Reimbursement Decisions Research Articles

Unlocking the potential of digital therapeutics: The need for consistent and granular inclusion in drug compendia for managed care.

The field of digital therapeutics (DTx), software programs that prevent, manage, and treat medical conditions, continues to grow. DTx offers new treatment options and has the potential to close gaps in care caused by unmet patient needs, provider shortages, or socioeconomic or geographical disparities. However, the field of DTx has not seen steady adoption owing to barriers, particularly related to coverage, payer acceptance of the category, provider use, and integration within existing health care delivery tools. One challenge for payers to effectively evaluate and cover DTx products is ensuring that consistent data elements are listed for these products in traditional drug compendia databases. Managed care organizations will need similar information about DTx product features as are available for traditional medications to inform coverage and reimbursement decisions. The Academy of Managed Care Pharmacy DTx Advisory Group developed and distributed a request for information to the 5 top drug compendia companies to assess how compendia products incorporate DTx and prescription DTx. This article summarizes how DTx are listed within different compendia products and offers insights on future data needs to adequately inform payers. As the DTx sector grows and consumer demand rises, compendia listing services will need to evolve to accommodate these new therapies and treatment modalities and facilitate patient access and efficient claims processing. Recommendations for how compendia companies can support managed care in these efforts are outlined.

Relugolix (Orgovyx)

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec. This review assesses relugolix, (Orgovyx), 120 mg, oral tablets. Indication: For the treatment of adult patients with advanced prostate cancer.

Analysis of factors associated with premiums for reimbursed medical devices in Japan.

The aim of this study is to examine factors that relate to receipt of a reimbursement premium in Japan, which is defined as an increase in the initially calculated reimbursement price based on certain criteria, or an increase in the operating profit ratio. Reimbursement submissions and decisions for newly reimbursed medical devices in Japan from fiscal year (FY) 2015 to FY 2023 were reviewed to consider their characteristics. Moreover, the relationship between reimbursement submission characteristics, as well as other characteristics such as regulatory submission category, risk class, location of the manufacturer headquarters, etc. and the receipt of a Novelty, Usefulness, or Improvement premium (hereafter "utility premium"), or an increase in the operating profit ratio, was examined using univariate and multivariate regression. Among 131 unique medical devices newly reimbursed in Japan from FY 2015 to FY 2023, 57 devices (44%) received a reimbursement premium. Among those, 30 devices (53%) were devices to treat cardiovascular conditions. Based on univariate regression, therapy area, reimbursement category and method used, duration since the comparator device was listed, and estimated peak annual patients for the new device, are factors that affect the receipt of a utility premium or an increase in the operating profit ratio. However, based on multivariate regression, only the therapy area, risk-related regulatory submission class, regulatory submission type (novelty), and orphan device designation are associated with the receipt of a utility premium or an increase in the operating profit ratio. Receipt of a utility premium can be challenging. Moreover, medical devices to treat cardiovascular conditions have benefited more from premiums. This may be due to those devices having more data on efficacy at the time of approval and listing. More opportunities for devices to obtain premiums following initial listing may be needed to adequately capture their value.

Advanced Therapy Medicinal Products: Availability, Access and Expenditure in Italy.

Advanced therapy medicinal products (ATMPs) are an innovative output of biomedical research, characterized by a high level of uncertainty on long-term efficacy and safety, elevated price tags and often complex administration. All these elements compounded make their European authorization, national price negotiation for reimbursement and subsequent dispensation and administration to the patient less straightforward and often less successful than for less innovative drugs. To assess if these hurdles have affected patient access and how are ATMPs used in Italy, we have analysed availability, access and expenditure of ATMPs in the period spanning from 2016 to 2023. We have analysed real world data on the duration of ATMP regulatory evaluations for authorisation and reimbursement, time to first patient access and expenditure for ATMPs through the Italian National Health System (INHS) expenditure data flow, as well as information on patient mobility and availability of health facilities specialized in administering ATMPs. Of the 18 ATMPs currently authorized in Europe, 9 are reimbursed by the INHS, but only 6 were actually used, generating a cumulative expenditure of roughly 300 Mln€ from 2016 to 2023, largely owing to CAR-T therapies. Time to patient access reaches an average of 340.6 days from the day publication in the official Gazette of the reimbursement decision to first patient treatment in one of the 107 health facilities authorized for ATMP administration, after an even longer evaluation time by regulatory agencies. Since the first reimbursement decision for an ATMP in Italy, back in 2016, these innovative drugs became progressively more and more available, both in terms of numbers and in terms of coverage across the country. Almost all Italian regions have at least one centre for ATMP administration and has performed a treatment in 2023. Notwithstanding their high per-treatment prices, ATMPs currently have a rather contained expenditure, however it is bound to keep growing in the next few years.

