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Abstract: Endometritis reduces reproductive performance in dairy cattle. Diagnosis of endometritis is undertaken using a variety of techniques including vaginoscopy, manual examination, cytology and ultrasonography. The current studies compared a novel test device (“metricheck”) that is inserted into the vagina with vaginoscopy and then examined the relationship between the metricheck test score at 35 days before the start of the seasonal breeding programme and subsequent reproductive performance. Cows (n =191; Study 1) with a history of a peripartum disease were examined by both vaginoscopy and the metricheck device and any material viewed within the vagina (using vaginoscopy) or retrieved (by the metricheck device) was scored on a 0 (no material) to 5 (grossly purulent and with an odour) scale. Within each herd the order of examination was randomized with sequentially presented pairs of cows. All cows (n =2793; Study 2) from nine herds were examined and scored using the metricheck device 35 days before the start of the seasonal breeding programme. All cows were pregnancy tested to determine date of conception. In Study 1, more cows were defined as infected (i.e. score>1) following metricheck than vaginoscopic examination (60% versus 43%, respectively; P <0.05) and the level of agreement between the two tests was moderate (κ =0.45). The metricheck device had a higher sensitivity, but lower specificity, than vaginoscopy. Endometritis (i.e. score>1) was detected in 21.2% of cows examined in Study 2. The prevalence of endometritis varied among herds, declined with time postpartum (P <0.05) and was higher in cows recorded as having a peripartum disease (P <0.01). Cows diagnosed with endometritis were at higher risk of not being detected in oestrus before the start of breeding (P <0.01), took longer to be inseminated after the start of the seasonal breeding programme (P <0.01), had a lower first service conception rate (P <0.01), had lower 56-day and final pregnancy rates (P <0.05) and took longer to conceive than cows without endometritis (P <0.05). It is concluded that examination with the metricheck device is more sensitive in detecting endometritis than vaginoscopy. Diagnosis of endometritis with the metricheck device was associated with poorer subsequent reproductive performance. [Copyright &y& Elsevier]

Since 2013, NICE appraise Highly Specialised Technologies (HST) ("for use in the provision of services for rare and very rare conditions") using a distinct appraisal framework. This research compares NICE HST appraisal outcomes with corresponding guidance by other European HTA bodies, stratified by archetype: cost-effectiveness versus clinical-effectiveness. Although NICE HST appraisals have more positive recommendations and have faster time to recommendations following European MA than other cost-effectiveness HTA bodies, time to positive recommendation is still substantially delayed compared to clinical-effectiveness HTA bodies. [Extracted from the article]

CCE-appraised products had a significantly lower mean delay from EC-approval to national HTA publication in comparison to non-CCE markets (223 days and 324 days respectively; p=0.025) To date, drugs appraised under EUnetHTA JAs have been assessed in a shorter time by CCE markets in comparison to those appraised by non-CCE markets with a similar rate of positive appraisal. This may reflect a greater alignment between the JA clinical framework to CCE market HTA decision-drivers than the non-CCE markets or, may rather reflect natural assessment timelines of the HTA bodies involved. [Extracted from the article]

National Health Technology Assessment (HTA) processes represent the most significant hurdle for new pharmaceuticals aiming to achieve market access, often requiring a substantially higher evidence base than that which is needed for regulatory approval. With the exception of the NICE FTA pathway, abbreviated pathways are restricted to new preparations of previously subsidized drugs, generics or biosimilars, with limited applicability in bringing innovative therapies to market. [Extracted from the article]

There are four Appraisal Committees (A, B, C, D); previous research indicated that single technology appraisals (STA) undertaken by NICE Appraisal Committee D were associated with a significantly lower rate of "recommended" outcomes than other committees (Macaulay et al., ISPOR EU 2017). NICE STA guidance for oncology drugs was screened (18/06/2009-20/03/2019) and EoL consideration data extracted alongside the Appraisal Committee. [Extracted from the article]

In 2016, the Cancer Drugs Fund (CDF) was launched as a temporary reimbursement fund, where manufacturers could collect observational data to resolve key areas of clinical uncertainty and demonstrate that the drug works in the NHS population in England. Methods Publicly-available Managed Access Agreements (MAAs) currently ongoing between NHS England and manufacturers within the CDF as of 15/01/2020 were identified and key data extracted. As of January 2020 five drugs (osimertinib, ixazomib with lenalidomide + dexamethasone, nivolumab [SCCHN], nivolumab [SQ NSCLC], nivolumab [NSQ NSCLC] have exceeded their pre-specified data collection windows on the CDF (range: 1-22 months, mean: 8-months). [Extracted from the article]

