Barriers in access to oncology drugs — a global crisis

Manju Sengar: In India, the major impediments to access to anticancer medicines include the lack of universal health-care (UHC) coverage, inconsistent drug pricing, variations in cost between private and public health-care systems owing to limited regulatory oversight, limited quality monitoring of generic medicines after regulatory approval, frequent drug shortages, and delays in approval of novel drugs with proven efficacy. In contrast with countries with UHC models, which spend on average 10% of their GDP on health care, India spends only 2.1% of its GDP for this purpose, which translates into a health-care system that requires substantial out-of-pocket (OOP) expenditure for the management of patients with cancer1. In India, a large number of individuals currently live below the poverty line, a majority of the population seeks care in private health-care systems, and private health insurance coverage is limited. This socioeconomic structure further compromises the affordability of treatment, leading to delays in seeking care and to frequent treatment abandonment1. The challenges have become even more relevant owing to the financial impact of the coronavirus disease 2019 (COVID-19) pandemic. In 2018, the Indian government rolled out one of the largest public health insurance systems, Ayushman Bharat-Pradhan Mantri Jan Arogya Yojana (AB-PMJAY), intending to cover 40% of the population and with a family-coverage cost of ₹ 500,000 (US$ 6,300) per year2; however, limited buy-in from private health-care systems restricts its reach mainly to patients treated in public hospitals.

Notably, the way drug prices are negotiated is one of the major factors contributing to inequitable access. Pricing remains a concern even after the National Pharmaceutical Pricing Authority set a ceiling price for medicines listed in the National List of Essential Medicines of India3, 4. Owing to their high cost, novel drugs for which generic versions are not yet available remain out of reach for a majority of the eligible population. A few years ago, the WHO Essential Medicines Cancer Working Group conducted a survey of oncologists worldwide to assess which medicines are considered a high priority and the extent of their availability5. A secondary analysis of the responses from those based in India highlighted issues associated with access to essential medicines6. Only a minority of Indian oncologists (3%) reported universal access to essential medicines, and the risk of substantial OOP expenditure for each medicine listed ranged between 19% and 58%. This risk and that of catastrophic expenditure (defined as ≥40% of total post-subsistence income) were higher in private health-care systems than in public hospitals5, 6. The downside of price control is that frequent drug shortages occur because, in many instances, manufacturers are unable to sustain production owing to the rising costs of raw materials and product distribution. This issue largely affects public health-care systems as suggested by the findings of a study evaluating access in New Delhi to medicines commonly used to treat paediatric cancers and considered essential; in this study, 43% and 70% of these medicines were available in pharmacies from public and private hospitals, respectively7. In addition, price control leads to several novel drugs ‘exiting’ the country owing to limited financial gains for the manufacturer. Finally, owing to price control orders, investment in drug development focused on locally prevalent cancers is low because of a perception of poor financial returns. The time taken to bring a novel and effective therapeutic agent to market in India is remarkably long owing to its perception as a poor business market and low affordability coupled with a challenging regulatory situation8.

Quality is another aspect that needs attention in an assessment of access to drugs. The regulatory approval of generic drugs is based on bioavailability data, without a requirement for clinical efficacy data. Indeed, generics do not undergo stringent, regularly scheduled quality-control monitoring. The risk of procuring low-quality drugs is greater in public health-care systems, in which the procurement process mandates the selection of generic drugs with the lowest price.

Mastura Md Yusof: In Malaysia, despite progressing towards achieving UHC coverage through a mixed public–private health-care delivery system, cancer survival rates remain below the average rate for middle-income countries9. Earlier cancer diagnosis to enable more efficient treatment, improved patient outcomes and reduced health-care costs are not yet fully achieved.

Taking breast cancer as an example, approximately 63.7% of Malaysian women with breast cancer present with stage III–IV breast disease9, which contributes in part to poor overall survival outcomes10. The ASEAN Costs in Oncology (ACTION) study, conducted in 2015 to assess the economic burden of cancer in Southeast Asia, found that cancer stage accounted for 80–98% of the risk of catastrophic expenditure (defined as an OOP medical expenditure exceeding 30% of annual household income) across six East Asian countries with comparable data available. Late-stage presentation was found to be one of three factors that increases the risk of adverse economic outcomes and death in Malaysia11.

