The aim of the study is to estimate the disability insurance costs (social security system in Italy is financed by public expenditure) induced by patients with Inflammatory Bowel Disease (IBD) and specifically for Crohn's disease (CD) and Ulcerative Colitis (UC) between 2009 and 2015.

We analyzed the database about the disability insurance awards and the mean cost per benefit of the National Institute of Social Security (INPS) for two types of social security benefits: incapacity pensions (IP - for people without workability) and disability benefits (DB - for people with reduced work ability). From this data, we have estimated the total benefit provided and the total costs for each disease. A probabilistic model with a Monte Carlo simulation was developed in order to estimate the total benefits provided and costs.

For CD, an average of 820 beneficiaries of social security benefits were detected per year (2009-2015): the total expenditure was EUR 50 million, EUR 7 million per year (about EUR 7,900 per patient); for UC, about 1,550 beneficiaries per year were detected and the total expenditure was EUR 93 million, EUR 13 million per year (about EUR 8,600 per patient).

The disability insurance costs related with the management of CD and UC showed a significant impact on the expenditure for the Italian system: the most important costs for disability for CD and UC in Italy in the analyzed period were DB (92 percent for CD and 95 percent for UC). Rapid access to innovative treatments could reduce the costs incurred by the social security system.

Due to the unprecedented increase in medicine prices in recent years, the socio-economic perspective started gaining importance in health economic evaluations. Productivity loss evaluations provide a long-term economic impact visualization for a more informed reimbursed medicine decisions.

A pooled analysis of patient-level data from 11 cross-sectional, retrospective, cost-of-illness studies was performed. SPSS software was used for our statistical analysis. Analysis of variance (ANOVA) and correlation analysis were utilized to measure the effect of different variables on lost productivity hours. All costs were recalculated to account for the cumulative inflation till 2018.

The sample size of included studies ranged between 68 (Multiple Sclerosis) and 480 (Diabetes), and the total number of patients enrolled in the analysis was 1,881 of which 956 were female. A total of 6,795 hours were reported as missed working hours per year. Overall, the female population reported a mean of 689.5 lost productive hours compared to 324.7 in males (p < 0.001). This translated into higher indirect costs at EUR 2,748 and EUR 1,530 for females and males, respectively. Patients with a college degree or higher reported lower yearly lost productive hours and indirect costs (358.4 hours and EUR 1,749) (p < 0.001) compared to patients with lower education level (845.6 hours and EUR 3,534) (p < 0.001). The average indirect cost as a percentage of gross domestic product per capita was highest in Schizophrenia patients at 97.5 percent and lowest in Benign Prostatic Hyperplasia at 1.9 percent. In patients below 65 years of age, a weak positive correlation was observed between age and lost productive hours with a Pearson value of 0.1 (p < 0.001).

Female gender and older age resulted in higher productivity loss, and Schizophrenia was the disease with the highest indirect costs per patient per year.

The rapid expansion of immuno-oncology treatment options has led to concerns around their long-term affordability. Evidence on the potential budget and health impact of these new treatment options is required to inform public health policy and ensure adequate allocation of budget for the future.

The Health Impact Projection model was developed to compare the economic impact and health outcomes observed with and without PD-1/PD-L1 inhibitors using traditional budget impact analysis. Seven types of high-incidence cancers were included: melanoma, first- and second-level non-small cell lung, bladder, head and neck, renal cell carcinoma, and triple negative breast. Inputs were based on publicly available data and literature, and over 10 key experts (oncologists, health economists) were involved in the model development. The model draws on five-year budget impact analysis.

Using the experience of Belgium, Slovenia, Switzerland, and Italy, the model estimates budget and health impact of the PD-1/PD-L1 inhibitor class. It shows that for 2018-2022, the class will provide additional life years and avoid high-grade adverse events (AEs) with a manageable budget impact per year compared to the standard of care. The model also enables policy-makers to assess the adequacy of their budget for the near future and explore the implications of different policy decisions. Results for Belgium show that over the five-year period the PD-1/PD-L1 inhibitors will save 10,635 additional life years, avoid 7,597 AEs and have a budget impact of approximately EUR 260 million. Results for Slovenia show 1,468 additional life years gained and 869 AEs avoided with a budget impact of approximately EUR 116 million; for Switzerland, 6,775 life years gained, 6,953 AEs avoided, and EUR 106 million budget impact; and for Italy, 5,019 life years gained, 2,040 AEs avoided, and EUR 627 million budget impact.

