More than 50 HTA agencies evaluate the clinical value of medicines in Europe, resulting in duplication of work for HTA agencies and manufacturers, and lengthy and variable time to reimbursement for patients across Europe. A consistent, single European relative clinical scientific benefit assessment of medicines could become a key element in ensuring patients get equitable and timely access across Europe. The European Network for Health Technology Assessment (EUnetHTA) is responsible under Joint Action 3 (JA3, 2016–2020) to pilot more than 30 Relative Effectiveness Assessments (REAs) of medicines. The first EUnetHTA JA3 REA pilots are now being completed and Roche, with its participation in the REA pilot for alectinib, has gathered relevant experience.

The goal of this analysis is to summarize and reflect upon the experience with one of the first EUnetHTA REA assessments in JA3. The authors also propose potential process improvements.

The experience with the alectenib REA shows that EUnetHTA processes have improved compared to JA2. The timing of the assessment has been aligned with the EU regulatory marketing authorization process by shortening the duration of the scoping phase. More EUnetHTA members than in JA2 seem to be committed to use the reports in national HTA, pricing and reimbursement processes. At the same time, the REA pilots have identified other areas that could benefit from further refinement, for example the active engagement of patient group representatives and clinical experts, rules and principles related to the handling of confidential information.

Based on the limited number of REA pilots for medicines it is too early to draw final conclusions on the state of EU-level collaboration. But first signals indicate a positive development compared to REA pilots conducted in JA2. Interim evaluations are recommended to assess progress, and capture learnings for future pilots.

Nusinersen is an orphan drug for spinal muscular atrophy (SMA) recently approved for marketing. Its high cost, striking but limited evidence of efficacy, and strong demand by media and patient organizations have generated a health policy conflict. We analyze the flaws of available evidence on nusinersen and its budget impact at a pediatric hospital, and report a collaborative strategy for drug procurement and financing.

Nusinersen is the highest-cost drug assessed by our hospital-based health technology assessment (HB-HTA) program so far. At the time of our assessment, only interim-analysis data of the pivotal randomized trial submitted to Federal Drug Administration (FDA) for approval and the European Medicines Agency (EMA) report containing unpublished final results were available. These secondary sources and other published phase II results were appraised. As a referral hospital, we concentrate most of the 300 SMA patients in our country. Hospital budget impact estimation included drug and hospitalization costs for the first and following years. The HTA report was submitted to the Ministry of Health to address this financing issue.

The available evidence of efficacy raised serious methodological and clinical uncertainties. First-year treatment cost per patient was estimated in ARS 13,008,688 (USD 752,000, 10 percent of pharmacy annual drug budget). Hospital budget impact (70 eligible patients) was ARS 910,608,160 (USD 52,000,000; 18 percent of total annual hospital budget). Our recommendation was to contact central level authorities to resolve both drug financing and patient access by negotiating a shared-risk approach for an expanded access program, allowing further data collection for reassessment after 12 months. This, in turn, fostered mutual collaboration and consensus within the health system where several lawsuits were demanding drug coverage. Negotiation with the industry was initiated by the Ministry.

This case is a clear example of forthcoming ultra-high-cost drugs unaffordable by hospital budgets. Their acquisition opportunity cost is a health policy matter requiring to display collaborative coping strategies with Ministries and other stakeholders including industry.

The European Union (EU) directive (2014/24) on public procurement strives to stimulate innovation and seeks for methodologies to implement a quality/cost based approach to search for the most economically advantageous tendering (MEAT). MedTech Europe launched the MEAT value-based-procurement (VBP) framework and tool which considers product's value from different perspectives/dimensions. Results from the first EU pilot, testing the feasibility to use the MEAT framework at a university hospital, are presented.

The framework and tool were tested using two types of technologies: high volume (underpads, diapers) and highly specialized (transcatheter aortic valve implantation). Companies were invited to participate following standard procurement rules. For each dimension, criteria, metrics and weights were defined, using multidisciplinary hospital teams. In parallel, companies were asked to do the same. Product performance scores were obtained from companies’ information. Challenges to implement MEAT in real life were identified through face-to-face meetings.

