Survey and analysis of accessibility, availability, and affordability of topical glaucoma medicines

Abstract

Purpose:

Affordability and availability of medicines is a growing global challenge for health-care systems. Access to medicines is recognized as an important determinant of treatment adherence. The access to glaucoma medicines and how it affects glaucoma management are not known. The purpose of this study was to determine the availability, affordability, and accessibility of topical intraocular pressure (IOP) -lowering eye drops in Haryana state of northern India using the World Health Organization (WHO)/Health Action International (HAI) methods.

Methods:

A cross-sectional study was done to collect data on prices and availability of glaucoma topical medications in public and private sector pharmacies and retail outlets using the WHO/HAI methodology between October 2021 and January 2022. The availability and affordability of topical glaucoma medicines was determined. Comparison of the local price with international prices was done by calculating the median price ratio (MPR).

Results:

A total of 191 facilities were randomly sampled across 11 (n = 55) urban, 29 (n = 92) semi-urban, and 44 (n = 44) rural places during the study period. The availability of topical medication for glaucoma was low (35.7 ± 22.3) across all sampled sites and all classes of topical glaucoma medications. The median price of topical medication and availability were negatively correlated, Pearson’s coefficient r (18) = -0.44, P 0.05, though the relationship was weak. A lowest paid, unskilled Indian government worker must spend between 15% and 203% of their daily wage to acquire a glaucoma medication.

Conclusion:

The availability and accessibility of topical glaucoma medications was low in this survey.

Glaucoma accounts for 5.5% of blindness in India, putting it among the leading causes of blindness.[1] The global prevalence of glaucoma in adults aged above 40 years is expected to increase from 64.3 million in 2013 to 111.8 million in 2040.[2] The blindness associated with glaucoma is multifactorial and characterized by progressive loss of the visual field. The only effective way known to prevent this loss is through a reduction of intraocular pressure (IOP).[3,4,5] Topical IOP-lowering drops have been shown to control IOP effectively and preserve visual fields in most patients, and are therefore offered as first-line treatment for most types of glaucoma.[3,6] However, the effectiveness of glaucoma medications depends not only on drug efficacy, but also on adherence to treatment.[7,8] Access to medicines is recognized as an important determinant of treatment adherence.[9,10,11,12] The five dimensions of access to medicine in the health system are availability, affordability, accessibility, acceptability, and quality of medicine.[13] Affordability and availability of medicines are growing global challenges for health-care systems.[14] According to a World Health Organization (WHO) report, close to 68% of the population in India has limited or no access to essential medicine.[15] The model list of essential medicines also includes some of the glaucoma medications.[16] Glaucoma medicine access and its effect on glaucoma management in India are not known. This study was intended to determine the availability, affordability, and accessibility of topical IOP-lowering eye drops in the Haryana state of northern India.

Methods

The study was approved by the Institutional Ethical Committee (No. MAMC/pharma/ICE/21/01) of Maharaja Agrasen Medical College, Agroha (Hisar), Haryana, India.

Study settings

India is a lower-middle-income economy with a gross national income (GNI) per capita of US$ 2256.6.[17] Haryana is a northern Indian state with 22 districts and a population of 25.4 million as per the 2011 census.[18] The net state domestic product (NSDP) per capita for Haryana is $ 3451, which is 1.75 times the national NSDP of $ 1964.[19] However, there is a disparity in the distribution of economy in the state.[20] Therefore, for the purpose of the survey, the districts were grouped into three economic categories: low income (<$ 666), middle income (≥$ 666–1326), and high income (>$1326), based on per capita income (PCI). To give equal representation to all geographic areas and districts belonging to different PCI categories, a total of 11 districts – two with high, four with middle, and five with lower PCI – were randomly selected [Fig. 1].

Figure 1.

Map of India showing the state of Haryana (left), map of Haryana showing the districts included in the survey and color coded based on per capita income (right)

Sample collection

The data on prices and availability of topical glaucoma medicines in public and private sector pharmacies and retail outlets was collected by adapting the WHO/Health Action International (HAI) methodology.[21] Random sampling was done from urban (district), semi-urban (sub-divisions/taluks), and rural (1% of total villages in that district) places in each district. Three sectors were sampled: public general/eye hospital (outpatient dispensary), private eye hospital/clinic pharmacy, and private retail outlet/shops. In each district, the largest public hospital and private hospital were sampled, along with five retail pharmacies located at least a 15-min walk or 5-min drive from the hospital. In each semi-urban place, three areas were sampled: one in a public hospital, one in a private hospital, and one retail pharmacy. At the village level, the largest retail pharmacy was sampled. Thus, a total of 191 facilities were sampled [Table 1].

