Transparent and consultative national medicine selection committees can facilitate implementation.

A key institutional feature in many countries is a national medicine selection committee (alternatively known as a pharmaceutical therapeutics committee) that is responsible for determining those medicines to be included on a national list. How medicine selection committees are formed, their management, and their decision-making processes influence the adaptation and implementation of NMLs. Three articles indicated that national policymakers recognized that the process for the establishment of national medicine selection committees should be consultative to facilitate genuine involvement of relevant stakeholders and that committee members should have clear roles [16,37,38]. For example, a study from Mali reported lack of clarity about whether it was the medical professionals or policymakers from the Ministry of Health who had overall responsibility to access relevant information for the committee’s decisions [38]: “You cannot place the responsibility on each person. If you do that it is not going to get done. You have to have a specific group whose job it is to get the information” [38].

Leadership and coordination capacity are needed to secure oversight, monitoring, and evaluation.

Decision-makers noted that gaps in leadership, such as coordination of committee discussions, weak institutional capacity, as well as limited oversight, monitoring, and evaluation are factors that impedes the implementation of NMLs [16,20,22,39–41]. Nsabagasani and colleagues studied how Uganda responded to the 2012 WHO recommendations on child-appropriate dosage formulations and identified weak institutional capacity in convening relevant stakeholders to assess how the country could move forward in adopting the recommendations [39]. In addition, technical advisory committees could have a wider mandate or longer-term role [16,18,41], with a study from Ghana suggesting the committees could have a role in advocating for greater adherence to NMLs [18]. To improve implementation, more attention to adherence and compliance strategies could be achieved through better coordination and oversight by scientific selection committees.

Legislative and regulatory measures can help harmonize and ensure that NMLs are implemented.

Enforcement strategies and policy controls from health authorities are crucial factors affecting the prescribing and availability of medicines prioritized by NMLs [16,20,42,43]. Key factors preventing effective implementation can be the lack of an enforceable regulatory or legislative framework supporting compliance to NMLs, including linkages to pharmaceutical services departments [41]. Odoch and colleagues found that domestic health changes such as the devolution of health services had influenced NML updates [16]. Implementation can be particularly challenging in decentralized health systems that enable autonomy for medicine selection and use within regions and hospitals, even when a national framework for essential medicines is in place [5,20,44]. Several studies described inconsistencies between NMLs and how they are implemented at a regional or hospital level at the discretion of local doctors [5,41,42,44]. The lack of oversight of monitoring and implementation of NMLs resulted in hospitals diverging from national recommendations and making their own decisions related to medicine selection provision. Moreover, a study by Zaidi and colleagues in Pakistan reported that federal stakeholders and experts expressed concern over uneven medicine policy across regions caused by too little national coordination, accountability, and drug regulation [20]. In this setting, the devolution of the powers of the Ministry of Health impacted the coordination of medicine policies across subnational levels [20].

Regional autonomy for medicine purchasing may conflict with NMLs.

A study by Matlala and colleagues examined implications of regional decision-making. They identified that on occasions, it was necessary for clinicians to prescribe nonformulary mechanisms and defer to hospital management for the decision if nonformulary medicines were perceived to be too expensive [5]. At a service delivery level, the balance of medicines selected and ensuring access to those medicines prescribed can be a particular challenge [22,40,41,45]. Experiences from different countries underscored how the lack of implementation guidance, including monitoring and evaluation, at a subnational level can lead to unregulated adaptation or disregard for NMLs by local policymakers or prescribers [20,22]. Experience from Pakistan indicated the need for strict regulation and monitoring for adhering to the NML and frequent surveillance of both the private and public sector to assess compliance [20]. Another study highlighted the need for drug utilization evaluations to understand drug use and patient outcomes [22].

Standard treatment guidelines play a crucial role in translating intentions of NML to clinical practice.

Another key prerequisite for NML implementation is how the medicine policy links to recommended clinical practice, which is referred to as STG in many settings. These are intended to offer guidance on standardized treatment protocols and influence clinical behavior by guiding the prescribing of medicines. A finding that was assessed to have moderate to high confidence from the CERQual assessment (Table 2) indicated that STGs to a varied extent facilitate implementation of a country’s NML [5,9,16,20,22,39,41,44]. A study from Trinidad and Tobago highlighted the value of national treatment protocols to harmonize the use of cancer medicines for adults that had been added to the essential medicines list and proposed that such an approach could also be applied to children’s cancer medicines. The healthcare provider interviewed discussed the addition of ifosfamide, topotecan, and irinotecan to the NML after clinicians had written to the Drug Advisory Committee [9]. An observation study of pharmaceutical therapeutic committee meetings in Gauteng Province in South Africa cited examples of clinicians needing to develop guidelines for the control and use of nonformulary drugs [5]. Another study from Ghana described that despite the intention of health officials to use an STG and a NML to guide healthcare providers in medicine selection, there was a lack of information about how they are used in clinical practice [18].

