Evaluation is crucial for integration of e-Health/m-Health applications into healthcare systems and their further sustainability. However, evaluation of these technologies is often challenged by poor quality of research design, lack of common outcome indicators and no consensus on appropriate methodology. Health Technology Assessment (HTA) could offer a sound methodological basis for these evaluations (1). The aim of this study was to look for HTA reports on e-Health/m-Health technologies and to describe their characteristics and analyze transparency, consistency and thoroughness, with the goal to detect fields for improvements.

A literature search was performed on PubMed, ISI WOS and University of York – Centre for Reviews and Dissemination (CRD) electronic databases, in order to identify reports that had evaluated e-Health/m-Health technologies, published until 1 April 2016. We used the International Network of Agencies for Health Technology Assessment (INAHTA) checklist (2) to evaluate transparency and consistency of included reports. We also assessed thoroughness of reports by checking the presence of the domains suggested by European Network for HTA (EUnetHTA) HTA Core Model (3).

Twenty-eight reports published between 1999 and 2015 were included. Most of reports (71.4 percent) were delivered by non-European countries and only 35.7 percent were classified as full reports. E-Health/m-Health technologies from several fields of medicine, mostly cardiology (21.4 percent) and psychiatry (17.9 percent) were evaluated. Policy question was clearly defined in 32.1 percent of reports, whereas ethical (21.4 percent) and legal implications (3.6 percent) were domains with the least presence. With respect to the EUnetHTA Core Model, around 70 percent of reports dealt with effectiveness and economic evaluation, more than 50 percent described health problem and around 40 percent organizational and social aspects. Remaining domains were evaluated in very few reports.

E-Health/m-Health technologies are increasingly present in the field of HTA. Our work identified a number of elements not being included in the available reports. Several reports missed to respond to relevant assessment elements especially ethical, social and organizational implications. There is a need for strengthening and standardizing methods used for the evaluation of these technologies.

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.

The method appraises the stakeholders value judgments in the Health Technology Assessment (HTA) process, through a new model of research that addresses clinical scenarios to simulate real world HTA dilemmas and support decision making. The scenarios are based on criteria, such as clinical and epidemiological elements, and also, economic, social and ethical factors. The stakeholders decisions can induce strategic impacts in different HTA fields. We agreed to call this model Decision Making Clinical Scenarios (DMCS).

The model of research is based on a cross exploratory research, through a DMCS questionnaire applied to stakeholder respondents. The first survey was composed of four scenarios. The scenarios introduce value judgments, preferences and structuring choices, under specific circumstances. The scenarios are based on trade-offs involving HTA, such as budget impact, sources of funding, patients eligibility, technology characteristics and disease epidemiology. The stakeholders points of view are analyzed, through groups that represent payers, suppliers, developers, researchers, prescribers, regulators, government, patients and society.

The scenarios have been shown to be understandable for all stakeholders groups. When testing the model with hypothetical dilemmas through clinical scenarios, the results are strongly influenced by each presented trade-off. We can observe specific trends and motivations when analyzing the stakeholders groups separately. The results are always evaluated and validated through statistical analysis. A total of 193 stakeholders answered the survey. The majority were male (n = 104; 53.9 percent) and aged between 31 and 40 years (n = 71; 36.8 percent). In scenario 1, almost half of respondents (n = 95; 49.2 percent opted not to incorporate the new drug and in scenario 2, an even higher proportion chose not to incorporate the new drug (n = 112; 58.0 percent). In scenario 3, most have responded to not incorporate the new treatment for any age group (n = 81; 42.0 percent). In scenario 4, 65 percent of respondents opted for the preferential allocation for prevention, rather than treatment (n = 125; 64.8 percent). Overall results showed a conservative trend, considering the presented criteria and trade-offs.

We concluded that most stakeholders are not guided only by the clinical benefit of a decision. They valorize the importance of funding mechanisms and budget control, and consider economic, social, ethical, clinical and epidemiological aspects. This study model seems to be useful to evaluate the trends of decision makers conduct. We understand that the use of clinical scenarios brings the discussion into the enviroment and dynamics of the HTA process, where outcome impacts can be analyzed properly. This model can be explored in further research, using flexible criteria for each desired scenario, through real world situations. This model can be used to evaluate impacts in strategic subjects, as budget allocation, public healthcare policies, and patient-shared decision making.

