ORIGINAL ARTICLE: GASTROENTEROLOGY

Cost-Effectiveness Analysis of Zinc Supplementation

for Treatment of Acute Diarrhea in Children
Younger Than 5 Years in Colombia


Aurelio Mejı́a, ySara Atehortúa, z§Iván D. Flórez, zJavier M. Sierra,
§
Marı́a E. Mejia, and §Carolina Ramı́rez

ABSTRACT
treatment without zinc (reduction of $15,210 COP [8.14 USD] per child).
Objective: The objective of this study was to determine the cost-effective-
The results are sensitive to changes in the probability of hospitalization and
ness of zinc supplementation for the treatment of acute diarrhea (AD) in
of persistent diarrhea.
children younger than 5 years in Colombia.
Conclusions: Zinc for the treatment of AD is a highly cost-effective strategy
Methods: The cost-effectiveness analysis was performed from the
and is recommended for inclusion in the benefit plan of the Colombian health
Downloaded from http://journals.lww.com/jpgn by BhDMf5ePHKbH4TTImqenVA+lpWIIBvonhQl60Etgtdnn9T1vLQWJq/+R2O4Kjt58 on 11/30/2021

perspective of the Colombian health system. The standard treatment with

the addition of zinc was compared with the standard treatment without zinc
in children younger than 5 years. The time horizon was 1 month.
Effectiveness was extracted from a systematic review of literature. The
specific data for Colombia were taken from local databases and
observational studies. To determine the costs, a typical case was
constructed by reviewing guidelines and medical records and validated
by experts. To evaluate the resources consumed, Colombian tariff manuals
were used. Costs were stated in Colombian pesos (COP) and US dollar
(USD) for 2010. Deterministic sensitivity analysis was performed to
evaluate the impact of changes in cost and effectiveness of the strategies
on the results from the model.
Results: The results from the model indicate that zinc supplementation is a
dominant strategy; it is less costly and more effective than standard
Received May 6, 2014; accepted November 13, 2014.
From the
Instituto de Evaluación Tecnológica en Salud—IETS, Bogota,
the yDepartment of Economy and Health Economics Group, School of
Economic Sciences, University of Antioquia, Medellin, the zDepartment
of Pediatrics, School of Medicine, Pediaciencias Research Group,
University of Antioquia, Medellin, and the §Health Economics Group,
School of Economic Sciences, University of Antioquia, Medellin,
Colombia.
Address correspondence and reprint requests to Iván D. Flórez,
Departamento de Pediatrı́a y Puericultura, Universidad de Antioquia,
Calle 67 No. 51–27, Quinto piso del Hospital Infantil San Vicente
Fundación—HUSVF, Medellı́n, Colombia (e-mail: ivan.florez@udea.
edu.co).
This study was part of the large project Guı́a de Práctica Clı́nica de
prevención, diagnostico, y tratamiento de la enfermedad diarreica aguda
en niños menores de cinco años (Clinical Practice Guideline of preven-
tion, diagnosis, and treatment of acute diarrheal disease), that was
financed by Departamento Administrativo de Ciencia, Tecnologı́a e
Innovación-COLCIENCIAS and the Ministry of Health and Social
Protection of Colombia, in the Grant of Convocatoria 500 of 2009–
2010. The development of the specific paper about economic evaluation
was supported by the Estrategia de 2011–2012 del Grupo de Economı́a
de la Salud de la Universidad de Antioquia. The authors were indepen-
dent from the funding body during the process of generating this
investigation.
I.D.F. served on the speakers’ bureau of Humax Pharmaceutical (Colombia)
between 2010 and 2011. The other authors report no conflicts of interest.
Copyright # 2015 by European Society for Pediatric Gastroenterology,
Hepatology, and Nutrition and North American Society for Pediatric
Gastroenterology, Hepatology, and Nutrition
DOI: 10.1097/MPG.0000000000000638
system. This intervention is more cost-effective in children with a higher risk
of persistent diarrhea and hospitalization.
