%; p = 0.07), which was not statistically significant. Contradictory results were found for fluoroscopy time, although RS was associated with a lower radiation dose than FS (p < 0.05). In relation to safety, studies only reported on rates of surgical revision, which ranged from 0 to 2 after FS and from 0 to 10 after RS. The risk or bias was unclear in most studies.

We found no conclusive results suggesting benefits for spinal fusion using RS compared with FS. Further research with adequate selection of patients, type of robot, and comparator is needed.

Endometrial and ovarian cancer are the first and second leading causes of death from gynecological cancer in Spain. Survival is generally determined by stage at diagnosis, but there is no test currently used for early detection of both tumor types. PapSEEK is a test developed to diagnose endometrial and ovarian cancer by detecting aneuploidies and somatic mutations commonly associated with both tumor types through DNA next-generation sequencing (NGS) of liquid from Papanicolaou test (Pap smear) samples. The objective of this work was to assess the effectiveness and safety of PapSEEK.

PapSEEK was identified by the Early Awareness and Alert System, “SINTESIS-new technologies”, of the Agencia de Evaluación de Tecnologías Sanitarias in Spain (AETS-ISCIII). An early assessment of the technology was conducted through a literature search of the following databases: PubMed, Embase, the Web of Science, the Trip database, the International Clinical Trials Registry Platform, ClinicalTrials.gov, and The Cochrane Library. Clinical studies on the effectiveness and safety of PapSEEK published up to February 2019 were reviewed.

The evidence comprised proof of concept and diagnostic accuracy studies, which showed good preliminary results regarding the accuracy of the test for diagnosing endometrial cancer (sensitivity ranged from 0.81 to 0.93), but not for ovarian cancer (sensitivity ranged from 0.33 to 0.45). The specificity for both tumor types ranged from 0.99 to 1.00. Since PapSEEK uses a sampling method that is routinely used in clinical practice (the Pap smear), no evidence was found in the literature on the safety of the test.

PapSEEK is a novel technology developed to diagnose endometrial and ovarian cancer by means of DNA-NGS of Pap smear samples. The identified studies showed good preliminary results regarding the ability of the test to diagnose endometrial cancer, but not ovarian cancer. PapSEEK may be useful as a screening tool for endometrial cancer. However, further research on PapSEEK is needed to prospectively evaluate its diagnostic accuracy, compare it with current tests used in the early diagnosis of both cancer types, evaluate its effect on patient survival and disease progression, and measure its economic impact.

Epigenetics is an innovative discipline that aims to provide biomarkers to aid in early diagnosis, patient risk classification, or outcome prediction. The identification of therapeutic targets is of particular interest in cancer therapy for selecting groups of patients who may benefit most from an intervention. Understanding the relationships between the immune system and tumor cells has led to new immunotherapy-based therapies that provide a promising alternative to conventional cancer therapies. The aim of this study was to conduct an early assessment of a novel epigenetic signature (EPIMMUNE) that could predict response to programmed cell death protein 1 (PD-1) inhibitor immunotherapy in patients with non-small cell lung cancer (NSCLC).

We identified the novel epigenetic signature EPIMMUNE through the Early Awareness and Alert System, “SINTESIS-new technologies” of the Agencia de Evaluación de Tecnologías Sanitarias in Spain (AETS-ISCIII). A literature search of PubMed, Embase, the Web of Science, the Trip database, the International Clinical Trials Registry Platform, ClinicalTrials.gov, The Cochrane Library, and the Centre for Reviews and Dissemination databases was conducted. Clinical studies on EPIMMUNE published in English or Spanish up to August 2019 were reviewed.

Only one retrospective study was found. Identification of EPIMMUNE was accomplished through interrogation of the DNA methylation status of CpG sites in 142 samples from adult patients with NSCLC who were treated with PD-1 inhibitors. EPIMMUNE was defined by 301 CpG sites whose methylation status was significantly associated with clinical response (progression-free and overall survival). No studies assessing the long-term clinical utility, impact on therapeutic decision making, or economic implications of EPIMMUNE were found.

