What Does Pharmaceutical 3D Printing Cost? A Framework and Case Study with Hydrocortisone for Adrenal Insufficiency.

Background: Pharmaceutical three-dimensional printing (3DP) technology offers an automated platform that can be utilized to manufacture personalized medicine, improving pharmacotherapy. Although 3D-printed products have entered clinical trials, no costing studies have been performed yet. Cost insights can aid researchers and industry in making informed decisions about the feasibility and scalability of 3DP.

A Systematic Review of Challenges and Opportunities in the Implementation of Managed Entry Agreements for Advanced Therapy Medicinal Products.

Purpose: Managed Entry Agreements (MEAs) are agreements between firms and competent authorities for pricing and reimbursement, designed to enable coverage of new medicines while managing uncertainties around their financial impact or performance. Although these agreements can facilitate patient access, their complexity and costs seem to dampen enthusiasm for implementation. Nevertheless, MEAs remain a potential route, particularly for high-cost drugs with uncertain value claims.

Cost-effectiveness of treating advanced melanoma with tumor-infiltrating lymphocytes based on an international randomized phase 3 clinical trial.

Introduction: In a multicenter, open-label randomized phase 3 clinical trial conducted in the Netherlands and Denmark, treatment with ex vivo-expanded tumor-infiltrating lymphocytes (TIL-NKI/CCIT) from autologous melanoma tumor compared with ipilimumab improved progression-free survival in patients with unresectable stage IIIC-IV melanoma after failure of first-line or second-line treatment. Based on this trial, we conducted a cost-utility analysis.

Methods: A Markov decision model was constructed to estimate expected costs (expressed in 2021€) and outcomes (quality-adjusted life years (QALYs)) of TIL-NKI/CCIT versus ipilimumab in the Netherlands.

Toward Transplantation of Liver Organoids: From Biology and Ethics to Cost-effective Therapy.

Liver disease is a common cause of morbidity and mortality, and many patients would benefit from liver transplantation. However, because of a shortage of suitable donor livers, even of those patients who are placed on the donor liver waiting list, many do not survive the waiting time for transplantation. Therefore, alternative treatments for end-stage liver disease need to be explored.

Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma.

Background: Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable benefit. Phase 1-2 trials of adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) have shown promising responses, but data from phase 3 trials are lacking to determine the role of TILs in treating advanced melanoma.

Methods: In this phase 3, multicenter, open-label trial, we randomly assigned patients with unresectable stage IIIC or IV melanoma in a 1:1 ratio to receive TIL or anti-cytotoxic T-lymphocyte antigen 4 therapy (ipilimumab at 3 mg per kilogram of body weight).

Key Considerations in the Health Technology Assessment of Advanced Therapy Medicinal Products in Scotland, The Netherlands, and England.

Objectives: Advanced therapy medicinal products (ATMPs) are highly innovative therapies. Their costs and uncertain value claims have raised concerns among health technology assessment (HTA) bodies and payers. Little is known about how underlying considerations in HTA of ATMPs shape assessment and reimbursement recommendations.

Modeling Benefits, Costs, and Affordability of a Novel Gene Therapy in Hemophilia A.

The objective was to undertake an early cost-effectiveness assessment of valoctocogene roxaparvovec (valrox; Roctavian) compared to factor (F)VIII prophylaxis or emicizumab (Hemlibra; Roche HQ, Bazel, Switzerland) in patients with severe Hemophilia A (HA) without FVIII-antibodies. We also aimed to incorporate and quantify novel measures of value such as treatment durability, maximum value-based price (MVBP) and break-even time (ie, time until benefits begin to offset upfront payment). We constructed a Markov model to model bleeds over time which were linked to costs and quality-of-life decrements.

Estimation of manufacturing development costs of cell-based therapies: a feasibility study.

Background Aims: Cell-based therapies (CBTs) provide opportunities to treat rare and high-burden diseases. Manufacturing development of these innovative products is said to be complex and costly. However, little research is available providing insight into resource use and cost drivers.

Cost-Effectiveness Assessment of Monitoring Abiraterone Levels in Metastatic Castration-Resistant Prostate Cancer Patients.

Objectives: Abiraterone acetate is registered for the treatment of metastatic castration-sensitive and resistant prostate cancer (mCRPC). Treatment outcome is associated with plasma trough concentrations (C) of abiraterone. Patients with a plasma C below the target of 8.

The Relative Impact of Urinary and Sexual Function vs Bother on Health Utility for Men With Prostate Cancer.

