1. Project Overview
The coronavirus disease 2019 (COVID-19) pandemic continues to threaten health system functioning, previous institutional care models, and pharmaceutical supply chains for critically essential medicines globally. In low-and middle-income countries (LMICs), these challenges are further exacerbated by lingering resource constraints, an insufficient number of health human resources, and a limited supply of supportive care medicines.1 Coupled with the rapid rate of spread of SARS-CoV-2, these pandemic drive challenge have yielded unprecedented consequences to urgent care and treatment access for vulnerable non-COVID patients with long-term chronic conditions. Particularly vulnerable to disruptions in drug access are immunocompromised patient cohorts, such as children with cancer, who are increasingly recognized as a significant contributor to childhood mortality in LMICs.2
The recent World Health Organization (WHO) Report on Cancer positions childhood cancer as an exemplar of a priority cancer for which significant improvements in outcome can be achieved at relatively low cost.3 However, the ultimate effect of the pandemic on LMIC health systems to maintain adequate care and treatment for non-COVID-19 patient groups, such as children with cancer with complex care needs, remains unknown. Leveraging a pre-existing partnership across five East African countries, the aim of this study is to elucidate the impacts of COVID-19 on drug access in LMIC contexts through comparative health system analyses of non-COVID care across a priority vulnerable population. Through an exploration of impacts to childhood cancer, the results generated will yield important empirical insight into LMIC health system disruptions, as they affect care and drug access for both COVID-related and non-COVID care.
2. Background and Rationale
2.1. Impacts of COVID-19 on LMIC health systems and drug access:
The number of COVID-19 cases reported in LMIC contexts, especially across Africa, is still relatively small.2 However, access to testing thus far has been low in comparison to many high-income contexts. Further, as many LMICs enter the rainy season in the coming months, COVID-19 rates are expected to rise substantially.2 As a result, the capacity of these health systems to manage a surge in COVID-19 cases is extremely limited. Disruption or complete breakdown of pre-existing patient workflow processes and in pharmaceutical supply chains for essential drugs would result in adverse outcomes for both COVID-19 and non-COVID-19 patients. For one, an increase in COVID-19 cases will likely siphon drugs forecasted for other health priorities and leave non-COVID patients vulnerable to deleterious and potentially fatal impacts.4 Further, physical distancing measures and reduced access to health facilities are likely to yield inadvertent consequences to drug access for non-COVID patients requiring follow-up treatment.
Fuelling supply side barriers, drug shortages are additional disruptions in the pharmaceutical supply chain. India, for instance, is one of the largest hubs supplying low-cost generic drugs to millions globally.5 In Africa, it is estimated that approximately 40% of imported generic medicines are from the Indian market.6 However, Indian pharmaceutical companies procure almost 70% of active pharmaceutical ingredients for their medicines from China.5 Earlier this year, the unexpected closure of many Chinese pharmaceutical companies to contain the spread of the virus, clearly demonstrated the vulnerability of pharmaceutical supply chains as social containment measures ensue across many countries.5 Access to essential medicines is a complex issue, involving phenomena from drug development to delivery. The paucity of empirical research capturing COVID-19 impacts on LMIC drug demand and supply dynamics, therefore reveals an opportunity to advance planning, forecasting and preparedness planning.
2.2. Childhood cancer: An emerging priority child health issue in LMICs and priority health population:
While advances in childhood cancer care have made cure a reality for over 80% of children in high-income countries (HICs),7 these developments have not translated into many systems of care in LMICs; where the burden of childhood cancer looms largest.8 A major impediment to the effective care of children with cancer in LMICs is lack of access to essential medicines.9 Drug access is determined by a range of interrelated factors: availability, accessibility, acceptability, affordability and quality.10
With the onset of the COVID-19 pandemic, health systems have been transformed in unprecedented ways—with documented impacts to cancer diagnostics, access to therapies, and palliative care options. Patients with cancer are among a high-risk group to COVID-19, in that their immunocompromised state makes them more vulnerable to viral infection and long-term complications. Further, it is difficult for cancer patients to remain in quarantine as a result of the need for adjuvant therapies and frequent follow-up.11
In their Special Report, Adapting childhood cancer services during COVID-19, global leaders in paediatric oncology have recommended that during the COVID-19 pandemic, standards of care for children with cancer not be compromised or electively modified.12 However, as the virus traverses each health system in nuanced ways, threats to reliable, equitable and effective cancer treatment are of utmost concern; particularly in LMIC contexts already confronted with erratic availability of essential medicines. Many clinicians and scholars further speculate that an inadvertent consequence of the pandemic will be an increase in late diagnoses of childhood cancers once the pandemic has stabilized (Lancet). It is therefore critical that we document COVID-related health system disruptions on vulnerable and priority populations in order to generate evidence-informed strategies for efficient, reliable and sustainable availability of drugs amidst competing allocative demands.
