The efficacy of second generation direct-acting antiviral agents (DAAs-2), in terms of sustained viral response (SVR) 12 weeks after the end of treatment (EOT), has widely been proven; however, long-term efficacy is still controversial due to the low number of available studies with a small number of patients. The objective of this study is to conduct a systematic review and, if possible, a meta-analysis of existing clinical evidence of the long-term efficacy (SVR longer than 12 weeks after EOT) of DAAs-2 for hepatitis C virus (HCV) treatment.

A systematic review was performed with the use of CENTRAL, MEDLINE, Embase, Pubmed and SBBL-CILEA/METACRAWLER databases. Trials were initially screened by the title; secondly, full papers and abstracts were analysed. The meta-analysis included randomised controlled trials (RCTs) with adult patients affected by HCV, treated with DAAs-2 and assessed for longer than 12 weeks after EOT. Study quality assessment was undertaken using the Jadad scale. Heterogeneity analysis of the studies was conducted with chi-square and I2. The statistical analysis of the efficacy rate was performed using the meta package with the R software. The effect estimate was expressed in risk ratio (RR) with 95% confidence interval (CI 95%) and pooled using a random effects model.

Of the 106 identified studies, 11 high quality RCTs were included for meta-analysis (25 were duplicate publications, 70 did not meet the inclusion criteria). Considered genotypes were 1 (n = 9), 2 (n = 1), 3 (n = 1). Meta-analysis included 3,720 patients (2,698 treated with DAAs-2; 1,022 treated with placebo or a first generation DAA±Ribavirin±Pegylated interferon). Heterogeneity between studies was high (p<0.001; I2 = 90.2%); however, it was absorbed by the model (τ2 = 0,08). Long-term efficacy was expressed as SVR 24 weeks after EOT, since longer timescales were not available. According to the pooled RR, the incidence of efficacy was 1.5 (CI 95%: 1.24−1.83, p < 0.001).

The meta-analysis demonstrated that DAAs-2 for HCV treatment have long-term efficacy at SVR 24 weeks after the EOT; however, the number of studies is mostly based on genotype 1. More RCTs are required to confirm long-term efficacy at more than six months after EOT for all treated genotypes.

According to guidelines, antibiotic prophylaxis in orthopedic surgery without implant is not recommended for the reduction of the incidence of surgical site infections (SSI); however, the evidence level is low. Surveys have shown that preoperative antibiotics for orthopedic procedures without implant are administered routinely by surgeons due to medico-legal concerns. Such practice may have an important impact on costs, side effects and the emergence of antibiotic resistance. Therefore, the objective of the review is to evaluate existing clinical evidence.

A systematic review was performed with the use of Pubmed, EMBASE/MEDLINE, CENTRAL, SBBL-CILEA/METACRAWLER, ISRCTN Registry, ICTRP and ClinicalTrials.gov databases. Trials were initially screened by the title and abstract; secondly, full papers were analysed. The meta-analysis included randomized controlled trials (RCT) with patients undergoing surgery as treatment for any orthopedic impairment that did not need implantation. Heterogeneity analysis of the studies was conducted with chi-square. The statistical analysis of the infection rate was performed using the meta package with the R software. The effect estimate was expressed in risk ratio (RR) and pooled using a random effects model. Study quality assessment was undertaken using the Jadad scale.

Of the 184 identified papers, 129 were excluded since they did not meet inclusion criteria and 45 were discarded because they were considered to be duplicate publications. After analyzing the 10 potentially relevant studies, only two were included. The study population consisted of 1,152 patients. No heterogeneity was observed; however, the studies were outdated and associated with a high risk of bias. According to the pooled RR, the incidence of infection in the intervention group was lower than the control group favoring prophylaxis (RR = 0.39, 95% CI: 0.16−0.96, p = 0.040).

The meta-analysis demonstrated, in contrast to the guidelines, that antibiotic prophylaxis can reduce the incidence of SSI in elective orthopedic surgeries without implant; however, the low number of available studies and the high risk of bias show that the effect estimate is not statistically significant. Considering that antibiotic prophylaxis is usually administered in clinical practice, RCTs are required to establish whether antibiotic prophylaxis in orthopedic procedures without implant is recommended or if this practice could cause more harm.

