Price Variation Among Registered Brands of Anti-Cancer Medicines Available in Pakistan

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Abstract

The current study aims to explore the number of registered anticancer medicine in Pakistan and the price variation of these single-ingredient medicines. A data-based study was conducted between March 2021 and May 2021. Pharmaguide (Mobile Version 2020 – 2021), Druginfosys.com and Medicialstore.com.pk were used to derive the price of anticancer medications sold in Pakistan. The difference in minimum and maximum costs of each formulation was calculated, and the price variations in 81 anticancer medicines belonging to 14 different categories were analysed.  There were 115 formulations registered for these 81 anticancer medications. Estimations in price difference revealed that topotecan (4mg / ml) had the highest price variation, while the lowest price variation of 4.01% was observed for abiraterone acetate (250mg). Price variations among different anti-cancer brands marketed in Pakistan are noticeable and substantial, therefore necessitating action from the drug regulatory authority of Pakistan, not only to gain awareness on this issue, but also to set pricing thresholds to make the prices of anti-cancer medications more affordable. In addition, external reference pricing and reimbursement programs partially sponsored by the government or insurance companies can be a possible way to control the price variation of anti-cancer drugs.

Introduction

Cancer is the leading cause of mortality and morbidity. Overall, carcinoma of the breast (11.7%), lung (11.4%), prostate (7.3%), stomach (5.6%) and other types of cancer (53.9%) are observed among the majority of cancer patients in both developed and developing countries [1]. Meanwhile, haematological cancers (leukaemia, lymphoma, lymphoma and multiple myeloma) contributed 10% to the cancer burden [2] and according to recently published statistics, leukaemia was found to be the 15th most commonly diagnosed cancer [3].

In the year 2020, there had been about 38 million deaths worldwide attributed to non-communicable diseases (NCDs), of which, about 10.0 million deaths occurred due to cancer. It is estimated that by 2040, approximately 28.4 million new cases of cancer will be diagnosed, with an estimated 47.0% increase in cases as compared to 2020 [4].  Delayed diagnosis as well as impeded access and affordability to healthcare facilities substantially contribute to mortality among the cancer patients. Moreover, genetic factors and lifestyle habits could be potential contributing factors towards new cases of cancer [5].

Furthermore, another important issue that cannot be ignored is the increasing treatment costs, leading to a consequent increase in spending by the governments in order to acquire newly developed treatments for the affected population [6].

In Pakistan, the 5th most populated nation globally [7], cancer has resulted in 10.0 million deaths in 2020 [4]. In addition, it has been reported by GLOBOCAN that in 2020, about 2million cases of cancer were diagnosed in Pakistan (90373females and 88015males), with breast cancer (14.5%) being the most prevalent cancer in Pakistan followed by lip and oral cavity cancer (9.5%), lung cancer (5.9%), cancer of the oesophagus (5.7%), and colorectal cancer (4.8%), with other types of cancer making up about 59.6% of cancer cases [8]. However, the actual number of cases could be more than these as-reported figures due to early mortalities and negligence in diagnosis of patients by health care providers [9]. Moreover, there is also lack of a national registry to date in order to timely document and report newly diagnosed cancer cases as well as the mortalities associated with them.

The recent development of new anticancer medicines, despite contributing to an increase in range of available medicines, causes an increase in the average cost of cancer medicines per month by approximately USD 100,000 from about USD 45,00 in 2014    to as much as USD300,000in 2015 (whereby 1USD is equivalent to 152.50PKR as of 20th April 2021) [10][11]. In the context of the Pakistani healthcare setting, the availability of new drugs might put an additional burden on the health spending of the government, which could translate to an increase in expenses paid by patients. These issues, of drugs, would cause sufficient problems, not only by aggravating the disease condition of patients, but also by being detrimental to the affordability of these treatments among patients [12]. The price of anticancer medicines is a great cause of worry for Pakistani patients. In fact, it is believed that the income of an average family would not be able to afford treatment considering the fact that 45.5% of the population live below the poverty line [13], an issue that persists despite constant endeavours by the National Health Ministry Services. In addition, most of these newly developed anticancer medications would remain under patent protection for a specific duration, potentially limiting the availability of their prospective lower-costing generic counterparts which could mitigate cost issues. In public and private sectors, the availability of generic medicines is found to be as low as 15% and 31% respectively [14]. In fact, such figures depicting medication availability can be extrapolated even beyond Pakistan, as evident from a study conducted in 49 European countries [15]. The current study aims to compare the prices of registered anticancer medicine brands in Pakistan and the price variation in their respective single-ingredient medicines. A large number of anticancer medicines, including those manufactured in Pakistan as well as those that are imported, are sold under different brand names by their respective national or multinational pharmaceutical firms [16]. Therefore, a comparison on the prices and price variations of various brands is necessary, particularly so for anticancer medicines. It is believed that data from this study would prove to be useful to prescribers, customers, and regulatory authorities in order to formulate and enforce more stringent policies aimed towards improving the availability and accessibility to anticancer medicines.