The process was well perceived by companies and hospital. Nevertheless, the level of information provided by companies was heterogeneous (quantity and quality). A match in the cost and outcome criteria was observed between hospital and companies; but relative weights assigned differed. Value propositions and robustness of information provided by companies varied across technologies and size of companies. Implementing the MEAT VBP framework and tool need extra time and knowledge.

MEAT VBP value technologies ahead of price, leading to the most economic advantageous purchasing. Nevertheless its implementation in real life is limited.

According to the Vietnamese Cardiovascular Association, one-fifth of Vietnam's population is suffering from cardiovascular disease (CVD) – now the leading cause of death in the country that accounts for about one-third of total deaths every year. Yet affordable and convenient solutions to monitor and detect CVDs remain limited and not available nation-wide. This study aimed to investigate the usability of a portable dry-electrode electrocardiography (ECG) device, paired with a mobile phone, in supporting ECG service delivery in Vietnam.

An evaluation study was designed to combine a portable dry-electrode ECG device to measure and a mobile phone to receive and record ECG signals. Healthy young college students were invited to participate in the study. Three rounds of ECG measurement were administered for each of the participants. Usability of the device was assessed through the reliability of the measures and feasibility of use during intervention. Standard error of measurement (SEM) and intra-class correlation coefficient (ICC) estimations were used for reliability, while structured questionnaire administered before and after measures was used for feasibility assessments.

A total of 234 participants enrolled in the study. No major difference was found in SEMs between trials one and two (4.96 percent, 90% CI: 4.61 − 5.37) and two and three (4.14 percent, 90% CI: 3.85 − 4.48). A slight improvement was observed in ICC of trials two and three (0.95, 90% CI 0.94 − 0.96) in comparison to one of trials one and two (0.94, 90% CI: 0.92 − 0.95). The SEM and average ICC of all trials were 3.41 (90% CI: 3.17 − 3.69) and 0.96 (90% CI: 0.95 − 0.96) respectively. Forty-five percent of participants thought the device would be suitable for their parents while 69 percent thought the device would benefit their grandparents the most.

High consistency of measures demonstrated that the device is reliable to provide ECG service delivery. The study also showed great potential of device usage in primary health care of Vietnam.

There has been a move towards the development of disease-modifying agents in Alzheimer's disease (AD) and it is likely that early disease-modifying treatments will initially be offered to people who have positive AD markers and mild cognitive impairment (MCI). Consequently, disease-modifying drugs will have distinctive features as compared to currently licensed symptomatic treatments, which makes the implications of these new agents for regulatory and health technology assessment (HTA) processes unclear.

The ROADMAP (Real-world Outcomes across the AD spectrum for better care: Multi-modal data Access Platform) project provides the foundation for a European data platform for real-world evidence in AD, and established an expert advisory group (EXAG) consisting of regulatory and HTA experts. This presentation will summarize the key lessons from the first year of ROADMAP's EXAG and identifies the next steps that are required to prepare Europe's healthcare systems for a disease-modifying drug.

The EXAG identified a need for: (i) establishing the rationale for the selection of priority outcomes in pre-clinical AD and MCI; (ii) establishing accepted outcomes for defining prevention of AD or delayed AD onset; (iii) exploring modern technology that could assist in testing cognition that could easily be used in clinical practice; and (iv) establishing caregiver-relevant outcomes (e.g. quality of life, loss of income, carer time) that are important to capture; and found that not all evidence to support modelling assumptions can be generated through RCTs, making the case for using real-world evidence.

Many of the challenges that the EXAG identified can be solved by generating better real-world data in AD. There is a clear need to agree on the outcomes that will facilitate and inform regulatory and HTA decision-making. Once the gaps in the availability of outcomes in AD will be closed, we will be one step closer towards being ready for a disease-modifying drug.

