Data collection infrastructure for patient outcomes in the UK - opportunities and challenges for cell and gene therapies launching.

Background: Cell and gene therapies are associated with uncertainty around their value claims at launch due to limitations of supporting clinical data; furthermore, their high costs present affordability issues for payers. Outcomes-based reimbursement can reduce payer decision uncertainty and improve patient access, however, requires data collection infrastructure and practice to be operational. Objective: To identify indications most likely to see launch of cell or gene therapies in the UK over the next five years, and to perform a qualitative assessment of how conducive the existing data collection infrastructure and clinical practice is in facilitating adoption of outcomes-based reimbursement in the corresponding indications. Methodology: Through secondary research, we identified target indications for cell or gene therapies at a mature clinical development stage (Phase III) with EU and/or US trial sites, and assessed availability of relevant data collection infrastructures in the UK. Secondary research findings were validated through primary research (expert interviews). Key parameters considered for the suitability of existing data collection infrastructure in supporting outcomes-based reimbursement include time horizon of data collection, whether data entry is mandatory and whether infrastructure is product or therapy area-specific. Findings: We identified 58 cell or gene therapies, spanning 47 indications, 20 of which are in oncology. Oncology seems well placed for outcomes data collection (through the mandatory Systemic Anti-Cancer Treatment database), however data entry compliance can be an issue (due to resource limitations), and upgrading will be needed for the purpose of outcomes-based reimbursement. Among non-oncology indications ~two-thirds have data collection infrastructures in place, but only three come close to the requirements for outcomes-based reimbursement. Conclusions: Existing data collection infrastructure in indications with potential cell or gene therapies launches in the next five years in the UK is overall not sufficient to facilitate outcomes-based reimbursement.

Establishing the cost of implementing a performance-based, managed entry agreement for a hypothetical CAR T-cell therapy.

Background: Market access stakeholders consider the adoption of Managed Entry Agreements (MEAs), however a clearly described methodology to quantify their implementation burden is not available in the public domain. Objective: To quantify the cost of implementing a performance-based MEA at the hospital level. Methods: The analysis involved a hypothetical one-off therapy targeting Acute Lymphoblastic Leukaemia. Data collection from five NHS Hospital Trusts in England captured costs by task, job band, personnel time and capital investment. We compared the administrative burden of the standard of care (SoC) to that of adopting the therapy with or without an MEA over 10 years. Findings: The 10-year cost for the activities required to support hospital payments for the target patient population in England varied as follows: for the SoC was £447,353, compared to £1,117,024 for the novel therapy with MEA, and £245,317 without MEA. Conclusions: The higher cost associated with the SoC compared to the novel therapy without an MEA, arises from the higher frequency of infusions requiring payments and the associated mandatory data capturing requirements for oncology therapies. The novel therapy with MEA presents the greatest burden due to increased frequency of monitoring in year one to compensate for the greater uncertainty in clinical data and to inform the performance-based reimbursement.

Improving clinical reality in chronic obstructive pulmonary disease economic modelling : development and validation of a micro-simulation approach.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible disease responsible for the deaths of 3 million people worldwide in 2005, and predicted to be the third leading cause of death worldwide by 2030. Many COPD models developed to date have followed a Markov structure, in which patients or populations can move between defined health states over successive time periods or cycles. In COPD, health states are typically based on disease severity defined solely by lung function, as described by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. These current modelling methods may restrict the ability to reflect the disease progression/clinical pathway or clinical practice. OBJECTIVES: Given these limitations in previous COPD models, the authors aimed to develop a more flexible model that could improve on the description of the clinical disease pathway. The overall objective of this model was to inform the development of policies, guidelines or cost-effectiveness analyses. A second objective was to validate the model in relation to existing epidemiology studies of COPD. METHODS: A patient simulation model was developed in Microsoft Excel™. The predictability of the model was tested by populating it with data from natural history of disease studies as well as with clinical trial data. Each patient moves through the model with demographic characteristics randomly generated from a set distribution. These characteristics determine the risk of clinical events occurring in the model. RESULTS: The validation with these studies found the model to have generally good predictive ability, yielding in this way a good degree of external validity. CONCLUSIONS: The micro-simulation model is a flexible approach for modelling COPD that allows consideration of complex COPD treatment pathways. The model was found to be generally robust in terms of predicting clinical outcomes of published studies when tested against other studies. It has significant potential as a tool for supporting future COPD treatment positioning decisions as well as to inform the development of policies, guidelines or cost-effectiveness analyses.

The Cost-Effectiveness and Budget Impact of Introducing Indacaterol into the Colombian Health System.