Influenza is a disease related to the human respiratory system, with economic and social burden a common cause of Influenza-Like-Illness (ILI) among children and the elderly. This study was conducted to estimate cost of illness based on social perspectives of ILI cases.

A prospective study was conducted between February and March 2016 in pharmacies and private clinics at Khanh Hoa, Lam Dong, Tay Ninh, Dong Nai province, Ho Chi Minh City and Hospital of Tropical Diseases. Demographic and clinical information was collected by face-to-face interview. Treatment costs included direct costs (for example, diagnosis, therapeutics) and indirect cost (cost of days lost).

Average costs associated with the ILI were USD88.09 per case among all age groups, direct non-medical costs were more dominant than direct medical costs accounting for 39.5 percent in pharmacies, 71.1 percent in clinics and 64.2 percent in hospitals. Total average cost was estimated to be EUR105 in children, and EUR514 in adults in Germany (1); and in South China, direct medical cost of ILI would be USD22.69 (2).

The cost of ILI was the reason for the economic burden of patients and their families. This study provides the data for the future research, programs and policies which can be applied for influenza or ILI in Vietnam.

Due to the rising costs caused by an increasing demand for Sexually Transmitted Infection (STI) care, the Dutch government changed the funding of STI-clinics (1). A more restrictive testing policy introduced in 2015 no longer required syphilis and human immunodeficiency virus (HIV) tests for younger, heterosexual clients. A less extensive testing policy could be detrimental to the aim of finding and treating STIs (2,3). Infections that remain undetected could possibly lead to an increase in both the total and individual burden of disease, due to transmission and the need for more intensive treatment resulting in higher healthcare costs in the long term. In this study, we evaluated the new Dutch testing policy with respect to intended savings and missed syphilis and/or HIV infections. Moreover, we explored the efficiency of alternative test policies.

Using national surveillance data from 2011 to 2013 with still comprehensive testing for all, we estimated the effects of restrictive testing on test costs, number of infections missed, costs per missed infection, costs per Quality Adjusted Life Year (QALY) lost, and calculated the net monetary benefit.

The 2015-policy led to estimated savings of EUR1.1 million, while missing approximately three of ten HIV infections and seven of twenty syphilis infections among all younger heterosexual clients (in total 143,612 consultations) per year. Savings were EUR435,000 per QALY lost. Standard testing second-generation immigrants for syphilis and HIV saved EUR525,000/QALY lost. Offering an HIV test when diagnosed with chlamydia or gonorrhoea resulted in savings of EUR568,000/ QALY lost.

The 2015-testing policy resulted in substantial savings as few missed HIV and syphilis infections caused QALY losses. Additional standard syphilis and HIV tests for second-generation immigrants and an additional HIV test in case of positive chlamydia or gonorrhoea diagnosis could reduce missed infections in a cost-effective way.

The analysis of cell-free fetal DNA in maternal blood, also called Non-Invasive Prenatal Testing (NIPT), represents an emerging technology and a possible alternative/complement to current prenatal screening based on biochemical and sonographic markers for Down Syndrome (DS) detection.

The aim of the study was to compare the application of NIPT with the prenatal diagnosis/screening procedures currently applied in the Basque Country.

An analytical decision model was developed to assess the costs and consequences, comparing current prenatal screening, NIPT as a contingency test in high-risk cases and NIPT as a first-line screening test. An economic analysis was conducted to determine which strategy was more cost-effective. Sensitivity analyses were performed (1).

For a population of 97,074 pregnant women in gestational week 14 and a cut-off point of 1:270, NIPT as a contingent test was not cost-effective, detecting two cases less of DS and causing a lower number of miscarriages related to invasive-testing (4 versus 23) at a slightly lower cost (EUR8,111,351 versus EUR8,901,872).

For risk cut-off points of 1:500 or 1:1000 for contingent NIPT, the number of DS cases detected increased, as did the cost. It could be cost-effective compared with current prenatal screening, (EUR61,763 or EUR256,123 per extra DS case detected, respectively).