Without good UHC coverage, the provision of high-quality and affordable cancer care for the whole population remains challenging. In addition to the number of oncology specialists being low, the distribution of oncology facilities and specialists within the country is also imbalanced. Nevertheless, the fact that a centre delivers a high volume of care does not necessarily equate to provision of high-quality care. A modelling study revealed that 50% of breast cancer-related deaths would be avoidable if all Malaysian patients with this cancer type had access to care in leading national cancer centres. Moreover, 50% of this mortality excess was attributed to a lack of access to optimum treatment and the other 50% to late presentation at first diagnosis12.

Malaysia spent only 4.3% of its GDP on health care in 2019 (ref.13) and the allocation for cancer care will change after the COVID-19 pandemic. The impact of this pandemic on the country’s health-care system has resulted in increased costs and disrupted or delayed cancer screening as well as an urgent need to clear a huge backlog of surgical and medical procedures.

Undoubtedly, disparities in cancer outcomes exist between affluent individuals and those of a lower socioeconomic status or without health insurance. This gap will widen as cancer care becomes more challenging and expensive. Malaysia’s Ministry of Health provides subsidized treatment to approximately 65% of the population, which includes civil servants and individuals without health insurance, while private health care is delivered via for-profit medical facilities and is funded by a combination of OOP payments, private health insurance and employer-sponsored health insurance14.

The National Health and Morbidity Survey (NHMS) of Malaysian adults in 2019 reported that only 22% of Malaysians have personal health insurance and 45.5% (including about 71% of the poorest 20%) do not have any means of supplementary financial coverage for medical treatment other than the existing tax-funded health-care coverage provided by the government15.

The use of novel drugs is severely limited in public hospitals and the waiting times to receive treatments, if approved, can be months. Although more affluent or health-insured patients are able to access innovative therapies at private centres, chaos and the threat of unaffordability still loom ahead for them if the prices of anticancer medicines keep rising. Furthermore, some archaic health insurance policies provide low pay-outs or coverage and might entirely refuse to reimburse outpatient oral formulations.

Many patients experience hardships in life and/or have poor health literacy that make it difficult for them to obtain and understand information on available care and to navigate health-care services in a way that enables sound decision-making and access to care. The NHMS from 2019 identified 35.1% of Malaysian adults as having a low level of health literacy, 28% in terms of managing medical issues and 32.3% in terms of disease prevention15. The increasing number of cancer diagnoses and the effect of the COVID-19 pandemic in exacerbating delayed presentation, detection and diagnosis further exert tremendous physical, emotional and financial strain on individuals, communities and the national health-care system. Late presentation necessitates more complex care by a multidisciplinary team, yet coordination of care can be non-existent or fractured owing to a lack of speciality services, human resources and/or an efficient patient navigation system.

Fidel Rubagumya: In Rwanda, as well as in East Africa and globally, the main barrier to drug access for patients with cancer is the high cost of these drugs16. However, the key difference between low-income and middle-income countries (LMICs) and high-income countries (HICs) is affordability17. Patients in LMICs struggle to afford well-established cytotoxic drugs, some of which have a substantial magnitude of clinical benefit (for example, cisplatin). By contrast, financial difficulties for those in HICs tend to be restricted to the newest targeted therapies or immunotherapies. Therefore, the high level of poverty in Rwanda — and other LMICs — exacerbates the lack of access to these drugs and leads to economic catastrophe.

As of 2018–2019, 41% of the population of countries in sub-Saharan Africa lived below the national poverty line18. This percentage translates into more than 500 million people who cannot afford cancer care, including anticancer drugs. Therefore, a large proportion of individuals who develop cancer will either rely on support from their government, sell their possessions to afford cancer treatment or, in most cases, die without treatment.

The unaffordability of cancer drugs cannot be considered in isolation; the complexity of cancer care compounds it. Let us consider stage III breast cancer as an example: after the cost of diagnostics, treatment will consist of surgery, radiotherapy and chemotherapy, with the latter two taking up to 12 weeks in total. The direct cost of the whole treatment package and other supportive care is unattainable for many Rwandans and Africans. Additionally, given the scarcity of cancer centres in Rwanda and many African countries, patients often have to travel long distances for treatment, thus also incurring transport and accommodation expenses.

Owing to the increasing cancer burden in Rwanda and Africa and the high cost of care, government agencies are reluctant to cover cancer treatment through national health insurance schemes. The lack of UHC coverage for cancer care in most African countries exacerbates the situation as patients usually incur OOP expenses and eventually have to sell possessions to afford care, including anticancer drugs. In Rwanda, the community-based health insurance scheme is a form of UHC that covers >90% of the population and involves patient co-payments of ~10% of the medical bill19. This scheme enables access to some oncology treatments, including surgery and radiotherapy but not chemotherapy.

