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Access to Medicines for Improving Access to Safe Anesthetic Care

Nickerson, Jason, W., RRT, PhD*,†; Chikumba, Edson, MMed, FCA‡,§

doi: 10.1213/ANE.0000000000002746
The Open Mind: The Open Mind

From the *Bruyère Research Institute, Ottawa, Ontario, Canada

Centre for Health Law, Policy and Ethics, Faculty of Law, University of Ottawa, Ontario, Canada

Department of Anaesthesia and Critical Care Medicine, Parirenyatwa Hospital, Harare, Zimbabwe

§College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.

Accepted for publication November 10, 2017.

Funding: None.

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Jason W. Nickerson, RRT, PhD, Bruyère Research Institute, 85 Primrose Ave, Room 308-B, Ottawa, Ontario, K1R 6M1, Canada. Address e-mail to jason.nickerson@uottawa.ca.

Beginning in the 1970s, the concept of essential medicines as a central part of an efficient and equitable health system became the focus of considerable advocacy, research, and policy reforms. The development of essential medicine lists, including national lists and, internationally, the World Health Organization’s (WHO) Model List of Essential Medicines,1 creates a framework of minimum standards for medicines that need to be available in health systems to meet the basic health needs of populations. Indeed, medicines and other health products are one of the health system building blocks, along with the health workforce, health service delivery, financing, leadership, and information systems, that are essential for building equitable and responsive health systems as identified by the WHO.2 More obviously, the practice of anesthesia is inextricably linked to the availability of reliable supplies of high-quality medicines; without anesthetic medicines, the safe provision of anesthetic care is virtually impossible. The impediments to accessing safe, affordable, and reliable medicines, however, are numerous, including legislative and regulatory barriers, market dynamics, supply chains, pharmaceutical companies’ priorities, and others.

Despite the centrality of medicines (and the other building blocks) in the delivery of health services, many health programs focused on capacity building in low- and middle-income countries (LMICs) do not adequately address the connections and relationships between the health system building blocks, particularly related to access to medicines.3 A trained health workforce with no medicines, little financial stability, or nowhere to deliver clinical care will be severely limited in their impact. Surgery and anesthesia are, regrettably, not exceptions to this imbalance in priorities, particularly as they relate to health programming in LMICs.4 Indeed, while much work has been done to estimate and reduce the burden of surgical diseases, a global understanding of the barriers to accessing the medicines that are necessary to sustain gains that are made in global surgical care is surprisingly limited.

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GENERAL OVERVIEW

Here, we present an overview of some of the challenges and barriers that patients, providers, and health systems face in improving access to essential anesthetic medicines. We focus on the problems rather than the solutions simply because, in the absence of understanding the problems, it is not possible to propose solutions. Furthermore, we present a global assessment of possible and probable barriers to accessing anesthetic medicines. The reality of medicines and other health technologies is that barriers and facilitators of their availability are nuanced to specific contexts and subject to influences that may or may not be universally present. Economic factors may play an oversized role in some contexts, while regulatory barriers dominate in others. The salient point is that the continuous availability of high-quality anesthetic medicines is subject to many factors, most of which have gone unaddressed by surgery and anesthesia development programs in LMICs, and are poorly understood globally, including in high-income countries, which are also far from immune from things like drug shortages.5

Failing to understand the dynamics of medicines specific to anesthesia clearly comes at a detriment to safe perioperative care for numerous reasons, most notably being that the absence of only a handful of essential medicines such as ketamine, propofol, or thiopentone can cripple a health system’s ability to deliver safe anesthetic care. As the importance of safe surgical care gains traction among policymakers internationally and becomes integrated into universal health coverage, addressing barriers to accessing the medicines essential for delivering safe anesthesia is a vital component in addressing the global burden of unmet surgical needs.6

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POSSIBLE ROLE OF ACTIVISTS

Decades of activism by patients, local health actors, and international organizations to improve access to medicines in other disease areas (eg, tuberculosis, malaria, and human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS)) and therapeutic classes have resulted in significant policy reforms and programming, as well as a better understanding of the global pharmaceutical landscape and market dynamics for them. These improvements have not been negligible: millions of people today are on antiretroviral medicines that prolong and improve lives and yet did not exist 20 years ago. Activism by patients, civil society, and local and international health actors around access to medicines, specifically, has fostered a productive response to these global health challenges. Indeed, significant gains have been made to scale up care for people living with HIV globally, for example, precisely because of a more nuanced understanding of the antiretroviral market and facilitators (and barriers) for access. While this is unquestionably good, we must not lose sight of the fact that many of these patients will, at some point in their lives, also present with conditions requiring safe surgery and anesthesia, where access to essential medicines is far less advanced or understood.