Using the NIPT as a primary test detected more DS cases (296 versus 271) and caused less miscarriages (5 versus 23), at a substantially higher cost (EUR41,395,645 versus EUR8,901,872). Cost-effectiveness analysis indicated that it was more expensive and more effective.

Univariant sensitivity-analysis showed that when the price of the NIPT as primary test was EUR76, it was dominant compared with current prenatal screening. It was also cost-effective compared with the NIPT as a contingent test (EUR9,869 per extra DS case detected).

The study shows that NIPT had higher detection rates for DS in different scenarios, but the cost constitutes a limiting factor for implementation in the Basque Health System.

Despite several therapeutic options existing for the patients with type I diabetes, the patients are still at high risk for severe acute and chronic complications (1). Pancreatic islet transplantation is a promising therapy to achieve good glycemic control with no or little additional insulin (2). This study was to evaluate the effectiveness, safety, economics and social ethics of islet transplantation (IT) for the patients with type I diabetes.

We searched PubMed, Cochrane Library, CNKI and CBM to retrieve eligible literatures. The values of H1bAc before and after transplantation, the rates of insulin independence and functional islet graft at the last follow-up, and the insulin dose per patient-day were analyzed. Descriptive statistics, t tests and random effects meta-analyses were used in the study.

Totally 21 original papers with 488 cases from 9 different countries were reviewed and analyzed. The studies showed that the H1bAc was decreased from 7.7 percent (95 percent Confidence Interval, CI: 7.4, 8.1) before IT to 6.2 percent (95 percent CI: 5.9, 6.4) after IT. At the last follow-up, the rate of insulin independence was 48.96 percent (95 percent CI: 31.32, 66.73) and the rate of functional islet graft was 65.79 percent (95 percent CI: 47.06, 82.21). The daily insulin requirement dropped from 0.52U/kg/d to 0.21 U/kg/d. The main adverse events of islet transplantation were bleeding (7.01 percent) and the complications related to immunosuppression therapy (6.37 percent), but they were less than those of whole pancreas transplantation.

Another study with a 20-year follow-up also showed that the cost-effectiveness of islet transplantation (USD47,800 per QALY) was better than that of insulin therapy (USD71,000 per QALY). In spite of the better evidences of islet transplantation, the insufficient organ donation and issues of cell purification and immunological rejection limited islet transplantation's widespread utilization (1).

The islet transplantation therapy for the patients with type I diabetes has a potential to achieve insulin independence and better cost-effectiveness, and is relatively safe. But there are some obstacles for its wide utilization.

High-intensity focused ultrasound (HIFU) is a non-invasive ablative technique to treat breast fibroadenomas and benign thyroid nodules. A rapid Health Technology Assessment (HTA) was commissioned to inform the Changi General Hospital's decision on procuring a HIFU system.

A systematic literature search was conducted for systematic reviews, HTA reports and clinical practice guidelines on the clinical effectiveness of HIFU systems with the following PICO elements:

Patients = patients with benign breast fibroadenomas or thyroid nodules

Intervention = HIFU

Comparator = conventional treatment

Outcomes = clinical outcomes

Retrieved studies were summarized in a narrative synthesis.

A few small case series showed reduction in volume of fibroadenomas/nodules in the short term and side effects were minor. Additionally, in HIFU for benign thyroid nodules, conference abstracts described a small open-label, randomized controlled trial where patients receiving HIFU had nodule volume reduction of over 30 percent compared to no reduction in the observation group, at 6 months; and a small non-randomized controlled study where volume reduction was about 70 percent in patients receiving HIFU compared to active observation.

Recent clinical guidelines do not mention HIFU as a therapeutic option for fibroadenomas/nodules.

Major United States health insurers do not cover HIFU and consider it experimental, investigational or unproven. In Germany, HIFU for breast fibroadenomas and benign thyroid nodules are covered by some insurers under special integrated care contracts.

HIFU for fibroadenomas/nodules is a technology still developing its evidence base. The peer-reviewed literature comprises a few small case series and two controlled trials showing fibroadenoma/nodule reduction in the short term (up to 12 months) but no long term outcomes. Professional opinion from current guidelines does not mention HIFU as an option.

