Discrepancies in listed adverse drug reactions in pharmaceutical product information supplied by the regulatory authorities in Denmark and the USA

Abstract

Pharmaceutical product information (PI) supplied by the regulatory authorities serves as a source of information on safe and effective use of drugs. The objectives of this study were to qualitatively and quantitatively compare PIs for selected drugs marketed in both Denmark and the USA with respect to consistency and discrepancy of listed adverse drug reaction (ADR) information. We compared individual ADRs listed in PIs from Denmark and the USA with respect to type and frequency. Consistency was defined as match of ADRs and of ADR frequency or match could not be ruled out. Discrepancies were defined as ADRs listed only in one country or listed with different frequencies. We analyzed PIs for 40 separate drugs from ten therapeutic groups and assigned the 4003 identified ADRs to System Organ Classes (Medical Dictionary for Regulatory Activities [MedDRA] terminology). Less than half of listed ADRs (n = 1874; 47%) showed consistency. Discrepancies (n = 2129; 53%) were split into ADRs listed only in the USA (n = 1558; 39%), ADRs listed only in Denmark (n = 325; 8%) and ADRs listed with different frequencies (n = 246; 6%). The majority of listed ADRs were of the type “gastrointestinal disorders” and “nervous system disorders”. Our results show great differences in PIs for drugs approved in both Denmark and the USA illuminating concerns about the credibility of the publicly available PIs. The results also represent an argument for further harmonization across borders to improve consistency between authority-supplied information.

Retrospective analysis of non-laboratory-based adverse drug reactions induced by intravenous radiocontrast agents in a Joint Commission International-accredited academic medical center hospital in China

“…Regarding frequency of ADRs, “rare” means the occurrence rate ≥0.01% but <0.1% whereas “uncommon” represents the occurrence rate ≥0.1% but <1% 8. Therefore, moderate or severe ADRs induced by 12 kinds of radiocontrast agents in our study were rare whereas mild ADRs were uncommon and accounted for 83.76% of ADRs (263/314), suggesting that enhanced CT and MRI examinations are highly safe.…”

Types, frequencies, and burden of nonspecific adverse events of drugs: analysis of randomized placebo‐controlled clinical trials

“…The lack of explicit decision rules to define ADRs based on AE data is reflected by substantial discrepancies in ADRs listed in product labels across countries. 29,30 The practical implications of our findings include the consideration that ADR information presented as absolute event rates in summaries of product characteristics and patient information leaflets is difficult to interpret without comparative data from a placebo or other relevant control group. The possibility that the current rules used to define ADRs results in the dissemination of nonspecific safety concerns implies the risk of misleading practitioners in making risk-benefit decisions and negatively affecting consumers' tolerability of drugs.…”

“…Suggested criteria to define ADRs are AEs occurring more frequently in active‐drug than placebo recipients, common AEs and rare but serious AEs, but our findings question the reliability of using such criteria to accurately single out true ADRs. The lack of explicit decision rules to define ADRs based on AE data is reflected by substantial discrepancies in ADRs listed in product labels across countries …”

Systematic Review and Meta-Analysis of The Efficacy And Safety Of Amfepramone and Mazindol As A Monotherapy for The Treatment of Obese or Overweight Patients

“…A feasible explanation lies in the low quality of primary and secondary studies that have already been published. Although differences between Anvisa, FDA, EMA and others countries are likely to occur, all organizations are strongly dependent on the quality of randomized clinical trials (RCT) (12,13). Treatment discontinuation, small sample size, low methodological quality and high levels of heterogeneity in meta-analyses are the most common limitations (14)(15)(16).…”