The cost-consequence analysis is not the preferred method for economic evaluation, although it could be useful in specific cases. When an intervention produces many different outcomes that are difficult to aggregate into a combined measure of benefit, the cost-consequence analysis could be appropriate. In a cost-consequence analysis, costs and outcomes are listed in a disaggregated format. This forces a greater involvement of the decision maker, since he needs to weigh the relative importance of each individual outcome and consider the overall difference between interventions in terms of costs and outcomes.

When interventions are considered similar in all relevant aspects, a cost-minimization analysis can be considered. In a cost-minimization analysis, the preferred intervention would be the alternative with the lowest cost. For this type of economic evaluation, the critical issue is to confirm that there are no meaningful differences between the alternatives for all important patient outcomes, including efficacy, adverse events, impact on quality of life, treatment adherence or convenience, etc. Once the equivalence of the compared alternatives is established, then the less expensive alternative should be selected. The necessity to demonstrate that alternatives are equivalent limits the use of cost-minimization analyses.

The cost-effectiveness analysis is a very popular method for economic evaluation. In this type of economic evaluation, the interventions’ outcomes or effectiveness are measured in terms of natural units. These comprise life-years gained, life saved, deaths avoided, clinical benefits obtained, or clinical events avoided. For a cost-effectiveness analysis, the selected outcomes have to be shared by the evaluated alternatives and should represent a significant outcome for these interventions. The result of a cost-effectiveness analysis is expressed in terms of incremental cost-effectiveness ratio (ICER). The ICER is calculated by dividing the difference in effectiveness by the difference in costs:
For example, if a new intervention costs $10,000 and is associated with a 10 life-years gain and if the alternative intervention costs $5000 and is associated with an 8 life-years gain, then the ICER for the new intervention would be $2500 per incremental life-year gained ($10,000–$5000/10 LYG – 8 LYG). There are some constraints with the cost-effectiveness analysis. Only one outcome can be considered when estimating the cost-effectiveness of an intervention. As most interventions produce multiple outcomes, the full impact of an intervention thus cannot be taken into consideration. Also, the ICER associated with an intervention cannot be easily compared with the ICER of other interventions. Even if the selected outcome is the same, for example, life-years saved, the life-years saved produced by one intervention may not be the same as the life-years saved by another intervention. The quality of life of these life-years saved may be different.

To overcome some of the limitations of cost-effectiveness analysis, the cost-utility analysis has been proposed. The cost-utility analysis is very similar to the cost-effectiveness analysis, except that the outcomes of interventions are expressed in terms of quality-adjusted life years (QALY). The main advantage with the QALY is that it enables the integration of a multitude of outcomes (positive or negative), including quality of life. A QALY is basically equivalent to a year in perfect health. As for the cost-effectiveness analysis, the result of a cost-utility analysis is expressed in terms of incremental cost-utility ratio (ICUR). The ICUR is calculated by dividing the difference in QALY between interventions by the difference in costs:
For example, if a new intervention costs $10,000 and is associated with 10 QALY while the alternative intervention costs $5000 and is associated with 8 QALY, then the ICUR for the new intervention would be $2500 per QALY ($10,000–$5000/10 QALY – 8 QALY). Since the ICUR estimated for any intervention is based on a same outcome, the QALY, comparison can therefore be made between ICUR associated with different interventions. Cost-utility analyses have become very popular over the recent years and now represent, for most healthcare decision makers, the preferred method for economic evaluation.

Finally, although very promising, the cost-benefit analysis is now less frequently used, as it faces many methodological issues. In a cost-benefit analysis, both cost and outcomes are expressed in monetary value. The main difficulty with this method is to derive the monetary value of health outcomes. For this, the willingness-to-pay approach has been developed, but this approach is associated with significant difficulties, especially because it depends on individual’s ability to earn income.

There are some specifics to consider when performing an economic evaluation. These comprise: the comparator, the perspective, the time horizon, and the generalizability.