The EPIMMUNE signature could provide an accurate and valid biomarker for identifying patients with NSCLC who may benefit from treatment with PD-1 inhibitors. However, the technology is under development, and there is only a single study on detecting the EPIMMUNE epigenetic profile and identifying the DNA methylation profiles associated with increased survival after PD-1 inhibitor therapy. More diagnostic accuracy studies and prospective, long-term trials are needed to evaluate the clinical impact this technology may have on therapeutic decision making. Given the limited evidence available, further research is needed before the technology can be disseminated.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a minimally invasive therapeutic option for stage IV or terminal stage peritoneal carcinomatosis, which has a very low survival rate. PIPAC is aimed at patients whose only therapeutic alternative is systemic chemotherapy because they are unable to undergo other treatments, such as cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. PIPAC consists of a micro-pump connected to a double-contrast injector, which is used to apply cytotoxic agents laparoscopically using pressurized aerosols. The objective of this study was to update the evidence regarding the effectiveness and safety of PIPAC.

A systematic review (SR) was conducted by searching PubMed, Embase, and The Cochrane Library database. ClinicalTrials.gov and the European Union Drug Regulating Authorities Clinical Trials Database were consulted to identify registered clinical studies. All articles published up to April 2019 were considered for inclusion. Abstracts, letters, single case studies, non-clinical and animal studies, and studies published in languages other than English or Spanish were excluded. Validated checklists were used to assess the quality of the included studies.

Seventeen studies were included (three SRs and fourteen cases series) and eighteen ongoing clinical trials were identified. The quality of the SRs and cases series studies was low and moderate, respectively. Adverse events were categorized according to the National Cancer Institute Common Terminology Criteria for Adverse Events as grade 1–2 (mild-moderate: 11% to 40% of patients) and grade 3–4 (severe-fatal: 0% to 37% of patients). Overall complete histological regression according to the Peritoneal Regression Grading Score and the Peritoneal Cancer Index occurred in at least sixty percent of patients. The survival time ranged from 11 to 16 months.

Effectiveness data for PIPAC were promising, with high carcinomatosis regression rates. Most studies showed a moderate safety profile, with generally mild to moderate complications (nausea, abdominal pain, and vomiting). This is an advantage over systemic chemotherapy, which has severe systemic side effects. Economic evaluation studies are needed to estimate the cost effectiveness and cost utility of this technology. Diffusion of PIPAC is expected, but the criteria used to select patients in the studies carried out so far must be considered, as well as the need to follow strict safety protocols for preventing leakage of aerosolized cytotoxic drugs.

The Stride Management Assist (SMA®) device consist in a portable robotic exoskeleton designed for gait rehabilitation and training by repetition of walking patterns with automated regular gait cycles. Used for adult population with gait disorders of neurological or musculoskeletal origin that require rehabilitation. The objective of this work is to assess its efficacy and safety.

This technology was identified by the early Awareness and Alert System, “SINTESIS-new technologies” of AETS-ISCIII. An early assessment of the technology was conducted. The searched databases were: Pubmed, Embase, WOS, Tripdatabase, ClinicalTrials.org and Cochrane Library. Clinical studies using the device published in any language until 10 October 2018 were reviewed.

We found 3 abstracts to congresses and 6 clinical trials that evaluated the use of the device. Outcomes measures among studies included spatiotemporal gait parameters, energy expenditure, muscular activity and functional performance. Five studies consisted in proof-of-concept analysis; 3 studies evaluated the effect of gait training with SMA® compared with conventional therapy alone in individuals after stroke (2 studies) and Parkinson disease (1 study); and 1 before-and-after study assessed the effect of gait training with SMA® in elderly adults. During its use, improvements in spatiotemporal gait parameters were described in 4/5 studies, and 2/5 studies showed less energy expenditure versus 2/5 studies that found no differences. After gait training, 3/4 studies described greater improvements in gait parameters when associated its use. Only one clinical trial collected safety data reporting no adverse events.

The SMA® device allows to increase the efficiency and parameters of the march during its use. The assistance in the stride might have an impact on health by facilitating the recovery of the gait; however, further research is needed to determine the feasibility in the latter case since comparative studies with conventional therapy are limited.

Autism is a neurodevelopmental disorder characterized by alterations in the intellectual, social, communication, and behavioral capabilities of an individual, and is rarely detected in children before 24 months of age. Early diagnosis and intervention may be more effective at a younger age. Functional connectivity magnetic resonance imaging (fcMRI) of 6-month old infants may be able to identify brain connection patterns related to at least one of the characteristics of autism, which normally appear at 24 months of age, by using a mathematical model to analyze the neuroimaging data.

Clinical studies published up to December 2018 that used fcMRI to detect autism in infants were reviewed. The literature databases searched included PubMed, Web of Science, the Trip Database, DynaMed, the Cochrane Library, the International Clinical Trials Registry Platform, and ClinicalTrials.gov. Early assessments of fcMRI analysis were identified through the Early Awareness and Alert System of the Agencia de Evaluación de Tecnologías Sanitarias.

