Effect of etranacogene dezaparvovec on quality of life for severe and moderately severe haemophilia B participants:Results from the phase III HOPE-B trial 2 years after gene therapy

Introduction:For people with haemophilia B (PwHB), bleeding may occur despite prophylaxis, negatively affecting health-related quality of life (HRQoL). The pivotal phase 3 HOPE-B trial investigating the adeno-associated virus gene transfer product, etranacogene dezaparvovec (EDZ), demonstrated sustained factor IX (FIX) activity and bleed protection in PwHB with baseline FIX levels ≤2%. Aim: Assess how EDZ affects HRQoL in HOPE-B trial participants. Methods: HRQoL was evaluated using generic and disease-specific patient reported outcomes (PROs) including the EQ-5D-5L and the Hem-A-QoL questionnaires. Mean domain and total scores were compared 6 months pre- and the first 2 years post-EDZ administration using repeated measures linear mixed models. The percentage of participants with minimal clinically important improvements in HRQoL was also evaluated. Results: Two years post-EDZ, there were nominally significant increases in the least squares (LS) mean score for the EQ-5D-5L Index Value (.04; p =.0129), reflecting better HRQoL. Nominally significant decreases in the LS mean scores, reflecting better HRQoL, were also found for the Hem-A-QoL total score (−6.0; p &lt;.0001) and the Treatment (−13.94; p &lt;.0001), Feelings (−9.01; p &lt;.0001), Future (−6.45; p =.0004) and Work/School (−5.21; p =.0098) domains. The percentage of participants with ≥15-point improvement ranged from 45.83% (95% CI: 31.37%, 60.83%) for Treatment to 13.89% (95% CI: 4.67%, 29.50%) for Family Planning. Results were similar for Year 1. Conclusion:In conclusion, gene therapy with EDZ improved HRQoL in the first and second years in several Hem-A-QoL domains, including Treatment, Feelings, Work/School and Future domains, whereas improvement in other aspects of HRQoL were not demonstrated.</p

Efficacy of the Pentavalent Rotavirus Vaccine, RotaTeq (RV5), Between Doses of a 3-Dose Series and With Less Than 3 Doses (Incomplete Regimen)

Post-hoc analyses of the Rotavirus Efficacy and Safety Trial (RES T) were conducted to determine whether the pentavalent rotavirus vaccine (RV5) confers early protection against rotavirus gastroenteritis (RVGE) before completion of the 3-dose regimen. To evaluate the efficacy of RV5 between doses in reducing the rates of RVGE-related hospitalizations and emergency department (ED) visits in infants who ultimately received all 3 doses of RV5/placebo, events occurring from 2 weeks after the first and second doses to receipt of the subsequent dose (Analysis A) and events occurring from 2 weeks after the first and second doses to 2 weeks after the subsequent dose (Analysis B) were analyzed. In Analysis A, RV5 reduced the rates of combined hospitalizations and ED visits for G1-G4 RVGE or RVGE regardless of serotype between doses 1 and 2 by 100% [95% confidence interval (CI): 72-100%] or 82% (95% CI: 39-97%), respectively, and between doses 2 and 3, RV5 reduced the rates of combined hospitalizations and ED visits for G1-G4 RVGE or RVGE regardless of serotype by 91% (95% CI: 63-99%) or 84% (95% CI: 54-96%), respectively. Similar rate reductions were observed in Analysis B. These data suggest that RV5 provides a high level of protection between doses against hospitalizations and ED visits for RVGE starting as early as 14 days after the first dose

Cost-effectiveness of introducing a rotavirus vaccine in developing countries: The case of Mexico

