Infectious
diseases contribute immensely to the global burden of disease that impacts
public health systems and economies especially affecting children. In 2013,
infectious diseases resulted in over 45 million years lost due to
disability and over 9 million deaths. According to UNICEF, pneumonia, diarrhea
and malaria were responsible for approximately 30 per cent of global deaths
among children under the age of 5 in 2019. In India, infectious diseases account for 58%
of all deaths among children aged 5 to 14 years.
Even among neonates, the frequency of infectious diseases,
such as typhoid, diarrhea, measles, tuberculosis, and jaundice, remains the
primary cause of infant morbidity and mortality in India. Hasan et al
reported that around 3.69 lacs children aged below five years die
every year from acute respiratory infections in India, accounting for 13-16% of
all child deaths. Pneumonia and diarrhea remain the leading causes of mortality
in India among children, causing about 2 lacs under five mortalities.
Antibiotics are
among the most commonly administered medications in children. In ambulatory
settings in the USA, antibiotics are prescribed during as many as one in five pediatric
visits. Cross-sectional point prevalence studies have shown that more than 35%
and 40% of hospitalized children are receiving antimicrobials at any given time
in European and non-European countries, respectively. There are Indian studies done on
off-label use of drugs in children which show that antibiotics are the most
common off-label prescribed drugs (10 to 70%). Chauthankar et al. showed that
in NICU, of all the drugs prescribed, antibiotics were the most common
off-label prescription drugs (69.6%). Saiyed et al. states that almost 70% of
the antibiotics prescribed in hospitalized children are off-label.
An Indian study
showed that use of antibiotics in PICU is up to 45%. While another study showed
that in a PICU of tertiary care hospital, of all of the
patients admitted 43% received antibiotics prophylactically, 42% empirically,
and 15% therapeutically.
There are few
studies documenting prescription pattern of antibiotics in hospitalized
children in India. However, the studies have not looked at drug consumption pattern
of antibiotics in hospitalized children.
The reason for increased off-label use of drugs
being more prevalent in children is a smaller number of pediatric clinical
trials. Both economic and ethical factors can discourage pharmaceutical
companies from conducting trials on children which results in potential delay
in the authorization of antibiotics for children. Moreover, given the scarcity
of information of new drugs including antibiotics in children, data on drug safety and
tolerability are often extrapolated from adult studies, with the consequent
risks of underestimating toxicity, inadequate dosages and clinical failures.
Defined daily dose (DDD) as defined by WHO is the assumed
average maintenance dose per day for a drug used for its main
indication in adults.
Prescribed daily dose (PDD) as per WHO is the dose actually prescribed by a physician for an individual
person. The ratio of PDD to DDD is a useful metric to measure drug
consumption in a defined population and it is a valuable WHO indicator in drug utilization
studies. These indicators can only be used in adult population as per WHO. Pediatric
DDDs are challenging to assign because of the variability in children’s doses
as per the age and body weight.
Child Defined Daily Dose (cDDD), Child
Drug Utilization index (cDUI), PDD/cDDD ratio indicators have been derived
based on adult DDD and were used in a study by Hu et al. from pediatric
patients.
There is no Indian
study reporting evaluation of prescription pattern of antibiotics in pediatric
population in terms of WHO indicators, PDD/cDDD ratio and using cDDD and cDUI.
Due to
higher number of infectious diseases in developing countries like India
especially in children, the use of antibiotics is widespread. Because of lack
of stringent regulations in India and other developing countries, it is not
difficult to obtain over the counter antibiotics and hence, antibiotics misuse
is common. It has been observed that although parents are concerned about the
use of over-the-counter antibiotics, they still demand it for faster relief.
In earlier studies assessing parents’ awareness regarding antibiotics, 42.6%
declared that antibiotics act against both viruses and bacteria, 55.9% believed
antibiotics are required to treat fever, 50% didn’t know the consequences of
antibiotics misuse, 58.4% believed that a doctor’s prescription is not required
every time to administer antibiotics and 66.7% trusted the pharmacist in the
antibiotic prescription. In an Indian study to find out level of awareness
among parents, it was found that there were misconceptions about which diseases
require antibiotics and the concept of antibiotic overuse leading to resistance
was not known. Majority of them believed antibiotics are required every time
the child falls sick. Misinformation and confusion was more among mothers and
those with lower formal education.