Although limitations exist, the model informs planning by helping quantify the potential impact of immune-oncology treatments on health and budget in different scenarios.

This study has two key aims. The first is to review cost-effectiveness (CE) models for chimeric antigen receptor T-cell (CAR-T) therapies that have been appraised by health technology assessment (HTA) authorities. The second is to identify the key challenges of CE modeling of CAR-T therapies based on the main points raised in the HTA appraisals.

A targeted HTA review of published CE models for CAR-T therapies in the United Kingdom (UK) and United States (US) was undertaken.

Four relevant CE models were identified – three from the UK and one in the US. Of the three UK models, two were single technology submissions to the National Institute for Health and Care Excellence (NICE) and one was a ‘mock’ appraisal undertaken by NICE with a hypothetical evidence dataset. The one US model was published by the Institute for Clinical and Economic Review (ICER) committee. Two key model structures were adopted across the appraisals: a three-health state partitioned survival analysis model and a short-term decision tree followed by a three-health state partitioned survival model. The key modeling challenges identified can by summarized into five main categories: comparator evidence generation, estimation of long-term survival, curative benefit, health-related quality of life, and infrastructure/training requirements.

There are many challenges associated with the CE modeling of CAR-T therapies, with the most critical issues related to how uncertainty for long-term efficacy and safety can be addressed and mitigated. With more mature evidence sets in the future, stakeholders will get a clearer picture for the long-term benefit and risk of CAR-T therapies, but until then it is likely that HTA authorities will take a conservative stand when appraising the comparative value of CAR-T therapies.

Beta-lactams (BLs), especially penicillins, are the most commonly used antibiotics, particularly in primary care, and one of the most reported drug allergies. Fearing cross-reactivity, clinicians refrain from prescribing another BL (e.g., cephalosporin or carbapenem) to penicillin-allergic patients. This can have significant consequences for the patients and the health-care system (e.g., exposure to broad-spectrum antibiotics, increased risk adverse effects, and increased healthcare costs).

To assess the absolute cross-reactivity risk, two systematic reviews with meta-analysis were conducted. Then, an approach based on a knowledge mobilization framework considering scientific, contextual and experiential evidences was used. Focus groups with stakeholders, including primary care clinicians, pediatricians, infectious disease specialists and allergists/immunologists, were also held to meet the needs of all actors concerned.

Following this work, it appears that true allergies to penicillin are very rare. Indeed, in patients with a history of penicillin allergy, very few are truly allergic and thus the risk of cross-reaction with another BL is even lower, varying according to structural and physicochemical similarities with alleged-penicillin. Moreover, the risk of having an anaphylactic reaction after penicillin exposure is very low, especially among children. As well, in patients with confirmed penicillin allergy, the observed reactions are usually delayed non-severe skin reactions. However, with a confirmed penicillin allergy, it is important to remain cautious when administering a new BL, especially if the initial reaction was serious or severe. Based on these key messages, a decision aid including an algorithm was developed. Likewise, individualized algorithms for common infections met in primary care were produced.

From this work, health professionals non-specialized in allergology should be able to better manage the risks attributed to penicillin allergies. Therefore, patients should receive the most effective and safe antibiotics to treat their clinical conditions in primary care.

Frequent standard International Normalized Ratio (INR) monitoring by health professionals is one of the major inconveniences reported by warfarin users. However, portable coagulometers are now available to reduce this burden by allowing patients to self-monitor their INR in the comfort of their home, thereby reducing their visiting frequency to a medical clinic. The aim of this work was thus to elaborate recommendations on the use of self-monitoring in the management of warfarin-treated patients in the province of Quebec.

Systematic literature reviews were conducted to retrieve the most up-to-date scientific data from primary studies and pharmacoeconomic evaluations as well as recommendations from published clinical practice guidelines. This information was then triangulated with the experiential knowledge of Quebec experts and clinicians collaborating on the project.

The scientific, contextual and experiential evidence gathered during this work provided convincing support for the use of self-monitoring for long-term warfarin-treated patients, leading to a more effective treatment than standard monitoring while being safe, cost-effective and potentially improving patients’ quality of life. However, physical and mental limitations can hinder the use of portable coagulometers, outlining the need for caution in the selection and support of self-monitoring patients.

