The Philippines has an increasing number of newly diagnosed cases of human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS). In 2010, the Philippine National Health Insurance Corporation (PhilHealth) introduced an Outpatient HIV/AIDS Treatment (OHAT) package to cover the necessary basic healthcare expenses of patients. The objective of this study was to review patients’ perspectives on the OHAT package in terms of meeting health needs and providing economic risk protection.

The study was divided into two phases: (i) patient surveys (PS); and (ii) health provider interviews (HPI). The PS focused on the health needs of package utilizers and non-utilizers, specifically their satisfaction with the current package coverage. The HPI focused on key personnel working at treatment hubs to gain insight on the impact of the OHAT package on facility operations, service delivery, and patient care.

The majority of patients were satisfied with the current package because of the reduced annual out-of-pocket (OOP) costs. However, continuing OOP expenditure was also the main reason for dissatisfaction. This was due to non-uniform provision of services across different hubs, mainly resulting from the unavailability of services and health provider discretion on final package inclusions. Non-coverage of opportunistic infection (OI) treatment and privacy issues were also noted as causes of dissatisfaction. Claim filing for formal membership requires an employer's signature for proof of contribution. Due to the fear of stigma some members created a second insurance account or shifted to an individual payment type, which increased OOP expenses.

The OHAT package has increased access to services and medications for HIV/AIDS patients in the Philippines. Despite increasing package utilization there is still room to improve the package, especially with regard to addressing privacy needs and non-uniform package inclusions, and extending coverage to the treatment of OIs.

Pompe disease is a rare disease, in which therapies are aimed at improving the function of the heart and skeletal muscles, and the quality of life of patients. This review aims to update and evaluate the safety and efficacy of alpha-alglucosidase therapy for treating Pompe disease.

We performed a literature search of Medline, EMBASE, the Center for Reviews and Dissemination, the Latin American and Caribbean Health Sciences Literature, and Cochrane. Publications of the National Institute for Health and Care Excellence and national and international guidelines have been consulted. The quality of the evidence was assessed using the criteria of the Grading of Recommendations Assessment, Development and Evaluation - GRADE. We performed annual cost estimates of alpha-alglucosidase for the treatment of adult and pediatric patients.

In a randomized clinical trial comparing alpha-alglucosidase enzyme replacement therapy (20 mg / kg) with placebo for 78 weeks, the results favored alpha-alglucosidase (an increase of 28.1 ± 13.1 m in the six minute walk and an absolute increase of 3.4 ± 1.2 percent in forced vital capacity, p = 0.03 and p = 0.006, respectively). In another systematic review, it was observed that patients treated with alpha-alglucosidase had a mortality rate five times lower than untreated patients (rate ratio = 0.21, 95% CI: 0.11 − 0.41). In a pediatric population with advanced disease, biweekly infusions prolonged survival and survival free of invasive ventilation. The quality of the evidence was classified as very low. The annual treatment costs were USD 296,187.64 (adult patient with 70 kg) and USD 42,312.52 (pediatric patient with 10 kg).

The limited available evidence suggests alpha-algalsidase is efficacious in Pompe disease patients with some clinical conditions who do not present negative cross-reactive immune material. The balance between the limited quality of the evidence and the demonstrated benefits is favorable, especially for clinical improvement, reduction of mortality and intangible benefits.

There is no consensus on which methods to use to estimate an opportunity cost threshold for the efficient allocation of resources. Researchers have attempted to estimate an evidence-based threshold value, but only a few approaches have been considered and any estimate is currently used by policy makers. This study aims at exploring three assumptions normally applied in the threshold estimation: (i) approaches assume that there is always a displacement involving a loss of health; however, empirical studies suggest that one of the first responses of local health care purchasers is to squeeze greater efficiency out of providers; (ii) to be sure about the appropriate threshold it is necessary to know which health services purchasers are giving up to introduce a new treatment; current estimates bypass this lack of information by averaging the effects of changes in expenditure by clinical area; (iii) recent methodologies consider a single health outcome: mortality; however, health outcomes of many clinical areas may not be well reflected in mortality.

We propose data envelopment analysis (DEA) as a methodology that can help to address these issues by considering efficiency to measure opportunity cost per Primary Health Trust (PCT) in England and by including several outcomes in addition to mortality. This is the first time that DEA is tested in this context.

