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Purpose Patients' self-reported vaccine exposure (PS) may be subject to memory errors and other biases. Physicians' prescription records and other medical records (MR) do not capture noncompliance with vaccination. This study compared PS with MR for influenza, 23-valent pneumococcal, and human papillomavirus (HPV) vaccines. Methods The Pharmacoepidemiologic General Research Extension (PGRx) database uses a network of over 300 general practitioners across France, who systematically recruit an age- and sex-stratified sample of patients (≥ 14 years old), without reference to their diagnoses or prescriptions. Patients received a structured telephone interview, combined with an interview guide listing vaccines commonly given. Patients' self-reported vaccination in the 3 years before their recruitment was compared with medical records kept by the physician or the patient. Results Concordance between PS and MR was assessed for 7613 patients for whom both sources of information were available. Agreement within 3 years before the recruitment date was substantial for influenza vaccines (prevalence and bias-adjusted kappa [PABAK] = 0.74, sensitivity PS relative to MR 81.5%) and high for 23-valent pneumococcal vaccines (PABAK = 0.98, sensitivity PS 49.6) and HPV vaccines (PABAK = 0.92, sensitivity PS 91.6). In adjusted analyses, agreement varied with sociodemographic and health-related factors, particularly for influenza and 23-valent pneumococcal vaccines. Conclusions The PGRx method for drug exposure assessment is a new tool in pharmacoepidemiology that shows substantial to high agreement between PS and MR for exposure to various vaccines. Our finding of high agreement between PS and MR for HPV vaccination status in young women is a significant addition to the literature. Copyright © 2013 John Wiley & Sons, Ltd.

The cause of immune thrombocytopenia (ITP) remains unknown. Studies have suggested immunizations as possible triggering factors of ITP through molecular mimicry. This case-control study explored potential associations between adult ITP and various routinely administered vaccines. A network of internal medicine and hematology centers across France recruited 198 incident (ie, newly diagnosed) cases of ITP between April 2008 and June 2011. These cases were compared with 878 age- and sex-matched controls without ITP recruited in general practice. Information on vaccination was obtained from patients' standardized telephone interviews. Sixty-six of 198 cases (33.3%) and 303 of 878 controls (34.5%) received at least 1 vaccine within the 12 months before the index date. We found no evidence of an increase in ITP after vaccination in the previous 6 or 12 months (adjusted odds ratio [OR] for the previous 12 months = 1.0; 95% confidence interval, 0.7-1.4). When the 2-month time window was used, higher ORs were observed for all vaccines (OR = 1.3). This increase was mainly attributable to the vaccination against diphtheria-tetanus-pertussis-poliomyelitis (OR = 1.5) and was not statistically significant. The results of the present study show that in an adult population, the exposure to common vaccines is on average not associated with an observable risk of developing ITP.

Inherited risk determinants for follicular lymphoma (FL) have recently been described in the immune gene-rich human leukocyte antigen region on chromosome 6p. The known importance of host immune response to FL survival led us to evaluate these germline factors in FL outcome. We confirm the association of single nucleotide polymorphisms rs10484561 (P = 3.5 × 10−9) and rs6457327 (P = .008) with risk of FL and demonstrate that rs6457327 predicts both time to (P = .02) and risk of (P < .01) FL transformation independently of clinical variables, including the Follicular Lymphoma International Prognostic Index.

Multiple myeloma (MM) is a progressive, malignant neoplasia with a worldwide, age-standardized annual incidence of 1.5 per 100 000 individuals and 5-year prevalence around 230 000 patients. Main favorable prognostic factors are younger age, low/standard cytogenetic risk, and undergoing stem cell transplantation. Our aim was to estimate the size of the patient population with MM eligible to receive a new MM therapy at different lines of therapy in the USA.We constructed a compartmental, differential equation model representing the flow of MM patients from diagnosis to death, via two possible treatment pathways and distinguished in four groups based on prognostic factors. Parameters were obtained from published references, available statistics, and assumptions. The model was used to estimate number of diagnosed MM patients and number of patient transitions from one line of therapy to the next over 1 year. Model output included 95% credible intervals from probabilistic sensitivity analyses.The base-case estimates were 80 219 patients living with MM, including 70 375 on treatment, 780 symptomatic untreated patients, and 9064 asymptomatic untreated patients. Over a 1-year period, the number of MM patients on treatment line 1 was estimated at 23 629 (credible intervals 22 236-25 029), and the number of transitions from treatment line 1 to treatment line 2 was estimated at 14 423.The size of the patient population with MM on different lines of therapy and in patient subgroups of interest estimated from this epidemiologic model can be used to assess the number of patients who could benefit from new MM therapies and their corresponding budgetary impact. Copyright © 2016 John WileySons, Ltd.