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THE ESSENTIAL MEDICINE LIST

Since 1977, the WHO has maintained a model list of essential medicines, which is updated every 2 years. The most recent version, released in March 2017,1 contains 13 medicines in the Anaesthetics, Preoperative Medicines and Medical Gases core and complementary lists, and 6 opioid, nonopioid, and nonsteroidal anti-inflammatory medicines. Medicines contained in other sections—such as antiemetics, emergency medicines, antidotes, and others—all have relevance to safe anesthetic care and may even be essential for providing it (such as intravenous fluids). While perhaps other medicines could be included, a great deal of human suffering could be relieved through reliable and affordable access to high-quality anesthetic and analgesic medicines contained in the existing list. Evidence from the antiretroviral market suggests that competition among manufacturers that can produce quality drugs at affordable prices is the best way of bringing down prices and improving access.7 The challenge comes when there is just 1 pharmaceutical company that has monopoly over certain medicines where they can charge exorbitant prices. These monopolies can be deliberate—intellectual property rights being the most obvious—or simply from a lack of subsequent entrants in a given market to compete among one another. Ideally, essential medicines should be procured using mechanisms (eg, tendering) to reduce the costs of anesthetic medicines, which can be artificially high in a given market for a variety of reasons.

Surgery has been called the “neglected stepchild of global health.”8 If surgery is the neglected stepchild, anesthetic medicines are its distant cousin with an even less clear family tree. Despite multiple assessments conducted across low-resource settings consistently demonstrating a critical lack of anesthetic and surgical infrastructure and commodities—the availability of essential anesthetic medicines, anesthetic machines, monitors, compressed oxygen, and others—a systematic understanding of the barriers to accessing them locally, nationally, and internationally is still lacking. Despite this, the access challenges confronting providers on a daily basis are often obvious, even if their root cause is not: a global epidemic of substandard medicines (across all therapeutic areas), stock-outs and shortages, irrational usage policies (particularly for controlled medicines), and other supply chain blockages or failures. The pathways that medicines use to move through supply chains from the factory to a patient are complex and often nonlinear. In many health systems in LMICs, patients purchase their own medicines and rely heavily on informal and nonregulated sources, many of whom lack formal training in pharmacy and often sell medicines that are counterfeit or substandard, often at more affordable prices.9–11 The dynamics of these informal markets for anesthetics are even more poorly understood but are almost certainly undermining the safety of safe anesthetic care.

None of the medicines relevant to anesthetic care currently on the WHO’s Model List of Essential Medicines has a valid patent,12 meaning that no one individual or entity has a monopoly to produce and sell any of these medicines as a result of intellectual property ownership. In essence, each is available as a generic medicine and can be produced and sold by different pharmaceutical companies. Competition among generic manufacturers has been found to be the most effective mechanism for bringing down prices of antiretroviral and other medicines, and most of the medicines of interest to anesthesia providers have long been available as generics with a large global marketplace. Many of these medicines are available on international markets for pennies per milligram.

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THE REGULATORS

Yet the affordability of medicines can quickly be skewed by external forces. Regulatory barriers and small markets can quickly drive up the cost of doing business and push out competition, resulting in exaggerated high prices for what should be cheap medicines. Many of the medicines relevant to anesthesia, for example, are under international control: listed on one of the 3 international treaties that establish the international drug control system.13 This international system—which has neither reduced illicit drug consumption, use, or prices nor improved access to controlled medicines, despite having a mandate to do both14—establishes national requirements for legislation concerning how controlled medicines are manufactured, distributed, stored, and dispensed and international mechanisms for importations and exportation, all of which can drive up the price of medicines affected by them.15 More pragmatically, complying with these regulations is cumbersome and likely a disincentive for generic pharmaceutical distributors whose profits are generated through the sale of medicines with small profit margins, a profit that could be made through the sale of less restrictive and cumbersome products. The result of this complex web is that when controlled medicines are available in LMICs, they are often substantially more expensive than in high-income countries, a perverse finding that further places these medicines out of reach of patients who need them.15

Beyond these policies, a relatively small domestic market size and small profit margins for low-cost medicines can result in shortages or the absence of products all together. For example, Zimbabwe (where one of the authors is a practicing clinician) has had challenges reliably supplying vasoconstrictors, with some health institutions having only epinephrine (adrenaline) available to manage hypotension after spinal anesthesia. Ephedrine was not available because it was considered by pharmaceutical companies to be a cheap medicine with low profit margins and low turnover relative to the cost of registering it in Zimbabwe. Country-specific requirements for medicine registration can pose a barrier for obtaining affordable medicines by increasing the barriers to market entry for multiple producers and, therefore, potentially limiting competition. Efforts are being made to attempt to harmonize regulation among countries and improve the quality and safety of medicines that are often regulated by underresourced authorities and, hopefully, reducing the barriers to accessing low-cost, high-quality medicines.16

