Cost-effectiveness Of New Drugs Research Articles

Impact of Incorporating Future Mandatory Price Reductions with Generic Drug Entry on the Cost-Effectiveness of New Drugs: A Policy Simulation Study of Dupilumab in Atopic Dermatitis Treatment.

The introduction of high-cost medications often poses challenges in achieving cost-effectiveness for drug insurance coverage. Incorporating future price reductions for these medications may enhance their cost-effectiveness. We examined the influence of future cost reductions mandated by the national insurer's equal pricing for equivalent drugs (EPED) policy on the cost-effectiveness of dupilumab, a biologic drug for moderate to severe atopic dermatitis in the Korean healthcare system. We conducted a policy simulation study using semi-Markovian cost utility analysis of dupilumab in combination with supportive care (SC) versus SC alone, with and without the EPED policy adjustment. The EPED would lower dupilumab's price to 70% following the entry of a biosimilar drug in 10.3 years. Scenario analyses quantified the impact of changing time to the EPED, chemical versus biological designation, response criteria, discount rates, and time horizons on the Incremental Cost-Effectiveness Ratio (ICER) and acceptability with and without EPED adjustment. The EPED adjustment of dupilumab's future price significantly improved its cost-effectiveness, with a 9.7% decrease in ICER and a substantial 14.6% increase in acceptability. Assuming EPED in 5 years, the ICER fell below the predefined willingness-to-pay threshold. If dupilumab were a chemical drug, EPED adjustment demonstrated a 19.1% increase in acceptability. Incorporating future cost reductions via the EPED system in economic evaluations is crucial, especially for drugs facing imminent generic entry. This study underscores the importance of EPED adjustment in the cost-effectiveness analysis of innovative medications, especially for those nearing willingness-to-pay thresholds.

HPR189 Estimating the Impact of Generic Drug Entry on Cost Effectiveness of New Drugs

HPR189 Estimating the Impact of Generic Drug Entry on Cost Effectiveness of New Drugs

810-P: The Diminishing Cost-Effectiveness of the Newer Glucose-Lowering Drugs in the United States, 2010-2018

Background: The difference between the costs of the newer and older glucose-lowering drugs has been steadily increasing since 2010. In 2018, newer drugs cost 8-12 times more than older drugs (except for insulin). This study aimed to understand how this change in drug cost influenced the cost-effectiveness (CE) of newer drugs compared with older drugs. Methods: We conducted a systematic literature review to identify US-based CE studies comparing newer (i.e., dipeptidyl peptidase-4 inhibitors (DPP4), glucagon-like peptide 1 receptor agonists (GLP1-RA), and sodium-glucose transport protein 2 inhibitors) with older glucose-lowering drugs. The identified 12 studies all reported the CE of newer drugs based on drug costs estimated before 2010. We have updated the corresponding CE of each study by replacing the old cost estimates with 2018 estimates from the 2018 IBM® MarketScan® Commercial Claims Databases. The time window and willingness to pay threshold were consistent with each original study. Results: Only 8% of the original studies suggested that the older drugs were cost-effective. However, 58% of studies were in favor of the older drugs after the cost update. Among the 4 studies comparing newer drugs with thiazolidinediones, all studies suggested thiazolidinedione to be cost-effective in the updated analysis, while the original results all favored newer drugs. For the 4 studies comparing newer drugs with sulfonylureas, 2 studies suggested the sulfonylureas to be cost-effective after the cost update. All 4 studies suggested newer drugs to be cost-effective when compared with insulin in the original study. Only 1 flipped its conclusion when 2018 costs were used. Our sensitivity analysis shows that our results are robust up to a 30% rebate. Conclusion: Significant changes in the cost of glucose-lowering drugs have impacted the economic value of different glucose-lowering agents substantially. More CE analyses are warranted to support the drug choice in T2DM management. Disclosure P. Li: None. R. S. Patel: None. S. M. Vouri: None. L. Shi: Research Support; Self; AstraZeneca, Sanofi. V. Fonseca: Consultant; Self; Abbott Diabetes, Asahi Kasei Corporation, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Stock/Shareholder; Self; Amgen Inc., Bravo4health, Mellitus Health. H. Shao: Research Support; Self; Sanofi.

