A Dutch cost-effectiveness analysis of fremanezumab versus best supportive care in patients with chronic migraine and inadequate response to prior preventive therapy.

BACKGROUND: Chronic migraine (CM) is the most severe and burdensome subtype of migraine. Fremanezumab is a monoclonal antibody that targets the calcitonin gene-related peptide pathway as a migraine preventive therapy. This study aimed to conduct a cost-effectiveness analysis of fremanezumab from a societal perspective in the Netherlands, using a Markov cohort simulation model. METHODS: The base-case cost-effectiveness analysis adhered to the Netherlands Authority guidelines. Fremanezumab was compared with best supportive care (BSC; acute migraine treatment only) in patients with CM and an inadequate response to topiramate or valproate and onabotulinumtoxinA (Dutch patient group [DPG]). A supportive analysis was conducted in the broader group of CM patients with prior inadequate response to 2-4 different classes of migraine preventive treatments. One-way sensitivity, probabilistic sensitivity, and scenario analyses were conducted. RESULTS: Over a lifetime horizon, fremanezumab is cost saving compared with BSC in the DPG (saving of €2514 per patient) and led to an increase of 1.45 quality-adjusted life-years (QALYs). In the broader supportive analysis, fremanezumab was cost effective compared with BSC, with an incremental cost-effectiveness ratio of €2547/QALY gained. Fremanezumab remained cost effective in all sensitivity and scenario analyses. CONCLUSION: In comparison to BSC, fremanezumab is cost saving in the DPG and cost effective in the broader population.

Differences in Evidentiary Requirements Between European Medicines Agency and European Health Technology Assessment of Oncology Drugs-Can Alignment Be Enhanced?

OBJECTIVES: National health technology assessments (HTAs) across Europe show differences in evidentiary requirements from assessments by the European Medicines Agency (EMA), affecting time to patient access for drugs after marketing authorization. This article analyzes the differences between EMA and HTA bodies' evidentiary requirements for oncology drugs and provides recommendations on potential further alignment to minimize and optimally manage the remaining differences. METHODS: Interviews were performed with representatives and drug assessment experts from EMA and HTA bodies to identify evidentiary requirements for several subdomains and collect recommendations for potentially more efficiently addressing differences. A comparative analysis of acceptability of the evidence by EMA and the HTA bodies and for potential further alignment between both authorities was conducted. RESULTS: Acceptability of available evidence was higher for EMA than HTA bodies. HTA bodies and EMA were aligned on evidentiary requirements in most cases. The subdomains showing notable differences concerned the acceptance of limitation of the target population and extrapolation of target populations, progression-free survival and (other) surrogate endpoints as outcomes, cross-over designs, short trial duration, and clinical relevance of the effect size. Recommendations for reducing or optimally managing differences included joint early dialogues, joint relative effectiveness assessments, and the use of managed entry agreements. CONCLUSIONS: Differences between assessments of EMA and HTA bodies were identified in important areas of evidentiary requirements. Increased alignment between EMA and HTA bodies is suggested and recommendations for realization are discussed.

Market Access Challenges and Solutions in Cell and Gene Therapy in The Netherlands.

With the increasing pipeline of cell and gene therapies (CGTs) and the expected surge in the number of approvals, understanding the market access landscape becomes crucial for timely patient access. This study evaluates the challenges Dutch stakeholders encounter in CGT market access, offering insights for improving time-to-patient access. A traditional literature review was conducted to identify market access challenges and solutions for CGTs. Based on the findings, participants for semi-structured interviews, designed using an interview guide adapted to the Dutch context, were selected to capture diverse perspectives on market access. This review included 124 relevant articles out of 2449, covering several aspects of market access of CGTs. Subsequently, interviews with 16 stakeholders from academia, patient advocacy groups, manufacturers, health insurers, payers, hospital pharmacists, healthcare practitioners, and the Association of Innovative Medicines were conducted. Stakeholders identified challenges and proposed solutions for reimbursement package management, clinical trials, health economics, payment models, and procedural and organisational aspects. Thematic analysis revealed unique country-specific challenges and solutions in the Netherlands. This research provides insights into these challenges and potential solutions, emphasising the need for collaborative efforts among stakeholders to develop practical and multidisciplinary measures to improve the market access landscape for CGTs in the country.