It may be prudent to await stronger evidence on long-term patient-important outcomes before offering the treatment as a hospital service. HIFU may be suitable for further clinical research.

Popliteal artery aneurysm (PAA) is the most common peripheral arterial aneurysm and the second most common aneurysm after abdominal aortic aneurysm (AAA). It presents a risk of occlusion, which may lead to acute ischemia and leg amputation. To prevent these risks, asymptomatic PAA >2cm and symptomatic PAA must be treated. Although open PPA repair (OPAR) is still the gold standard, endovascular PAA repair (EPAR) is increasingly used to manage PAA. The objective of this study is to compare the cost of these two medical procedures from the hospital perspective.

Data were retrieved from the administrative database of Lausanne University Hospital (CHUV – Switzerland). Based on diagnostic codes and medical procedure codes, we selected all patients who underwent OPAR or EPAR between 2011 and 2015. Patient's age, length of stay and cost were compared between both groups using Student t-test.

We included seventy-three patient stays (OPAR forty and EPAR thirty-three). Gender balance was identical between groups (97 percent of male), but age was statistically significantly different (OPAR 67.5, EPAR 73, p = .04). EPAR induced shorter mean length of stay (5.1 days versus 11.7 days, p = .0000) and lower mean global cost (CHF 16,555 versus CHF23,514, p = .0085). Cost of procedure amounted to CHF 9,536 for OPAR versus CHF 3,848 for EPAR, medical supply and implants amounted to CHF 1,284 for OPAR versus CHF 7,041 for EPAR and other costs of hospital stay amounted to CHF 12,694 for OPAR versus CHF 5,666 for EPAR. (CHF 1.00 = USD1.00 = EURO 0.93)

With higher patency rate, OPAR is still associated with better medical outcomes than EPAR. But EPAR is significantly less costly than OPAR. Implant cost of EPAR is more than offset by longer length of stay and operating time of OPAR.

The purpose of the study was to evaluate different type and manufacturers of intensive care ventilators in order to support the healthcare decision-making process about the choice to adopt the best available technology for ventilation of pediatric patient in intensive care units at Bambino Gesù Children's Hospital.

The technology assessment process was developed by using a new methodology, the Decision-oriented Health Technology Assessment (HTA) (DoHTA), a new implementation of the European Network for Health Technology Assessment (EUnetHTA) CoreModel, integrating the Analytic Hierarchy Process (1). A literature review was carried out to gather evidence on safety and overall effectiveness of different kind of intensive care ventilators, with several ventilation modalities and strategies. The synthesis of scientific evidence, and results of the specific context analysis resulted in the definition of components of the decisional hierarchy structure, consisting in detailed characteristics of the technology's performances covering the aspects on feasibility, safety, efficacy, costs, and organizational and technical characteristics of the technology. A subgroup of these indicators has been included in a checklist form for the evaluation of different type and manufacturers of intensive care ventilators, each of which was tested in three independent runs performed in three different departments. In addition, an economic evaluation was also carried out.

Preliminary DoHTA results showed that the domains with the highest impacts within the evaluation are safety and clinical effectiveness (34.8 percent and 25.7 percent, respectively) followed by organizational aspects, technical characteristics of technology and costs and economic evaluation. The final objective is to define the alternatives’ ranking through a comparison between alternative technologies’ performances.

The technology assessment project allowed to identify strengths and limits of the most recent intensive care ventilator’ models in the specific contexts of use by involving all health professionals interested, and eventually identify the best option for the hospital.

Many countries that have used Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis (TB) have switched from universal vaccination of infants and children to selective vaccination, or discontinued with vaccination at all. The aim of the study is to assess the costs and cost-effectiveness of BCG vaccination in Estonia.

A Markov cohort model and budget impact analysis were used to compare the current, universal BCG vaccination to selective and non-vaccination strategies. The epidemiological and economic impact of BCG vaccination were estimated for the period 2018–2032 following the hypothetical change in the vaccination policy in 2018. The results were presented as the cost per case of TB adverted, changes in the occurrence of TB and yearly (undiscounted) costs associated with vaccination and TB treatment.

