NTG, as a prevalent subgroup of POAG, is an important disease entity that affects millions of individuals worldwide. While controlling the IOP remains the mainstay of management in NTG, no research has tried to examine its cost-effectiveness. This study showed that, compared with observation, the ICER was US $34,225 per QALY gained for treating all NTG patients with IOP reduction interventions. The cost per QALY gained drops to US $27,000 or below when only those with risk factors for progression were treated. The World Health Organization (WHO) defines a health care intervention as highly cost-effective when the cost per disability-adjusted life year is less than the country's gross national product (GNP) per capita. It should be understood that QALY is not the same as disability-adjusted life year and should not be used interchangeably; however, it is worthwhile to draw reference using this WHO benchmark. Assuming equivalent thresholds can be applied to QALY, the QALY-based cost-effectiveness of treating all NTG patients was 0.72 times the US 2008 GNP per capita of US $47,580.
20 The year 2008 was chosen to match the data on costs of medications adopted from the cost analysis by Rylander and Void published in 2008,
19 as medications constitute the major expenditure in treatment of NTG. Apart from the WHO standards, the National Institute for Health and Clinical Excellence (NICE) under the National Health Service (NHS) of the United Kingdom, in its website stated that “if a treatment costs more than £20,000 to 30,000 per QALY, then it would not be considered cost effective.”
21 This converts to US $29,805 to $44,707 per QALY (Conversion rate 1 US Dollar [USD] = 0.67 British Pound Sterling [GBP]). Since the ICER for treating all NTG patients was US $34,225 per QALY gained, it is considered to be cost-effective.
According to the Ocular Hypertension Study Group,
10 the ICERs were US $3670/QALY and US $42,430/QALY for treating ocular hypertension subjects with a greater than or equal to 5% and greater than or equal to 2% annual risk of developing POAG, respectively. In Stewart's model,
11 the ICER for treating all people with ocular hypertension to prevent one case from progressing to POAG was US $89,072/QALY and was not considered cost-effective. The author suggested that treatment might be offered selectively to those with risk factors, namely age above 76, IOP above 29 mm Hg, central corneal thickness less than 533 μm, or cup-to-disc ratio wider than 0.6, where ICER values ranged from US $35,633 to $45,155 per QALY gained. Similarly, Rein et al.,
12 using a computer simulation of 20 million people followed from age 50 to death or to age 100, reported that the ICER values of routine office-based management of POAG ranged from US $28,000 to $46,000 per QALY, depending on treatment efficacy. The ICER of treating all NTG patients as revealed in the current Markov model, thus, compares favorably with the cost-effectiveness of treating POAG and ocular hypertension. In both cases of NTG and ocular hypertension, the cost-effectiveness of treatment improves when treatment is offered selectively to individuals at higher risk of progression.
In the models for ocular hypertension, the cost-effectiveness decision was sensitive to the incidence of POAG without treatment, treatment efficacy, cost of medications, and utility loss from POAG. Likewise, the cost-effectiveness of treating NTG in the current model was sensitive to changes in the cost of medications and estimated utility loss from progressed states. These consistent findings could be explained by the fact that treatments of ocular hypertension and NTG, both known to have slow progression, largely rely on medical therapies. Medications incur recurrent costs that constitute the main bulk of the total cost of the intervention as time goes by.
Despite an earnest effort to stimulate the real life situation, there are several limitations to this current model. Firstly, only direct costs were considered. Indirect costs encompassing patients' time attending follow-ups, impact on the quality of life due to surgery or frequent instillation of eye drops, caregivers' time and productivity loss from time off work were not incorporated as relevant information was not available in the literature. Since the majority of NTG patients are aged well over 60, the cost arising from loss of productivity might be of less significance. Secondly, the entire model was built based on the results from the CNTG study, despite being a landmark study with the largest cohort and longest follow-up, it had a sample of only 230 subjects. However, it is still a reasonable choice as subsequent low-tension glaucoma treatment study, which has included 178 subjects randomized to receive either brimonidine tartrate 0.2% or timolol maleate 0.5% showed a similar rate of visual field progression of 15% to 24% measured by various methods.