This work led to the development of specific recommendations on the use of self-monitoring along with a clinical tool to help discussion between patients and health professionals leading to a shared decision-making. This work will be part of two optimal usage guides on oral anticoagulant therapy to be published by the Institut national d'excellence en santé et en services sociaux.

Systematic reviews (SRs) are today's cornerstone of evidence-based medicine. However, their risk of bias (ROB) may critically impact their findings. Hence, an impartial assessment of their ROB is paramount to their interpretation. The objective of this study is to evaluate the potential association between the results of the ROB assessment for a series of SRs and their corresponding journal's impact factor as determined by the citation reports.

A sample of over 500 SRs and their corresponding ROB will be employed in this study. The source for these data will be the database KSR Evidence. The corresponding impact factor (IF) for the publishing journal as reported by the Science Citation Index will also be retrieved. The total of ROBIS signaling questions answered as ‘yes’ or ‘probably yes’ will be used to approximate the awarded quality (Quality) for each systematic review. An analysis of the potential correlation between Quality and the IF will be performed with a simple linear regression.

Results will be presented in tables and figures. Preliminary results confirm that a statistically significant association between the suggested variables exists, though this is of low magnitude.

Findings confirm that the ROB of an SR and the IF of the publishing journal are correlated.

The relationship between heath technology assessment (HTA) recommendations and drug prices has received little attention in the published literature. We consider whether target population sizes estimated as part of positive HTA decisions impact future price changes. We hypothesize that larger target populations may result in larger drug price reductions, as overall budget impact is an important component of price negotiations.

HTA and pricing data were obtained from the Context Matters Market Access Platform (MAP) and IHS Markit's PharmOnline International (POLI) pricing database, respectively. We analyzed 55 HTA decisions from the Gemeinsame Bundesausschuss (G-BA; Germany) and the Haute Autorité de Santé (HAS; France) for oncology products receiving European Medicines Agency approval between 2011 and the end of 2014. Pricing and HTA histories were tracked from the beginning of 2012 until October 2018. Using multiple regression to control for HTA agency, country-specific scores (Improvement in Actual Benefit and Additional Benefit scores), pack size, and initial price, we examined the relationship between a drug's price change in the year following an HTA review and the increase in target population resulting from the HTA decision.

We found that larger increases in target population were related to larger reductions in drug prices (p = 0.014). The magnitude of the effect size was low.

For the sample evaluated, we found a small but statistically significant association between target population size increases (as estimated by HTA bodies) and price reductions, supporting our hypothesis that target population plays a role in price negotiations. Confidential discounts and managed-access agreements likely account, in part, for the low magnitude of the observed association. Future work on this topic will involve larger samples covering a greater number of HTA agencies to improve the power and generalizability of the analysis.

Medicines regulation has become increasingly adaptive to support earlier patient access but the immature clinical data is often challenging for health technology assessment decision-makers due to high levels of uncertainty on long term risks and benefits. Scottish Medicines Consortium (SMC) is therefore exploring new, more adaptive approaches to help manage this challenge.

SMC consulted with key stakeholders including clinicians, the pharmaceutical industry and patient groups on a number of options that would allow the committee to make an interim decision that would be revisited based on later evidence. The ability to collect robust patient level data given data capabilities in National Health Service Scotland (NHSScotland) was an important consideration.

To ensure that additional evidence would be available to inform a re-assessment, the new approach applies to medicines with a Conditional Marketing Authorisation (MA) from the European Medicines Agency (EMA). This obligates the company to provide specified clinical data to the regulator within a pre-set timeframe. For these medicines, the SMC decision-making committee can accept or not recommend the medicine as at present but can also accept the medicine on an interim basis, if the regulator's mandated Specific Obligations are likely to address the uncertainties in the clinical evidence. When the regulator converts the MA from conditional to standard, the company is required to make a further SMC submission to allow a reassessment and a final decision. The company can also provide additional supplementary post-licensing patient level evidence at reassessment.

This new decision option allows SMC to test an approach to managing uncertainty targeted at a small number of promising new medicines where there is unmet patient need, with the reassurance that a final decision will be supported by additional clinical data.

Many patients presenting with arrhythmias are treated with antiarrhythmic drug therapy. However, for some patients, usually survivors of previous serious ventricular arrhythmias, treatment implies the use of implantable cardioverter defibrillators (ICDs) and/or Cardiac Resynchronization Therapy (CRT) devices.

