Rising costs and the rapidly increasing volume of findings from research in health care are driving the demand for comprehensive information to inform the allocation of resources. Health technology assessment (HTA) applies rigorous processes to provide high-quality synthesized information to policymakers and healthcare payers. HTA involves combining large amounts of research publications to systematically evaluate the properties, effects, and impacts on a topic of interest.

The time and resources required to complete a full HTA are often demanding. There is an opportunity to apply high-performance computing (inclusive of artificial intelligence and machine learning disciplines) to HTA. This project applied high-computing technology to create a research synthesis tool to support HTA and then developed a service that integrates as much relevant data as possible to strengthen HTA. This was a joint project that combined expertise from the areas of health technology, machine learning, information technology, and innovation.

The information gathered for this phased project from HTA subject matter experts and other stakeholders was collated to inform a research synthesis tool and a broader concept of the project.

The results of this study will inform the design of a research synthesis tool that covers the entire HTA process (literature search, screening titles and abstracts, data extraction, quality assessment, and analysis). The collaborators included Alberta Innovates, the Alberta Machine Intelligence Institute, the University of Alberta, Cybera, and PolicyWise. Alberta Innovates, which is an accelerator and innovator of research in the province of Alberta, Canada, was the primary source of funding for this project.

Deep brain stimulation (DBS), which uses an implantable device to modulate brain activity, is an adjunctive treatment for partial-onset seizures in patients with medically refractory epilepsy. Our objective was to perform an exploratory cost-utility analysis of DBS in conjunction with medical therapy, compared with medical therapy alone, using the latest clinical data and costs for the Australian healthcare system.

A deterministic five-state Markov model was used to project treatment response and outcomes over the patients’ lifetimes, based on 5-year data from the recent Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTE) DBS trial and drug outcome data identified through a literature search. Costs were based on 2017 data for the Australian healthcare system, and response-specific utilities were derived from published literature. We estimated the lifetime discounted incremental cost-effectiveness ratio (ICER) in Australian dollars per quality-adjusted life-year (QALY) for patients 36 years of age, fifty-five percent of whom were men. Costs and effects were discounted at five percent per annum. The robustness of projections was evaluated through scenario and sensitivity analyses.

Under assumed continued treatment benefit, DBS was projected to add 3.48 QALYs over the patients’ lifetimes, at an increased cost of AUD 142,304 (USD 105,960), resulting in an ICER of AUD 40,951 (USD 30,492) per QALY gained. Reducing the analysis horizon to 20 years increased the ICER to AUD 49,803 (USD 37,083). Increasing the DBS generator life from 3 to 6 years decreased the ICER to AUD 23,956 (USD 17,838) per QALY. Longer follow-up periods and younger age at treatment were associated with greater cost effectiveness. Results were sensitive to assumptions about health state-specific utility estimates and long-term treatment effects.

Our exploratory findings suggest that DBS is a cost-effective treatment strategy in the Australian healthcare system for patients with medically refractory epilepsy. DBS therapy might meaningfully improve patient outcome at a health economic profile that compares favorably to other well accepted therapies. Consideration of indirect costs would further add to this value proposition.

Mechanical ventilation in the intensive care unit (ICU) increases the risk of hospital-acquired conditions (HACs) such as ventilator-associated pneumonia (VAP) and pressure injuries (PrI). Continuous lateral rotation therapy (CLRT) has been shown to reduce VAP and PrI incidence, but the value of switching to CLRT over standard care is presently unknown. We evaluate the cost-effectiveness of CLRT beds compared to standard care in ICUs and determine the return on investment (ROI) associated with its implementation.

A Markov model was constructed to predict health state transitions from the time of ventilation through 28 days using the healthcare sector perspective. Daily transition probabilities were extrapolated from prospective clinical studies comparing CLRT with standard care. Costs were estimated in 2014 USD. Utility scores were extracted from the published literature. Cost per quality-adjusted life-years (QALYs) was calculated and sensitivity analyses were conducted. A secondary analysis from a societal perspective with a one-year time horizon included the costs of patient and caregiver lost productivity. ROI analysis was performed to estimate the net benefit and breakeven point of the investment. Value of Information analysis was performed to determine whether further research is warranted.

From both perspectives, CLRT was dominant. From the healthcare sector perspective, the expected cost for CLRT per patient was USD 47,165 compared to standard care at USD 49,258 per patient, showing that CLRT saves cost per patient. The expected effectiveness of CLRT per patient was 0.0418 QALYs compared to 0.0416 QALYs for standard care. CLRT was dominant in 99.94 percent of Monte Carlo simulations. CLRT also reached the break-even point after 5 months. Expected Value of Perfect Information was equal to 0.019, indicating little value of additional evidence at the current level of parameter uncertainty.