Timely recommendation by Health Technology Assessment (HTA) agencies for drug reimbursement is critical to ensure patient access to medicines of therapeutic value. In this study, HTA performance was examined in terms of their outcome and timing by looking at how 103 drugs, which gained regulatory approval from 2013 to 2015, were assessed by HTA agencies from 2014 to 2016.

Products must have received regulatory approval from one of the following regulatory agencies: EMA (Europe), Health Canada (Canada) and TGA (Australia). The first HTA recommendations were then collected from PBAC (Australia), CADTH (Canada), HAS (France), IQWiG (Germany), SMC (Scotland) and TLV (Sweden). The HTA decisions were classified as positive, positive with restrictions, negative and multiple.

Eighty-four drugs were approved in Europe before Australia and Canada. Of the studied HTA agencies, PBAC had the highest percentage of products recommended within a year from regulatory approval (93 percent). In addition, Australia had the shortest median time between first regulatory submission by any of the three agencies and HTA recommendation (553 days) as compared to Europe (616 days) and Canada (722 days). This can be attributed to the TGA/PBAC parallel process. However, Australia has the highest proportion of products receiving a negative PBAC recommendation (62 percent).

The majority of drugs were first submitted for reimbursement in Europe, but the time from regulatory submission to HTA decision was the fastest in Australia. This can be attributed to the TGA/PBAC parallel review process, which showed its benefit in reducing the overall time. A parallel review process is also available in Canada; however, it is not utilized as frequently by companies as in Australia.

In an effort to speed the assessment of new medicines while maintaining the quality of the regulatory review, facilitated regulatory pathways (FRPs) have been introduced in many countries. In this study, the effects of FRPs (expedited and conditional reviews) were investigated in terms of their influence on HTA outcomes and timing.

HTA recommendations issued between 2014 and 2016 were collected from CADTH (Canada), HAS (France), IQWIG (Germany), SMC (Scotland) and TLV (Sweden) for 90 internationalized medicines (new active substances approved between 2012 and 2016 by all regulatory agencies in the five jurisdictions). The HTA decisions were then classified into the following categories: positive, positive with restrictions, negative and multiple.

Of this cohort of internationalized medicines that received an HTA recommendation, 31 percent in Canada and 28 percent in Europe were approved via a FRP. With the exception of Scotland, expedited medicines were more likely to be appraised within a year from regulatory approval and had a shorter median time between regulatory approval to HTA recommendation than standard medicines. The largest difference was seen in Sweden, where medicines were 66.5 days faster than standard pathways when it underwent the expedited pathways. Compared to standard pathways, there were generally a higher proportion of positive and positive with restrictions recommendations when expedited pathways were used. Germany reported the largest proportional difference (31 percent) between the two pathways.

Medicines being designated for an expedited review pathway show a reduced time from regulatory approval to HTA decision. This finding suggests there is an alignment between regulators and HTA agencies on which medicines require expedited HTA pathways; however, from this data it cannot be assessed whether the reduced time from approval to HTA decision is attributed to the company strategy, HTA review time or both. Further investigation is required.

Several early access schemes (EAS) exist, which aim to accelerate patient access to new, potentially life-saving therapies. While some information exists on key schemes and their modalities, the determinants that drive adoption of a new medicine under an EAS remain unclear. We aimed to map eligibility criteria for inclusion of new medicines into the different EAS available across countries.

Health technology assessment (HTA) stakeholders across 23 countries globally were invited via email to complete a web-survey with questions on (i) items that define product eligibility for EAS designation, (ii) standards for minimum level of evidence, monitoring, and additional evidence generation for early access products, and (iii) funding arrangements for these products across settings and types of schemes. Anonymized responses were analysed using descriptive statistics.

