Implementing new health interventions in developing countries: why do we lose a decade or more?

Abstract

Background: It is unclear how long it takes for health interventions to transition from research and development (R&D) to being used against diseases prevalent in resource-poor countries. We undertook an analysis of the time required to begin implementation of four vaccines and three malaria interventions. We evaluated five milestones for each intervention, and assessed if the milestones were associated with beginning implementation.

Methods: The authors screened World Health Organization (WHO) databases to determine the number of years between first regulatory approval of interventions, and countries beginning implementation. Descriptive analyses of temporal patterns and statistical analyses using logistic regression and Cox proportional hazard models were used to evaluate associations between five milestones and the beginning of implementation for each intervention. The milestones were: (A) presence of a coordinating group focused on the intervention; (B) availability of an intervention tailored to developing country health systems; (C) international financing commitment, and; (D) initial and (E) comprehensive WHO recommendations. Countries were categorized by World Bank income criteria.

Results: Five years after regulatory approval, no low-income countries (LICs) had begun implementing any of the vaccines, increasing to an average of only 4% of LICs after 10 years. Each malaria intervention was used by an average of 7% of LICs after five years and 37% after 10 years. Four of the interventions had similar implementation rates to hepatitis B vaccine (HepB), while one was slower and one was faster than HepB. A financing commitment and initial WHO recommendation appeared to be temporally associated with the beginning of implementation. The initial recommendation from WHO was the only milestone associated in all statistical analyses with countries beginning implementation (relative rate = 1.97, P < 0.001).

Conclusions: Although possible that four milestones were not associated with countries beginning implementation, we propose an alternative interpretation; that the milestones were not realized early enough in each intervention's development to shorten the time to beginning implementation. We discuss a framework built upon existing literature for consideration during the development of future interventions. Identifying critical milestones and their timing relative to R&D, promises to help new interventions realize their intended public health impact more rapidly.

Figure 1

New interventions: From R&D to implementation (illustrative). *Drugs, Vaccines Diagnostics, Reproductive health supplies. **WHOPES: WHO Pesticide Evaluation Scheme

Figure 2

Frost and Reich’s (2008) access framework. The figure presents access as depending on a coordinating architecture that ensures that availability, affordability and adoption considerations are addressed for an intervention. Architecture: Organizational structures and relationship established with the purpose of coordinating and steering the availability, affordability, and adoption activities. Availability: Logistics of making, ordering, shipping, storing, distributing, and delivering a new health technology to ensure it reaches the hands (or mouths) of the end-user. Affordability: Ensuring that health technologies and related services are not too costly for the people who need them. Adoption: Gaining acceptance and creating demand for a new health technology from global organizations, government actors, providers and dispensers, and individual patients. The concept of “acceptability” is inherent in “End-User Adoption and Appropriate Use” but was made explicit in the graphic above to illustrate this framework’s consistency with the work of other authors. Reproduced under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License [8]

Figure 3

Proportion of implementing countries over time in each income category, stratified by intervention. The figure presents the proportion of countries implementing each intervention by year since regulatory approval. Panel A = High income countries; B = Upper middle income countries; C = Lower middle income countries; D = Low income countries. Color code: Hepatitis B vaccine (HepB) = Blue; Haemophilus influenzae type b vaccine (Hib) = Dark red; Rotavirus vaccine (RV) = Green; Pneumococcal vaccine (PC) = Purple; Artemisinin-based combination therapy (ACT) = Light red; Insecticide-treated mosquito net (ITN) = Orange; Rapid diagnostic test (RDT) = Black

Figure 4

Beginning implementation of each intervention by countries, by income group, including hypothesized milestones. Panels A-G present the proportion of countries beginning to implement each intervention by year since the year of regulatory approval. Panel A = Hepatitis B vaccine; B = Haemophilus influenzae type b vaccine; C = Rotavirus vaccine; D = Pneumococcal conjugate vaccine; E = Insecticide-treated mosquito net; F = Rapid diagnostic test; and G = Artemisinin-based combination therapy. For vaccines, countries are stratified according to World Bank income groups: High = Blue dotted line; Upper‐ middle = Red short dashed line; Lower‐ middle = Green long dashed line; Lower = Purple line. Malaria-endemic countries are stratified by low income versus all other endemic countries. LICs = Purple line; Other endemic countries = Red dash and dot line. Year of regulatory approval (year 0) is provided in the bottom left hand corner of each panel. Ar indicates establishment of a group providing coordination (i.e. architecture). II indicates availability of an improved intervention better aligned with the needs of developing countries. Fi indicates year of a global financing commitment, such as through GAVI or GFATM. IR indicates year of initial WHO recommendation. CR indicates year of comprehensive (e.g. global) WHO recommendation

Figure 5

Time from regulatory approval to WHO recommendation and financing, by intervention. Interventions are presented from earliest to most recent year of regulatory approval. The year of regulatory approval and intervention name are indicated below each set of bars. Dark blue bars indicate the number of years to an initial recommendation, when relevant, while light blue bars indicate the number of years to a comprehensive recommendation. Green bars indicate the number of years to a financing commitment

Figure 6

Effect of time since regulatory approval on rate of beginning implementation. The vertical axis shows the rate of beginning implementation (i.e. adoption) of interventions according to the number of years since regulatory approval. All interventions are included, except where too few countries were relevant to the analysis, as noted below. The grey area indicates the 95% confidence region around the result. A. High income countries only. Analysis includes all interventions except those against malaria. B. Low income countries only. Analysis includes all interventions except rotavirus vaccination

Figure 7

Proposed access framework incorporating R&D and implementation periods. The area in grey represents the original access framework as shown in Figure 2. Other areas are new to the framework. Actions that take place during the R&D period are described in the space above the black strip, “Regulatory Approval”, while actions carried out in the decision and implementation period are described in the space below. Area in grey is reproduced under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License [8]