There is increasing interest in utilizing real‐world data (RWD) to produce real‐world evidence (RWE) on the benefits and risks of medical products that could support regulatory approval decisions. ...The field of pharmacoepidemiology has a long history of focusing on data and evidence that would now be termed “real‐world,” including evidence from healthcare claims, registries, and electronic health records. However, several emerging trends over the past decade are converging to support the use of these and other RWD sources for approval decisions, and there are several recent examples and ongoing research that demonstrate how RWE may be used to support regulatory approval of new or expanded indications. The goal of this article is to review the current landscape and future directions of the use of RWE in this context. This manuscript is endorsed by the International Society for Pharmacoepidemiology (ISPE).
A fundamental question in using real‐world data for clinical and regulatory decision making is: How certain must we be that the algorithm used to capture an exposure, outcome, cohort‐defining ...characteristic, or confounder is what we intend it to be? We provide a practical framework to help researchers and regulators assess and classify the fit‐for‐purposefulness of real‐world data by study variable for a range of data sources. The three levels of certainty (optimal, sufficient, and probable) must be considered in the context of each study variable, the specific question being studied, the study design, and the decision at hand.
Background Safety concerns associated with long-acting β2 -agonists (LABAs) have led to many US Food and Drug Administration (FDA) regulatory activities for this class of drugs. Little is known about ...the effect of these regulatory activities on use of LABA-containing agents or other asthma medications. Methods We created rolling cohorts of pediatric and adult asthmatic patients in the Mini-Sentinel Distributed Database between January 2005 and June 2011. The proportions of asthmatic patients using LABA-containing products, inhaled corticosteroids (ICSs), leukotriene modifiers, short-acting β2 -agonists, oral corticosteroids, other bronchodilators, and no medications were measured on a monthly basis, and the changes were evaluated by using interrupted time series with segmented regression analysis. Results When the 2005 regulatory activity was announced, there were statistically significant decreases in the use of fixed-dose ICS-LABA agents in children (−0.98 percentage points) and adults (−1.24 percentage points). Increased use of ICSs and leukotriene modifiers was observed just after the regulatory activities were announced in both children and adults. Although of smaller magnitude, continued favorable changes in the use of LABA agents were observed after the 2010 FDA regulatory activity. Conclusion The 2005 and 2010 FDA regulatory activities might have contributed to reduced use of LABA agents, as intended; however, their effect, independent of other factors, cannot be determined. Use of other classes of asthma medications was similarly affected.
Purpose
The goal of this study is to summarize trends in rates of adverse events attributable to acetaminophen use, including hepatotoxicity and mortality.
Methods
A comprehensive analysis of data ...from three national surveillance systems estimated rates of acetaminophen‐related events identified in different settings, including calls to poison centers (2008–2012), emergency department visits (2004–2012), and inpatient hospitalizations (1998–2011). Rates of acetaminophen‐related events were calculated per setting, census population, and distributed drug units.
Results
Rates of poison center calls with acetaminophen‐related exposures decreased from 49.5/1000 calls in 2009 to 43.5/1000 calls in 2012. Rates of emergency department visits for unintentional acetaminophen‐related adverse events decreased from 58.0/1000 emergency department visits for adverse drug events in 2009 to 50.2/1000 emergency department visits in 2012. Rates of hospital inpatient discharges with acetaminophen‐related poisoning decreased from 119.8/100 000 hospitalizations in 2009 to 108.6/100 000 hospitalizations in 2011. After 2009, population rates of acetaminophen‐related events per 1 million census population decreased for poison center calls and hospitalizations, while emergency department visit rates remained stable. However, when accounting for drug sales, the rate of acetaminophen‐related events (per 1 million distributed drug units) increased after 2009. Prior to 2009, the rates of acetaminophen‐related hospitalizations had been slowly increasing (p‐trend = 0.001).
