Discussion
Argus II is a novel healthcare technology that restores vision in RP patients. Improvements in visual acuity are expected to lead to improvements in patient self-confidence, decreasing their dependency, and to reduction in their depression/anxiety and risk of falls.
To our knowledge, this is the first formal cost-effectiveness analysis of a retinal prosthesis (Argus II) for RP patients. Compared to usual care, we found the Argus II device to be a cost effective intervention for RP patients from perspective of the healthcare payers. Over the lifetime of RP patient, the ICER for Argus II was below the published societal maximum willingness to pay thresholds of Eurozone countries.
The safety study of the Argus II Retinal Prostesis System has shown positive clinical results.[13] Since initial costs associated with the Argus II implantation may be regarded as high, it was important to conduct an economic evaluation in order to quantify the value for money of this technology in long-term health gain and costs. Cost-effectiveness analysis determines the expected impact of alternative treatment/care options. Cost-effectiveness results assist in medical decision-making by quantifying the societal benefits of a health technology against its costs and indicate treatment/care option providing the best value for money. We chose to perform the cost-utility analysis where outcome measures are QALYs. This approach allows policymaker to compare the benefits of a health technology across the health care areas due to a 'common currency' i.e. QALY.
Cost utility thresholds in many countries are either specified by authorities or are determined from pricing and reimbursement decisions taken in these countries. The acceptable range of this threshold in Canada is CAN$ 20,000 - 100,000 per QALY,[23] in United States is US$50,000 per QALY,[24] in England and Wales is £20,000–30,000 per QALY,[25,26] and in The Netherlands is €20,000–80,000 per QALY.[10] Decision analytic model for the Argus II Retinal Prosthesis System predicted an ICER of 28,588 Euros per QALY for an RP patient. This lifetime ICER value is well within the range of these thresholds or societal Willingness To Pay (WTP) in the countries inside and outside the Eurozone.
This retinal prosthesis is of considerable public health interest as one of the most realistic approaches in currently untreatable retinal dystrophies. European policy towards rare diseases defines RP a rare disease: affecting less than one person in every 2000 persons. One of the objectives defined by the EU Commission's Directorate General for Health and Consumer in article 12 of European reference network is to maximize the cost-effective use of resources particularly in the area of rare diseases.[27] Products intended for the diagnosis, prevention or treatment of a life threatening or chronically debilitating rare disease are called as orphan medicinal products. These products are often too expensive and have significant impact on patient's health care expenditure.[28] Therefore, orphan medical products are eligible for many incentives as mentioned in the European Parliament and Council Regulation (EC) No 141/2000 of 16 December 1999 on orphan medicinal products.[29] Orphan products are likely to have higher prices for modest effectiveness and their ICERs are expected to be higher than the cost effectiveness thresholds. It has been reported that societal considerations are taken in account while evaluating orphan products as these products target medical conditions with no alternative therapy. A higher cost effectiveness threshold has been debated for products with high social value.[30] However, economic evaluation of Argus II Retinal Prosthesis System shows that it is a cost effective intervention even for conventional Willingness To Pay (WTP) thresholds. In various scenario analyses, higher ICERs for shorter time horizons are due to high initial costs of the device.
Markov model for the Argus II Retinal Prosthesis System begins at the age of 46 years as most of the RP patients are legally blind by this age. The model runs for 25 years to extrapolate associated costs and health outcomes in RP patients in view of the shorter life expectancy of visually impaired individuals. The productivity loss in RP patients is difficult to fathom. Currently it would be too optimistic to expect any change in RP patient's productivity status after successful Argus II implantation. Realistically, in RP patients improved quality of life and self-dependence should be aimed by this device. On the other hand, Argus II is a novel technological breakthrough incurring high initial cost to the payers. Therefore, this cost-utility analysis for Argus II Retinal Prosthesis System has been performed from health care payer's perspective. It should be noted that the Argus II subjects who participated in the clinical trial did not receive specific rehabilitation after implantation of their Argus II Retinal Prosthesis System. The analyses presented in our article were based on FLORA study data from two years of follow up of Argus II fitted patients. Based on this data an assessment of cost- effectiveness of Argus II in RP patients is suggestive of significant QALY gain for these patients. Argus II fitted patients are expected to get regular product support in terms of software updates, special training and rehabilitation etc. The company Second Sight Medical Products Inc. mandated a committee of experts in rehabilitation specialized in low vision to develop a functional rehabilitation program for both low vision and mobility. This rehabilitation program will allow Argus II fitted patients to integrate visual information in a complete way. This program starts with teaching the basic skills necessary to use the prosthesis, then identify the personal aims and objectives of the patients, and offer a combination of conventional low vision, mobility re-education, very specific for prosthetic vision, to help patients reach their objectives. This program will certainly accelerate integration of the vision prosthesis and probably increase the functional utility of the Argus II Retinal Prosthesis System for most patients. Furthermore, an improvement has been observed over the results of the clinical trial because of the refinement of the surgical procedure. At this point, it is probable that these improvements will translate into a substantial benefit. Functional utility improvement and surgical refinement would make Argus II device even more cost-effective in future economic evaluations.
A single Argus II Retinal Prosthesis System was explanted due to conjunctival erosion associated with hypotonia. The patient was successfully explanted at the 14th month postoperatively (the implant and the retinal tack) without any complication. Argus II explantation is an expensive procedure leading to the return to the minimal light perception Markov state for a RP patient. We have modeled explantation probabilities for the life time of Argus II patients based on the available data for two years. However, long term complications such as explantation cannot be predicted accurately and longer follow up data is required to model such events. The model incorporates costs for Serious Adverse Events (SAEs) in the first cycle only. As only 30% of the Argus II fitted patients had SAEs and 70% of the SAEs occurred in 3 months and 82% of the SAEs in 6 months after implantation. Similarly the utility reduction caused by SAEs is assigned to the patients experiencing the SAEs in the first year of implantation.
Strength of this analysis is its potential transferability as model inputs can be adapted to different settings. Inter- or intra-country variations in costs or patient reported outcomes can be incorporated into the model. The model's robustness was explored in terms of uncertainty around the input parameters by varying point estimates by 25% lower and 25% higher. Running probabilistic simulations did validation of the model results. The mean of 1000 probabilistic draws revealed ICERs very similar to the deterministic values. This model conforms to the principles of good practice for decision analytic models with use of transparent data and modeling technique as per the guidelines laid by International Society for Pharmacoeconomics and Outcome Research (ISPOR) task force.[10]
This study shares the general limitations of economic modeling. The analysis presented in this paper was based on the data from only 30 Argus II fitted patients followed up for 24 months. This retinal prosthesis is a novel technology that requires surgical intervention and incurs considerable costs. Data from increased numbers of Argus II fitted patients with longer follow up in the coming years provides an opportunity re-consolidate the results of our analysis. The costs and utility values for our model are taken from comparable patients. Future research should estimate costs and elicit RP patients' preferences to determine the utility values in these patients at various visual acuity levels.
BMC Ophthalmol. 2014;14(49) © 2014 BioMed Central, Ltd.
