Relevance of the Weber effect in contemporary pharmacovigilance of oncology drugs

Arora, Ankur; Jalali, Rajinder K.; Vohora, Divya

doi:10.2147/tcrm.s137144

Cited by 33 publications

(35 citation statements)

References 25 publications

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“…6 A review of the literature indicates that this effect has been sought after on several occasions with varying results, thereby leading some authors to question the reproducibility of the Weber effect. [7][8][9][10][11] It has also been observed that most of the evaluations conducted on Therefore, the current study was designed to evaluate the validity of the Weber effect in the context of medicines used in a specialty care setting on a more granular level, utilising sales volume data as a proxy for patient exposure. The study also evaluated the reporting trend differences among solicited and unsolicited safety reports, as well as the type of information reported via these systems i.e.…”

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confidence: 99%

“…The authors evaluated AR reports from the FAERS database,and adjusted the number of reports to the number of dispensed prescriptions from US outpatient retail pharmacies, as a proxy for drug exposure 9. Similarly, analyses conducted by Arora et al7 and Hoffman et al20 studied recently approved drugs and utilised data from FAERS.There was no observation of a second-year peak nor of a subsequent fall in the volume of AR reports. One important observation evident from the review of studies conducted with drugs used in a specialty care setting is that whilst Weber 5 attributed the changing trends in AR reporting to drug exposure and familiarity of the drug, the studies thus far have primarily relied upon the absolute number of ARs from the source system (usually the Adverse Event Reporting System for the USA, which was the predecessor of FAERS).…”

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confidence: 99%

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Reporting rates of adverse reactions to specialty care medicines exhibit a direct positive correlation with patient exposure: A lack of evidence for the Weber effect

Modgill

Dormegny

Lewis³

2020

Brit J Clinical Pharma

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The classical Weber effect describes an increase in adverse reaction (AR) reports after medicinal product authorisation, with a peak in AR reporting at the end of the second year followed by a decline, despite increasing patient exposure. The present study aimed to evaluate the validity of the Weber effect in the context of authorised medicines in a specialty care setting. Methods: Using 6-monthly sales data as a proxy for exposure, the exposure-adjusted reporting rates for AR reports for 10 selected specialty care medicines were plotted against time. These data were also evaluated based on the source of report (solicited or unsolicited) and the nature of the AR contained within the reports (listed or unlisted). Unsolicited reports were analysed against sales volumes. Goodness of fit (R 2) was calculated and the trend representing the highest R 2 was selected. Results: Study data comprised a total of 1 222 852 AR reports for 10 specialty care medicines. Amongst all of the products evaluated, none of the associated data represented reporting patterns entirely consistent with the classical Weber effect (see Figure 1). The results, however, showed a systemic direct correlation between AR reporting and sales volumes, especially throughout the first 5 years postauthorisation. Conclusion: The study not only presents evidence of the absence of the Weber effect with specialty care medicines but also provides a substantial evidence of linear AR reporting correlating with sales volumes, especially during the first 5 years after marketing.

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confidence: 99%

Reporting rates of adverse reactions to specialty care medicines exhibit a direct positive correlation with patient exposure: A lack of evidence for the Weber effect

Modgill

Dormegny

Lewis³

2020

Brit J Clinical Pharma

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“…The result of which could underestimate the effect IAC had on the incidence of hemolysis. Finally, the Weber effect, which describes the effect where spontaneous reporting of adverse events peaks at the end of the second year after regulatory approval and declines steadily thereafter, is a potential confounder for reporting database studies . However, considering that IVIG has been around for decades, the clear directional shift in hemolysis reporting rates following implementation of IAC in 2016 is unlikely to be attributable to the Weber effect.…”