<p>Abstract</p> <p>Background</p> <p>In developing countries rotavirus is the leading cause of severe diarrhoea and diarrhoeal deaths in children under 5. Vaccination could greatly alleviate that burden, but in Mexico as in most low- and middle-income countries the decision to add rotavirus vaccine to the national immunisation program will depend heavily on its cost-effectiveness and affordability. The objective of this study was to assess the cost-effectiveness of including the pentavalent rotavirus vaccine in Mexico's national immunisation program.</p> <p>Methods</p> <p>A cost-effectiveness model was developed from the perspective of the health system, modelling the vaccination of a hypothetical birth cohort of 2 million children monitored from birth through 60 months of age. It compares the cost and disease burden of rotavirus in an unvaccinated cohort of children with one vaccinated as recommended at 2, 4, and 6 months.</p> <p>Results</p> <p>Including the pentavalent vaccine in the national immunisation program could prevent 71,464 medical visits (59%), 5,040 hospital admissions (66%), and 612 deaths from rotavirus gastroenteritis (70%). At US$10 per dose and a cost of administration of US$13.70 per 3-dose regimen, vaccination would cost US$122,058 per death prevented, US$4,383 per discounted life-year saved, at a total net cost of US$74.7 million dollars to the health care system. Key variables influencing the results were, in order of importance, case fatality, vaccine price, vaccine efficacy, serotype prevalence, and annual loss of efficacy. The results are also very sensitive to the discount rate assumed when calculated per life-year saved.</p> <p>Conclusion</p> <p>At prices below US$15 per dose, the cost per life-year saved is estimated to be lower than one GNP per capita and hence highly cost effective by the WHO Commission on Macroeconomics and Health criteria. The cost-effectiveness estimates are highly dependent upon the mortality in the absence of the vaccine, which suggests that the vaccine is likely to be significantly more cost-effective among poorer populations and among those with less access to prompt medical care – such that poverty reduction programs would be expected to reduce the future cost-effectiveness of the vaccine.</p

Healthcare utilization and cost of cancer-related care prior to allogeneic hematopoietic cell transplantation for hematologic malignancies in the US: a retrospective real-world analysis

Abstract Background Hematopoietic cell transplantation (HCT) is a potentially curative therapy as well as a costly procedure. Published studies have examined the cost of HCT in the US and the complications that follow but little is known about the cancer-related healthcare costs and resource utilization prior to the procedure and none of the studies have examined the variability in cost based on the type of hematologic malignancy involved. The aim of this study was to estimate mean cancer-related costs and resources incurred before the HCT is performed from the time the hematologic malignancy first develops. Methods The IBM® MarketScan® Research Databases were used to identify adult patients ≥18 years of age with commercial or Medicare supplemental insurance who had undergone allogeneic HCT for hematologic malignancies from January 1, 2008 to December 31, 2017. Healthcare utilization and costs were assessed during the 6 months prior to diagnosis (pre-diagnostic period) and the follow-up period from diagnosis just prior to the HCT (pre-HCT period). Multivariable regression models were constructed to estimate total all-cause costs and cancer-related costs as well as healthcare utilization by type in each time period. Results A total of 2663 commercially insured patients and 266 with Medicare supplemental insurance were included in the study population. The mean-adjusted incremental cancer-related costs for commercially insured patients was $399,011 in the overall observation period including the pre-diagnostic and pre-HCT periods combined, 9$195,575 for the same time period but the patterns of healthcare utilization were similar to the commercially insured population. Inpatient care accounted for approximately one-half the cost in both patient populations. By type of hematologic malignancy, costs were lowest for myeloproliferative disorders ($211,561) and highest for acute lymphocytic leukemia ($462,072) in the commercially insured population. Conclusion This study demonstrates that overall patients with hematologic malignancies requiring HCT have considerable cancer-related healthcare resource utilization and costs leading up to HCT compared to the period of time prior to developing cancer. </jats:sec

Acute/Subacute Herpes Zoster: Healthcare Resource Utilisation and Costs in a Group of US Health Plans

Background: Although there are estimated to be nearly 1 million cases of herpes zoster diagnosed in the US each year, the economic costs associated with herpes zoster in the US have not been well described. Objective: To describe the healthcare resource utilisation and costs associated with physician-diagnosed acute/subacute herpes zoster, from a payer perspective, using a large US healthcare claims database. Methods: Data for the period 2000-1 were obtained from the Medstat Marketscan healthcare claims database. The duration of acute/subacute herpes zoster was considered to include the 21 days preceding, and 90 days following, the initial herpes zoster diagnosis. Resource utilisation was examined for individuals with newly diagnosed acute/subacute herpes zoster (n_=_8741) and compared, through regression analyses, with that observed for control individuals from the same population (n_=_50_000). Similar analyses were conducted for costs; the costs included reflected healthcare payments from patients, insurers and other sources. Regression analyses controlled for demographics (age, gender), conditions that have been observed with greater frequency among patients with acute/subacute herpes zoster in prior studies (cancer, HIV infection, organ transplantation, other immunosuppressive conditions and therapies) and the number of billed services within each of seven categories of care that were potentially related to acute/subacute herpes zoster and that were utilised within the 30-180 days prior to the diagnosis for affected patients, and over an analogous period for controls. Results: The acute/subacute phase of herpes zoster was estimated to result in an average of 1.7 (standard error [SE] 0.02) additional physician and hospital outpatient visits, 0.05 (SE 0.003) additional emergency room visits, 0.03 (SE 0.003) additional inpatient hospital admissions, 2.1 (SE 0.03) additional prescriptions filled and $US431 (SE 17.60) in additional healthcare costs per patient. Among patients with acute/subacute herpes zoster, 21.1$US258 (SE 37.70) among patients aged =80 years. The numbers of additional outpatient visits, inpatient admissions, prescriptions filled for pain medications and coded complications were also substantially higher among older than younger patients with acute/subacute herpes zoster. Conclusions: The management of acute/subacute herpes zoster was found to result in substantial healthcare costs, with outpatient care and prescription drugs comprising the majority of the cost burden. To more fully understand the overall cost of herpes zoster disease to society, future studies should examine the healthcare costs associated with post-herpetic neuralgia and productivity losses due to herpes zoster and post-herpetic neuralgia.Cost-analysis, Cost-of-illness, Herpes-zoster, Resource-use