Bimekizumab (Bimzelx)

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec. This review assesses bimekizumab (BIMZELX), 160 mg/mL, solution for injection, subcutaneous injection. Indication: The treatment of adult patients with active ankylosing spondylitis who have responded inadequately or are intolerant to conventional therapy.

Metreleptin (Myalepta)

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec. This review assesses metreleptin (Myalepta), 3 mg, 5.8 mg, and 11.3 mg, powder for solution, subcutaneous injection. Indication: As an adjunct to diet as a replacement therapy to treat the complications of leptin deficiency in lipodystrophy patients: with confirmed congenital generalized lipodystrophy (Berardinelli-Seip syndrome) or acquired generalized lipodystrophy (Lawrence syndrome) in adults and children 2 years of age and above with confirmed familial partial lipodystrophy (PL) or acquired PL (Barraquer-Simons syndrome), in adults and children 12 years of age and above with persistent significant metabolic disease for whom standard treatments have failed to achieve adequate metabolic control.

Cost-Effectiveness of Fruquintinib for Refractory Metastatic Colorectal Cancer in the USA.

The FRESCO-2 trial established the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer. However, its cost-effectiveness in the US context is not well documented. This study evaluates the cost-effectiveness of fruquintinib versus placebo for this patient population from the perspective of US payers. We developed a partitioned survival model on the basis of patient-level data reconstructed from the survival curves of the FRESCO-2 trial. Parametric estimation was conducted to estimate long-term clinical outcomes and medical costs over a lifetime horizon. Cost inputs and utilities were sourced from public data and previous literature. We used a discount rate of 3.0% per year for both clinical outcomes and costs. We adopted an incremental cost-effectiveness ratio (ICER) threshold of US$100,000 per quality-adjusted life-year (QALY) gained. We performed sensitivity and scenario analyses to examine the robustness of cost-effectiveness results. Fruquintinib treatment resulted in incremental gains of 0.108 life years (LYs) and 0.073 QALYs compared with the placebo, at an additional cost of US$112,294, primarily driven by medication expenses. The ICER for fruquintinib versus placebo was calculated at US$1,037,855 per LY and US$1,546,619 per QALY gained, exceeding the predefined cost-effectiveness threshold. The cost-effectiveness results were robust across all sensitivity and scenario analyses. Despite the survival benefit, fruquintinib was not cost-effective compared with the placebo in patients with refractory metastatic colorectal cancer in the US setting, on the basis of the conventional willingness-to-pay threshold. Our findings may provide a basis for informing the pricing and reimbursement decisions regarding fruquintinib.

Calculating the Expected Net Benefit of Sampling for Survival Data: A Tutorial and Case Study.

The net value of reducing decision uncertainty by collecting additional data is quantified by the expected net benefit of sampling (ENBS). This tutorial presents a general-purpose algorithm for computing the ENBS for collecting survival data along with a step-by-step implementation in R.The algorithm is based on recently published methods for simulating survival data and computing expected value of sample information that do not rely on the survival data to follow any particular parametric distribution and that can take into account any arbitrary censoring process.We demonstrate in a case study based on a previous cancer technology appraisal that ENBS calculations are useful not only for designing new studies but also for optimizing reimbursement decisions for new health technologies based on immature evidence from ongoing trials.

Nivolumab (Opdivo)

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec. This review assesses nivolumab (Opdivo); strength: 40 mg nivolumab/4 mL (10 mg/mL) and 100 mg nivolumab/10 mL (10 mg/mL); route of administration: IV infusion. Indication: Opdivo, as monotherapy, is indicated for the adjuvant treatment of adult patients with stage IIB or IIC melanoma following complete resection.

