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Background/Aims Nested within the HMO Research Network (HMORN), the Cancer Research Network (CRN) is a collaboration among the National Cancer Institute, 9 funded HMORN sites, 6 affiliate sites, and scientific collaborators from multiple institutions. Now in its fourth cycle, the CRN has been funded continuously since 1999. CRN’s goals are to build data infrastructure, expertise, and collaborations to promote successful cancer research involving integrated healthcare delivery systems. Understanding characteristics of incident and prevalent cancer cases in the CRN is essential for investigators to evaluate the feasibility of CRN research projects.

Background/Aims The colony stimulating factors (CSFs), filgrastim and its long-acting form, pegfilgrastim, are indicated by the Food and Drug Administration to decrease infections in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy. Roughly 25–40% of treatment-naive patients receiving common chemotherapy regimens develop febrile neutropenia (FN). FN is associated with treatment delays, dose reductions, hospitalizations, and a high cost burden. CSFs decrease the incidence, length and severity of chemotherapy-related neutropenia in several solid tumors and prophylactically, decrease infection rates and neutropenia, infection-related mortality, and early deaths associated with chemotherapy. A reduction in absolute and relative risk for all-cause mortality is associated with CSF use and in combination with antibiotics for the treatment of FN, CSFs decrease the length of hospitalization; however, recent studies have shown these agents are frequently administered in a manner inconsistent with the recommended guidelines. The high costs associated with FN treatment, the high cost of CSFs and administration of CSFs in a manner inconsistent with scientific evidence creates both a clinical and economic challenge for health plans. To date, CSF data within the Virtual Data Warehouse (VDW) has not been evaluated for accuracy.

Five-year breast cancer survivors, diagnosed after 65 years of age, may develop more incident comorbidities than similar populations free of cancer. We investigated whether older breast cancer survivors have a similar comorbidity burden 6-15 years after cancer diagnosis to matched women free of breast cancer at start of follow-up and whether incident comorbidities are associated with all-cause mortality. In this prospective cohort study, 1,361 older 5-year early-stage breast cancer survivors diagnosed between 1990 and 1994 and 1,361 age- and health system-matched women were followed for 10 years. Adjudicated medical record review captured prevalent and incident comorbidities during follow-up or until death as collected from the National Death Index. Older 5-year breast cancer survivors did not acquire incident comorbidities more often than matched women free of breast cancer in the subsequent 10 years [hazard ratio (HR) 1.0, 95 % confidence interval (95 % CI) 0.93, 1.1]. Adjusted for cohort membership, women with incident comorbidities had a higher mortality rate than those without incident comorbidities (HR 4.8, 95 % CI 4.1, 5.6). A breast cancer history continued to be a hazard for mortality 6-15 years after diagnosis (HR 1.3, 95 % CI 1.1, 1.4). We found that older breast cancer survivors who developed comorbidities had an increased all-cause mortality rate even after adjusting for age and prevalent comorbidity burden. Additionally, survivors acquire comorbidities at a rate similar to older women free of breast cancer. These results highlight the association between comorbidity burden and long-term mortality risk among older breast cancer survivors and their need for appropriate oncology and primary care follow-up.

Objective: To assess the accuracy of electronic health record (EHR)–derived diagnoses in identifying children with incident (i.e., newly diagnosed) ADHD. Method: In 10 large health care organizations, electronic diagnoses data were used to identify all potential cases of incident ADHD among 3- through 9-year-old children. A random sample of records was manually reviewed to determine whether a diagnosis of ADHD was documented in clinician notes. Results: From electronic diagnoses data, a total of 7,362 children with incident ADHD were identified. Upon manual review of 500 records, the diagnosis of incident ADHD was confirmed in clinician notes for 71.5% (95% confidence interval [CI] = [56.5, 86.4]) of records for 3- through 5-year-old children and 73.6% (95% CI = [65.6, 81.6]) of records for 6- through 9-year-old children. Conclusion: Studies predicated on the identification of incident ADHD cases will need to carefully consider study designs that minimize the likelihood of case misclassification.

Late effects of breast cancer affect the quality of survivorship. Using administrative data, we compared the occurrence of almost all ICD9 codes among older breast cancer survivors to that among a matched comparison cohort to generate new hypotheses. Breast cancer patients 65 years or older diagnosed 1990–1994 in 6 integrated care settings and who survived at least 5 years were matched with a cohort of women without a history of breast cancer on care setting, age, and calendar time. We collected data on the occurrence of incident ICD9 codes beginning 6 years after the breast cancer diagnosis date and continuing to year 15, and comparable data for the matched woman. We calculated hazard ratios (HRs) and 95 % confidence intervals associating breast cancer survivorship with incidence of each ICD9 code. We used semi-Bayes methods to address multiple comparisons. Older breast cancer survivors had about the same occurrence of diseases and conditions 6–15 years after breast cancer diagnosis as comparable women. The median of 564 adjusted HRs equaled 1.06, with interquartile range 0.92–1.3. The distribution of HRs pertaining to cancer-related ICD codes was shifted toward positive associations, and the distribution pertaining to cardiovascular-related ICD codes was shifted toward negative associations. In this hypothesis-scanning study, we observed little difference in the occurrence of non-breast cancer-related diseases and conditions among older, long-term breast cancer survivors, and comparable women without a history of breast cancer.