Table 1.

Demographic and economic characteristics of districts surveyed and number of facilities sampled

Characteristics						No. of facilities sampled
Districts		Geographic location		Economic categorya		Urban		Semi-urban		Rural
Ambala		North		Middle		5		8		5
Fatehabad		West		Low		5		9		3
Gurugram		Southeast		High		5		8		4
Hisar		West		Middle		5		9		4
Jhajjar		Central		Low		5		9		3
Kaithal		Northeast		Low		5		8		4
Karnal		Northeast		Middle		5		12		5
Mohendragarh		South		Low		5		9		5
Nuh		Southeast		Low		5		6		4
Panipat		East		High		5		7		4
Rohtak		Central		Middle		5		7		3
11 Districts						55		92		44

^aEconomic category based on per capita income: low <$ 666, middle $ 666–1326, and high >$ 1326

The field survey was conducted from October 2021 to January 2022. It was carried out by trained pharmacy and paramedical graduates, who were introduced to survey methodology and drug price and availability sampling techniques as per WHO/HAI methodology. A verbal consent was obtained from the person in charge of the pharmacy or the operator of the retail outlet. Using a standardized data collection sheet, the field team member collected information on the retail sale price (maximum retail price [MRP]) and availability of 20 topical glaucoma medicines, which included 12 single-drug formulations (SDF) and eight fixed drug combinations (FDCs). Prices for all the brands available at the time of sampling were recorded.

Data analysis

The data was entered in an Excel spreadsheet (Microsoft, Redmond, Washington, USA), cross-checked, and verified by one of the investigators as per WHO/HAI methodology. Accessibility was measured in terms of the availability and affordability of the medicine. Access has been defined as having medicines continuously available and affordable at public or private health facilities or medicine outlets that are within 1 h walk of the population.[21] Availability was defined as the percentage of retail pharmacies where IOP-lowering topical drops were available at the time of the survey. The availability was categorized as very low (<30%), low (30%–49%), fairly high (50%–80%), and high (>80%).[22] Affordability was defined as the number of days the lowest paid, unskilled government worker needs to work to purchase 30 days’ supply of drug(s) on average (median) treatment costs.[21] The lowest wages paid to unskilled Indian government workers were used to calculate affordability, and topical glaucoma medicine was classified as unaffordable if the median price exceeded the 1-day salary of the worker.[21,23]

The high/low (H/L) ratio was calculated to determine the difference in price between the different brands of the same medication. To compare the local price of a drug with international prices, the median price ratio (MPR) was calculated by comparing the local median unit price of the drug with the median unit price in Management Sciences for Health (MSH) 2003, recommended by the WHO/HAI methodology as the source of the international reference price (IRP).[24] However, it was noted that IRP for topical glaucoma medicine was available only for four topical glaucoma medicines: timolol, pilocarpine, dorzolamide, and latanoprost, hence it is of limited value. Therefore, prices from the Australian Pharmaceutical Benefit Scheme (PBS) were used as IRPs. We standardized all prices to USD for each milliliter of topical glaucoma medicine and then calculated the MPRs. MPR was calculated by dividing the selling price of each milliliter of topical glaucoma medicine in India in USD by the selling price of each milliliter of topical glaucoma medicine in USD in Australian PBS. An MPR below 3 is interpreted as an acceptable price for private sector pharmacies.[22]

Using a repeated analysis of variance (ANOVA) with a post-test (P < 0.05) for nonparametric data and an unpaired t-test for parametric data, the availability of topical medicines in various settings was examined. Pearson’s correlation coefficient was used to determine the relationship between availability and the median price.

Results

During the study period, 199 facilities were sampled in 11 (n = 55) urban, 29 (n = 92) semi-urban, and 44 (n = 44) rural locations [Table 1]. The availability, brand name, and MRP (in Indian rupees) of 20 different types of topical glaucoma treatments, including 12 monotherapies and 8 FDCs, were all gathered.