Avatrombopag (Doptelet)

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec. This review assesses avatrombopag (Doptelet), 20 mg, tablets, oral. Indication: Proposed: the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia who have had an insufficient response to a previous treatment.

Teclistamab (Tecvayli)

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec. This review assesses teclistamab (Tecvayli), 10 mg/mL or 90 mg/mL single-dose vials containing 30 mg teclistamab in 3 mL solution or 153 mg teclistamab in 1.7 mL solution, subcutaneous injection. Indication: Teclistamab injection is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.

Estimating natural history of a treatment-eligible type 2 diabetes mellitus population in Scotland using linked primary and secondary care data: Scottish Diabetes Research Network - National Diabetes Dataset

Healthcare commissioners and those making reimbursement decisions require data on the “natural history” of diseases to estimate quantities such as life expectancy and quality of life. However, such data are commonly acquired from unrepresentative sources like trial placebo arms or case series. We used Scottish Diabetes Research Network-National Diabetes Dataset to characterise life expectancy for people with type 2 diabetes mellitus (T2DM). Data from >99% of people with diabetes in Scotland are available from primary and secondary care (including from clinical investigations) and can be linked to hospital admission and death records for research purposes. As part of an MRC-funded (MR/T017112/1) systematic review and modelling study (PROSPERO registration CRD42020184174) building on work funded by the Chief Scientific Office for Scotland (CSO HIPS_17_26), we used these linked data to define a treatment-eligible population for three drug classes — SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors. Fitting a Gompertz model, we estimated life expectancy for this ‘treatment-eligible’ group. The treatment-eligible population, compared to the entire Scottish T2DM population, was younger (63.8 (12.1) vs. 66.7 (12.7) year-old), with larger proportions of men (60.6% vs. 56.2%), higher HbA1c levels (67.4 (13.1) vs. 60.2 (15.1) mmol/L), larger proportions prescribed metformin (69.2% vs 55.2%) and higher life expectancy at age 65 (in women 21 vs 19 years and in men 20 vs 18 years). Using linked data to define and characterise treatment-eligible populations is feasible and may impact decision models. These findings will be useful to those making resourcing decisions and future economic analyses.

Is health-related quality of life sufficiently addressed in trials for breast cancer treatments? An assessment based on reimbursement opinions from the French health technology assessment body, 2009–2023

BackgroundBreast cancer treatments can impact the patients’ health-related quality of life (HR-QoL). This criterion is relevant for drug reimbursement decisions. We wanted to assess the usage of HR-QoL in health technology assessments (HTA). MethodsAll HAS (Haute Autorité de Santé, the French HTA body) opinions published between January 1, 2009 and March 31, 2023 for the reimbursement of breast cancer drugs were analysed. Results51 distinct appraisals were found during the period, corresponding to 45 product-specific indications, of which 36 (80 %) including clinical studies in which HR-QoL was an endpoint. HAS explicitly rejected HR-QoL data in 25 out of 36 (69 %) indications with such data. Rejections are justified by methodological weaknesses, including lack of adjustment for type I error inflation (n=21 indications), open-label treatment (n=7), lack of a pre-specified clinically relevant HR-QoL threshold (n=6) or missing data (n=6). Regardless of rejection status, HR-QoL results were not mentioned as a determinant of value assessment in 3/36 (8 %) instances (2/25 for rejected data). ConclusionsHR-QoL data are inconsistently present in HTA assessments of new breast cancer drugs. Their methodological quality often hinders their use in determining the drug’s value. Policy summaryA rigorous and acceptable comparative experimental framework is expected for HR-QoL assessments. More detail on the precise impact of the absence or presence of HR-QoL data in the determination of the drug’s added value could help understanding how this dimension is influential in the assessments.

Budget impact models for lung cancer interventions: A systematic literature review.