Only one prospective study of 59 infants at 6-months of age was retrieved. A fcMRI analysis was performed to identify 2,635 pairs of functional connections from 230 brain regions. The infants were subsequently assessed for autism at 24 months of age using gold standard tests. The functional connections correlated with at least one of the behaviors related to autism evaluated at 24 months of age. Eleven infants (19%) were diagnosed with autism at 24 months. Compared with the gold standard test results, the predictive model achieved the following: sensitivity 0.82 (95% confidence interval [CI]: 0.52 - 0.95); specificity 1.00 (95% CI: 0.93–1.00); positive predictive value 1.00 (95% CI: 0.70–1.00); negative predictive value 0.96 (95% CI: 0.87–0.99); and negative likelihood ratio 0.18 (95% CI: 0.05–0.64). Adverse effects were not reported in the study.

The fcMRI analysis could help in early detection of autism and the development of preventive interventions. However, the evidence is sparse and more well-designed studies are needed.

Mitral regurgitation (MR) is the most prevalent heart valve condition in Western countries. Open-heart mitral valve reconstruction is the conventional surgical treatment for MR, whereby the valve's cords are replaced with expanded polytetrafluoroethylene cords. Novel devices have introduced minimally invasive alternatives, such as transapical beating-heart valve repair. Among these alternatives, the Harpoon™ Mitral Valve Repair System (Edwards Lifesciences LLC) may have potential advantages (a smaller diameter valve introducer to minimize bleeding and a different anchoring mechanism). This study aimed to assess the efficacy and safety of Harpoon in minimally invasive mitral valve surgery.

An early assessment of the technology was conducted by reviewing relevant literature from the following databases: PubMed, EMBASE, Web of Science, the Trip Database, the International Clinical Trials Registry Platform, ClinicalTrials.gov, the Cochrane Library, and the Centre for Reviews and Dissemination. Relevant clinical studies published up to 30 January 2018 were included.

Only two publications, by the same research group, were included: an observational study of 11 patients and the prospective, nonrandomized TRACER trial (n = 30). During the procedure, MR was reduced from severe to none in 73 to 86 percent of patients and severe to mild in 14 to 27 percent. At one month, MR was rated as mild or lower in 82 to 89 percent of patients. At six months, MR had worsened to moderate or severe in 16 percent of patients from the TRACER trial. Safety issues within 30 days (18% to 27% of patients) included intraoperative conversion to open surgery, reoperation, pleural effusion, hemopericardium, and atrial fibrillation. There were no intra- or postoperative deaths.

Current evidence on the Harpoon device is scarce. Although published studies showed improvement in MR in most patients, there are still issues regarding safety, lack of long-term results, comparability with other procedures, and costs. While promising, further research is required before recommending routine use of this technology.

Minimally invasive capsulorhexis is an incision in the anterior capsule in the peripheral zone for cataract extraction. It allows reduction of the size of the lesion, ensuring a better transparency of the visual axis, preserving the capsule almost intact and a layer of lenticular epithelial cells. The procedure could have a potential regenerative effect of the lens in a natural way. The objective of this study is to assess the efficacy and safety of minimally invasive capsulorhexis to promote lens regeneration in children's cataracts.

This technology was identified by the early Awareness and Alert System, “SINTESIS-new technologies” of Agencia de Evaluación de Tecnologías Sanitarias (AETS) Instituto de Salud Carlos III (ISCIII). An early assessment was conducted. The searched databases were: PubMed, Centre for Reviews and Dissemination (CRD), and Cochrane Library. Clinical studies using the procedure published in any language until 29 September 2017 were reviewed.

An open-label, randomized trial in pediatric cataract patients (age: 0–2 years) was retrieved. Twelve patients underwent minimally invasive capsulorhexis, while twenty-five patients received the standard treatment. Regarding efficacy, a transparent regenerated biconvex lens was found in 100 percent of eyes three months after surgery, but wasn't found in the control group. 100 percent of capsular openings healed within one month after surgery in the experimental group, but not in the control group. Both groups increased their visual acuity parameters without significant differences. Regarding safety, children receiving the standard technique had a higher incidence of corneal edema (eight percent in the intervention vs thirty percent in the control group), anterior chamber inflammation (seventeen percent vs seventy-four percent), additional laser capsulotomy (zero percent vs eighty-four percent) and increased visual axis opacification (four percent vs eighty-four percent).