In a cohort of 13,500 infants over a time-period of 15 years Estonian universal BCG vaccination prevents around two TB cases compared to selective or non-vaccination strategies. The cost per one TB case averted for the universal strategy compared to non-vaccination strategy was EUR12,234 (EUR4,059–28,748 in sensitivity analysis) and compared to selective vaccination EUR3,847 (EUR504–10,568). The number of TB cases in 0–14-year old children in 2032 was estimated to be 1.3 for universal vaccination, 2.7 for selective and 2.9 for non-vaccination strategy. The total costs of vaccination and TB treatment in 2032 were estimated to be EUR23,764, EUR16,459 and EUR7,553 respectively.

The cost per case of TB averted is dependent on vaccine efficacy, and is high compared with the cost of treating one case of TB. At the same time, the total costs of BCG vaccination and TB treatment are marginal compared to other vaccination programs used in Estonia. Despite the limited budget impact, several organizational challenges need to be addressed if the universal program is replaced with selective BCG vaccination.

Dengue virus is a serious global health problem with an estimated 3.97 billion people at risk for infection worldwide. In December 2015, the first vaccine (CYD-TDV) for dengue prevention was approved in Brazil, developed by Sanofi Pasteur (1). However, given that the vaccine will potentially be paid via the public health system, information is needed regarding consumers willingness to pay for the dengue vaccine in the country, as well as discussions related to the possible inclusion of this vaccine into the public health system at prices suggested by the manufacturer. This was the objective of this research.

We conducted a cross-sectional study with residents of Greater Belo Horizonte, Minas Gerais, about their willingness to pay for the CYD-TDV vaccine. Respondents had to be over 18 years and not currently have the disease although they may have had dengue in the past (2,3).

Five-hundred and seven individuals were interviewed, who were mostly female (62.4 percent), had completed high school (62.2 percent), were working (74.4 percent), had private health insurance (64.5 percent) and did not have dengue (67.4 percent). The maximum median value of consumers willingness to pay for the CYD-TDV vaccine, assuming vaccine efficacy against virologically-confirmed symptomatic dengue illness of approximately 60 percent, is USD33.61 (BRL120.00) for the complete 3-course schedule and USD11.20 (BRL40.00) per dose. At the price currently being assessed by the Brazil's regulatory chamber of pharmaceutical products market (CMED) for Dengvaxia® for three doses, only 17 percent of the population expressed a willingness to pay for the vaccine at this price.

Brazil is currently one of the largest markets for dengue vaccine in the world and the price established is a key issue. The manufacturer should asses the possibility of lowering its price in Brazil to reach a larger audience among the Brazilian population, especially as other public health activities to control the disease will continue.

Existing evidence on clinical and economic effectiveness of one long-acting injectable antipsychotic (LAI) versus another in successful management of schizophrenia is scarce. The study was conducted to compare all-cause inpatient healthcare utilization and associated costs among Medicaid patients with schizophrenia who initiated LAIs.

This retrospective cohort analysis used the Truven Health Analytics MarketScan® Medicaid claims database. Schizophrenia patients >18 years with at least one claim for one of the following LAI were identified between 1 January 2013 and 30 June 2014 (identification period): aripiprazole, fluphenazine, haloperidol, paliperidone palmitate, and risperidone. The first day of initiating an LAI was considered the index date. Patients were followed for 1 year from index date. Logistic and general linear regression models were used to estimate risk of inpatient hospitalization and associated costs during follow up.

Of the identified Medicaid patients with schizophrenia, 1,672 (36.7 percent) initiated an LAI: 44.0 percent received paliperidone, 26.4 percent haloperidol, 13.8 percent risperidone, 9.2 percent aripiprazole, and 6.6 percent fluphenazine. With the aripiprazole cohort as the reference group, the odds of having any inpatient hospitalizations were significantly higher in haloperidol [Odds Ratio, OR (95 percent Confidence Interval, CI): 1.51 (1.05 - 2.16)] and risperidone [OR (95 percent CI): 1.58 (1.07 - 2.33)] cohorts. Fluphenazine and paliperidone palmitate cohorts also had higher risk of having any inpatient hospitalizations compared with aripiprazole, but the differences were not statistically significant (p>.05). Among LAI initiators with any inpatient hospitalizations, the adjusted mean inpatient costs were lowest in the aripiprazole cohort (USD25,616), followed by haloperidol (USD30,811), paliperidone (USD30,833), risperidone (USD31,584), and fluphenazine (USD37,338), although differences were not statistically significant.

