Efficacy of m-Health for the detection of adverse events following immunization – The stimulated telephone assisted rapid safety surveillance (STARSS) randomised control trial

IntroductionPassive surveillance is recommended globally for the detection of adverse events following immunisation (AEFI) but this has significant challenges. Use of Mobile health for vaccine safety surveillance enables a consumer-centred approach to reporting. The Stimulated Telephone Assisted Rapid Safety Surveillance (STARSS) a randomised control trial (RCT) sought to evaluate the efficacy and acceptability of SMS for AEFI surveillance.MethodsMulti-centre RCT, participants were adult vaccinees or parents of children receiving any vaccine at a trial site. At enrolment randomisation occurred to one of two SMS groups or a control group. Prompts on days 2, 7 and 14 post-immunisation, were sent to the SMS group, to ascertain if a medical event following immunisation (MEFI) had occurred. No SMS’s were sent to the control participants. Those in the SMS who notified an MEFI were pre-randomised to complete a computer assisted telephone interview or a web based report to determine if an AEFI had occurred whilst an AEFI in the controls was determined by a search for passive reports. The primary outcome was the AEFI detection rate in the SMS group compared to controls.ResultsWe enrolled 6,338 participants, who were equally distributed across groups and who received 11,675 vaccines. The SMS group (4,225) received 12,675 surveillance prompts with 9.8% being non-compliant and not responding. In those that responded 90% indicated that no MEFI had been experienced and 184 had a verified AEFI. 6 control subjects had a reported AEFI. The AEFI detection rate was 13 fold greater in the SMS group when compared with controls (4.3 vs 0.3%).ConclusionWe have demonstrated that the STARSS methodology improves AEFI detection. Our findings should inform the wider use of SMS-based surveillance which is particularly relevant since establishing robust and novel pharmacovigilance systems is critical to monitoring novel vaccines which includes potential COVID vaccines.     

Consumer acceptability and validity of m-Health for the detection of adverse events following immunization – The Stimulated Telephone Assisted Rapid Safety Surveillance (STARSS) randomised control trial

IntroductionMonitoring for adverse events following immunisation (AEFI) is critical for vaccine pharmacovigilance. Given the global and expanding availability of mobile phones their utility for consumer-based vaccine safety surveillance is of interest but little is known about consumer acceptability. This study nested within the Stimulated Telephone Assisted Rapid Safety Surveillance (STARSS) randomised control trial sought to evaluate the acceptability of SMS for AEFI surveillance.MethodsThe primary STARSS study was a multi-centre RCT evaluating the efficacy of repeated SMS prompts for AEFI surveillance with participants being adult vaccinees or parents of children receiving any vaccine. This nested study enrolled primary RCT participants who completed a detailed computer assisted telephone interview to determine their attitudes towards SMS-based surveillance and ascertain their knowledge and attitudes toward vaccine safety, efficacy, data privacy and use of electronic health records. Attitudes to surveillance and related behaviour were used as measures of acceptability.Results20% (1200/6555) of the participants were enrolled and 1139 completed the full-length questionnaire. 96% indicated that SMS-based surveillance after immunisation to check the safety of the vaccine “should be done” but 62% of all respondents said it should be done but consent should be sought first. Neither vaccine safety attitudes nor attitudes toward privacy were associated with opposition to SMS-based surveillance. In terms of SMS related behaviour demographic rather than attitudinal factors were associated with non-compliance.ConclusionOverall, the attitude towards SMS-based surveillance was very favourable. Experiencing the SMS surveillance has the effect of reducing opposition to an SMS surveillance system, and at the same time increasing the likelihood of a preference for prior consent. Detection of a vaccine safety signal could be impeded in particular demographic groups who are non-compliant and we should undertake further research to understand why these groups are non-compliant and how this can be improved.     

Identifying pregnancy episodes,outcomes, and mother–infant pairs in the Vaccine Safety Datalink

Background

The need for research on the safety of vaccination during pregnancy is widely recognized. Large, population-based data systems like the Vaccine Safety Datalink (VSD) may be useful for this research, but identifying pregnancies using electronic medical record (EMR) and claims data can be challenging.