A framework for monitoring of new drugs in Sweden

In order to monitor the net public health benefit of new drugs, especially in the light of recent stepwise approval approaches, there is a need to optimize real-time post-marketing evaluation of new drugs using data collected in routine care. Sweden, with its unique possibilities for observational research, can provide these data. We herein propose a framework for continuous monitoring of the effectiveness, safety, and cost-effectiveness of new drugs, using prospectively determined protocols designed in collaboration between all relevant stakeholders. We believe that this framework can be a useful tool for healthcare authorities and reimbursement agencies in the introduction of new drugs.

OP97 Cost-effectiveness Model Appraisal Guidelines For Health Technology Assessments In Ireland

IntroductionThe National Centre for Pharmacoeconomics (NCPE) assesses the cost-effectiveness of new drugs for which reimbursement by the healthcare payer, the Health Service Executive (HSE), is sought in Ireland. This research aims to create a systematic approach for the NCPE review group (RG) to assess each of the cost-effectiveness models submitted by the applicant by creating cost-effectiveness model appraisal guidelines.MethodsThe RG consists of clinical, statistical and health economic expertise. In order to systematically appraise the HTA submission, which includes a cost-effectiveness model, clear guidelines on how each of the members of the RG can work together are required. The current members of the RG in the NCPE were given a draft of the guidelines created by the primary author, and additional feedback and testing was performed using the expert experience of the team. A version of the guidelines was tested for its usefulness.ResultsThree checklists were created. The purpose of the first checklist is to evaluate if the cost-effectiveness model works correctly. The second checklist ensures that each of the assumptions included in the HTA dossier are the same as those included in the cost-effectiveness model. The final checklist validates the assumptions used in the cost-effectiveness model to ensure they are reasonable and appropriate for decision making. The final version of the checklists were validated by choosing cost-effectiveness models with known errors and/or discrepancies and testing that the issues were captured by the checklists.ConclusionsThese guidelines are not an exhaustive list of checks that should be performed, but are presented as the minimum requirements for consideration to be included with each RG assessment of the corresponding HTA submission. The guidelines will be constantly updated as the process evolves over time. The cost-effectiveness models should follow the National Health Information and Quality Authority (HIQA) Guidelines for the Economic Evaluation of Health Technologies in Ireland.

Estimating The Drug Treatment Cost of Breast Cancer

Objectives Overall treatment costs in oncology are increasing rapidly due to the increasing availability of expensive drugs. Comparing the costs of currently used drugs and assessing the cost-effectiveness of new drugs requires a transparent overview of actual breast cancer treatment prices. As such an overview is lacking, this study aims to synthesize evidence on the reimbursement and costs to estimate the total treatment cost of expensive breast cancer drugs for the Netherlands. Methods Evidence on the approval, reimbursement and list prices of expensive breast cancer drugs was identified from the Dutch Administrative Health Authority (ZINL). Data on the average length of treatment and dosing schedules was obtained from European Parliament Assessment Reports (EPARs) or ZINL reports. All evidence was aggregated in the estimation of actual treatment cost. Results In the Netherlands, 31 breast cancer drugs are approved (available in 41 different forms). Based on drug list prices Pertuzumab, Trastuzumab Emtansine and Trastuzumab are the most expensive drugs. For 17/41 (41.5%), no evidence on the average treatment length was available in EPARs or ZINL reports. Comparing list prices to the estimated treatment cost per patient resulted in substantial differences in the ranking of expensiveness of the drugs. Overall, estimated treatment costs were highest for Bevacizumab, Pertuzumab and Trastuzumab Emtansine. Conclusions Estimating treatment costs is far from trivial, given the wide range of evidence sources that need to be synthesized. This complicates rapid and transparent assessment of actual cancer drug treatment cost, which is necessary to focus strategies aiming to limit the increasing healthcare costs. Differences exist in list prices within countries and between countries, thereby influencing the corresponding estimated treatment costs and resulting in list prices having limited value in this context. Therefore, extending standardization in presenting information on costs per cancer drug and implementing real world price estimates in such calculations is highly recommended.

Utilisation patterns and cost of hospital care for people living with HIV in Ireland in 2012: a single-centre study.

