Céline Caillet

First French Experience of ADR Reporting by Patients After a Mass Immunization Campaign with Influenza A (H1N1) Pandemic Vaccines

AbstractBackground: Available data concerning the contribution of patient adverse drug reaction (ADR) reporting in practice are scarce. Few studies have compared patients’ reports with reports from healthcare professionals (HCPs). During the 2009–10 mass immunization campaign with A (H1N1)v2009 pandemic influenza vaccines, a reinforced pharmacovigilance plan was introduced in France according to European Medicines Agency recommendations. For the first time, patients were offered the opportunity to report suspected ADRs to pandemic vaccines directly to regional pharmacovigilance centres. Objective: The aim of the study was to compare the characteristics of patient and HCP ADR reports in order to assess the qualitative and quantitative contribution of patient reporting to the French Pharmacovigilance System. Methods: All spontaneous ADRs registered into the French Pharmacovigilance Database from 21 October 2009 to 15 June 2010, in which either one of the most frequently administered pandemic vaccines (i.e. Panenza® or Pandemrix®) was involved, were analysed. ADRs were classified as ‘serious’, ‘medically serious’ and ‘non-serious’. This study focused on ‘serious’ and ‘medically serious’ ADRs. An ADR was ranked as ‘medically serious’ when it required medical intervention or hospitalization within less than 24 hours. In each level of seriousness, frequency of ‘unlabelled’ ADRs, ADRs of ‘special interest’, imputability scores and category of ADRs according to Medical Dictionary for Regulatory Activitives (MedDRA®) primary System Organ Class were compared between patient and professional reports. Results: Among the 4746 reports received during the study period, 1006 (21.2%) originated from patients. HCPs reported significantly more ‘medically serious’ or ‘serious’ ADRs than patients (15.1% [565/3740] vs 8.4% [85/1006], respectively; p < 0.001). No difference was found in ‘unlabelled, serious’ ADRs between patients and HCPs (56.5% [n= 13] vs 56.7% [n= 136], respectively). Conclusions: In this first French experience of formal patient participation to ADR reporting, patient contribution to the total number of ADRs reached 21.2%. This study revealed no major qualitative difference between patient and HCP reports. ADR profiles reported by patients appeared to be consistent with those from professionals. Further investigations are necessary to assess the intrinsic quality of notification forms coming from non-professional reporters. However, this study is of particular interest in the context of publication of the first governmental decree that will formally integrate patient participation to the current French ADR reporting scheme.

A link between poor quality antimalarials and malaria drug resistance

Malaria remains a major public health problem for most of the world. The tragedy remains that many more malaria patients would survive if they had timely access to good quality, affordable and efficacious medicines. Antimalarial resistance has been a major impediment to malaria control. Since the 1950s, Plasmodium falciparum parasites have developed resistance to the main antimalarials used in national and international policies, including chloroquine, sulphadoxinepyrimethamine (SP) and these have spread globally and increased mortality [1]. Recently, resistance to the artemisinin derivatives, associated with falciparum parasite kelch13 mutations, has been described in mainland South East Asia [2], but not yet confirmed in other endemic regions. With few new antimalarials in the development pipeline, concern that key artemisinin-combination therapies (ACTs) may fail is of great public health alarm, with both resistance to artemisinin derivatives and partner drugs reported [3,4]. The risk of geographic spread is very high and would have dramatic consequences for many aspects of society, including health, education, and economy. Suboptimal antimalarial use both poor prescribing and poor adherence, has been invoked as a driver for poor patient outcome and parasite resistance, although see the caution of Noranate et al. (2007) [5]. Improved use, through better prescription and discussion with patients so that they know why and how to adhere will be important. Here, we argue that poor quality antimalarials also contribute to drug resistance.

Safety surveillance of influenza A(H1N1)v monovalent vaccines during the 2009–2010 mass vaccination campaign in France

In June 2009, the World Health Organization declared a pandemic due to A(H1N1)v 2009 influenza virus. In France, a mass vaccination campaign started following European Medicines Agency (EMA) recommendations, and a Pharmacovigilance plan was launched. The aim of this study was to describe safety data collected from 21 October 2009 to 15 June 2010 for Pandemrix® (ASO3 adjuvant vaccine, indicated in adults and children >9 years) and Panenza® (a nonadjuvant vaccine primarily administered to children <9 years old and pregnant women), the two most frequently used vaccines in France. The French Pharmacovigilance system consists of a network of 31 regional centres and is based on mandatory spontaneous reports of “serious” and/or “unexpected” adverse events (AEs) [1]. However, it is well known that spontaneous notifications suffer from underreporting, the magnitude of which varies between 82% and 98% [2]. For the 2009–2010 vaccination campaign, French health authorities heightened awareness to extensive notifications with online health practitioner and patient reports via the regional centre concerned. All

Safety profile of enantiomers vs. racemic mixtures: it's the same?