Purpose Little is known about opioid use after bariatric surgery among patients who did not use opioids chronically before surgery. Our purpose was to determine opioid use the year after bariatric surgery among patients who did not use opioids chronically pre-surgery and to identify pre-surgery characteristics associated with chronic opioid use after surgery. Methods This retrospective cohort study across nine US health systems included 10 643 patients aged 21 years or older who underwent bariatric surgery and who were not chronic opioid users pre-surgery. The main outcome was chronic opioid use the post-surgery year (excluding 30 post-operative days) defined as ≥10 dispensings over ≥90 days or ≥120 total days' supply. Results Overall, 4.0% (n = 421) of patients became chronic opioid users the post-surgery year. Pre-surgery opioid total days' supply was strongly associated with chronic use post-surgery (1–29 days adjusted odds ratio [OR] 1.89 [95%CI, 1.24–2.88]; 90–119 days OR, 14.29 [95%CI, 6.94–29.42] compared with no days). Other factors associated with increased likelihood of post-surgery chronic use included pre-surgery use of non-narcotic analgesics (OR, 2.22 [95%CI, 1.39–3.54]), antianxiety agents (OR, 1.67 [95%CI, 1.12–2.50]), and tobacco (OR, 1.44 [95%CI, 1.03–2.02]). Older age (OR, 0.84 [95%CI, 0.73–0.97] each decade) and a laparoscopic band procedure (OR, 0.42 [95%CI, 0.25–0.70] vs. laparoscopic bypass) were associated with decreased likelihood of chronic opioid use post-surgery. Conclusions Most patients who became chronic opioid users the year after bariatric surgery used opioids intermittently before surgery. Copyright © 2014 John Wiley & Sons, Ltd.

To evaluate the prevalence, trends, timing and duration of exposure to antiviral medications during pregnancy within a US cohort of pregnant women and to evaluate the proportion of deliveries with a viral infection diagnosis among women given antiviral medication during pregnancy. Live-born deliveries between 2001 and 2007, to women aged 15–45 years, were included from the Medication Exposure in Pregnancy Risk Evaluation Program, a collaborative research program between the U.S. Food and Drug Administration and eleven health plans. They were evaluated for prevalence, timing, duration, and temporal trends of exposure to antiviral medications during pregnancy. We also calculated the proportion of deliveries with a viral infection diagnosis among those exposed to antiviral medications. Among 664,297 live births, the overall prevalence of antiviral exposure during pregnancy was 4 % (n = 25,155). Between 2001 and 2007, antiviral medication exposure during pregnancy doubled from 2.5 to 5 %. The most commonly used antiviral medication was acyclovir, with 3 % of the deliveries being exposed and most of the exposure occurring after the 1st trimester. Most deliveries exposed to antiviral medications were exposed for less than 30 days (2 % of all live births). Forty percent of the women delivering an infant exposed to antiviral medications had a herpes diagnosis. Our findings highlight the increased prevalence of women delivering an infant exposed to antiviral medications over time. These findings support the need for large, well-designed studies to assess the safety and effectiveness of these medications during pregnancy.

Obesity is associated with chronic noncancer pain. It is not known if opioid use for chronic pain in obese individuals undergoing bariatric surgery is reduced.To determine opioid use following bariatric surgery in patients using opioids chronically for pain control prior to their surgery and to determine the effect of preoperative depression, chronic pain, or postoperative changes in body mass index (BMI) on changes in postoperative chronic opioid use.Retrospective cohort study in a distributed health network (10 demographically and geographically varied US health care systems) of 11,719 individuals aged 21 years and older, who had undergone bariatric surgery between 2005 and 2009, and were assessed 1 year before and after surgery, with latest follow-up by December 31, 2010.Opioid use, measured as morphine equivalents 1 year before and 1 year after surgery, excluding the first 30 postoperative days. Chronic opioid use is defined as 10 or more opioid dispensings over 90 or more days or as dispensings of at least a 120-day supply of opioids during the year prior to surgery.Before surgery, 8% (95% CI, 7%-8%; n = 933) of bariatric patients were chronic opioid users. Of these individuals, 77% (95% CI, 75%-80%; n = 723) continued chronic opioid use in the year following surgery. Mean daily morphine equivalents for the 933 bariatric patients who were chronic opioid users before surgery were 45.0 mg (95% CI, 40.0-50.1) preoperatively and 51.9 mg (95% CI, 46.0-57.8) postoperatively (P .001). For this group with chronic opiate use prior to surgery, change in morphine equivalents before vs after surgery did not differ between individuals with loss of more than 50% excess BMI vs those with 50% or less (50% BMI loss: adjusted incidence rate ratio [adjusted IRR, 1.17; 95% CI, 1.07-1.28] vs ≤50% BMI loss [adjusted IRR, 1.03; 95% CI, 0.93-1.14] model interaction, P = .06). In other subgroup analyses of preoperative chronic opioid users, changes in morphine equivalents before vs after surgery did not differ between those with or without preoperative diagnosis of depression or chronic pain (depression only [n = 75; IRR, 1.08; 95% CI, 0.90-1.30]; chronic pain only [n = 440; IRR, 1.17; 95% CI, 1.08-1.27]; both depression and chronic pain [n = 226; IRR, 1.11; 95% CI, 0.96-1.28]; neither depression nor chronic pain [n = 192; IRR, 1.22; 95% CI, 0.98-1.51); and P values for model interactions when compared with neither were P = .42 for depression, P = .76 for pain, and P = .48 for both.In this cohort of patients who underwent bariatric surgery, 77% of patients who were chronic opioid users before surgery continued chronic opioid use in the year following surgery, and the amount of chronic opioid use was greater postoperatively than preoperatively. These findings suggest the need for better pain management in these patients following surgery.