Results suggest that the majority of health locations have the possibility of decreasing their expenditures between 1 percent and 15 percent without affecting outcomes.

Estimation of the threshold should allow for observation of the actual level of inefficiencies as well as an ability to consider the previous capacity of health locations to respond to changes in expenditures. Moreover, it is crucial to select the appropriate set of health outcomes, such that they reflect health system priorities, otherwise, we would be estimating a threshold that does not reflect likely displacement.

Diabetes causes complications and collateral diseases, reducing quality of life and increasing medical costs. The Japanese government has promoted measures for the prevention of diabetes aggravation. Although glycemic control is reported to prevent the development of complications, assessment of the effects on overall medical cost is insufficient. We examined the medical cost by the analysis of hemoglobin A1c (HbA1c) level.

A Japanese employee-based health insurance claims database with annual medical check-up data was analyzed. Excess medical cost was calculated as the difference between medical cost and standard medical cost (defined as the average medical cost for individuals of same age and sex). Percentage of excess medical cost was calculated by dividing excess medical cost by standard cost, and compared between individuals with or without treatment for diabetes.

Of 4,307,184 individuals with HbA1c data, four percent of them received treatment for diabetes. For treatment of 6.5 percent of HbA1c, excess medical cost increased to 124 percent. The medical cost increased by an additional 20.4 percent (95% CI: 17.1–23.8) when the HbA1c level increased one percent. Treatment for less than six percent of HbA1c caused an increase consistent with the HbA1c level. The relative risk of iron deficiency anemia, unspecified of those with less than six percent of HbA1c against those with seven to eight percent was the highest, 2.15.

An increase of medical cost for individuals with treatment for high HbA1c is likely associated with diabetic complication. The raise for individuals with lower HbA1c level may be related to anemia. Despite the younger age and healthier life of the analyzed individuals, since they were insured by employee-based health insurance who took regular medical check-ups, more expensive medical cost was observed for those having higher HbA1c level.

The role of Health technology assessment (HTA) as a systematic approach in the evaluation of health interventions and technologies is becoming increasingly important as the quest for attaining universal health coverage globally continues to increase. Some developed countries in Europe and the Americas now apply HTA extensively in healthcare policy decisions, however, developing regions and countries like sub-Saharan Africa and Nigeria respectively, seem not to be making significant progress in this area. Given that evidence suggests that Nigeria and indeed several countries in sub-Saharan Africa are performing poorly on most healthcare indices as the region continues to be ravaged by predictable and avoidable epidemics and disease outbreaks, the need to build HTA capacity has never been more paramount.

A review of HTA capability in Nigeria was done. Pharmacists in Nigeria's Capital were randomly sampled. Semi-structured questionnaires were administered. Descriptive statistics was used in data analysis. P values less than 0.05 were considered to be significant.

In Nigeria, there is no institution tasked with undertaking HTA and there seems to be limited knowledge, capacity and awareness on the issue. Pharmacists, being the most accessible healthcare professionals according to evidence, are a key group that could play an active role in HTA and its implementation in developing countries like Nigeria. However, out of 322 pharmacists randomly sampled, ninty-three percent were not aware of HTA and its application in healthcare decision-making.

There is no paucity of healthcare programs and plans in Nigeria but they seem to fail due to lack of evidence-based assessment, decision-making and implementation. Hence, there is increasing need to raise awareness on the importance of HTA in healthcare decision-making; strengthen HTA capacity by developing and sustaining institutional capacity and adequate human resource for HTA; and creating regional annexes of HTA organizations in Africa.

The objectives of this study were to estimate the economic burden of human papillomavirus (HPV) in Italy, accounting for total direct medical costs associated with nine major HPV-related diseases, and to provide a measure of the burden attributable to HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 infections.

A cost-of-illness incidence-based model was developed to estimate the incidences and costs of invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, oropharyngeal, anogenital warts, and recurrent respiratory papillomatosis (RRP) in the context of the Italian National Health System (NHS). We used data from hospital discharge records (HDRs) of an Italian region and conducted a systematic literature review to estimate the lifetime cost per case, the number of incident cases, the prevalence of HPV9 types. Costs of therapeutic options not included in the diagnosis-related group (DRG) tariffs were estimated through a scenario analysis.

