Budget projections and clinical impact of an immuno-oncology class of treatments: Experience in four EU markets

Background Immunotherapies have revolutionized oncology, but their rapid expansion may potentially put healthcare budgets under strain. We developed an approach to reduce demand uncertainty and inform decision makers and payers of the potential health outcomes and budget impact of the anti-PD-1/PD-L1 class of immuno-oncology (IO) treatments. Methods We used partitioned survival modelling and budget impact analysis to estimate overall survival, progression-free survival, life years gained (LYG), and number of adverse events (AEs), comparing “worlds with and without” anti-PD-1/PD-L1s over five years. The cancer types initially included melanoma, first and second line non-small cell lung cancer (NSCLC), bladder, head and neck, renal cell carcinoma, and triple negative breast cancer [1]. Inputs were based on publicly available data, literature, and expert advice. Results The model [2] estimated budget and health impact of the anti-PD-1/PD-L1s and projected that between 2018−2022 the class [3] would have a manageable economic impact per year, compared to the current standard of care (SOC). The first country adaptations showed that for that period Belgium would save around 11,100 additional life years and avoid 6,100 AEs. Slovenia - 1,470 LYGs and 870 AEs avoided; Austria - respectively 4,200, 3,000; Italy – 19,800, 6,800. For Austria, the class had a projected share of about 4.5 % of the cancer care budget and 0.4 % of the total 2020 healthcare budget. For Belgium, Slovenia, and Italy - respectively 15.1 % and 1.1 %, 12.6 %, 0.6 %, and 6.5 %, 0.5 %. Conclusion The Health Impact Projection (HIP) is a horizon scanning model designed to estimate the potential budget and health impact of the PD-(L)1 inhibitor class at a country level for the next five years. It provides valuable data to payers which they can use to support their reimbursement plans

Insulin-like growth factor binding protein-2 (IGFBP2) is a key molecule in the MACC1-mediated platelet communication and metastasis of colorectal cancer cells

Tumor cell crosstalk with platelets and, subsequently, their activation are key steps in hematogenous tumor metastasis. MACC1 is an oncogene involved in molecular pathogenesis of colorectal cancer (CRC) and other solid tumor entities, mediating motility and metastasis, making MACC1 an accepted prognostic biomarker. However, the impact of MACC1 on platelet activation has not yet been addressed. Here, we investigated the activation of platelets by human CRC cells upon MACC1 modulation, indicated by platelet aggregation and granule release. These approaches led to the identification of insulin-like growth factor binding protein-2 (IGFBP2) as a functional downstream molecule of MACC1, affecting communication with platelets. This was confirmed by an shRNA-mediated IGFBP2 knockdown, while maintaining MACC1 activity. Although IGFBP2 displayed an attenuated platelet activation potential, obviously by scavenging IGF-I as a platelet costimulatory mediator, the MACC1/IGFBP2 axis did not affect the thrombin formation potential of the cells. Furthermore, the IGFBP2/MACC1-driven cell migration and invasiveness was further accelerated by platelets. The key role of IGFBP2 for the metastatic spread in vivo was confirmed in a xenograft mouse model. Data provide evidence for IGFBP2 as a downstream functional component of MACC1-driven metastasis, linking these two accepted oncogenic biomarkers for the first time in a platelet context

Search for markers of invasive growth in breast cancer: association with disease prognosis

In the present study, we analyzed the gene expression profiles of various morphological structures of breast cancer (GEO, GSE80754) to identify new markers of invasion and to assess their association with disease prognosis. Nine proteins (KIF14, DSC3, WAVE, etc.) was selected based on the literature analysis of the involvement of genes up- and down-regulated in solid and trabecular structures in cancer invasion and a heterogeneity in expression of their proteins in breast tumors. The association of these proteins with patients' survival was assessed

Physical and mental health comorbidity is common in people with multiple sclerosis: nationally representative cross-sectional population database analysis

<b>Background</b> Comorbidity in Multiple Sclerosis (MS) is associated with worse health and higher mortality. This study aims to describe clinician recorded comorbidities in people with MS. <p></p> <b>Methods</b> 39 comorbidities in 3826 people with MS aged ≥25 years were compared against 1,268,859 controls. Results were analysed by age, gender, and socioeconomic status, with unadjusted and adjusted Odds Ratios (ORs) calculated using logistic regression. <p></p> <b>Results</b> People with MS were more likely to have one (OR 2.44; 95% CI 2.26-2.64), two (OR 1.49; 95% CI 1.38-1.62), three (OR 1.86; 95% CI 1.69-2.04), four or more (OR 1.61; 95% CI 1.47-1.77) non-MS chronic conditions than controls, and greater mental health comorbidity (OR 2.94; 95% CI 2.75-3.14), which increased as the number of physical comorbidities rose. Cardiovascular conditions, including atrial fibrillation (OR 0.49; 95% CI 0.36-0.67), chronic kidney disease (OR 0.51; 95% CI 0.40-0.65), heart failure (OR 0.62; 95% CI 0.45-0.85), coronary heart disease (OR 0.64; 95% CI 0.52-0.71), and hypertension (OR 0.65; 95% CI 0.59-0.72) were significantly less common in people with MS. <p></p> <b>Conclusion</b> People with MS have excess multiple chronic conditions, with associated increased mental health comorbidity. The low recorded cardiovascular comorbidity warrants further investigation