CLRT is highly cost-effective compared to standard care by preventing ventilator-associated infections and PrIs in an ICU setting.

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

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

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

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

Systematic reviews are useful for identifying gaps in research, setting priorities for future research, and informing clinical practice and public policy decisions. However, appropriate methods are needed to ensure that systematic reviews are of suitable quality in order to maximize their potential to achieve impact. The aim of this study was to evaluate the quality and transparency of systematic reviews conducted on prostate artery embolization (PAE), a topic of considerable interest in urology.

We conducted a cross-case analysis. Existing reviews were identified through a systematic search of four biomedical databases (Cochrane Library, York Centre for Reviews and Dissemination, Embase, Medline) from inception up to 8 December 2016. Systematic reviews that evaluated the safety and effectiveness of PAE to treat benign prostatic hyperplasia were included. Included reviews were critically appraised using the AMSTAR (A MeaSurement Tool to Assess systematic Reviews) tool, and were scored against the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) criteria.

From 536 search results, nine relevant systematic reviews were identified, of which eight were published in 2016. None of the included reviews were prospectively registered on the PROSPERO database. The median AMSTAR score was four of 11 (range 0–7). The most common methodological concerns were related to comprehensive searches (33 percent), inclusion of grey literature (0 percent), and evaluation of publication bias (0 percent). Reviews adequately reported a median of 17 of 21 items (range 6–19) against the PRISMA checklist.

Despite the availability of robust guidelines for conducting systematic reviews, methodological limitations in reviews of PAE are prolific, leading to considerable heterogeneity. There is also a significant duplication of effort, which can be prevented by prospectively registering systematic reviews on PROSPERO. Reducing duplication and increasing methodological quality are imperative to reducing waste in urological research.

Failure at the proximal neck for endovascular aortic repair (EVAR) in abdominal aortic aneurysm (AAA) is more common in the presence of unfavorable proximal neck anatomy. In patients with hostile neck, EndoAnchors provide proximal fixation and reduces potential type I endoleak or endograft migration. However, the population size for AAA patients with hostile anatomic neck among Korean is unknown and cost-analysis with regard to EndoAnchors has not been established.

To figure out the population size of AAA patients with hostile neck anatomy, retrospective medical chart review was conducted from four major medical centers. Hostile proximal aortic neck was defined as any or all of neck length 28 mm, infrarenal neck angulation >60°, ≥50 percent of circumferential thrombus, ≥50 percent of calcified neck, and conical neck. Cost-analysis on EndoAnchor use for treatment purpose was conducted based on Korean National Health Insurance Claims dataset (HIRA-NIS 2015).

Two-hundred and ten patients’ anatomic data treated with EVAR were included; 130 (61.9 percent) patients met the criteria for a hostile aortic neck and 32 (15.2 percent) patients had multiple hostile anatomy parameters. Endograft migration was reported in four (1.9 percent) patients and intra or post-op type I endoleak was reported in 21 (10.0 percent) patients. Based on 1-year claims data, 1,607 patients were treated with EVAR in 2015 and the annual average medical costs for open repair were USD 16,151. Given the patients with type I endoleak or endograft migration needs open repair if not treated with EndoAnchors, the estimated annual costs for patients treated with EndoAnchor were USD 2,234,321 and those for patients without EndoAnchor were USD 2,595,508, therefore USD 361,187 can be saved annually.

The population size with hostile aortic neck in Korea was comparable with those in western countries. Economically, EndoAnchor is a cost-saving treatment for type I endoleak and migration after EVAR from Korean payer.

Health technology assessments (HTAs) are increasingly used by Norwegian health authorities as the evidence base when prioritizing which health care services to offer. HTAs typically consist of a systematic review of the effects and safety of two or more health care interventions, and an economic evaluation of the interventions, based on systematic literature searches in bibliographic databases. Objective: To identify the best performing of seven search filters to retrieve health economic evaluations used to inform HTAs, by comparing the cost-effectiveness analysis (CEA) filter to six published filters in Ovid Embase, and achieve a sensitivity of at least 0.90 with a precision of 0.10, and specificity of at least 0.95.

In this filter validation study, the included filters’ performances were compared against a gold standard of economic evaluations published in 2008–2013 (n = 2,248) from the National Health Service Economic Evaluation Database (NHS EED), and the corresponding records (n = 2,198) in the current version of Ovid Embase.

The CEA filter had a sensitivity of 0.899 and precision of 0.029. One filter had a sensitivity of 0.880 and a precision of 0.075, which was closest to the objective. The filter with lowest sensitivity (0.702) had a precision of 0.141.

Developing search filters for identifying health economic evaluations, with a good balance between sensitivity and precision, is possible but challenging. Researchers should agree on acceptable levels of performance before concluding on which search filter to use.