Fourteen responses from 10 countries (including Belgium, England, France, Japan and Mexico, among others) demonstrated that “unmet clinical need” was paramount for EAS designation across all countries and types of schemes. The next most important factors were “phase-III trials underway” and “serious condition” for Compassionate Use Programme (CUP) and Named Patient Programme (NPP) inclusion (21 percent and 20 percent of respondents, respectively). “Measures in place to monitor risk” was key for CUP and NPP designation (43 percent and 27 percent of respondents, respectively), followed by “innovative product designation” for CUP and “scientific opinion” for NPP eligibility (14 percent and 23 percent of respondents, respectively). “No specific monitoring requirements” exist in Germany and Austria, whereas “reporting of adverse events” is crucial in France, England, Japan and Spain. NPP eligible products are mainly funded at a negotiated price and CUP designated products are largely provided by manufacturers free-of-charge (i.e. England, Scotland, Germany).

Eligibility criteria/requirements and funding arrangements for early access vary considerably across settings and their respective EAS. Information from a larger sample of countries is required for an all-encompassing mapping of the early access products’ characteristics.

The lack of institutional mechanisms in the Philippine Health Insurance Corporation (PhilHealth) for rationalizing spending has led to a less than optimal allocation of financial resources. The study's objective is an explicit and systematic priority setting process of selecting new interventions for PhilHealth through identification of relevant literature evidence on the themes under study, then subjecting these to stakeholder and expert consultations.

The qualitative study followed a problem solving approach to policy analysis. Bardach's Eightfold Path, supplemented by a World Health Organization (WHO) guideline on policy analysis, provided the framework. Eightfold path recommends that the analysis proceed by (i) defining the problem, (ii) assembling the evidence, (iii) constructing the alternatives, (iv) selecting the criteria for identifying the best alternative, (v) projecting the outcomes, (vi) confronting the tradeoffs, (vii) making the decision, and (viii) disseminating the results.

A six-step priority setting process to facilitate the assessment of new interventions for PhilHealth coverage was developed. The process is governed by seven accountability-based principles and four explicit criteria to evaluate interventions. Additionally, the study provided proof-of-concept for conducting local cost-effectiveness and budget impact analyses as key inputs to a national systematic priority-setting process.

This study recommended four criteria and a seven-step process for priority setting to be adopted and an overarching set of principles that will guide the conduct of such activities. The proposed priority-setting process was approved by the PhilHealth. The same process was adopted by the Department of Health in the draft administrative order for health technology assessment. This study stimulated research projects for economic evaluations of health interventions.

Decisions about which health and social services to include in the publicly funded services basket are complex. Several criteria need to be taken into account in decision-making (DM), as well as ethical, economic and organizational issues. Nowadays a global consensus supports the view that citizens’ values and preferences must guide DM. To elicit these values and concerns regarding publicly funded services, the Quebec Health and Welfare Commissioner recently conducted a vast public consultation on the population viewpoints. Parts of this consultation targeted criteria for DM, approaches to assess new or current services and perspectives on appropriateness of care.

Various consultation methods were used in complementary steps: a representative population survey (n=1850), six regional focus groups (n=62), a call for briefs (n=52) for groups that wished to share their views, consultation meetings (n=35) with diverse stakeholders and a call for personal accounts (n=2633). It also held five deliberation sessions (18 citizens and 9 experts) over the course of the project on major related issues.

The need to ensure the appropriateness of covered services was one of the strongest themes emerging from the consultation. Citizens want that the appropriateness evaluation be carried out under certain conditions: transparently, in explicit DM processes, using criteria that are clear and adaptable according to the disease or problem. The whole evaluation process needs to be well documented, showing clearly the data used and rejected, so that they can understand the decision and see on what basis it is supported. Among the usual criteria for DM, those related to cost are less valued whereas others are considered incomplete.

Citizens have clear viewpoints and expectations regarding DM criteria and processes for resource allocation. Decision-makers must take them into account to ensure that the basket of insured services is representative of social values and preferences.

Health technology has no or low added value when it is harmful and/or is deemed to deliver limited health gain relative to its cost, representing inefficient health resource allocation. A joint effort by the Health Technology Assessment International (HTAi) interest group (IG) on disinvestment and early awareness, the IG on ethics, the EuroScan network and the International Network of Agencies for Health Technology Assessment (INAHTA) is aiming to design a toolkit that could aid organizations and individuals considering disinvestment activities. We synthesized state of the art methods for identifying candidate technologies for disinvestment, and propose a framework for executing this task.