Section: Discussionmentioning

confidence: 99%

Isoagglutinin reduction in intravenous immunoglobulin (IgPro10, Privigen) by specific immunoaffinity chromatography reduces its reporting rates of hemolytic reactions: an analysis of spontaneous adverse event reports

et al. 2020

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BACKGROUND Hemolysis is an infrequent but recognized and potentially serious adverse effect of intravenous immunoglobulin (IVIG). Relatively elevated hemolysis reporting rates were seen with some IVIG products with high anti‐A/B isoagglutinin content, among which IgPro10 (Privigen, CSL Behring). For IgPro10, two isoagglutinin reduction measures were successively implemented: 1) anti‐A donor screening and 2) immunoaffinity chromatography (IAC; Ig IsoLo)–based isoagglutinin reduction step included in the production process. The aim of this analysis was to investigate the effects of these isoagglutinin reduction measures on the reporting rates of IgPro10 hemolysis worldwide. STUDY DESIGN AND METHODS Between February 2008 and December 2018, hemolysis reports from the CSL Behring Global Safety Database were analyzed in relationship to changes in IVIG IgPro10 production methods. Further analysis classified hemolysis reports by indication and blood group. RESULTS Median (minimum‐maximum) anti‐A/anti‐B titers were 32 (8‐64)/16 (8‐32) at baseline, 32 (8‐64)/16 (8‐32) after donor screening, and 8 (8‐32)/4 (2‐8) after implementation of IAC. The reporting rate of hemolytic reactions per 1000 kg IgPro10 sold was 4.05 cases at baseline, 2.00 after donor screening, and 0.50 after implementation of IAC. In 2018, there were seven reports of hemolytic reactions; representing 0.18 cases per 1000 kg IgPro10 sold, with a reduction of 95.6% versus baseline. CONCLUSION Following implementation of the IAC isoagglutinin reduction step, spontaneous reports of hemolytic events with IgPro10 were significantly and consistently reduced versus IgPro10 without isoagglutinin reduction, offering patients a more favorable benefit‐risk profile.

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“…However, our analysis focused on severe events where underreporting is less likely, as practitioners continue to report serious adverse drug reactions after the initial years of marketing [24]. It is also worth noting that recent research has challenged the existence of a Weber effect, originally described in 1984 [26,27].…”

Section: Discussionmentioning

confidence: 99%

Reported Severe Hypersensitivity Reactions after Intravenous Iron Administration in the European Economic Area (EEA) Before and After Implementation of Risk Minimization Measures

Nathell¹,

Gohlke²,

Wohlfeil³

2019

Drug Saf

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Introduction Severe hypersensitivity reactions (HSRs) such as anaphylaxis are of great clinical concern because of their life-threatening potential. The adverse events attributable to intravenous iron products include HSRs. An investigation by the European Medicines Agency presented in late 2013 resulted in the implementation of risk minimization measures (RMMs). Objective This study evaluated the number of severe HSRs reported for intravenous iron substances related to exposure for the 4-year periods before and after this implementation. Methods This was a retrospective pharmacoepidemiologic study with a case-population design. We obtained information from the safety surveillance database EudraVigilance on spontaneously reported severe HSRs using the Medical Dictionary for Regulatory Activities preferred terms "anaphylactic reaction/shock" and "anaphylactoid reaction/shock". Exposure was estimated using IQVIA MIDAS sales data in European economic area countries. Results Reporting rates for individual products were heterogenous, and the implementation of RMMs appeared to have no clear impact. Reporting rates remained low for the full study period for iron sucrose (0.03-0.20) and ferric gluconate (0.02-0.14) and were higher at the beginning and lower at the end of the study period for ferric carboxymaltose (1.47-0.18). No clear trend was detected for iron dextran (range 0.22-2.80) and iron (III) isomaltoside 1000 (range 0-7.94). Conclusions Future research is needed to investigate whether the wide variability in reporting rates for severe HSRs associated with these intravenous iron products are due to potential differences in the safety profiles of these substances.

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Relevance of the Weber effect in contemporary pharmacovigilance of oncology drugs

Cited by 33 publications

References 25 publications

Reporting rates of adverse reactions to specialty care medicines exhibit a direct positive correlation with patient exposure: A lack of evidence for the Weber effect

Reporting rates of adverse reactions to specialty care medicines exhibit a direct positive correlation with patient exposure: A lack of evidence for the Weber effect

Isoagglutinin reduction in intravenous immunoglobulin (IgPro10, Privigen) by specific immunoaffinity chromatography reduces its reporting rates of hemolytic reactions: an analysis of spontaneous adverse event reports

Reported Severe Hypersensitivity Reactions after Intravenous Iron Administration in the European Economic Area (EEA) Before and After Implementation of Risk Minimization Measures

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