Availability

Across all studied sites and all classes of topical glaucoma drugs, the overall accessibility to topical glaucoma medications was low (35%) [Table 2]. When compared to semi-urban areas, the accessibility of topical drugs was significantly better in urban than in rural areas (P 0.0001). In districts with a higher PCI (48%) compared to those with a middle PCI (32%), availability was better and the difference was significant (P 0.04). Although the mean percentage of topical drug availability was higher in low-PCI districts (35%) compared to middle-PCI districts, the difference was not statistically significant (P = 0.6). When compared to pharmacies outside the hospital’s grounds, there was no discernible difference in the accessibility of topical drugs (P = 0.7).

Table 2.

Availability of topical medications for glaucoma at the time of survey

Topical medication		Availability (in percentage)
		Overall (n=191)		U (n=55)		SU (n=92)		7 R (n=44)		Inside (n=39)		Outside (n=152)		Ia (n=27)		IIa (n=71)		IIIa (n=93)
Betaxolol		9.4		18		9		0		10		9		41		7		2
Timolol		84.2		98		83		70		92		82		96		82		83
Brimodineb		44		53		52		16		46		43		56		51		35
Brinzolamide		36.6		49		42		9		38		36		45		33		38
Dorzolamide		63.3		75		68		39		54		66		85		50		68
Pilocarpine		50.7		70		55		16		44		53		96		41		45
Bimatoprostc		37.6		67		28		20		44		36		41		37		34
Latanoprost		40.3		73		34		14		38		41		56		31		43
Tafluprost		6.8		18		3		0		13		5		22		8		1
Travoprost		54.4		71		52		0		59		53		59		41		63
Netarsudil		6.2		15		4		0		10		5		15		8		2
Ripasudil		12		31		7		0		23		9		15		16		9
Timolol + pilocarpine		21		20		28		7		18		22		22		17		24
Timolol + brimodine		70		76		67		68		69		70		70		65		75
Timolol + brinzolamide		40.3		53		47		11		44		39		41		32		46
Timolol + dorzolamide		50.7		71		51		25		74		45		78		48		45
Timolol + bimatoprost		14.6		22		17		0		10		16		23		11		15
Timolol + latanoprost		12		24		11		11		13		12		15		14		10
Timolol + travoprost		26		25		34		11		23		27		33		24		26
Brimodine + brinzolamide		34		53		42		0		36		34		44		30		34
Overall		35		49		37		17		38		35		48		32		35

PCI=per capita income, R=rural, SU=semi-urban, U=urban. ^aDistricts grouped on the basis of PCI: I=high PCI, II=middle PCI, III=low PCI. ^bBrimodine available in three strengths: 0.1%, 0.15%, and 0.2%. ^cBimatoprost available in two strengths: 0.01% and 0.03%

Affordability

The H/L ratio was >2 for eight topical medicines [Table 3], with the lowest for FDC of timolol and latanoprost (1.0069) and the highest for travoprost (4.7187).

Table 3.

Topical glaucoma medicines included in the survey, their available number of brands and pricing

Topical glaucoma medicine								Price (in ₹)				H/L ratioc
Class		Drugs		Brandsa		Packing		MRP range		Medianb
Beta-blockers		Betaxolol		1		5		50		50		---
		Timolol 0.5%		14		5		39-66		60		1.6923
Alpha-agonist		Brimodined		12		5		120–402		217		2.7724
CAI		Brinzolamide		6		5		392–502		437		1.2806
		Dorzolamide		6		5		172–440		283		2.5581
Parasympathomimetic		Pilocarpine 2%		3		5		52–55		53		1.0784
PGA		Bimatoproste		9		2.5–3		200–657		349		3.2850
		Latanoprost 0.5		6		2.5		249–595		515.5		2.3855
		Tafluprost		1		2.5		540		540		---
		Travoprost		14		2.5		160–755		305.5		4.7187
Rho kinase inhibitors		Netarsudil		2		3		495–520		459.5		1.0505
		Ripasudil		1		3		262		262		---
FDCs		Timolol + pilocarpine		1		5		126		126		---
		Timolol + brimodine		22		5		115–424		225		3.8032
		Timolol + brinzolamide		3		5		317–399		339		1.2586
		Timolol + dorzolamide		11		5		195–448		275		2.2974
		Timolol + bimatoprost		3		2.5		349–844		517		1.6324
		Timolol + latanoprost		2		2.5		576–580		578		1.0069
		Timolol + travoprost		6		2.5–3		190–820		288		4.3157
		Brimodine + brinzolamide		7		5		350–580		399		1.4536