Data on the pattern and cost of health service use by HIV patients are required for evaluations of the cost-effectiveness of new drugs and technologies as well as being essential for service planning. The aim of this study was to identify the utilisation patterns and cost of hospital care for HIV patients in a single centre in Ireland in 2012. Data on the frequency and non-drug costs of all hospital resources used by HIV patients were extracted from a hospital activity-based costing system. Cost data were analysed using a generalised linear model. A total of 328 patients, 3672 patient months, were included in this study. Patients had a mean of 4.4 scheduled infectious disease outpatient appointments per patient year; 37% of patients also used another outpatient service, 15% in-patient services, 4% day-case service and 18% emergency department services in 2012. Patients with very advanced HIV disease continue to incur a disproportionate amount of the total cost of providing care. This study provides baseline utilisation and cost data for use of both infectious-disease and non-infectious disease hospital services and will be useful for service planning in light of the likely increases in resource demands.

Double Relapsed and/or Refractory Multiple Myeloma: Clinical Outcomes and Real World Healthcare Costs.

Double relapsed and/or refractory multiple myeloma (DRMM), MM that is relapsed and/or refractory to bortezomib and lenalidomide, carries a poor prognosis. The healthcare costs of DRMM have not previously been reported. We analyzed detailed medical resource utilization (MRU) costs, drug costs and outcomes for 39 UK patients receiving standard DRMM therapy. Median OS in this cohort was 5.6 months. The mean cost of DRMM treatment plus MRU until death was £23,472 [range: £1,411–£90,262], split between drug costs £11,191 and other resource use costs £12,281. The cost per assumed quality-adjusted life year (QALY) during DRMM was £66,983. These data provide a standard of care comparison when evaluating the cost-effectiveness of new drugs in DRMM.

PHP150 - Practical problems of comparator selection to assess cost-effectiveness of New Drugs for reimbursement decision: a qualitative study in South Korea

Under the positive drug listing system, pharmaceutical companies in Korea are required to provide cost-effectiveness (CE) evidence of newly approved drugs for listing on the National Health Insurance (NHI) drug formulary. It has been argued that selection criteria of comparator treatments suggested by the CE guideline are too limited and unrealistic to conduct a valid CE assessment. Therefore, our study was conducted to investigate types of practical problems in comparator selection in order to improve the validity of CE analysis. We conducted focus group interviews (FGI) with experts working in research-based drug companies, charged of submitting CE evidence of their products to NHI. Each participant received an interview question via an e-mail beforehand and presented their opinions at round-table discussion. Examples of the problems associated with selecting appropriate comparators identified from FGI are as follows: drugs with the same indication, but therapeutically nonequivalent, were used as comparators ; there is no guidance on whether to include off-label drugs as comparators; when off-patent products were selected as comparators, the price of the new drug was compared with the price of generic products rather than the initial price of the original products set during the patent period; it is difficult to obtain reliable market share data needed for selecting a comparator; and the best supportive care was selected as a comparator when there’s no appropriate treatment alternatives. We expect that the results of our investigation would contribute to improve the quality of CE guidelines in South Korea as well as other countries, and to improve assessment of the true value of pharmaceutical intervention.

Biophysical Characterization of Therapeutic Proteins for Early Prediction of Manufacturability

Biopharmaceuticals or therapeutically relevant proteins have become one of the fastest growing parts of the pharmaceutical industry. These innovative molecules are much more complex than conventional drugs and their processing is much more demanding. Assessing, at a very early stage in the development process, the ease of manufacture (the manufacturability) would allow the candidates proteins to be ranked and thus help controlling the cost-effectiveness of new drugs. Our research project aims to identify critical properties of protein candidates allowing the prediction of their behaviour in large-scale bioprocesses. Our multidisciplinary approach combines computational analysis (Molecular Dynamics simulations), the pilot-scale production and the biophysical characterization of a set of Fragment antibody (Fab) mutants.This allowed the identification of regions of unstable structure helping to predict the stability of Fab candidates prior to experiments. Extensive aggregation kinetics were measured at a wide range of temperature, pH and ionic strength allowing the determination of a model for Fab aggregation and the development of a rapid micro-scale Fragment antibody aggregation screening method.