The total annual direct costs were EUR 540.7 million, with a range of EUR 338.3 – EUR 789.7 million. These costs could increase considering innovative therapies for cancers treatment (range EUR 16.2 – EUR 37.6 million). The fraction attributable to the HPV9 genotypes without innovative cancers treatment was EUR 329.2 million (range EUR 150.1 – EUR 576.7 million), accounting for sixty-one percent of the total annual burden of HPV-related diseases in Italy. Of this amount, EUR 136.7 million (forty-two percent) was related to men, accounting for sixty-four percent of the costs associated with non-cervical conditions.

The infections by HPV9 strains and the economic burden of non-cervical HPV-related diseases in men were found to be the main drivers of direct costs. The fraction of the total direct lifetime costs attributable to infections by HPV9 strains and the economic burden of non-cervical HPV-related diseases in men were found to be the main drivers of direct costs.

Eliciting implicit value-judgments (VJs) in the HTA process is one way of integrating ethics in HTA since the latter is recognized as a value-laden process. An analysis of the diversity of opinions on implicit VJs in HTA and of their role, highlights the connection there exists between VJs and the different decisions involved in the whole HTA process. Such a link is corroborated by a conceptual analysis of VJ using a speech-act philosophical approach grounded in the philosophy of language, since VJs are linked with normative speech-acts such as commands, recommendations and advices.

We propose an analysis of the published citations mentioning VJs, extracted from our systematic review on the challenges of integrating ethics in HTA. In order to do so, those quotes were categorized in a chart, the latter of which presents: (i) the different steps of decision-making in the HTA process, (ii) the description of the implicit VJ(s) and (iii) the criteria involved. This chart was elaborated with the participation of the HTA local evaluators involved as co-investigators in our research group. The final version was discussed, debated and validated by the entire research group.

The chart shows 18 decision-making steps in the HTA process in which twenty-three implicit VJs can be observed. The range of such VJs encompasses the whole HTA process from the initial mandate to the agency presenting the decisional issues, to the dissemination of the final report. The published citations gathered for each category compile different expectations on the elicitation of the implicit VJs, thus making the latter VJs more explicit.

This chart allows a better understanding of the expectations that are at the core of the appeal for more transparency in the HTA process, since stakeholders need to understand which value-judgments the final conclusion of a report is relying on.

The pan-Canadian Oncology Drug Review (pCODR) was established in 2010 to bring consistent oncology drug assessments across Canadian provinces/territories. In April 2014, pCODR was transferred to the Canadian Agency for Drugs and Technologies in Health (CADTH). This transfer comprised two phases. In phase one, pCODR staff, processes, funding, and expertise remained intact as a program but under the government of CADTH. In phase two, beginning April 2015, better alignment of pCODR and CADTH evaluation criteria and review processes were explored. This research aims to see what effect the CADTH transfer has had on the number of appraisals conducted by pCODR and their recommendation rates.

All publically available pCODR reports were extracted up to 22nd November 2017. The drug, indication, date and outcome were extracted. Statistical comparisons were made using Student's t-test.

Ninety-six appraisals have been conducted by pCODR, reflecting an average of 16 per year (10 in 2012, 18 in 2013, 9 in 2014, 24 in 2015, 19 in 2016, and 20 in 2017). The rate of appraisals was similar pre-CADTH transfer (14.2 per year [32 from January 2012 to March 2014]) versus post-CADTH transfer (13.7 per year [56 from April 2014 to November 2017]). Seventy-eight percent of pCODR outcomes were positive recommendations (defined as full recommendations [10 percent] or restricted/conditional recommendations [68 percent]) with 22 percent not recommended. Annually, positive recommendation rates were 70 percent in 2012, 89 percent in 2013, 78 percent in 2014, 79 percent in 2015, 74 percent in 2016, and 75 percent in 2017. There were no significant differences in recommendation rates since pCODR was transferred to CADTH irrespective if the phase one or phase two cut-off dates were used (p = 0.434 and 0.307, respectively).

The number of appraisals and likelihood of a positive recommendation for oncology drugs has not been affected by the pCODR transfer to CADTH.