Methods

A data-based study was conducted from 1st March 2021 to 31st May 2021. In situations where a comparison has to be made between two dosage forms (with the same active component) produced by two different manufacturers, comparisons are made on the basis of their active ingredients, specifically as they appear in their respective salt forms(whereby each salt of an active alkylating agents, anti-metabolites, vincaalkoids, taxanes, topoisomerase 1 inhibitor, miscellaneous agents, hormonal agents, biological agents, anti-cancer antibiotics, cytotoxic agents, aromatase inhibitor, anti-androgen, 5-α-reductase and histone deacetylase inhibitor are considered separately) .

Study Design

Pharmaguide (Mobile Version 2020 – 2021), Druginfosys.com and Medicialstore.com.pk and other relevant sources of pricing notifications from the drug regulatory authority of Pakistan were used to derive the prices of anticancer medications sold locally in Pakistan. Pharmaguide is a reliable source of information related to the cost and availability of medications, serving as such for the past thirty years with consistent updates every three months. Costs in Pharmaguide are presented as actual retail (consumer) costs as it is depicted on packs.  Dosage forms containing a combination of active ingredients (either drug or drug salts) of different strengths, as they are manufactured by one or multiple different manufactures, were excluded from the study.

Price Estimation

Information concerning the quantity of registered brands, formulations, and manufacturer were collected, and information regarding the price of all enclosed medicine manufactured by completely different manufacturers, with respect to the varying strengths of medications, were identified and gathered into an MS excel sheet. In situations where comparisons are made between items of different pack sizes, the number of pills in each pack is used to compare their costs. The difference in minimum and maximum costs of each formulation was calculated, whereby the value does not take into account the manufacturer (that is, whether it was local or multinational) of the more costly brands [17]. Furthermore, the cost of medicines with only a single brand is calculated by obtaining the difference between the maximum price of per unit tablet and the minimum cost of the per unit tablet, with 15% profit compared to the actual price [18]. To elaborate further on that point, the medicines had been sold by retail pharmacies with 15% profit to their customers. Therefore, the retail price was considered to be the maximum price and the trade price (which is 15% less than the retail price) is considered to be the minimum price. Medicines were classified based on their pharmacological categories; alkylating agents, anti-metabolites, vincaalkolides, taxanes, topoisomerase 1 inhibitor, hormonal agents, targeted therapy/biological agents, anti-cancer antibiotics, cytotoxic agents, aromatase inhibitor agents, anti-androgen agents, 5-α –reductase agents, miscellaneous agents, and histone deacetylase inhibitor agents.

Data Analysis

 All brands of the varying salts of anticancer medicines registered in the country were noted in conjunction with the retail value per unit pill. Then, the specific details pertaining to the type of drug (with specification of its salt species) are tabulated, while including a number of important factors such as the number of brands associated with the drug, the corresponding doses of the drug and their contribution, by percentage, within their drug class as well as with respect to their brands. The brands of each drug with the least and most value for their price were identified. Finally, with the consideration of all the prices of anticancer drugs (inclusive of all brands) that had been gathered in the datasheet, the difference between the highest and lowest value was calculated, from which, the value of price variation was calculated as follows [19]:

Result

A total of 81 drugs were registered with 115 different strengths (mg). In total 560 brands for 14 different classes of anticancer medications were identified. Of the many classes of anticancer medications studied in this research, the highest contribution is seen in hormonal agents with a total contribution of 20.53% (115 / 560), while anti-metabolites were found to be second, account for 15.35% (86 / 560). The details are described in Table I.

The results show that the letrozole (2.5mg) tablets is ranked top among the retailed medications across 19 registered brands, making up 3.39% (19 / 560) of the total registered brands of anticancer drugs, followed by ibandronic acid (150mg) tablets at 2.85% (16 / 560) and p Prednisolone(5mg) tablets at 2.32% (13/560). Tamoxifen (10mg) tablets follow suit with a share of 2.14% (12 / 560) among total registered brands of anticancer medication. The percentage contribution of all the anticancer medications within their classes, with respect to their registered anti-cancer brands, are presented in Table II.

