Evaluation of Switching Patterns in FDA’s Sentinel System: A New Tool to Assess Generic Drugs

Gagne, Joshua J.; Popovic, Jennifer R.; Nguyen, Michael; Sandhu, Sukhminder K.; Greene, Patty; Izem, Rima; Jiang, Wenlei; Wang, Zhong; Zhao, Yueqin; Petrone, Andrew B.; Wagner, Anita K.; Dutcher, Sarah K.

doi:10.1007/s40264-018-0709-4

Cited by 13 publications

(19 citation statements)

References 22 publications

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“…Using the other generics on the market as comparisons for the new generic would provide additional comparisons (ie, new generic vs other generics) to further detect signals. Given the limitations of FAERS data related to reporting bias and lack of a “denominator” to standardize event reports, administrative claims data and distributed data networks like the FDA Sentinel Initiative provide an ideal data and analytic environment to capture near‐real‐time signals using quarterly data and the demonstrated outcome metrics used here …”

Section: Discussionmentioning

confidence: 99%

“…Further, with issuance of FDA warning letters, utilization could become biased as physicians defer to the brand over generic formulations . We further limited the analysis (measures 2 and 3) to generic formulations released during this time period (Sandoz, Nesher) that were eventually recalled due to bioequivalence concerns …”

Section: Methodsmentioning

confidence: 99%

“…26 We further limited the analysis (measures 2 and 3) to generic formulations released during this time period (Sandoz, Nesher) that were eventually recalled due to bioequivalence concerns. 25 The analysis incorporated 3 measurements to serve as proxies for signals of formulation issues: (1) generic market share, or generic uptake, would be lower; (2) patients would discontinue treatment or switch back to trade formulations more frequently; and (3) event rates for common cardiovascular clinical adverse events or indicated therapeutic uses of the medications would be elevated. For measures 1 and 2, an "active comparator" was used to provide a reference point for all comparisons.…”

Section: Signal Verification Using Claims Datamentioning

confidence: 99%

“…The first generic of metoprolol ER was approved in July 2006 (Sandoz), an authorized generic in November 2006 (Par), and another in May 2007 (Nesher) . Dissolution‐related quality concerns were apparent as soon as late 2007, which eventually led to voluntary recalls and eventual discontinuations of the Sandoz and Nesher versions.…”

mentioning

confidence: 99%

“…The first generic of metoprolol ER was approved in July 2006 (Sandoz), an authorized generic in November 2006 (Par), and another in May 2007 (Nesher). 25 Dissolution-related quality concerns were apparent as soon as late 2007, which eventually led to voluntary recalls and eventual discontinuations of the Sandoz and Nesher versions. While this study used the Sandoz/Nesher time period to avoid potential biases related to patient and physician knowledge of these historic examples, it is worth noting that generic formulations of metoprolol ER have suffered recalls as recently as 2014 (Wockhardt, Dr. Reddy's).…”

mentioning

confidence: 99%

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Real‐World Data Approaches for Early Detection of Potential Safety and Effectiveness Signals for Generic Substitution: A Metoprolol Extended‐Release Case Study

Brown

Henriksen

Vozmediano

et al. 2019

The Journal of Clinical Pharma

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Real‐world spontaneous adverse event reports and administrative health care data were utilized as one part of a multipronged approach to verify surveillance signals related to generic drug formulations. This study used metoprolol succinate extended release as a historic case example from which to develop an analytic framework. The US Food and Drug Administration Adverse Event Reporting System was utilized for disproportionality analyses and to identify outcomes of interest. Claims data were analyzed for generic uptake, proportion of prescriptions with “dispense as written” orders, time to discontinuation or switching, and relative rates of clinical events. Adverse Event Reporting System data showed that the Medical Dictionary for Regulatory Activities terms for product quality were higher for generic metoprolol cases and that a number of clinical events were increased that could be side effects of high or low variability in drug levels. Compared to amlodipine‐benazepril, which also had a first‐approved generic at the same time, market share data showed that metoprolol succinate had lower utilization and more prescriptions written as dispense as written. Switching and discontinuation were generally higher for metoprolol users compared to amlodipine‐benazepril users. Finally, clinical event rates were generally higher for generic versus brand metoprolol but lower for the same comparison for amlodipine‐benazepril users. In the claims‐based analyses, the 90‐day period immediately after generic entry provided stronger signal capture than using the entire study period. This analytic framework can be implemented to actively monitor new generic formulations for potential bioequivalence failures. Signals from these analyses require confirmation (eg, via pharmacometric analyses) to be informative for regulatory action.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Signal Verification Using Claims Datamentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Real‐World Data Approaches for Early Detection of Potential Safety and Effectiveness Signals for Generic Substitution: A Metoprolol Extended‐Release Case Study

Brown

Henriksen

Vozmediano

et al. 2019

The Journal of Clinical Pharma

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Role of Authorized Generics in Postapproval Surveillance of Generic Drug Products

Gagne

Sarpatwari

Desai

2018

Clin Pharma and Therapeutics

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Postapproval surveillance of generic drugs is critical because these products comprise ≈90% of prescription medications dispensed in the United States. However, observational studies of generic drugs are challenging because of potential negative perceptions of generics and potential confounding by socioeconomic status. Authorized generics, which are brand-name drugs that are marketed, sold, or distributed as generic medications, can and should play an important role in evaluating the performance of generic drugs in the postapproval setting.

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Lower Proportion of Spontaneous Adverse Event Reports for Generic Drugs by Comparison With Original Branded Drugs at the Postmarket Stage in Japan

Takami

Hirata

Ishiguro

et al. 2019

Clin Pharma and Therapeutics

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We investigated impacts of increased generic drug use on spontaneous adverse event reports (SAERs), because SAERs have been a major source of data for drug safety assessment at the postmarket stage. Reporting proportion of SAERs for the generic drugs was consistently and significantly lower than that for the original branded drugs. The reporting proportion targeting for 55 active product ingredients, which had the longest follow-up period after generic drug marketed, gradually decreased for the original branded drugs and increased for the generic drugs. However, these transitions did not parallel the changes in market share over the same period. These results suggest that the reporting proportion of SAERs for generic drugs may not keep pace with growth in market share. When generic drugs account for the majority of market share, utilization of multiple sources of information and data, in addition to SAERs, may be a key to assuring drug safety at the postmarket stage.

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Evaluation of Switching Patterns in FDA’s Sentinel System: A New Tool to Assess Generic Drugs

Abstract: This developed tool was able to elucidate novel utilization and switching patterns in two case studies. Such information can be used to support surveillance of generic drugs and biosimilars.

Cited by 13 publications

References 22 publications

Real‐World Data Approaches for Early Detection of Potential Safety and Effectiveness Signals for Generic Substitution: A Metoprolol Extended‐Release Case Study

Real‐World Data Approaches for Early Detection of Potential Safety and Effectiveness Signals for Generic Substitution: A Metoprolol Extended‐Release Case Study

Role of Authorized Generics in Postapproval Surveillance of Generic Drug Products

Lower Proportion of Spontaneous Adverse Event Reports for Generic Drugs by Comparison With Original Branded Drugs at the Postmarket Stage in Japan

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