This retrospective study evaluated a cohort of patients with arrhythmia requiring the use of ICDs, CRT or ICDs + CRT from January 2004 to March 2018. Data from a private healthcare organization in Belo Horizonte, Brazil were used to assess all-cause mortality and the need for replacement of the device. Continuous variables were expressed as mean and standard deviation. Cox proportional regression model and Log-Rank test were used to adjust the survival curve.

Five hundred and ninety-three patients were included in the study (median age 67.6 years, range 23 to 89 years; male 62 percent). According to the type of device used to treat these patients, the distribution was 338 (57.0 percent), 169 (28.5 percent), 86 (14.5 percent), for ICDs, ICDs + CRT, CRT, respectively. After a mean follow-up time of 3.12 years (range 0 to 13.6 years), 283 devices were replaced (ICDs n = 140; ICDs + CRT n = 90; CRT n = 53) and 284 deaths occurred (median survival of 6.9 years). The median survival was 7.3, 5.8, 4.8, 5.5 years for ICDs single-chamber, ICDs dual-chamber, ICDs + CRT, CRT, respectively.

Randomized trials are often criticized for their enrollment of highly selected patients. Studies on real-word data can provide reliable information regarding the use of ICDs and/or CRT devices in the treatment of patients with serious ventricular arrhythmias.

Open repair was considered for several years the gold standard therapy for the treatment of peripheral artery aneurysms (PAAs). However, with advancements in endovascular technology increasing attention has been directed toward repairing PAAs using an endovascular stent graft.

This retrospective study evaluated a cohort of patients after the correction of PAAs with Viabahn. Patients treated from January 2011 to January 2018 were assessed for all-cause mortality, amputation and the need for re-intervention. Data were extracted from an administrative database from a healthcare organization in Belo Horizonte, Brazil.

Fifty-two patients were included in the study (median age 69.1 years, range 15 to 90 years; male 63.5 percent), three of whom also received Viabahn for contralateral PAAs. In total, 84 devices were used (average 1.5 per PAA); distribution: popliteal and tibial arteries (n = 30; 57 percent), femoral and iliac arteries (n = 19; 37 percent), axillary artery (n = 1; 2 percent), splenic artery (n = 1; 2 percent), abdominal aorta (n = 1; 2 percent). After a mean follow up time of 1.98 ± 1.68 years, we observed death (n = 3; 5.8 percent), amputation (n = 3; 5.8 percent) and the need for re-intervention (n = 17; 32.6 percent) in 23 patients (44.2 percent). The combined overall survival for the first, second and third year of follow up was 70.2 percent (Confidence Interval [95% CI]: 58.9 - 83.6); 63 percent (95% CI: 51.0 - 78.0) and 57.3 percent (95% CI 44.6 - 73.6).

There are still several unanswered questions regarding the best approach for patients with PAAs. In the absence of well-designed clinical studies, the assessment of databanks on real-world patients may contribute to improve our understanding of treatment alternatives and provide guidance to improve current clinical results.

Severe aortic stenosis with symptoms or left ventricular dysfunction has commonly a poor prognosis and therefore, aortic valve replacement is usually performed for patients aiming at improving their functional class and survival rate.

This retrospective study evaluated a convenience sample of patients at high risk for open surgery for the correction of aortic valve dysfunction treated with TAVI from 2013 to 2018. Data from a private healthcare organization in Belo Horizonte, Brazil were used to assess all-cause mortality. Continuous variables were expressed as mean and standard deviation. Cox proportional regression model and Log-Rank test were used to adjust the survival curve.

Fifty-two patients were included in the study (mean 83 ± 5.7 years of age, range 67 to 93 years; female 55.8 percent). Patients were characterized by: left ventricular ejection fraction (n = 30; mean 52.9 percent, range 26 to 81 percent); aortic valve area (n = 36; mean 0.68 cm2, range 0.4 to 1.2 cm2); left atrium size (n = 14; range 30 to 61 ml/m2); pulmonary artery pressure (n = 20; mean 53 mmHg, range 31 to 70 mmHg). Death occurred in 19 patients during the follow-up period (mean 8.4 months, range 0 to 60 months). Nine deaths occurred within the first 30 days of follow-up (17.3 percent) and 14 (26.9 percent) in the first year. Stroke occurred in three patients (5.8 percent) in the post-implant period. A pacemaker device was required for nine patients (17.3 percent).