PRM11 Real-World Data to Calculate Cost-Effectiveness of Monoclonal Antibodies: Problems and Solutions

Real-world data is considered to be the gold standard by decision makers to inform on cost-effectiveness of new drugs. Unfortunately real-world data are often lacking in important parameters needed to inform on cost-effectiveness, and RCT data can be used to address this problem. Illustrated by two cases this abstract will show that the manner in which RCT and real-world data are combined can have a profound influence on the resulting ICER. Two case studies in which real-world data on cetuximab for the indication of locally advanced head and neck cancer and panitumumab for the indication of chemo-refractory metastatic colorectal cancer was collected retrospectively served as examples. The problem: In the case of cetuximab, patient selection in daily practice resulted in too much disparity in baseline characteristics between the treated and control group. The solution: survival data for both treatment groups from the pivotal RCT was used and corrected according to the results seen in the real-world data to better represent survival in daily practice. Using unadjusted RCT data resulted in a difference of approximately 5,000 euro/QALY in the ICER. In the case of panitumumab no data were available on progression of disease in the control group. The solution: progression free survival and survival after progression of the control group were drawn from the pivotal RCT and adjusted according to the survival observed in the control group of the outcomes research. Unadjusted RCT data resulted in an ICER that was approximately 20,000 euro/QALY higher. RCT data are often necessary to supplement missing data that cannot be collected through outcomes research, however the manner in which RCT data is used can have a profound effect on the resulting cost-effectiveness.

Common Drug Review Recommendations

The Common Drug Review (CDR) was created to provide a single process to review the comparative clinical efficacy and cost effectiveness of new drugs, and then to make formulary listing recommendations to Canadian publicly funded drug benefit plans. The objective was to conduct an in-depth analysis of Canadian Expert Drug Advisory Committee (CEDAC) recommendations to date, to explore predictors and possible explanatory factors associated with negative recommendations. Final recommendations were identified from inception (September 2003) to 31 December 2009. Using only publicly available information, recommendations were analysed under the following categories: submission specifics, drug characteristics, clinical factors and economic factors. Descriptive analyses were conducted, followed by statistical analyses, to determine which factors independently predicted a 'do not list' (DNL) recommendation. The database consisted of 138 unique final recommendations. The overall DNL rate was 48%. Significant differences in DNL rates were observed between therapeutic areas, ranging from 0% for HIV antivirals up to 88% for analgesic drugs. In the univariate analysis, several factors were significantly associated with a DNL recommendation, including first-in-class drugs and use of clinical scales as an outcome. In the multivariate regression, four factors were significantly predictive of a DNL recommendation: clinical uncertainty (odds ratio [OR] 14), price higher than comparators (OR 9), request for reconsideration (OR 10) and price as the only economic evidence used (OR 18). Incremental cost-effectiveness thresholds were not predictive of recommendations. The hypothesis that economic factors did not impact recommendations when clinical factors were included first was supported by the analysis. This analysis documented an evidence-driven process that simultaneously weighted multiple factors. Clinical uncertainty and price considerations, but not economic results, had a strong impact on the recommendations. Insufficiency of clinical evidence may have resulted from the gap in evidence available at the time of product launch and the absence of demonstrated benefits to support innovative drugs.

Different Policy Outcomes of the New Drugs and Currently Listed Drugs under the Positive List System in South Korea

Four years have passed since the positive list system was implemented in South Korea. The system was received well because it has fulfilled its intended objective of enhancing the cost-effectiveness of new drugs. With regard to currently listed drugs, however, debate has lingered since the reevaluation of the cost-effectiveness by therapeutic group. This study intended to review the lessons learned and compromises reached in implementing an evidence-based national formulary. Currently listed drugs are very different from new drugs. In terms of effectiveness, the level of existing evidence tends to be lower for currently listed drugs. Also, the evaluation plan was quite delayed because of the vast amount of literature. In the political decision-making process, a coalition was formed by the pharmaceutical companies with physicians, and the government had difficulty responding because of the strong resistance against the reevaluation of currently listed drugs. Although idealistic, it was an attempt to apply the same standard of cost-effectiveness for currently listed drugs as that for new drugs. To successfully implement the system, however, some factors that need to be considered were limitation of available evidence on currently listed drugs and specific strategies employed against political resistance.