Formal links to medicines reimbursement decisions is critical to the policy salience and NML’s effects on prescribing, which may differ between HICs and LMICs.

The salience of NMLs to national policy settings is deeply intertwined with its relationship to medicine reimbursement decisions. A finding with moderate to high confidence (Table 2) was the lack of a shared understanding of what the concept of “essential medicines” precisely entail for their populations and that decision-makers in HICs perceived the essential medicines concept to be less relevant to their countries than to LMICs [17,46]. A partial explanation was because reimbursement decisions, and not revisions of an essential medicines list, determine the national or local formulary and the prioritization of medicines in national healthcare systems of most high-income countries (HICs). However, reimbursement processes are increasingly critical in LMICs with respect to achieving UHC, which means financial risk protections and prevent the patient from incurring high out-of-pocket expenses for essential medicines. Several papers in our review described the high out-of-pocket costs for patients, regardless of whether medicines are listed on NMLs [20,22,39,45,47].

We also identified that a NML can improve or worsen prescribing practices [22,40,41,43–45]. A Bulgarian study reported limited impact on prescribing behavior, because no formal body had approved the NML [43]. Other papers discussed the lack of dissemination as a reason for divergence [22,45] and the misalignment of actual use with forecasts when clinicians prescribed outside of the NML [41].

Locally relevant updates of NMLs requires balancing global evidence, expert knowledge, and local data.

Differences between WHO EML and NMLs are expected given the diversity of countries’ health challenges and resources. Ideally, countries have a wide range of tools at their disposal for securing sound adaptation, including global evidence, local specialist clinical expertise and experience, and local data on key criteria (e.g., efficacy, safety, availability, and affordability) that can be used to guide decisions about inclusion. Many countries use key global public goods, like globally produced evidence syntheses such as WHO technical reports and Cochrane reviews, to inform their decisions [9,18,37,39]. Globally produced evidence syntheses were key, for example, in Ghana, where the national medicines selection committee was supported by an evidence summaries group trained in the retrieval, appraisal, and interpretation of systematic reviews [18]. Moreover, WHO National Program Officer for Essential Drugs and Medicines was an important source of guidance about global best practices and lessons from other health systems [18].

A key gap facing countries when adapting WHO EML was the lack of relevant research and local data specific to the decision context [20,22,38], a finding that was assessed with CERQual to have moderate to high confidence. In a study from South Africa, Perumal-Pillay and colleagues identified that past and present members of the South African National Essential Medicines List Committee expressed concern that locally relevant data were lacking and that pharmacoeconomic studies were seldom directly applicable to their environment [22].

Local expert knowledge is crucial for adapting global recommendations domestically. However, studies reported the challenges of striking the right balance between evidence generation and a reliance on expert opinion [5,38,39,44]. Those deciding on which medicines to include, such as national policymakers or members of national committees, may perceive research evidence to have limited relevance and applicability. For example, policymakers involved in the update of the EML in Mali indicated that most research was not applicable to policymaking and wanted greater involvement in shaping research on essential medicines [38]. In a study related to pediatric medicines, a roundtable discussion about prioritized policy and research concerns flagged that there was limited research related to the surveillance of the impact of the NML policy, including consequences of devolution of decision-making, and medicine availability and quality [20]. The hospital formulary management committee decision-making processes described by Matlala and colleagues highlighted the importance of clinicians sharing their clinical experience with the use of medicines that were not currently on WHO EML [5].

There is insufficient utilization of cost-effectiveness information to manage cost considerations.