Paroxysmal atrial fibrillation (PAF) represents a significant economic burden to the healthcare system. Catheter ablation is a commonly adopted treatments for PAF, and cryoballoon ablation (CBA) has been recently proven to be as effective as radiofrequency ablation (RFA). This study aims to evaluate the cost-effectiveness of CBA versus RFA in patients with drug-refractory PAF in China.

A Markov model was developed to study the effects and the costs of CBA versus RFA. Cost and probability inputs data were obtained mainly from a real-world study of 85 CBA and 284 RFA patients treated in a tertiary hospital between July 2014 and July 2016. Propensity score matching was used to overcome retrospective bias, resulting in including 75 patients in each group. Input data gaps were closed with literature review and advisory board. A simulation was carried out for 14 cycles/years, and a discount rate of 3 percent was used. Then, a probabilistic sensitivity analysis was carried out with Monte Carlo approach.

In the base case scenario, the cumulative costs incurred by the CBA and RFA groups were CNY 132,222 (USD 20,767) and CNY 147,304 (USD 23,136), respectively. Over the 14-year period, the quality-adjusted life years (QALYs) gained by the CBA group was 7.85 versus 7.71 in the RFA group. The incremental cost-effectiveness ratio for CBA versus RFA was thus CNY 107,729 (USD 16,920)/QALY. Model results were most sensitive to the cost incurred during the first hospitalization, recurrence rate, and relative utility weights. The probability of CBA being cost-effective for willingness to pay thresholds of per capita GDP in China was estimated to be 99 percent.

Compared with RFA, CBA is a cost-saving treatment providing increased QALYs. It represents good value for money for patients with drug-refractory PAF in China. However, further evidence needs to be generated from larger-scale studies in China.

We aimed to pilot the evaluation of the PEGASO system, a smartphone-based intervention (apps/wearables/game) to improve lifestyles and increase awareness.

We conducted a before-after quasi-experimental pilot controlled study. Teenagers aged 13–16 in a 2:1 (intervention: comparative group [IG:CG]) basis from Spain, Italy and the United Kingdom were recruited. The IG had access to the apps and game for six months, and to smart sensors for the last two months. Schools were recruited by convenience sampling. Participants in both groups undertook (i) anthropometric measurements, (ii) diet (KIDMED), physical activity (PAQ-A) and sleep (HELENA study) validated questionnaires, and (iii) ad-hoc lifestyles knowledge questionnaire. PEGASO, if used, continuously recorded diet and physical activity. User experience was assessed through focus groups.

Five hundred and fifty-eight participants were included (IG:365 / CG:193). The mean (standard deviation; SD) age was 14.8 (0.8), and 52.3 percent were girls. At baseline, mean scores (SD) of KIDMED, PAQ-A and weekday and weekend sleep hours were 5.60 (2.41), 2.48 (0.66), 8.34 (1.07) and 9.99 (1.66), respectively. The percentage of correct answers of lifestyle's knowledge was 65.2 percent (range 13–100 percent). The IG and CG did not show differences for main outcome variables. At six months, a higher percentage of participants in the IG reported an increase of at least one point in the adherence to Mediterranean Diet (43.8 percent vs. 35.4). No differences were observed for other lifestyles. Focus group results showed a predisposition of adolescents to use mHealth for health promotion; the platform was considered to be useful and complete and personalized suggestions were positively valued. Participants reported few limited interest ion the game and several technical issues.

Although participants were motivated and excited about their involvement in the study, and that PEGASO was something desirable for them, the system only showed some impact in specific areas – namely, diet – and could improve some its technological features. Several challenges and opportunities are associated with the implementation of mHealth.

Colorectal cancer (CRC) is the fourth leading cause of cancer deaths in the Philippines. In 2014, the Philippine Health Insurance Corporation (PhilHealth) created a CRC treatment package. The study aimed to determine the cost-utility and budget impact of CRC screening strategies.

A discrete-event microsimulation model was used to simulate four screening modalities: (i) guaiac-fecal occult blood test (gFOBT) followed by colonoscopy every 10 years; (ii) fecal immunochemical test (FIT) followed by colonoscopy every 10 years; (iii) FIT followed by flexible sigmoidoscopy; and (iv) colonoscopy screening every 10 years. These interventions were all compared to no screening. Parameter values were taken from a rapid review of the medical literature and primary data collection from a nationally representative sample of tertiary hospitals.