In Canada, reimbursement recommendations on drugs for common and rare indications (for example, orphan drugs) are made through the pan-Canadian Oncology Drug Review (pCODR) and the Common Drug Review (CDR). However, some stakeholders have called for a separate mechanism for orphan drugs, arguing that existing processes place too much weight on their high price tags. The purpose of this study was to examine factors associated with positive recommendations on drugs for rare diseases.

Information was extracted from CDR and pCODR recommendations on drugs for diseases (prevalence of less than 1 in 2,000) up to April 2018. Univariate and multivariate logistic regression models were applied to explore the influence of the following variables on recommendations: year; prevalence; clinical safety and effectiveness (safety, quality of life, symptoms, surrogate outcomes, and survival); quality of evidence (availability of comparative data, external validity, and bias); unmet need; treatment cost; and incremental cost-effective ratio (ICER). Two-way interactions were also tested.

Of 128 recommendations, fifty-four (77 percent) and forty (69 percent) were positive for cancer and non-cancer indications, respectively. For cancer indications, all submissions reporting meaningful improvements in surrogate, quality of life, and survival outcomes were significantly more likely to have a positive recommendation. Submissions showing a lack of external validity were significantly less likely to receive a positive recommendation. For non-cancer indications, more recent submissions and those presenting no safety issues were associated with positive recommendations. Prevalence, treatment cost, and ICER were not determinants of positive or negative recommendations.

For both cancer and non-cancer orphan drugs, impact on clinical safety and effectiveness, rather than cost, appears to be a key factor in the formulation of recommendations.

In recent years, the National Institute for Health and Care Excellence (NICE) has increasingly agreed to reimburse innovative products with high levels of uncertainty as part of managed access agreements (MAAs) while new data are collected; namely, this has occurred through the new Cancer Drugs Fund (CDF) and highly specialized technology (HST) appraisal pathway. This research aimed to provide a review of ongoing data collection arrangements as part of MAAs agreed with NICE.

We reviewed all current MAAs entered into between the National Health Service (NHS) England and manufacturers as of 24 November 2017 and extracted relevant information related to the data collection arrangements.

Thirteen MAAs were identified (10 through the CDF; 3 through HST). All MAAs involved an observational data collection agreement. The source of observational data collection was existing NHS databases (11 MAAs: 85 percent), existing independent registries (1 MMA: 8 percent [ataluren]); bespoke MAA registry maintained by manufacturer (1 MAA: 8 percent [asfotase alfa]), and registries developed as a requirement for regulatory approval and maintained by the manufacturer (1 MAA: 8 percent [elosulfase alfa]). Only 4 MAAs (asfotase alfa, ataluren, elosulfase alfa, and venetoclax) had observational data collection as the sole basis of the data collection agreement. The other 9 MAAs (69 percent; all from the CDF) also required on-going data collection from clinical trials as a key component of the data collection agreement.

This research shows that current MAAs have predominantly utilized either ongoing data collection (e.g. from RCTs) or existing registries to date for which limited additional set-up administration and costs would be required. However, NICE plan to increase the use of MAAs, with ongoing NICE consultation for changes in the appraisal process to expand MAAs to include all indications. In future, manufacturers will have more opportunities to explore and leverage innovative and bespoke MAAs to help achieve access.

The Cancer Drugs Fund (CDF) was set up in 2011 in England to enable patients to access oncology therapies that are not routinely publicly funded. In April 2016, the CDF became a temporary reimbursement fund under the remit of the National Institute for Health and Care Excellence (NICE) with the aim of collecting observational data to inform subsequent technology appraisals. This study aims to evaluate how the reformed CDF has been utilized in the 18 months since this reform.

NICE Final Appraisal Determinations for Single Technology Appraisals of oncology drugs from (29 July 2016 to 24 November 2017) were identified and key data extracted.