Transcatheter aortic valve implantation (TAVI) has become an alternative to surgical aortic valve replacement for patients at high risk for surgery. Real-world studies might result in a better understanding of the local team expertise on TAVI utilization.

Decision making regarding national population-based prenatal and newborn screening policies is recognized to be highly challenging. This paper aims to describe the formalized collaboration that has been established between the Spanish National Public Health Screening Advisory Committee (PHSAC) and the Spanish Network of Health Technology Assessment (HTA) agencies to support the development of evidence- and consensus-based recommendations to support this process.

In-depth description and analysis of the strategic and methodological processes that have been implemented within the Spanish National Health System prenatal and newborn screening frameworks, with special emphasis on the role, actions, and responsibilities of HTA agencies.

The role of HTA agencies is threefold: (i) support the PHSAC by providing evidence on safety, effectiveness and cost/effectiveness of the screening tests/strategies, as well as contextualized information regarding costs, organizational, social, legal and ethical issues; (ii) collaborate with the PHSAC in the development of formal evidence- and consensus-based recommendations for defining population screening programs, when required; (iii) analyze real-world data that is generated by piloted programs. This paper will provide real-life examples of how these processes were implemented in practice, with a special focus on the development of the non-invasive prenatal testing (NIPT) policy. Recommendations for NIPT were developed by a multidisciplinary group based on the European network for Health Technology Assessment (EUnetHTA) rapid assessment report and the predictive models that were built using national statistics and other contextualized data.

The current work represents an innovative approach for prenatal and newborn screening policymaking, which are commonly difficult to evaluate due to the low quality of evidence and the confounding public health issues. The paper raises awareness regarding the importance of joint collaborations in areas where evidence is commonly insufficient for decision making.

Advanced Therapy Medicinal Products (ATMPs) comprise medicines for human use based on gene therapy, somatic cell therapy or bioprocessed tissue products. ATMPs are pharmaceutically manufactured drugs and mostly subject to central authorization requirements. In terms of social law, it is an ambiguous situation and more heterogeneously dealt with. ATMPs are assigned to method evaluation as well as to the Arzneimittelmarkt-Neuordnungsgesetz (AMNOG) procedure designated for drugs.

Guidelines from Gemeinsame Bundesausschuss (G-BA), Institute for Quality and Efficiency in Health Care (IQWiG) and respective legislation, consultation results and methods/medical devices (MDs) evaluations according to §137h and for drugs according to AMNOG were reviewed and analyzed. Decision criteria and reasoning, assessment outcomes and potential impact on price negotiations were the main aspects for comparison.

ATMPs are subject to benefit assessment, with a decision at first on whether to be evaluated as a drug (e.g., Alofisel) or a method/device (e.g., Holoclar). By definition, an ATMP is classified as a treatment method, if the correct administration has at least the same significance for a successful therapy outcome as its mode of action. Depending on the respective decision, an evaluation as method follows or it must undergo the AMNOG process. According to G-BA's and IQWiG's point of view, randomized controlled trials (RCTs) are the “gold standard” for a benefit assessment of new therapies, including ATMPs. However, conduction of RCTs is not always possible for ATMPs which creates a disadvantage in the assessment right from the beginning. Otherwise no distinction is made between drugs and ATMPs in terms of reimbursement modalities. Outcomes based agreements could help overcoming inequalities and lead to quality-oriented reimbursement.

ATMPs represent a grey zone causing difficulties in classifying them either as method or drug. For individualized therapies evidence beyond RCTs and new reimbursement possibilities should be considered. Until new regulations are in place it is advisable to enter early into respective discussions with authorities.

In Estonia, organized cervical cancer screening program is targeted at women aged 30–55(59) years and Pap-tests are taken every five years. Since cervical cancer is associated with human papillomavirus (HPV), a number of countries have introduced the HPV-test as the primary method of screening. The objective of this study was to evaluate the cost-effectiveness of organized cervical cancer screening program in Estonia by comparing HPV- and Pap-test based strategies.

For the cost-effectiveness analysis, a Markov cohort model was developed. The model was used to estimate costs and quality-adjusted life-years (QALYs) of eight screening strategies, varying the primary screening test and triage scenarios, upper age limit of screening, and testing interval. Incremental cost-effectiveness ratios (ICERs) were calculated in comparison to current screening practice as well as to the next best option. Sensitivity analysis was performed by varying one or more similar parameter(s) at a time, while holding others at their base case value. The analysis was performed from the healthcare payer perspective adopting a five percent annual discount rate for both costs and utilities.

