Publications

2016
Shah S, Bourgeois F, Mannix R, Nelson K, Bachur R, Neuman MI. Emergency Department Management of Febrile Respiratory Illness in Children. Pediatr Emerg Care 2016;32:429-34.Abstract
BACKGROUND: There are limited data regarding testing and treatment patterns for children presenting to the emergency department (ED) with a febrile respiratory illness. OBJECTIVES: The aims of the study were to evaluate the rates of diagnostic testing, antibiotic use, and pneumonia diagnosis among children presenting to an ED with a febrile respiratory illness and to evaluate whether differences exist on the basis of care at a pediatric versus a general ED. METHODS: Cross-sectional study of children presenting to an ED with a febrile respiratory illness from 2001 to 2010 used the National Hospital Ambulatory Medical Care Survey. Using extrapolated estimates from the weighted population sample, rates of laboratory and radiographic testing, antibiotic use, and pneumonia diagnosis were ascertained. Comparisons were made between children treated at a general versus pediatric ED. A subpopulation of children undergoing chest radiograph was identified to target those with concern for radiographic pneumonia. RESULTS: Fifteen percent of the 12 million visits for febrile respiratory illness occurred in a pediatric ED. Thirteen percent (95% confidence interval [CI], 11-15) of patients had a complete blood count, 4% (95% CI, 3-5) had a blood culture, and 33% (95% CI, 30-35) had a chest radiograph obtained; no differences were observed on the basis of ED type. Despite similar rates of pneumonia diagnosis, antibiotics were prescribed less often for children cared for in a pediatric (35% [95% CI, 30-41]) versus general ED (50% [95% CI, 47-53]). Similar findings were observed among the subgroup of children with febrile respiratory illness undergoing chest radiograph. CONCLUSIONS: High rates of diagnostic testing were observed among children with febrile respiratory illnesses, despite low rates of pneumonia diagnosis. Antibiotic use was higher among children cared for at a general ED compared with pediatric ED.
Dunn AG, Zhou X, Hudgins J, Arachi D, Mandl KD, Coiera E, Bourgeois FT. Financial competing interests were associated with favorable conclusions and greater author productivity in nonsystematic reviews of neuraminidase inhibitors. J Clin Epidemiol 2016;80:43-49.Abstract
OBJECTIVE: To characterize the conclusions and production of nonsystematic reviews about neuraminidase inhibitors relative to financial competing interests held by the authors. STUDY DESIGN AND SETTING: We searched for articles about neuraminidase inhibitors and influenza (January 2005 to April 2015), identifying nonsystematic reviews and grading them according to the favorable/nonfavorable presentation of evidence on safety and efficacy. We recorded financial competing interests disclosed in the reviews and from other articles written by their authors. We measured associations between competing interests, author productivity, and conclusions. RESULTS: Among 213 nonsystematic reviews, 138 (65%) presented favorable conclusions. Financial competing interests were identified for 26% (137/532) of authors; 51% (108/213) of reviews were associated with a financial competing interest. Reviews produced exclusively by authors with financial competing interests (33%; 71/213) were more likely to present favorable conclusions than reviews with no competing interests (risk ratio 1.27; 95% confidence interval 1.03-1.55). Authors with financial competing interests published more articles about neuraminidase inhibitors than their counterparts. CONCLUSION: Half of nonsystematic reviews about neuraminidase inhibitors included an author with a financial competing interest. Reviews produced exclusively by these authors were more likely to present favorable conclusions, and authors with financial competing interests published a greater number of reviews.