22 Thirdly, the calculation of the cost of medication in this study was based on the data published in 2008. With some of the effective IOP-lowering agents going out of their license protection, generic substitutes of a much lower cost might be available in the market, thus, altering the results of this study, in the direction of increasing the cost-effectiveness of the treatment. Fourthly, the “effectiveness” of the treatment is a result of the prevention of utility loss from the progressed state. If a patient has poor vision at presentation secondary to irreversible ocular comorbidities, such as macular degeneration, amblyopia and occipital blindness, and so on, leading to poor baseline utility, the results from this model would not apply. Lastly, the findings of this study, like many other cost-effectiveness analyses, were calculated from a model of hypothetical cohort created based on clinical data drawn from multiple studies from the literature. Assumptions were made when essential information was not directly available. Such assumptions may limit the accuracy of the results from the model. For example, the assumption that half of the patients intended for surgical intervention would have undergone laser trabeculoplasty might not be entirely true as the choice of intervention as well as the treatment efficacy is related to the baseline IOP. In reviewing the treatment and associated cost of US and European POAG patients, Lee reported a laser trabeculoplasty rate of 54% to 58% among all patients who have received surgery.
23 However, in the treatment of NTG where the baseline IOP is consistently lower than that in POAG, the rate might differ. Furthermore, apart from supplementary medication, second surgery or refinement surgery might be required when laser trabeculoplasty or trabeculectomy fails, thus, affecting the overall surgical costs. We attempted to assess the impact of such related cost by increasing the cost for surgery by 50% in the sensitivity analysis and found that it would only change the ICER by 2%. This might be explained by the fact that compared with the recurrent cost incurred by medical therapy, the costs of surgery constitute a relatively minor portion in the overall treatment cost, which included all the expenses from follow-up consultations and investigations.
It might be noted that despite there was a substantial increase in the incidence of cataracts in the treated group observed in the CNTG Study, the loss of utility from cataract and the cost of cataract surgery was not included in the current Markov model. It is because it was commented by the CNTG Study Group that “the rate of development of cataracts in the untreated control subjects was significantly lower than in the surgically treated subgroup but not statistically different from the rate in the medically treated subgroup.”
1,2 Nowadays, given the availability of potent IOP-lowering agents such as topical beta-blockers and prostaglandin analogues, we would expect fewer patients requiring surgical intervention to achieve IOP control than in the CNTG Study where treatment modality was restricted by the study design, thus, less filtration surgery related cataract. Moreover, the development of visually impairing cataract and the threshold for cataract surgery is known to be variable, depending on one's lifestyle, visual demand and general condition. Therefore, it would be very difficult to define which part of the cost of cataract surgery should be attributed to the treatment for NTG. Again, a crude reference could be drawn from the sensitivity analysis. When the cost of surgery was increased by 50%, which should be able to cover the further expenses arise from extraction of filtration surgery related cataract, the resultant ICER would change from US $34,225 per QALY to US $35,000 per QALY.
It is apparent that results of cost-effectiveness analyses are highly sensitive to the utility value of various disease states quoted. However, utility loss secondary to glaucoma has not been investigated widely. Unlike other ophthalmic conditions, like cataract and macular disease where disease severity is almost proportionately reflected in the level of visual acuity, glaucoma causes mainly a constricted visual field, and central visual acuity may remain unchanged even in advanced disease. Therefore, further research on glaucoma-specific utility values would be very helpful in defining the true effectiveness of existing treatment strategies and new interventions to be offered.
This economic evaluation of NTG treatment aims to provide reference materials in addition to clinical evidence. In any case, modeled data should not supersede clinical judgment. It is recommended that the ultimate decision on management should balance the benefits and risks of treatment, and take into account the perceived life span of the patient. Open discussion with the patient is highly recommended.