Analysis of drug coverage before and after the implementation of Canada's Common Drug Review

Canada's Common Drug Review was implemented to provide publicly funded drug plans (provincial and federal) with a transparent, rigorous and consistent approach for assessing the clinical effectiveness and cost-effectiveness of new drugs. We compared uptake of drug coverage across jurisdictions before and after the implementation of the Common Drug Review. Using the IMS Brogan formulary acceptance: monitoring and evaluation database, we identified new drug products in Canada five years before and five years after the first recommendation was made by the Common Drug Review. For each jurisdiction, we compared the proportion of drugs listed, the median time-to-listing and the agreement between the listing decisions of the drug plans and the recommendations of the Common Drug Review. We identified 198 new drugs approved for use in Canada between May 26, 1999, and May 27, 2009, of which 53 had a recommendation from the Common Drug Review. The proportion of drugs listed decreased after the introduction of the Common Drug Review for all participating drug plans (81.1% to 71.3% overall [p ≤ 0.01 for all plans, with the exceptions of Ontario and Quebec [p = 0.07]). The change in median time-to-listing between the periods before and after the Common Drug Review varied by jurisdiction, ranging from a decrease of 691 days to an increase of 250 days. The change in median time-to-listing was not statistically significant for most jurisdictions, with the exceptions of Saskatchewan (increased, Mann-Whitney U test p = 0.01) and New Brunswick, Prince Edward Island, and Newfoundland and Labrador (all decreased, Mann-Whitney U test p < 0.01). There was a decline in the proportion of new drugs listed after the introduction of the Common Drug Review for both participating and nonparticipating jurisdictions. The introduction of the review was associated with a decreased time-to-listing for certain smaller provinces.

A clinician's critique of rheumatoid arthritis health economic models

Modelling cost-effectiveness of new drugs for RA has become increasingly prevalent and sophisticated. This situation has arisen largely because regulatory agencies, such as the National Institute for Health and Clinical Excellence, have demanded models from industry and have commissioned independent models. Many technical aspects of health economic models have converged-yet the results of models differ greatly. These differences can be accounted for in large part by differences in assumptions about the nature of patients likely to be treated; likely treatment sequences; likely responses to treatment; likely continuation on drug and likely disease progression, in particular. Such parameters cannot be fixed and evolve with changing practice and are ideally captured by contemporary data. Importantly, data from the local setting to which a health economic problem is applied are necessary, but in the absence of ideal sources, for the many contributions needed, considerable differences in opinion and biases are commonplace. In the final analysis, all models are just that, models, and as such an approximation of real life. Thus, although considerable heat is generated during debates about model parameters, model outputs may just yield sufficient light for regulatory agencies allocating resources.

Estimating the Relationship between Preference-Based Generic Utility Instruments and Disease-Specific Quality-of-Life Measures in Severe Chronic Constipation

Many clinical trials that generate evidence on the quality-of-life (QOL) improvements provided by new health technologies do not incorporate a preference-based generic measure, but generate only disease-specific data. However, in order to meet the information needs of regulators such as the UK National Institute for Health and Clinical Excellence (NICE), such disease-specific data need to be converted into a broader generic measure; for NICE, the preferred instrument is the EQ-5D. The process of converting QOL data from one instrument to another is known as 'mapping'. The objective of this study was to examine the extent to which disease-specific measures generated in the clinical trials for a new treatment for chronic constipation (prucalopride) can be 'mapped' onto a preference-based generic measure (EQ-5D and SF-6D) to generate robust and reliable utility estimates. Disease-specific QOL data generated in the clinical trials of prucalopride (PAC-QOL scores) were converted into utility values estimated using the preference-based generic measure EQ-5D. SF-36 data were also collected in the clinical trials and used to generate SF-6D estimates for comparative purposes. Regression analysis was used to derive a range of mapping functions to identify the extent to which increasing the complexity of the hypothesized underlying mapping function enhanced the robustness and reliability of the obtained mapping relationship. The mean utility observed at baseline for chronic constipation, based on SF-36 data, was 0.813 with the EQ-5D and 0.723 with the SF-6D. An examination of the differences between predicted and observed values generally found that the mapping functions generated were robust and reliable, with little evidence of bias across the range of the dependent variable. However, the nature of the symptoms explored in the PAC-QOL measure was, in general, less severe than those explored in the EQ-5D. For example, the condition-specific measures explored the degree to which patients experienced 'discomfort', rather than 'pain' as evaluated in the EQ-5D. Given this limitation in the severity range covered in the disease-specific measures, it is perhaps not surprising that a 'floor effect' was identified, with certain health dimensions mapping only to the upper range of the EQ-5D measure. In circumstances where direct utility measurement is not available, mapping provides a valuable method by which to estimate utility data for incorporation into cost-effectiveness analyses. Our findings emphasize the importance of the structure and nature of the mapping analysis undertaken as being a fundamental determinant of the utility estimates generated. Unfortunately, the theoretical guidance available to steer such analyses is still comparatively underdeveloped and this remains an area of health economic analysis in which empiricism largely rules. Ensuring that such mapping is undertaken and interpreted in as transparent and robust a manner as possible is therefore crucial in allowing regulators to accurately compare the clinical and cost effectiveness of new drugs across therapeutic areas.