PRM253 An EPidEMiologic ModEling APPlicAtion to PhARMAcoEconoMics foR iMPRovEd hEAlth cARE PlAnning Cid Ruzafa J., Cox A., Merinopoulou E., Baggaley R., Leighton P., Desai K. Evidera, London, UK Epidemiologic and pharmacoeconomic models differ in terms of populations considered, mathematical techniques used, and questions addressed. A typical pharmacoeconomic model assesses chronic or acute conditions, uses Markov techniques, and considers a closed patient group receiving a defined therapy to assess incremental costs needed to achieve gains in quality adjusted life years. A typical epidemiologic model assesses vaccination or public health interventions for infectious disease using differential equations and considers open populations representing communities to estimate prevalence or numbers of disease cases averted. The manner of conducting sensitivity analyses also differs. In oncology, in which multiple lines of treatment are available, the epidemiologic approach has application to estimate the patient point prevalence or the number of patients who can start on a line of therapy over a certain time period, when this cannot be determined from clinical trials or registers (which usually focus on single lines of therapy or limited types of patients that are not representative of the overall patient population). The approach consists of conceptualizing an open population that incorporates incidence of the condition and the transition of patients through various lines of treatment until death, and uses systems of difference/differential equations. Parameterization is challenging if there are several prognostic factors to describe the patient population, multiple or complex treatment pathways, and a wide range of variability. Parameters are obtained from the published literature, analyses of database information, and/ or surveys to experts in the field. Steady state solutions of the model equations estimate point and period prevalence. This approach is applicable to gastrointestinal stromal tumours and multiple myeloma. Resulting estimates are important for budget impact analysis and health care services planning by reducing uncertainty associated with identifying the patient numbers eligible for a given treatment. Epidemiologic modelling permits a framework to estimate disease prevalence that is little used in pharmacoeconomics.

Objective.In neonatal intensive care units (NICUs), monitoring hospital-acquired bloodstream infection (BSI) is critical to alert clinicians to variations in the incidence of infection between units and over time. We demonstrate a toolkit of monitoring techniques that account for case mix and could be implemented using routinely available clinical data. This toolkit could enable quality of care comparisons between hospitals to facilitate the sharing of improved practices.Design.Prospective study over 4 years.Setting and Patients.Babies admitted to 2 tertiary London NICUs.Methods.We derived expected numbers of BSI episodes using a Poisson regression risk model adjusting for variations in birth weight, transfers to the NICU from other hospitals, postnatal age, and days spent at each National Health Service level of care. We compared observed and expected numbers of BSI episodes using 2 monitoring techniques: standardized infection ratios (SIRs) and the sequential probability ratio test (SPRT).Results.Using the SIR method, observed BSI incidence increased over expected incidence in 2002 at both NICUs, but this increase did not reach statistical significance at the 1% level. Using the SPRT method, neither unit showed a clinically important increase or decrease, defined as a 30% deviation from expected incidence.Conclusions.Risk-adjusted BSI monitoring can be performed using routine hospital data. NICUs could use SIRs for an annual look back at infection incidence and SPRTs for prospective, quarterly monitoring. The SIR and the SPRT methods have different strengths, and both could help clinicians improve infection control and patient care in NICUs.

Patients' self-reported vaccine exposure (PS) may be subject to memory errors and other biases. Physicians' prescription records and other medical records (MR) do not capture noncompliance with vaccination. This study compared PS with MR for influenza, 23-valent pneumococcal, and human papillomavirus (HPV) vaccines.The Pharmacoepidemiologic General Research Extension (PGRx) database uses a network of over 300 general practitioners across France, who systematically recruit an age- and sex-stratified sample of patients (≥ 14 years old), without reference to their diagnoses or prescriptions. Patients received a structured telephone interview, combined with an interview guide listing vaccines commonly given. Patients' self-reported vaccination in the 3 years before their recruitment was compared with medical records kept by the physician or the patient.Concordance between PS and MR was assessed for 7613 patients for whom both sources of information were available. Agreement within 3 years before the recruitment date was substantial for influenza vaccines (prevalence and bias-adjusted kappa [PABAK] = 0.74, sensitivity PS relative to MR 81.5%) and high for 23-valent pneumococcal vaccines (PABAK = 0.98, sensitivity PS 49.6) and HPV vaccines (PABAK = 0.92, sensitivity PS 91.6). In adjusted analyses, agreement varied with sociodemographic and health-related factors, particularly for influenza and 23-valent pneumococcal vaccines.The PGRx method for drug exposure assessment is a new tool in pharmacoepidemiology that shows substantial to high agreement between PS and MR for exposure to various vaccines. Our finding of high agreement between PS and MR for HPV vaccination status in young women is a significant addition to the literature.