Hawkins JB, Brownstein JS, Tuli G, Runels T, Broecker K, Nsoesie EO, McIver DJ, Rozenblum R, Wright A, Bourgeois FT, Greaves F. Measuring patient-perceived quality of care in US hospitals using Twitter. BMJ Qual Saf 2016;25:404-13.Abstract
BACKGROUND: Patients routinely use Twitter to share feedback about their experience receiving healthcare. Identifying and analysing the content of posts sent to hospitals may provide a novel real-time measure of quality, supplementing traditional, survey-based approaches. OBJECTIVE: To assess the use of Twitter as a supplemental data stream for measuring patient-perceived quality of care in US hospitals and compare patient sentiments about hospitals with established quality measures. DESIGN: 404 065 tweets directed to 2349 US hospitals over a 1-year period were classified as having to do with patient experience using a machine learning approach. Sentiment was calculated for these tweets using natural language processing. 11 602 tweets were manually categorised into patient experience topics. Finally, hospitals with >/=50 patient experience tweets were surveyed to understand how they use Twitter to interact with patients. KEY RESULTS: Roughly half of the hospitals in the US have a presence on Twitter. Of the tweets directed toward these hospitals, 34 725 (9.4%) were related to patient experience and covered diverse topics. Analyses limited to hospitals with >/=50 patient experience tweets revealed that they were more active on Twitter, more likely to be below the national median of Medicare patients (p<0.001) and above the national median for nurse/patient ratio (p=0.006), and to be a non-profit hospital (p<0.001). After adjusting for hospital characteristics, we found that Twitter sentiment was not associated with Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) ratings (but having a Twitter account was), although there was a weak association with 30-day hospital readmission rates (p=0.003). CONCLUSIONS: Tweets describing patient experiences in hospitals cover a wide range of patient care aspects and can be identified using automated approaches. These tweets represent a potentially untapped indicator of quality and may be valuable to patients, researchers, policy makers and hospital administrators.
Bourgeois FT, Olson KL, Tse T, Ioannidis JP, Mandl KD. Prevalence and Characteristics of Interventional Trials Conducted Exclusively in Elderly Persons: A Cross-Sectional Analysis of Registered Clinical Trials. PLoS One 2016;11:e0155948.Abstract
BACKGROUND: Elderly patients represent the greatest consumers of healthcare per capita but have historically been underrepresented in clinical trials. It is unknown how many trials are designed to focus exclusively on elderly patients. OBJECTIVE: To define the prevalence of interventional trials that study exclusively elderly persons and describe the characteristics of these trials, including their distribution across conditions most prevalent in the elderly. DESIGN: All interventional clinical trials enrolling exclusively elderly patients (>/=65 years), conducted primarily in high-income countries, and initiated between 2006 and 2014, identified through ClincialTrials.gov. MAIN MEASURES: Trials were identified and characterized according to design features and disease categories studied. Across disease categories we examined the burden of disease in the elderly in high-income countries (measured in disability-adjusted life years [DALYs]) and compared to the number of trials conducted exclusively in the elderly. RESULTS: Among 80,965 interventional trials, 1,112 (1.4%) focused on elderly patients. Diverse types of interventions were studied in these trials (medications 33%, behavioral interventions 18%, and dietary supplements 10%) and the majority was funded by non-profit organizations (81%). Studies tended to be small (median sample size 122 participants [IQR 58, 305]), single-center studies (67%). Only 43% of 126 disease categories affecting elderly persons were studied in trials focused on the elderly. Among these disease categories, there was a 5162-fold range in the ratio of DALYs per trial. Across 5 conditions where over 80% of DALYs are in the elderly, there were a total of only 117 trials done exclusively in the elderly. CONCLUSIONS: Very few and mostly small studies are conducted exclusively in elderly persons, even for conditions that affect almost exclusively the elderly.
2015
Zhou X, Y. Wang, Tsafnat G, Coiera E, Bourgeois FT, Dunn AG. Citations alone were enough to predict favorable conclusions in reviews of neuraminidase inhibitors. J Clin Epidemiol 2015;68:87-93.Abstract
OBJECTIVES: To examine the use of supervised machine learning to identify biases in evidence selection and determine if citation information can predict favorable conclusions in reviews about neuraminidase inhibitors. STUDY DESIGN AND SETTING: Reviews of neuraminidase inhibitors published during January 2005 to May 2013 were identified by searching PubMed. In a blinded evaluation, the reviews were classified as favorable if investigators agreed that they supported the use of neuraminidase inhibitors for prophylaxis or treatment of influenza. Reference lists were used to identify all unique citations to primary articles. Three classification methods were tested for their ability to predict favorable conclusions using only citation information. RESULTS: Citations to 4,574 articles were identified in 152 reviews of neuraminidase inhibitors, and 93 (61%) of these reviews were graded as favorable. Primary articles describing drug resistance were among the citations that were underrepresented in favorable reviews. The most accurate classifier predicted favorable conclusions with 96.2% accuracy, using citations to only 24 of 4,574 articles. CONCLUSION: Favorable conclusions in reviews about neuraminidase inhibitors can be predicted using only information about the articles they cite. The approach highlights how evidence exclusion shapes conclusions in reviews and provides a method to evaluate citation practices in a corpus of reviews.