Therefore,
the need was felt to understand parents’ knowledge, attitude and practice
regarding the disease condition which the child is suffering from and use of
antibiotics for infectious diseases in their children.
Antimicrobials
contributed around 16.8% of the of the total medicine sales worth USD 12.6
billion in India between 2013 and 2014. According to National Sample Survey Organization (NSSO) data on
Key Indicators of Social Consumption in India: Health, (2017–18), the monthly
per patient Out of Pocket (OOP) expenditure on infectious diseases by
infection-affected populations is INR 881.56 and INR 1,156.34 in inpatient and
outpatient care in India. One cost analysis study in pediatric
population showed that average cost of management of pneumonia in children is 12245 ± 593
($187.34 ± 9.07). About 58% of India’s health expenditure is done out of pocket
of the patient. In spite of public health
system and availability of generic drugs, the financial burden of infectious
diseases in India is substantial owing to various factors. However, there are no cost analysis Indian
studies for antibiotics used for different types of infections. It is important to know how much financial burden is faced by
parents when children are admitted with infections and whether they get the
required antimicrobial agents from the hospital formulary.
The infections in children require prompt use of
antimicrobial agents. It is necessary to find out the clinical outcome of
antibiotic treatment in children as febrile period and number of hospitalization
days largely depend on response to treatment. Unlike most children getting
cured in developed nations, infectious diseases leading to morbidity and
mortality has been reported to be higher in Indian patients. There are very few
global studies that has recorded response to treatment with antibiotics in
children while there are no Indian studies assessing this aspect.
Hence it was of
interest to evaluate prescription pattern, awareness of parents regarding use
of antibiotics, cost analysis and clinical outcome of treatment of infectious
diseases.
Primary Objective:
1.
To analyze the prescription pattern of
antibiotics in hospitalized children using WHO drug use indicators and derived
pediatric indicators.
Secondary Objectives:
1.
To find out awareness of parents of children
regarding disease and use of antibiotics.
2.
To analyze cost of treatment during the
hospital stay
3.
To assess the clinical outcome of treatment of
infection.
Methodology:
Study Design- An Observational,
cross- sectional, single-center, Questionnaire based Study
Study Site- In-Patient ward of Department of Pediatrics
of a Tertiary Care Hospital.
Study duration
- The total duration of the study will be of 15 months, of which data will be
collected over a period of 12 months and analyzed over a period of 3 months.
Sampling method-
Convenient sampling till the required sample size is achieved.
Study Population:
The study population will include all admitted children receiving antibiotics
in one unit of the Pediatrics department.
Duration of study participation: The study
involves a single interview with every parent at the end of hospital stay and
hence the duration of participation equals the duration of the interview, which
is expected to be 30 minutes for the parents.
Sample Size Calculation:
The expected frequency of use of antibiotics in pediatric
population is 67%.(28) With confidence level of 95%, keeping margin of
error as 5%, a non-response rate of 10%(29), the sample size can be calculated as follows:
n = z^2 * p * q / e^2
where:
- z = the z-value for the desired confidence level
(1.96 for a 95% confidence level)
- p = the expected frequency of antibiotic use (0.67)
- q = 1 - p (0.33)
- e = the desired level of precision (0.05)
n = (1.96) ^2 * 0.67 * 0.33* / (0.05)^2
n = 340
Therefore, the sample size required for the study is
340 patients. However, to account for the non-response rate of 10%, we will
have to recruit additional 38 patients as follows.
(N’=N/(1-d))
d = non-response rate
Therefore, N’=340/ (1-0.1) = 340/0.9 = 378
Ethical considerations and informed consent:
This study will be conducted in
compliance with the protocol, the IEC, and Indian GCP guidelines and national ICMR
guidelines on biomedical health research. During the study, any amendment or
modification to the protocol will be submitted to IEC.
The study will begin after approval
from Institutional Ethics Committee. Children
who are being admitted to the ward for treatment of infection and fulfilling
the inclusion-exclusion criteria will be enrolled in the study.
Written informed consent will be taken
from LAR and impartial witness (when applicable) and verbal assent will be
taken in children aged 7-12 years in addition to parent/ LAR consent. |