In the base-case scenario, ICER for HPV-test based strategies in comparison to the current screening practice was estimated at EUR 8,596–9,786 per QALY. For alternative Pap-test based strategies ICER was estimated at EUR 2,332–2,425 per QALY. In comparison to the next best option, HPV-test based strategies were dominated by Pap-test based strategies. At the cost-effectiveness threshold of EUR 10,000 per QALY Pap-testing every three years would be the cost-effective strategy for women participating in the screening program from age 30 to 63 (ICER being EUR 3,112 per QALY).

Decreasing Pap-test based screening interval or changing to HPV-test based screening can both improve the effectiveness of cervical cancer screening program in Estonia, but based on the current cost-effectiveness study Pap-test based screening every three years should be preferred.

The aim of the study was to estimate the cost-effectiveness of esophageal cancer (EC) screening compared to non-screening in China.

A Markov model was conducted that followed the history of EC. Screening strategies targeted a population aged 40-69 years, classified into six age groups. Each age group had three cohorts: screening without follow-up, screening with yearly follow-up for low-grade intraepithelial neoplasia (LGIN), and non-screening. Life years (LYs) and quality-adjusted life years (QALYs) presented the effectiveness and utility. The incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) were evaluating indicators. Eighteen cohorts from 100,000 hypothetical individuals were used to run the model, until aged 79 years or death. Costs were changed into USD using the purchasing power parity of 3.506 in 2017. The willingness-to-pay was set as three times the gross domestic product per capita (USD 51,340.6) in 2017. A sensitivity analysis was introduced to assess model robustness.

Screening with follow-up compared to non-screening, ages 40-44, 45-49, and 50-54 years, showed cost-effectiveness, with one LY gained costing USD 6,875.0, USD 9,204.6, and USD 25,278.6, respectively. Ages 40-44 and 45-49 years explained cost-utility, with ICURs of USD 6,709.4/QALY and USD 13,991.4/QALY, respectively. Screening without follow-up compared to non-screening, ages 40-54 years, addressed cost-effectiveness, with one LY gained costing USD 6,934.8, USD 9,760.0, and USD 35,126.0 in ages 40-44, 45-49, and 50-54 years, respectively; the 40-44 years age group demonstrated cost-utility with an ICUR of USD 8,512.3/QALY. Screening with follow-up compared to screening without follow-up, all ages, explained cost-effectiveness and cost-utility. The probabilistic sensitivity analysis supported the outcome of the base cohort analysis.

Compared to non-screening, screening with follow-up targeting ages 40-54 years was highly recommended with the ICER as the evaluated indicator, whereas it targeting ages 40-49 years was suggested with the ICUR as indicator.

When making decisions in health care, it is essential to consider economic evidence about an intervention. The objective of this study was to analyze the methods applied for systematic reviews of economic evaluations in Health Technology Assessment (HTA) and to identify common challenges.

We manually searched the webpages of HTA organizations and included HTA-reports published since 2015. Prerequisites for inclusion were the conduct of a systematic review of economic evaluations in at least one electronic database and the use of the English, German, French, or Spanish language. Methodological features were extracted in standardized tables. We prepared descriptive statistical (e.g., median, range) measures to describe the applied methods. Data were synthesized in a structured narrative way.

Eighty-three reports were included in the analysis. We identified inexplicable heterogeneity, particularly concerning literature search strategy, data extraction, assessment of quality, and applicability. Furthermore, process steps were often missing or reported in a nontransparent way. The use of a standardized data extraction form was indicated in one-third of reports (32 percent). Fifty-four percent of authors systematically appraised included studies. In 10 percent of reports, the applicability of included studies was assessed. Involvement of two reviewers was rarely reported for the study selection (43 percent), data extraction (28 percent), and quality assessment (39 percent).

The methods applied for systematic reviews of economic evaluations in HTA and their reporting quality are very heterogeneous. Efforts toward a detailed, standardized guidance for the preparation of systematic reviews of economic evaluations definitely seem necessary. A general harmonization and improvement of the applied methodology would increase their value for decision makers.

We conducted an analysis of the key factors triggering cost-sharing mechanisms to understand the status of out-of-pocket (OOP) healthcare expense in the United States (US), Europe, and emerging markets and better appreciate the implications of OOP healthcare expense on patients’ health management.

