Mira Zuidgeest

Prescription of respiratory medication without an asthma diagnosis in children: a population based study

BackgroundIn pre-school children a diagnosis of asthma is not easily made and only a minority of wheezing children will develop persistent atopic asthma. According to the general consensus a diagnosis of asthma becomes more certain with increasing age. Therefore the congruence between asthma medication use and doctor-diagnosed asthma is expected to increase with age. The aim of this study is to evaluate the relationship between prescribing of asthma medication and doctor-diagnosed asthma in children age 0–17.MethodsWe studied all 74,580 children below 18 years of age, belonging to 95 GP practices within the second Dutch national survey of general practice (DNSGP-2), in which GPs registered all physician-patient contacts during the year 2001. Status on prescribing of asthma medication (at least one prescription for beta2-agonists, inhaled corticosteroids, cromones or montelukast) and doctor-diagnosed asthma (coded according to the International Classification of Primary Care) was determined.ResultsIn total 7.5% of children received asthma medication and 4.1% had a diagnosis of asthma. Only 49% of all children receiving asthma medication was diagnosed as an asthmatic. Subgroup analyses on age, gender and therapy groups showed that the Positive Predictive Value (PPV) differs significantly between therapy groups only. The likelihood of having doctor-diagnosed asthma increased when a child received combination therapy of short acting beta2-agonists and inhaled corticosteroids (PPV = 0.64) and with the number of prescriptions (3 prescriptions or more, PPV = 0.66). Both prescribing of asthma medication and doctor-diagnosed asthma declined with age but the congruence between the two measures did not increase with age.ConclusionIn this study, less than half of all children receiving asthma medication had a registered diagnosis of asthma. Detailed subgroup analyses show that a diagnosis of asthma was present in at most 66%, even in groups of children treated intensively with asthma medication. Although age strongly influences the chance of being treated, remarkably, the congruence between prescribing of asthma medication and doctor-diagnosed asthma does not increase with age.

What drives prescribing of asthma medication to children? A multilevel population-based study.

PURPOSE Diagnosing asthma in children with asthmatic symptoms remains a challenge, particularly in preschool children. This challenge creates an opportunity for variability in prescribing. The aim of our study was to investigate how and to what degree patient, family, and physician characteristics influence prescribing of asthma medication in children. METHODS We undertook a multilevel population-based study using the second Dutch national survey of general practice (DNSGP-2), 2001. Participants were 46,371 children aged 1 to 17 years belonging to 25,537 families registered with 109 general practitioners. Using a multilevel multivariate logistic regression analysis with 3 levels, our main outcome measure was the prescribing of asthma medication, defined as at least 1 prescription for β2-adrenergic agonists, inhaled corticosteroids, cromones, or montelukast during the 1-year study period. RESULTS We identified characteristics significantly associated with prescribing asthma medication on all 3 levels (child, family, and physician). The variance in prescribing among physicians was significantly higher with children who were younger than 6 years than with children aged 6 years and older (95% CI, 3.5%–25.2% vs 2.4%–13.4%). Several diagnoses other than asthma and asthmatic complaints were strongly associated with prescribing asthma medication, including bronchitis/bronchiolitis (OR = 9.04; 95% CI, 7.57–10.8) and cough (OR = 6.51; 95% CI, 5.68–7.47). CONCLUSIONS Our study shows a much higher variance in prescribing patterns among general practitioners for children younger than 6 years compared with older children, which could be a direct result of the diagnostic complexities found in young children with asthmatic symptoms. Thus diagnostic gaps may lead to more physician-driven prescribing irrespective of the clinical context.