Bourgeois FT, Olson KL, Poduri A, Mandl KD. Comparison of Drug Utilization Patterns in Observational Data: Antiepileptic Drugs in Pediatric Patients. Paediatr Drugs 2015;17:401-10.Abstract
PURPOSE: Physicians require information on the comparative benefits and harms of medications for optimal treatment decisions. However, this type of data is limited, especially for pediatric patients. OBJECTIVE: Our aim was to use observational data to measure and compare medication utilization patterns in a pediatric patient population. METHODS: Using pharmacy claims data from a large, national-scale insurance program in the USA, we identified all patients with a diagnosis of epilepsy treated with a first-generation antiepileptic drug (carbamazepine, ethosuximide, phenobarbital, phenytoin, or valproate) or a second-generation antiepileptic drug [carbamazepine extended release (XR), gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, valproate XR, or zonisamide]. Treatment periods were defined on the basis of prescription fill dates and medication days supplied. Medication use was measured for individual antiepileptic drugs and for first-generation and second-generation drugs as groups. RESULTS: There were 2527 patients (54 %) who initiated therapy with first-generation antiepileptics and 2139 patients (46 %) who initiated therapy with second-generation antiepileptics. First- and second-generation drugs had the same 1-year retention rates [26 % (95 % confidence interval (CI) 24-28) and 26 % (95 % CI 25-28), respectively], and 26 % of patients (95 % CI 25-28) and 29 % of patients (95 % CI 27-31) who started on a first- or second-generation antiepileptic medication, respectively, resumed treatment with the initial drug after discontinuation. Overall, 73 % of patients (95 % CI 71-74) were treated with only one antiepileptic drug, with similar rates for patients started on first- and second-generation drugs [71 % (95 % CI 69-73) versus 74 % (95 % CI 72-76)]. CONCLUSION: Comparing drug utilization patterns in a pediatric population using observational data, we found similar rates of retention and therapeutic changes. These findings are consistent with the available comparative data and demonstrate an approach that could be extended to other drug classes and conditions in pediatric populations to examine drug effectiveness.
Dunn AG, Arachi D, Bourgeois FT. Identifying Clinical Study Types from PubMed Metadata: The Active (Machine) Learning Approach. Stud Health Technol Inform 2015;216:867-71.Abstract
We examined a process for automating the classification of articles in MEDLINE aimed at minimising manual effort without sacrificing accuracy. From 22,808 articles pertaining to 19 antidepressants, 1000 were randomly selected and manually labelled according to article type (including, randomised controlled trials, editorials, etc.). We applied a machine learning approach termed 'active learning', where the learner (machine) selects the order in which the user (human) labels examples. Via simulation, we determined the number of articles a user needed to label to produce a classifier with at least 95% recall and 90% precision in three scenarios related to evidence synthesis. We found that the active learning process reduced the number of training instances required by 70%, 19%, and 14% in the three scenarios. The results show that the active learning method may be used in some scenarios to produce accurate classifiers that meet the needs of evidence synthesis tasks and reduce manual effort.
Murthy S, Mandl KD, Bourgeois FT. Industry-sponsored clinical research outside high-income countries: an empirical analysis of registered clinical trials from 2006 to 2013. Health Res Policy Syst 2015;13:28.Abstract
BACKGROUND: Industry-sponsored clinical trials, in the past performed almost exclusively in more developed countries, now often recruit participants globally. However, recruitment from outside high-income countries may not represent the ultimate target population for the intervention. Clinical trial registries provide an opportunity to quantify and examine the type of clinical research performed in various geographic regions. We sought to characterize industry-sponsored randomized controlled trials conducted in high-income countries and to compare these trials to those performed outside high-income countries. METHODS: Clinical trial data on all industry-funded randomized controlled trials conducted between 2006 and 2014 were obtained from the registry ClinicalTrials.gov. Trials were classified according to their study sites as conducted in high or non-high income countries, and data on trial characteristics were collected. RESULTS: Of 22,511 relevant trials, a total of 6,085 (27.0 %) trials included study sites outside a high-income country, and 2,045 (9.1 %) were conducted exclusively outside high-income countries. Of country groups, Central Europe had the greatest number of trials (3,127), followed by Eastern Europe (2,075). The percentage of trials with study sites outside high-income countries remained relatively constant over the study period. Studies with sites outside high-income countries tended to recruit more participants (median enrolled participants 265 vs. 71, P <0.001), to be longer (median study duration 20 vs. 13 months, P <0.05), and to study more advanced phase interventions (Phase 3 or 4 trial 58 % vs. 33 %, P <0.001). CONCLUSIONS: More than a quarter of industry-sponsored trials include participants from outside high-income countries and this rate remained stable over the 7-year study period. Trials conducted outside high-income countries tend to be larger, have a longer duration, and study later phase interventions compared to studies performed exclusively in high-income countries.