We searched systematic reviews on disinvestment and compared the methods used for identifying potential candidates. A descriptive analysis was performed including sources of evidence used and methods for selection / filtration.

Ten systematic reviews were retrieved, and the methods of 29 disinvestment initiatives were compared. A new framework for identifying potential candidates was proposed which comprises seven basic approaches based on the wide definition of evidence provided by Lomas et al.; 11 triggers for disinvestment were adapted from Elshaug's proposal, and 13 methods for applying these triggers that were grouped in embedded and ad-hoc methods.

Identification methods have been described in the literature, and have been tested in different contexts. Context is crucial in determining the ‘not to do’ practices as they are described in different sources.

In recent years, unlike developing countries, developed countries have seen an increase in the survival of women diagnosed with breast cancer and this has been attributed to early detection through screening and best treatments such as adjuvant systemic therapies with medications like Tamoxifen. The burden of breast cancer in Africa, including Ghana, lies among premenopausal women, with mean age of diagnosis being 46 years. However, survival among these women is low due to reasons such as inability to afford treatment including Tamoxifen, an older but cheaper and effective adjuvant therapy. This study therefore sought to assess the cost effectiveness of Tamoxifen compared to nothing for the adjuvant treatment of early breast cancer among pre- and peri-menopausal women in Ghana to inform funding decisions.

A Markov model was developed using TreeAge pro to incorporate effectiveness, costs and utility data. Effectiveness of Tamoxifen, rate of events and utility weights were derived from published literature. Resource utilization and costs were estimated from Ghanaian clinical expert, national health insurance scheme tariffs and medicines. The analysis was conducted from the perspective of the payer.

Patients on Tamoxifen incurred additional costs compared to those who received nothing. The key driver of costs was the cost of Tamoxifen. However, these costs were offset by the QALY gained: 3.51. The incremental cost effectiveness ratio (ICER) was GHC 666.15 (USD 150) per QALY gained. In line with the effective measure commonly used in developing countries, the ICER per DALYs averted was GHC 219.96 (USD 50). The results were sensitive to variations in the utility weights and the cost of Tamoxifen. There were no significant differences between the ICERs of premenopausal and peri-menopausal women in a subgroup analysis.

Compared to no treatment, Tamoxifen therapy is highly cost-effective for the adjuvant treatment of breast cancer among pre- and peri-menopausal women in Ghana. The results can be applied to other African countries with similar resource use and treatment protocols

Botulinum toxin type A (BoNT-A) is used in the management of lower limb spasticity in children, which affects more than 2.5 million children worldwide. BoNT-A aims to improve active function and to prevent or delay future musculoskeletal complications. The objective was to evaluate the relative efficacy and safety of different BoNT-A to manage spasticity in children, in the absence of head-to-head evidence.

A systematic literature review was conducted in March 2016 to identify all relevant randomized controlled trials. The evidence base was synthesized by means of Bayesian network meta-analyses. Scenario analyses included standardized mean differences (SMD). The endpoints were Modified Ashworth Scale (MAS), Tardieu scale-spasticity grade and Goal Attainment Scale (GAS) (SMD only) at twelve weeks post-injection, and any adverse events.

Thirty-eight studies were identified, ten of which met the inclusion criteria for quantitative synthesis. For MAS, abobotulinumtoxinA 15 U/kg/leg was significantly better compared to onabotulinumtoxinA 4 U/kg/leg (−0.99 [−1.49; –0.50]), onabotulinumtoxinA 4 U/kg/leg + casting (−0.81 [−1.30; –0.32]) and numerically (although not statistically significantly) better than onabotulinumtoxinA 8 U/kg (−0.70 [−1.64; 0.22], Pbetter=93%). For GAS, abobotulinumtoxinA 15 U/kg/leg was numerically better than onabotulinumtoxinA 12 U/kg/leg. On Tardieu scale-spasticity grade, abobotulinumtoxinA was comparable to other treatments. AbobotulinumtoxinA 15 U/kg/leg showed the highest SUCRA value on MAS and GAS. On tolerability, abobotulinumtoxinA was found to have comparable or fewer adverse events than onabotulinumtoxinA 4 U/kg/leg.