Persistence of asthma medication use in preschool children

OBJECTIVE In young children with asthmatic symptoms diagnostic difficulties lead to use of trials of asthma medication as a diagnostic tool. Our aim is to quantify the persistent use of asthma medication, initiated in the first year of life and identify determinants of this persistent use. PATIENTS AND METHODS We identified 165 children within the PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort who used asthma medication before the age of one. Persistent use was investigated during three years after the first prescription. A Cox regression analysis was performed to identify factors associated with persistent use. RESULTS A total of 58.8% of children continued using asthma medication after the first prescription and 10.3% continued during three years. Children with doctor-diagnosed asthma (Hazard ratio of discontinuation (HR)=0.64, 95% CI: 0.45-0.91) or prescribed inhaled corticosteroids in the first year of life (HR of discontinuation=0.59, 95% CI: 0.40-0.86) were 1.6-1.7 times more likely to continue using asthma medication. CONCLUSIONS Persistence of asthma medication, prescribed in the first year of life is very low and is positively associated with doctor-diagnosed asthma and use of inhaled corticosteroids. Characterizing persistent users of asthma medication is important to understand prescribing of asthma medication in this age group.

Series: Pragmatic trials and real world evidence: Paper 1. Introduction

This is the introductory paper in a series of eight papers. In this series, we integrate the theoretical design options with the practice of conducting pragmatic trials. For most new market-approved treatments, the clinical evidence is insufficient to fully guide physicians and policy makers in choosing the optimal treatment for their patients. Pragmatic trials can fill this gap, by providing evidence on the relative effectiveness of a treatment strategy in routine clinical practice, already in an early phase of development, while maintaining the strength of randomized controlled trials. Selecting the setting, study population, mode of intervention, comparator, and outcome are crucial in designing pragmatic trials. In combination with monitoring and data collection that does not change routine care, this will enable appropriate generalization to the target patient group in clinical practice. To benefit from the full potential of pragmatic trials, there is a need for guidance and tools in designing these studies while ensuring operational feasibility. This paper introduces the concept of pragmatic trial design. The complex interplay between pragmatic design options, feasibility, stakeholder acceptability, validity, precision, and generalizability will be clarified. In this way, balanced design choices can be made in pragmatic trials with an optimal chance of success in practice.

Asthma therapy during the first 8 years of life: a PIAMA cohort study

Objective. Many studies evaluated asthma medication use in children in a cross-sectional manner, yet little is known about longitudinal use patterns. This study describes the formation of a longitudinal data set on asthma medication use and shows first results regarding the prevalence and incidence of medication use. Methods. The PIAMA (Prevention and Incidence of Asthma and Mite Allergy) study is a prospective birth cohort study among 3963 Dutch children. Recruitment took place in 1996–1997. The data of the PIAMA birth cohort study were complemented with pharmacy data. Prescription information of family members was used to determine whether medication histories were complete from birth until age 8. The prevalence and incidence of asthma medication use was studied in children for whom complete medication histories were available. Results. A first prescription for asthma medication was filled before age 8 by 280 (36%) children, with 88% starting therapy before age 5. Of all children who started therapy, 91.1% received short-acting β2-agonists and 61.1% inhaled corticosteroids. Conclusion. The applied method of data collection rendered a data set including 777 children with complete medication histories for their first 8 years of life. This data set provides the opportunity to study longitudinal medication use patterns. First analyses show that asthma medication is initiated in a rather high percentage of children in this cohort and mainly at an age at which an asthma diagnosis cannot yet be firmly established.

Patterns of asthma medication use: Early asthma therapy initiation and asthma outcomes at age 8

Wheeze has many underlying pathophysiologies in childhood, but is the main reason for anti‐asthma drugs prescription. This study was conducted to describe asthma medication use patterns among children in their first eight years of life. Longitudinal medication use data from 777 children participating in the PIAMA study were used. Medication patterns were described for four groups that started therapy before the third birthday, when the peak in prescriptions occurred in our cohort; short‐acting β‐agonists (SABA), inhaled corticosteroids (ICS), SABA + ICS or none of these. One third (n = 255) of the children received a first SABA or ICS prescription before age 8. Only three children (1.2%) used medication continuously during follow‐up. Of the children who started SABA, 53.8% discontinued within 1–2 years. Of the children who started ICS before age 3, 42.1% discontinued within 1–2 years and 31.6% received additional SABA. 41.5% of the children who started SABA + ICS used this short‐term (≤1–2 years) and 21.5% long‐term (≥3 years). Fifteen percent of children who did not start asthma therapy in their first 3 years of life did receive prescriptions between age 3 and 8. Children prescribed SABA + ICS before age 3 had the highest prevalence of hyper responsiveness at age 8, and similar prevalence of atopy as the other groups. Asthma medication is prescribed frequently in the first 8 years of life, particularly before age 3, and only few children use it continuously. ICS and SABA prescription occurs especially in those who were more likely to develop signs of asthma at age 8. Copyright