2.3. The ACCESS East Africa Initiative: Leveraging a pre-existing network to examine impacts of COVID-19
Access to Childhood Cancer Essentials (ACCESS) (https://accessentials.org) is an international initiative with a mission to create and implement innovative solutions to childhood cancer drug access in LMICs. Through this initiative, ACCESS East Africa (EA) was cultivated through the engagement of health system stakeholders, clinicians and researchers from Canada, the USA and five East African countries—Ethiopia, Kenya, Tanzania, Rwanda and Uganda—with the vision to strategize sustainable solutions for improved paediatric cancer treatment. Throughout 2019, our ACCESS EA Core Team—comprised of 14 clinicians and researchers from each country—have been engaged in a program of research to identify current barriers to childhood cancer drug availability in each respective East African country. The emergent impacts of COVID-19 have left our partners concerned for both the safe management of immunocompromised children with cancer, and for the availability of important supportive care drugs that may be increasingly utilized for COVID-related care.
2.4. A detailed comparative health systems analysis of COVID impacts on non-COVID care
Children with cancer in LMICs are exemplar of a uniquely vulnerable priority group, where impacts of COVID-19 on non-COVID-19 care may have outsized impact and, therefore, serve as a priority population for pandemic impacts on non-COVID care. Given the comparative element of this study, there is an opportunity to gauge various health system approaches to ensuring continuity of cancer drug treatment availability and access. In this current pandemic context, and on the strength of our pre-existing ACCESS East Africa collaborative network, this investigation will yield transferable lessons and models relevant to drug policy and program development across a range of LMIC settings. The results generated will yield important empirical insight into LMIC health system disruptions, as they affect drug availability and access for both COVID and non-COVID-related care.
3. Aim and Objectives
The aim of this study is to evaluate the impacts of COVID-19 on drug access in LMICs through comparative analysis of effects on non-COVID care in a priority vulnerable population.
Objective 1: To provide a detailed metrics of drug availability and cost for essential cancer and supportive care drugs, including priority agents for COVID-related care, in five East African countries;
Objective 2: To identify and compare COVID-19-related health system barriers to and facilitators of drug access for childhood cancer care across five East African country contexts.
4. Methods
4.1. Design and Setting: We will undertake a comparative health systems analysis of access to essential drugs for childhood cancer care across five LMIC contexts (Ethiopia, Kenya, Tanzania, Rwanda and Uganda) through a convergent parallel mixed-methods design. Case studies of childhood cancer care in each of these countries will enable inferences on the impacts of COVID-19 on the availability of both cancer and supportive care drugs, including agents relevant to COVID care, in the context of emerging global shortages of such agents.
4.2. Objective 1: COVID-19 impacts on drug availability and price: We will collect and analyze drug availability and cost data in 9 collaborating institutions: Tikur Anbessa Specialized Hospital (TASH) (Addis Ababa, Ethiopia), Aga Khan Hospital (AKH) (Nairobi, Kenya), Kenyatta National Hospital (Nairobi, Kenya), Jaramogi Oginga Odinga Referral and Teaching Hospital (Kisumu, Kenya), Moi University Teaching and Referral Hospital (Eldoret, Kenya), Bugando Medical Centre (Mwanza, Tanzania), Muhimbili National Hospital (Dar es Salaam, Tanzania), Butaro Cancer Centre (Butaro, Rwanda), and Uganda Cancer Institute (Kampala, Uganda). Retrospective and prospective collection will facilitate comparisons of drug availability prior to and during the COVID pandemic. Data collection will be led by local data managers (pharmacists) who have already been recruited at each partnering site.
Data collection: We will leverage existing institutional drug inventory systems in each of the 8 East African partner sites to collect data for a 6-month period prior to the onset of COVID-19 (June-December 2019). Data for a set of 53 essential cancer and supportive care drugs, based on the WHO Essential Medicines List for Children (2019), will include weekly drug stock quantities and stockout periods; available formulations; unit prices; and supplier and manufacturer details. Prospective collection of identical data fields for the same drugs will proceed weekly for 24 months (May 2020-May 2022) in an established REDCap database that has been pilot-tested and contextually modified in each of the 9 participating institutions (Figure 1). Aggregate, de-identified clinical data on institutional childhood cancer diagnoses, stage, treatment protocols and timing, and other relevant covariates (e.g. geography, socio-economic status[SES]) will be captured retrospectively (June-Dec 2019) and prospectively on a monthly basis in each of the 9 partner sites to ascertain the impacts of drug shortages on receipt of optimal care.
Figure 1. Snapshot of REDCap database to track institutional drug stock data
Data Analysis: Descriptive statistics on cumulative stock-out days per drug, annual trends in stocks-outs by month, and mean/median stock-out days and prices will be computed. A multivariable mixed model will analyze the relationships between drug prices and stock-outs, temporal variance in drug availability, and drug price fluctuation over time. We will model the impact of shortages on optimal cancer care through comparisons of stockout type and duration with annual disease-specific incidence of childhood cancers and institutional treatment protocols at participating sites.
4.3. Objective 2: COVID-19-related determinants of childhood cancer drug access: To investigate COVID-19-related determinants to drug access, we will conduct: (1) in-depth, semi-structured interviews with stakeholders involved in childhood cancer care, systems of drug procurement and supply, and/or health policy and program development in participating countries; and (2) document and policy analysis to contextualize each health system and their COVID-19 response. Qualitative data collection and analysis will draw on a constructivist grounded theory approach. Questions will seek to elicit challenges in drug access prior to and during the COVID-19 pandemic to ascertain variance in care and treatment access as a result.