Candidate health technologies identified for disinvestment will require prioritization depending on the system's capacity for dealing with the assessments or for further considerations. Compilations of low value lists, such as the National Institutes for Health and Clinical Excellence's, “Do not do recommendations”, can serve as databases for prioritization topics. Prioritization processes can also be triggered by experience or event-based regional requests and decisions; new evidence on safety, effectiveness and cost-effectiveness, variations in clinical practice, patient or consumer voicing, discrepancies between practice and guidelines; and or time-based mechanisms, such as approval of new health technologies and reassessment five years after introduction.

A search of the published and grey literature was conducted to identify the current methods or tools used to prioritize potential health technologies and services for disinvestment. The description of the methods and tools identified, the prioritization criteria, and the stakeholders involved in the process were reviewed and summarized.

The methods and tools used for prioritization that were identified in the literature include the PriTec Prioritization tool, nominal group technique, Program Budgeting and Marginal Analysis, consensus building, and online surveys. Further, common criteria for prioritization centered on the disease burden, possible risks and benefits, costs and cost-effectiveness, utilization, and time-based criteria. Prioritization can be conducted by health care professionals, decision makers, patients or patient groups and representative community members.

The prioritization process for disinvestment candidates should be transparent and guided largely by evidence. It is highly recommended that the list of predefined criteria be developed with input from all relevant stakeholders to meet the objectives of the specific health care setting. The commonly cited basic requirements include clinical parameters, economic measures, and social, ethical or legal considerations.

The pan-Canadian Oncology Drug Review (pCODR) program was established by Canada's provincial and territorial Ministries of Health (except Quebec) to assess cancer drug therapies and make recommendations to guide drug reimbursement decisions. The pCODR Expert Review Committee (pERC) makes reimbursement recommendations, providing a rationale for the recommendation and next steps for stakeholders. The objective of this analysis was to identify reviews and reasons pERC has requested real-world evidence (RWE) data collection.

A retrospective analysis of pERC Final Recommendations (January 2012 – May 2017) was conducted. pERC Final Recommendations include drug information, reimbursement recommendation, rationale for recommendation following pERC's Deliberative Framework (clinical benefit, patient-based values, economic evaluation, and adoption feasibility), next steps for jurisdictions to consider to support their funding decisions, summary of deliberations, and evidence in brief. Reviews were included if there was a next step advising the collection of RWE to reduce uncertainty in the drug under review.

Out of eighty-four reviews, forty-one (forty-eight percent) included a next step to collect RWE to address a gap in the available evidence. Reasons for RWE data collection, in descending order of frequency, were to inform: sequencing of available therapies; magnitude of clinical benefit and cost-effectiveness or the true cost-effectiveness; duration of treatment and cost-effectiveness; defining the population or disease progression; quality of life; and dosage.

In almost half of pERC's recommendation there is an indication that there is a gap in the existing evidence that could potentially be addressed through the collection of RWE. This reflects the rising number of new cancer drugs, limited evidence supporting submissions (for example non-comparative studies), and newer drugs such as immunotherapies which may not have a fixed treatment duration. Further research includes development of mechanisms for RWE data collection to help inform pERC recommendations and assist stakeholders with adoption feasibility of reviewed drugs.

Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasians, occurring in one out of every 2,500–2,800 births worldwide, and is associated with a high burden of disease. In Australia, prenatal testing for CF is indicated for pregnant couples identified as carriers or when a fetus is found to have an ‘echogenic bowel’ (FEB). We aimed to determine the effectiveness of prenatal CF testing and to assess ethical dimensions. A key challenge in assessing a prenatal test is selecting appropriate endpoints to indicate clinical effectiveness.

A systematic review was conducted and a linked evidence approach was used to answer the effectiveness question. The literature on ethical considerations relating to prenatal testing was also reviewed.

No studies were identified on the direct effectiveness of prenatal CF testing or downstream consequences. Linked evidence showed good diagnostic performance with a test failure rate of 4.5 percent. Termination of pregnancy occurred in the majority of cases where two mutations were identified in a fetus of carrier parents (155/163; 95 percent), indicating testing impacts clinical management. In FEB cases with CF, termination occurred in around sixty-five percent of pregnancies. Both terminating a pregnancy and having a child with CF were associated with poor short term parental psychological outcomes. Evidence indicates prenatal testing leads to a decreased number of CF-affected births. However, ethical analyses indicated that ‘informed decisions’ should have been the primary outcome of interest.

Proper counselling prior to testing ensures that the aim of prenatal testing is informing reproductive choices in a non-directive way, rather than decreasing the number of CF-affected births (which is ethically problematic). These results suggest that for health technology assessments undertaken on contentious topics, ethical analysis should be undertaken first so appropriate endpoints are selected for the subsequent systematic review of clinical evidence and for the economic model.