CAI=carbonic anhydrase inhibitors, FDCs=fixed drug combinations, H/L ratio=high/low ratio, MRP=maximum retail price, PGA=prostaglandin analogs. ^aNumber of brands available on the day of sampling across retail outlets. ^bMedian price calculated on the maximum retail price (MRP). ^cH/L ratio compares the highest unit price with the lowest unit price. ^dBrimodine available in three strengths: 0.1%, 0.15%, and 2%. ^eBimatoprost available in two strengths: 0.01% and 0.03%

The median price for topical medications for 1-month usage varied between US$ 0.8 (timolol) and 10.9 (brinzolamide), for which an unskilled Indian government worker must spend 15%–203% of their daily wage. Out of 20 medicines included in the survey, the median price of 12 (60%) exceeded the 1-day wage of the lowest paid, unskilled government Indian worker. MPR for topical glaucoma medicine ranged between 0.048 (betaxolol) and 1.156 (tafluprost). MPR was nearly 1 or more than 1 for three topical glaucoma medicines [Table 4].

Table 4.

Median price ratio and average affordability of topical medications for glaucoma

Topical glaucoma medicine		Median price (in USD)				IRP per milliliter (in USD)		MPR		Daily wages spent for 1-month supply (%)b
		Monthlya		Per milliliter
Betaxolol		0.8		0.17		3.49		0.048		0.15 (15)
Timolol		1		0.2		3.28		0.061		0.18 (19)
Brimodine		5.4		1.09		4.13		0.263		1 (101)
Brinzolamide		10.9		2.18		4.45		0.492		2 (203)
Dorzolamide		7		1.41		3.57		0.397		1.3 (131)
Pilocarpine		1.7		0.35		1.12		0.315		0.3 (33)
Bimatoprost		5.8		2.33		2.24		1.040		1 (108)
Latanoprost		8.5		3.43		6.57		0.523		1.6 (159)
Tafluprost		9		3.6		3.11		1.156		1.7 (167)
Travoprost		5		2.04		11.70		0.174		1 (94)
Netarsudil		6.3		2.13		NA				1.2 (118)
Ripasudil		7.2		2.43		NA				1.3 (135)
Timolol + pilocarpine		2.1		0.42		NA				0.4 (39)
Timolol + brimodine		3.7		0.75		4.84		0.155		0.7 (70)
Timolol + brinzolamide		5.6		1.13		4.94		0.229		1 (105)
Timolol + dorzolamide		4.5		0.92		3.94		0.232		0.8 (85)
Timolol + bimatoprost		7.2		2.39		2.44		0.980		1.3 (133)
Timolol + latanoprost		8		2.68		7.80		0.343		1.5 (149)
Timolol + travoprost		4		1.33		11.70		0.114		0.7 (74)
Brimodine + brinzolamide		10		1.99		4.77		0.418		1.9 (185)

IPR=international reference price, MPR=median price ratio. ^aMedian price for 1-month monotherapy in USD (1$ = ₹72) rounded off to the nearest tens calculated for the cost of number of bottles required while using the commercially available bottle packing in both eyes in recommended doses, and one drop is equal to 0.05 ml. ^bCalculated on the basis of the daily wage of lowest paid unskilled worker in Haryana at the time of survey, which was ₹388.42, that is, $ 5.4 (1 USD = ₹72)

Discussion

In this study, the overall availability of topical glaucoma drugs was found to be low, even in urban areas and cities with high PCI. This is far short of the WHO target of 80% availability of affordable essential medicines for noncommunicable diseases in any sector.[25] Some of the topical glaucoma medications are included in the WHO model list of essential medicines (2019) and the National Essential List of Medicines (NLEM) of India (2015).[16,26] There was no significant difference in the availability of drugs between pharmacies located within hospital premises and retail pharmacies located away from these hospitals. This suggests that the prescribing pattern of local ophthalmologists determines the availability of drugs in that place and perhaps in neighboring places as well. Timolol as monotherapy and timolol–brimodine FDC were the most prescribed medications in an observational study on the prescribing pattern of glaucoma medication.[27] In our survey, the availability of timolol (84.2%) and timolol–brimodine FDC (70%) was high and fairly high, respectively, as per WHO/HAI categorization.