All screening modalities were very cost effective considering that the incremental cost-effective ratios (ICERs) were lower than the gross domestic product per capita threshold suggested by the World Health Organization. Sensitivity analysis showed that the ICERs of all screening modalities evaluated remained below this threshold. The strategy of using FIT followed by colonoscopy every 10 years had an ICER of USD 6,025, with an annual budget impact of USD 6.5 million, assuming low compliance. With moderate compliance this could increase to USD 18.7 million annually.

PhilHealth may introduce a benefit package for outpatient screening of colorectal cancer using the screening modality of annual FIT followed by colonoscopy every 10 years.

Influenza A (H1N1) virus is the most relevant virus in death by flu complications. Oseltamivir and zanamivir are used for influenza prophylaxis in epidemics. We aimed to evaluate the efficacy of chemoprophylaxis for influenza A (H1N1) for the Brazilian health care system.

We systematically searched the literature to identify efficacy results. Costs assessed from the system perspective were obtained from official Brazilian Ministry of Health systems, and completed from medical care at a university hospital of Campinas, Sao Paulo. Model outcomes were quality-adjusted life years (QALY) with willingness to pay BRL 30,000 (USD 8,212)/QALY and prevention of H1N1. A decision-tree model was used to calculate the incremental cost-effectiveness ratios for prophylaxis, compared to no prophylaxis. Deterministic and probabilistic sensitivity analyses were used to test robustness of the model.

Prophylaxis had 70 percent adherence to treatment, 9 percent adverse events, effectiveness in avoiding H1N1 (relative risk = 0.43; 95% confidence interval: 0.33, 0.57); no evidence of prophylaxis efficacy for complication, hospitalization and death was found. Both scenarios had 14 percent H1N1 attack rate, 67 percent of ambulatorial consult, 43 percent of inpatient care, 14 percent of deaths in hospital, 23 percent of intensive care where death was 40 percent. Utility was 0.50 during H1N1 infection, 0.23 with hospitalization, 0.195 less with adverse events, 0 for deaths and 0.885 for healthy. Cost was BRL39 (USD 11) for chemoprophylaxis; BRL 12 (USD 4) for outpatient care; BRL 5,728 (USD 1,568) for hospital admission; BRL 19,217 (USD 5,260) for intensive care; and BRL 292 (USD 80) for adverse events. Incremental cost of prophylaxis was BRL 40 (USD 11) and utility increased 0.004, which mean saving of BRL 2,921 (USD 780)/QALY. Prophylaxis saves BRL 338 (USD 92) per H1N1 case avoided. Univariate and probabilistic sensitivity analysis assure the robustness of results, with 43 percent probability of being of lower cost and higher effectiveness.

Prophylaxis is cost-effective from the health care system perspective using utility and avoided H1N1 cases outcomes.

The purpose of the study is to estimate both the number of beneficiaries and the burden of the Disability Insurance (DI) benefits provided for neoplastic diseases (ND) and for five cancer types, focusing on the expenditure by the social security system.

To estimate the current DI benefits and their cost, we analyzed the databases of DI awards and the mean cost per benefit of the Italian National Social Security Institute (INPS) for two types of social security benefits: the disability benefits (DB) for people with reduced work ability and the incapacity pensions (IP) for people without work ability. A probabilistic model with a Monte Carlo simulation was developed in order to estimate the total benefits provided and costs.

Between 2009 and 2015, a yearly average was estimated of about 122,000 beneficiaries of DI for cancer. The total estimated expenditure for ND in the seven years, supported and provided by INPS for these social security benefits, amounted to EUR 8.1 billion (corresponding to 27.4 percent of the total expenditure for disability provided by INPS) of which 66.7 percent was associated with DB and the remaining 33.3 percent with IP. The percentage increase related to the costs show that DB have the most significant increase starting from the 2013 with 11.3 percent from 2013 to 2014 and 9.7 percent from 2014 to 2015, while. IP have an increase from 2009 to 2011, with a maximum during 2011, with a percentage difference of 7.6 percent.

