Marjolijn van Keep - Academia.edu (original) (raw)

Papers by Marjolijn van Keep

Value in health, Jun 1, 2024

PharmacoEconomics - open, Jan 30, 2024

Background Resistant hypertension (rHTN) is defined as blood pressure (BP) of ≥ 140/90 mmHg despi... more Background Resistant hypertension (rHTN) is defined as blood pressure (BP) of ≥ 140/90 mmHg despite treatment with at least three antihypertensive medications, including a diuretic. Endovascular ultrasound renal denervation (uRDN) aims to control BP alongside conventional BP treatment with antihypertensive medication. This analysis assesses the cost effectiveness of the addition of the Paradise uRDN System compared with standard of care alone in patients with rHTN from the perspective of the United Kingdom (UK) health care system. Methods Using RADIANCE-HTN TRIO trial data, we developed a state-transition model. Baseline risk was calculated using Framingham and Prospective Cardiovascular Münster (PROCAM) risk equations to estimate the long-term cardiovascular risks in patients treated with the Paradise uRDN System, based on the observed systolic BP (SBP) reduction following uRDN. Relative risks sourced from a meta-analysis of randomised controlled trials were then used to project cardiovascular events in patients with baseline SBP ('control' patients); utility and mortality inputs and costs were derived from UK data. Costs and outcomes were discounted at 3.5% per annum. Modelled outcomes were validated against trial meta-analyses and the QRISK3 algorithm and real-world evidence of RDN effectiveness. One-way and probabilistic sensitivity analyses were conducted to assess the uncertainty surrounding the model inputs and sensitivity of the model results to changes in parameter inputs. Results were reported as incremental cost-effectiveness ratios (ICERs). Results A mean reduction in office SBP of 8.5 mmHg with uRDN resulted in an average improvement in both absolute life-years (LYs) and quality-adjusted life-years (QALYs) gained compared with standard of care alone (0.73 LYs and 0.67 QALYs). The overall base-case ICER with uRDN was estimated at £5600 (€6500) per QALY gained (95% confidence interval £5463-£5739 [€6341-€6661]); modelling demonstrated > 99% probability that the ICER is below the £20,000-£30,000 (€23,214-€34,821) per QALYs gained willingness-to-pay threshold in the UK. Results were consistent across sensitivity analyses and validation checks. Conclusions Endovascular ultrasound RDN with the Paradise system offers patients with rHTN, clinicians, and healthcare systems a cost-effective treatment option alongside antihypertensive medication.

With parameter optimization ±25% and incremental cost-effectiveness ratio calculated wit... more With parameter optimization ±25% and incremental cost-effectiveness ratio calculated with reference to the “no routine screening” strategy.LYG:life years gained.ICER: incremental cost-effectiveness ratio.</p

Diagram A) describes scenario 1a and diagram B) scenario describes scenario 1b. Both dia... more Diagram A) describes scenario 1a and diagram B) scenario describes scenario 1b. Both diagrams show the change in ICER when reducing or increasing each parameter with 25%.</p

The incremental cost-effectiveness ratio (ICER) is calculated with reference to the “no ... more The incremental cost-effectiveness ratio (ICER) is calculated with reference to the “no routine screening” strategy.LYG:life years gained.ICER: incremental cost-effectiveness ratio.</p

Journal of Comparative Effectiveness Research, 2018

To develop a modeling approach to compare clinical outcomes of nonacog beta pegol to a standard-a... more To develop a modeling approach to compare clinical outcomes of nonacog beta pegol to a standard-acting factor IX (FIX) product. Methods: Regression analysis linked FIX activity to bleed rates. Pharmacokinetic parameters were used to estimate FIX activity over time. The probability of bleeds was estimated for both treatment arms. A Markov model estimated the presence of target joints and annualized bleed rates (ABRs). Results: Higher FIX activity showed reduced ABRs (p < 0.001). Target joints resulted in higher bleed rates (p < 0.001). When FIX activity levels and bleed risks were applied to the Markov model, ABRs for nonacog beta pegol and its comparator were 2.40 and 6.36, respectively. Conclusion: This model provides a starting point for assessing the added value of new FIX products.