Seventy-four oncology drug:indication appraisals were identified, 54 (73 percent) were recommended/optimized, 10 (14 percent) were not recommended and 10 drug:indication pairings (14 percent: osimertinib, brentuximab vedotin, pembrolizumab, olaratumab, obinutuzumab, venetoclax, nivolumab [3 indications], and ibrutinib) were referred to the CDF. For most, the greatest uncertainty in their cost-effectiveness analyses related to their survival benefits, intended to primarily be resolved through subsequent clinical trial readouts. However, for venetoclax, ibrutinib and brentuximab, the main areas of uncertainty (relating to comparative survival benefit, pre-progression mortality, and rate of subsequent stem cell transplants, respectively) are expected to be resolved primarily through observational data collected under the CDF.

The newly reformed CDF has been utilized in a minority of cases. Typically, the CDF acts as a temporary access mechanism for treatments that receive market authorization based on early/single-arm trial data until longer-term and/or Phase III data are available. However, venetoclax, brentuximab, and ibrutinib demonstrate how the CDF may address significant areas of uncertainty through the collection of uncontrolled observational data. For venetoclax, with only single-arm supportive clinical trial data, observational data of this intervention and appropriate comparator are to be collected, providing a potential case study of how to appropriately manage reimbursement in the face of significant clinical uncertainty.

The Health Technology Assessment (HTA) of esthetic procedures was performed by the French National Authority for Health (HAS), at the request of the French Ministry of Health (MoH), and under a new regulatory framework enabling the government to ban esthetic procedures considered harmful or potentially harmful to patients and consumers by HAS. Objectives: Describe HAS’ seven year experience with the safety assessment of four esthetic procedures.

This is an HAS review of its methods used in four HTAs for the following evaluated techniques: lipolysis; cryolipolysis; esthetic mesotherapy; and, ultraviolet (UV) radiation in tanning devices. The review aimed to describe how these assessments have been undertaken and information sources used, from 2010 to 2017, to appreciate the safety profile of these procedures.

A systematic literature review (SRL) and analysis was performed for all four HTAs. Since findings did not allow for thorough appreciation of safety, additional sources of information were consulted to address evidence gaps. Sources may have included any combination of the following: i) National and international health care authority data and alerts ii) Legal and ethical frameworks iii) Public consultation iv) Expert opinion v) Patient-consumer association opinion vi) Economic analysis

An adaptation of the HTA methodology was necessary to meet the specific requirements of these assessments. Despite sources accumulated and consulted within the seven year period, quantitative data were found insufficient to fully appreciate the safety profile for any one of the studied esthetic procedures. National regulatory reinforcement on the reporting of adverse events, with implementation of a centralized online tool, is expected to generate and capture reliable data on the frequency and severity of adverse events associated with esthetic procedures. Recent European Union (EU) regulatory requirements on the safety and performance of medical devices include equipment used for esthetic procedures, indicating agreement and alignment on national and EU-level monitoring efforts.

Systematic mixed studies reviews are a type of systematic review that combine qualitative, quantitative and mixed methods studies. They are gaining in popularity due to their potential for providing in-depth answers to complex clinical problems and practical concerns. However, several challenges are encountered in systematic mixed studies reviews because of the heterogeneity of included study designs. One of these challenges is related to the quality appraisal of included studies. To address this challenge, a critical appraisal tool for assessing the quality of quantitative, qualitative and mixed methods studies was developed in 2007: the Mixed Methods Appraisal Tool (MMAT). The aim of this project was to strengthen the content validity of the MMAT.

A new version of the MMAT was developed using the results from a literature review on critical appraisal tools and a modified e-Delphi study with methodological experts (n = 73) to identify the core relevant criteria to include in the MMAT.

The results of this project and the new version of the MMAT will be presented. The MMAT has three main characteristics. First, it can be used for different study designs since it includes criteria for qualitative, quantitative and mixed methods studies. Second, the MMAT focuses on the core relevant methodological criteria and has five criteria per category of study. Third, it includes specific criteria for assessing mixed methods studies.

Currently, there exists over 500 critical appraisal tools, making the task of selecting the proper tools for use in systematic mixed studies reviews more difficult. The MMAT offers an alternative solution by proposing a unique tool that can appraise the quality of different study designs. Also, by limiting to core criteria, the MMAT can provide a more time efficient assessment.

