Sandeep Kishore, Rachel Kiddell-Monroe, and Ruth Lopert, Yale University

Name of Lead Author: Sandeep Kishore, Rachel Kiddell-Monroe, and Ruth Lopert
Organization: Yale University
Country: United States

Abstract

In 2015, the 20th World Health Organization (WHO) Expert Committee on the Selection and Use of Essential Medicines (the EML Committee) added highly expensive cancer, hepatitis C, and tuberculosis medicines to the WHO Essential Medicines List (WHO EML) for the first time. The EML Committee went on to acknowledge that several of these essential drugs, such as trastuzumab for HER2+ breast cancer, were clearly unaffordable in many countries. Although there were a handful of patented and expensive medications for rare diseases (for example, factor VIII for hemophilia) already on the WHO EML, the Committee has been criticized in the past ---predominantly before 2002---for its recommendations of only affordable medicines. The 2015 additions remedied this. Further steps are, however, critical to turn this important initiative into practical benefits for patients and payers. Given that no official entity is entrusted with making essential medicines on the WHO EML affordable, we suggest that the WHO take a leadership role in addressing this policy gap. Here, we propose a mechanism that could help. By adopting an Essential and Affordable Medicines Board to complement the EML Committee, and by actively engaging civil society organizations in its work, the WHO can bridge the gap and fulfill its mandate to ensure the highest attainable health standard for all.

Submission

Introduction
In 2015, the 20th World Health Organization (WHO) Expert Committee on the Selection and Use of Essential Medicines (the EML Committee) added highly expensive cancer, hepatitis C, and tuberculosis medicines to the WHO Essential Medicines List (WHO EML) for the first time. The EML Committee then went on to acknowledge that several of these essential drugs, such as trastuzumab for HER2+ breast cancer, were clearly unaffordable in many countries. For the EML Committee, these recommendations were “…the starting block and not the finishing line…[t]he hard work begins with efforts to ensure that those medicines are actually available to patients.”1

The decision to include medicines like trastuzumab on the WHO EML has been the clearest indication to date of a revitalization of the concept of essentiality. Although there are a handful of patented and expensive medications for rare diseases (for example, factor VIII for hemophilia) on the WHO EML, the Committee has been criticized in the past for its recommendations of only affordable medicines. Indeed, for several years, compelling arguments have been made to add certain patented and relatively expensive drugs to the WHO EML, because essentiality cannot, and should not, be contingent on price or affordability.

The 2015 additions to the WHO EML are a bold and welcome development. The WHO expects that this will support efforts to reduce prices. However, in its report, the EML Committee recognized that the additions alone would not be enough to bring prices down.4 Indeed, placing a drug on an EML “does not guarantee patient access.” The EML Committee “therefore recommended that WHO collaborate with countries in taking measures to ensure that this objective is achieved.”4

It could be argued that including a medicine with a high unit cost from the WHO EML on a national EML would prompt efforts to moderate price and promote affordability. But whose responsibility should it be to stimulate lower costs? Although we commend the EML Committee for taking this important step, we must go further to realize its ambition and make essential medicines affordable.

In this article, we raise three issues:
(1) the need for renewed clarity in the definition of essential;
(2) the need to address the ongoing policy gap between essential and affordable medicines; and
(3) a potential strategy to bridge this gap using a multi-centric approach.

Defining essential medicines: context and recent developments
The WHO EML is a formulary of 406 medications for adults that should be accessible to populations globally. When it was first published in 1977, the WHO EML was intended to underscore the idea that some medicines are essential and to recognize that access to these medicines is unequal across countries and across populations.

Today, the WHO EML serves as a global standard to guide countries in identifying medicines that should be not only widely available in national health care systems, but also affordable to individuals and the community. By updating the WHO EML every two years, the WHO has demonstrated that it is a dynamic document that can be readily updated as new treatments emerge and as public health priorities change with changing patterns of disease. It is used by all UN organizations and by more than 150 countries, where it forms the basis for coverage-program formularies and national EMLs. Since the first WHO EML, there have been at least 134 national EMLs established, and 94% of countries with EMLs claim to use them as the basis for public drug procurement.