Value in Health, Oct 1, 2017

Results were most sensitive to changes in HAQ score and discount rates. At the defined willingnes... more Results were most sensitive to changes in HAQ score and discount rates. At the defined willingness-to-pay threshold of € 34,000, apremilast sequence was estimated to have a 79% probability of being cost-effective. ConClusions: Placing apremilast before biologics was found to be a cost-effective strategy for the treatment of active PsA in the Greek healthcare setting.

Blood, Nov 13, 2019

Introduction: The standard of care for patients with hemophilia A without inhibitors is factor VI... more Introduction: The standard of care for patients with hemophilia A without inhibitors is factor VIII (FVIII) replacement therapy. The availability of non-factor therapy such as emicizumab (Hemlibra®; Genentech, Inc., South San Francisco, CA, USA) is changing the treatment landscape. A model was developed from the perspective of the US healthcare system to compare the cost-effectiveness of recombinant FVIII (rFVIII) products (standard half-life [SHL] and extended half-life [EHL]) versus non-factor therapy emicizumab in the treatment of patients with severe hemophilia A without inhibitors. Methods: The Markovian model used in this analysis included 5 mutually exclusive hemophilia A-related health states: with/without target joints (TJs), with/without arthropathy, and death. Health states changed or remained constant, depending on bleeds and recovery probability. Transition to the health state "death" was derived from mortality rates in the general US population according to age. Each health state was associated with costs and utilities that were summed over time. Estimated total costs and treatment effectiveness as measured by quality-adjusted life years (QALYs; a measure of health outcome that incorporates the impact on both quantity and quality of life) for each health state were then used to calculate incremental cost-effectiveness ratios for pairwise comparisons of treatments (prophylaxis or on-demand for a pooled analysis of 6 rFVIII products [SHL and EHL] vs emicizumab prophylaxis; Table 1) over a life-time horizon. Patient data used in the model were based on a systematic literature review and clinical trial results, and network meta-analysis. Model parameters included patient baseline characteristics, change in body weight by age, prior prophylaxis or on-demand treatment, annualized bleeding rate (ABR), probability of developing or resolving TJs or arthropathy, mortality, number infusions per bleed, medical check-ups, and hospitalization. Based on these data, patients in the model were assumed to be male and 33 years of age at baseline; 72.0% had TJs and 58.4% had arthropathy. Probability of developing TJs per joint bleed was estimated to be 0.9% (prophylaxis and on-demand treatment). Probability of developing arthropathy per joint bleed was estimated to be 2.2% for patients who received prior on-demand treatment and patients who received prior prophylaxis were assumed to have no risk of developing arthropathy. The model assumed life-long adherence to the same prophylactic hemophilia treatment. Drug cost was based on 2018 average sales price and dosing was on label. The model did not include treatment-specific adverse events or inhibitor development. Results: Prophylaxis with rFVIII (SHL and EHL) was estimated to be less costly and more effective (total 13,656,238;QALYs17.61)versusnon−factorprophylaxiswithemicizumab(total13,656,238; QALYs 17.61) versus non-factor prophylaxis with emicizumab (total 13,656,238;QALYs17.61)versusnon−factorprophylaxiswithemicizumab(total16,447,843; QALYs 17.58) over an estimated 70-year lifespan of a patient with severe hemophilia A, which suggests rFVIII prophylaxis is an economically preferable strategy. Total cost consists of costs directly related to prophylactic treatment (rFVIII 12,850,894vsemicizumab12,850,894 vs emicizumab 12,850,894vsemicizumab15,555,379) and costs associated with healthcare resources (rFVIII 805,344vsemicizumab805,344 vs emicizumab 805,344vsemicizumab892,464). rFVIII prophylaxis was also estimated to be less costly and more effective (total 13,656,238;QALYs17.61)versuson−demandrFVIIItreatment(total13,656,238; QALYs 17.61) versus on-demand rFVIII treatment (total 13,656,238;QALYs17.61)versuson−demandrFVIIItreatment(total13,823,123; QALYs 12.29). Conclusions: In this pooled analysis of select SHL and EHL rFVIII products, the results suggest that rFVIII prophylaxis is a cost-effective long-term intervention for patients with severe hemophilia A without inhibitors compared with non-factor prophylaxis with emicizumab and on-demand rFVIII treatment. Disclosures Sun: Shire US Inc., a Takeda company: Employment, Other: a Takeda stock owner. Wu:Shire US Inc., a Takeda company: Employment, Other: a Takeda stockowner. McDermott:BresMed Health Solutions Ltd.: Employment. van Keep:BresMed Health Solutions Ltd.: Employment.