Key Words: Colombia, costs and cost analysis, diarrhea, dietary
supplements, gastroenteritis, health care financing, infantile,
micronutrients, zinc
(JPGN 2015;60: 515–520)
A cute diarrhea (AD) is the third leading cause of mortality
among children younger than 5 years in the world, after
neonatal diseases and respiratory infections (1,2). It is a self-limit-
ing disease but still continues to claim lives, especially in children
from developing countries, where the conditions of poverty, limited
access to health services, and nutritional deficiencies are highly
prevalent (3). Most deaths from AD are from medical compli-
cations, such as dehydration and malnutrition as well as persistent
diarrhea (PD), which is an important link in the chain of events that
lead to a fatal outcome. Although only 10% to 15% of the children
with diarrhea who seek medical treatment have PD, it is present in
half of the patients who die (4).
The mainstay of treatment of AD according to the World
Health Organization (WHO) is summarized in Plan A for the
treatment of diarrhea, which includes measures such as prevention
of dehydration with adequate liquids at home and oral rehydration
salts (ORS), maintenance of oral feeding, and administration of zinc
supplements (5,6). Zinc supplementation is the only pharmacologi-
cal intervention recommended by the WHO in children with
diarrhea because it has shown efficacy in several clinical trials
and systematic reviews (SRs) (7) and is especially useful in children
with deficiencies of this micronutrient. Despite the proven efficacy
of this intervention, its implementation has not been possible in all
developing countries (8). In the case of Colombia, this supplement
was not covered by the mandatory health plan until 2013, despite
the fact that 43% of children between 1 and 4 years have a zinc
deficiency (9) and that the strategy outlined in the Integrated
Management of Childhood Illness (IMCI) recommends the admin-
istration of zinc to all of the children with acute diarrhea in the
country since 2005 (10).
Studies evaluating zinc for the treatment of diarrhea from an
economical perspective have not been performed in Colombia or
Latin America. Although the intervention is not particularly expens-
ive, it is necessary to take into account that it is a strategy directed at

JPGN  Volume 60, Number 4, April 2015 515

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 Flórez et al
a broad population, which may have an important impact on health
system costs. Thus, the objective of this study was to perform a cost-
effectiveness analysis on zinc as a treatment of AD in children
younger than 5 years from the perspective of the Colombian health
system.
METHODS
The cost-effectiveness analysis was performed from the
perspective of the Colombian health system. The health options
considered were the following: the addition of zinc to the standard
treatment for AD and the standard treatment without supplement-
ation. The standard treatment for AD comprises Plan A recom-
mended by WHO, which includes continual feeding of the child
during the episode and maintaining hydration with ORS. The
recommended and used zinc dosage for treatment is 10 mg in
children younger than 6 months and 20 mg in children older than
6 months for 10 to 14 days. These doses are based on the recom-
mendation of administering twice the recommended dietary allow-
ance, which is the minimum daily dietary requirement, by age, of a
nutrient required to maintain normal function (4). Zinc was eval-
uated in its pharmacological presentation of any of its salts (sulfate,
acetate, or gluconate) and without additional micronutrients.
To estimate the expected costs and health outcomes of the 2
alternatives, a decision model that reflects the health outcomes of
patients with AD who are younger than 5 year was constructed
(Fig. 1). The analysis only considers children from birth until they
are 5 years old, and children with AD and an underlying chronic
disease (severe malnutrition and immunosuppression) were
excluded. The model assumes that the major risk to assess in the
context of this intervention is that of death associated with PD
requiring hospitalization, and therefore this was the outcome
selected for the cost-effectiveness analysis. Although zinc has
been associated with decreased fecal output and thus a decrease
in dehydration and death caused by dehydration, the relation
between treatment with zinc and mortality from dehydration has
not been proven directly. For this reason, the effect on the duration
of diarrhea (represented by the probability of PD) was emphasized,
which is an effect of greater clinical significance.