The incidence and the prevalence of the ND are expected to increase in the coming years in Italy. In order to minimize the consequences of this scenario, rapid access to innovative treatments would reduce the costs borne by the social security system, accompanied by an improvement in the effectiveness of interventions and increase in quality of life for patients.

Quality of life (QoL) is an important health measure and is widely used to assess the difference between treatments for Type 1 Diabetes Mellitus (T1DM) since the desirable glycemic control and the minimization of episodes of hypoglycemia are fundamental aspects for a better QoL. This study aims to identify the factors associated with QoL in patients with T1DM.

A cross-sectional study (approved by ethics committee) was carried out in the state of Minas Gerais with 401 T1DM patients who used insulin glargine (GLA) selected in March 2017, and 179 patients who used insulin-neutral protamine (NPH) selected between January and February 2014, and both groups were treated by Brazilian National Health System (SUS). A questionnaire with three blocks was used: A) sociodemographic data; B) clinical data and access to the service; and C) QoL by Euroqol (EQ-5D-3L). We used multiple linear regression model by the forward stepwise method to access the correlation between the utilities of the EQ-5D-3L and all the explanatory variables (blocks A and B). We adopted the significance level and confidence interval of 95 percent (95% CI).

Of the 580 patients evaluated, 54 percent were women, 47 percent were in the age group between 18–40 years, 53 percent reported to be non-black. The EQ-5D-3L analysis showed patients treated with insulin analogue GLA had an average utility of 0.849 and those treated with NPH insulin 0.722 (p < 0.000). Individuals young, very good/good health self-perception, having not been bedridden in the last 15 days, zero to three medical appointments in the last year, no hospitalization in the last year, regular physical activity in the last 15 days to practice physical exercise, having between zero and three comorbidities and no severe hypoglycemia in the last 30 days were explained 41.3 percent of QoL. The type of insulin therapy, GLA or NPH, did not enter into the final multiple regression model.

The findings of this study pointed to a lack of correlation between insulin therapy and QoL of patients with T1DM. Sociodemographic and clinical factors were more important to explain the QoL of diabetics. In addition, the evidence pointed to the importance of episodes of hypoglycemia for Qol. Of the 191 episodes of hypoglycemia (non-severe and severe) reported, 66 percent were from patients treated with GLA.

Clinical practice guidelines (CPGs) are a key vehicle for converting evidence into action. CPGs can be produced by various methods: de novo, adaptation, adoption, or a combination of these. Deciding whether and how to develop a guideline can be challenging. Health technology assessment (HTA) researchers from the Institute of Health Economics developed a multi-step decisional algorithm highlighting the decision nodes in the initial phase of guideline development where HTA products and expertise can be valuable in demystifying these decisions.

A literature search was conducted for articles comparing methods of developing CPGs, with particular focus on finding a priori criteria for deciding when to use one method versus another.

The published literature is sparse and there are no specific criteria available for deciding when to use one method of development versus another. The proposed multi-step algorithm identifies similar steps in the production of all types of CPGs: the set-up phase; establishing the need for a new CPG in consultation with a guideline development group and local stakeholders; developing research question(s); conducting searches for suitable existing guidelines; and finalizing the guideline. HTA can help set the health question(s) and identify and screen existing CPGs. When CPGs are not available, HTA methods are implemented to update the evidence in a blend of de novo and adaptation processes by reviewing umbrella reviews, systematic reviews, and primary studies. Quality appraisal of existing guidelines and syntheses of evidence in a rapid review fashion help determine whether there are enough studies to support the guideline scope.

Deciding which method of guideline development to employ requires ample methodological expertise, an intimate knowledge of the clinical practice environment, and access to detailed contextual information. The proposed multi-step algorithm shows how to successfully leverage HTA resources to support CPG production and move research evidence into practice.

This study was done to assess the cost effectiveness of nivolumab plus ipilimumab (NIV+IPI) versus nivolumab alone (NIV) for previously untreated patients with advanced melanoma (AM) from the Dutch health system perspective.