Value in Health, Jun 1, 2021

Journal of The National Comprehensive Cancer Network, Feb 1, 2021

Background: Durvalumab was approved by the FDA in February 2018 for patients with unresectable st... more Background: Durvalumab was approved by the FDA in February 2018 for patients with unresectable stage III NSCLC that has not progressed after platinum-based concurrent chemoradiotherapy (cCRT), and this regimen is the current standard of care. The objective of this study was to examine the cost-effectiveness of durvalumab following cCRT versus cCRT alone in patients with locally advanced, unresectable stage III NSCLC. Methods: A 3-state semi-Markov model was used. Modeling was performed in a US healthcare setting from Medicare and commercial payer perspectives over a 30-year time horizon. Clinical efficacy (progression-free and post progression survival) and utility inputs were based on PACIFIC study data (Clin-icalTrials.gov identifier: NCT02125461; data cutoff March 22, 2018). Overall survival extrapolation was validated using overall survival data from a later data cutoff (January 31, 2019). The main outcome was the incremental cost-effectiveness ratio (ICER) of durvalumab following cCRT versus cCRT alone, calculated as the difference in total costs between treatment strategies per quality-adjusted life-year (QALY) gained. Results: In the base-case analysis, durvalumab following cCRT was cost-effective versus cCRT alone from Medicare and commercial insurance perspectives, with ICERs of 55,285and55,285 and 55,285and61,111, respectively, per QALY gained. Durvalumab was thus considered cost-effective at the $100,000 willingness-to-pay (WTP) threshold. Sensitivity analyses revealed the model was particularly affected by variables associated with subsequent treatment, although no tested variable increased the ICER above the WTP threshold. Scenario analyses showed the model was most sensitive to assumptions regarding time horizon, treatment effect duration, choice of fitted progression-free survival curve, subsequent immunotherapy treatment duration, and use of a partitioned survival model structure. Conclusions: In a US healthcare setting, durvalumab was costeffective compared with cCRT alone, further supporting the adoption of durvalumab following cCRT as the new standard of care in patients with unresectable stage III NSCLC.