Methods

We modified an existing data processing algorithm to identify pregnancies within seven of the ten VSD sites. We validated the algorithm by calculating the agreement in pregnancy outcome type, end date, and gestational age between the algorithm and manual medical record review. At each participating site, we randomly sampled 15 episodes within four outcome type strata (live births, spontaneous abortions, elective abortions, and other pregnancy outcomes) for a total of 60 episodes per site. We also developed and validated methods to link mothers to their infants in the electronic data.

Results

We identified 595,929 pregnancy episodes ending in 2002 through 2006 among women 12 through 55 years of age. Of these pregnancies, 75% ended in live births, 12% in spontaneous abortions, and 9% in elective abortions. We were able to confirm a pregnancy within 28 days of the algorithm-estimated pregnancy start date for 99% of live births, 93% of spontaneous abortions, 92% of elective abortions, and 90% of other outcomes sampled. The agreement between the algorithm-identified and the abstractor-identified outcome date ranged from 70% (elective abortion) to 96% (live birth) depending on outcome type. When gestational age was available in the EMR, agreement ranged from 82% (other) to 98% (live birth) depending on outcome type. We confirmed 100% of the 350 sampled mother–infant linkages with manual medical record review.

Conclusions

The VSD algorithm accurately identifies pregnancy episodes and mother–infant pairs across participating sites. Additional manual record review may be needed to improve the precision of the pregnancy date estimates depending on specific study needs. These algorithms will allow us to conduct large, population-based studies of the safety of vaccination during pregnancy.     

From program suspension to the pandemic: A qualitative examination of Australia’s vaccine pharmacovigilance system over 10 years

BackgroundIn 2010, the Australian seasonal influenza vaccination program for children under 5 years of age was suspended due to an unexpected increase in fever and febrile convulsions causally associated with one particular influenza vaccine brand. A subsequent national review made seven recommendations to improve vaccine pharmacovigilance. Ten years on, in advance of implementing the COVID-19 immunisation program, we evaluated views on the capacity of Australia’s vaccine pharmacovigilance system to promptly detect, examine and communicate a signal.MethodsSemi-structured interviews were conducted between July and October 2020 with individuals with expertise in vaccine safety in Australia using an interview guide informed by key Australian and international frameworks. Interviews were digitally recorded and transcribed verbatim. Thematic analysis was used to code data using a deductive approach.ResultsInterviews with seventeen participants enabled six themes to be identified. Participants described improvement and significant innovation within Australia’s vaccine pharmacovigilance system over the decade since 2010, particularly through establishment of a new active, cohort event monitoring system using short message service surveys. Participants thought Australia had a good foundation for COVID-19 vaccine safety surveillance; implementation of the COVID-19 immunisation program was seen as a potential driver for ongoing enhancement through: a) improved integration of the active surveillance and spontaneous reporting systems, and; b) development of population-level active surveillance, including through data linkage. Transparent communication was considered essential to address the unprecedented challenges of COVID-19 and broader vaccine safety concerns.ConclusionsVaccine safety experts in Australia convey confidence in the innovative pharmacovigilance systems implemented over the past 10 years. While Australia has a multifaceted system incorporating both active surveillance and spontaneous reporting systems, COVID-19 vaccine implementation represents an opportunity to enhance current systems and to develop new, systematic approaches to vaccine pharmacovigilance that should make both a local and global contribution.     

Vaxtracker: Active on-line surveillance for adverse events following inactivated influenza vaccine in children

Vaxtracker is a web based survey for active post marketing surveillance of Adverse Events Following Immunisation. It is designed to efficiently monitor vaccine safety of new vaccines by early signal detection of serious adverse events. The Vaxtracker system automates contact with the parents or carers of immunised children by email and/or sms message to their smart phone. A hyperlink on the email and text messages links to a web based survey exploring adverse events following the immunisation. The Vaxtracker concept was developed during 2011 (n = 21), and piloted during the 2012 (n = 200) and 2013 (n = 477) influenza seasons for children receiving inactivated influenza vaccine (IIV) in the Hunter New England Local Health District, New South Wales, Australia. Survey results were reviewed by surveillance staff to detect any safety signals and compare adverse event frequencies among the different influenza vaccines administered. In 2012, 57% (n = 113) of the 200 participants responded to the online survey and 61% (290/477) in 2013. Vaxtracker appears to be an effective method for actively monitoring adverse events following influenza vaccination in children.     