Our study findings highlight the value of aripiprazole in reducing inpatient hospitalizations and associated costs among patients with schizophrenia. However, our study is limited as our results are reflective of a multi-state Medicaid population. Future studies are warranted to confirm the results in non-Medicaid patient populations.

Rheumatoid arthritis (RA) is an inflammatory, autoimmune disease of unknown etiology that usually results in joint lesions and physical incapacitation. RA treatment includes disease-modifying antirheumatic drugs (DMARD), synthetic (sDMARD) and/or biologics (bDMARD). In this study we carried out a cost-utility analysis comparing Adalimumab (ADA) versus Etanercept (ETA), with or without synthetic DMARDs (± sDMARD).

Effectiveness measures used were the Clinical Disease Activity Index (CDAI) and Quality-Adjusted Life Years (QALY) obtained from an open prospective cohort study with Brazilian RA patients. Costs were obtained from a historical cohort composed of every patient who was prescribed medicines to treat RA in the State of Minas Gerais, Brazil. A public sector perspective was adopted. The Markov model included six-month cycles, time horizon of 5 years and 5 percent discount rates. Sensitivity analyses were performed by varying costs and outcome values.

There was no significant difference in effectiveness between the two bDMARDs. Treatment with ETA (± sDMARD) was more expensive after 5 years of follow-up: incremental cost of USD28,210.87. Overall, treatment with ADA (± sDMARD) was more cost-effective: incremental cost-effectiveness ratio for ETA (± sDMARD) was USD79,148.34/ QALY. Sensitivity analysis showed that this was sensitive to changes in the cost of ETA (± sDMARD).

Currently two Anti-tumour Necrosis Factor Alpha (anti-TNF alpha) medicines – ADA and ETA are available within the Brazilian public health system in addition to infliximab. Treatment with ADA (±sDMARD) was more cost-effective with an incremental cost effectiveness ratio for ETA (±sDMARD) at USD79,148.34 per QALY. Sensitivity analysis showed that outcomes are sensitive to changes in the cost of ETA (± sDMARD) treatment. Overall, both therapeutic alternatives are valuable from the public sector perspective especially when the Clinical Protocol and Therapeutic Guidelines are properly applied in patients no longer responding to treatment. Alternatives are needed as some patients will respond differently to different anti-TNF alpha medicines.

This study estimated, from the societal perspective, the costs and benefits of the intensive inpatient rehabilitation treatments (IIRT) on patients after stroke using the interim results of a large ongoing registry in Korea, the Korean Stroke Cohort for Functioning and Rehabilitation (KOSCO) (1).

Among others, the benefits were measured by two major cost savings: (i) decrease in government disability subsidy and (ii) caregiver savings. One of the KOSCO study results showed the functional status of the post-stroke patients, measured by the Korean Modified Barthel Index (K-MBI), improved significantly and the disability grades, which the government is using to classify the subsidy amount, reduced as well. Caregiver cost savings were calculated by K-MBI improvements, the average daily compensation of caregivers (USD58.33) and the average period of caregiving. To measure the cost of IIRT on post-stroke patients, the average costs reported by a National Evidence-based Healthcare Collaboration Agency (NECA) Health Technology Assessment report was used (2).

The disability grade improvements showed savings of government subsidy by USD58.65 to USD478.39 depending on the patient income from the registry. The average caregiving cost decrease was USD6,042 annually. The average cost of IIRT on post-stroke patients was USD926.34 for the first year.

This study estimated the cost-benefit of IIRT on post-stroke patients using the KOSCO study interim data. The intensive rehabilitation treatment improves patients functional status significantly enough to save two major cost items, the disability grades which also resulted in a decrease in government subsidy amounts and the caregiver costs which the patient family has to pay in Korea. The results warrant the use of IIRT for the post-stroke patients in Korea from the societal perspective.