PharmacoEconomics - open, Sep 16, 2021

Background In the phase III PACIFIC study, durvalumab improved survival versus placebo in patient... more Background In the phase III PACIFIC study, durvalumab improved survival versus placebo in patients with unresectable stage III non-small-cell lung cancer (NSCLC) whose disease had not progressed after platinum-based concurrent chemoradiotherapy. The appraisal by the UK's National Institute for Health and Care Excellence (NICE) included a cost-effectiveness analysis based on an early data readout from PACIFIC [March 2018 data cutoff (DCO); median follow-up duration 25.2 months; range 0.2-43.1]. Uncertainties regarding long-term survival outcomes with durvalumab led to some challenges in estimating the cost effectiveness of this therapy. Objective Here, we validate the survival extrapolations used in the original company base-case analysis by benchmarking them against updated survival data from the 4-year follow-up analysis of PACIFIC (i.e. approximately 4 years after the last patient was randomised; March 2020 DCO; median follow-up duration 34.2 months; range 0.2-64.9). Moreover, we update the original analysis with these more mature survival data to examine the consistency of key economic outputs with the original analysis. Methods The original analysis used a semi-Markov (state-transition) approach and was based on patients whose tumours expressed programmed cell death-ligand 1 on ≥ 1% of cells (to reflect the European licence for durvalumab). We benchmarked the survival extrapolations used in the original company base-case analysis against survival data from the 4-year follow-up of PACIFIC and updated the cost-effectiveness analysis with these more mature survival data. Early deaths avoided by the adoption of durvalumab into the UK Cancer Drugs Fund (CDF) in March 2019 were estimated using the 4-year follow-up survival data and an assumed uptake of 125 patients/year (lower estimate) and 367 patients/year (higher estimate). Results The original company base-case analysis had a good visual fit with the observed overall survival (OS) distribution for the durvalumab arm and accurately predicted the 48-month OS rate (predicted 55%; observed 55%); by comparison, the fit was less precise for the placebo arm, for which the analysis underestimated the 48-month OS rate (predicted 32%; observed 38%). In the updated company base-case analysis, durvalumab yielded 2.51 incremental quality-adjusted life-years (QALYs) (− 0.43 vs. the original company base-case analysis), corresponding to an incremental cost-effectiveness ratio of £22,665/QALY (+£3298 vs. the original analysis), which falls within the upper bound of NICE's willingness-to-pay threshold (£30,000/QALY gained). We estimate that between 31 and 91 early patient deaths may have been avoided by the adoption of durvalumab into the CDF. Conclusions These findings reinforce the patient benefit observed with durvalumab in unresectable stage III NSCLC, support the routine use and cost effectiveness of this therapy, and demonstrate how appropriate modelling can inform the early adoption of therapies by payers to achieve patient benefit. Plain Language Summary Based on the results of a clinical trial, the European Medicines Agency approved durvalumab for the treatment of adults with a specific type of advanced lung cancer whose tumours cannot be removed surgically and whose disease has not progressed after chemotherapy and radiotherapy. The UK's National Institute for Health and Care Excellence (NICE) invites Extended author information available on the last page of the article W. Dunlop et al. companies to submit cost-effectiveness analyses to help with decision making about adopting new therapies. The company included an analysis based on early trial data that suggested durvalumab was cost effective compared with other previous treatments. As patients in the study at the time of the initial submission to NICE were only followed for approximately 2 years, the long-term survival benefit that could be achieved with durvalumab was uncertain. Therefore, NICE recommended durvalumab for use within the Cancer Drugs Fund (CDF) to allow patients to access the drug while more data were being collected. Here, we demonstrate that the original cost-effectiveness model accurately predicted the rates of long-term survival for patients receiving durvalumab and that durvalumab remains a cost-effective use of healthcare resources based on recently published data from the trial (which added approximately 2 further years of follow-up). Moreover, we estimate that adopting durvalumab into the CDF may have avoided 31-91 early patient deaths from lung cancer. These findings support NICE's early decision to make durvalumab available within the CDF and the adoption of durvalumab for routine use within the UK national health service.

Journal of Hepatology, Apr 1, 2013

Introduction: Hepatitis C virus (HCV) infection can lead to severe liver disease. Pregnant women ... more Introduction: Hepatitis C virus (HCV) infection can lead to severe liver disease. Pregnant women are already routinely screened for several infectious diseases, but not yet for HCV infection. Here we examine whether adding HCV screening to routine screening is cost-effective. Methods: To estimate the cost-effectiveness of implementing HCV screening of all pregnant women and HCV screening of first-generation non-Western pregnant women as compared to no screening, we developed a Markov model. For the parameters of the model, we used prevalence data from pregnant women retrospectively tested for HCV in Amsterdam, the Netherlands, and from literature sources. In addition, we estimated the effect of possible treatment improvement in the future. Results: The incremental costs per woman screened was J41 and 0.0008 life-years were gained. The incremental costeffectiveness ratio (ICER) was J52,473 which is above the cost-effectiveness threshold of J50,000. For screening firstgeneration non-Western migrants, the ICER was J47,113. Best-case analysis for both scenarios showed ICERs of respectively J19,505 and J17,533. We estimated that if costs per treatment were to decline to J3,750 (a reduction in price of J31,000), screening all pregnant women would be cost-effective. Conclusions: Currently, adding HCV screening to the already existing screening program for pregnant women is not costeffective for women in general. However, adding HCV screening for first-generation non-Western women shows a modest cost-effective outcome. Yet, best case analysis shows potentials for an ICER below J20,000 per life-year gained. Treatment options will improve further in the coming years, enhancing cost-effectiveness even more.