The multiple sclerosis risk sharing scheme monitoring study - early results and lessons for the future

Background: Risk sharing schemes represent an innovative and important approach to the problems of rationing and achieving cost-effectiveness in high cost or controversial health interventions. This study aimed to assess the feasibility of risk sharing schemes, looking at long term clinical outcomes, to determine the price at which high cost treatments would be acceptable to the NHS. Methods: This case study of the first NHS risk sharing scheme, a long term prospective cohort study of beta interferon and glatiramer acetate in multiple sclerosis ( MS) patients in 71 specialist MS centres in UK NHS hospitals, recruited adults with relapsing forms of MS, meeting Association of British Neurologists (ABN) criteria for disease modifying therapy. Outcome measures were: success of recruitment and follow up over the first three years, analysis of baseline and initial follow up data and the prospect of estimating the long term cost-effectiveness of these treatments. Results: Centres consented 5560 patients. Of the 4240 patients who had been in the study for a least one year, annual review data were available for 3730 (88.0%). Of the patients who had been in the study for at least two years and three years, subsequent annual review data were available for 2055 (78.5%) and 265 (71.8%) patients respectively. Baseline characteristics and a small but statistically significant progression of disease were similar to those reported in previous pivotal studies. Conclusion: Successful recruitment, follow up and early data analysis suggest that risk sharing schemes should be able to deliver their objectives. However, important issues of analysis, and political and commercial conflicts of interest still need to be addressed

The cost-effectiveness of long-term antiviral therapy in the management of HBeAg-positive and HBeAg-negative chronic hepatitis B in Singapore

The purpose of this study was the economic evaluation of short-duration treatments of chronic hepatitis B (CHB) and longer duration antiviral treatment for up to 5 years. Two 10-health state Markov models were developed for hepatitis B e antigen (HBeAg)-positive and HBeAg-negative CHB patients respectively. The perspective of this economic evaluation was the Singapore healthcare system and CHB patient. The models followed cohorts of HBeAg-positive and HBeAg-negative CHB patients, respectively, over a period of 40 years, by which time the majority of the cohorts would have died if left untreated. Costs and benefits were discounted at 5% per annum. Annual rates of disease progression and the magnitude of treatment effects were obtained from the literature, with a focus on data obtained in Asian patients and meeting the criteria for therapy as described in internationally recognized management guidelines. Short-course therapy with α-interferon, or 1-year treatment with pegylated interferon α-2a, lamivudine or adefovir had limited impact on disease progression. In contrast, treatment of CHB with antiviral therapy for 5 years substantially decreased the rate of disease progression. Treatment with lamivudine for 1-year is highly cost-effective compared with no treatment of CHB but has limited effect on reducing the rate of disease progression. Compared with 1-year treatment with lamivudine, sequential antiviral therapies for up to 5 years (i.e. lamivudine plus adefovir on emergence of lamivudine resistance or adefovir plus lamivudine on emergence of adefovir resistance) are highly cost-effective by international standards. These conclusions are robust to uncertainties in model inputs and are consistent with the findings of other recently published studies

An assessment of validity and responsiveness of generic measures of health-related quality of life in hearing impairment

This article is made available through the Brunel Open Access Publishing Fund. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Purpose: This review examines psychometric performance of three widely used generic preference-based measures, that is, EuroQol 5 dimensions (EQ-5D), Health Utility Index 3 (HUI3) and Short-form 6 dimensions (SF-6D) in patients with hearing impairments. Methods: A systematic search was undertaken to identify studies of patients with hearing impairments where health state utility values were measured and reported. Data were extracted and analysed to assess the reliability, validity (known group differences and convergent validity) and responsiveness of the measures across hearing impairments. Results: Fourteen studies (18 papers) were included in the review. HUI3 was the most commonly used utility measures in hearing impairment. In all six studies, the HUI3 detected difference between groups defined by the severity of impairment, and four out of five studies detected statistically significant changes as a result of intervention. The only study available suggested that EQ-5D only had weak ability to discriminate difference between severity groups, and in four out of five studies, EQ-5D failed to detected changes. Only one study involved the SF-6D; thus, the information is too limited to conclude on its performance. Also evidence for the reliability of these measures was not found. Conclusion: Overall, the validity and responsiveness of the HUI3 in hearing impairment was good. The responsiveness of EQ-5D was relatively poor and weak validity was suggested by limited evidence. The evidence on SF-6D was too limited to make any judgment. More head-to-head comparisons of these and other preference measures of health are required.Medical Research Counci

CAR-T cell. the long and winding road to solid tumors

Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles

Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis

Abstract (provisional) Background Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. Methods This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. Discussion This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Trial registration: Current Controlled Trials ISRCTN7651747