Table I. Contribution of anticancer in total registered brands

With relation to the price variations within the alkylating agents group, the maximum cost variation was 159.61%  (with price per tablet ranging from PKR 1363 to PKR 525), as seen in ifosfamide (1g), while the minimum cost variation was 8.0% (with a price per tablet of PKR 540 to PKR 500), as seen in decarbazine 200mg. However, among the anti-metabolites, 5-fluurouracil (250mg / mL) injections demonstrated the highest price variation, that is, 1520% (with a price per tablet of PKR 810 to PKR 50), and the minimum cost variation was 17.71% as seen in 6-mercaptopurine (50mg) tablets. Among Vinca alkaloids, the highest price variation was noted in vinblastine (10mg / ml) injections, that is, 48.75% (price per tablet of PKR 595 to PKR 400), while vinorelbine 10mg/ml demonstrated the minimum price variation of the group at 17.64%.  

In the cytotoxic agents’ group, the maximum price variation is 658.82%, as shown by etoposide (5mg) tablets, while the minimum price variation within in the group was 20%, as seen for etoposide (20mg) tablets. Finasteride was the only drug of the 5-α-reductase inhibitors that was available in three different strengths, the maximum and minimum price variation was 47.61% and 37.71% for its 1mg and 5mg strengths respectively. Meanwhile, flutamide (250mg) and (calutamide) 50mg, two drugs among the anti-androgen agents, the maximum and minimum price variations was noted to be 40.84% and 547.69% respectively. Letrozole and anastrazole were the two drugs of the aromatase inhibitor class, with maximum and minimum price variations of 700 % and 39.18% for the 2.5mg and 1mg strengths of different drugs respectively. Of the hormonal agents, the maximum price variation is 1674.54% (price per tablet of PKR 6832 to PKR 385) as seen for ibandronic acid 150mg, while the minimum price variation is 4.01%, as shown by abiraterone acetate (250mg). As for taxanes, docetaxel 20mg / ml showed a maximum price variation of 386.66%, while the minimum price variation is 4.66% as seen for paclitaxel (300mg / mL)

Table II. Contribution of registered brands in different classes and individual anticancer

Among miscellaneous agents, different doses of cisplatin consisted of the most expensive and cheap brands, specifically, the 50mg / ml and 10mg / 20ml variations demonstrated price difference of 646.7% and 8 % price respectively. Among anti-cancer antibiotics, highest price difference was found in doxorubicin (20mg / vial) injections (7092.98%), while the smallest price difference was 5.36% as seen in epirubicin HCl 50mg/vials. In the group of biological agents, erlotinib 150mg showed the maximum price variation of 13418.29%, while the minimum price variation was 5.32% as seen in imatinib 100mg. Among topoisomerase 1 inhibitors, the highest price variation of 19912.25% was found in Topotecan 4mg / ml, while the smallest variation was 5.26% as seen in irinotecan 100mg / 5m.l Panobinostat was the only histone deacetylase inhibitor drug available in two different strengths (20mg and 15mg). The data on the percentage of price variation among different brands is summarized in Table III.

Table III. Percentage Variations among different brands

Since panobinostatwas available in single brand, the price variation was calculated using the retail price as the maximum price per tablet and the trade price (which was 15% less than the actual retail price) as the minimum price per tablet. This gives a price variation of 17.64%. Similarly, all the drugs of different classes of anti-cancer which were available in single brands had the same price difference of 17.64% [10]. The data on the percentage price variation among different brands with 15% profit is summarized in Table IV.

Table IV. Percentage Variations among different brands with 15% Profit

Discussion

To date, this is perhaps the first study aimed towards evaluating the price variation of anticancer drugs in Pakistan. The present study aims to compare the cost of different brands of anticancer drugs registered in Pakistan. Our findings have shown that there is large variation in the cost of different brands; price variations of 4.01% to 19,912.25% have been observed across 115 different formulations of anticancer drugs. In fact, nine formulations demonstrated prices that varied from 4.01% to 20%, while seven formulations showed price variations that exceed 30%. Furthermore, the price of nine formulations varied from 500% to as high as 10,000%. Topotecan 4mg / ml had the highest price variation 19,912.25% and the lowest price variation 4.01% was observed for abiraterone acetate (250mg).

The result of this research seems to strongly suggest that, in Pakistan, drugs are registered in different brands and formulations with a huge variations in price. The pricing of drugs in Pakistan is regulated under the Drug Regulatory Authority of Pakistan (DRAP) which works under the Federal Government. As of yet, there exists no clear price calculation formula in the Drug Act, 1976 [20]. 