Function and bother are related but distinct aspects of health-related quality of life. The objective of this study was to compare quantitatively the relative impacts of function and bother in urinary, sexual, and bowel outcomes on health utility as a reflection of health-related quality of life in men with prostate cancer. Our analysis included participants in the Cancer of the Prostate Strategic Urologic Research Endeavor utility supplementary study, with a final cohort of 1617 men.

A Review of Methodological Considerations for Economic Evaluations of Gene Therapies and Their Application in Literature.

Objectives: To identify methodological considerations discussed in literature addressing economic evaluations (EEs) of gene therapies (GTs). Additionally, we assessed if these considerations are applied in published GT EEs to increase understanding and explore impact.

Methods: First a peer-reviewed literature review was performed to identify research addressing methodological considerations of GT EEs until August 2019.

What does cell therapy manufacturing cost? A framework and methodology to facilitate academic and other small-scale cell therapy manufacturing costings.

Background Aims: Recent technical and clinical advances with cell-based therapies (CBTs) hold great promise in the treatment of patients with rare diseases and those with high unmet medical need. Currently the majority of CBTs are developed and manufactured in specialized academic facilities. Due to small scale, unique characteristics and specific supply chain, CBT manufacturing is considered costly compared to more conventional medicinal products.

Development and Regulation of Gene and Cell-Based Therapies in Europe: A Quantification and Reflection.

Gene and cell-based therapies (GCTs) are said to hold great promise as treatments for previously untreatable and high-burden diseases. Here, we provide insight into GCT development and regulation activities in Europe, quantify clinical and regulatory success, and compare these with other medicinal products in order to reflect on regulatory changes and challenges.

Understanding the Major Factors Affecting Response Shift Effects on Health-Related Quality of Life: What the Then-Test Measures in a Longitudinal Prostate Cancer Registry.

Background: Localized prostate cancer (PCa) treatments provide high survival rates, with patients often surviving a decade or longer after treatment. Therefore, treatment options are progressively based on quality of life. The objective of this research was to investigate magnitude of response shift (RS) in health-related quality of life (HRQOL) responses in men with clinically localized PCa using a generic questionnaire and a disease-specific questionnaire in an observational longitudinal patient registry study.

Robust Health Utility Assessment Among Long-term Survivors of Prostate Cancer: Results from the Cancer of the Prostate Strategic Urologic Research Endeavor Registry.

Background: Valid health utility values are essential for comparative effectiveness analyses. However, subjective utilities in long-term survivors of prostate cancer (PCa) with various oncological and functional outcomes have not been well described.

Objective: To quantify utilities in long-term survivors of PCa using the standard gamble method, generally regarded as the approach best grounded in economic theory.

Challenges in Advanced Therapy Medicinal Product Development: A Survey among Companies in Europe.

Advanced therapy medicinal products (ATMPs) hold promise as treatments for previously untreatable and high-burden diseases. Expectations are high and active company pipelines are observed, yet only 10 market authorizations were approved in Europe. Our aim was to identify challenges experienced in European ATMP clinical development by companies.

Use of Social Media in the Assessment of Relative Effectiveness: Explorative Review With Examples From Oncology.

Background: An element of health technology assessment constitutes assessing the clinical effectiveness of drugs, generally called relative effectiveness assessment. Little real-world evidence is available directly after market access, therefore randomized controlled trials are used to obtain information for relative effectiveness assessment. However, there is growing interest in using real-world data for relative effectiveness assessment.

Policies for Use of Real-World Data in Health Technology Assessment (HTA): A Comparative Study of Six HTA Agencies.

Background: Randomized controlled trials provide robust data on the efficacy of interventions rather than on effectiveness. Health technology assessment (HTA) agencies worldwide are thus exploring whether real-world data (RWD) may provide alternative sources of data on effectiveness of interventions. Presently, an overview of HTA agencies' policies for RWD use in relative effectiveness assessments (REA) is lacking.

Targeted Therapies Compared to Dacarbazine for Treatment of BRAF(V600E) Metastatic Melanoma: A Cost-Effectiveness Analysis.

Purpose. Two BRAF(V600E) targeted therapies, dabrafenib and vemurafenib, have received US approval for treatment of metastatic melanoma in BRAF(V600E) patients, a mutation that affects ~50% of patients. We evaluated the cost-effectiveness of BRAF inhibitors and traditional chemotherapy for treatment of metastatic melanoma.