Because of the acute nature of the disease and the charac-
teristics of the interventions, the time horizon was 1 month, and thus
it was not necessary to apply a discount rate. This horizon is
adequate because the relevant costs and outcomes that may influ-
ence the decision are present while the diarrheic episode persists
(which usually does not last >1 month), and zinc must be adminis-
tered each time the child presents with an AD episode.
Persistent diarrhea
Standard treatment
with zinc
No persistent
diarrhea
Children <5 years
of age with
acute diarrhea
Persistent diarrhea
Standard treatment
without zinc
No persistent
diarrhea
FIGURE 1. Decision tree for the evaluation of zinc for the treatment of acute diarrhea.
516
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JPGN  Volume 60, Number 4, April 2015
To estimate transition probabilities, an exhaustive search was
performed in the MEDLINE, EMBASE, LILACS, and CINAHL
databases and in the Centre for Reviews and Dissemination data-
base of the University of York in all languages from September
1966 to June 2012 to obtain SRs and meta-analyses that included
controlled clinical trials comparing zinc with placebo for the
treatment of acute diarrhea. In addition, we also searched references
from clinical practice guidelines for the management of a child with
diarrhea or gastroenteritis.
The search used MeSH terms and free text words related with
zinc and its pharmaceutical presentations (tablets, syrup, sulfate,
gluconate, acetate, and supplementation) combined with terms
related to diarrhea (diarrh
, diarrhoea, diarrhea, gastroenteritis,
and gastrointestinal infections, among others). SRs that exclusively
analyzed articles for the prevention of diarrhea or other diseases
were excluded. Two researchers evaluated the quality of the
SRs independently.
Because the SRs evaluated different clinical outcomes, we
used the Grading of Recommendations Assessment, Development,
and Evaluation (GRADE) working group methodology (11) to
prioritize reviews that had the best clinical outcome, that is, the
effect on the duration of the diarrheic episode. To evaluate this
effect, outcomes based on categorical variables that used different
cutoffs for the persistence of diarrhea in number of days were
considered. The WHO defined PD as an episode that lasts for
14 days or more (6). It is considered a problem of great magnitude
because of its association with malnutrition and is the cause of half
to one-third of deaths as a result of diarrhea (12). Because the
outcome of the incidence of PD was not analyzed in any of the SRs,
but some studies and SRs analyzed the outcome of the incidence of
AD on the seventh day after the start of the intervention or the
placebo, it was decided that this outcome could be an approximation
of the incidence of PD. This decision is based on the fact that, in
these studies, zinc was administered to children with episodes of
diarrhea between 3 and 14 days in duration, and having diarrhea on
day 7 implies it will remain for approximately 10 to 21 days;
therefore, it can be assumed that an estimate of AD >7 days after
the beginning of the intervention will meet the definition of PD
(>14 days).
Of the 7 SRs (13–19), 3 considered the outcome of diarrhea
of >7 days. The SR by Bhutta et al (13) was ruled out because it
included studies up to 1999, and of the 3 remaining SRs, the 2 most
recent were more comprehensive, and of both, the Cochrane
publication by Lazzerini and Ronfani (14) was chosen because it
used GRADE methodology to evaluate the outcome of interest,
Outpatient
treatment
Alive
Inpatient treatment
Death
Outpatient
treatment
Alive
Inpatient treatment
Death
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 JPGN  Volume 60, Number 4, April 2015
provided more information about the 6 pooled studies for this
outcome, and provided as well a more exhaustive assessment of
heterogeneity (which was not so high, I2 index 35%) compared with
Lamberti et al (19). In spite of these differences, effect size of both
the SRs for our outcome was almost the same (Lazzerini relative
risk [RR] 0.73 vs Lamberti RR 0.74), and if we assume that the same
6 studies were used in both the SRs (Lamberti does not describe
them), the difference must be because of the methods of combi-
nation: Lazzerini used mixed-effects model, whereas Lamberti used
the random effects model. Therefore, we decided to use RR 0.73 as
the measure of the effect. The outcome of diarrhea >7 days had a
moderate quality, which increases the reliability of the results (14).
