Under-reporting of Adverse Events in the Biomedical Literature

Kostoff, Ronald N.

doi:10.20309/jdis.201623

Cited by 7 publications

(5 citation statements)

References 37 publications

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“…Other barriers could be lack of knowledge about adverse events and whether they are related to the actual condition or the medications [51,52]. Complacency and other personal factors related to clinicians such as fear of being ridiculed of reporting merely suspected ADRs and fatigue were also reported [53].…”

Section: Discussionmentioning

confidence: 99%

Adverse drug reactions in primary care: a scoping review

Khalil

Huang

2020

BMC Health Serv Res

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Background: Medication-related adverse events, or adverse drug reactions (ADRs) are harmful events caused by medication. ADRs could have profound effects on the patients' quality of life, as well as creating an increased burden on the healthcare system. ADRs are one of the rising causes of morbidity and mortality internationally, and will continue to be a significant public health issue with the increased complexity in medication, to treat various diseases in an aging society. This scoping review aims to provide a detailed map of the most common adverse drug reactions experienced in primary healthcare setting, the drug classes that are most commonly associated with different levels/types of adverse drug reactions, causes of ADRs, their prevalence and consequences of experiencing ADRs. Methods: We systematically reviewed electronic databases Ovid MEDLINE, Embase, CINAHL Plus, Cochrane Central Register of Controlled Trials, PsycINFO and Scopus. In addition, the National Patient Safety Foundation Bibliography and the Agency for Health Care Research and Quality and Patient Safety Net Bibliography were searched. Studies published from 1990 onwards until December 7, 2018 were included as the incidence of reporting drug reactions were not prevalent before 1990. We only include studies published in English. Results: The final search yielded a total of 19 citations for inclusion published over a 15-year period that primarily focused on investigating the different types of adverse drug reactions in primary healthcare. The most causes of adverse events were related to drug related and allergies. Idiosyncratic adverse reactions were not very commonly reported. The most common adverse drug reactions reported in the studies included in this review were those that are associated with the central nervous system, gastrointestinal system and cardiovascular system. Several classes of medications were reported to be associated with adverse events. Conclusion: This scoping review identified that the most causes of ADRs were drug related and due to allergies. Idiosyncratic adverse reactions were not very commonly reported in the literature. This is mainly because it is hard to predict and these reactions are not associated with drug doses or routes of administration. The most common ADRs reported in the studies included in this review were those that are associated with the central nervous system, gastrointestinal system and cardiovascular system. Several classes of medications were reported to be associated with ADRs.

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Section: Discussionmentioning

confidence: 99%

Adverse drug reactions in primary care: a scoping review

Khalil

Huang

2020

BMC Health Serv Res

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“…Prescribers and patients might reasonably expect that accurate information would be available about the frequency, severity, and persistence of a common adverse effect of a drug approved for marketing more than two decades ago and prescribed to an estimated 2.6 million men annually. However, a meta-analysis of 34 reports of clinical trials of finasteride for androgenic alopecia found inadequate safety reporting and systematic underreporting of adverse events ( Belknap et al, 2015 ), exemplifying a known flaw in the detection or reporting of adverse drug effects in the medical literature ( Kostoff, 2016 ). While a few reports of trials of 5α-RIs for prostatic hyperplasia and lower urinary tract symptoms provide assessments of sexual dysfunction using universal evaluation and validated instruments ( Fwu et al, 2014 ); most rely on spontaneous voluntary reporting for adverse event detection and on global introspection for causality assessment ( Belknap et al, 2013 ); these methods are considered unreliable for detecting and evaluating adverse events in general ( Arimone et al, 2007 ; Koch-Weser, Sellers & Zacest, 1977 ; Kramer et al, 1985 ), and sexual dysfunction in particular ( Althof et al, 2013 ; Moore, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Persistent erectile dysfunction in men exposed to the 5α-reductase inhibitors, finasteride, or dutasteride