The price of cancer drugs and care can be improved through the establishment of policies and intervention aimed towards lowering the prices of the drugs [11]. It should be noted that availability and affordability are considered to be key requirements for the ubiquitous access of medicines, even more so as far as the availability and affordability of anticancer drugs are concerned, which are drugs essential for saving lives.

One of the most important, yet difficult, challenges faced towards equity in healthcare is the price of medicine. The health budget of smaller developing countries such as Pakistan is greatly affected by their buying power for such medications. Numerically, it is expected that drug and drug-related expenditures can be anywhere between 50 – 90% of the total, non-personnel costs. Due to lack of knowledge on the cost of drug as well as drug quality and non-availability, it is difficult for physicians to decide on and to prescribe the most economical treatment [21]. Manufacturing companies instate a high cost of anti-cancer medications which are presented by sales representatives [22].

A study conducted by Volger S et al. showed that the costs of the anti-cancer drugs in higher income countries (namely, 16 European countries as well as Australia and New Zealand) vary widely from 28 to 388%. Meanwhile, the cost of the different anti-cancer medicines was found to be low in Greece and high in Sweden, Switzerland and Germany [23].  In a separate study by S. Salmasi., whereby the price of cancer drugs in high-, middle- and low-income countries are surveyed (including 10 Asian countries, South-East Asian countries, as well as countries in Western Pacific and Eastern Mediterranean regions), it is found that the costs of the anti-cancer medicines were low in Taiwan, while highest prices was found in Oman [6]. Furthermore, a study by Tadesse and Fang found that in the public and private sectors of Ethiopia, the lowest price of generic anti-cancer drugs were sold at prices between 1.29 and 2.62 times the international reference price [24]. As for our current study, a large price variation in between different anticancer drugs can be attributed to many factors, such as differences in the cost of production, prescribing of patented brands instead of generic brands, and the lack of subsidy schemes.

In the developed countries like Australia, the cost of the anti-

cancer treatment is funded through different Health

Technology Assessment (HTA) reimbursement programmes such as the Pharmaceutical Benefit Scheme (PBS), the National Immunization Program (NIP) and the Medicare Benefit Schedule (MBS), as well as through several other means involving the public and private sectors [25]. The aim of these programmes is to improve the health care interventions through use of money from taxpayers, thus and lowering the cost of, and increase the quality and efficacy of, treatment with anticancer drugs [26]. In addition to all the government is spendings is an extra 6.7 million dollars to assist all Australian cancer patients to support and improve the results of cancer treatments [27]. In contrast, the government of Pakistan provides a limited amount free medications exclusively for the public health sector. Furthermore, limited funding for serious health issues like cardiac surgery, dialysis, renal transplant, and cancer is a prominent issue. The Punjab CML Project, for example, used to provided PKR 13 billion (approximately $85,274,371) for the free cancer treatment until 2017, before it was forced to close down due to lack of funding from the government, subsequently causing pharmaceutical companies to discontinue the provision of free medicines. Although the project had been re-initiated on June 2020, the provision of free medicines were again halted as of the 28th of February,2021 due to the delay in the signing process of the memorandum of understanding (MOU) [28]. To ascertain the availability and affordability of medicines, proper policies, external reference pricing, promotion of generics and reimbursement programmes must be developed for medicine pricing [29]. The first step in pursuit of that goal would involve quantitatively measuring and properly understanding the cost of medicines and the rationale behind their use. Therefore, considering the direness of the situation, the government, health care providers, and the general public should make strenuous efforts towards convincing the pharmaceutical manufacturing companies to ensure that medications are affordable to the general public.

Conclusion

Our study shows that there is a huge price variation among different brands of anticancer drugs marketed in Pakistan.  The highest price variation was observed for topotecan (4mg / ml). In light of such issues, there is deemed necessary for the government to set appropriate pricing systems in order to mitigate cancer-related mortality. External reference pricing, reimbursement programmes, effective strategies to implement policies, and creating monopoly rules for the exemption of tax would stabilise the price variations of anticancer drugs, whilst providing low budget medicines and treatment options for the relief of patients.

Conflict of Interest

The authors have no conflicts of interest to declare. This research did not receive any specific grant from funding agencies in public, commercial or not-for-profit sectors.

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Please cite this article as:

Amal K Sulaiman, Fiza Ayub, Imtiaz Rabbani, Kah Seng Lee, Khang Wen Goh, Muhammad Faisal Nadeem and Tahir Mehmood Khan, (2022) Price Variation Among Registered Brands of Anti-Cancer Medicines Available in Pakistan: 42-56. Malaysian Journal of Pharmacy (MJP). https://mjpharm.org/price-variation-among-registered-brands-of-anti-cancer-medicines-available-in-pakistan/

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