Minimally invasive capsulorhexis in children's cataracts seems to be a promising new procedure. Preliminary efficacy results were good and safety profile was better than standard treatment. However, it would be necessary to continue further studies to confirm these results.

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.

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.

Conventional gastric balloons for weight loss require endoscopy for placement and removal. The ELIPSETM is a new gastric balloon designed for weight loss that is swallowed and does not require endoscopy or anesthesia. The device is designed to remain in the stomach and be expelled after a predetermined time of 4 months. The objective of this work is to assess the efficacy and safety of the ELIPSETM procedureless gastric balloon for weight loss.

The ELIPSETM procedureless gastric balloon was identified by the early Awareness and Alert System, “SINTESIS-new technologies,” of The Instituto De Salud Carlos III (AETS-ISCIII). An early assessment of the technology was conducted. The searched databases were: MEDLINE (PubMed), Centre for Reviews and Dissemination, and the Cochrane Library. Clinical studies using the device published in any language until 10 January 2017 were reviewed.

A prospective, non-randomized, open label study supported by industry was retrieved. Thirty-four patients were enrolled. Six patients treated with an experimental device were excluded. Twenty-eight patients successfully swallowed the device. No endoscopy or anesthesia was required. All devices were excreted safely. Of the twenty-five patients finally studied, the mean percent total body weight loss was 10 percent (95 percent Confidence Interval, CI 7.3–12.7) and the mean waist circumference was reduced by 8.4cm (95 percent CI 5.7-11.8) at 4 months. Improvements were also seen in metabolic parameters (HbA1c, Low density lipoprotein, triglycerides and blood pressure). All aspects of quality of life measured by the Impact of Weight on Quality of Life (IWQoL) questionnaire demonstrated significant improvements. About safety, there were no serious adverse events or serious adverse device effects, however 64 percent of patients had vomiting, 54 percent experienced nausea, 25 percent had abdominal pain and 2 patients were excluded because of symptoms.

The ELIPSETM gastric balloon for weight loss seems to be an effective therapy with an acceptable safety profile. However it would be necessary to continue further studies to confirm these results, including comparative studies with current treatments.

Alzheimer's disease (AD) is the most common type of dementia. Plasmapheresis is a procedure consisting of removing the plasma, or specific elements which are considered to be involved in pathological processes. Plasmapheresis could reduce the A beta peptides load in the brain. The objective is to study the safety and efficacy of plasmapheresis for AD.

Systematic review, with all studies published before April 2016 reviewed. Selected studies included patients with AD treated with plasmapheresis. GRADE was used to assess quality. Efficacy outcomes include: (i) Cognitive, functional and behavior status, through Mini Mental State Examination, and Alzheimer Disease Assessment Scale-Cognitive test; (ii) Plasma and cerebrospinal fluid A beta levels; (iii) Brain-imaging and functional neuroimaging studies. Safety outcomes included side effects related to the treatment.

Two papers reporting results from three studies were selected: (i) pilot study (n = 10), (ii) its extended study (12 months more of follow-up) (n = 7), and (iii) clinical trial (n = 39). The quality of evidence was very low. About efficacy, the studies didn't report quantitative results and were inconclusive. The pilot study and its extended study reported (1): a tendency towards stabilization in cognitive status; the plasma levels of A beta peptides didn't show a clear pattern; and the brain-imaging assessment suggested a progressive volume increase in the hippocampus. The clinical trial reported in the experimental group vs control (2): a better score for the cognitive status; an increase of plasma A beta peptides; and did not find significant differences between groups for cerebrospinal fluid A beta peptides. The brain-imaging assessment showed a progressive loss of hippocampus volume in both groups. Regarding safety, the studies didn't report quantitative data. We didn't find economic evaluation studies.

The included studies had very high risk of bias and very low quality. We found no evidence on efficacy and safety of plasmapheresis treating AD. Plasmapheresis isn't a priority line in research of AD treatment.

Ischaemic heart disease is the leading cause of death worldwide. Magmaris™ is a new drug-eluting resorbable stent used for coronary reperfusion during a balloon angioplasty. Magmaris™ is composed of absorbable magnesium scaffold and its surface is coated with bioresorbable poly-L-lactide, which incorporates Sirolimus. Magmaris™ has theoretical advantages as the stent body disappears after vascular constrictive remodeling. It would provide the stability and elasticity of non-resorbable metal stents, but without long-term problems such as endothelial dysfunction, delay in endothelialization, risk of thrombosis and complications due to long-term antiplatelet medication. The objective of this work is to assess efficacy and safety of Magmaris ™ in patients with angina or silent ischaemia.