Background/AimsFew published studies have evaluated the validity of health plan administrative and claims data to identify anaphylaxis. Given the severity of the condition, drug-induced anaphylaxis is a major public health concern. We developed and evaluated the positive predictive value (PPV) of algorithms for identifying anaphylaxis in the Mini-Sentinel Distributed Database.MethodsWe conducted a retrospective study among members enrolled in 8 geographically diverse health plans (HealthCore, Inc.; Humana; three member health plans within the Kaiser Permanente Center for Effectiveness and Safety Research; and two member health plans in the HMO Research Network). Diagnosis and procedure codes were used to identify potential cases of anaphylaxis recorded in the Mini-Sentinel Distributed Database between January 1, 2009 and December 31, 2010. A random sample of medical charts (n = 131) was abstracted and adjudicated and positive predictive values (PPVs) were calculated based upon diagnostic criteria by Sampson et al.ResultsOf the 131 potential available cases, adjudicators determined that 77 were anaphylaxis, 45 were not anaphylaxis, and 9 were determined to have inadequate information to confirm whether or not a case was anaphylaxis. Overall, the PPV was 63.1% (95% confidence interval, 53.9%–71.7%). PPVs ranged from 48.1% to 78.9% across the Data Partners. In comparing different criteria, algorithms which included codes for allergy (ICD-9-CM 995.3) or adverse effects of drug, medicinal and biological substance (ICD-9-CM 995.2, E930-E949) in combination with additional treatment or symptom codes, such as injection of epinephrine, had a lower PPV (PPV = 45.8%) than algorithms that included codes specifically indicating anaphylaxis (ICD-9-CM 995.0, 999.4), although confidence intervals were wide and overlapped.ConclusionsWhile the PPV of the developed algorithm was higher than those reported in previously published studies, the PPV of anaphylaxis remains low. Further evaluation of individual codes and combinations of codes is ongoing as part of the present study.

We aim to develop and validate the positive predictive value (PPV) of an algorithm to identify anaphylaxis using health plan administrative and claims data. Previously published PPVs for anaphylaxis using International Classification of Diseases, ninth revision, Clinical Modification (ICD-9-CM) codes range from 52% to 57%.We conducted a retrospective study using administrative and claims data from eight health plans. Using diagnosis and procedure codes, we developed an algorithm to identify potential cases of anaphylaxis from the Mini-Sentinel Distributed Database between January 2009 and December 2010. A random sample of medical charts (n = 150) was identified for chart abstraction. Two physician adjudicators reviewed each potential case. Using physician adjudicator judgments on whether the case met diagnostic criteria for anaphylaxis, we calculated a PPV for the algorithm.Of the 122 patients for whom complete charts were received, 77 were judged by physician adjudicators to have anaphylaxis. The PPV for the algorithm was 63.1% (95%CI: 53.9-71.7%), using the clinical criteria by Sampson as the gold standard. The PPV was highest for inpatient encounters with ICD-9-CM codes of 995.0 or 999.4. By combining only the top performing ICD-9-CM codes, we identified an algorithm with a PPV of 75.0%, but only 66% of cases of anaphylaxis were identified using this modified algorithm.The PPV for the ICD-9-CM-based algorithm for anaphylaxis was slightly higher than PPV estimates reported in prior studies, but remained low. We were able to identify an algorithm that optimized the PPV but demonstrated lower sensitivity for anaphylactic events.

The lack of adherence to prescribed medication is an important health challenge. Despite evidence indicating the therapeutic benefit for adhering to a prescribed regimen, many patients do not take medications as prescribed. Several studies have been conducted examining medication adherence for various conditions, and adherence has consistently been found to be suboptimal.1–7 Failure to take medication as prescribed increases the risk that patients will not get the intended benefit, often leading to negative sequelae.3,8–12 Further, not adhering to one’s prescribed medications is likely to result in higher healthcare costs overall.10 Thus, understanding factors associated with maintaining one’s medication regimen is important to patients, providers, and health plans. External factors such as cost and access to the needed medication play a role in non-adherence. However, within our integrated health care system, where most patients have access to care, a covered pharmacy benefit, and easy access to pharmacies, one might expect a lower rate of non-adherence than in the general population. Pharmacies are available in all clinics owned by the medical group. In addition, phone-in, mail order, and internet prescription refill options allow patients the ability to order medications 24 hours a day. Nevertheless, the health system has identified non-adherence as a major area of concern. While the literature has reported some evidence of variation of adherence by age, race, co-morbidity status, and socioeconomic status (SES) (higher adherence in those older, white, lower co-morbidity, and higher SES),8,9,13–17 the majority of studies conducted have examined adherence within a given disease state. Few have examined adherence across multiple conditions to determine whether associations between adherence and patient characteristics are consistent. Such information could be helpful in health systems such as ours to develop focused interventions. Therefore, to increase the understanding of medication adherence in our population, we examined adherence across multiple health conditions, examining associated patient and drug-related characteristics. The purpose of this paper is to report on the patient characteristics associated with adherence within this large integrated health system.