Monuteaux MC, Bourgeois FT, Mannix R, Samnaliev M, Stack AM. Variation and Trends in Charges for Pediatric Care in Massachusetts Emergency Departments, 2000-2011. Acad Emerg Med 2015;22:1164-71.Abstract
OBJECTIVES: Emergency department (ED) utilization by children is common and growing more expensive. Tracking trends and variability in ED charges is essential for policymakers who strive to improve the efficiency of the health care system and for payers who prepare health care budget forecasts. Our objective was to examine trends and variability in ED charges for pediatric patients across Massachusetts. METHODS: This was a comprehensive analysis of the statewide database containing all the visits of children aged 0 to 18 years evaluated in any of the state's EDs from 2000 to 2011, excluding patients with chronic medical conditions and those whose visits resulted in hospital admission. A validated system designed to specifically classify pediatric emergency patients into major diagnostic groups was used. Mean charges as well as interhospital variability of charges over time were examined for the most common diagnostic groups. RESULTS: Seventy-six hospitals provided emergency care in Massachusetts during the study period, with 6,249,923 pediatric patients treated and discharged. Statewide charges significantly increased from 2000 until 2007/2008, before plateauing or decreasing through 2011. There was no evidence that interhospital variability changed over time. With the exception of academic teaching status, no hospital-level factors emerged as consistent predictors of charges. CONCLUSIONS: Charges for common pediatric emergency conditions varied widely across Massachusetts EDs, and hospital-level factors by and large could not consistently explain the variability. Although a plateau (and in some cases decrease) of statewide pediatric emergency health care charges was observed after 2007, no evidence was found that interhospital variability decreased. These data may be useful in the ongoing effort to reform the economics of health care delivery systems.
Zhou X, Y. Wang, Tsafnat G, Coiera E, Bourgeois FT, Dunn AG. Citations alone were enough to predict favorable conclusions in reviews of neuraminidase inhibitors. J Clin Epidemiol 2015;68:87-93.Abstract
OBJECTIVES: To examine the use of supervised machine learning to identify biases in evidence selection and determine if citation information can predict favorable conclusions in reviews about neuraminidase inhibitors. STUDY DESIGN AND SETTING: Reviews of neuraminidase inhibitors published during January 2005 to May 2013 were identified by searching PubMed. In a blinded evaluation, the reviews were classified as favorable if investigators agreed that they supported the use of neuraminidase inhibitors for prophylaxis or treatment of influenza. Reference lists were used to identify all unique citations to primary articles. Three classification methods were tested for their ability to predict favorable conclusions using only citation information. RESULTS: Citations to 4,574 articles were identified in 152 reviews of neuraminidase inhibitors, and 93 (61%) of these reviews were graded as favorable. Primary articles describing drug resistance were among the citations that were underrepresented in favorable reviews. The most accurate classifier predicted favorable conclusions with 96.2% accuracy, using citations to only 24 of 4,574 articles. CONCLUSION: Favorable conclusions in reviews about neuraminidase inhibitors can be predicted using only information about the articles they cite. The approach highlights how evidence exclusion shapes conclusions in reviews and provides a method to evaluate citation practices in a corpus of reviews.
2014
Hwang TJ, Bourgeois FT, Seeger JD. Drug safety in the digital age. N Engl J Med 2014;370:2460-2.
Hwang TJ, Bourgeois FT. New regulatory paradigms for innovative drugs to treat pediatric diseases. JAMA Pediatr 2014;168:879-80.