To make itself more relevant in a longer perspective health technology assessment (HTA) will have to make use of novel ways to improve its services; in particular in terms of rapid response, cost savings and reduction of risk of bias. The use of artificial intelligence (AI) offers significant assistance at essentially all stages of any HTA. It can search, retrieve, read and organize relevant literature, not only from traditional databases but from numerous data sources related to specific issues (e.g. clinical trials, health outcomes, payment of services), and from databases in other areas such as in social, justice, and educational services, and public health.

This presentation will explain the use and feasibility of AI in HTAs based on the findings from a currently ongoing project in the province of Alberta Canada. It will (i) provide an overview of AI in healthcare, (ii) outline selected international efforts of using AI in systematic reviews, such as the Robotreviewer, (iii) describe the information needed, and the development of the algorithms for using AI in HTAs, and (iv) report on the findings from a comparative study of human versus AI resources in performing an HTA.

This project has just started, however preliminary findings from the comparative analysis of AI versus human performance on a specific topic for HTA will be presented.

It is expected that the comparative study will demonstrate that artificial intelligence will become a useful tool in HTA in that it will significantly speed up systematic reviews, and decrease the risk of bias in syntheses of findings from research.

The best available research and funding policy evidence regarding the regulatory status, patient selection criteria, safety, clinical effectiveness, and financial impact of peroral endoscopic myotomy (POEM) for the treatment of achalasia was synthesized for statewide decision making for a South Australian local health network.

A comprehensive systematic search of twenty-three gray literature sources and three published literature databases for international evidence was conducted, based on a priori inclusion criteria. The methodological quality of the included studies was critically appraised. Data extraction and synthesis were conducted in narrative form.

Short-term safety and clinical data from very low-level studies showed that POEM appears to be a relatively safe and clinically effective endoscopic treatment for esophageal achalasia, compared with laparoscopic Heller myotomy (LHM). One primary safety concern consistently highlighted by the literature was gastroesophageal reflux (GER) after POEM, since no anti-reflux procedure is involved. Operative time and length of hospital stay for POEM were comparable with LHM and potentially favor POEM. The comparative long-term outcomes for the POEM procedure are not known. No studies have investigated the cost-effectiveness of POEM. Conflicting findings were reported on whether POEM is cheaper or more expensive than LHM. POEM is a technically challenging procedure with a substantial learning curve. Patients who undergo POEM may require postoperative surveillance and testing to evaluate procedural success and to identify potential complications. Current literature showed limited analysis and systematic elucidation of an optimal patient group that may best benefit from POEM.

The POEM procedure should be carried out at an experimental or trial level only, with strict auditing of results. POEM procedures should ideally be performed at institutions where an adequate level of surgical and critical care backup is available to provide expert care should complications arise. Monitoring of patient outcomes, including symptom improvement, is recommended for clinical assessment and reporting to determine future adoption in the South Australian public health sector.

Improving universal health coverage is a big challenge in many nations. Nevertheless, in countries like Brazil, the Constitution provides for universal access to meet population needs. Medical equipment is indispensable for the diagnosis and treatment of diseases in public and private health services. This study aims to analyze medical diagnostic equipment incorporation in a Brazilian state.

This evaluative research was carried out using data from Brazil's Unified Health System (SUS) and Private Health Services. The research took place in Ceará, Northeastern Brazil. It is the eighth most populous Brazilian state, with 8.8 million inhabitants. Data on the types and quantity of medical devices in the public and private services were collected from August 2005 to August 2017. The results were analyzed by comparing population and normative parameters with technology incorporation in Brazil.

A mean of 17.6 +/− 10.6 (SD) devices were incorporated each year in SUS versus 31.7 +/− 15.7 (SD) in the private services. Over a twelve year period, the incorporation of equipment increased 59.7 percent in the public system and 152.6 percent in the private services. The production from these technologies increased to 18.1 percent. Considering both public and private services, tomography equipment coverage exceeds (147.4 percent) the parameter established by the Ministry of Health while magnetic resonance imaging equipment coverage is 90.5 percent.

An expressive number of medical devices were incorporated in public and private health services, with higher rates in the latter. Both services presented a downward trend, suggesting that the incorporation of equipment is no longer needed. Such an extra coverage reveals an uncritical incorporation of these devices, that was not based on real needs; therefore, it is necessary to develop an action plan aimed at a better distribution of these devices to allow effective universal coverage.