The first two CAR-T cell therapies, Kymriah® (tisagenlecleucel) and Yescarta® (axicabtagene ciloleucel) received European marketing authorizations in August 2018 (Kymriah® for ALL and DLBCL and Yescarta® for DLBCL/PMBCL). Results Twenty five HTA evaluations of CAR-T cell therapies in scope countries were identified (8 Kymriah® ALL, 8 Kymriah® DLBCL, 7 Yescarta® DLBCL/PMBCL, 1 Yescarta® DLBCL, and 1 Yescarta® PMBCL) completed at an average of 7.5 months after European marketing authorization. The NLT accepted Kymriah® (ALL) and Yescarta® (DLBCL/PMBCL) following a delay, but rejected Kymriah (DLBCL). [Extracted from the article]

With the emergence of transformative therapies for rare and neglected diseases, several HTA bodies have implemented alternative appraisal pathways (e.g. the highly specialized technology [HST] pathway by NICE in 2015) to ensure that recommendations on these potentially high-cost therapies are made consistently and fairly, whist recognizing and rewarding the scale of the benefit they provide. This research aims to evaluate the relationship between the epidemiology of the disease, the HST recommendation for the treatment, and the number of patients treated. In only one HST was uptake substantially higher than predicted: eculizumab (HST1), with an estimated 20-30 patients diagnosed-per-year (estimated total uptake of 75 from recommendation), where the actual number treated since January 2015 was 154 patients. [Extracted from the article]

PNS141 PATIENT INVOLVEMENT IN REIMBURSEMENT DECISION-MAKING - HOW ARE THEY INVOLVED? Patient participation in national reimbursement or Health Technology Assessment (HTA) processes has been increasingly gaining traction. Methods A targeted literature review and internal expert validation was undertaken in 20 countries across Europe, Asia-Pacific, and the Americas in order to understand the extent of patient involvement in HTA decisions. [Extracted from the article]

BACKGROUND: NICE evaluates the clinical-and cost-effectiveness of pharmaceuticals to inform recommendations on whether they should be publicly-reimbursed in England and Wales. In April 2017, NICE introduced a new Fast Track Appraisal (FTA) process, under which drugs which offer exceptional value for money (defined as an incremental cost per QALY gained of <£10,000, or where a cost-comparison case can be made that similar/greater benefits can be provided at similar/lower cost). Payers offering faster evaluations with reimbursement incentives for new therapies at comparable costs could offer a best-practice HTA process for incentivizing lower company pricing. [Extracted from the article]

The schemes in the UK, France and Sweden are the Early Access to Medicines Schemes (EAMS), cohort Temporary Authorization for Use (cohort-ATU) and Compassionate Use Program (CUP), respectively. Their main distinction relates to reimbursement: the cohort-ATU allows manufacturers to charge whereas under EAMS and CUP the manufacturer must provide for no charge. Conclusions The EAMS, CUP and cohort-ATU schemes appear to attract a largely distinct group of therapies and the cohort-ATU scheme has attracted over double and triple the drug:indication pairings than EAMS and CUP respectively. [Extracted from the article]

The Institute for Clinical and Economic Review (ICER) publishes reports on the clinical and economic value of drugs for US payers. Each report is subject to a public meeting by one of three independent expert committees (the California Technology Assessment Forum [CTAF], Midwest Comparative Effectiveness Public Advisory Council [CEPAC], and New England CEPAC) discusses the report and votes on the evidence presented. Of the 51 votes for healthcare value, most drugs had a majority vote of low or intermediate value: CTAF: 9 (90%); Midwest CEPAC: 12 (86%); New England CEPAC: 22 (81%). [Extracted from the article]

PNS73 THE RIPPLE EFFECT â€" HOW PMPRB REFORMS COULD IMPACT DRUG PRICES GLOBALLY The Patented Medicine Prices Review Board (PMPRB) was created in 1987 as an independent quasi-judicial tribunal with a statutory mandate to ensure that the prices of patented medicines in Canada are not excessive. Conclusion Over the last 10 years, the PMPRB have been investigating a greater number of drugs and are increasingly issuing VCUs to regulate drug prices (applying to over a tenth of drugs reviewed in 2017). [Extracted from the article]

The Italian Medicines Agency (AIFA), is responsible for setting the national reimbursement status and pricing of pharmaceuticals. This research evaluates all therapies granted AIFA innovative designation under this new algorithm. Conclusions AIFA is only applying innovative status to a minority of new therapies, most of which are either for oncology indications and/or EMA-designated orphan indications. [Extracted from the article]

Large, multicentre, randomised Phase III trials that demonstrate statistically significant comparative benefits according to a pre-specified primary endpoint are regarded as the gold standard basis for marketing authorization. Some products have secured marketing authorizations despite not showing statistical significance in the primary endpoint of their phase III trials. Conclusions Despite failed primary endpoints in phase III trials, some therapies have secured regulatory approvals and translated these into successful payer reimbursement. [Extracted from the article]