Piotr Rutkowski: In Poland, expenditure on health care is among the lowest in the EU (<6% of the GDP), and expenditure on cancer care accounts for <7% of the overall health-care budget (versus an average of 8% in the other EU countries). About 1 million individuals in the current population of Poland have been diagnosed with and/or cured of cancer. Around 100,000 Polish citizens die from cancer every year, and this number has been predicted to increase by 28% in the next 10 years20. Most patients with cancer in Poland are treated at large regional comprehensive cancer centres. In Poland, health insurance is obligatory and public only, and therefore a drug reimbursement system is legitimated constitutionally to provide equitable access to health-care services for all citizens. Anticancer medicines are reimbursed after formal procedures, including mandatory assessment by a health technology agency21. All well-established systemic therapies are fully available and reimbursed in Poland for the whole range of registered cancer indications.

In Poland, novel anticancer drugs are covered within a specific framework referred to as drug programmes, which are initiated by pharmaceutical companies. This legal framework regulates the delivery of treatment according to specific rules and in designated centres, according to a mandate from the National Health Fund. Drug programmes have a key role in patient access to free-of-charge contemporary expensive systemic therapies for cancer. A downside of drug programmes is that not all such drugs are reimbursed and patients must meet strict criteria included in the programme description to be eligible for treatment22.

This framework is unique because it enables reimbursement of expensive novel therapies for cancer treatment under programmes that are time-limited (they are reassessed every 2 years) and involve lengthy bureaucratic procedures21. The final decision to reimburse a drug within the programme is based on the recommendation of the Polish Agency for Health Technology Assessment (HTA) and Tariff System, price negotiations between the drug manufacturer and the Economic Commission of the Ministry of Health, and the Ministry of Health. As a result, the average time between market authorization and patient access was one of the longest across the EU23, although it has decreased substantially in the past 2 years. The final financial decision is usually based on confidential discounts, which serve a double purpose: they diminish cost to the payer and are a countermeasure against external reference pricing (ERP). Moreover, the only requirement for patients is complete adherence to a drug programme, which tend to have strict inclusion and exclusion criteria24, including timely participation in follow-up examinations.

Other limitations include organizational issues related to poor coordination of the diagnostic–therapeutic process for individual patients with cancer and insufficient deployment of molecularly based diagnostic procedures, which can limit access to novel targeted therapies. Finally, an additional situation worth mentioning is the unexpected increase in the number of new patients with cancer in Poland owing to the arrival of war refugees from Ukraine. These individuals are currently authorized to receive the same health care as the citizens of Poland, but their presence might increase the waiting lists for starting therapies owing to the limited availability of medical staff and health expenditure on cancer medicines.

Carlos Barrios: In Brazil and across all of Latin America, a number of different barriers have been identified that hamper access to optimal care; other LMICs have reported similar obstacles25, 26. Most countries in the region spend a very small proportion of their GDP on health care. Brazil reports a global health expenditure of 9% of its GDP, although, of note, only 4% is strictly provided by government expenditure (to cover 75% of the population under the public health-care system) and the other 5% represents investments from the 25% of Brazilians with private health insurance25. Unequitable or non-existent access to new medicines is one of the main reasons underlying the profound and increasing worldwide discrepancies that currently compromise the outcomes of patients with cancer. Optimal cancer care is also seriously affected by disparities in access to new technologies and in the quality of delivered services. Patients living in LMICs do not have access to more than half of the drugs listed on the WHO Essential Medicines List (EML)5.

The high cost of new medications is certainly the major feature limiting access to optimal care, which in turn contributes to the considerable discrepancies observed in the outcomes of patients with cancer worldwide. In many countries, and more frequently in LMICs, access to some drugs in the EML is associated with catastrophic expenditure5. Although we should acknowledge that drug development is a risky pursuit with increasing multifactorial associated costs, the current non-transparent drug-pricing practices need a global and more detailed institutional discussion27.

In Latin America, access to optimal cancer care is a multidimensional and complex situation. The existence of fragmented health-care systems with incomplete coverage of the population and deficient health-care infrastructures is probably a good starting point to explain care disparities. Unequal geographical distribution of health-care units and workforce are major contributors to the problem, leading to delays in diagnosis, late-stage presentations and poor outcomes.