A Markov model was constructed with a lifetime horizon. Future effects and costs were discounted at 1.5 and four percent, respectively. Risks of progression and death were based on progression-free survival rates obtained from a phase III clinical trial (NIV+IPI and NIV versus ipilimumab). Conjectural overall survival rates were calculated indirectly by using progression-free survival and overall survival rates from another trial (NIV versus dacarbazine), and were extrapolated later using the Weibull distribution. Utility values of health states and disutility values of adverse events were derived from the literature. Unit costs were derived from the Dutch Diagnosis Treatment Combination Care Products Tariff, Erasmus University Medical Center prices, and Dutch pharmacy purchase prices. Chronic management costs of AM and treatment costs of adverse events were calculated based on the results of a survey of clinicians that determined the necessary healthcare services and their utilization rates.

On average, over a lifetime an AM patient treated with NIV+IPI was estimated to live 4.2 years and 2.6 quality-adjusted life-years (QALYs) at a discounted net cost of EUR 262,824 per patient, while a patient treated with NIV was estimated to live 3.3 years and 2.0 QALYs at a discounted net cost of EUR 195,341 per patient. The incremental cost-effectiveness ratio was EUR 70,770 per life-year saved, and the incremental cost-utility ratio was EUR 115,533 per QALY gained.

At a willingness-to-pay threshold of EUR 80,000 per QALY gained, NIV+IPI may not be a cost-effective tool, compared with NIV, for preventing the high mortality and morbidity associated with AM from the Dutch health system perspective.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of olaratumab (Lartruvo®), Eli Lilly & Company Limited, to submit evidence for the clinical and cost effectiveness of this drug, in combination with doxorubicin, for advanced soft tissue sarcoma (STS) not amenable to surgery or radiotherapy, as part of the Institute's Single Technology Appraisal. The Peninsula Technology Assessment Group critically reviewed the submitted evidence.

Clinical effectiveness was derived from an open-label, randomized controlled trial, JGDG. The economic analysis was based on a partitioned survival model with a time horizon of 25 years. The perspective was of the UK National Health Service (NHS) and Personal Social Services. Costs and benefits were discounted at 3.5 percent per year. The company's evidence was submitted in anticipation that olaratumab would be considered as an alternative to doxorubicin, which has been used as a first-line treatment for advanced STS. To improve the cost effectiveness of olaratumab, the company offered a discount through a Commercial Access Agreement with the NHS England.

In the company's submission, the mean base-case and probabilistic incremental cost-effectiveness ratios (ICERs) for olaratumab plus doxorubicin versus doxorubicin alone were GBP 46,076 (USD 61,403) and GBP 47,127 (USD 62,804) per quality-adjusted life-year (QALY) gained, respectively; the probability of this treatment being cost effective at the willingness-to-pay threshold of GBP 50,000 (USD 66,632) per QALY gained, applicable to end-of-life treatments, was 0.54. The respective estimates in our analysis were approximately GBP 60,000 (USD 79,959) per QALY gained, and the probability of cost-effectiveness was 0.21. The increase in the ICERs was primarily due to differences in extrapolation of overall survival, and drug administration costs.

Based on the available evidence, olaratumab in combination with doxorubicin improves the survival of patients with advanced STS. However, this treatment is unlikely to be cost-effective. Olaratumab is now recommended for use within the Cancer Drugs Fund.

Many countries use Health Technology Assessment (HTA) organizations to evaluate the clinical and economic impact of new therapeutic interventions. In some markets, HTA outcomes directly link to reimbursement decision-making based on the manufacturer's submitted price (e.g. NICE and SMC [UK]). In others, the HTA outcome leads to price negotiations with manufacturers by a separate body (e.g. HAS/CEPS [France] and G-BA/GKV [Germany]). This research compares major examples of each approach to inform a discussion on whether such price negotiations align with HTA best practice.

Publically-available technology assessment outcomes for G-BA/GKV, NICE and SMC (01/01/2011-31/12/2015) were extracted and compared.

Of 112 G-BA benefit assessments, 45 percent offered no additional benefit with automatic reference pricing; 55 percent offered additional benefit, qualifying for price negotiations; 77 percent had prices negotiated, 14 percent had price fixed by court, and eight percent withdrew from market. Of 156 NICE Single Technology Appraisals, 51 percent were recommended, 17 percent restricted, 20 percent not recommended, and 12 percent non-submissions. Of 497 SMC appraisals, 35 percent were accepted, 28 percent restricted, 17 percent not recommended and 19 percent non-submissions. Forty-eight percent and 24 percent of NICE and SMC positive appraisals were associated with a Patient Access Scheme (PAS), with 86 percent and 88 percent being simple discounts schemes, respectively.

