National Centre For Pharmacoeconomics Research Articles

Examining the Feasibility and Utility of Estimating Partial Expected Value of Perfect Information (via a Nonparametric Approach) as Part of the Reimbursement Decision-Making Process in Ireland: Application to Drugs for Cancer.

In Ireland, all new drugs for which reimbursement by the healthcare payer is sought undergo a health technology assessment by the National Centre for Pharmacoeconomics. The National Centre for Pharmacoeconomics estimate expected value of perfect information but not partial expected value of perfect information (owing to computational expense associated with typical methodologies). The objective of this study was to examine the feasibility and utility of estimating partial expected value of perfect information via a computationally efficient, non-parametric regression approach. This was a retrospective analysis of evaluations on drugs for cancer that had been submitted to the National Centre for Pharmacoeconomics (January 2010 to December 2014 inclusive). Drugs were excluded if cost effective at the submitted price. Drugs were excluded if concerns existed regarding the validity of the applicants' submission or if cost-effectiveness model functionality did not allow required modifications to be made. For each included drug (n=14), value of information was estimated at the final reimbursement price, at a threshold equivalent to the incremental cost-effectiveness ratio at that price. The expected value of perfect information was estimated from probabilistic analysis. Partial expected value of perfect information was estimated via a non-parametric approach. Input parameters with a population value at least €1million were identified as potential targets for research. All partial estimates were determined within minutes. Thirty parameters (across nine models) each had a value of at least €1million. These were categorised. Collectively, survival analysis parameters were valued at €19.32million, health state utility parameters at €15.81million and parameters associated with the cost of treating adverse effects at €6.64million. Those associated with drug acquisition costs and with the cost of care were valued at €6.51million and €5.71million, respectively. This research demonstrates that the estimation of partial expected value of perfect information via this computationally inexpensive approach could be considered feasible as part of the health technology assessment process for reimbursement purposes within the Irish healthcare system. It might be a useful tool in prioritising future research to decrease decision uncertainty.

The Pharmacoeconomic Evaluation Process in Ireland.

In Ireland, all new drugs are considered for a formal pharmacoeconomic evaluation (PE) prior to a reimbursement decision. All evaluations are conducted by the National Centre for Pharmacoeconomics (NCPE). The objectives of this study were to describe the evaluation process and to examine the movement of drugs through the process. The movement of all drugs submitted to the NCPE (from January 2010 to December 2015 inclusive) was investigated. A total of 230 Rapid Review submissions (each pertaining to one drug for one indication) were made. The Rapid Review process determines the requirement for a full PE. A full PE was deemed unnecessary in 108 cases (47%). A positive reimbursement recommendation was made in 100 of these (a price reductions was advised in 25 cases and a recommendation to restrict/monitor usage was made in 35). The requirement for a full PE was recognised in 122 cases (53%). In 12, subsequent payer-led price negotiations negated the requirement for a full PE, and reimbursement was recommended. In 24 cases, a timely full submission was not made; cost effectiveness could not be established. Fifteen interventions are currently going through the submission process. To date, 71 full PEs have been completed by the NCPE. Reimbursement was recommended in 19 and was not recommended in eight. Reimbursement was not recommended 'at the submitted price' in 44. Of these, reimbursement was subsequently approved in 34 (77%) following price negotiations. To date, negotiations are on-going in a further six cases. In all, negotiations have been informed by the NCPE. A negative recommendation was reached in the remaining four. Over the study period, the NCPE evaluated 230 drugs for which reimbursement was sought. In total, a positive reimbursement recommendation has been made in 165 cases (72% of all drugs submitted, or 79% when drugs currently undergoing the process are excluded). A price reduction was deemed necessary in 71 (43%) of the 165 cases, and a recommendation to restrict/monitor usage was made in 35 cases (21%).

