Bivalent human papillomavirus vaccine and the risk of fatigue syndromes in girls in the UK

Donegan, Katherine; Beau-Lejdstrom, Raphaëlle; King, Bridget; Seabroke, Suzie; Thomson, Andrew; Bryan, Philip

doi:10.1016/j.vaccine.2013.08.024

Cited by 61 publications

(44 citation statements)

References 13 publications

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“…An epidemiological study in The Netherlands was designed to investigate the potential for an increased risk of migraine headaches after HPV vaccination [21]. As part of a proactive pharmacovigilance plan, the Medicines and Health Regulatory Authority (MHRA) performed an epidemiological study using self-controlled case-series methodology in which they identified cases reporting ‘fatigue-containing’ terms, such as chronic fatigue, chronic fatigue syndrome, post-viral fatigue and fibromyalgia [22]. Although laudable that it considered a variety of fatigue-related terms, the study did not account for co-reported symptoms of a more varied nature.…”

Section: Discussionmentioning

confidence: 99%

Current Safety Concerns with Human Papillomavirus Vaccine: A Cluster Analysis of Reports in VigiBase®

et al. 2016

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IntroductionA number of safety signals—complex regional pain syndrome (CRPS), postural orthostatic tachycardia syndrome (POTS), and chronic fatigue syndrome (CFS)—have emerged with human papillomavirus (HPV) vaccines, which share a similar pattern of symptomatology. Previous signal evaluations and epidemiological studies have largely relied on traditional methodologies and signals have been considered individually.ObjectiveThe aim of this study was to explore global reporting patterns for HPV vaccine for subgroups of reports with similar adverse event (AE) profiles.MethodsAll individual case safety reports (reports) for HPV vaccines in VigiBase® until 1 January 2015 were identified. A statistical cluster analysis algorithm was used to identify natural groupings based on AE profiles in a data-driven exploratory analysis. Clinical assessment of the clusters was performed to identify clusters relevant to current safety concerns.ResultsOverall, 54 clusters containing at least five reports were identified. The four largest clusters included 71 % of the analysed HPV reports and described AEs included in the product label. Four smaller clusters were identified to include case reports relevant to ongoing safety concerns (total of 694 cases). In all four of these clusters, the most commonly reported AE terms were headache and dizziness and fatigue or syncope; three of these four AE terms were reported in >50 % of the reports included in the clusters. These clusters had a higher proportion of serious cases compared with HPV reports overall (44–89 % in the clusters compared with 24 %). Furthermore, only a minority of reports included in these clusters included AE terms of diagnoses to explain these symptoms. Using proportional reporting ratios, the combination of headache and dizziness with either fatigue or syncope was found to be more commonly reported in HPV vaccine reports compared with non-HPV vaccine reports for females aged 9–25 years. This disproportionality remained when results were stratified by age and when those countries reporting the signals of CRPS (Japan) and POTS (Denmark) were excluded.ConclusionsCluster analysis reveals additional reports of AEs following HPV vaccination that are serious in nature and describe symptoms that overlap those reported in cases from the recent safety signals (POTS, CRPS, and CFS), but which do not report explicit diagnoses. While the causal association between HPV vaccination and these AEs remains uncertain, more extensive analyses of spontaneous reports can better identify the relevant case series for thorough signal evaluation.Electronic supplementary materialThe online version of this article (doi:10.1007/s40264-016-0456-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Current Safety Concerns with Human Papillomavirus Vaccine: A Cluster Analysis of Reports in VigiBase®

et al. 2016

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“…Recently, an observational analysis (performed by UK Medicines and Healthcare products Regulatory Agency, MHRA) investigated the association between bivalent HPV vaccine and the development of CFS. However, no change of incidence of spontaneous reports of CFS in girls aged 12-20 years after the introduction of the vaccination was observed [64].…”

Section: Resultsmentioning

confidence: 91%

A sudden onset of a pseudo-neurological syndrome after HPV-16/18 AS04-adjuvated vaccine: might it be an autoimmune/inflammatory syndrome induced by adjuvants (ASIA) presenting as a somatoform disorder?

et al. 2014

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In last centuries, vaccines reduced the incidence of several infectious diseases. In last decades, some vaccines aimed at preventing also some cancers, where viruses play a causative role. However, several adverse events have been described after vaccines, but a causal relationship has been established only in a minority of cases. Here, we describe a pseudo-neurological syndrome occurred shortly after the administration of the bivalent HPV vaccine. Some autoimmune disorders, including neurological demyelinating diseases, have been reported after HPV vaccines, but the patient showed no organic lesions. The patient was diagnosed as having a functional somatoform syndrome, which was supposed to be autoimmune/inflammatory syndrome induced by adjuvants (ASIA), seen the temporal link with vaccination and the presence of anti-phospholipid autoantibodies. Immunological mechanisms of vaccines-and of adjuvants-have not been completely elucidated yet, and although there is no evidence of statistical association with many post-vaccination events, a causal link with vaccine cannot be excluded in some individuals.