Conclusions
Acetaminophen‐related adverse events continue to be a public health burden. Future studies with additional time points are necessary to confirm trends and determine whether recent risk mitigation efforts had a beneficial impact on acetaminophen‐related adverse events. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
To examine risk factors for sudden infant death syndrome (SIDS) with the goal of reducing SIDS mortality among blacks, which continues to affect this group at twice the rate of whites.
We analyzed ...data from a population-based case-control study of 260 SIDS deaths that occurred in Chicago between 1993 and 1996 and an equal number of matched living controls to determine the association between SIDS and factors in the sleep environment and other variables related to infant care.
The racial/ethnic composition of the study groups was 75.0% black; 13.1% Hispanic white; and 11.9% non-Hispanic white. Several factors related to the sleep environment during last sleep were associated with higher risk of SIDS: placement in the prone position (unadjusted odds ratio OR: 2.4; 95% confidence interval CI: 1.7-3.4), soft surface (OR: 5.1; 95% CI: 3.1-8.3), pillow use (OR: 2.5; 95% CI: 1.5-4.2), face and/or head covered with bedding (OR: 2.5; 95% CI: 1.3-4.6), bed sharing overall (OR: 2.7; 95% CI: 1.8-4.2), bed sharing with parent(s) alone (OR: 1.9; 95% CI: 1.2-3.1), and bed sharing in other combinations (OR: 5.4; 95% CI: 2.8-10.2). Pacifier use was associated with decreased risk (unadjusted OR: 0.3; 95% CI: 0.2-0.5), as was breastfeeding either ever (OR: 0.2; 95% CI: 0.1-0.3) or currently (OR: 0.2; 95% CI: 0.1-0.4). In a multivariate model, several factors remained significant: prone sleep position, soft surface, pillow use, bed sharing other than with parent(s) alone, and not using a pacifier.
To lower further the SIDS rate among black and other racial/ethnic groups, prone sleeping, the use of soft bedding and pillows, and some types of bed sharing should be reduced.
Sudden infant death syndrome (SIDS) is a leading cause of postneonatal mortality among American Indians, a group whose infant death rate is consistently above the US national average.
To determine ...prenatal and postnatal risk factors for SIDS among American Indians.
Population-based case-control study of 33 SIDS infants and 66 matched living controls among American Indians in South Dakota, North Dakota, Nebraska, and Iowa enrolled from December 1992 to November 1996 and investigated using standardized parental interview, medical record abstraction, autopsy protocol, and infant death review.
Association of SIDS with maternal socioeconomic and behavioral factors, health care utilization, and infant care practices.
The proportions of case and control infants who were usually placed prone to sleep (15.2% and 13.6%, respectively), who shared a bed with parents (59.4% and 55.4%), or whose mothers smoked during pregnancy (69.7% and 54.6%) were similar. However, mothers of 72.7% of case infants and 45.5% of control infants engaged in binge drinking during pregnancy. Conditional logistic regression revealed significant associations between SIDS and 2 or more layers of clothing on the infant (adjusted odds ratio aOR, 6.2; 95% confidence interval CI, 1.4-26.5), any visits by a public health nurse (aOR, 0.2; 95% CI, 0.1-0.8), periconceptional maternal alcohol use (aOR, 6.2; 95% CI, 1.6-23.3), and maternal first-trimester binge drinking (aOR, 8.2; 95% CI, 1.9-35.3).
Public health nurse visits, maternal alcohol use during the periconceptional period and first trimester, and layers of clothing are important risk factors for SIDS among Northern Plains Indians. Strengthening public health nurse visiting programs and programs to reduce alcohol consumption among women of childbearing age could potentially reduce the high rate of SIDS.
To describe changes in infant mortality rates, including birthweight-specific rates and rates by age at death and cause.
We analyzed US linked birth/infant-death data for 1989-1991 and 1998-2000 for ...American Indians/Alaska Native (AIAN) and White singleton infants at > or =20 weeks' gestation born to US residents. We calculated birthweight-specific infant mortality rates (deaths in each birthweight category per 1000 live births in that category), and overall and cause-specific infant mortality rates (deaths per 100000 live births) in infancy (0-364 days) and in the neonatal (0-27 days) and postneonatal (28-364 days) periods.
