Assessment of Use of Combined Dextromethorphan and Quinidine in Patients With Dementia or Parkinson Disease After US Food and Drug Administration Approval for Pseudobulbar Affect

Fralick, Michael; Sacks, Chana A.; Kesselheim, Aaron S.

doi:10.1001/jamainternmed.2018.6112

Cited by 28 publications

(25 citation statements)

References 34 publications

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“…MarketScan and Optum primarily include adults with employer based health plans. The average age of adults is generally higher in Optum than in MarketScan, because about 10% of adults in Optum have Medicare Advantage (a supplemental insurance plan for patients in Medicare) 16. Medicare predominantly includes adults aged over 65 years.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Risk of amputation with canagliflozin across categories of age and cardiovascular risk in three US nationwide databases: cohort study

Fralick

Kim

Schneeweiß

et al. 2020

BMJ

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ObjectiveTo estimate the rate of lower limb amputation among adults newly prescribed canagliflozin according to age and cardiovascular disease.DesignPopulation based, new user, cohort study.Data sourcesTwo commercial and Medicare claims databases, 2013-17.ParticipantsPatients newly prescribed canagliflozin were propensity score matched 1:1 with patients newly prescribed a glucagon-like peptide-1 (GLP-1) receptor agonist. Hazard ratios and rate differences per 1000 person years were computed for the rate of lower limb amputation in the following four groups: group 1, patients aged less than 65 years without baseline cardiovascular disease; group 2, patients aged less than 65 with baseline cardiovascular disease; group 3, patients aged 65 or older without baseline cardiovascular disease; group 4, patients aged 65 or older with baseline cardiovascular disease. Within each group, pooled hazard ratio and rate difference per 1000 person years were calculated by meta-analysis.InterventionCanagliflozin versus a GLP-1 agonist.Main outcome measuresLower limb amputation requiring surgery.ResultsAcross the three databases, 310 840 propensity score matched adults who started canagliflozin or a GLP-1 agonist were identified. The hazard ratio and rate difference per 1000 person years for amputation in adults receiving canagliflozin compared with a GLP-1 agonist for each group was: group 1, hazard ratio 1.09 (95% confidence interval 0.83 to 1.43), rate difference 0.12 (−0.31 to 0.55); group 2, hazard ratio 1.18 (0.86 to 1.62), rate difference 1.06 (−1.77 to 3.89); group 3, hazard ratio 1.30 (0.52 to 3.26), rate difference 0.47 (−0.73 to 1.67); and group 4, hazard ratio 1.73 (1.30 to 2.29), rate difference 3.66 (1.74 to 5.59).ConclusionsThe increase in rate of amputation with canagliflozin was small and most apparent on an absolute scale for adults aged 65 or older with baseline cardiovascular disease, resulting in a number needed to treat for an additional harmful outcome of 556 patients at six months (that is, 18 more amputations per 10 000 people who received canagliflozin). These results help to contextualize the risk of amputation with canagliflozin in routine care.

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Section: Methodsmentioning

confidence: 99%

“…The average age of adults is generally higher in Optum than in MarketScan, because about 10% of adults in Optum have Medicare Advantage (a supplemental insurance plan for patients in Medicare). 16 Medicare predominantly includes adults aged over 65 years. Collectively, these three databases include over 100 million people in the US.…”

Section: Methodsmentioning

confidence: 99%

Risk of amputation with canagliflozin across categories of age and cardiovascular risk in three US nationwide databases: cohort study

Fralick

Kim

Schneeweiß

et al. 2020

BMJ

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“…and thus the results may be more generalizable. 32,33 There are a number of important limitations of our study. First, our study was limited to new medications approved in 2011, and it is unclear whether our findings are generalizable to drugs approved in other years, to non-drug products, to new indications of approved drugs, or to post-approval confirmatory trials.…”

Section: Discussionmentioning

confidence: 93%

Understanding when real world data can be used to replicate a clinical trial: A cross‐sectional study of medications approved in 2011