The symptom experience of hereditary angioedema (HAE) patients beyond HAE attacks: literature review and clinician interviews

Abstract Background Hereditary angioedema (HAE) is a genetic disorder characterized by re-occurring swelling episodes called “attacks,” usually in the limbs, face, airways, and intestinal tract. New prophylactic therapies have reduced the frequency of these attacks. This study describes results from a literature review and clinician interviews assessing patient HAE symptom experiences and timing, and then evaluates whether existing patient-reported outcome (PRO) tools adequately reflect this experience. Methods A targeted literature review as well as interviews with key opinion leaders (KOLs), were conducted to capture information about the patient experience and their symptoms. An assessment of various PROs was then conducted to determine how well they each covered HAE symptoms and impacts. Results Nineteen HAE symptoms were identified. KOLs reported that patients on prophylactic therapy experienced some symptoms indicating an attack was imminent, but then never experienced an attack. The comparison of the different PROs found that the Hereditary Angioedema Patient-Reported Outcome was the instrument that most thoroughly examined the symptoms of patients with HAE. Conclusions Given the introduction of new prophylactic therapies, further research is needed to determine the effect of being attack-free for longer periods of time on health-related quality of life. </jats:sec

Cost-effectiveness of introducing a rotavirus vaccine in developing countries: the case of Mexico.

BackgroundIn developing countries rotavirus is the leading cause of severe diarrhoea and diarrhoeal deaths in children under 5. Vaccination could greatly alleviate that burden, but in Mexico as in most low- and middle-income countries the decision to add rotavirus vaccine to the national immunisation program will depend heavily on its cost-effectiveness and affordability. The objective of this study was to assess the cost-effectiveness of including the pentavalent rotavirus vaccine in Mexico's national immunisation program.MethodsA cost-effectiveness model was developed from the perspective of the health system, modelling the vaccination of a hypothetical birth cohort of 2 million children monitored from birth through 60 months of age. It compares the cost and disease burden of rotavirus in an unvaccinated cohort of children with one vaccinated as recommended at 2, 4, and 6 months.ResultsIncluding the pentavalent vaccine in the national immunisation program could prevent 71,464 medical visits (59%), 5,040 hospital admissions (66%), and 612 deaths from rotavirus gastroenteritis (70%). At US$10 per dose and a cost of administration of US$13.70 per 3-dose regimen, vaccination would cost US$122,058 per death prevented, US$4,383 per discounted life-year saved, at a total net cost of US$74.7 million dollars to the health care system. Key variables influencing the results were, in order of importance, case fatality, vaccine price, vaccine efficacy, serotype prevalence, and annual loss of efficacy. The results are also very sensitive to the discount rate assumed when calculated per life-year saved.ConclusionAt prices below US$15 per dose, the cost per life-year saved is estimated to be lower than one GNP per capita and hence highly cost effective by the WHO Commission on Macroeconomics and Health criteria. The cost-effectiveness estimates are highly dependent upon the mortality in the absence of the vaccine, which suggests that the vaccine is likely to be significantly more cost-effective among poorer populations and among those with less access to prompt medical care - such that poverty reduction programs would be expected to reduce the future cost-effectiveness of the vaccine

Additional file 1 of Healthcare utilization and cost of cancer-related care prior to allogeneic hematopoietic cell transplantation for hematologic malignancies in the US: a retrospective real-world analysis

Additional file 1