Several papers describe how the cost of a medicine is an important consideration for national medicine committee selection processes [5,17,20,37,39,41,48]. Recent additions to WHO EML have been high-cost medicines with potential to impose a significant strain on government health budgets. These drugs underscore the need for countries to consider the cost and financial implications of adding new essential medicines to NMLs [12]. In Brazil, cost has always been an important consideration, and additions of several high-priced cancer medicines have strained public and private hospital budgets [45,48]. A study from Tanzania found that there was disagreement between clinicians and pharmacists about the cost of medicines, with pharmacists expressing concern about budget implications [37]. A review finding with high confidence was the opportunity to use health economic methods, such as context-specific economic evaluations and drug utilization evaluations to support development of NMLs [16,22,37]. Several studies indicated the value of using Health Technology Assessment (HTA) as a tool to make medicines more affordable by evaluating the comparative effectiveness of drugs and to monitor and evaluate NMLs and decision-making processes for medicine selection [5,16,22]. However, they indicated a lack of access to the relevant data [16] or health economic expertise within country as a limitation to ensuring this [5,22].

NMLs may influence provider incentives and drug-related incomes.

NMLs can have financial implications for some private health providers as regulation of medicine selection by governments can influence the price and type of medicines sold by providers [42,44,45,49,50]. For example, studies from China suggested that the implementation of NMLs had shifted the cost of medicines to hospitals. A study from Anhui Province county-level public hospitals described how the implementation of the NML meant that the hospitals lost an income source (so-called “drug price addition revenue”) and that other hospitals had indicated that income was insufficient to make up for losses [42].

To translate into availability and access, NML revisions must be linked to systems for financing and procurement of pharmaceuticals.

Our findings indicate that the price, production, and procurement of medicines can be influenced by a NML [20,44,51]. Matlala and colleagues described the processes used by committees in South Africa to align the NML with formulary procurement and associated cost implications [5]. Prescribing outside of EML is possible, and the nonadherence to NMLs has cost implications for the health budgets [41]. Additionally, the result of adding a medicine to the list could, on the one hand, mean savings through bulk purchasing of medicines [51]. On the other hand, this can result in price inflation [20,44].

In China, by linking essential medicines lists to policies that address the financing of pharmaceuticals, they have sought to reduce cost and increase efficient prescribing [44]. For example, the National Essential Medicines Scheme involved linking 3 key policies to their National Drugs List for primary healthcare institutions. First, a “zero mark-up policy” for essential medicines prescribed in primary healthcare institutions, to eliminate financial incentives for overprescribing drugs. Second, making medicines on the National Essential Drugs List reimbursable by health insurance schemes, thereby transferring the financing of these drugs from out-of-pocket expenses by patients to mostly government-funded insurers. Finally, the Chinese National Essential Medicines Scheme required collective provincial bidding and procurement for medicines on the list [44].

Brhlikova and colleagues found that in Uganda, following increases to government funding for essential medicines, demand for locally produced medicines also increased [47]. While adding drugs to a NML is a sign of increased priority by the government, pharmaceutical manufacturers may not necessarily respond unless other factors, such as the potential for profits, are addressed. A study from Pakistan found that locally based manufacturers had a decreasing interest in manufacturing “orphan drugs” (e.g., drugs for neglected or rare diseases), despite the Ministry of Health mandating the production of these drugs [20]. In this instance, the key factor was the limited profitability of producing these medicines.

A lack of clarity between the role of medicine selection and pharmaceutical services of government authorities, a finding that was considered to have moderate to high confidence, indicated that there is a need to strengthen NMLs as a tool that supports availability and efficient procurement [16,20,22,41,52]. Inclusion in a NML based on efficacy and cost is, by itself, insufficient to promote access. A study from Brazil highlighted that there was limited interaction between the processes for selecting medicines and the processes for procuring them. The study described how a medicine would be selected based on efficacy and cost without considering how widely available it was in terms of pharmaceutical procurement. This negatively affects patients’ health outcomes, as medicines may be prescribed, but lack of access means that they lapse in supply and result in incomplete treatment [22]. In Trinidad and Tobago, when updating WHO Children’s List, poor communication and siloed paper-based information systems between agencies involved in children’s access to medicines was cited as a challenge to implementation [9].

Reliance on donors can influence additions to NMLs and subsequent procurement and supply.

An external factor affecting NML implementation in LMICs was dependence on donors in securing financing and supply of new medicines that are added to a country’s NML [16,18,39]. In Uganda, policymakers struggled to respond to global EML changes recommending child-appropriate dosage formulations due to the additional cost implications of these medicines and expressed reliance on global financing from the Gates Foundation and other donors such as the Global Fund to Fight AIDS, Tuberculosis and Malaria [39]. Moreover, donors in Uganda were operating outside of the national policy environment and distributing medicines at the community level through vertical health programs [39]. In their study from Uganda, Brhlikova and colleagues reported that donor procurement policies were hindering local production of medicines [47].