To estimate the remaining probabilities of the model, infor-
mation on the effectiveness of treatment with zinc was comple-
mented with data from Colombian descriptive studies that clinically
characterized the progress of >17,000 children with diarrhea
treated in a hospital in Medellı́n, Colombia (20,21). Although
the studies are not recent, treatment with zinc is rather uncommon
in Colombia, and therefore we can use these data as an approximate
measure of baseline probabilities. Bearing this in mind, we per-
formed sensitivity analysis on these variables to assess their impact
on the cost-effectiveness of zinc (see below).
A publication of the WHO (22) was used to analyze the
impact of zinc supplementation on mortality and hospitalization
rates because of diarrhea. The transition probabilities are shown in
Table 1.
Identification and measurement of resource use was based on
clinical practice guidelines and the IMCI, WHO, and UNICEF
strategy, considered the most important strategy for diarrhea treat-
ment in Colombia and a lot of developing countries. In addition,
medical records of children diagnosed as having AD and treated in 2
hospital centers in Medellı́n and Bogotá were reviewed to validate
the previous step. Finally, the results were discussed with clinical
experts on the management of children with AD.
To estimate drug unit costs, we consulted reports of the
SISMED database (official database of the Colombian Ministry of
Health and Social Protection) (23) between January and December
2010. Other costs were obtained from a wholesale distributor of
medical supplies and the cost of zinc from one of the pharmaceu-
tical companies that produced the drug during the study. To estimate
the unit cost of procedures, the Institute of Social Security (ISS)
tariff manual was used with a 30% adjustment and a range of 25% to
48% for the sensitivity analysis. These values were determined from
TABLE 1. Transition probabilities
Variable Variable description
Probability of PD Children with PD in a study performed in
Medellı́n
Probability of hospitalization Hospitalized children with PD in a study
in children with PD performed in Medellı́n
Probability of mortality Mortality caused by diarrhea reported in
in children with PD different studies
RR of the incidence of PD Effect of zinc in the incidence of diarrhea on
day 7 after starting the intervention or the
placebo. This value is used as an
approximation of the RR of the incidence
of PD, as specific data for PD is unavailable
RR of mortality Effect of zinc on mortality caused by diarrhea
RR of hospitalizations Effect of zinc on requiring hospitalization
because of diarrhea
PD ¼ persistent diarrhea; RR ¼ relative risk.
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Cost-Effectiveness Analysis of Zinc Supplementation
a consultation on the rates used for contracting health services in
2010 by representative insurers of the country. Costs for each of the
outcomes of the model, by level of care, are presented in Table 2. All
costs are expressed in Colombian pesos (COP) for 2010. Costs in
US dollars (USD) were calculated using the representative
exchange rate for 2010 reported by the Bank of the Republic of
Colombia (1898.68 COP for each USD).
We present average and incremental expected costs and
effects for each strategy. We performed extensive deterministic
sensitivity analysis (1- and 2-way) for the unit cost and effectiveness
of zinc and baseline probabilities of PD and hospitalization. We
present the results of this sensitivity analysis as a tornado diagram,
which shows how each variable affects the results of the analysis.
For this analysis, we used the net monetary benefits, which
represent the value of the intervention over and above its additional
costs (including opportunity costs, represented by the cost-effec-
tiveness threshold). In Colombia, a threshold has not been explicitly
defined, and the aim of this evaluation is not to develop an estimate
of willingness to pay for health results; however, to interpret the
results of this study, we will use the WHO recommendation, which
establishes that an intervention can be considered cost-effective if
the incremental cost-effectiveness ratio is <3 times the per-capita
GDP, corresponding to 36,143,349 COP (19,036 USD) for 2010.