31 Comprehensive cost analysis of inpatient and outpatient heart failure patients – a microcosting approach: Abstract 31 Table 1

Background In the era of improved care and outcomes of heart failur e (HF) patients the cost of management of such patients is set to rise exponentially. Recently published figures from the HSE reveal an annual rate of HF admissions of 4826 with a resultant annual cost of 25,917,762 euro. Aims 1. To formally assess the cost of inpatient care of HF patients, and to assess the cost of running a Disease Modifying Programme, through the process of microcosting. 2. To compare this cost to (a) Locally derived costs for the same admission, (b) National costs applied to HF admissions and (c) HF costs from the NHS. Methods Inpatient HF patients were examined at two separate timepoints: 1: patients admitted with HF over 3 years (n = 1196) retrospectively identified through the Hospital In Patient Enquiry (HIPE) record. 2: A second inpatient group (n = 56), admitted and subsequently enrolled on the HF programme. Separate time points were studied to ascertain if the cost of management of HF is increasing over time and whether the implementation of a HF service impacts on this cost. Outpatient heart failure programme (HFP) patients were examined to ascertain the real life cost of running a recently set up HF service. A microcosting exercise was carried out on both groups, as advised by the National Centre for Pharmacoeconomics. Costs were calculated from the perspective of the health service provider. Results 1196 patients were identified through the HIPE search for HF admissions 2008–2010, mean age 75 years, 52% male. A cardiologist was the primary physician for 1/3 of patients admitted with a primary or secondary diagnosis of HF during this period. AF was the most commonly recorded comorbidity (38%). There was an 11% all cause death rate. HF readmission at 30 days was 9.6%; at 90 days was 16%. Mean length of stay was 17 ± 34 days. Costs are outlined in the Table 1 below. Fifty six patients were enrolled to the HFP in its initial stages. Mean age was 70 years and 58% were male. Two thirds (66%) had known prior CAD. Outpatient Costs: The mean cost of a standard 12 week programme patient was €1063.57. The mean cost per programme for extended programme patients was higher €4710.3 with a median cost of €1206.37. Conclusion When compared to a microcosting exercise, patient level costing is accurate. In comparison, using DRG costs can significantly underestimate inpatients HF costs. The most expensive component of inpatient HF admissions remains LOS. Mean LOS pre dedicated HFC was 17 (±34) days. Post HFC implementation, mean LOS was 15 (±18) days. There was a significant increase in mean cost of HF admission from 2008–2010 (pre HFC) to 2012 (post HFC) despite the lower LOS. This can be explained by increased utilisation of costly cardiac investigations such as coronary angiography, cardiac MRI, and device therapies such as ICDs or biventricular pacemakers. References Executive HS. Ready Reckoner. http://www.hse.ie/eng/services/list/1/schemes/cbd/Ready%20Reckoner.pdf UK TDoH. NHS schedule of reference costs 2010/2011 UK NIoCE. Costing statement: Acute heart failure. Implementing the NICE guideline on acute heart failure 2014

PCN37 - Survival Analysis Used in Company Submissions to the National Centre for Pharmacoeconomics, Ireland

Many company submissions received by Health Technology Assessment (HTA) Agencies evaluate the cost effectiveness of interventions which impact on survival. An accurate estimate of the survival benefit is required to calculate a reliable estimate of cost effectiveness. Generally the relevant trial data is immature and must be extrapolated. Many extrapolation models are available. Model choice is critical; different models can lead to different cost effectiveness results. The objectives were to review the methods/justification of the survival analysis used in company submissions to the National Centre for Pharmacoeconomics (NCPE). A further aim was to develop NCPE Guidance for the future handling of survival analysis. Relevant submissions to the NCPE (economic evaluations which had dealt with advanced and/or metastatic cancer) were reviewed to determine the methods/justification of the survival analysis used. Twelve submissions were evaluated. Appropriately, the mean overall survival (OS) had been estimated and used in eight cases (67%). Median OS estimates had been estimated/used in three (25%). It was unclear which measure had been used in the remaining submission. The submissions which had used mean OS estimates were further investigated. Parametric model-based extrapolation techniques had been used to calculate the mean estimates in all eight. The most popular parametric models were the Weibull (n=3) and the loglogistic (n=3). The methods used to fit the parametric models varied. Most commonly the model was fitted using individual patient-level data. Some justification for the choice of extrapolation technique was offered in five submissions; AIC +/or BIC were estimated in three and visual inspection was reported in two. Survival analysis has not been conducted appropriately in all HTAs. Justification of the choice of model is not always offered. Moving forward, NCPE Guidance is required to ensure that survival analysis using patient-level data is conducted appropriately. These will be presented.