Health Technology Assessment From a Canadian Device Industry Perspective

Health technology assessment has significantly improved the decision-making process via the thorough and systematic evaluation of the clinical utility and cost-effectiveness of new drugs and health technologies. However, the device industry faces a significant challenge in meeting the evidentiary demands of the health technology assessment process, particularly given the small size of the Canadian market and device manufacturers. This is further compounded by the somewhat short-sighted nature of health care budgets, which see medical devices as a cost-driver given the sometimes significant upfront investment required to implement a technology producing downstream benefits in the long-term. Industry is the research and development of the health care system, but innovative development could be stifled unless the health technology assessment process recognizes the risk of manufacturers. The authors propose that health technology assessment can be improved by recognizing the challenges that device manufacturers face and by sharing the risk associated with evaluations of effectiveness. Health technology assessment is a powerful tool that can be used to evaluate new and potentially obsolete technologies alike, with the goal of meeting the needs of patients as customers of both the device industry and the health care system.

Estimating the microcosts of blood transfusion for hemato-oncological patients

There are several ways of treating and preventing chemotherapy-associated anaemia, namely with erythropoiesis stimulating agents and blood transfusion, that remains an option. Since erythropoiesis stimulating agents have a high unitary cost, it is crucial to evaluate their cost-effectiveness, namely versus transfusion. The objective of this study is to calculate the cost of a blood transfusion, carried out at the Immunohemotherapy Outward of Instituto Português de Oncologia, Francisco Gentil, in Lisbon as treatment for neoplasia-associated anaemia. Cross sectional, observational study from the perspective of the Hospital and the National Health Service, which evaluates the resources and direct costs, associated with a blood transfusion of two erythrocyte concentrate (EC) units in hemato-oncology patients. Data regarding consumables, human resources, laboratory analysis and occupation of facilities was collected for a period of seven consecutive days, regarding both blood donation and transfusion procedures in the Immunohemotherapy Outward of Instituto Português de Oncologia, Francisco Gentil, in Lisbon. The total cost of a two EC unit transfusion was estimated at euro 676.2, with the greatest part of this cost being attributed to blood preparation, analysis and storage. Determining reliable costs in relation to medical actions and procedures is essential in analysing the cost-effectiveness of new drugs. This study evaluated the cost for the transfusion of two EC units and the results presented are similar to those obtained in other European countries by several authors.

The cost-effectiveness of newer drugs as add-on therapy for children with focal epilepsies

Epilepsies in children are complex diseases. Guidelines are needed on the appropriate use of newer versus older anti-epileptic drugs (AEDs). This paper presents an individual patient-sampling model to assess the cost-effectiveness of using newer AEDs as add-on therapy in line with UK prescribing guidance. Identification of the relevant parameters and treatment pathways for the model were achieved by a systematic review of the literature and discussions with clinical experts. Data were obtained from the literature and supplemented with data elicited from paediatric neurologists. The model considered paediatric patients over the period of childhood from the age of diagnosis to 18 years. The results suggest that the older and newer AEDs are similar in terms of drug retention rates and the average time in 'good' treatment outcomes. In terms of cost, the results indicate a consistent increase in cost (compared to older AEDs) when all of the newer AEDs are considered. The decision analysis results indicate that there are no important health benefits from the use of newer AEDs when used as add-on therapy. However, the analysis also reveals that the uncertainties in the model are greater than the differences between the drug strategies. To develop guidelines on the appropriate use of newer AEDs, better information is required from randomised controlled trials as there is insufficient data available in the public domain to accurately estimate the nature of the trade off between older versus newer AEDs.

The clinical effectiveness and cost-effectiveness of newer drugs for children with epilepsy. A systematic review

The clinical effectiveness and cost-effectiveness of newer drugs for children with epilepsy. A systematic review