Evaluation of signal detection algorithms within the Elanco Animal Health Pharmacovigilance database.

Statistical algorithms for detecting safety signals are beginning to be applied to Animal Health Pharmacovigilance (PV) databases. How these signal detection algorithms (SDAs) perform in an animal health PV database is the subject of this report. Statistical methods and SDAs were assessed against a set of known signals in order to identify which SDAs were most appropriate for signal detection using the Elanco Animal Health PV database. A reference set of adverse events that should signal was created for 31 products across four species. Nine SDAs based on five disproportionality statistical methods were evaluated against the reference set. The performance metrics were sensitivity, precision, specificity, accuracy, and F score. For bovine and porcine products, the Observed-to-Expected (O/E) SDA was the closest in terms of geometric distance to 100% sensitivity and 100% precision. For canine and feline products, the Information Component (IC) SDA was geometrically closest to 100% sensitivity and 100% precision. Principal Component Analysis confirmed that the O/E and IC SDAs were unique performers with respect to one another and other SDAs. The performance of the SDAs was dependent on the choice of the statistical method with differences seen between animal species.

Laboratory evaluations of the immediate and sustained efficacy of lotilaner (Credelio™) against four common species of ticks affecting dogs in North America.

BACKGROUND: Effective control of tick infestations on dogs is important to reduce the risk of transmission of bacterial, viral, and protozoal pathogens. Laboratory studies were initiated to determine the efficacy of lotilaner against common ticks infesting dogs in the United States. METHODS: Eight studies investigated the efficacy of lotilaner against ticks. In two studies dogs were infested with both Dermacentor variabilis and Rhipicephalus sanguineus: one additional study was completed for each of these species. Two studies assessed infestations with Amblyomma americanum and two with Ixodes scapularis. In all studies, dogs were ranked and blocked by counts from pre-treatment infestations and randomly allocated, at least eight per group, to be treated orally with lotilaner (minimum dose rate 20 mg/kg), or to be untreated controls. Treatments were administered on Day 0, within 30 min after dogs were fed. In all studies, infestations were performed with 50 adult ticks on Days -2, 7, 14, 21 and 28, and also on Day 35 for R. sanguineus, D. variabilis and I. scapularis. Tick counts were completed 48 h after treatment or after each subsequent challenge. An adequate infestation was defined as at least 25% of the infestation dose recovered from each of at least six control animals at each evaluation. Efficacy calculations for the primary objective were based on geometric means. RESULTS: In all studies, lotilaner was 100% effective against existing infestations. For post-treatment assessments, on only two occasions did efficacy fall below 99%: in one D. variabilis study efficacy was 98.0% on Day 35 and in one I. scapularis study efficacy on Day 16 was 98.4%. Only mild and transient adverse events were observed, and none were considered to be related to treatment. CONCLUSION: Lotilaner was completely effective against existing infestations with four common species of ticks, D. variabilis, R. sanguineus, A. americanum and I. scapularis, that affect dogs in North America, with at least 4 weeks efficacy of 98.0% or more against subsequent challenge infestations. These results show that lotilaner is a highly effective isoxazoline that offers sustained efficacy against ticks through and beyond the one-month end-of-dose treatment interval.

Who is unlikely to report adverse events after vaccinations to the Vaccine Adverse Event Reporting System (VAERS)?

BACKGROUND: Healthcare provider (HCP) reporting to the Vaccine Adverse Event Reporting System (VAERS) is important to assuring the safety of U.S. licensed vaccines. HCP awareness of and practices regarding reporting of adverse events following immunization (AEFI) is understudied. METHODS: A large, nationally representative sample of U.S. office-based HCP across three occupational groups (physicians, mid-level providers [physician assistants, advanced practice nurses] and nurses) and three primary care practice areas (pediatrics, family medicine, internal medicine) were surveyed utilizing standardized methodology. We assessed HCP familiarity with VAERS, the situations under which they were likely to report an AEFI, and the methods they used and preferred for reporting. We used logistic regression to determine factors associated with HCP not reporting AEFI to VAERS. RESULTS: Our survey response rate was 54.9%. The percentage of HCP aware of VAERS (71%) varied by occupation and primary care practice area. About 37% of HCP had identified at least one AEFI with only 17% of these indicating that they had ever reported to VAERS. More serious events were more likely to be reported. Factors associated with HCP not reporting AEFI included: HCP not familiar versus very familiar with filing a paper VAERS report (OR=12.84; p<0.0001), primary care practice area of internal medicine versus pediatrics (OR=4.22; p=0.0005), and HCP not familiar versus very familiar with when it was required to file a VAERS report (OR=5.52; p=0.0013). CONCLUSIONS: Specific educational interventions targeted to HCP likely to see AEFI but not currently reporting may improve vaccine safety reporting practices.

Vaccination and risk of type 1 diabetes mellitus in active component U.S. Military, 2002-2008.

AIMS/HYPOTHESIS: To evaluate whether vaccination increases the risk of type 1 diabetes mellitus in active component U.S. military personnel. METHODS: We conducted a retrospective cohort study among active component U.S. military personnel age 17-35 years. Individuals with first time diagnoses of type 1 diabetes between January 1, 2002 and December 31, 2008 were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. We used Poisson regression to estimate risk ratios between individual vaccine exposures and type 1 diabetes. Secondary analyses were performed controlling for receipt of multiple vaccines and available demographic variables. RESULTS: Our study population consisted of 2,385,102 individuals followed for approximately 7,644,098 person-years of service. This included 1074 incident type 1 diabetes cases. We observed no significant increased risk of type 1 diabetes after vaccination with anthrax vaccine adsorbed (AVA) [RR=1.00; 95% CI (0.85, 1.17)], smallpox vaccine [RR=0.84; 95% (CI 0.70, 1.01)], typhoid vaccine [RR=1.03; 95% CI (0.87, 1.22)], hepatitis B vaccine [RR=0.83; 95% CI (0.72, 0.95)], measles mumps rubella vaccine (MMR) [RR=0.71, 95% CI (0.61, 0.83)], or yellow fever vaccine [RR=0.70; 95% CI (0.59, 0.82)]. CONCLUSIONS: We did not find an increased risk of diagnosed type 1 diabetes and any of the study vaccines. We recommend that follow-up studies using medical record review to confirm case status should be considered to corroborate these findings.