Value-of-Information Analysis to Reduce Decision Uncertainty Associated with the Choice of Thromboprophylaxis after Total Hip Replacement in the Irish Healthcare Setting

The National Centre for Pharmacoeconomics, in collaboration with the Health Services Executive, considers the cost effectiveness of all new medicines introduced into Ireland. Health Technology Assessments (HTAs) are conducted in accordance with the existing agreed Irish HTA guidelines. These guidelines do not specify a formal analysis of value of information (VOI). The aim of this study was to demonstrate the benefits of using VOI analysis in decreasing decision uncertainty and to examine the viability of applying these techniques as part of the formal HTA process for reimbursement purposes within the Irish healthcare system. The evaluation was conducted from the Irish health payer perspective. A lifetime model evaluated the cost effectiveness of rivaroxaban, dabigatran etexilate and enoxaparin sodium for the prophylaxis of venous thromboembolism after total hip replacement. The expected value of perfect information (EVPI) was determined directly from the probabilistic analysis (PSA). Population-level EVPI (PEVPI) was determined by scaling up the EVPI according to the decision incidence. The expected value of perfect parameter information (EVPPI) was calculated for the three model parameter subsets: probabilities, preference weights and direct medical costs. In the base-case analysis, rivaroxaban dominated both dabigatran etexilate and enoxaparin sodium. PSA indicated that rivaroxaban had the highest probability of being the most cost-effective strategy over a threshold range of &U20AC;0-&U20AC;100 000 per QALY. At a threshold of &U20AC;45 000 per QALY, the probability that rivaroxaban was the most cost-effective strategy was 67%. At a threshold of &U20AC;45 000 per QALY, assuming a 10-year decision time horizon, the PEVPI was &U20AC;11.96 million and the direct medical costs subset had the highest EVPPI value (&U20AC;9.00 million at a population level). In order to decrease uncertainty, a more detailed costing study was undertaken. In the subsequent analysis, rivaroxaban continued to dominate both comparators. In the PSA, rivaroxaban continued to have the highest probability of being optimal over the threshold range &U20AC;0-&U20AC;100 000 per QALY. At &U20AC;45 000 per QALY, the probability that rivaroxaban was the most cost-effective strategy increased to 80%. At &U20AC;45 000 per QALY, the 10-year PEVPI decreased to &U20AC;3.58 million and the population value associated with the direct medical costs fell to &U20AC;1.72 million. This increase in probability of cost effectiveness, coupled with a substantially reduced potential opportunity loss could influence a decision maker's confidence in making a reimbursement decision. On discussions with the decision maker we now intend to incorporate the use of VOI into our HTA process.

Pharmacoeconomic Evaluation in Ireland

To describe the pharmacoeconomic assessment process in Ireland and to provide examples of recent appraisals and the subsequent impact on pricing and reimbursement decisions. The pharmacoeconomic appraisals conducted by the National Centre for Pharmacoeconomics (NCPE) between September 2006 and February 2009 were reviewed. The NCPE recommendations and subsequent reimbursement decisions by the Health Service Executive (HSE) were recorded. Recommendations made by the NCPE were compared with those of UK agencies. The duration of the NCPE pharmacoeconomic process and the time from marketing authorization to reimbursement was estimated. The budget impact assessments from the pharmaceutical companies were reviewed and compared for consistency. The NCPE conducted 12 single technology appraisals during the study period. Eight of the medicines assessed were either recommended as a cost-effective use of resources or recommended with certain restrictions, and were funded by the HSE. Of the four medicines that were not considered cost effective, two were reimbursed after a price reduction was negotiated and the remaining two were not. The NCPE recommendations concurred with those of the UK agencies for the majority of appraisals, with the exception of sunitinib and lapatinib. The average duration of the NCPE process was 2.7 months. The average time from marketing authorization to reimbursement was 7 months. The review of budget impact assessments highlighted a high degree of variability between submissions. The findings of this review highlight the efficiency of the pharmacoeconomic process and the acceptance of the NCPE recommendations by the HSE for pricing and reimbursement decisions. NCPE recommendations broadly concurred with those of UK agencies for the majority of appraisals.