Developing the Sentinel System — A National Resource for Evidence Development

Behrman, Rachel E.; Benner, Joshua S.; Brown, Jeffrey S.; McClellan, Mark; Woodcock, Janet; Platt, Richard

doi:10.1056/nejmp1014427

Cited by 301 publications

(246 citation statements)

References 2 publications

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“…17,18 One of the current MiniSentinel activities is an assessment of diabetes risk in youth newly initiating an SGA and, as part of assessing diabetes risk, we explored the feasibility of using blood glucose data available from these youth for baseline confounding adjustment. The population for this overall MiniSentinel assessment of diabetes risk in youth initiating an SGA has been previously described.…”

Section: Methodsmentioning

confidence: 99%

“…We sought to examine baseline glucose monitoring in youth prescribed SGAs in the United States by using data from the Mini-Sentinel project, a pilot program funded by the FDA to develop national capacity to rapidly conduct postmarket active medical product safety surveillance and to demonstrate the usefulness of this information to the FDA. 17 …”

Section: (Continued On Last Page)mentioning

confidence: 99%

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Adherence to Guidelines for Glucose Assessment in Starting Second-Generation Antipsychotics

Raebel

Penfold

McMahon³

et al. 2014

Pediatrics

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OBJECTIVES: In 2003, the US Food and Drug Administration issued warnings about hyperglycemia and diabetes with second-generation antipsychotics (SGAs); guidelines have recommended metabolic screening since 2004. However, little is known of contemporary practices of glucose screening among youth initiating SGAs. Our objective was to evaluate baseline glucose assessment among youth in the Mini-Sentinel Distributed Database starting an SGA. METHODS: The cohort included youth ages 2 through 18 newly initiating SGAs January 1, 2006, through December 31, 2011, across 10 sites. Baseline glucose was defined as fasting/random glucose or hemoglobin A1c (GLU) measurement occurring relative to first SGA dispensing. Differences in GLU assessment were evaluated with χ2 tests and logistic regression. RESULTS: The cohort included 16 304 youth; 60% boys; mean age 12.8 years. Risperidone was most commonly started (43%). Eleven percent (n = 1858) had GLU assessed between 90 days before and 3 days after first dispensing. Assessment varied across SGAs (olanzapine highest), sites (integrated health care systems higher), ages (16–18 highest), years (2007 highest), and gender (female higher; all P < .001). GLU assessment among those starting olanzapine was more likely than among those starting quetiapine (odds ratio [OR]: 1.72 [95% confidence interval (CI): 1.37–2.18]), aripiprazole (OR: 1.49 [95% CI: 1.18–1.87]), or risperidone (OR: 1.61 [95% CI: 1.28–2.03]). CONCLUSIONS: Few children and adolescents starting SGA have baseline glucose assessed. This is concerning because those at high diabetes risk may not be identified. Further, lack of screening impedes determining the contribution of SGAs to hyperglycemia development.

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Section: Methodsmentioning

confidence: 99%

Section: (Continued On Last Page)mentioning

confidence: 99%

Adherence to Guidelines for Glucose Assessment in Starting Second-Generation Antipsychotics

Raebel

Penfold

McMahon³

et al. 2014

Pediatrics

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“…In the USA, the FDA was only allowed after 1938 to demand safety documentation of drugs, and only in 1962, manufacturers could be required to prove the effectiveness of their drugs. Newer developments include the opportunity to ask drug safety questions electronically in the Sentinel system which encompasses up to 100 million patient records [2]. Nevertheless, pre-and especially post-marketing drug surveillance may have some systematic pitfalls.…”

Section: Existing Pharmacovigilance System and Its Limitationsmentioning

confidence: 99%

The out-of-focus bias in drug surveillance

Gnädinger

Mellinghoff²

2012

Eur J Clin Pharmacol

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PURPOSE: Existing drug safety systems with phase II and III studies and post-marketing surveillance by principle do not allow for the recognition of an important class of adverse drug reactions (ADRs). ADRs that are resistant to being detected reliably may a) appear as if they are age-related chronic diseases, which also manifest themselves in a high degree without drug treatment, b) arise in "old" drugs, c) arise during long-term application, and d) arise with the administration to frail and aged populations. CONCLUSIONS: "Silent" and multi-factorial health problems evolving from long-term drug treatment must therefore be addressed with a systematic search strategy, as a third track along with the phase II and III studies and spontaneous reporting systems which still exist. SummaryExisting drug safety systems with phase II and III studies and post-marketing surveillance do not allow recognizing an important class of adverse drug reactions (ADRs) by principle. ADRs which are resistant to being detected reliably may a) be appearing like and age-related chronic diseases which also manifest themselves in a high degree without drug treatment, b) arriving in "old" drugs, c) during long-term application, and d) with the administration to frail and aged populations. "Silent" and multi-factorial health problems evolving from long-term drug treatment must therefore be addressed with a systematic search strategy, as a third track along with the phase II and III studies and spontaneous reporting systems which still exist. Existing pharmacovigilance system and its limitations

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“…The FDA's Sentinel Initiative is an example of a program designed to improve the evaluation of safety across a large array of FDA-regulated medical products. 1 This paper describes statistical methods for the evaluation of recently approved products using a prospective cohort observational design with existing electronic healthcare data for pre-specified safety outcomes. The goal of this study design is to quickly detect potential safety concerns by sequentially monitoring effect estimates multiple times throughout an evaluation.…”

Section: Introductionmentioning

confidence: 99%

Statistical approaches to group sequential monitoring of postmarket safety surveillance data: current state of the art for use in the Mini‐Sentinel pilot

Cook

Tiwari

Wellman

et al. 2012

Pharmacoepidemiology and Drug

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Purpose This manuscript describes the current statistical methodology available for active postmarket surveillance of pre-specified safety outcomes using a prospective incident user concurrent control cohort design with existing electronic healthcare data. Methods Motivation of the active postmarket surveillance setting is provided using the Food and Drug Administration's Mini-Sentinel Pilot as an example. Four sequential monitoring statistical methods are presented including the Lan-Demets error spending approach, a matched likelihood ratio test statistic approach with the binomial MaxSPRT as a special case, the conditional sequential sampling procedure with stratification, and a generalized estimating equation regression approach using permutation. Information on the assumptions, limitations, and advantages of each approach is provided, including how each method defines sequential monitoring boundaries, what test statistic is used, and how robust it is to settings of rare events or frequent testing. Results A hypothetical example of how the approaches could be applied to data comparing a medical product of interest, drug A, to a concurrent control drug, drug B, is presented including providing the type of information one would have available for monitoring such drugs. Summary We have described the current state of methodology for postmarket surveillance of pre-specified safety outcomes. We describe the limitations and advantages of the approaches while acknowledging areas for future development.

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Developing the Sentinel System — A National Resource for Evidence Development

Cited by 301 publications

References 2 publications

Adherence to Guidelines for Glucose Assessment in Starting Second-Generation Antipsychotics

Adherence to Guidelines for Glucose Assessment in Starting Second-Generation Antipsychotics

The out-of-focus bias in drug surveillance

Statistical approaches to group sequential monitoring of postmarket safety surveillance data: current state of the art for use in the Mini‐Sentinel pilot

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