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SUBSTANDARD MEDICINES

When medicines are available, serious concerns about their quality exist and have long been anecdotally known among the global surgical community for years. Anesthetics that produce no sedation, let alone anesthesia; analgesics that fail to relieve pain; and local anesthetics that result in suspiciously high rates of failed spinal anesthetics are all-too-common occurrences in many countries. Evidence is beginning to emerge that validates concerns about anesthetic medicine quality, including a report confirming the presence of grossly substandard propofol in Zambia containing substantially less than the stated amount of the active pharmaceutical ingredient.17 Given that the presence18 and harms19 of a global pandemic of substandard medicines have been documented in other therapeutic areas, it would be naive to assume that anesthetic and analgesic medicines are immune or less affected. The problem is at its worst in LMICs where up to half of medicines for some diseases are fake and too many regulatory authorities lack the technical capacity to effectively intervene. Despite the potentially massive threat to public health and patient safety, no international treaty exists to harmonize medicine quality among countries, leading to significant gaps that have long been addressed by other industries (including aviation, to which anesthesia is often compared, and which has a large body of international law and coherent rules among countries).

It is time for the global anesthesia community to take concerted action to improve access to medicines that are necessary for safe anesthetic care. Failing to understand in detail and improve the situation of poor access to medicines essential for perioperative care risks compromising the many gains that have been achieved in improving global surgical capacity and means that, today, far too many patients, providers, and health systems lack access to anesthetics and analgesics that will save or improve their lives.

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THE KETAMINE STORY

The consequences of inaction have been acutely tested for the anesthesia community over the past years. For example, in 2014, the government of Thailand introduced a nonbinding resolution at the United Nations Commission on Narcotic Drugs calling on member states to place ketamine under national controls akin to other existing restrictions on medicines like benzodiazepines and opioids.20 After this, later in 2014, the Chinese government notified the United Nations that it intended to recommend that ketamine be placed under schedule I of the 1971 Convention on Psychotropic Substances.21 A substance listed in schedule I of the convention, by definition, is a substance with no legitimate medical or scientific use; this is a far cry from ketamine, an essential medicine used globally in anesthetic care, and which is the only anesthetic available in many low-resource settings.22 , 23 After global resistance to the proposal, China revised its notification to schedule IV and has deferred the issue for the past 3 years; however, the matter is not closed, and the risk remains.

In this instance, global anesthesia came dangerously close to having severe restrictions placed on a medicine that is at the cornerstone of safe anesthetic care for billions of people. While access to ketamine, for now, is preserved as is, the deplorably poor global access to controlled medicines (notably, opioid analgesics) remains a global health scandal, with the gap in access between patients in high- and low-income countries being perhaps an unparalleled global health disparity.24 , 25 The Lancet Commission on Palliative Care and Pain Relief estimates that the cost of meeting the global shortfall of morphine-equivalent opioids is only $145 million per year if countries had access to the lowest retail price paid by high-income countries.26 Progress is achievable but only with effective and equitable policies and the political will from practitioners, patients, and policymakers to take action.

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CONCLUSIONS

There is a need to understand and engage in health policy and programming that affect perioperative medicines locally, nationally, and internationally and a need to venture outside of the normal realms of anesthetic research and activism. A great deal of emphasis has appropriately been placed on the World Health Assembly resolution 68.15, “Strengthening emergency and essential surgical care and anesthesia as a component of universal health coverage,” but viewing this 1 resolution in isolation of other World Health Assembly agenda items on, for example, the global shortage of, and access to, medicines and vaccines,27 fails to properly situate surgery and anesthesia within global health policy and, consequently, health systems. Opportunities to advance access to safe anesthetic medicines as well as safe perioperative care more broadly will continue to be lost unless these opportunities are seized and connections are made.

What this points to is not just a need to improve access to anesthetic medicines, but a need to view the impacts of surgical programs on health systems. It is high time that global anesthesia and surgery programs consider their impact and sustainability beyond easily quantifiable metrics of surgeries performed or clinicians trained and instead shift to assess the impacts that these programs have on health systems more broadly. Assessing and improving access to medicines is 1 aspect of this understanding. Until sustainable and reliable supplies of high-quality anesthetic and analgesic medicines are available for patients and health systems, the success of global surgery will be severely limited. We cannot continue to ignore this problem.

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DISCLOSURES

Name: Jason W. Nickerson, RRT, PhD.

Contribution: This author helped design, write, and edit the manuscript; and approve the final version.

Name: Edson Chikumba, MMed, FCA.

Contribution: This author helped design, write, and edit the manuscript; and approve the final version.

This manuscript was handled by: Angela Enright, MB, FRCPC.

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© 2018 International Anesthesia Research Society