Finally, taking into account that the rates for a hospital stay of high
and low complexity are different, the results are presented for both
levels of care (the base case results correspond to a low-complexity
hospital stay). The analysis was performed with the TreeAge Pro
2009 software (Tree Age, Williamston, MA).
RESULTS
The average cost of an episode of diarrhea in Colombia is
$79,432 COP (42.5 USD), and an episode of a child receiving zinc
would decrease it to $64,222 COP (34.36 USD), a reduction of
$15,210 COP (8.14 USD). The zinc strategy is more effective (lower
mortality associated with diarrhea) and of a lower cost (Table 3).
In the 1-way sensitivity analysis, the decision is not modified
by changes in the effectiveness of the treatment, the cost of zinc, or the
costs of PD care (of low or high complexity). Using the rates
ISS þ 25% or ISS þ 48%, zinc continues to be the dominant strategy.
The results are more sensitive to changes in the probability of
PD and in the probability of hospitalization. Variations in these
parameters influence the risk of mortality and thus the effectiveness
Base case Minimum Maximum Source
0.11 0 0.11 Bernal et al, 2001 (21)
0.568 0 0.568 Bernal et al, 1994 (20)
0.0009 0 0.0105 Bernal et al, 1994 (20)
0.73 0.61 0.88 Lazzerini and Ronfani,
2012 (14)
0.77 0.69 0.85 Fischer-Walker et al,
2009 (22)
0.77 0.69 0.85 Fischer-Walker et al,
2009 (22)
517
 Flórez et al
TABLE 2. Cost for each outcome in the base case (rates ISS þ 30%)
Outcome
Acute diarrhea without dehydration, outpatient $27,397 COP (14.66 USD)
PD, outpatient $97,811 COP (52.33 USD)
Inpatient PD, alive $803,551 COP (429.91 USD)
Inpatient PD, death
COP ¼ Colombian pesos; ISS ¼ Institute of Social Security; PD ¼ persistent diarrhea; USD ¼ US dollar.
achieved with zinc. Specifically, if the probability of hospitalization
is <13% or the probability of PD is <12.4%, which are uncommon
scenarios, treatment with zinc would not be cost-effective, assum-
ing a willingness to pay threshold of 3 times the Colombian GDP
per capita.
The results of 1-way sensitivity analysis are shown in Figure 2
as a tornado diagram. In this figure, vertical black lines show points
where decision changes from one strategy to another. Changes in the
effectiveness or cost of zinc do not modify decision, and treatment
with zinc is a dominant strategy. However, if the probability of PD is
<0.036 or the probability of hospitalization in children with PD is
<0.158, treatment with zinc would not be considered cost-effective.
In a 2-way sensitivity analysis we found that with a probability of PD
close to 10%, the probability of hospitalization must be close to 13%
for zinc to be a cost-effective strategy.
DISCUSSION
The results indicate that zinc supplementation is a dominant
strategy; therefore, it is recommended for the routine treatment of
acute diarrhea in children younger than 5 years of age in Colombia.
The intervention would be particularly cost-effective in children
with a high risk of PD and a high risk of mortality as a consequence
of AD (20,24). The results of this analysis are similar to those
reported in the literature for other developing countries, such as
India, the Philippines, and Tanzania (25–27), and are additional
evidence for adopting the WHO recommendation. In these analyses,
the strategy was dominant, with a lower cost and a stronger effect
than the standard treatment. Those findings recommend the admin-
istration and incorporation of zinc as a therapeutic strategy that
would reduce costs and even save lives (28).
The strategy to administer zinc as a treatment for AD has its
origin in 2004, when the WHO and UNICEF established 2 recom-
mendations to impact mortality rates of children with diarrhea
around the world: the use of oral rehydration solutions of low
osmolarity for the prevention and treatment of diarrhea, replacing
those with normal osmolarity, and the administration of zinc for 10
to 14 days (22). These recommendations have been implemented in
the IMCI strategy since the last decade. Several clinical trials
analyzed in SRs by Lazzerini and Ronfani (14) and Lamberti
et al (19) have shown that the administration of zinc reduces the
duration and the probability that an AD episode becomes PD
compared with the administration of a placebo.