Asthma is one of the most common chronic diseases in women of reproductive age, occurring in up to 8 % of pregnancies. The objective of this study is to assess the prevalence of asthma medication use during pregnancy in a large diverse cohort. We identified women aged 15-45 years who delivered a live born infant between 2001 and 2007 across 11 U.S. health plans within the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP). Using health plans' administrative and claims data, and birth certificate data, we identified deliveries for which women filled asthma medications from 90 days before pregnancy through delivery. Prevalence (%) was calculated for asthma diagnosis and medication dispensing. There were 586,276 infants from 575,632 eligible deliveries in the MEPREP cohort. Asthma prevalence among mothers was 6.7 %, increasing from 5.5 % in 2001 to 7.8 % in 2007. A total of 9.7 % (n = 55,914) of women were dispensed asthma medications during pregnancy. The overall prevalence of maintenance-only medication, rescue-only medication, and combined maintenance and rescue medication was 0.6, 6.7, and 2.4 % respectively. The prevalence of maintenance-only use doubled during the study period from 0.4 to 0.8 %, while rescue-only use decreased from 7.4 to 5.8 %. In this large population-based pregnancy cohort, the prevalence of asthma diagnoses increased over time. The dispensing of maintenance-only medication increased over time, while rescue-only medication dispensing decreased over time. Refereed/Peer-reviewed

Background: In metastatic colorectal cancer (mCRC), mutations in the KRAS gene predict poor response to EGF receptor (EGFR) inhibitors. Clinical treatment guidelines now recommend KRAS testing if EGFR inhibitors are considered. Our study investigates the clinical uptake and utilization of KRAS testing. Methods: We included 1,188 patients with mCRCs diagnosed from 2004 to 2009, from seven integrated health care delivery systems with a combined membership of 5.5 million. We used electronic medical records and targeted manual chart review to capture the complexity and breadth of real-world clinical oncology care. Results: Overall, 428 patients (36%) received KRAS testing during their clinical care, and 266 (22%) were treated with EGFR inhibitors. Age at diagnosis (P = 0.0034), comorbid conditions (P = 0.0316), and survival time from diagnosis (P < 0.0001) influence KRAS testing and EGFR inhibitor prescribing. The proportion who received KRAS testing increased from 7% to 97% for those treated in 2006 and 2010, respectively, and 83% of all treated patients had a KRAS wild-type genotype. Most patients with a KRAS mutation (86%) were not treated with EGFR inhibitors. The interval between mCRC diagnosis and receipt of KRAS testing decreased from 26 months (2006) to 10 months (2009). Conclusions: These findings show rapid uptake and incorporation of this predictive biomarker into clinical oncology care. Impact: In this delivery setting, KRAS testing is widely used to guide treatment decisions with EGFR inhibitors in patients with mCRCs. An important future research goal is to evaluate utilization of KRAS testing in other delivery settings in the United States. Cancer Epidemiol Biomarkers Prev; 22(1); 91–101. ©2012 AACR.

The aim of this study was to examine Lynch syndrome screening of patients with metastatic colorectal cancer in integrated health-care-delivery organizations. We determined the availability of Lynch syndrome screening criteria and actual Lynch syndrome screening in the medical records of 1,188 patients diagnosed with metastatic colorectal cancer between 2004 and 2009 at seven institutions in the Cancer Research Network. We found infrequent use of Lynch syndrome screening (41/1,188). Family history was available for 937 of the 1,188 patients (79%). There was sufficient information to assess Lynch syndrome risk using family history–based criteria in 719 of the 937 patients (77%) with family history documentation. In 391 individuals with a family history of a Lynch syndrome–associated cancer, 107 (27%) could not be evaluated due to missing information such as age of cancer onset. Eleven percent of patients who met the Bethesda criteria and 25% of individuals who met the Amsterdam II criteria were screened for Lynch syndrome. Recommended guidelines were adhered to during screening, but no testing method was preferred. The information required for Lynch syndrome screening decisions is routinely collected but seldom used. There is a critical gap between collection of family history and its use to guide Lynch syndrome screening, which may support a case for implementation of universal screening guidelines. Genet Med 15 12, 933–940.

Research on medication safety in pregnancy often utilizes health plan and birth certificate records. This study discusses methods used to link mothers with infants, a crucial step in such research.We describe how eight sites participating in the Medication Exposure in Pregnancy Risk Evaluation Program created linkages between deliveries, infants and birth certificates for the 2001-2007 birth cohorts. We describe linkage rates across sites, and for two sites, we compare the characteristics of populations linked using different methods.Of 299,260 deliveries, 256,563 (86%; range by site, 74-99%) could be linked to infants using a deterministic algorithm. At two sites, using birth certificate data to augment mother-infant linkage increased the representation of mothers who were Hispanic or non-White, younger, Medicaid recipients, or had low educational level. A total of 236,460 (92%; range by site, 82-100%) deliveries could be linked to a birth certificate.Tailored approaches enabled linking most deliveries to infants and to birth certificates, even when data systems differed. The methods used may affect the composition of the population identified. Linkages established with such methods can support sound pharmacoepidemiology studies of maternal drug exposure outside the context of a formal registry.

In post-marketing drug safety surveillance, data mining can potentially detect rare but serious adverse events. Assessing an entire collection of drug-event pairs is traditionally performed on a predefined level of granularity. It is unknown a priori whether a drug causes a very specific or a set of related adverse events, such as mitral valve disorders, all valve disorders, or different types of heart disease. This methodological paper evaluates the tree-based scan statistic data mining method to enhance drug safety surveillance.We use a three-million-member electronic health records database from the HMO Research Network. Using the tree-based scan statistic, we assess the safety of selected antifungal and diabetes drugs, simultaneously evaluating overlapping diagnosis groups at different granularity levels, adjusting for multiple testing. Expected and observed adverse event counts were adjusted for age, sex, and health plan, producing a log likelihood ratio test statistic.Out of 732 evaluated disease groupings, 24 were statistically significant, divided among 10 non-overlapping disease categories. Five of the 10 signals are known adverse effects, four are likely due to confounding by indication, while one may warrant further investigation.The tree-based scan statistic can be successfully applied as a data mining tool in drug safety surveillance using observational data. The total number of statistical signals was modest and does not imply a causal relationship. Rather, data mining results should be used to generate candidate drug-event pairs for rigorous epidemiological studies to evaluate the individual and comparative safety profiles of drugs.