OBJECTIVES: The main objectives were to estimate the cost-effectiveness and budget impact of indacaterol (a once-daily, long-acting-beta2-agonist) compared with 1) salmeterol/fluticasone, 2) formoterol/budesonide, and 3) tiotropium for the treatment of chronic obstructive pulmonary disease in Colombia. METHODS: A Markov model was utilized to simulate the progressive course of chronic obstructive pulmonary disease, distinguished by forced expiratory volume in 1 second predicted according to the four Global Initiative for Chronic Obstructive Lung Disease severity stages by using prebronchodilation values. Efficacy was based on the initial improvement in forced expiratory volume in 1 second, taken from either a network meta-analysis (salmeterol/fluticasone and formoterol/budesonide) or a randomized controlled trial (tiotropium). Colombian direct costs and life tables were incorporated in the adaptation, and analysis was performed from a health care payer perspective, discounting future costs (presented as US dollars) and benefits at 5%. A budget impact model was built to estimate the cost impact of indacaterol in Colombia over 3 and 5 years. RESULTS: Indacaterol was found to be dominant (i.e., less costly and more effective) against both salmeterol/fluticasone and formoterol/budesonide per life year and quality-adjusted life-year gained after a 5-year time horizon. The average cost saving against salmeterol/fluticasone and formoterol/budesonide was US $411 and US $909 per patient, respectively. All probabilistic sensitivity analysis simulations indicated indacaterol to be less costly than salmeterol/fluticasone and formoterol/budesonide. Indacaterol was more effective and more costly than tiotropium, corresponding to an incremental cost-utility ratio of US $2584 per quality-adjusted life-year. CONCLUSIONS: The results indicate that by replacing salmeterol/fluticasone or formoterol/budesonide with indacaterol, there are possible cost savings for the Colombian health care system. This was demonstrated by both cost-effectiveness and budget impact models.

Cost-utility analysis of indacaterol in Germany: a once-daily maintenance bronchodilator for patients with COPD.

INTRODUCTION: Indacaterol is a novel inhaled once-daily long-acting beta(2)-agonist (LABA) for the maintenance treatment of COPD that has been compared to existing inhaled monotherapies on a number of symptomatic endpoints in clinical studies. With constrained healthcare budgets, the objective of this analysis was to evaluate the cost-effectiveness of indacaterol 150 µg, the approved starting dose for maintenance therapy, from a German heath service perspective against the most widely used bronchodilator tiotropium, and the twice-daily LABA, salmeterol. METHODS: A Markov model was developed with the following main health states: Mild, Moderate, Severe, and Very Severe COPD, based on pre-bronchodilator FEV(1) measures reported in the indacaterol clinical trials, and death. Each disease severity health state had two associated health states for severe or non-severe exacerbation. The model considered patients with moderate to severe COPD, with a mean age of 64 years. The base case time horizon was three years, with discounting set at 3% for costs and benefits. Selected clinical inputs and health state utilities were derived from indacaterol clinical trials, while costs were based on publicly available drug prices and tariffs or published sources. Inputs describing disease progression were based on published data on the rate of FEV(1) decline. RESULTS: Point-estimates show that indacaterol 150 µg is dominant (lower total costs and better outcomes) against tiotropium and salmeterol. An alternative analysis comparing indacaterol 300 µg (maximum dose) against tiotropium, showed an incremental cost-effectiveness ratio (ICER) of approximately €28,300 per QALY. CONCLUSION: Indacaterol is cost-effective compared to tiotropium and salmeterol.

The economic impact of overactive bladder syndrome in six Western countries.

OBJECTIVE: To calculate up-to-date estimates of the economic impact of overactive bladder syndrome (OAB) with and without urgency urinary incontinence (UUI) on the health sector of six countries (Canada, Germany, Italy, Spain, Sweden and the UK), as OAB is a significant health concern for adults aged >18 years living in Western countries. MATERIALS AND METHODS: The prevalence data derived from the EPIC study were combined with healthcare resource-use data to derive current direct and indirect 1-year or annual cost of illness estimates for OAB including UUI in Canada, Germany, Italy, Spain, Sweden and the UK. This model estimates the direct healthcare costs attributed to OAB, as well as the impact of work absenteeism. RESULTS: The estimated average annual direct cost of OAB per patient ranged between 262 in Spain and 619 in Sweden. The estimated total direct cost burden for OAB per country ranges between 333 million in Sweden and 1.2 billion in Germany and the total annual direct cost burden of OAB in these six countries is estimated at 3.9 billion. In addition, nursing home costs were estimated at 4.7 billion per year and it was estimated that work absenteeism related to OAB costs 1.1 billion per year. CONCLUSIONS: The cost of illness for OAB is a substantial economic and human burden. This study may under-estimate the true economic burden, as not all costs for sequelae associated with OAB have been included. Cost-effective treatments and management strategies that can reduce the burden of OAB and in particular UUI have the potential to significantly reduce this economic burden.