Our analyses suggest that abobotulinumtoxinA offers a comparable or favourable efficacy on tone (measured by MAS), spasticity (Tardieu scale-spasticity grade), functional outcomes (GAS) and tolerability versus onabotulinumtoxinA, in the management of children with lower limb spasticity. The results must be interpreted in the context of the heterogeneity of the evidence base and sparse evidence base.

Decision-making about replacement or modification of an implantable cardioverter defibrillator (ICD) must be patient-centered and clinically appropriate. We engaged both patients and health care professionals in a multi-method approach in order to recommend structures and processes that facilitate informed and shared decision-making.

A systematic literature review (2000 to 2017) was performed focusing on the patient's perspective and the optimal organization of structures and processes for decision-making. A province-wide field evaluation based on medical chart review was carried out to provide ‘real world’ evidence in Québec's six ICD implanting centers (1 July to 31 December, 2016; N = 418). Patients and health care professionals reviewed the findings of the review and field evaluation, and deliberated recommendations in an anonymous manner by electronic mail. A joint meeting focused on proposed recommendations concerning shared decision-making.

The patients provided feedback on the literature review based on their ICD experience, and highlighted the need for better and more interactive decision aids, clinical information and time, and a private space for sensitive discussions. The field evaluation underlined the variability of treatment choices at the time of replacement and that more than one in ten patients had undergone ICD deactivation. Proposed recommendations focus on multi-disciplinary, integrated follow-up of patients and outline best practice for incorporating patient wishes and life objectives when discussing treatment options. The multi-round consultation process allowed both patients and professionals to co-construct recommendations with our evaluation team.

This multi-method approach enriched our interpretation of literature and ‘real world’ data and facilitated identification and prioritization of important themes. Partnership with both patients and clinicians added a new and energizing dynamic to our evaluation and recommendation processes. We acknowledge the contribution of the members of the patient committee and the clinical experts committee.

Clinical background: Until recently, populations living in remote areas did not have access to specialist care and quality diagnostic services and thus depended on the low response capacity of their local health system. Subsequently, there were equity issues between urban and rural populations. Therefore it was considered telediagnosis applications should be directed towards developing better equity in the provision of services in remote locations without access to specialists. This study has evaluated the results of a new telemedicine system in remote public hospitals in Paraguay, in order to show how the response capacity of the local integrated health service delivery networks has been improved by providing access to tertiary level diagnostic services by specialists. Objective: This study aims to evaluate the utility of telemedicine as a tool for developing better equity in the provision of services in remote locations.

This was a descriptive study, where the results of using telemedicine for diagnosis in remote public hospitals were evaluated as a tool to improve access to diagnostic services countrywide between 2014–2017. For these purposes, type and frequency of pathology diagnosed was determined.

A total of 311,562 telediagnoses were performed in fifty-seven hospitals. The 191,435 electrocardiogram diagnosis performed in the fifty-five hospitals were mainly normal (62.1%), unspecified arrhythmias (12.5%), and sinus bradycardia (10.4%). Also 115,924 teletomography tests were performed in twelve hospitals, where 54.4 percent corresponded to head as a consequence of accidents (motorcycles) and cerebrovascular diseases, 13.8 percent to chest, and the rest the other anatomical regions. Regarding the 4,184 electroencephalogram tests performed, antecedents of seizure (54.3%), evolutionary controls (14.0%), and headache (11.5%), were mainly diagnosed. The nineteen ultrasound studies corresponded to prenatal controls.

Despite the results of the telediagnosis implemented in the public health to develop better equity in the provision of services in remote locations, a widespread use-assessment should be analyzed before this tool is adopted.