To evaluate the validity of health plan and birth certificate data for pregnancy research.A retrospective study was conducted using administrative and claims data from 11 U.S. health plans and corresponding birth certificate data from state health departments. Diagnoses, drug dispensings, and procedure codes were used to identify infant outcomes (cardiac defects, anencephaly, preterm birth, and neonatal intensive care unit [NICU] admission) and maternal diagnoses (asthma and systemic lupus erythematosus [SLE]) recorded in the health plan data for live born deliveries between January 2001 and December 2007. A random sample of medical charts (n = 802) was abstracted for infants and mothers identified with the specified outcomes. Information on newborn, maternal, and paternal characteristics (gestational age at birth, birth weight, previous pregnancies and live births, race/ethnicity) was also abstracted and compared to birth certificate data. Positive predictive values (PPVs) were calculated with documentation in the medical chart serving as the gold standard.PPVs were 71% for cardiac defects, 37% for anencephaly, 87% for preterm birth, and 92% for NICU admission. PPVs for algorithms to identify maternal diagnoses of asthma and SLE were ≥ 93%. Our findings indicated considerable agreement (PPVs 90%) between birth certificate and medical record data for measures related to birth weight, gestational age, prior obstetrical history, and race/ethnicity.Health plan and birth certificate data can be useful to accurately identify some infant outcomes, maternal diagnoses, and newborn, maternal, and paternal characteristics. Other outcomes and variables may require medical record review for validation.

More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety.To examine whether current use of medications prescribed primarily to treat ADHD is associated with increased risk of serious cardiovascular events in young and middle-aged adults.Retrospective, population-based cohort study using electronic health care records from 4 study sites (OptumInsight Epidemiology, Tennessee Medicaid, Kaiser Permanente California, and the HMO Research Network), starting in 1986 at 1 site and ending in 2005 at all sites, with additional covariate assessment using 2007 survey data. Participants were adults aged 25 through 64 years with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n = 150,359) was matched to 2 nonusers on study site, birth year, sex, and calendar year (443,198 total users and nonusers).Serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), or stroke, with comparison between current or new users and remote users to account for potential healthy-user bias.During 806,182 person-years of follow-up (median, 1.3 years per person), 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use (median, 0.33 years), with a crude incidence per 1000 person-years of 1.34 (95% CI, 1.14-1.57) for MI, 0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The multivariable-adjusted rate ratio (RR) of serious cardiovascular events for current use vs nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Among new users of ADHD medications, the adjusted RR was 0.77 (95% CI, 0.63-0.94). The adjusted RR for current use vs remote use was 1.03 (95% CI, 0.86-1.24); for new use vs remote use, the adjusted RR was 1.02 (95% CI, 0.82-1.28); the upper limit of 1.28 corresponds to an additional 0.19 events per 1000 person-years at ages 25-44 years and 0.77 events per 1000 person-years at ages 45-64 years.Among young and middle-aged adults, current or new use of ADHD medications, compared with nonuse or remote use, was not associated with an increased risk of serious cardiovascular events. Apparent protective associations likely represent healthy-user bias.

Background/Aims The International Serious Adverse Events Consortium (iSAEC) is a pharmaceutical industry and FDA-led consortium focused on identifying DNA variants useful for predicting risk of drug-induced rare serious adverse events (SAEs). We assessed the feasibility of using electronic medical databases at six HMORN sites to identify provisional cases of three SAEs: drug-induced liver injury (DILI), serious skin rashes (SSR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and angioedema, and extreme weight gain (EWG) among adults on atypical antipsychotics.

Background/Aims Provisional clinical guidelines, published by the American Society of Clinical Oncology in 2009, recommend that patients with metastatic colon cancer (mCRC) be tested for mutations in the Kirsten ras (KRAS) oncogene, and that patients found to have the non mutated KRAS gene be offered anti-epidermal growth factor receptor (EGFR) antibody therapy. Such therapy has been shown to extend life; yet it is also expensive and frequently associated with severe side-effects. Currently, little is known about how clinicians are using KRAS testing in clinical practice. This study compares the adoption of policies for and usage of KRAS testing and anti-EGFR therapy in clinical practice among seven integrated health delivery systems. The purposes were to examine 1) physicians’ attitudes toward and experiences with KRAS testing and the communication process with their patients, 2) patients’ experiences with KRAS testing and anti-EGFR therapy and associated quality-of-life issues, and 3) the adoption of policies for KRAS testing and anti-EGFR therapy at the different health plans.

Background New prescriptions unfilled by patients (primary non-adherence) contribute to the overwhelming problem associated with medication non-adherence. Little research has been conducted in this area relative to refill non-adherence. The overall impact of unclaimed prescriptions is potentially significant depending on the medication and its indication. Because primary non-adherence has been recognized as an issue within our organization, we are conducting a retrospective study to evaluate fills up to twelve months following a new prescription in order to assess patient and clinical variables associated with primary non-adherence.

Objective To help understand medication adherence within HealthPartners, we developed a study to assess factors associated across eight different conditions. This presentation focuses on associated patient-related characteristics

Background Literature has shown many patients do not adhere to prescribed medications. To help understand factors related to medication adherence, we conducted a survey of adherent and non-adherent patients.