In 2013, two coalitions of civil society organizations (CSOs) independently submitted requests for additions to the EML. One was for imatinib mesylate (Glivec®, Novartis) to treat chronic myeloid leukemia, and the other was for trastuzumab for HER2+ breast cancer. Both medications were still patented at the time, and both carried high price tags. The EML Committee acknowledged their effectiveness but rejected the applications, noting that a new, systematic approach would have to be developed to consider the pricing and addition of such expensive therapies.

In conjunction with the Union for International Cancer Control, the EML Committee subsequently undertook a major review of the oncology section of the WHO EML. On 8 May 2015, they announced that 16 oncology drugs (including imatinib and two biologics, trastuzumab and rituximab) and four major medications for hepatitis C would be added to the WHO EML,1 knowing that these drugs are unaffordable for many governments. In the United States, the hepatitis C drug sofosbuvir (Sovaldi) costs more than $80,000 for a 12-week treatment course, and imatinib typically sells for over $10,000 for a 30-day supply of the 400-mg dose.

We agree with the recent Lancet commentary, which noted that the inclusion of the newly listed drugs---without regard to price---“is consistent with the definition of essential medicines.”5 However, the outstanding question is whether the additions reflect a new interpretation of essential.

Prior to 2001, the way essential medicines were selected suggested that a medicine needed to be available at a low unit price to be included on the WHO EML. A WHO technical report from 1977 stated that “[c]ost represents a major selection criterion. In cost comparisons between drugs, the cost of the total treatment, and not only the unit cost must be considered.” This prevented many HIV/AIDS medicines from inclusion, implying that the treatments were not essential. Countries were not adding these antiretroviral therapies to national EMLs, nor were they receiving or allocating funds to treat HIV/AIDS patients.
The enormity of the HIV/AIDS crisis, and specifically the lack of access to lifesaving medication for people living with HIV/AIDS, challenged this approach once and for all. A special session of the EML Committee convened in 2001 to revise the criteria. These criteria, which still appear on the WHO website, state that although “the absolute cost of the treatment would not constitute a reason to exclude a medicine from the Model List… cost-effectiveness comparisons may be made among alternative medicines within the same therapeutic group.” This established a framework for comparing value for money among similar medicines. However, it provided no guidance for assessing drugs with a high unit cost that were the only available treatments for a particular condition or population (e.g., trastuzumab for HER2+ breast cancers) or represented a major advance in therapy (e.g., sofosbuvir for hepatitis C).

The recent additions to the WHO EML spotlight the term essential. We urge the WHO to take this opportunity to make a clear public policy statement that (1) clarifies that the designation of a medicine as essential depends on its clinical utility and (2) states explicitly that neither the unit price nor the overall cost of a medicine are relevant considerations. Such a move would both confirm and reinforce the important step the EML Committee has made to ensure that “those [medicines] that satisfy the priority health care needs of the population” are included in the WHO EML.

The policy gap in governance
Reinforcing clinical essentiality as the sole criterion for adding a medicine to the WHO EML also highlights a policy gap in the governance of essential medicines that has been known for decades but has yet to be formally addressed by the WHO. The gap lies between the addition of an essential medicine to the WHO EML and the transformation of that medicine into one that is both essential and affordable.

We propose the creation of both a policy space and a mechanism to transition medicines from essential to essential and affordable. There is currently no WHO department or group focused solely on ensuring that medicines on the WHO EML become sufficiently affordable for inclusion on all national lists. This gap needs to be filled to reinforce the concept of the EML. Since the adoption of the Trade Related Aspects of Intellectual Property Agreement (TRIPS) in 1994, CSOs have taken on the responsibility for filling the policy space. Recognizing that affordability is one of the most important barriers to medicine access in a majority of countries, CSOs have promoted the use of TRIPS flexibilities to address the barriers created by patent monopolies and have developed alternative incentive mechanisms for access and innovation in biomedical research and development (R&D).