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT The physicochemical properties of racemates and stereoisomers of medicines can differ significantly, and this may affect the side-effect profile in addition to the pharmacokinetics and intended pharmacology. WHAT THIS STUDY ADDS This is a study to investigate the profile of adverse drug reactions of racemic and enantiomeric forms of drugs. Our data suggest differences in the safety profile for ofloxacin and omeprazole. This area requires more work to investigate this for other compounds. AIMS The objective was to investigate the safety profile of four drugs marketed as racemic and enantiomeric forms in France. METHODS Data from the French PharmacoVigilance Data Base (January 2005 to June 2010) were analysed for four pairs of racemic/isomeric drugs. A case-noncase approach was used to measure the disproportionality of combination between adverse drug reaction (ADR) and exposure to drug. RESULTS No significant difference in the number of ADRs was observed between Rac-cetirizine/(R)-cetirizine or Rac-citalopram/(S)-citalopram pairs. (S)-Omeprazole induced more haematological effects than Rac-omeprazole. Rac-Ofloxacin induced more haematological, renal and neuropsychiatric ADRs than (S)-ofloxacin, whereas levofloxacin was associated with more reports of musculoskeletal ADRs. CONCLUSIONS The profile of ADRs could differ for some drugs marketed as racemic and enantiomeric forms. Further studies would be necessary to confirm these data.

Triboelectric nanogenerator (TENG) mass spectrometry of falsified antimalarials

Rationale An epidemic of low‐quality medicines continues to endanger patients worldwide. Detection of such ‘medicines’ requires low cost, ambient ionization sources coupled to fieldable mass spectrometers for optimum sensitivity and specificity. With the use of triboelectric nanogenerators (TENGs), the charge required to produce gas‐phase ions for mass analysis can be obtained without the need for high‐voltage electrical circuitry, simplifying and lowering the cost of next‐generation mass spectrometry instruments. Methods A sliding freestanding (SF) TENG was coupled to a toothpick electrospray setup for the purposes of testing if falsified medicines could be fingerprinted by this approach. Extracts from both genuine and falsified medicines were deposited on the toothpick and the SF TENG actuated to generate electrical charges, resulting in gas‐phase ions for both active pharmaceutical ingredients and excipients. Results Our previous work had shown that direct analysis in real time (DART) ambient mass spectrometry can identify the components of multiple classes of falsified antimalarial medicines. Experiments performed in this study show that a simple extraction into methanol along with the use of a SF TENG‐powered toothpick electrospray can provide similar detection capabilities, but with much simpler and rugged instrumentation, and without the need for compressed gases or high‐voltage ion source power supplies. Conclusions TENG toothpick MS allows for rapid analyte ion detection in a safe and low‐cost manner, providing robust sampling and ionization capabilities.

Field detection devices for screening the quality of medicines: a systematic review

Background Poor quality medicines have devastating consequences. A plethora of innovative portable devices to screen for poor quality medicines has become available, leading to hope that they could empower medicine inspectors and enhance surveillance. However, information comparing these new technologies is woefully scarce. Methods We undertook a systematic review of Embase, PubMed, Web of Science and SciFinder databases up to 30 April 2018. Scientific studies evaluating the performances/abilities of portable devices to assess any aspect of the quality of pharmaceutical products were included. Results Forty-one devices, from small benchtop spectrometers to ‘lab-on-a-chip’ single-use devices, with prices ranging from US

First French experience of ADR reporting by patients after a mass immunization campaign with Influenza A (H1N1) pandemic vaccines: a comparison of reports submitted by patients and healthcare professionals.

20 000, were included. Only six devices had been field-tested (GPHF-Minilab, CD3/CD3+, TruScan RM, lateral flow dipstick immunoassay, CBEx and Speedy Breedy). The median (range) number of active pharmaceutical ingredients (APIs) assessed per device was only 2 (1–20). The majority of devices showed promise to distinguish genuine from falsified medicines. Devices with the potential to assay API (semi)-quantitatively required consumables and were destructive (GPHF-Minilab, PharmaChk, aPADs, lateral flow immunoassay dipsticks, paper-based microfluidic strip and capillary electrophoresis), except for spectroscopic devices. However, the 10 spectroscopic devices tested for their abilities to quantitate APIs required processing complex API-specific calibration models. Scientific evidence of the ability of the devices to accurately test liquid, capsule or topical formulations, or to distinguish between chiral molecules, was limited. There was no comment on cost-effectiveness and little information on where in the pharmaceutical supply chain these devices could be best deployed. Conclusion Although a diverse range of portable field detection devices for medicines quality screening is available, there is a vitally important lack of independent evaluation of the majority of devices, particularly in field settings. Intensive research is needed in order to inform national medicines regulatory authorities of the optimal choice of device(s) to combat poor quality medicines.