Molecular techniques play a critical role in identifying breast cancer patients with overexpressed human epidermal growth factor receptor-2 (HER2). New bright field techniques such as chromogenic in-situ hybridization (CISH) and silver in-situ hybridization (SISH) have emerged to overcome some of the challenges associated with the reference standard, fluorescence in-situ hybridization (FISH). We conducted a literature review and synthesis to characterize the accuracy of HER2 tests, and inform decisions about test selection.

We searched MEDLINE and EMBASE databases using these eligibility criteria: studies evaluating invasive breast cancer samples which examined agreement between CISH or SISH, and FISH, and reported sensitivity, specificity, or concordance. We performed a bivariate meta-analysis of sensitivity and specificity using a generalized linear mixed model in Stata. We used likelihood ratio tests from meta-regression to compare accuracy between HER2 tests.

The search identified 4,475 articles, of which thirty-one were included. A total of thirteen studies (43%) evaluated dual-color SISH, twelve single-color CISH, and six dual-color CISH. The summary estimates for sensitivity and specificity were, respectively, 0.97 (95%CI 0.83–0.99) and 0.99 (95%CI 0.96–1.00) for single-color CISH, 0.98 (95%CI 0.92–0.99) and 0.98 (95%CI 0.91–0.99) for dual-color CISH; 0.92 (95%CI 0.86–0.95), and 0.96 (95%CI 0.91–0.98) for SISH. Significantly higher specificity was reported for single-color CISH than SISH (chi-square 4.12; p = 0.04), while dual-CISH had higher sensitivity than SISH (chi-square: 4.63; p = 0.03). These differences were not maintained when studies with cohorts enriched with equivocal samples were excluded.

The agreement between new bright field tests (SISH and CISH) and FISH is high (>92 percent). Indirect comparison of HER2 tests indicated that overall CISH performance exceeds that of SISH. However, low agreement between SISH and FISH in equivocal cases affects these comparative estimates. The pooled estimates from this meta-analysis can help inform future HER2 test selection decisions.

Microfracture (MF) has been the main intervention in symptomatic articular cartilage knee defects. Autologous chondrocyte implantation (ACI) has looked promising, but was not recommended by the UK National Institute for Health and Care Excellence (NICE) in 2015 due to the short-term follow-up data from trials.

Most long-term data comes from observational studies. We provided new unpublished analyses to NICE based on survival data of these studies, with appropriate caveats. They included: a large ACI study by Nawaz with useful subgroup data by osteoarthritis Kellgren-Lawrence stage and previous repair attempts; a very large MF study by Layton, and a small RCT by Knutsen indicating MF was as ‘good’ as ACI. A Markov model explored the cost-effectiveness of ACI vs. MF. Different scenarios were explored: ACI or MF as a first procedure, followed by ACI or MF in those needing a second repair. A NHS England perspective was adopted. Health outcomes were expressed as quality-adjusted life-years (QALYs).

The revised base-case analysis, used a list price of £16,000 (EUR 17,380 in 2013 prices) for cells, used ACI failure data from Nawaz with no previous procedures for ACI, and pooled MF failure data from two studies-Saris and Knutsen. ACI was more expensive but provided more QALYs. The incremental cost-effectiveness ratio comparing ACI then MF with MF then ACI was £8,000 (EUR 8,690) per QALY. Various sensitivity analyses were conducted assuming a threshold of £20,000 (EUR 21,730) per QALY: previous repair attempts reduced success of ACI (£22,000 (EUR 23,900) per QALY); reducing cell costs, ACI improved its cost-effectiveness; and limiting intervention to patients with higher Kellgren-Lawrence score did not appear cost-effectiveness.

The final NICE guidance published in October 2017 approved the use of ACI for patients who had no previous knee repairs, for people with minimal osteoarthritic damage to the knee, and for people with articular defects of over 2cm2.

In April 2017, the National Institute for Health and Care Excellence (NICE) updated its guidance for highly specialized technology (HST) appraisals, whereby it would automatically fund technologies for very rare diseases that fall below a threshold of an incremental cost-effectiveness ratio (ICER) of GBP 100,000 (USD 133,000) per quality-adjusted life year (QALY). In addition, NICE proposed to introduce a ‘QALY modifier’, weighting QALYs gained by the size of gain, which will advantage treatments that offer greater QALY gains.