Using the 2001 Doha Declaration on TRIPS and Public Health that attempted to redress the ethical gaps created by TRIPS, CSOs (together with some national governments) have been trying, with widespread and notable success, to bridge the gap between “essential” and “essential and affordable”. Through its innovative and remarkably resilient efforts, civil society has made a profound difference, and in doing so, has highlighted the incongruity of a biomedical R&D paradigm that continues to fail patients worldwide. It is time for the WHO to leverage its role as a global health steward to capitalize on the strength and experience of civil society to facilitate access to and affordability of medicines globally. Nowhere is this more relevant than for new products for cancer, hepatitis C, and tuberculosis.

Minding the gap: a multi-centric governance proposal
In its report, the EML Committee cited a number of policy levers at the disposal of individual countries to make essential medicines affordable.4 Particular mention is made of individual country/WHO collaboration. However, rather than concentrating on parallel bilateral relationships, the objective should be the establishment of a global multi-centric mechanism that brings together the WHO, national governments, and civil society to develop a comprehensive, systematic, and collective approach to promoting affordability and access.

Although it is beyond the scope of this paper to fully elaborate a mechanism, not least because any such mechanism should be developed in consultation with relevant stakeholders, we offer a broad suggestion: the establishment of a WHO Essential and Affordable Medicines Board (EAMB). The EAMB would operate under the auspices of the WHO, with full and open formalized collaboration with CSOs and national governments. Inspired by and benefitting from the lessons of the UNITAID governance model, which utilizes innovative financing to drive down drug prices, the EAMB would strive to make affordable WHO EML medicines currently out of reach for most countries because of their high unit price or overall cost. With a mandate to receive proposals on country-specific and general barriers to access and affordability from countries and CSOs, the EAMB could prioritize, propose, and monitor the resulting bilateral-, multilateral-, and mixed-stakeholder solutions. The EAMB would be positioned to deal with system financing issues such as downstream barriers to affordability (e.g., over-pricing by distributors, prescriptions, tariffs, and the paucity of financial support pledged by countries) as well as oversee inter-governmental organizations for medicines, particularly for non-communicable diseases (NCDs).

The EAMB would utilize the WHO EML as its principal reference tool. Initially, the EML Committee could flag essential medicines considered unaffordable in one or more member states. The EAMB would then use their knowledge of the biomedical R&D environment to bring about the necessary changes. To ensure transparency and accountability, the EAMB would publish regular reports of its progress, highlighting successes and challenges, and presenting proposals for systemic solutions.

An EAMB would play a critical role in publicly recognizing and accounting for medicines that need special measures to ensure affordability and would reinforce the concept of an essential medicine. Because another body would work to make an otherwise unaffordable essential medicine affordable, the mandate of the EML Committee would no longer be clouded by concerns that medicines on the WHO EML are, in reality, unavailable to national governments. The implementation of an EAMB would move the issue of medicine affordability from the informal realm, where individual patients or lobby groups have to fight for the right to access a medicine, to a formal space, where government policy makers and NGOs work together to promote access for all.

Conclusion

We welcome the important step taken by the EML Committee and commend the recent addition of several important medicines with high unit costs to the WHO EML. Not only did this clarify the role of the EML Committee, but it also officially recognized the policy gap in access to medicines that CSOs have attempted to fill for years.

Further steps are, however, critical to turn this important initiative into practical benefits. The WHO’s adoption of an Essential and Affordable Medicines Board and active engagement of CSOs can bridge the gap and fulfill the WHO’s mandate to ensure the highest attainable health standard for all.

Bibliography and References

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22 A proposal has been made by Knowledge Ecology International to create a category in the EML for drugs (and diagnostics) that are essential, if available at affordable prices. This is an interesting approach but the authors of this paper believe that it could wrongly imply that medicines should be essential only if they are offered at affordable prices. In this paper, we argue the contrary---medicines are essential based on clinical need (irrespective of cost), and we must make them affordable. In other words, affordability should be the consequence of, not the precondition for, essentiality. http://www.who.int/selection_medicines/committees/expert/ 20/reviews/open-session_KEI-statement_18-apr-15.pdf