Background The definitive local therapy options for early-stage breast cancer are mastectomy and breast-conserving surgery followed by radiation therapy. Older women and those with comorbidities frequently receive breast-conserving surgery alone. The interaction of age and comorbidity with breast cancer severity and their impact on receipt of definitive therapy have not been well-studied. Study Design In a cohort of 1,837 women aged 65 years and older receiving treatment for early-stage breast cancer in 6 integrated health care delivery systems in 1990–1994 and followed for 10 years, we examined predictors of receiving nondefinitive local therapy and assessed the impact on breast cancer recurrence within levels of severity, defined as level of risk for recurrence. Results Age and comorbidity were associated with receipt of nondefinitive therapy. Compared with those at low risk, women at the highest risk were less likely to receive nondefinitive therapy (odds ratio=0.32; 95% CI, 0.22–0.47), and women at moderate risk were about half as likely (odds ratio=0.54; 95% CI, 0.35–0.84). Nondefinitive local therapy was associated with higher rates of recurrence among women at moderate (hazard ratio=5.1; 95% CI, 1.9–13.5) and low risk (hazard ratio=3.2; 95% CI, 1.1–8.9). The association among women at high risk was weak (hazard ratio=1.3; 95% CI, 0.75–2.1). Conclusions Among these older women with early-stage breast cancer, decisions about therapy partially balanced breast cancer severity against age and comorbidity. However, even among women at low risk, omitting definitive local therapy was associated with increased recurrence.

Background: New genomic and personalized medicine (GPM) applications have the potential to enhance our ability to screen for disease predisposition and treatment responsiveness. Surveying colorectal cancer (CRC) tissue for mutations in the KRAS gene is one such test that can help decide how to treat patients with metastatic colorectal cancer (mCRC). KRAS testing provides an opportunity for oncologists to tailor the use of anti-EGFR therapy to increase treatment effectiveness and potentially minimize adverse events. The FDA has recently changed the labeling of anti-EGFR therapies to indicate that it is not effective for the treatment of patients with KRAS mutations. KRAS testing has already become standard clinical practice in many settings. In this study, we will assess the patterns of diffusion and utilization of KRAS testing and evaluate the characteristics of patients, providers, and health systems as they relate to the uptake of KRAS testing. We will also conduct a comparative analysis of KRAS testing for mCRC patients treated in community practices to evaluate its effectiveness in terms of both progression-free survival and overall survival. Methods: This study will include a total of 800 mCRC cases diagnosed between January 1, 2005 and July 31, 2010 from 7 HMORN sites. Using electronic records at each site, we will capture information on relevant patient characteristics including disease characteristics, comorbidities, history of all cancer-directed therapies, acute complications, receipt of palliative care and contextual socioeconomic variables. We will use chart review to supplement, or in some cases verify, the electronic data. Conclusion: The study will serve as a model for evaluating the potential impact of GPM applications to improve health outcomes, reduce costs, and influence patient and physician decision-making in the area of personalized therapies.

Background/Aims Chemotherapy for advanced (stage III/IV) colon cancer has changed with new drugs and combination regimens. Treatment guidelines for advanced disease are broad thus allowing for treatment variation. We evaluated cases enrolled at 7 HMO Research Network sites through the Comparative Effectiveness in Genomic and Personalized Medicine for Colon Cancer (CERGEN) study to describe characteristics and patterns of chemotherapy treatment by geographic site and patient characteristics.

Background/Aims Adherence to prescribed medications is a widespread problem and determinants of medication non-adherence have been previously described as health system, social/economic, therapy-related, condition-related, and patient-related factors. Medication non-adherence clearly represents a multifaceted challenge among patients and health care providers. The impact of drug characteristics on medication adherence has not been studied across disease states. The purpose of this study was to describe medication adherence by drug characteristics across multiple disease states to identify drug-specific factors that may serve as targets for future intervention to improve medication adherence.

203 Background: Cancer-related pain is common, negatively impacts quality of life and survival, and often requires opioid analgesics. Patient level data describing the incidence and severity of pain, medication utilization, and patient satisfaction associated with care are lacking. An understanding of cancer pain prevalence and analgesic utilization is needed to initiate quality improvement (QI) interventions. Methods: We analyzed 2 months of outpatient oncology clinic encounters from the electronic medical record (EMR) and conducted a patient survey of 163 cancer patients to obtain baseline data on pain levels, opioid and non-opioid treatments, and patient satisfaction. Our survey incorporated questions from the Brief Pain Inventory to validate EMR reports and obtain patient satisfaction data. Results: Moderate to severe pain is reported in nearly 1 of every 9 cancer patient encounters (Table 1). On average, we achieved a personal pain goal (PPG) in 83.5 % of all patients (n=109). Among patients receiving opioids, a PPG was achieved in 16 of 29 patients (55.2%). Of the 13 opioid-consuming patients not achieving a PPG, 12 were not on a long-acting opioid, and 5 had never discussed a pain management plan with their physician. Oxycodone CR is the most commonly prescribed long-acting opioid (40.4% versus morphine SR (26.1%), methadone (23.0%), and fentanyl transdermal (10.6%)). Conclusions: Moderate to severe pain is commonly encountered among patients receiving cancer care in the clinic setting. Increasing the proportion of patients achieving a PPG is a critical quality and patient satisfaction goal, and may be improved by creating a pain plan incorporating a long-acting opioid. Our QI intervention aims to improve pain assessment documented in the EMR and educate both patients and staff regarding appropriate pain management. [Table: see text]

Background/Aims Convenient for its oral route of administration, capecitabine is increasingly used in the older population with colorectal and other solid tumors. Since renal impairment increases with age, we designed a pilot study to assess adherence to standard dose reductions for renal insufficiency and dosing recommendations for older patients. We sought to describe patterns of capecitabine use in older patients and factors that influence dosing; specifically age and renal insufficiency.