Birthweight-specific infant mortality rates declined among AIAN and White infants across all birthweight categories, but AIAN infants generally had higher birthweight-specific infant mortality rates. Infant mortality rates declined for both groups, yet in 1998-2000, AIAN infants were still 1.7 times more likely to die than White infants. Most of the disparity was because of elevated post-neonatal mortality, especially from sudden infant death syndrome, accidents, and pneumonia and influenza.
Although birthweight-specific infant mortality rates and infant mortality rates declined among both AIAN and White infants, disparities in infant mortality persist. Preventable causes of infant mortality identified in this analysis should be targeted to reduce excess deaths among AIAN communities.
Emerging safety issues associated with long-acting beta
-agonist (LABA) have led to multiple regulatory activities by the US Food and Drug Administration (FDA) since 2003, including Drug Safety ...Communications (DSCs) in 2010. These DSCs had three specific recommendations for the safe use of LABA products in adult asthma treatment.
We examined the initiation of LABA-containing products for adult asthma treatment using an intermittent time series approach in a claims database from 2003 to 2012. We assessed the alignment of dispensing patterns with the following 2010 FDA recommendations: 1) contraindicated use of single-ingredient (SI)-LABA without an asthma controller medication (ACM); 2) a LABA should only be used when asthma is not adequately controlled on inhaled corticosteroids (ICSs) or ACM; and 3) step-down asthma therapy (e.g., discontinue LABA) when asthma control is achieved.
There were 477,922 adults (18-64 years old) dispensed a new LABA during 2003-2012. Among LABA initiators, patients who initiated an SI-LABA and who did "not" have an ACM dispensed on the same date decreased from >9% in 2003 (the initial labeling change) to <2% post 2010 DSCs (
-value <0.0001 in the segmented regression model). The proportion of asthma patients dispensed an ICS in 6 months prior to initiating LABA treatment did not increase. The proportion of patients with longer than 4 months of continuous treatment did not decrease over the study period.
Although the decrease in SI-LABA initiation is consistent with FDA's recommendations, low ICS dispensing before initiating a LABA and LABA continuation practices require further efforts to move toward the recommended safe practices.
Objectives Pharmacoepidemiological studies are an important hypothesis-testing tool in the evaluation of postmarketing drug safety. Despite the potential to produce robust value-added data, ...interpretation of findings can be hindered due to well-recognised methodological limitations of these studies. Therefore, assessment of their quality is essential to evaluating their credibility. The objective of this review was to evaluate the suitability and relevance of available tools for the assessment of pharmacoepidemiological safety studies. Design We created an a priori assessment framework consisting of reporting elements (REs) and quality assessment attributes (QAAs). A comprehensive literature search identified distinct assessment tools and the prespecified elements and attributes were evaluated. Primary and secondary outcome measures The primary outcome measure was the percentage representation of each domain, RE and QAA for the quality assessment tools. Results A total of 61 tools were reviewed. Most tools were not designed to evaluate pharmacoepidemiological safety studies. More than 50% of the reviewed tools considered REs under the research aims, analytical approach, outcome definition and ascertainment, study population and exposure definition and ascertainment domains. REs under the discussion and interpretation, results and study team domains were considered in less than 40% of the tools. Except for the data source domain, quality attributes were considered in less than 50% of the tools. Conclusions Many tools failed to include critical assessment elements relevant to observational pharmacoepidemiological safety studies and did not distinguish between REs and QAAs. Further, there is a lack of considerations on the relative weights of different domains and elements. The development of a quality assessment tool would facilitate consistent, objective and evidence-based assessments of pharmacoepidemiological safety studies.
The safety of tiotropium--the FDA's conclusions Michele, Theresa M; Pinheiro, Simone; Iyasu, Solomon
The New England journal of medicine,
2010-Sep-16, Letnik:
363, Številka:
12
Journal Article
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