DOI: 10.5061/dryad.ksn02v7c4
title: Caffeine citrate status, availability and practice across Nigeria, Ethiopia, Kenya, South Africa and five States in India

description: Apnea of prematurity (AOP) is a common complication among preterm infants
 (&lt;37 weeks gestation), globally. However, access to caffeine
 citrate (CC) that is a proven safe and effective treatment in high income
 countries is largely unavailable in low-and-middle income countries, where
 most preterm infants are born. Therefore, the overall aim of this study
 was to describe the demand, policies, and supply factors affecting the
 availability and clinical use of CC in LMICs. A mixed methods approach was
 used to collect data from diverse settings in LMICs including Ethiopia,
 Kenya, Nigeria, South Africa, and India. Qualitative semi-structured
 interviews and focus group discussions were conducted with different
 health care providers, policymakers, and stakeholders from industry.
 Additional data was collected using standard questionnaires. A thematic
 framework approach was used to analyze the qualitative data and
 descriptive statistics were used to summarize the quantitative data. The
 findings indicate that there is variation in in-country policies on the
 use of CC in the prevention and treatment of AOP and its availability
 across the LMICs. As a result, the knowledge and experience of using CC
 also varied with clinicians on Ethiopia having no experience of using it
 while those in India have greater knowledge and experience of using it.
 The in turn influenced the demand and our findings show that only 29% of
 eligible preterm infants are receiving CC in these countries. There is an
 urgent need to address the multilevel barriers to accessing CC for
 management of AOP in Africa. These include cost, lack of national policies
 and therefore lack of demand stemming from its clinical equivalency with
 aminophylline.  Practical ways to reduce the cost of CC in LMICs
 could potentially increase its availability and use.
description: <strong>Study design, setting, population,
 sampling</strong> We conducted a landscape
 evaluation involving stakeholders in Africa (Ethiopia, Kenya, Nigeria,
 South Africa) and South Asia (India – five states of Delhi; Bihar, Uttar
 Pradesh, Telangana and Madhya Pradesh) on CC availability and use from 1
 July 2022 to 31 December 2022. We used a mixed methods study design to
 understand the complexity of CC availability and use across these LMICs.
 We selected a geographically and culturally diverse countries with high
 annual preterm births (~200,000). The selection of stakeholders within
 each focus country was by convenience and/or purposive sampling. We
 selected health facilities providing care for preterm infants and were
 able to provide the data required to achieve the study’s objectives.
 Proximity and ease of data collection was also factored into selection by
 research teams. <strong>Data
 collection</strong>
 <em>Qualitative</em> The research
 teams conducted key informant interviews and focus group discussions
 (FGD’s) with stakeholders in newborn health. The interviews with
 healthcare providers sought to explore their experience of using CC as a
 treatment for AOP. Interviews with WHO and Ministry of Health officials
 sought to understand current global and national health policies and CC’s
 inclusion in the essential drug list for using CC to treat AOP. 
 Interviews with major drug suppliers and distributors of CC aimed
 to determine the current local market pricing of CC and its alternatives
 within and between countries. Also, to evaluate the factors determining
 the end-customer price of CC. The available average end-customer price per
 country was used to determine the daily cost of managing AOP for
 aminophylline and CC. We compared the average daily cost between
 aminophylline and cc for both public and private hospitals in each
 country. The dosing regimen for CC was a loading dose of 20 mg/kg/dose and
 a daily maintenance dose of between 5 to 10 mg/kg/day. The dosing regimen
 for aminophylline was a loading dose of 6 mg/kg administered intravenously
 (IV), followed by a maintenance dose of 2.5 mg/kg/dose/IV administered
 every 8 hours.  Interviews and FGD’s were done in
 person or virtually over video or audio teleconferencing based on the
 preferences of the participants. All interviews were conducted in English.
 teams were situated in each country of focus and had previous training and
 experience conducting qualitative interviews and FGDs and in qualitative
 data analysis. The interviews and FGDs were semi structured using guide
 with a set of open-ended questions, in a set order and allowing for
 in-depth insights into the subject area. These guides were pilot tested
 across the 3 countries prior to data collection.