Series: Pragmatic trials and real world evidence: Paper 4. Informed consent

The GetReal consortium of the Innovative Medicines Initiative aims to develop strategies to incorporate real-world evidence earlier into the drug life cycle to better inform health care decision makers on the comparative risks and benefits of new drugs. Pragmatic trials are currently explored as a means to generate such evidence in routine care settings. The traditional informed consent model for randomized clinical trials has been argued to pose substantial hurdles to the practicability of pragmatic trials: it would lead to recruitment difficulties, reduced generalizability of the results, and selection bias. The present article analyzes these challenges and discusses four proposed alternative informed consent models: integrated consent, targeted consent, broadcast consent, and a waiver of consent. These alternative consent models each aim at overcoming operational and methodological challenges, while still providing patients all the relevant information they need to make informed decisions. Each consent model, however, relies on different attitudes toward the principle of respect for persons and the related duty to inform patients as well as represents different views on whether the common good demands moral duties from patients. Such normative consequences of modifying consent requirements should be at least acknowledged and ought to be assessed in light of the validity of empirical claims.

Pragmatic trials and real world evidence – an introduction to the series

This is the introductory paper in a series of eight papers. In this series, we integrate the theoretical design options with the practice of conducting pragmatic trials. For most new market-approved treatments, the clinical evidence is insufficient to fully guide physicians and policy makers in choosing the optimal treatment for their patients. Pragmatic trials can fill this gap, by providing evidence on the relative effectiveness of a treatment strategy in routine clinical practice, already in an early phase of development, while maintaining the strength of randomized controlled trials. Selecting the setting, study population, mode of intervention, comparator, and outcome are crucial in designing pragmatic trials. In combination with monitoring and data collection that does not change routine care, this will enable appropriate generalization to the target patient group in clinical practice. To benefit from the full potential of pragmatic trials, there is a need for guidance and tools in designing these studies while ensuring operational feasibility. This paper introduces the concept of pragmatic trial design. The complex interplay between pragmatic design options, feasibility, stakeholder acceptability, validity, precision, and generalizability will be clarified. In this way, balanced design choices can be made in pragmatic trials with an optimal chance of success in practice.

Pragmatic trial design elements showed a different impact on trial interpretation and feasibility than explanatory elements.

OBJECTIVES To illustrate how pragmatic trial design elements or inserting explanatory trial elements in pragmatic trials affect validity, generalizability, precision, and operational feasibility. STUDY DESIGN AND SETTING From illustrative examples identified through the IMI Get Real Consortium, we selected randomized drug trials with a pragmatic design feature. We searched all publications on these trials for information on how pragmatic trial design features affect validity, generalizability, precision, or feasibility. RESULTS We present examples from the Salford lung study, International Suicide Prevention Trial, Sequenced Treatment Alternatives to Relieve Depression, and Cluster Randomized Usual care vs. Caduet Investigation Assessing Long-term-risk trial. These examples show that incorporating pragmatic trial design elements in trials may affect generalizability, precision and validity and may lead to operational challenges different from traditional explanatory trials. Inserting explanatory trial elements into pragmatic trials may also affect validity, generalizability, and operational feasibility, especially when these trial elements are incorporated in one arm of the trial only. Design choices that positively affect one of these domains (e.g., generalizability) may negatively affect others (e.g., feasibility). CONCLUSION Consequences of incorporating pragmatic or explanatory trial design elements in pragmatic trials should be explicitly considered and balanced for all relevant domains, including validity, generalizability, precision, and operational feasibility. Tools are needed to make these consequences more transparent.

Guideline-recommended use of asthma medication by children is associated with parental information and knowledge

We investigated the use of asthma medication by children and the association of use as recommended by guidelines with modifiable risk factors: parental attitudes, knowledge of asthma medication and information provided by health care providers.