By definition, an economic evaluation is always comparative, thus at least two interventions are compared [3]. The appropriate comparator should represent the intervention to be eventually replaced by the intervention of interest. For example, lamellar keratoplasty was compared to penetrating keratoplasty (PK). As well, PK was compared to the absence of surgical intervention, since at the time PK was introduced, no other type of surgery was available.

The perspective of the analysis is also an important consideration for an economic evaluation. It basically defines the point of view of the analysis. The most common perspectives are the societal perspective, the healthcare system perspective, and the third-party payers perspective. The selected perspective defines which cost would be considered in the economic evaluation. For example, the cost of the surgery will be comprised in all of these three perspectives, but the cost associated with the productivity losses while the patient is hospitalized would be included in the societal perspective only.

An economic evaluation should encompass all relevant costs and health consequences associated with the intervention under evaluation. For this, the time horizon should be long enough to capture all related events and costs. For example when performing an economic evaluation of corneal transplantation, the time horizon of the evaluation should be long enough to capture all the costs and health consequences associated with the intervention but also all those associated with short-term and long-term complications and recurrences.

Generally in medicine, outcomes of an intervention performed in one location are expected to be replicable in other places. For example, the success of a medication or the rate of complications of a surgery is expected to be similar from one country to another, as long as the medication is used and the surgery is performed in similar conditions. Therefore, results of health intervention are in general considered to be generalizable. This is not the case with the results of an economic evaluation. Given the significant differences in cost structure and dispensation of care from one country to another, an intervention deemed cost-effective in one country may not be cost-effective in another country.

Another key consideration with economic evaluation is the interpretation of the results. Results of the cost-minimization and the cost-benefit analyses are easy to interpret. In the first instance, the least costly alternative is selected, while in the latter, the alternative with the highest net benefits will be selected. For the cost-consequence analysis, the decision maker has to determine which of the alternative interventions would be preferable after considering the various vectors of efficacy and costs. The cost-effectiveness and cost-utility analyses are the most frequently used methods for economic evaluation, and these analyses result in an ICER or an ICUR, respectively. The ICER and the ICUR basically estimate the incremental cost required to obtain an additional unit of health benefit. For example, results can be expressed in terms of $20,000 per life-year gained or $5000 per surgical success or $40,000 per QALY. To determine if an intervention is cost-effective, the decision maker has to decide if the ICER or the ICUR is below its willingness to pay for the health benefit. If the decision maker is willing to pay $50,000 for a QALY and the ICUR for the intervention is $40,000, then this intervention would be considered cost-effective. In contrast, an intervention with an ICUR of $60,000 would not be considered cost-effective.

The cornea is one of the most commonly transplanted tissues, with more than 120,000 corneal transplantations performed each year all over the world, approximately 52,000 of which in North America only [4–6]. Such a high degree of corneal transplant activity represents a relatively high economic burden. Over the past decades, improvements in surgical procedures, development of pharmacological and immunological strategies, as well as changes in corneal storage and eye banking regulations have made corneal transplantation one of the most successful transplantations in humans.

Although corneal transplantation is associated with high success rates, it has practical limitations. Firstly, there is a shortage of corneal donor tissue, which in several countries impacts on the waiting time from diagnosis to surgery. Secondly, not rarely, there is insufficient access to operating room time, which also contributes to extend the waiting period. In Canada, wait times for corneal transplantation remains a challenging problem in several provinces, with more than 2300 patients waiting for a corneal transplantation in 2009, excluding the province of Quebec [5]. A Canadian study suggested that the average wait time for corneal transplantation was between 7 and 36 months in 2009 [5]. The waiting period for surgery is associated with anxiety, poor levels of visual acuity, and the negative impact on patients’ quality of life is substantial. As demonstrated in several studies, reduced visual acuity highly correlates with low quality of life values [7–9].

The surgical techniques for corneal transplantation have been relentlessly evolving during the past decades. The paradigm of systematic full-thickness corneal replacement has been fundamentally revised, to be replaced by that of lamellar transplantation designed to replace only the diseased tissue while leaving intact the healthy corneal layers.