Hwang TJ, Kesselheim AS, Bourgeois FT. Postmarketing trials and pediatric device approvals. Pediatrics 2014;133:e1197-202.Abstract
BACKGROUND: Medical devices can be useful in a variety of diseases, but few devices have been specifically approved for use in children. The 2007 Pediatric Medical Device Safety and Improvement Act was passed to stimulate pediatric device development. The current state of trial evidence underpinning the approval of pediatric devices remains poorly described. METHODS: We identified all high-risk (ie, class III) devices approved through the premarket approval or humanitarian device exemption pathways for therapeutic use in children between 2008 and 2011. We collected key information on clinical trial design (randomization, blinding, controls, and types of end points) as well as age distribution of trial participants. We also identified US Food and Drug Administration (FDA)-mandated postmarketing trials. RESULTS: Twenty-two devices were approved for use in children via the premarket approval pathway and 3 via the humanitarian device exemption pathway. Twenty-two (88%) qualified as pediatric despite minimum approval ages of >/=18 years (the FDA Center for Devices and Radiologic Health considers patients 18-21 years old as pediatric). Most devices were approved on the basis of nonrandomized (59%), open-label (68%) studies with surrogate effectiveness end points (86%). Overall, 21 (84%) devices were not studied in any patients <18 years of age. Postmarketing studies were mandated by the FDA for 19 (76%) devices, although only 3 (18%) required enrollment of pediatric patients. CONCLUSIONS: Most high-risk pediatric devices are approved on the basis of trials in patients >/=18 years old, with few pediatric patients exposed to the devices before market availability. Few postmarketing studies require additional study in pediatric patients.
Tay KY, Ewald MB, Bourgeois FT. Use of QT-prolonging medications in US emergency departments, 1995-2009. Pharmacoepidemiol Drug SafPharmacoepidemiol Drug SafPharmacoepidemiol Drug Saf 2014;23:9-17.Abstract
PURPOSE: Emergency department (ED) patients receive medications that place them at risk for adverse events, including drug-induced prolongation of the QT interval, which can lead to Torsade de Pointes and sudden cardiac death. We report the frequency of prescription and co-prescription of QT-prolonging medications in US EDs and factors associated with high-risk prescribing practices. METHODS: We analyzed the ED component of the National Hospital Ambulatory Medical Care Survey for 1995 through 2009. Yearly rates of visits involving the prescription of QT-prolonging medications were determined. Multivariate regression analyses identified factors associated with the prescription of two or more QT-prolonging medications. RESULTS: Approximately 16.5 million visits annually (15.0%) involved prescription of a QT-prolonging drug, with 1.7 million (1.6%) involving multiple prescriptions. Visits associated with QT-prolonging drugs more than doubled over the study period (10.4% to 22.2%). Diphenhydramine, azithromycin, and ondansetron were most frequently implicated (46.1% of cases). The most commonly prescribed combination was diphenhydramine and famotidine, both QT-prolonging medications available over-the-counter. Female gender and older age were associated with co-prescription of QT-prolonging medications. The rate of EKG screening among visits associated with QT-prolonging drug combinations was low (20.9%), but more common than among visits without a QT-prolonging drug (OR 1.3; 95% CI 1.2-1.5). CONCLUSION: Use of QT-prolonging medications is increasing in EDs nationally. A small number of agents account for a large proportion of these visits and may represent an area for targeted screening or monitoring interventions in the ED.
Dunn AG, Arachi D, Hudgins J, Tsafnat G, Coiera E, Bourgeois FT. Financial conflicts of interest and conclusions about neuraminidase inhibitors for influenza: an analysis of systematic reviews. Ann Intern MedAnn Intern MedAnn Intern Med 2014;161:513-8.Abstract
BACKGROUND: Industry funding and financial conflicts of interest may contribute to bias in the synthesis and interpretation of scientific evidence. OBJECTIVE: To examine the association between financial conflicts of interest and characteristics of systematic reviews of neuraminidase inhibitors. DESIGN: Retrospective analysis. SETTING: Reviews that examined the use of neuraminidase inhibitors in the prophylaxis or treatment of influenza, were published between January 2005 and May 2014, and used a systematic search protocol. MEASUREMENTS: Two investigators blinded to all information regarding the review authors independently assessed the presentation of evidence on the use of neuraminidase inhibitors as favorable or not favorable. Financial conflicts of interest were identified using the index reviews, other publications, and Web-based searches. Associations between financial conflicts of interest, favorability assessments, and presence of critical appraisals of evidence quality were analyzed. RESULTS: Twenty-six systematic reviews were identified, of which 13 examined prophylaxis and 24 examined treatment, accounting for 37 distinct assessments. Among assessments associated with a financial conflict of interest, 7 of 8 (88%) were classified as favorable, compared with 5 of 29 (17%) among those without a financial conflict of interest. Reviewers without financial conflicts of interest were more likely to include statements about the quality of the primary studies than those with financial conflicts of interest. LIMITATIONS: The heterogeneity in populations and outcomes examined in the reviews precluded analysis of the contribution of selective inclusion of evidence on the discordance of the assessments made in the reviews. Many of the systematic reviews had overlapping authorship. CONCLUSION: Reviewers with financial conflicts of interest may be more likely to present evidence about neuraminidase inhibitors in a favorable manner and recommend the use of these drugs than reviewers without financial conflicts of interest. PRIMARY FUNDING SOURCE: Australian National Health and Medical Research Council.