Participant centred safety surveillance of health care workers receiving influenza vaccination

Following the introduction of mandatory influenza vaccination for staff working in high risk clinical areas in 2018, we conducted active surveillance for adverse events following immunisation utilising an automated online survey to vaccine recipients at three and 42?days post immunisation. Most participants 2285 (92%) agreed to participate; 515 (32%) staff reported any symptom and eight (1.6%) sought medical attention. The odds of having a reaction decreased with age by approximately 2% per year. The system was acceptable to staff, and the data demonstrated rates of reported symptoms within expected rates for influenza vaccines from clinical trials. Rates of medical attendance were similar to previous surveillance. Participant centred real-time safety surveillance proved useful in this staff influenza vaccination context, providing reassurance with expected rates and profile of common adverse events following staff influenza vaccination.     

Understanding factors influencing vaccination acceptance during pregnancy globally: A literature review

Maternal vaccination has been evaluated and found to be extremely effective at preventing illness in pregnant women and new-borns; however, uptake of such programmes has been low in some areas.To analyse factors contributing to uptake of vaccines globally, a systematic review on vaccine hesitancy was carried out by The Vaccine Confidence Project in 2012. In order to further analyse factors contributing to uptake of maternal immunisation, a further search within the broader systematic review was conducted using the terms ‘Pregnan*’ or ‘Matern*’. Forty-two articles were identified. Pregnancy-related articles were further screened to identify those focused on concerns, trust and access issues regarding maternal vaccination reported by pregnant women and healthcare workers. Thirty-five relevant articles were included which were then searched using the snowballing technique to identify additional relevant references cited in these articles. A search alert was also conducted from February to April 2015 in PubMed to ensure that no new relevant articles were missed. A total of 155 relevant articles were included.Most of the literature which was identified on hesitancy surrounding vaccination during pregnancy reports on determinants of influenza vaccine uptake in North America. Research conducted in low-income countries focused primarily on tetanus vaccine acceptance. The main barriers cited were related to vaccine safety, belief that vaccine not needed or effective, not recommended by healthcare worker, low knowledge about vaacines, access issues, cost, conflicting advice. From the point of view of healthcare workers, barriers included inadequate training, inadequate reimbursement and increased workload. Twenty-seven out of 46 (59%) articles mentioning ethnicity reported lower rates of coverage among ethnic minorities.Barriers to vaccination in pregnancy are complex and vary depending on context and population. There are wide gaps in knowledge regarding the attitudes of healthcare workers and how ethnicity and gender dynamics influence a pregnant woman's decision to vaccinate.     

Review of prescribing information for influenza vaccines for pregnant and lactating women

Information provided by most influenza vaccine manufacturers do not reflect the recommendations of WHO and/or national public health advisory groups with regard to the use of influenza vaccines in pregnant or lactating women. The majority of vaccines contain precautionary language which could discourage use in pregnant women and some include stronger language discouraging or contradicting use in pregnant or lactating women. Regulators and manufacturers should regularly assess the language of pregnancy and lactation sections in product information for vaccines and include information from national public health advisory groups regarding use by pregnant or lactating women and data from relevant studies.     

Application of the immunological disease continuum to study autoimmune and other inflammatory events after vaccination

In vaccine safety monitoring, the evaluation of possible autoimmune events is challenging. Developing grouping systems based on pathophysiology, instead of organ systems, may enhance our ability to identify or verify associations between vaccines and adverse immunologically mediated events in clinical trials and post-licensure surveillance. Emerging data suggest that self-directed tissue inflammation occurs along a continuum from innate immune-driven diseases to adaptive immune-driven diseases. Herein, we develop this proposed classification for the vaccination setting in which inflammatory diseases are placed along a continuum according to the two major arms of the immune system, the innate immune arm (mediated by cells including neutrophils, macrophages and complement) and the adaptive immune arm (cell-mediated and humoral response). We incorporate hypersensitivity reactions and molecular mimicry vaccine-related reactions into this mechanistic scheme. We show how this could have important implications to assess mechanisms of potential immune-mediated adverse events following vaccination.