Background/Aims Elective induction of labor is controversial and has been linked to adverse pregnancy outcomes including higher rates of cesarean delivery. Many institutions have implemented measures to limit this practice. Our aim was to describe recent trends in the prevalence of elective induction.

Background/AimsThe HMO Research Network (HMORN) Virtual Data Warehouse (VDW) is a series of dataset standards and automated processes that aim to streamline the process of multi-site research. The Pharmacy file contains data on all outpatient dispensings captured within the HMORN. The objective was to assess the overall quality and completeness of the Pharmacy file.MethodsThe VDW Pharmacy Working Group created a data verification protocol to assess the overall quality and completeness of Pharmacy file data (e.g., to identify missing data or out-of-range values). A distributed SAS program was run at each HMORN site that maintains a VDW Pharmacy file (n=14 of 19 HMORN sites), and de-identified summary data were returned for analysis. Pharmacy file variables that were assessed included National Drug Code (NDC), days supplied, amount dispensed, and prescribing physician (which joins to the VDW Provider Specialty file). An ?invalid? NDC was defined as any value not having exactly 11 digits or containing a non-numeric character. The days supplied variable was considered out-of-range if the value was 20 years of data. There were 93.4 million dispensings in 2009, with an average of 7.8 million dispensings per month among 3.1 million monthly users (average per user: 2.6 dispensings per month; range across sites 2.3?5.8). Across all sites from 2000?2009, 0.082% (712,131/870,182,026) and 0.072% (629,656/870,182,026) of dispensings had missing or ?invalid? NDCs, respectively; and 0.083% (724,210/870,182,026) and 0.315% (2,736,756/870,182,026) had out-of-range days supplied and amount supplied, respectively. The prescribing physician was identified in 96% (1,038,725,660/1,079,370,265) of all dispensings. The prescriber?s specialty was identified in 62% (539,944,688/870,182,078) of dispensings overall and improved from 61% (46,678,731/77,078,104) in 2000 to 63% (60,160,629/95,867,812) in 2009.DiscussionThe VDW Pharmacy file has excellent overall data quality results, and has improved in identification of prescriber specialty. It has measurably comprehensive and consistent outpatient dispensing data across 14 HMORN sites.

Background/Aims The Hyperlink study is a cluster randomized trial in patients with uncontrolled blood pressure. The objectives of this analysis were: to compare measures of self reported adherence with actual adherence to medications at study enrollment to study predictors of adherence. Methods We analyzed prescription claims data for 146 participants who had prescription coverage through HealthPartners for at least one year prior to study enrollment and were taking at least 1 antihypertensive medication. Self reported adherence was measured using a 4-item Morisky scale. Actual adherence was defined as a continuous measure of Medication Possession Ratio (MPR) as well as a binary measure defining adherence as an MPR of >80%.

Genetic testing to inform health professionals and patients of disease risk, diagnostic, prognostic, or treatment information such as KRAS mutation testing to determine colorectal cancer (CRC) treatment is an evolving health care approach. KRAS, a pharmacogenomic marker normally expressed in wild type form, confers a lack of response to epidermal growth factor receptor (EGFR) inhibitor treatment in metastatic CRC when mutated. Mutations occur in 30–50% of CRC cases and a gap in knowledge exists regarding the impact of KRAS testing on treatment outcomes in metastatic CRC. The CERGEN-C (Comparative Effectiveness Research in Genomics & Personalized Medicine for Colorectal Cancer) study is a collaboration of eight Cancer Research Network members and four academic partners evaluating connections between evidence synthesis and evidence generation in cancer-related genomics and personalized medicine. We are conducting a comparative effectiveness study to evaluate overall survival in patients who received KRAS testing during routine medical care compared to those who did not before and after recommendations for KRAS testing were published in mid-2008. We identified 800 members from seven integrated health care organizations diagnosed with stage III (n=200) or IV (n=600) colorectal cancer from 1/1/05–7/31/2010. To date, 293 charts have been reviewed, 224 (76%) from pre-KRAS testing recommendations (pre-) and 69 (24%) from post-KRAS testing (post-) recommendations. All cases were Stage IV and the majority of cases were Caucasian, 133 (61%) pre and 51 (76%) post. A family history of any cancer was identified in 97 (43%) pre- and 29 (42%) post- cases and KRAS testing was performed in 60/293 (20%) of cases reviewed to date, 41 (18%) pre- and 19(26%) post-, respectively. Wild type KRAS was found in 28 tested cases, 21 pre- and 7 post- cases. Of the identified wild type cases, 17 pre- and 6 post- were treated with EGFR inhibitors. Overall, EGFR inhibitors were administered in 48 cases, 42 (18%) pre- and 6 (19%) post-. EGFR inhibitor treatment began with 3rd line therapy in those tested for KRAS compared to first line in those not tested. The most common chemotherapy regimen including an EGFR inhibitor was irinotecan and cetuximab, n=25 (52%).

Background/Aims Mastectomy and breast conserving surgery followed by radiotherapy are considered initial guideline therapies for early stage breast cancer with randomized trials demonstrating reduced risk of recurrence. However, older women and those with comorbidities frequently receive only breast conserving surgery. The interaction of age and comorbidity with breast cancer severity and their impact on receipt of guideline therapy have not been well studied.