A shorter duration of diarrhea leads to fewer days of hos-
pitalization and a decrease in the mortality and morbidity caused by
TABLE 3. Zinc for the treatment of AD
Strategy Cost Incremental cost
Zinc $64,222 COP (34.36 USD)
No zinc $79,432 (42.5 USD) $15,210 (8.14 USD)
Base case results. AD ¼ acute diarrhea; COP ¼ Colombian pesos; USD ¼ US dollar.
518
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JPGN  Volume 60, Number 4, April 2015
Low complexity High complexity
$27,397 COP (14.66 USD)
$97,811 COP (52.33 USD)
$1,207,591 COP (646.08 USD)
— $4,136,880 COP (2213.3 USD)
AD (22). If the recommendations to use zinc and ORS of low
osmolarity were implemented universally, more than three-fourths
of the mortality caused by diarrhea in the world would be eradicated
(29). The Copenhagen Consensus (a group of economic leaders)
recognized in 2008 that the administration of zinc is a cost-effective
intervention for the advance of human development around the
world (30).
Despite the known effectiveness of zinc and its relatively low
cost, uptake across many countries has been insufficient for diverse
reasons, one of them being the lack of an adequate pharmacological
presentation (22). In India and Bangladesh, large-scale zinc incorp-
oration programs have been effective in decreasing the indiscrimi-
nate use of antibiotics for episodes of AD while maintaining costs
(28,31). Despite the fact that the WHO and UNICEF issued
recommendations for the routine administration of zinc to all
children with diarrhea in 2004, by 2009, only 22 countries had
incorporated it into their programs in some way (22).
In Colombia, as in many countries in the region, until
recently, an adequate pharmacological presentation of zinc was
not available (without other micronutrients, as recommended by
WHO), which prevented the implementation of this recommen-
dation. Based on this present availability and the cost-effectiveness
evidence, the implementation of this recommendation should be
more feasible for decision makers in Colombia.
It is important to highlight that there are differences in the
costs of hospitalization among countries that prevent direct extra-
polation of these findings (27,32,33). Considering that the effec-
tiveness was extracted from an updated SR that reviewed studies
performed in developing countries, there is little reason to think that
effectiveness would vary in similar areas or argue that the transition
probabilities based on such studies could not be used as a model for
Colombia. The differences between our findings and those from
other countries with similar conditions will depend greatly on the
differences in costs; however, it is important to note that the effect
of zinc in children with diarrhea in developed countries is uncertain
(34); hence, the results can be extrapolated to a lesser extent in
that context.
This study was based on the cost of the presentation of zinc
available in Colombia, and other presentations that may be effective
and recommended, such as dispersible tablets, were not taken into
account (22). WHO only recommends tablet and syrup pharmaceu-
tical forms, without additional micronutrients that could compete for
absorption and does not recommend zinc mixed with ORS for the
treatment of diarrhea in children (35). The analysis of other accepted
presentations as tablets could change the results obtained, and
Effectiveness Incremental effectiveness Incremental C/E ratio
0.0000243 Deaths
0.0000562 Deaths 0.0000319 deaths Dominated
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 JPGN  Volume 60, Number 4, April 2015
Tornado analysis (net benefits)
EV: –69220.79681270916
–80000 –70000 –60000 –50000 –40000 –30000
FIGURE 2. Tornado diagram. Each row is a 1-way sensitivity analysis, and black lines represent points where decision changes from one strategy to
another. PD ¼ persistent diarrhea, RR ¼ relative risk.
considering that these are even less expensive, the cost-effectiveness
would be higher (36). The variables with a higher impact on the
results are the probability of PD and the risk of hospitalization, which
are outcomes on which this strategy has an effect.