Fralick

Bartsch

Darrow

et al. 2020

Pharmacoepidemiology and Drug

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Purpose: To determine how commonly pre-approval clinical trials could potentially be replicated using real-world data from insurance claims databases. Methods: We conducted a cross-sectional study of medications approved by the FDA in 2011. For each medication, we reviewed the drug's label and the details of the pivotal clinical trials supporting its approval. We assessed whether each clinical trial could be replicated using an insurance claims databases by determining whether the following pivotal trial features could be reliably captured in claims data: study outcome, inclusion criteria, exclusion criteria, and the presence of an appropriate active comparator. Results: In 2011, 28 new medications were approved. The most common disease areas were oncology (N = 8, 29%), infectious disease (N = 5, 18%), and neurology (N = 4, 14%). The primary outcome of pre-approval clinical trials was identifiable in claims databases for six (21%) of the medications. Two (ticagrelor and linagliptin) had at least 80% of inclusion and exclusion criteria that could be identified in claims databases and had an available active comparator. The non-identifiable primary outcomes were related to patient-reported symptoms (N = 9, 32%), imaging findings (N = 5, 18%), laboratory values (N = 5, 18%), or other measurements (eg, blood pressure) not typically available in insurance claims databases (N = 4, 14%). Conclusions: Among drugs FDA-approved in 2011, two (7%) had a pre-approval trial that could be replicated using insurance claims databases. In such qualifying trials, replication using claims databases could be useful in assessing whether they provide concordant results.

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“…For example dextromethorphan is the top predicted candidate. Despite approval by the FDA for pseudobulbar affect based on studies of patients with amyotrophic lateral sclerosis or multiple sclerosis, Fox et al (2017) and Fralick et al (2019) provided evidence of clinical benefit with dextromethorphan–quinidine for treating PD. Atomoxetine was also predicted by our model to be associated with PD.…”

Section: Resultsmentioning

confidence: 99%

Toward heterogeneous information fusion: bipartite graph convolutional networks for in silico drug repurposing

Wang

Zhou²,

Arnold

2020

Bioinformatics

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Motivation Mining drug–disease association and related interactions are essential for developing in silico drug repurposing (DR) methods and understanding underlying biological mechanisms. Recently, large-scale biological databases are increasingly available for pharmaceutical research, allowing for deep characterization for molecular informatics and drug discovery. However, DR is challenging due to the molecular heterogeneity of disease and diverse drug–disease associations. Importantly, the complexity of molecular target interactions, such as protein–protein interaction (PPI), remains to be elucidated. DR thus requires deep exploration of a multimodal biological network in an integrative context. Results In this study, we propose BiFusion, a bipartite graph convolution network model for DR through heterogeneous information fusion. Our approach combines insights of multiscale pharmaceutical information by constructing a multirelational graph of drug–protein, disease–protein and PPIs. Especially, our model introduces protein nodes as a bridge for message passing among diverse biological domains, which provides insights into utilizing PPI for improved DR assessment. Unlike conventional graph convolution networks always assuming the same node attributes in a global graph, our approach models interdomain information fusion with bipartite graph convolution operation. We offered an exploratory analysis for finding novel drug–disease associations. Extensive experiments showed that our approach achieved improved performance than multiple baselines for DR analysis. Availability and implementation Source code and preprocessed datasets are at: https://github.com/zcwang0702/BiFusion.

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Assessment of Use of Combined Dextromethorphan and Quinidine in Patients With Dementia or Parkinson Disease After US Food and Drug Administration Approval for Pseudobulbar Affect

Cited by 28 publications

References 34 publications

Risk of amputation with canagliflozin across categories of age and cardiovascular risk in three US nationwide databases: cohort study

Risk of amputation with canagliflozin across categories of age and cardiovascular risk in three US nationwide databases: cohort study

Understanding when real world data can be used to replicate a clinical trial: A cross‐sectional study of medications approved in 2011

Toward heterogeneous information fusion: bipartite graph convolutional networks for in silico drug repurposing

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