We observed that the availability of topical medications was significantly better in urban areas compared to semi-urban areas and rural areas. This could have been influenced by the urban-centric distribution of ophthalmologists. The availability of topical glaucoma medication was very low in rural areas (merely 17%). It means that to refill their supply of drops, rural patients must travel to nearby towns or cities, and this adds to the cost of medication. The availability of topical glaucoma medication was better in districts with higher PCI, but there was a significant difference between middle- and low-PCI districts. This could be due to the comparable availability of eyecare services in these places. The density of ophthalmologists in Haryana is high in districts with high PCI, followed by middle- and low-PCI districts.[28]

The topical medicines were available for free in government-run hospitals, but their availability was dismal at merely 3%. Other than timolol, pilocarpine and latanoprost were available in only one pharmacy. Such a low and limited availability of topical medicines is not sufficient to manage glaucoma. In November 2008, the Government of India launched Pradhan Mantri Bhartiya Janaushadhi Pariyojana (PMBJP) to provide quality generic medicines and surgical equipment at affordable prices to the general public. More than 8000 retail outlets, known as Jan Aushadhi Kendras, were opened till August 2021 under the PMBJP scheme. A total of 11 topical glaucoma medicines are included in the product list, and these are priced much lower than their branded counterparts.[29] The availability of topical glaucoma medicine at these stores was not part of the study design, though one of the authors visited three such stores and found that none of these 11 medicines were available. The operator at one of the stores told the author that drugs are made available based on demand. The unavailability of topical glaucoma medicines at these stores may be due to a lack of demand, which in turn could have resulted from poor awareness about the availability of these drugs in these stores. A study done on patients found that nearly 75% of the participants were unaware of the existence of these stores.[30]

The availability varied widely among the types of glaucoma medication. The availability was affected by the median price of the drug; however, the relationship was found to be weak in our study. MRP for three topical medications, betaxolol, timolol, and pilocarpine, was less than 1 USD (1$ = ₹72). Of these, the availability of timolol and pilocarpine was high and fairly high, respectively, and both are included in NELM of India (2015).[26] The WHO model list of essential medicines (2019) also includes latanoprost 0.05% along with timolol and pilocarpine. In our survey, besides timolol and pilocarpine, four topical medications had fairly high availability: FDC of timolol–brimodine (70%), dorzolamide (63.3%), travoprost (54%), and FDC of timolol–dorzolamide (50.7%). All four medications have an H/L ratio of >2. The higher H/L ratio indicates wide difference in price between the different brands of the same medication, and low-priced brands might have favored the availability of some of the topical medications in this survey. The newly available drugs, like Rho kinase inhibitors, were less commonly available.

MPR of 1 means that the medicine’s price is exactly equal to IRP.[22] MPR for all the topical glaucoma medicines was <4, implying these medicines in India are less expensive compared to international standards. However, a lowest wage, unskilled Indian government worker must spend between 15% and 203% of their daily wage on the monthly supply of topical glaucoma medications. The actual expenditure would be higher if a patient is on more than one type of topical glaucoma medication. Nearly 68% of prescriptions for glaucoma treatment had more than one medication in a study by Sharma et al.[31] In a survey, the average number of drugs per prescription was 2.18 ± 1.68.[26] Moreover, the expenditure on drugs in India is out-of-pocket expenses. Access to medicines in India is severely restricted, as approximately 64% of all health spending is in the form of out-of-pocket spending by households, two-thirds of which goes toward drugs.[32] Therefore, the low accessibility of topical glaucoma medicines in India raises concern for several reasons. First, as low accessibility adversely affects treatment adherence, it might increase the proportion of people becoming blind due to glaucoma.[9,10,11,12] Secondly, the number of glaucoma cases is expected to double in India by 2040, which already accounts for 5.5% of blindness.[1,2]

The study has some limitations. First, affordability was only accessed based on the standard criteria of the WHO/HAI methodology, which ignores other costs involved in the management of glaucoma, including the actual cost of all the medicines on prescription, travel expenses, loss of productivity and income, and so on. Secondly, we chose the PBS prices from Australia as reference prices rather than the IPR recommended by WHO/HAI, which may lead to some inaccuracies in the estimated prices.

Conclusion

The result of this survey provides some information on the availability and affordability of topical glaucoma medicines in one of the Indian states, as per the WHO/HAI standard survey method, and the influence of PCI on the availability of drugs. The accessibility of most of these drugs was found to be low. This suggests that measures directed toward improving the availability of glaucoma medicines must be taken, and the price of these drugs should be brought within the reach of economically weaker sections of the society.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.