Background/Aims Drug Induced Liver Injury (DILI) is a major cause of liver failure in the US and the leading reason for failure of investigational drugs in clinical trials, lack of drug approval, and post-market withdrawal of approved drugs. Recent genome-wide association studies have identified variations within the major histocompatibility complex in Caucasians to be linked with flucloxacillin and lumiracoxib-related liver injury. The need for replication of these findings and extension of these investigations to other drug exposures and other ethnic groups will require substantial case numbers with supporting medical record documentation. With support from The Serious Adverse Event Consortium, an international consortium led by the pharmaceutical industry in conjunction with the FDA, we conducted a feasibility study to evaluate the potential for using electronic clinical and administrative data from two HMORN sites to identify provisional DILI cases.

Membership of the CERGEN Study Team is provided in the Acknowledgments. The Comparative Effectiveness Research in Genomics of Colon Cancer (CERGEN) Study Team includes: Gwen Alexander, Henry Ford Health System (HFHS); Chris Anderson, Health Partners Institute for Education and Research (HPIER); Ajay Behl, HPIER; Kris Bennett, Kaiser Permanente Northwest (KPNW); Kathleen Bow, Kaiser Permanente Hawai'i (KPHI); Jennifer Carney, KPHI; Ned Colange, Denver Public Health of Colorado; Christopher Cold, Marshfield Clinic Research Foundation (MCRF); Deanna Cross, MCRF; YeeHwa Daida, KPHI; Padmavati Dandamudi, KPNW; Robert Davis, KPG; Teri Defor, HPIER; Thomas Delate, Kaiser Permanente Colorado (KPCO); Jessica Engel, MCRF; Rene Faryniarz, HFHS; Heather Spencer Feigelson, KPCO (lead author); Thomas Flottemesch, HPIER; Mamie Ford, KPNC; Jared Freml, KPCO; Kellyan Funk, KPCO; Joan Garhy, HFHS; Katrina Goddard, KPNW; Julie Harris, Kaiser Permanente Northern California (KPNC); Mia Hemmes, Kaiser Permanente Georgia (KPG); Paul Hitz, MCRF; Rebecca Holmes, KPNW; Stacey Honda, KPHI; Stephen Houston, KPNW; Karl Huang, KPNC; Clara Hwang, HFHS; Sheng-Fang Jiang, KPNC; Monique Johnson, Oregon Health and Sciences University (OHSU); Tia Kauffman, KPNW; Terrie Kitchner, MCRF; Richard Krajenta HFHS; Tatjana Kolevska, KPNC; Lawrence Kushi, KPNC; Smyth Lai, KPNW; Anh Q Le, KPCO; Loic LeMarchand, University of Hawaii; Petra Liljestrand, KPNC;Jennifer Lin KPNW; Celeste Machen, KPNW; Michael Maciosek, HPIER; Catherine McCarty, MCRF; Jennifer McCance, KPCO; Richard Meenan, KPNW; Alex Menter, KPCO; Jill Mesa,KPNW; Paul Meier, HFHS; Anousheh Mirabedi, KPNC; Judith Morse, KPNC; Kristin Muessig,KPNW; Andrew Nelson, HPIER; Carsie Nyirenda, KPCO; Maureen O'Keeffe Rosetti, KPNW; Kim Olson, KPNW; Suzanne O'Neill, Georgetown University; Adedayo Onitilo, MCRF; Brian Owens, HPIER;Pamala Pawloski, HPIER; Alanna Rahm, KPCO; C. Sue Richards, OHSU; Denise Schwarzkopf, KPNW; Caitlin Senger, KPNW; Carol Somkin KPNC; Amy Stone-Murai, KPHI;Nagendra Tirumali, KPNW; Laurie VanArman, HPIER; David Veenstra, University of Washington; Aleli Vinoya, KPHI; Carmel Wax, KPNW; Elizabeth Webber, KPNW; Jennifer Webster, KPNW; Evelyn Whitlock KPNW; Andrew Williams, KPHI; Carmen Wong, KPHI; Chan Zeng, KPCO; Sarah Zuber, KPNW. Purpose: Epidermal growth factor receptor (EGFR) inhibitors are approved for treating metastatic colorectal cancer (CRC); KRAS mutation testing is recommended prior to treatment. We conducted a non-inferiority analysis to examine whether KRAS testing has impacted survival in CRC patients. Patients and Methods: We included 1186 metastatic CRC cases from seven health plans. A cutpoint of July, 2008, was used to define two KRAS testing time period groups: "pre-testing" (n = 760 cases) and ''post-testing'' (n = 426 cases). Overall survival (OS) was estimated, and the difference in median OS between the groups was calculated. The lower bound of the one-sided 95% confidence interval (CI) for the difference in survival was used to test the null hypothesis of post-testing inferiority. Multivariable Cox regression models were constructed to adjust for covariates. Results: The median unadjusted OS was 15.4 months (95% CI: 14.0-17.5) and 12.8 months (95% CI: 10.0-15.2) in the pre-and post-testing groups, respectively. The OS difference was -2.6 months with one-sided 95% lower confidence bound of -5.13 months, which was less than the non-inferiority margin (-5.0 months, unadjusted p = 0.06), leading to a failure to reject inferiority of OS in the post-testing period. In contrast, in the adjusted analysis, OS non-inferiority was identified in the post-testing period (p = 0.001). Sensitivity analyses using cutpoints before and after July, 2008, also met the criteria for non-inferiority. Conclusion: Implementation of KRAS testing did not influence CRC OS. Our data support the use of KRAS testing to guide administration of EGFR inhibitors for treatment of metastatic CRC without diminished OS.