Bourgeois FT, Olson KL, Ioannidis JP, Mandl KD. Association between pediatric clinical trials and global burden of disease. PediatricsPediatricsPediatrics 2014;133:78-87.Abstract
BACKGROUND: The allocation of research resources should favor conditions responsible for the greatest disease burden. This is particularly important in pediatric populations, which have been underrepresented in clinical research. Our aim was to measure the association between the focus of pediatric clinical trials and burden of disease and to identify neglected clinical domains. METHODS: We performed a cross-sectional study of clinical trials by using trial records in ClinicalTrials.gov. All trials started in 2006 or after and studying patient-level interventions in pediatric populations were included. Age-specific measures of disease burden were obtained for 21 separate conditions for high-, middle-, and low-income countries. We measured the correlation between number of pediatric clinical trials and disease burden for each condition. RESULTS: Neuropsychiatric conditions and infectious diseases were the most studied conditions globally in terms of number of trials (874 and 847 trials, respectively), while intentional injuries (5 trials) and maternal conditions (4 trials) were the least studied. Clinical trials were only moderately correlated with global disease burden (r = 0.58, P = .006). Correlations were also moderate within each of the country income levels, but lowest in low-income countries (r = .47, P = .03). Globally, the conditions most understudied relative to disease burden were injuries (-260 trials for unintentional injuries and -160 trials for intentional injuries), nutritional deficiencies (-175 trials), and respiratory infections (-171 trials). CONCLUSIONS: Pediatric clinical trial activity is only moderately associated with pediatric burden of disease, and least associated in low-income countries. The mismatch between clinical trials and disease burden identifies key clinical areas for focus and investment.
Bourgeois FT, Kim JM, Mandl KD. Premarket safety and efficacy studies for ADHD medications in children. PLoS OnePLoS OnePLoS One 2014;9:e102249.Abstract
BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a chronic condition and pharmacotherapy is the mainstay of treatment, with a variety of ADHD medications available to patients. However, it is unclear to what extent the long-term safety and efficacy of ADHD drugs have been evaluated prior to their market authorization. We aimed to quantify the number of participants studied and their length of exposure in ADHD drug trials prior to marketing. METHODS: We identified all ADHD medications approved by the Food and Drug Administration (FDA) and extracted data on clinical trials performed by the sponsor and used by the FDA to evaluate the drug's clinical efficacy and safety. For each ADHD medication, we measured the total number of participants studied and the length of participant exposure and identified any FDA requests for post-marketing trials. RESULTS: A total of 32 clinical trials were conducted for the approval of 20 ADHD drugs. The median number of participants studied per drug was 75 (IQR 0, 419). Eleven drugs (55%) were approved after <100 participants were studied and 14 (70%) after <300 participants. The median trial length prior to approval was 4 weeks (IQR 2, 9), with 5 (38%) drugs approved after participants were studied <4 weeks and 10 (77%) after <6 months. Six drugs were approved with requests for specific additional post-marketing trials, of which 2 were performed. CONCLUSIONS: Clinical trials conducted for the approval of many ADHD drugs have not been designed to assess rare adverse events or long-term safety and efficacy. While post-marketing studies can fill in some of the gaps, better assurance is needed that the proper trials are conducted either before or after a new medication is approved.