Value in Health, 2022

OBJECTIVES Since 2015, Zorginstituut Nederland (ZIN) has linked disease severity ranges of 0.10 t... more OBJECTIVES Since 2015, Zorginstituut Nederland (ZIN) has linked disease severity ranges of 0.10 to 0.40, 0.41 to 0.70, and 0.71 to 1.00 with willingness-to-pay (WTP) reference values of €20 000, €50 000, and €80 000 per quality-adjusted life year gained, respectively. We sought to review whether these changes have affected ZIN health technology assessment (HTA) outcomes for specialist and outpatient drugs. METHODS ZIN recommendations for specialist and outpatient drugs published between January 1, 2012, and December 31, 2020, that included a pharmacoeconomic report were reviewed. Data were extracted on disease severity, proportional shortfall calculation, reported WTP reference value, outcomes related to the cost-effectiveness of the product, budget impact, and ZIN's recommendation including rationale for their advice. RESULTS A total of 51 HTAs were included. Of the 20 HTAs published before June 2015, a total of 9 received positive recommendations, 7 were conditionally reimbursed, and 4 received negative recommendations. None reported WTP reference values. Of the 31 evaluations published after June 2015, a total of 4 products received positive recommendations, 1 was conditionally approved, and 26 received negative recommendations initially. Most products (65%) reported disease severity to be >0.70. CONCLUSIONS Since 2015, most products have fallen within the highest category of disease severity. Although pre-2015 outcomes were varied, post-2015 products overwhelmingly received negative recommendations, and the proportion of products for which price negotiations were recommended has increased. These differences in outcomes may result from the introduction of an explicit WTP reference value, whether or not in combination with the severity-adjusted ranges, but may also reflect other national policy changes in 2015.

Value in Health, Nov 1, 2019

criteria. The step-by-step process and interdependencies between stakeholders under FIBS were imp... more criteria. The step-by-step process and interdependencies between stakeholders under FIBS were implemented in Anylogic, to simulate a counterfactual ideal level of biosimilars utilization over time for all patients on infliximab, etanercept, rituximab,

HCV: hepatitis C virus.HCC: hepatocellular carcinoma.#<p... more HCV: hepatitis C virus.HCC: hepatocellular carcinoma.#In the prevalence a clearance rate of 42% <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070319#pone.0070319-Rozenbaum1" target="_blank">[14]</a> was included. The prevalence used in the model for all pregnant women is 0.2% (9/4563; 95% CI: 0.10–0.37) and for first generation non-Western women 0.43% (7/1612; 95% CI 0.21–0.89).$Transition rate is age-dependent.*same distribution was used for first-generation non-Western women.**new protease inhibitors are added to the standard of care regimen (peginterferon alfa and ribavirine).</p

Frontiers in Medical Technology

BackgroundAntimicrobial resistance (AMR) is a growing threat to global health. With pathogenic ba... more BackgroundAntimicrobial resistance (AMR) is a growing threat to global health. With pathogenic bacteria inevitably becoming more resistant to existing antimicrobials, mortality and costs due to AMR will significantly increase over the next few decades if adequate action is not taken. A major challenge in addressing AMR is the lack of financial incentives for manufacturers to invest in developing new antimicrobials. This is partly because current approaches in health technology assessment (HTA) and standard modeling methods fail to capture the full value of antimicrobials.AimWe explore recent reimbursement and payment frameworks, particularly pull incentives, aimed to address the market failures in antimicrobials. We focus on the “subscription-style” payment model recently used in the UK and discuss the learnings for other European countries.MethodsA pragmatic literature review was conducted to identify recent initiatives and frameworks between 2012 and 2021, across seven European ma...

List of local Independent Ethics Committees and Institutional Review Boards. (DOCX 24 kb)