The evaluation of orphan drugs raises both positive and normative issues. Due to the rarity of the disease, higher drug costs and greater uncertainty on effectiveness often result in incremental cost-effectiveness ratios (ICER) far beyond the usually accepted thresholds for reimbursement. However, decision makers may need to consider other criteria to assess the social value of orphan drugs such as equity, the rule of rescue, and the perceived need in the community. Hereditary Angioedema (HAE) is a rare congenital deficiency resulting in recurrent attacks of angioedema in affected patients. These episodes cause extreme pain and distress, and may even be fatal when air pathways are involved. In Italy, icantibant or C1-Esterase-Inhibitors (C1-INH) are the indicated treatments for acute attacks. Although more expensive, icantibant may reduce time to symptom-relief and the need for further treatments. Nonetheless, evidence on its social value is missing. The present study aims at evaluating the cost-effectiveness of icantibant and providing new insights on other potentially relevant criteria for decision making on HAE treatments.

A cost-effectiveness model of icantibant versus C1-INH (Berinert) was developed. Using a two-part bayesian model, costs were estimated from real-world data of an unpublished national registry. Efficacy data were synthesized from both the registry and an indirect comparison of existing trials, whereas utilities were derived from the literature.

In our Italian registry, respectively 98 percent and 60 percent of patients self-administered icatibant or Berinert at home in absence of medical personnel. On average, per treatment costs were 60 percent higher and attack duration 25 percent shorter with icantibant compared to Berinert. The resulting ICER greatly exceeded the considered threshold of EUR30,000.

On cost-effectiveness grounds icantibant did not demonstrate good value for money compared to Berinert. However, further considerations are needed on whether standard health-related quality of life measures are able to truly reflect societal preferences for HAE treatments.The use of real-world data for the economic evaluation of orphan drugs can support decision making when evidence from clinical studies is too sparse.

The Patient Reported Outcomes Burdens and Experiences (PROBE) questionnaire was developed with direct patient involvement in questionnaire design, conduct and analysis using patient-centered outcomes to assess health status in patients with hemophilia (PWH). Phase 1 confirmed robustness of the methodology and feasibility. Phase 2a investigated individual test-retest reliability. Phase 2b will explore population level reproducibility.

PWH and non-PWH individuals who attended a hemophilia-related workshop were asked to complete the PROBE questionnaire 3 times (paper-based survey on 2 consecutive days and then a web-based version). Test-retest reliability was analyzed using the percentage agreement and Kappa statistic. Kappa coefficient interpretation .81-1.00 almost perfect, .61- .80 substantial; .41- .60 moderate; .21 -.40 fair; .00 -.20, slight; and < .00 poor agreement.

Sixty-three participants from twenty-one countries were enrolled with a median age of 50 (range 14–76) years. Of these, thirty (47.6 percent) were PWH or carriers, thirty-three (52.5 percent) were participants with no known bleeding disorders. On general health domain, Kappa coefficients ranged from .69 to .92, indicating substantial to almost perfect agreement, for all items. Reliability of the web-based questionnaire showed moderate to substantial agreement for all except one item. For the hemophilia-related domain, Kappa coefficients ranged from .5-1.0. Of these, five of eleven items were in perfect agreement (Kappa = 1.0). Reliability of web-based questionnaire items were in substantial to almost perfect agreement. For overall health related quality of life, the EuroQol five dimensions questionnaire (EQ-5D) had Kappa coefficients of .62 to .92. Intraclass correlation coefficient of visual analog scale (VAS) was .90 (95 percent Confidence Interval, CI; .83-.94). Test-retest reliability was comparable between hemophilia patients and participants with no known bleed.

Phase 2a demonstrated individual test-retest reliability and suggests PROBE is a reliable tool to assess Patient Reported Outcomes in PWH. The Web-based questionnaire has an acceptable agreement with the standard paper-based version in all domains. PROBE Phase 2b, to demonstrate reproducibility at the population level, is on-going. To date, 1,039 participants have been recruited from 10 countries.

Patient evidence is submitted to the National Institute for Health and Care Excellence (NICE) by patient organizations and individual patient experts. Previously NICE developed a new patient organization evidence submissions template, based on the international HTAi patient submission template for medicines (1). The NICE template was reviewed by surveying committee members and also patient organizations who had used the submission template. The findings were presented at HTAi 2016.