We reviewed all technologies reviewed through the NICE HST process until November 2017 and assessed whether additional QALYs may be awarded, and subsequently result in ICERs below the new NICE threshold.

Six products (eculizumab, elosulfase alfa, ataluren, migalistat, eliglustat, and asfotase alfa) have been through HST process. Within the appraisal documents, most analyses were cost consequence analyses with no ICERs reported. The estimated cost per patient per year ranged from approximately GBP 100,000 (USD 133,000) to GBP 400,000 (USD 532,000; listed prices). Of the six technologies, three resulted in at least ten incremental QALYs (eclizumab, elosulfase alfa and asfotase alfa). From the information in the public domain, it is unclear whether this would result in ICERs below GBP 100,000 (USD 133,000) per QALY.

It may become more difficult for HSTs to get recommended by NICE under the new guidance, which requires cost-effectiveness analyses, whereas previously there was no official ICER threshold. The additional weighting of QALYs may be insufficient to meet an ICER threshold of GBP 100,000 (USD 133,000) per QALY.

Bridging gaps between registry-holders, Health Technology Assessment (HTA) producers and users is one of the aims of the European Network for HTA (EUnetHTA) Joint Action 3. In this context, a post-launch evidence generation tool is being developed, including a quality standards tool for registries in HTA. The standards tool for registries in HTA will enable, among others, registry owners to consistently collect high quality registry data, and HTA agencies to use proper registry data collected by others as evidence for their assessments. The objective is to present the first draft version of the tool structure, which is going to be piloted during the forthcoming months.

A review and description of the currently available first version (November 2017) sections, items and criteria for HTA studies.

The tool is divided in three sections; “Methodological Information”, “Essential Standards” and “Additional Requirements”. The first section enables users to analyze not only the ability of the registry to answer to research questions but also to check the registry transparency. The second section encloses the essential elements of good practice and evidence quality (therefore all of them must be met before an HTA report can use the registry data). Finally, the third section includes elements of good practice and evidence quality useful to consider in planning and evaluating registries for specific purposes. Although suggestions are defined, the third section item requirements could depend on the individual HTA agency perspectives and needs.

There is a clear growing availability and requirement for real world data for health technology assessment. A piloted and robust registry standards tool for HTA can provide a relevant basis to improve both the evidence generation but also to make more trustful and excellent evaluations.

To address local workability, cross-setting variation, and clinician and patient perspectives, health technology assessment (HTA) practitioners and health system decision-makers incorporate varying forms of qualitative evidence into evaluations of novel health technologies. Employing principles and methods from long-established sociotechnical fields such as participatory design (PD) may help HTA teams in the production of formal, rigorous ‘practice-based evidence’.

We draw on a theoretical review of foundational PD literature and experiences using PD for a large-scale health information technology project to summarize principles and strategies for the effective introduction and evaluation of new technologies in healthcare.

HTA may benefit from observing some of the core commitments of PD: (i) Ensuring that technologies enhance rather than detract from the quality of working life; (ii) Fostering democratic engagement in the implementation and evaluation of technologies; and (iii) Proceeding via direct partnership with technology users. These are practical commitments stemming from the recognition that technology implementation entails re-configuring existing practices and social arrangements. The experts of this existing milieu are the people on the ground, who may reject or underutilize technologies that they perceive as impractical, ill-adapted to their needs, or having negative consequences on their work. At the same time, PD recognizes that local activities occur within larger systems and that effective technology introduction also requires attention to macro-politics (e.g. governance challenges, competing priorities). PD employs a diversity of methods (e.g. participant observation, focus groups, workshops, interviews) to develop evidence that is holistically informed.

Many of the challenges that HTA faces, both in terms of evidence production and translation, have been encountered before in PD. Given that decision-making around health technologies necessarily involves consideration of many forms of qualitative evidence, there is value in producing and evaluating such evidence in carefully designed manner – a challenge to which fields like PD can lend a wealth of experience.