Observational studies are important tools for providing information on the safety and benefit of approved medications; they provide data on real-life use, rare outcomes and long-term effects that were undetectable in randomized controlled trials. We review various administrative databases in the US and Canada, in addition to European medical records databases, which have been used extensively to assess drug safety. We present their advantages, which include their large size and the availability of systematic and accurate medication data from pharmacies and extensive outcome data from hospital records, and limitations, including the questionable validity of diagnostic information and absence of information on confounders (e.g. disease severity) and over-the-counter drugs. We illustrate these challenges in the investigation of the cardiovascular risks of the cyclo-oxygenase 2 inhibitor rofecoxib and highlight important methodological issues, beyond the limitations of the databases, which could explain the contradictory findings from three observational studies that used these databases. We show that issues relating to the duration of drug use, immortal time, depletion of susceptibles and overadjustment were problematic sources of bias in these studies and discuss remedies to avoid these pitfalls. With careful attention to their design and analysis, observational database studies are powerful and modern tools for providing crucial data on drug effects.
"Yet, many prescribing decisions are informed by incomplete or conflicting evidence, or by the results of randomized trials that may not be transferrable to clinical practice [7,34,35]. In addition, off-label use of medications and varying compliance behavior of patients contribute to suboptimal treatment outcomes, leading to a growing interest in developing improved methods to capture adverse drug event data from the real-world to generate more robust estimates about the comparative safety and effectiveness of medications, and to develop interventions to improve patient care [6-8,17,18]. "
[Show abstract][Hide abstract] ABSTRACT: Adverse drug events are a frequent cause of emergency department presentations. Administrative data could be used to identify patients presenting with adverse drug events for post-market surveillance, and to conduct research in patient safety and in drug safety and effectiveness. However, such data sources have not been evaluated for their completeness with regard to adverse drug event reporting. Our objective was to determine the proportion of adverse drug events to outpatient medications diagnosed at the point-of-care in emergency departments that were documented in administrative data.
We linked the records of patients enrolled in a prospective observational cohort study on adverse drug events conducted in two Canadian tertiary care emergency departments to their administrative data. We compared the number of adverse drug events diagnosed and recorded at the point-of-care in the prospective study with the number of adverse drug events recorded in the administrative data.
Among 1574 emergency department visits, 221 were identified as adverse drug event-related in the prospective database. We found 15 adverse drug events documented in administrative records with ICD-10 codes clearly indicating an adverse drug event, indicating a sensitivity of 6.8% (95% CI 4.0--11.2%) of this code set. When the ICD-10 code categories were broadened to include codes indicating a very likely, likely or possible adverse event to a medication, 62 of 221 events were identifiable in administrative data, corresponding to a sensitivity of 28.1% (95% CI 22.3-34.6%).
Adverse drug events to outpatient medications were underreported in emergency department administrative data compared to the number of adverse drug events diagnosed and recorded at the point-of-care.
BMC Health Services Research 11/2013; 13(1):473. DOI:10.1186/1472-6963-13-473 · 1.71 Impact Factor
"Recently, Samy Suissa has illustrated time-related biases in 20 published studies – most of them in several respected journals and claimed for a re-assessment of all those studies for immortal time bias (Suissa, 2007). "
"These databases are a collection of health insurance claims that are maintained largely for billing and administrative purposes. Nevertheless, they permit the evaluation of not only a diverse population, but also a large number of subjects followed over a relatively long period of time in a real-world setting . "
[Show abstract][Hide abstract] ABSTRACT: Little data exist on how opioid doses vary with the length of exposure among chronic opioid users.
To characterize the change in the dosage of opioids over time, a retrospective cohort study using the PharMetrics database for the years 1999 through 2008 was conducted. Individuals exposed to opioids in 2000 who had 2 opioid dispensings at least 6 months apart and were opioid naive (did not receive any opioid 6 month before their exposure in 2000) were included. The date of the first dispensing in 2000 was defined as the index date and the dispensing had to be for a strong and full agonist opioid. All opioid doses were converted to oral morphine equivalent doses. Exposure was classified as continuous or intermittent. Mean, median, interquartile range, and 95th percentile of opioid dose over 6-month periods, as well as the percentage of subjects who ever received a high or very high opioid dose, were calculated.
Among the 48,986 subjects, the mean age was 44.5 years and 54.5% were women. Intermittent exposure was observed in 99% of subjects; continuous exposure was observed in 1% of subjects. The mean duration of exposure for the subjects who were continuously exposed to opioids was 477 days. In subjects with no cancer diagnosis who were continuously exposed to opioids, the mean, 25th, 50th, and 75th percentile of dose was stable during the first 2 years of use, but the 95th percentile increased. Seven percent of them were exposed to doses of 180 mg or more of morphine at some point.
Dose escalation is uncommon in subjects with intermittent exposure to opioids. For subjects with continuous exposure to opioids who have cancer, doses rise substantially with time. For those without cancer, doses remain relatively stable for the first 2 years of use, but subsequently increase. Seven percent of subjects with no cancer diagnosis will be exposed to daily doses of 180 mg or more of morphine equivalent at some point.
BMC Palliative Care 06/2010; 9(1):14. DOI:10.1186/1472-684X-9-14 · 1.78 Impact Factor
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