According to the searches performed to date, this is the first
cost-effectiveness study of the use of zinc for treatment of a child
with diarrhea in a Latin American country and the first study to
analyze the outcome based on the effectiveness extracted from an
SR of high quality.
Therefore, decisions for the region may be adopted relying
on these results. The appropriate knowledge translation audience
for this research includes decision makers, such as Ministries of
Health or Health Technology Assessment Agencies, among others.
We believe clinicians, in particular in developing countries, to be
important recipients who should be encouraged to uptake the
clinical recommendation of prescribing zinc in children with diar-
rhea. Cost-effective analysis is underused in pediatrics as a way for
ensuring that resources are maximized to achieve optimal health for
all patients (37), so we believe that this study will help to increase its
use to improve utilization of resources and to enhance health
outcomes in children.
Regarding the limitations of the study, the short-term horizon
of the model may underestimate the effects of the interventions;
however, considering that zinc can be administered each time a new
episode is presented, we believe that the framework of analysis used
offers an adequate approximation for the decision problem that the
health system faces. Additionally, whereas mortality caused by PD
is linked tightly with death from dehydration, there is also mortality
because of dehydration in acute diarrhea; therefore, both mortality
rates are related. We think that we are underestimating mortality to
some degree, so this can be related with a small underestimation of
the benefits of zinc. Thus, the results presented reflect the minimum
benefit that would be expected with this strategy. Additionally, we
did not perform a probabilistic sensitivity analysis, but extensive
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Cost-Effectiveness Analysis of Zinc Supplementation
Probability PD (0.0–0.11) probability hospitalization
Children with PD (0.035–0.5681)
RR incidence diarrhea 7th day with zinc (0.72–0.94)
Cost zinc 80 mL (6300.0–12,600.0)
RR hospitalization with zinc (0.69–0.85)
Probability death children with PD (0.0–9.0E-4)
RR death with zinc (0.69–0.85)
–20000 –10000
sensitivity analyses were performed to evaluate the robustness
of results.
Using the probability of children with diarrhea >7 days after
the beginning of the intervention, which will result in a probability
of having diarrhea >12 days, taking into account that children in the
studies were included if they had >3 days of diarrhea and most of
the children had >4 to 5 days of diarrhea, can be considered a
limitation as we extrapolated this as having PD. None of the trials
had PD as an outcome, but we considered this approximation as the
only way to get an estimation of PD, which is the main outcome not
only for us but also for clinicians who must avoid that an AD
becomes PD. Perhaps an exact measure of proportion of PD, if any,
could reduce the cost-effectiveness of zinc.
Finally, the data used to estimate some parameters in the
model was considerably old. Although we made every effort to find
the most recent data in Colombia, there were no more recent studies,
and therefore the baseline probabilities for some parameters in the
model are subject to substantial uncertainty. Future research could
be designed to reduce this uncertainty, particularly around the
probabilities of PD and hospitalization in children with PD.
In conclusion, zinc supplementation is a dominant interven-
tion, effective for decreasing the probabilities of PD and hospital-
ization for AD, and is economically beneficial. Based on these
results, the administration of zinc in children with AD should be a
routine treatment in Colombia, with the aim of reducing the burden
of disease and costs for the health system.
Acknowledgments: The authors thank the other members of the
Colombian Clinical Practice Guideline of Prevention, Diagnosis
and Treatment of Acute Diarrheal Disease in Children Under Five
Years for their contributions because this project would not be
possible without their work: Luz Helena Lugo, Javier Contreras,
Jorge Luis Acosta, Marı́a Eulalia Tamayo, Clara Inés Serna, Álvaro
Quintero, José Fernando Vera, Marı́a Isabel Lalinde, Claudia
519
 Flórez et al
Granados, Carlos Bernal, Germán Briceño, Juan Manuel Lozano,
Fernando Sarmiento, Lina Mabel Vélez, Jesenia Avendaño, and
Ángela Marı́a Orozco. We also thank Mateo Ceballos and Paola
Ramı́rez for preparation of the article and copyediting.
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