Kiguradze

Temps

Yarnold³

et al. 2017

PeerJ

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ImportanceCase reports describe persistent erectile dysfunction (PED) associated with exposure to 5α-reductase inhibitors (5α-RIs). Clinical trial reports and the manufacturers’ full prescribing information (FPI) for finasteride and dutasteride state that risk of sexual adverse effects is not increased by longer duration of 5α-RI exposure and that sexual adverse effects of 5α-RIs resolve in men who discontinue exposure.ObjectiveOur chief objective was to assess whether longer duration of 5α-RI exposure increases risk of PED, independent of age and other known risk factors. Men with shorter 5α-RI exposure served as a comparison control group for those with longer exposure.DesignWe used a single-group study design and classification tree analysis (CTA) to model PED (lasting ≥90 days after stopping 5α-RI). Covariates included subject attributes, diseases, and drug exposures associated with sexual dysfunction.SettingOur data source was the electronic medical record data repository for Northwestern Medicine.SubjectsThe analysis cohorts comprised all men exposed to finasteride or dutasteride or combination products containing one of these drugs, and the subgroup of men 16–42 years old and exposed to finasteride ≤1.25 mg/day.Main outcome and measuresOur main outcome measure was diagnosis of PED beginning after first 5α-RI exposure, continuing for at least 90 days after stopping 5α-RI, and with contemporaneous treatment with a phosphodiesterase-5 inhibitor (PDE5I). Other outcome measures were erectile dysfunction (ED) and low libido. PED was determined by manual review of medical narratives for all subjects with ED. Risk of an adverse effect was expressed as number needed to harm (NNH).ResultsAmong men with 5α-RI exposure, 167 of 11,909 (1.4%) developed PED (persistence median 1,348 days after stopping 5α-RI, interquartile range (IQR) 631.5–2320.5 days); the multivariable model predicting PED had four variables: prostate disease, duration of 5α-RI exposure, age, and nonsteroidal anti-inflammatory drug (NSAID) use. Of 530 men with new ED, 167 (31.5%) had new PED. Men without prostate disease who combined NSAID use with >208.5 days of 5α-RI exposure had 4.8-fold higher risk of PED than men with shorter exposure (NNH 59.8, all p < 0.002). Among men 16–42 years old and exposed to finasteride ≤1.25 mg/day, 34 of 4,284 (0.8%) developed PED (persistence median 1,534 days, IQR 651–2,351 days); the multivariable model predicting PED had one variable: duration of 5α-RI exposure. Of 103 young men with new ED, 34 (33%) had new PED. Young men with >205 days of finasteride exposure had 4.9-fold higher risk of PED (NNH 108.2, p < 0.004) than men with shorter exposure.Conclusion and relevanceRisk of PED was higher in men with longer exposure to 5α-RIs. Among young men, longer exposure to finasteride posed a greater risk of PED than all other assessed risk factors.

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“…There are three main obstacles these agencies face in determining the degree to which Exposure Limits are protective:Sufficiency of existing data for setting safe exposure limits (Has adequate research been done and reported on the toxic stimulus in question and does the research that has been conducted and reported reflect real-world exposures? )Sufficiency of incorporating relevant existing data from the biomedical literatureTrustworthiness of existing data in the biomedical literature [1].…”

Section: Introductionmentioning

confidence: 99%

The role of toxic stimuli combinations in determining safe exposure limits

2018

Self Cite

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This editorial addresses the effects of toxic stimuli combinations on determination of safe Exposure Limits. Examination of thousands of Medline abstracts showed typically that combinations of toxic stimuli can produce damage even when the exposure level of each member of the combination is less than the lowest exposure level of the member that produced damage when tested in isolation. The synergy of the toxic stimuli in combination means less of each component stimulus is required to cause damage compared to exposure levels when tested in isolation. This Editorial concludes there is no reason to believe today that the Exposure Limits on potentially toxic stimuli that have been set by the regulatory agencies are fully protective against serious adverse health effects in all real life exposure scenarios. The conclusion is applicable to essentially all potential contributing factors to disease amenable to Exposure Limits, including not only chemicals but other types of exposures such as radiofrequency radiation (RFR).

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Under-reporting of Adverse Events in the Biomedical Literature

Cited by 7 publications

References 37 publications

Adverse drug reactions in primary care: a scoping review

Adverse drug reactions in primary care: a scoping review

Persistent erectile dysfunction in men exposed to the 5α-reductase inhibitors, finasteride, or dutasteride

The role of toxic stimuli combinations in determining safe exposure limits

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