 <em>Quantitative</em> Additional
 interviews were conducted using standard questionnaires and had been
 piloted and refined in these settings prior to being used for data
 collection.The research team surveyed 107 providers: 20 from Ethiopia, 18
 from India, 23 from Kenya, 28 from Nigeria, and 18 from South Africa.
 Providers were from 45 private or public health facilities across the five
 study countries. Of these, 12 (27%) were primary or secondary public, 7
 (16%) were primary or secondary private, 25 (56%) were tertiary public,
 and 1 (2%) tertiary private <strong>Demand
 forecast for caffeine citrate.</strong> A demand
 forecast was conducted to determine the amount of CC needed per country.
 Using data from demographic health survey data from each country, we
 estimated the proportion of infants who would be eligible for CC
 treatment. Given AOP risk can be as high as 80% in preterm infants with
 birthweight ≤1500g (very low birth weight (VLBW)), we estimated that all
 VLBW infants met eligibility criteria for treatment with CC. We limited
 this forecast to public facilities where limited government funding
 constrains drug availability. We applied country-specific policies and
 assumptions to determine the percentage of VLBW infants who received or
 had a missed opportunity for CC treatment. These assumptions included,
 availability of CC, VLBW infants born in secondary facilities will be
 transferred to a tertiary center capable of providing AOP treat; some
 transfers will be unsuccessful and even when successful, AOP treatment
 will be unavailable. <strong>Data management and
 analysis</strong> All interviews were transcribed
 verbatim by an experienced transcriber. Authors reviewed the interview
 transcripts for errors. A coding framework was generated, and an emergent
 thematic analysis approach was used to analyze the data, to identify
 patterns and themes. Descriptive statistics were used to summarize the
 quantitative data.
description: # Caffeine Citrate data across five low- and middle-income countries
 [https://doi.org/10.5061/dryad.ksn02v7c4](https://doi.org/10.5061/dryad.ksn02v7c4) This dataset is responses from stakeholders and providers describing the demand, policies, and supply factors affecting the availability and clinical use of Caffeine Citrate (CC) across Nigeria, Ethiopia, South Africa, Kenya and five States in India (where permission was given to share with the public). The dataset covers responses on the presence or absence of caffeine citrate in the Essential Medicines List (EML) and treatment guidelines, apnea of prematurity treatment protocols and practices, different brands of drugs registered in countries, procurement information and barriers limiting access. The data gives insights into status of caffeine, the treatment practices and barriers to access in each country. Apnea of prematurity (AOP) is a common complication among preterm infants (&lt; 37 weeks' gestation), globally. However, access to that is a proven safe and effective treatment in high income countries is largely unavailable in low-and-middle income countries, where most preterm infants are born. ## Description of the data and file structure The country excel file structure is structured in a question and response manner which qualitative and quantitative responses to policy, guidelines, treatment practices on caffeine citrate for the prevention or treatment of apnea of prematurity. While some deviations exit in the country data set, the questions and responses are structured within the theme below: 1. **EML & Guidelines:** Knowing if Caffeine Citrate (CC) is already on the Essential Medicines List (EML) and represented in the guidelines for treatment of Apnea of Prematurity (AOP). 2. **Treatment Protocol:** Understanding how Apnea of Prematurity (AOP) is treated and what drugs are used and how he decision on which drug to use is made. Differences between national treatment guidelines for AOP and how AOP is treated in practice and what is causing those differences. 3. **Procurement:** Understanding how drugs used for Apnea of Prematurity (AOP) treatment are procured, what funding is available to procure them. 4. **Registration:** Understanding what drugs used for Apnea of Prematurity (AOP) treatment are registered, and if Caffeine Citrate (CC) products are not registered, how long registration would take. 5. **Introduction Preparation:** Understanding whether preparation activities would be required to introduce Caffeine Citrate (CC) if it is not already available and how long those would take. 6. **Caffeine Citrate Demand:** Understanding why Caffeine Citrate (CC), specifically, is not utilized. 7. **Other information:** Additional findings or information that you wish to share. In addition, the word doc with table Supplement, provides forecast data inputs and assumptions for the demand forecast determine the amount of CC needed per country. Where data is not available, the code NA is used to indicate missing data codes. Where data is not applicable, the code N/A is used to indicate unapplicable data. ## Sharing/Access information Data was derived from the following sources: * Stakeholder interviews * Health facility provider interviews and FGDs * Facility procurement and stock information