The Ministry of Health in Uruguay has a health technology assessment division that provides decision makers with evidence-based information on the efficacy, safety, and costs of health technologies to be included in the Comprehensive Plan of Health Care. Since 2010, patients have begun to demand access to unfunded, high-cost technologies through writs of protection. Judicialization of the right to health increased rapidly from 2010 to 2014. In this context, a Technical Advisory Commission was created in 2015 to assess patient requests on a case-by-case basis. The purpose of this study was to evaluate the results obtained with a new strategy developed to face the judicialization of access to high-cost technologies.

The methodology used to evaluate the implementation of the strategy consisted of reviewing a database of access requests from October 2016 to October 2017. The demographic characteristics, technologies requested, prescriptions, and results of the process were analyzed.

In the study period 654 technologies were requested for funding through the process. The included population had a mean age of 60 years; sixty-two percent were men. Of the technologies requested, eighty-five percent were drugs and fifteen percent were devices. The requested technologies included cancer treatments (thirty-five percent) or drugs and devices for the treatment of rheumatologic, ophthalmologic, infectious, neurologic, and cardiovascular conditions. The six most requested technologies (forty-five percent of all requests) were: abiraterone for prostate cancer; aortic endoprosthesis for vascular aneurysm; lenalidomide, rituximab, and azacitidine for oncohematologic diseases; and cetuximab for colorectal cancer. The Ministry of Health funded thirty-six percent of the requests.

The new strategy was successful in reducing the judicialization of access to unfunded, high-cost technologies in Uruguay, and it helped to prioritize the inclusion of new drugs in the national formulary.

Trastuzumab is the most recent biological therapy incorporated by the Brazilian Health Ministry for HER-2 overexpressed metastatic breast cancer treatment (2012). The aim of this study was to investigate if access to this technology is appropriate.

We performed a web-based questionnaire, which received answers from October 2016 to April 2017. Oncologists that work in the care of patients with overexpressed HER-2 metastatic breast cancer were the focus of the survey. Forty-three professionals informed work location, sector (public, private or both) and trastuzumab access. This research was approved by Brazilian Ethics Committee (CAE 59076316300005260).

Among 43 valid answers, nine informed they work in the public sector, 10 in the private sector and 24 in both sectors. In total, 33 reported to work in public and 34 in private sector. We observed that 17 (51.5 percent) participants who work in the public sector do not have access to trastuzumab, while in private sector only one participant (2.9 percent) reported the lack of access to this technology for HER-2 overexpressed metastatic breast cancer treatment. Regarding the respondents who informed the lack of access, six (33.3 percent) work in Northeast Brazilian region, six (33.3 percent) in Southeast, two (11.1 percent) in South, one (5.6 percent) in Central-West and three (16.7 percent) did not give this information. Eleven respondents reported they do not have another treatment option for these patients, while seven informed access only to chemotherapy without biological therapy.

Trastuzumab is a biological therapy that can increase HER-2 overexpressed metastatic breast cancer patients overall survival by nine months on average. The questionnaire results indicate that its access in Brazil is still irregular, mainly in public sector, even five years after its incorporation by the Brazilian Health Ministry. Although universal access is one of Brazilian Public Health System main directives, there is evidence of a serious issue regarding its services equity.

Since established in 2009, the National Evidence-based healthcare Collaborating Agency (NECA) has been the sole government-funded Health Technology Assessment (HTA) institution in Korea, yet little effort has been made to systematically evaluate the influence of its products. In this study, we aimed to measure the impact of the HTA products of NECA on clinical and policy decisions by introducing a systematic framework.

We included HTA reports published from 2009 to 2015. Among the 141 research reports published during this period, there were 67 HTA reports. We gathered data on the influence by literature and news article search, review of administrative documents and directly listening to the decision makers. The influence was categorized into three decision types: changes in clinical guidelines, administrative decision on investment/disinvestment and healthcare policy making. Whether a research report was used directly in decision making, or followed by subsequent researches or round-table conference, was recorded to examine the knowledge transfer process.

In total, 67.2 percent of the included HTA reports were used to support clinical and policy decisions. Twenty-seven reports had influenced administrative decisions on investment/disinvestment. Ten provided evidence for new health policies or legislation. Eight were reflected in clinical guidelines. The impact of HTA reports published by NECA was more evident when the research was directly requested by decision-making bodies such as government institutions. Although most HTA reports were conducted in collaboration with clinicians, the use of results by clinicians was limited. Definitive results were more likely to be used, but reports with competing interests had fewer impacts.

HTA by NECA had impacts on the rational use of healthcare resources in Korea, and NECA has established its role as an intermediary between governmental decision-making bodies and clinicians. However, more continuous approaches rather than one-time HTA research are needed for HTA on controversial topics to have impacts on decision making.

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.