Budget impact models (BIMs) forecast the financial implications of adopting new technologies and the potential need for budget reallocation, thus playing a crucial role in reimbursement decisions. Despite the importance of accurate forecasts, studies indicate large discrepancies between estimates and reality. We are developing an artificial intelligence-based clinical decision tool to identify patients with non-small cell lung cancer who are most likely to benefit from immunotherapy. To evaluate the budgetary implications and describe a systematic literature review of published lung cancer BIMs. We searched PubMed and EMBASE for studies published between 2010 and 2023 that include BIMs that describe lung cancer interventions. Forward and backward reference searches were performed for all qualifying studies. We extracted author and publication year, country, interventions, disease stages, time horizon, analytical perspective, modeling methods used, types of costs included, sensitivity analyses conducted, and data sources used. We then evaluated adherence to the Professional Society for Health Economics and Pharmacoeconomics Research best-practice guidelines. A total of 25 BIMs were identified, spanning 14 different countries. Model structure could not be ascertained definitively for nearly half of the models. The cost calculator approach was most common among the others. Time horizons ranged from 1 to 5 years, in line with recommendations. Most models compared drugs, 4 compared nondrug interventions, and 7 compared diagnostic technologies. Assumptions about market uptake were poorly documented and poorly motivated. Inclusion of cancer-related costs was rare. Adherence to best practices was variable and did not appear to improve over time. The number of published BIMs for lung cancer exceeded expectations. There were modest trends toward publication frequency and model quality over time. Our analysis revealed variability across the models, as well as their adherence to best practices, indicating substantial room for improvement. Although none of the models were individually suitable for the purpose of evaluating an artificial intelligence-based treatment selection tool, some models provided valuable insights.

Estimating the value of new antibiotic treatment strategies in Zhejiang province, China: cost-effectiveness analysis based on a validated dynamic model

ObjectivesThis analysis aims to better reflect the value of new antibiotic treatment strategies, thereby informing clinical antibiotic use, antimicrobial reimbursement and/or hospital formulary decision-making in China.DesignWe adapted a published and...

Infliximab (Remsima SC)

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec. This review assesses Description infliximab (Remsima SC), 120 mg/mL solution for subcutaneous injection. Indication: Maintenance treatment of adults with moderately to severely active Crohn disease who have had an inadequate response to or were intolerant of conventional therapy. Remsima SC should be used only as maintenance therapy after the completion of an induction period with IV infliximab.

Developing and validating a discrete-event simulation model of multiple myeloma disease outcomes and treatment pathways using a national clinical registry.

Multiple myeloma is a haematological malignancy typically characterised by neoplastic plasma cell infiltration of the bone marrow. Treatment for multiple myeloma consists of multi-line chemotherapy with or without autologous stem cell transplantation and has been rapidly evolving in recent years. However, clinical trials are unable to provide patients and clinicians with long-term prognostic information nor policymakers with the full body of evidence needed to perform economic evaluation of new therapies or make reimbursement decisions. To address these limitations of the available evidence, this study aimed to develop and validate the EpiMAP Myeloma model, a discrete-event simulation model of multiple myeloma disease outcomes and treatment pathways. Risk equations were estimated using the Australian and New Zealand Myeloma & Related Diseases Registry after multiple imputation of missing data. Risk equation coefficients were combined with multiple myeloma patients at diagnosis from the Registry to perform the simulation. The model was validated with 100 bootstraps of an out-of-sample prediction analysis using a 70/30 split of the 4,121 registry patients diagnosed between 2009 and 2023, resulting in 2,884 and 1,237 patients in the training and validation cohorts, respectively. For 90% of the 120 months in the 10-year post-diagnosis period, there was no significant difference in overall survival between the validation and simulated cohorts. These results highlight that the EpiMAP Myeloma model is robust at predicting multiple myeloma disease outcomes and treatment pathways in Australia & New Zealand. In the future, clinicians will be able to use the EpiMAP Myeloma model to provide personalised estimates of life expectancy to patients based on their specific characteristics, disease stage, and response to treatment. Policymakers will also be able to use the model to perform economic evaluation, to forecast the number of patients receiving treatment at different stages, and to determine the downstream impact of listing new, effective therapies.

Implementing routine collection of EQ-5D-5L in a breast cancer outpatient clinic.