Differences in evidentiary requirements for oncology drug effectiveness assessments among six European health technology assessment bodies - can alignment be improved?

OBJECTIVES: Evidentiary requirements for relative effectiveness assessment vary among European health technology assessment (HTA) bodies, affecting the time to HTA decision-making and potentially delaying time to patient access. Improved alignment may reduce this time; therefore, we aim to analyze the differences in evidentiary requirements for oncology drug assessments among European HTA bodies and provide recommendations toward an increased alignment. METHODS: Interviews were conducted with stakeholders in drug assessments of Italy, the Netherlands, Poland, Portugal, England and Wales, and Sweden about evidentiary requirements for several subdomains to identify differences and obtain recommendations for addressing differences. The interview results were analyzed on degrees of evidence acceptability per HTA body and alignment on evidentiary requirements among HTA bodies. RESULTS: Subdomains demonstrating noteworthy differences concerned the acceptability of extrapolation to other populations, class effects, progression-free survival and (other) surrogate endpoints as outcomes, the absence of quality-of-life data, single-arm trials, cross-over trial designs, short trial duration, and the clinical relevance of effect size. CONCLUSION: Alignment can be enhanced to reduce time to decision-making and to improve equity in patient access. Proposed recommendations to achieve this included joint early dialogues, intensified collaboration and exchange between countries, joint relative effectiveness assessments, and the use of access agreements.

Trends in NICE technology appraisals of non-small cell lung cancer drugs over the last decade.

OBJECTIVES: The aim of this study is to analyse the trends in technology appraisals for non-small cell lung cancer (NSCLC) treatments performed by the National Institute for Health and Care Excellence (NICE) over the last ten years. METHODS: A systematic search was conducted for single technology appraisals of NSCLC drugs in the online NICE database from 2012 to 2022. Search terms used were 'non small cell lung cancer', and 'NSCLC'. Appraisals that were under development or terminated as well as multiple technology appraisals were considered out of scope. RESULTS: In the 30 included appraisals for targeted therapies and immunotherapies within NSCLC, a total of 53 different comparators were included by NICE for 41 assorted indications or subgroups. Partitioned survival models were most frequently used, often including three health states and time horizons of up to 30 years. Throughout the decade the use of indirect comparisons was high and became more established and complex over time. Of all appraisals, 90% positively recommended the treatment for use in the UK. CONCLUSION: Technology appraisals became more complex over time due to the emergence of targeted therapies and immunotherapies, leading to multiple different indications, subpopulations and comparators that needed to be included in appraisals. Partitioned Survival Analysis (PartSA) models became the cornerstone within NSCLC, with time horizons up to 30 years and over time methods for indirect treatment comparisons became more established. The majority of the appraisals resulted in a positive recommendation for reimbursement.

Cardiovascular Risk Management and Hepatitis C: Combining Drugs.

Direct-acting antivirals (DAAs) are known victims (substrate) and perpetrators (cause) of drug-drug interactions (DDIs). These DAAs are used for the treatment of hepatitis C virus (HCV) infections and are highly effective drugs. Drugs used for cardiovascular risk management are frequently used by HCV-infected patients, whom also are treated with DAAs. Therefore, the aim of this review was to describe DDIs between cardiovascular drugs (CVDs) and DAAs. An extensive literature search was performed containing search terms for the marketed DAAs and CVDs (ß-blocking agents, ACE inhibitors, angiotensin II antagonists, renin inhibitors, diuretics, calcium channel blockers, statins/ezetimibe, fibrates, platelet aggregation inhibitors, vitamin K antagonists, heparins, direct Xa inhibitors, nitrates, amiodarone, and digoxin). In particular, the drug labels from the European Medicines Agency and the US Food and Drug Administration were used. A main finding of this review is that CVDs are mostly victims of DDIs with DAAs. Therefore, when possible, monitoring of pharmacodynamics is recommended when coadministering these drugs with DAAs. Nevertheless, it is sometimes better to discontinue a drug on a temporary basis (statins, ezetimide). The DAAs are victims of DDIs in combination with bisoprolol, carvedilol, labetalol, verapamil, and gemfibrozil. Despite there are many DDIs predicted in this review, most of these DDIs can be managed by monitoring the efficacy and toxicity of the victim drug or by switching to another CVD/DAA.