Comparisons of bloodstream infection (BSI) rates between neonatal intensive-care units (NICUs) should take into account differences in babies' vulnerability and invasive procedures that can introduce infection. Our aim was to investigate which risk factors recorded in routine records should be adjusted for when NICUs are compared. This was a retrospective cohort study using routine records for two London NICUs. We analysed rates of BSI with Poisson regression models. The level of neonatal care used by the National Health Service was the strongest predictor of BSI incidence. The rate ratios for BSI, adjusted for birthweight, inborn/outborn status, and postnatal age, were 3.15 (95% CI 2.01–4.94) for intensive care and 6.58 (95% CI 4.18-10.36) for high-dependency care, relative to special care. Total parenteral nutrition was significantly associated with BSI incidence, but explained less of the variance among babies than level of care. A case—control study with the same dataset gave similar results. Further multicentre studies are required to confirm our predictive model. Until then, we recommend that comparisons of BSI rates between NICUs should include adjustments for level of care, birthweight, inborn/outborn status, and postnatal age, with the use of routinely recorded standardized measures in hospital administrative data.

PO-191 Patient population with Multiple Myeloma and transitions across lines of therapy in the United States: an epidemiologic model J. Cid Ruzafa, E. Merinopoulou, R.F. Baggaley, P. Leighton, W. Werther, D. Felici, A. Cox Retrospective Observational Studies, Evidera, London, UK: JCR, EM, PL, AC; Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK: RFB; Onyx Pharmaceuticals, an Amgen Subsidiary, San Francisco, CA, USA: WW, DF

Abstract 1169 Background and objectives Immune thrombocytopenia (ITP) is thought to result from an autoimmune mechanism, and some case-reports have suggested that immunizations could be involved and trigger the autoimmune process. This prospective multicenter case-control study investigated for the first time associations between ITP and vaccination in adults, particularly between ITP and influenza vaccinations. Methods Over a three year period, a network of 15 physicians from hematology and internal medicine referral centers across France recruited newly diagnosed cases of primary ITP in patients aged over 15 years fulfilling the ITP standardized criteria of the American Society of Hematology. Recruiting physicians completed standardized forms for each patient and every patient underwent a standardized 1 hour-interview focused on previous medications and vaccinations in the last 12 months. Incident ITP cases were compared to sex and age-matched controls selected and recruited from general practice settings, also from the same geographically areas of France. The method of referent recruitment has been described elsewhere (Grimaldi-Bensouda et al. 2010 Pharmacoepidemiol Drug Saf 2010;19(6):591–5). Controls were also interviewed in the same standardized way as cases. Cases and control were compared in respect of various descriptive factors and potential risk factors for ITP. Written or other confirmation of vaccinations was sought from both the patient and his/her physician. The time window defining exposure to vaccines was 12 months before the index date. In secondary analysis, the most prevalent vaccines in adults were analyzed. Results Two hundred and twenty four cases fulfilling the inclusion criteria and 4412 were included in the study. Seventy eight of the 224 cases (34.8%) and 1566 of 4412 controls (35.5%) received a vaccination within this time window [adjusted odds ratio 0.97, 95% confidence interval 0.70–1.33]. Twenty percent of the cases and 26% of controls received an influenza vaccine [adjusted odds ratio 0.66, 95% confidence interval 0.45–0.98]. Other prevalent vaccines in adult are currently under study. Conclusions This systematic case-control design is well-suited to study rare disorders such as ITP and few such studies have been conducted. Another advantage was the minimization of recall bias because questions about vaccinations were included in a standardized interview focusing on exposure to all medications. When all vaccines were considered, we found no association between vaccination and the incidence of ITP in either crude or adjusted analyses. Moreover, cases were less likely than controls to have been vaccinated against influenza in the 12 months before the index date. Disclosures: Grimaldi-Bensouda: LA-SER: Employment; INSERM: I was the recipient of a research fellowship from the INSERM (French National Institute for Health and Medical Research) at the time of the study. Leighton:LA-SER Europe Ltd: Employment. Aubrun:LA-SER Europe Ltd: Employment. Abenhaim:LA-SER Europe Ltd: I'm a stock owner and chairman of LA-SER, the company conducting the study.