Bourgeois FT, Monuteaux MC, Stack AM, Neuman MI. Variation in emergency department admission rates in US children's hospitals. PediatricsPediatricsPediatrics 2014;134:539-45.Abstract
OBJECTIVE: To measure the hospital-level variation in admission rates for children receiving treatment of common pediatric illnesses across emergency departments (EDs) in US children's hospitals. METHODS: We performed a multi-center cross sectional study of children presenting to the EDs of 35 pediatric tertiary-care hospitals participating in the Pediatric Health Information System (PHIS). Admission rates were calculated for visits occurring between January 1, 2009, and December 31, 2012, associated with 1 of 7 common conditions, and corrected to adjust for hospital-level severity of illness. Conditions were selected systematically based on frequency of visits and admission rates. RESULTS: A total of 1288706 ED encounters (13.8% of all encounters) were associated with 1 of the 7 conditions of interest. After adjusting for hospital-level severity, the greatest variation in admission rates was observed for concussion (range 5%-72%), followed by pneumonia (19%-69%), and bronchiolitis (19%-65%). The least variation was found among patients presenting with seizures (7%-37%) and kidney and urinary tract infections (6%-37%). Although variability existed in disease-specific admission rates, certain hospitals had consistently higher, and others consistently lower, admission rates. CONCLUSIONS: We observed greater than threefold variation in severity-adjusted admission rates for common pediatric conditions across US children's hospitals. Although local practices and hospital-level factors may partly explain this variation, our findings highlight the need for greater focus on the standardization of decisions regarding admission.
2013
Murthy S, Mandl KD, Bourgeois F. Analysis of pediatric clinical drug trials for neuropsychiatric conditions. PediatricsPediatricsPediatrics 2013;131:1125-31.Abstract
BACKGROUND AND OBJECTIVE: Neuropsychiatric conditions represent a large and increasing disease burden in children. A number of drugs are available for the treatment of these conditions, but most drugs have not been adequately tested in children, and off-label drug use remains widespread. We sought to define and quantify recent and ongoing clinical research on the use of neuropsychiatric drugs in children. METHODS: Drug trials registered in ClinicalTrials.gov between 2006 and 2011 and studying neuropsychiatric conditions were selected and classified based on the drug's Food and Drug Administration (FDA) approval status in children. We measured the proportion of trials seeking to expand the use of a drug to pediatric patients and the proportion of available drugs studied in children. RESULTS: Only 10% of neuropsychiatric trials focused on children. Of 303 drugs studied in both pediatric and adult populations, 90% lacked FDA approval in children and 97% were not approved in children for the indication studied. However, only 19% of all neuropsychiatric drugs were under study in pediatric populations, with as few as 8% of either antidepressant or antipsychotic drugs. Overall, 76% of pediatric drug trials examined a drug previously unapproved in children and 26% explored the use of a drug for a new indication. CONCLUSIONS: Despite the rising prevalence of neuropsychiatric disease and the paucity of FDA-approved pediatric drugs, only a small proportion of trials focus on pediatric populations and these trials cover only a fraction of available drugs. This deficiency is most pronounced for depression and schizophrenia.
Dunn AG, Mandl KD, Coiera E, Bourgeois FT. The effects of industry sponsorship on comparator selection in trial registrations for neuropsychiatric conditions in children. PLoS OnePLoS OnePLoS One 2013;8:e84951.Abstract
Pediatric populations continue to be understudied in clinical drug trials despite the increasing use of pharmacotherapy in children, particularly with psychotropic drugs. Most pertinent to the clinical selection of drug interventions are trials directly comparing drugs against other drugs. The aim was to measure the prevalence of active drug comparators in neuropsychiatric drug trials in children and identify the effects of funding source on comparator selection. We analyzed the selection of drugs and drug comparisons in clinical trials registered between January 2006 and May 2012. Completed and ongoing interventional trials examining treatments for six neuropsychiatric conditions in children were included. Networks of drug comparisons for each condition were constructed using information about the trial study arms. Of 421 eligible trial registrations, 228 (63,699 participants) were drug trials addressing ADHD (106 trials), autism spectrum disorders (47), unipolar depression (16), seizure disorders (38), migraines and other headaches (15), or schizophrenia (11). Active drug comparators were used in only 11.0% of drug trials while 44.7% used a placebo control and 44.3% no drug or placebo comparator. Even among conditions with well-established pharmacotherapeutic options, almost all drug interventions were compared to a placebo. Active comparisons were more common among trials without industry funding (17% vs. 8%, p=0.04). Trials with industry funding differed from non-industry trials in terms of the drugs studied and the comparators selected. For 73% (61/84) of drugs and 90% (19/21) of unique comparisons, trials were funded exclusively by either industry or non-industry. We found that industry and non-industry differed when choosing comparators and active drug comparators were rare for both groups. This gap in pediatric research activity limits the evidence available to clinicians treating children and suggests a need to reassess the design and funding of pediatric trials in order to optimize the information derived from pediatric participation in clinical trials.

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