BEST PRACTICE LESSONS OF REIMBURSEMENT INCENTIVES FOR INNOVATIVE PRODUCTS This research evaluates how many and what types of therapies have been granted AIFA innovative designation and included in the Innovative Drug Funds. METHODOLOGY: Therapies with an AIFA innovative designation were identified from the AIFA website and key information extracted (up to 10/01/2020) Results Since the new AIFA innovation algorithm was established in April 2017, 15 therapies have been included in the Innovative Drug Funds (0 in 2017, 9 in 2018 and 6 in 2019). [Extracted from the article]

Pharmaceutical product lifecycles are normally characterised by protracted clinical development followed by marketing under exclusivity/patent protection during which returns on investment (ROI) can be realised. However, we are entering an era of transformational therapies with curative potential (e.g. gene and CAR-T cell therapies) for whom the window to realise returns on investment may be greatly curtailed. Nusinersen has successfully translated marketing authorisation into rapid reimbursement across a wide range of payer bodies. [Extracted from the article]

Under this pathway, ultra-orphan medicines (definition: prevalence <1:50,000) would be made available for >=3-years whilst additional evidence is collected to inform a final Scottish Medicines Consortium (SMC) appraisal. Prior to this, the SMC had an ultra-orphan medicine evaluation process, with a broader decision-making framework versus the standard appraisal process. Further research can compare how SMC recommendations of ultra-orphan medicines will evolve according to other countries following the new decision-making pathway. [Extracted from the article]

In Spain, newly authorized medicines are assessed by the Inter-Ministerial Pricing Commission for Pharmaceuticals (CIPM), which provides national reimbursement recommendations with a maximum ex-factory price. Since November 2017, CIPM recommendations have been regularly published, giving the opportunity to evaluate the impact of TPRs on the speed and outcome of CIPM decisions, which is the focus of this research. Drug-indication pairings with "positive" and "alterative" TPR outcomes are associated with significantly better and faster CIPM decisions than those with "not recommended" TPR outcomes. [Extracted from the article]

This research aims to evaluate any correlation between the additional benefit manufacturers claim and the benefit that IQWiG and G-BA report. Manufacturers requesting lesser levels of benefits increased the odds of both GBA and IQWiG recognizing no additional benefits, with IQWiG less so than GBA (Wald tests: =11.4, p=0.077; =26.1, p<0.01, respectively). Further research is needed to identify whether manufacturers request greater additional benefit for drugs with a stronger supportive data package or whether manufacturer requests for additional benefit independently impact GBA and IQWiG decision-making. [Extracted from the article]

HAVE EMA PRIME DESIGNATIONS SUPPORTED ACCELERATED REGULATORY APPROVAL AND PATIENT ACCESS? For any with EC marketing authorisation (MA), the corresponding HTA assessments by NICE, SMC, G-BA and HAS were screened and their outcomes extracted. Nevertheless, the two EMA-approved therapies with PRIME designations have received broad reimbursement across several major markets, but these recommendations are frequently conditional and add additional delays to patient access. [Extracted from the article]

The traditional pharmaceutical market model focussed on large high-income countries is being challenged by the emergence of middle-income markets with rapidly growing economies, healthcare coverage, and willingness-to-pay for medicines. To best-inform pharmaceutical reimbursement decision-making, many emerging markets are establishing Health Technology Assessment (HTA) bodies with varying evidentiary requirements and decision-making criteria. This research illustrates how two emerging markets from the same region with similar GDP per capita, can have very different HTA systems in terms of implementation, requirements, and decision-making criteria. [Extracted from the article]

PMU64 UNLOCKING ACCESS FOR TRANSFORMATIONAL CAR-T CELL AND GENE THERAPIES. We are embarking upon an era of innovative new therapies e.g. CAR-T cell and gene therapies that offer transformational benefits for patients with severe unmet needs. Cumulatively, the budget impact of treating all eligible patients with a CAR-T cell therapy comes up to £116 million/year. [Extracted from the article]

The first two CAR-T cell therapies, Kymriah® (tisagenlecleucel) and Yescarta® (axicabtagene ciloleucel) received European marketing authorization in August 2018 (Kymriah® for ALL and DLBCL and Yescarta® for DLBCL/PMBCL). Seventeen completed HTA evaluations of CAR-T cell therapies were identified (6 Kymriah® ALL, 5 Kymriah® DLBCL, 6 Yescarta® DLBCL/PMBCL) at an average of 5.4 months after European marketing authorization. [Extracted from the article]