Making reimbursement decisions for new medicines based on a clear set of criteria may be the most objectively fair and transparent method of HTA; however, as the NICE and SMC examples show, although strong downward price pressure is exerted (high frequency of PASs), this may come at the cost of many therapies (~33 percent) being denied access. By contrast, the flexibility enabled by a distinct price negotiation phase may enable more therapies access, as shown by the G-BA/GKV example (<10% medicines withdrawn). Nevertheless, the relative effectiveness of the downward price pressures, a key determinant of HTA process effectiveness, cannot be compared due to the confidential nature of UK PAS discounts.

The Accountability for Reasonableness (A4R) framework addresses the legitimacy of coverage decision processes by defining four conditions for accountable and reasonable processes: Relevance, Publicity, Appeals, Implementation. Cost-per-quality-adjusted life year (QALY) and multicriteria-centered processes may have distinct implications for meeting A4R conditions. The aim of this study was to reflect on how the diverse features of decision-making processes can be aligned with A4R conditions to guide legitimized decision-making. Rare disease and regenerative therapies (RDRTs) pose special decision-making challenges and offer a useful case study.

To support reflection on how different approaches address the A4R conditions, thirty-four features operationalizing each condition were defined and organized into a matrix. Seven experts from six countries explored and discussed these features during a panel (Chatham House Rule) and provided general and RDRT-specific recommendations for each feature. Responses were analyzed to identify converging and diverging recommendations.

Regarding Relevance, panelists highlighted the importance of supporting deliberation, stakeholder participation and grounding coverage decision criteria in the legal framework, goals of sustainable healthcare and population values. Among seventeen criteria, thirteen were recommended by more than half of panelists. Although the cost-effectiveness ratio was deemed sometimes useful, the validity of universal thresholds to inform allocative efficiency was challenged. Regarding Publicity, panelists recommended communicating the values underlying a decision in reference to broader societal objectives, and being transparent about value judgements in selecting evidence. For Appeals, recommendations included clear definition of new evidence and revision rules. For Implementation, one recommendation was to perform external quality reviews of decisions. While RDRTs raise issues that may warrant special consideration, rarity should be considered in interaction with other aspects (e.g. disease severity, age, budget impact).

Improving coverage decision-making towards accountability and reasonableness involves supporting participation and deliberation, enhancing transparency, and more explicit consideration of multiple decision criteria that reflect normative and societal objectives.

Prostate neoplasia affects more than one million people worldwide. Surgical treatments have evolved from open or video prostatectomy, up to the High Intensity Focused Ultrasound (HIFU) technique. HIFU studies cite less costs and better quality of life during the first year of follow-up. The objective of this study is to describe a consecutive series of eligible patients, with Gleason score 6 and 7, and compare resources used along those three treatment techniques.

A comparative and retrospective study was conducted during the first 2017 semester, at Hospital de Transplantes de São Paulo, São Paulo city, Brazil. Consecutive eligible patients were matched by age, disease stage and profile and Gleason score 6 or 7. Resources used were assessed through medical records review and in- and out-patient visit interviews.

A total of 152 patients were followed: 50 underwent open surgery prostatectomy, 50 underwent video prostatectomy and 52 underwent HIFU. Mean age did not differ between groups (66.6, 64.1 and 65.6 years, respectively). All patients were followed for at least three months. The average operating room time was 4.7, 4.1 and 2.3 hours, and the average anesthetic recovery time was 2.0, 1.9 and 2.0 hours, respectively. Average inpatient length of stay was 2.5, 2.7 and 1.5 days, respectively. Postoperatively, nine (18 percent) open surgery patients, and 14 (28 percent) video-prostatectomy patients required an average of one full day of intensive care, compared to only one (2 percent) HIFU patient. During follow-up, the same effectiveness was observed between the groups, none required re-intervention. Thus, considering the 50 percent economy in hours of operating room and of days of hospital stay, as well as 10 times less use of intensive care unit days when the HIFU technique was compared to conventional surgeries, it is estimated the HIFU program allowed 30 percent cost savings.

The HIFU program presented effectiveness and savings. The hospital can increase access to care for prostate neoplasia patients.