The limitation of that review was the low response rate from patient organizations. The key recommendation was to extend the survey to include a larger number of patient organizations. These local findings are an opportunity to contribute to the global Health Technology Assessment (HTA) ecosystem.

A project group was convened consisting of NICE staff, a committee lay member and a patient organization representative. Together we reassessed the suitability of the previous feedback survey. This was then sent out to patient groups who had completed the submission template from July 2014 to November 2016. Additionally, public involvement staff telephoned selected patient organizations to increase the feedback response rate and gain greater understanding. The anonymized results were shared with patients involved in NICE who helped interpret the results from a patient organization's perspective.

Key findings are that patient organizations find:

• • the template clear

• • it was easiest to provide information about living with the condition

• • it was hardest to give information on equality issues and research evidence.

They would also like a submission guide, and to receive feedback on their submissions.

Although it was difficult to obtain feedback from the patient organizations on the submission template, the depth of information provided by them was fundamental to updating the template and producing a supporting guide.

This feedback on the local English needs can be used when evaluating the international submission template to form a greater part of the HTA ecosystem.

In Europe, the work done by the European Commission and the European Network for Health Technology Assessment (EUnetHTA) has consolidated the role of Health Technology Assessment (HTA), and promises to better harmonize its impact across European Union (EU) countries. However, more work is needed to improve patient involvement in assessing new health technology, and in developing research priorities.

The European Cancer Patient Coalition (ECPC) developed a model for engagement of patients in HTA based on the experience from:

• • ECPC's ‘Value of Innovation in Oncology’ White Paper, which includes input from ECPC's membership

• • ECPC's leading role in the Patient Preferences in Benefit-Risk Assessments during the Drug Life Cycle (PREFER) study, funded by the Innovative Medicines Initiative, to develop guidelines on how patient-preference studies should be performed throughout the development of new medical treatments.

The ECPC ‘Value of Innovation in Oncology’ White Paper was launched in 2017. The paper provides ECPC's policy position on key obstacles to equitable access to meaningful innovation. The paper recommends the establishment of an EU-wide HTA body to reduce delays and variations in access and to avoid duplication of effort by individual Member States. The paper also recommends that patients should be formally and routinely included in HTA policy and operations at EU and at national levels. These recommendations were also submitted to the European Commission's public consultation on strengthening EU cooperation on HTA.

Through its work in PREFER, ECPC is helping to improve how patient preferences are measured and valued to capture the impact of health technology on patients daily life. Patient preferences are concerned with measuring how patients value components such as treatment end points, route of administration, treatment duration, treatment frequency, frequency of side-effects, price, and quality of life.

Patient organization involvement in HTA is vital. Patient organizations offer unique insights, experiences, identify unmet needs, and can help to produce practical recommendations

The National Institute for Health and Care Excellence (NICE) medicines health technology assessments (HTAs) involve patients throughout (1): scoping the topic, evidence submission, attending committee as ‘patient experts’, consultation and appeal. A 2013 Health Select Committee report stated “It is important for the credibility of NICE and for the decisions that it makes that the patient voice is effectively and openly represented in all its work” (2). We thus wished to build on previous evaluation projects with more formal research into the views of patient organizations and individual patient experts on their involvement. We additionally sought to explore barriers to involvement.

The research was a collaboration between staff from three teams at NICE: public involvement, market research, and HTA committee support. A mix of interviews, focus groups and surveys was used to gather feedback – from patients and organizations who have engaged with NICE, but also those who had not, plus NICE committee chairs and staff. Facilitators and barriers to involvement were investigated, along with attitudes towards process and support. We used qualitative thematic analysis alongside quantitative methods.

Key findings were that patients and patient organizations mostly:

• • hold favourable opinions of NICE

• • have a good understanding of process and expectations

• • remain unsure of the impact of their inputs.

Improvements identified include clarifying communications, language and roles. Plus increasing transparency of decision making and patient impact.

The research findings and action plan, although specific to NICE, hopefully can inform others in the wider HTA ecosystem. Resources developed will be shared with Health Technology Assessment International (HTAi) networks, including updated correspondence templates and new videos explaining decision making in lay language. The research further adds to discussions around appropriate use of patient organizations scarce resources, and how best to feedback to participants and demonstrate impact of patient involvement.