A cross-sectional study was conducted to investigate the feasibility of implementing routine collection of the Euro-Qol 5 dimensions (EQ-5D) questionnaire, to inform drug and health technology reimbursement decision making. Women with breast cancer were recruited during scheduled clinic visits to an academic cancer centre. EQ-5D-5L was self-administered using electronic tablets. Diagnostic and treatment data were abstracted from patient charts. Feasibility was assessed primarily by the proportion of patients who fully completed EQ-5D-5L and by their willingness to complete the instrument at each clinic visit. 588 women were approached for study participation, 341 were enrolled. Fully completed EQ-5D-5L questionnaires were obtained in 323 participants (95% of participants, 95% CI 92-97%). Median time for EQ-5D-5L completion was 1.5 minutes (range:0.35 to 14.7). Mean age of participants was 58 years old. Most women who completed EQ-5D were White, born outside Canada and presented a high education level; one-quarter had metastatic disease. Most participants reported "No problems" in all EQ-5D-5L dimensions. Mean EQ-5D-5L index and mean EQ-5D-5L VAS values for all participants were respectively 0.83 (SD 0.13) and 75.7 (SD 17.45), with patients with metastatic disease scoring the lowest values. Seventy-eight percent of participants were willing to complete EQ-5D-5L at each clinic visit; lower Charlson comorbidity index and higher education level were predictors of willingness to continue to answer EQ-5D-5L. Tablet-based collection of EQ-5D-5L in the context of routine clinical practice proved to be feasible. However, many patients declined study participation or reported being in full health, raising concerns about whether this method of collecting EQ-5D adequately represents the health status of all breast cancer patients.

Adoption of a Societal Perspective in Economic Evaluations of Musculoskeletal Disorders: A Conceptual Paper.

Economic evaluations are used to compare the costs and consequences of healthcare interventions, including those for musculoskeletal (MSK) disorders, which are very common and a major source of morbidity and absence from work. Reimbursement decisions for interventions for MSK disorders by decision-makers rely on the findings of economic evaluations, the design and results of which depend largely on the perspective adopted. Despite methodological advancements in economic evaluations, there are no clear guidelines on the perspective to adopt. This paper explores the adoption of a societal perspective in economic evaluations of MSK disorders. Within health economics evaluations, the most commonly used perspectives include the payer perspective, the healthcare perspective, and the societal perspective. To facilitate optimal resource allocation decisions in order to reduce the significant economic burden of MSK disorders and improve the health outcomes of individuals with these disorders, all costs and benefits associated with interventions for them should be included. Thus, the societal perspective is arguably a preferable option to the others for economic evaluations of interventions for MSK disorders.

Scenario analysis and multi-criteria decision analysis to explore alternative reimbursement pathways for whole genome sequencing for blood cancer patients

BackgroundWhole genome sequencing (WGS) has transformative potential for blood cancer management, but reimbursement is hindered by uncertain benefits relative to added costs. This study employed scenario planning and multi-criteria decision analysis (MCDA) to evaluate stakeholders’ preferences for alternative reimbursement pathways, informing future health technology assessment (HTA) submission of WGS in blood cancer. MethodsKey factors influencing WGS reimbursement in blood cancers were identified through a literature search. Hypothetical scenarios describing various evidential characteristics of WGS for HTA were developed using the morphological approach. An online survey, incorporating MCDA weights, was designed to gather stakeholder preferences (consumers/patients, clinicians/health professionals, industry representatives, health economists, and HTA committee members) for these scenarios. The survey assessed participants' approval of WGS reimbursement for each scenario, and scenario preferences were determined using the geometric mean method, applying an algorithm to improve reliability and precision by addressing inconsistent responses. ResultsNineteen participants provided complete survey responses, primarily clinicians or health professionals (n = 6; 32 %), consumers/patients and industry representatives (both at n = 5; 26 %). “Clinical impact of WGS results on patient care" was the most critical criterion (criteria weight of 0.25), followed by "diagnostic accuracy of WGS" (0.21), "cost-effectiveness of WGS" (0.19), "availability of reimbursed treatment after WGS" (0.16), and "eligibility criteria for reimbursed treatment based on actionable WGS results" and "cost comparison of WGS" (both at 0.09). Participants preferred a scenario with substantial clinical evidence, high access to reimbursed targeted treatment, cost-effectiveness below $50,000 per quality-adjusted life year (QALY) gained, and affordability relative to standard molecular tests. Reimbursement was initially opposed until criteria such as equal cost to standard tests and better treatment accessibility were met. ConclusionPayers commonly emphasize acceptable cost-effectiveness, but strong clinical evidence for many variants and comparable costs to standard tests are likely to drive positive reimbursement decisions for WGS.