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“…VRMM has implemented proactive pharmacovigilance by the expert use of CPRD—the large-linked observational datasets from a range of primary and secondary care settings. This along with its “Yellow Card” scheme, a spontaneous reporting system, allows it to conduct a comprehensive review of selected healthcare products [19]. …”

Section: Resultsmentioning

confidence: 99%

“…Epidemiological analyses using the CPRD are then used to refine and evaluate these safety signals [19]. The team has evaluated the association between bivalent human papillomavirus vaccine (Cervarix) and fatigue syndromes with an ecological and a self-controlled case series design [19]. The DSRU (UK) using its M-PEM technique evaluated the safety of rimonabant, which was suspected of causing depressive episodes.…”

Section: Resultsmentioning

confidence: 99%

“…Linked drug prescription and outcome data are analyzed separately at provincial levelClaimsQuebec: 1983/Nova Scotia: 1989/Other provinces since mid-1990s40 millionVaries from monthly to quarterly by provinceEU-ADR Alliance [72, 73]A common database model with distributed data storage. Unique identifier is used to link personal data within a countryEHRs/claims/pediatrician records/pharmacy invoice/GP databases/registriesIPCI: 1996/PHARMO: 1998/HSD: 2003/Tuscany: 2003/Lombardy: 2000/Qresearch: 200245 million+UnknownAsPEN [78]Common data model with distributed data storage; raw data are retained in local inventoriesClaims/registries/EHRsJMDC: 2005–2009/NHRD: 1997–2008/HIRA: 2001–2010/Australian claims database: 2001–2010/Swedish prescribed drug register: 2005–2010/Medicaid Analytic Extract: 2001–2005/Medstat MarketScan: 2001–2007AU claims database: 300,000/JP-JMDaC: 300,000/HIRA: 53 million/NHIRD: 1 million/Swedish prescribed drug register: 9 million/USA- Medicaid Analytic Extract: 87 million; USA- Medstat MarketScan: 51 millionUnknownVRMM [19, 79]Centralized data modelGP databases with linkage to hospital data/spontaneous report/census data/death, birth, immunization, NHS registries/PROsCPRD (UK):198752 million+ with additional 12 million in Scotland, Wales, and North IrelandCPRD: 6 weeksVAESCO [51, 79]Common data model with distributed data storage approach, common protocol, and common case report forms for studiesGP and hospital databases/EHRs/registries/interviewIPCI since 1996 Italy, Tuscany, and Lombardy since 2003/CPRD (UK) since 198750 million+CPRD: 6 weeksDSRU: M-PEM [21]NHS sends data on prescriptions written by GPs to DSRU; M-PEM questionnaire is sent to GPs requesting patient demographic and general health data, which are stored in DSRU databaseNHS prescription data/M-PEM questionnairesSince 1984About 10,000 prescriptions per studyPer study launch ADR adverse drug reaction, CMS Centers for Medicare and Medicaid Services, DoD US Department of Defense, EHR electronic health record, GP general practitioner, HIS Hospital Information Systems, IPCI Dutch Integrated Primary Care Information, NACRS National Ambulatory Care Reporting System, PBM Pharmacy Benefit Manager, PRISM Post-Licensure Rapid Immunization Safety Monit...…”

Section: Methodsmentioning

confidence: 99%

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A Comparison of Active Adverse Event Surveillance Systems Worldwide

2014

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Post-marketing drug surveillance for adverse drug events (ADEs) has typically relied on spontaneous reporting. Recently, regulatory agencies have turned their attention to more preemptive approaches that use existing data for surveillance. We conducted an environmental scan to identify active surveillance systems worldwide that use existing data for the detection of ADEs. We extracted data about the systems’ structures, data, and functions. We synthesized the information across systems to identify common features of these systems. We identified nine active surveillance systems. Two systems are US based—the FDA Sentinel Initiative (including both the Mini-Sentinel Initiative and the Federal Partner Collaboration) and the Vaccine Safety Datalink (VSD); two are Canadian–the Canadian Network for Observational Drug Effect Studies (CNODES) and the Vaccine and Immunization Surveillance in Ontario (VISION); and two are European–the Exploring and Understanding Adverse Drug Reactions by Integrative Mining of Clinical Records and Biomedical Knowledge (EU-ADR) Alliance and the Vaccine Adverse Event Surveillance and Communication (VAESCO). Additionally, there is the Asian Pharmacoepidemiology Network (AsPEN) and the Shanghai Drug Monitoring and Evaluative System (SDMES). We identified two systems in the UK—the Vigilance and Risk Management of Medicines (VRMM) Division and the Drug Safety Research Unit (DSRU), an independent academic unit. These surveillance systems mostly use administrative claims or electronic medical records; most conduct pharmacovigilance on behalf of a regulatory agency. Either a common data model or a centralized model is used to access existing data. The systems have been built using national data alone or via partnership with other countries. However, active surveillance systems using existing data remain rare. North America and Europe have the most population coverage; with Asian countries making good advances.Electronic supplementary materialThe online version of this article (doi:10.1007/s40264-014-0194-3) contains supplementary material, which is available to authorized users.

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Bivalent human papillomavirus vaccine and the risk of fatigue syndromes in girls in the UK

Cited by 61 publications

References 13 publications

Current Safety Concerns with Human Papillomavirus Vaccine: A Cluster Analysis of Reports in VigiBase®

Current Safety Concerns with Human Papillomavirus Vaccine: A Cluster Analysis of Reports in VigiBase®

A sudden onset of a pseudo-neurological syndrome after HPV-16/18 AS04-adjuvated vaccine: might it be an autoimmune/inflammatory syndrome induced by adjuvants (ASIA) presenting as a somatoform disorder?

A Comparison of Active Adverse Event Surveillance Systems Worldwide

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