A review of literature and databases including The Organisation for Economic Co-operation and Development (OECD) and World Bank was performed to understand different cost-sharing mechanisms, factors triggering OOP expenditure and the country-wise trends of OOP expenditure. Additionally, the impact of OOP expenditure on healthcare budget and on patients in terms of medication adherence, uptake of newer therapies and generic substitution was explored.

The findings reveal that patients are concerned about rising healthcare OOP costs, and we observed an increase of 134 percent in the number of articles published on OOP from 2005 to 2017. The percentage of household spending that goes OOP as healthcare expense is higher in Brazil, Russia, India, and China (BRIC countries; ~11 percent) compared to France, Germany, Italy, United Kingdom, US, Japan, and Canada (G7 countries; ~2 percent). In addition, OOP expenditure increased with age (1.9 percent of take home income in 55-64 age group versus 1.2 percent in 18-25 age group) and is higher in the low-income population (2.8 percent of take home income versus 1 percent in high-income group). Whereas, increasing OOP expenditure reduces the overall healthcare expenditure due to generic substitution (28 percent reduction) and reduction in excessive consumption of supplementary medicines, it also reduces patient adherence (~20 percent decline in dispensed prescriptions) and may foster a reluctance to adopt newer therapies.

The population groups most impacted by increasing OOP expense are the older population, those in the low-income bracket and in poorer countries. While OOP expense may help in the effective and judicious utilization of healthcare system resources and medicines usage, its implementation requires a cautious and considered approach.

Opioids are being used increasingly to treat chronic noncancer pain despite the uncertainty regarding its long-term benefits. This study served to determine if problems are associated with opioid use in Québec for new users from 2006 to 2013 without history of cancer.

A retrospective longitudinal cohort study was conducted using administrative databases stored at the Régie de l'assurance maladie du Québec (RAMQ) to describe the annual proportion of new users to whom at least one of the five indicators of potentially inappropriate opioid use applied was estimated. These indicators are (i) overlapping opioid prescriptions, (ii) overlapping opioid and benzodiazepine prescriptions, (iii) the use of long-acting opioids at the start of treatment, (iv) a high mean daily dose, and (v) a rapid increase in the opioid dose.

The annual proportion of new users to whom at least one of the five indicators of potentially inappropriate opioid use applied decreased from 15.4 percent in 2006 to 12.3 percent in 2013. It was mainly the following three indicators that contributed the most to these proportions in 2013: (i) overlapping opioid prescriptions (5.8 percent), (ii) overlapping opioid and benzodiazepine prescriptions (8.2 percent), and (iii) the use of long-acting opioids at the start of treatment (1.8 percent).

The vast majority of new users with no history of diagnosed cancer used opioids adequately according to the five indicators of potentially inappropriate opioid use applied. Improvement could still be made to decrease mainly overlapping opioid prescriptions and overlapping opioid and benzodiazepine prescriptions.

With the fast speed of aging, burden from non-communicable diseases (NCDs) is increasing in China, and will continue to increase to 2020 and beyond. This study aims to estimate the potential gains in health-adjusted life expectancy (HALE) after hypothetical elimination of four NCDs among Chinese elderly from 1990 to 2016, including cardiovascular diseases (CVD), cancers, chronic respiratory diseases (CRD) and diabetes mellitus (DM).

Based on data from Global Burden of Disease 2016, we generated life table by gender using Sullivan method to calculate HALE. Disease-deleted method was used to calculate cause-elimination HALE, after hypothetical elimination of specific diseases. This method could combine the impact of mortality and morbidity, which are particularly useful for estimating the impact of the disease and setting priorities for health planning to get ready for the new challenges in upcoming decade.

From 1990 to 2016, HALE increased for all age groups. After hypothetically eliminating the four main NCDs, potential gain in HALE by CVD, DM and cancers increased, while CRD decreased from 1990 to 2016 for both genders. Among four main NCDs, potential gain in HALE after eliminating CVD was largest and increased most for both genders. Although elimination of DM led to the smallest gain in HALE, the increasing speed of gain in HALE by DM was faster than that by CVD and cancers from 1990 to 2016.

This study highlights the potential gains in HALE of NCDs among Chinese elderly from 1990 to 2016. HALE of Chinese elderly could further increase from the reduction of NCDs. Control measures and targeted prevention should be carried out to get ready for the new decade.