Expanding the WHO list of essential medicines for children: A call for further action

O ver 80% of children with cancer live in lowand middleincome countries (LMICs).[1] The survival gap between these children and those living in high-income countries (HICs) has received increasing attention from the pediatric oncology community. Most efforts addressing this disparity have focused on “twinning” initiatives between HIC and LMIC centers that allow bidirectional exchanges and combine disease-specific multidisciplinary expertise with local knowledge and capabilities, often with impressive local results.[2–4] More recent initiatives at the international level have advocated for the inclusion of pediatric cancer on the global child health agenda.[1,5] In this issue of Pediatric Blood & Cancer, Robertson et al. describe one such initiative: the inclusion of additional chemotherapeutic agents used for the treatment of childhood cancer onto the WHO Model of List of Essential Medicines for Children (EMLc). [6] Through a laborious process involving dozens of experts, the authors ultimately succeeded in the addition of several chemotherapy drugs, including etoposide and cisplatin. Their efforts lead to two important questions. First, are existing global child health frameworks well-suited to tackling childhood cancer disparities? Second, will the inclusion of chemotherapeutic agents on the EMLc lead to improvements in outcomes for LMIC children? The authors describe several criteria by which a specific agent may be designated as “essential”: incidence, prevalence, and burden of disease; region-specific needs; effectiveness; and even political impact. Robertson et al. too quickly dismiss the first criterion, stating that childhood malignancies are “rare rather than priority diseases based on estimates of incidence and prevalence.”[6] As strides against infectious death are made, cancer represents an increasing proportion of overall childhood mortality, for example causing 18.6% of deaths among 5–14 year-olds in upper-middleincome countries, a category that includes Brazil, China, and Mexico.[1] How to apply the remaining criteria to pediatric cancer is also unclear. When looking at impact, measures of “clinically relevant benefit” designed for adult oncology and based on prolongation of median overall survival are unlikely to be appropriate for children. The lack of cost and cost-effectiveness data on childhood cancer treatments in LMIC setting makes using these criteria difficult as well. Indeed the definition of an “essential”medicine, while obvious at first glance, is complicated in its application to pediatric oncology. Can a medicine be designated as essential when it is only effective when delivered as part of an entire package of care? The authors commendably address this issue by adopting a disease-based and not a drug-based approach. However, where does this leave other essential components of the overall treatment package, such as transfusion support; adequate nursing, pharmacy and laboratory resources; or surgical infrastructure, without which chemotherapeutic agents may be futile at best and dangerous at worst? Finally, and most importantly, we are obliged to ask ourselves whether having chemotherapeutic agents prominent on the EMLc will result in tangible improvements in cure rates for LMIC children. For this to be the case, two assumptions must be true: inclusion on the EMLc must lead to LMIC patients having improved and stable access to high-quality chemotherapeutics, and improved drug access must directly lead to improved outcomes. In regard to the first assumption, the evidence is disheartening. It is noteworthy that basic agents such as vincristine, cyclophosphamide, and doxorubicin have been included on the EMLc since 2011. No coordinated regional or global effort to ensure stable and accessible supplies of these medications has emerged; indeed drug shortages in both LMICs and HICs have, if anything, become more prominent.[7] The authors themselves acknowledge that few data support the assumption that the EMLc influences country level action, instead citing member country support for resolutions on improving access to essential medications. As international experience with the Millennium Development Goals illustrates, such resolutions alone are ineffective without public pressure, monitoring, and consequence.[8] In regard to the second assumption, the authors list multiple barriers to the delivery of high-quality pediatric oncology care in LMICs, including a lack of human and infrastructure resources, high rates of treatment-related mortality, and abandonment. These complicated challenges require coordinated solutions involving multiple levels of government and comprehensive childhood cancer policies, which include but go far beyond matters of drug access.[1,5] The authors are to be congratulated for their efforts, and the inclusion of more chemotherapeutic agents onto the EMLc should be applauded by the pediatric oncology community. The danger, however, lies in believing this a complete solution. No child has been cured of cancer by drugs alone in the absence of supportive