Since the inception of the Ghana National Health Insurance Scheme (NHIS), it has been pursuing a number of provider payment mechanisms that could not only control the continuous escalating costs of claims payout, but also facilitate the claims processing time. In lieu of this, electronic processing of claims (E-claims) was introduced in 2013 as part of the World Bank supported Health Insurance project that sought to facilitate the financial and operational management of the NHIS. It was piloted in 29 health facilities up to March 2014. They reported cost savings made by the NHIS using E-claims, creating interest in scaling it up. However, the comparative effectiveness and cost effectiveness of E-claims to the health system compared to manual claims processing is unknown. Therefore, to provide decision makers with the appropriate information to choose between manual and E-claims processing, this study sought to evaluate the cost-benefit of E-claims.

A benefit-cost analysis was used to evaluate the efficiency of E-claims from the perspective of the health system. Health providers and the purchaser (NHIS claims processing center) were the study population. Resource use and costs were obtained from the study population. The volumes and values of claims reimbursed and the claims rejection rate were used as the benefits of claims processing. The incremental benefit-cost ratio (IBCR) was estimated for the provider, purchaser and the entire health system. Analysis was conducted in Microsoft Excel.

The total cost per claim for providers were USD 1,177.04 and USD 1,240.65 for E-claims and paper claims respectively. The total cost per E-claims and paper claims for the purchaser were 592.17 and 502.19 respectively. Total benefit per E-claim and paper claim processing for the providers were USD 8,562.90 and USD 8,888.37 respectively while that for the purchaser was USD 11,037.62 and USD 8,737.60 respectively. Processing claims electronically led to incremental gains by both providers and purchasers. Providers gained additional USD 2008.51 while the purchaser gained USD 2,300.02. The IBCR was estimated at −19.75, 25.56 and 5.10 for all providers, purchaser and both providers and purchaser of the health system respectively. Thus the IBCR was less than 1for the providers and more than 1 for purchaser and both purchaser and providers.

The electronic processing of claims is more efficient compared to manual processing in the Ghana NHIS. This provides decision makers with evidence for scaling it up to all the facilities in Ghana.

The aging population means more men are diagnosed with prostate cancer, resulting in greater demand for treatment. Robot-assisted radical prostatectomy (RARP) claims to offer additional benefits to patients and providers. The independent Victorian Health Technology Program Advisory Committee assessed safety, clinical effectiveness and cost effectiveness evidence and financial impact to inform policy, access and reimbursement decision-making by state government policy makers and public hospital providers.

Public and private hospital activity and costs for 2008–09 to 2012–13 from the Victorian Admitted Episodes Database (VAED) and the Victorian Cost Data Collection (VCDC) were identified. Data were extracted and reviewed based on (i) DRGs M01A and B, (ii) primary diagnostic code C61 (ICD-10-AM), and (iii) Australian Classification of Health Interventions procedure codes for open (ORP), laparoscopic (LRP) and RARP, supplemented by Victorian Prostate Cancer Clinical Registry data. English language Health Technology Assessments (HTAs)/systematic reviews published January 2009 to January 2015 were identified and analysed with comparative clinical outcomes data for RARP vs. ORP and RARP vs. LRP analysed. Not all reported the same data and most outcomes data presented were odds ratios and risk ratios.

RARP offers patients a shorter length of stay (LOS) compared with ORP or LRP, but the procedure takes longer to perform. While RARP has similar safety and clinical effectiveness profiles compared with ORP and LRP, published data do not unequivocally demonstrate that RARP is superior to ORP or LRP in terms of clinical outcomes. RARP is more expensive than ORP and LRP. The cost differential increases when capital costs are taken into account. Cost offsets from a reduced LOS are insufficient to justify the higher cost.

Since RARP produces similar clinical outcomes to ORP and LRP but at a higher cost, the Victorian Health Technology Program Advisory Committee considered the case for public sector support of RARP is weak and provided two recommendations: (i) State Government resources are not used to procure RARP capital equipment; (ii) public hospitals can refer patients to a RARP provider, provided costs are negotiated prior to patient transfer and fully covered by the referring hospital.