Early assessment of Magmaris™ identified through the Early-Awareness and Alert-System, “SINTESIS-new technologies”, of The Instituto De Salud Carlos III (AETS-ISCIII). The searched databases were: MEDLINE (PubMed), EMBASE, WOS, Clinical Trials and Cochrane Library. Clinical studies using Magmaris™ published in any language until December 2016 were reviewed.

One prospective, non-randomized, non-controlled, multicenter, clinical trial with two publications was retrieved. The first publication (123 patients) showed mainly imaging outcomes of angiography, intravascular ultrasound and tomography at 6 months of follow up. The second publication (118 patients) with data from 12 months of follow up also reported: Target lesion failure in four patients (3.4 percent; 95 percent Confidence Interval, CI:0.9–8.4); one target-vessel myocardial infarction (0.8 percent; one myocardial infarction (0.8 percent); two clinically driven target lesion revascularisation (1.7 percent) and two clinically driven target-vessel revascularisation (1.7 percent). No definite scaffold thrombosis was observed. No procedural complications were reported. This trial is expected to continue up to 36 months of follow up.

Clinical data show that Magmaris™ seems to be an effective and safe treatment in patients with angina or silent ischaemia undergoing balloon angioplasty. More research specially randomized controlled trials are necessary to confirm these results.

The Spanish National Network (REDETS) is a group of eight agencies, units and services, depending on National and Regional Governments that coordinate their work within a common methodological framework, guided by the principles of mutual recognition and cooperation. The necessity of considering a Quality Management System has been detected and, consequently, a common tool for all the members needs to be developed. We describe in this study the process to achieve that goal.

Based on both a review of previous literature and the proposal for a self-evaluating tool, a group of experts from each agency through consensus have developed a tool for self-evaluation in Health Technology Assessment (HTA) agencies. Through the structure described in the handbook of the Andalusian Agency for Healthcare Quality (ACSA), each standard should have a statement or proposal that needs to also include evidence or good practices, and the corresponding evaluation questions. In separate workgroups, the definition of these proposals, evidence and evaluation questions were developed. One face-to-face meeting and two meetings via teleconference were necessary to achieve a final document with all the quality standards.

From a proposed structure of sixty-six standards, the titles, definitions, statements and evidence as well as good practices and evaluation questions were established in workgroups with consensus among all of the members (1 - 3). The final version of the self-assessment tool was composed of sixty-eight standards, grouped in twelve quality criteria structured in four dimensions: I Responsibility, II Clients and Stakeholders, III Production Process, and IV Resources.

Quality management requires an evaluation tool and this version, based on a systematic review and consensus, is a useful and practical instrument for developing a handbook by each member of REDETS. An online version of the tool is in process of development.

Early awareness and alert systems (EAAS) try to anticipate the impact of new technologies in the healthcare systems. Spain, which has a decentralized health system with public provision and universal health coverage, has been a pioneer in establishing EAAS activities. From 2006 a network of regional agencies coordinated EAAS activities. Taking into account the individual agencies scarce resources and in order to improve efficiency, this collaboration decided to distribute tasks when identifying and early assessment of new and emerging health technologies. The aim was to inform the common benefit package of the Spanish public health system.

Four out of eight Spanish Health Technology Assessment (HTA) agencies had EAAS in Spain (AETS-Carlos III Institute; AETSA-Andalusia; Avalia-t-Galicia; Osteba-Basque Country). Each agency has taken care of different sources for the identification of new and emerging non-drug health technologies: industry and innovator contacts, health expert networks, mass media and EAAS databases. Members of the network used the same filtration criteria to reach the final list. The system will run in parallel to a biannual identification process in major databases.

In 2016, the network identified and filtered sixty-three technologies: ten by mass media; five by health experts; thirty-five other EAAS and thirteen by direct contact with industry and innovators. Main represented specialties were: endocrinology (seven); gynecology and obstetrics (six); cardiology and cardiac surgery (five); emergency medicine (four); dermatology (three) and pneumology (three). Technologies were grouped by specialty in order to inform the different commissions that discuss inclusion in the Spanish Benefit Package. Specialty monographs will be published to inform stakeholders.

The approach is feasible, and increases the capacity of individual agencies to address the needs of the national and regional systems by improving their efficiency. There is a need to previously define the methods and the criteria that will be used for the identification and filtration.