In many countries, the lack of specific National Cancer Control Programmes results in a reactive and unplanned approach to health-care provision, ultimately leading to suboptimal resource utilization and higher expenditure25. Importantly, the lack of epidemiological data, such as information on the number of cancer diagnoses and stage at presentation, resource utilization data and economic evaluations of resource allocation hinder a more rational approach to financial planning.

Advances in the development of targeted therapies imply the delivery of treatment to appropriately identified populations. Therefore, this evolving personalized approach to optimal cancer care requires the development of particular and challenging diagnostic capabilities. The lack of molecular pathology laboratories with well-established quality assurance programmes is an unmet need that compromises access to new therapies in LMICs.

Non-transparent, complex and slow regulatory processes are another major hurdle compromising access to new drugs. In addition, incomprehensibly long approval times for clinical trials add to a bureaucratic burden that should be addressed with a well-intentioned reform of the regulatory infrastructure28.

The COVID-19 pandemic is an important added challenge. Although the pandemic is placing substantial strain on all health-care systems globally, it has deeply affected the most fragile infrastructures in LMICs. Long-lasting consequences should be expected as the resources drained to manage the pandemic will certainly compromise the much-needed investment in cancer care. Furthermore, we should expect an increase in the proportion of cancers diagnosed at more advanced stages in the next few years owing to a decrease in screening procedures during the pandemic. This shift will increase expenses and add further pressure on already strained health-care systems.

In summary, when discussing access to optimal cancer care in Latin America, we must be cognizant of the many different stakeholders with vested interests in the problem. In my view, the most important barrier is that most players are either comfortable with the current situation or have not been competent enough to take real action. Lack of effective leadership is probably a major need and the main barrier to overcome29.

Gilberto de Lima Lopes: In the USA and other HICs, access to cancer medicines seems easier than in LMICs but is not without barriers and challenges. Although the lack of health insurance coverage has decreased since the enactment of the Affordable Care Act (colloquially known as Obama Care) in 2010, 31.6 million people (9.7% of the population) were uninsured in 2020 — a number roughly equivalent to the population of Peru or Malaysia30. Cancer care is expensive, however, and even patients who have insurance coverage often suffer from financial toxicity, which is defined as the harmful effects of these high costs (especially OOP payments, in the form of co-payments, deductibles and co-insurance) on an individual’s quality of life (QOL). Given that nearly 40% of the population receives health insurance as part of their employment benefits, medical issues are responsible for two-thirds of personal bankruptcies in the USA31.

The economic consequences of cancer treatment on patients and their caregivers substantially influence access to care in the USA. Patients without insurance coverage are less likely to seek care at early stages of their disease and, when they are able to do so, might not be able to afford certain treatments that are too expensive. Even for insured patients, plans that require substantial co-payments decrease access to timely and comprehensive cancer care and provide inadequate financial protection from medical expenditures. When an individual with cancer undergoes treatment, they face an increasing burden of direct medical and surgical costs concurrent with income constraints as well as indirect costs to them and their caregivers. Patients usually cope by borrowing money, using their savings or selling assets, resulting in increased stress and reduced QOL32.

The cost of new oncology medications is higher in the USA than in other HICs. A study with results published in 2021 (ref.33) revealed that, for a panel of 65 anticancer drugs, the median monthly costs per patient were US$ 14,580 in the USA, US$ 5,888 in Germany, US$ 6,593 in Switzerland and US$ 6,867 in England. This imbalance reflects the inability of the biggest payer in the USA, the Center for Medicare and Medicaid Services, to negotiate prices, in sharp contrast with several different schemes active in European countries and other HICs.

The example of osimertinib, a drug with proven activity approved for the treatment of EGFR-mutated non-small-cell lung cancer, is illustrative. Osimertinib provides meaningful improvements in progression-free survival and overall survival with fewer adverse events than earlier-generation EGFR tyrosine kinase inhibitors and cytotoxic agents. However, with an average wholesale price of US$ 18,000 for a month of treatment, osimertinib is not cost effective, and co-payments are prohibitive for many patients who do not have adequate insurance coverage34. Finally, non-cost barriers, such as the need for prior authorization, are worth mentioning. Through this process, health insurance companies review which proposed medical treatments are deemed necessary and standard, often resulting in substantial delays in the delivery of appropriate treatment.

留言 (0)

沒有登入
gif