A model-based cost-effectiveness analysis of pharmacogenomic panel testing in cardiovascular disease management: preemptive, reactive, or none?

PURPOSE: Pharmacogenomics (PGx) studies how inherited genetic variations in individuals affect drug absorption, distribution, and metabolism. PGx panel testing can potentially help improve efficiency and accuracy in individualizing therapy. This study compared the cost-effectiveness between preemptive PGx panel testing, reactive PGx panel testing and usual care (no testing) in cardiovascular disease management. METHODS: We developed a decision analytic model from the US payer's perspective for a hypothetical cohort of 10,000 patients ≥45 years old, using a short-term decision tree and long-term Markov model. The testing panel included the following gene-drug pairs: CYP2C19-clopidogrel, CYP2C9/VKORC1-warfarin, and SLCO1B1-statins with 30 test-return days. Costs were reported in 2019 US dollars and effectiveness was measured in quality-adjusted life years (QALYs). The primary outcome was incremental cost-effectiveness ratio (ICER = ΔCost/ΔQALY), assuming 3% discount rate for costs and QALYs. Scenario and probabilistic sensitivity analyses were performed to assess the impact of demographics, risk level, and follow-up timeframe. RESULTS: Preemptive testing was found to be cost-effective compared with usual care (ICER $86,227/QALY) at the willingness-to-pay threshold of $100,000/QALY while reactive testing was not (ICER $148,726/QALY). Sensitivity analyses suggested that our cost-effectiveness results were sensitive to longer follow-up, and the age group 45-64 years. CONCLUSION: Compared with usual care, preemptive PGx panel testing was cost-effective in cardiovascular disease management.

Systematic review of the evidence on the cost-effectiveness of pharmacogenomics-guided treatment for cardiovascular diseases.

PURPOSE: To examine the evidence on the cost-effectiveness of implementing pharmacogenomics (PGx) in cardiovascular disease (CVD) care. METHODS: We conducted a systematic review using multiple databases from inception to 2018. The titles and abstracts of cost-effectiveness studies on PGx-guided treatment in CVD care were screened, and full texts were extracted. RESULTS: We screened 909 studies and included 46 to synthesize. Acute coronary syndrome and atrial fibrillation were the predominantly studied conditions (59%). Most studies (78%) examined warfarin-CYP2C9/VKORC1 or clopidogrel-CYP2C19. A payer's perspective was commonly used (39%) for cost calculations, and most studies (46%) were US-based. The majority (67%) of the studies found PGx testing to be cost-effective in CVD care, but cost-effectiveness varied across drugs and conditions. Two studies examined PGx panel testing, of which one examined pre-emptive testing strategies. CONCLUSION: We found mixed evidence on the cost-effectiveness of PGx in CVD care. Supportive evidence exists for clopidogrel-CYP2C19 and warfarin-CYP2C9/VKORC1, but evidence is limited in other drug-gene combinations. Gaps persist, including unclear explanation of perspective and cost inputs, underreporting of study design elements critical to economic evaluations, and limited examination of PGx panel and pre-emptive testing for their cost-effectiveness. This review identifies the need for further research on economic evaluations of PGx implementation.

Preoperative endoscopic ultrasound-guided fine needle aspiration does not impair survival of patients with resected pancreatic cancer.

OBJECTIVE: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) allows preoperative tissue confirmation of malignancy, but fear of tumour cell dissemination along the needle track has limited its use. We hypothesised that if tumour cell dissemination occurs with EUS-FNA, survival after complete resection would be impaired. We aimed to evaluate the association of preoperative EUS-FNA with long-term outcomes of patients with resected pancreatic cancer. DESIGN: Using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified patients with locoregional pancreatic cancer who underwent curative intent surgery from 1998 to 2009. The patients who received EUS-FNA within the peridiagnostic period were included in the EUS-FNA group. Patients who did not receive EUS evaluation or who underwent EUS without FNA were included in the non-EUS-FNA group. Overall survival and pancreatic cancer-specific survival were compared after controlling for relevant covariates. RESULTS: A total of 2034 patients with pancreatic cancer were included (90% pancreatic adenocarcinoma). Of these, 498 (24%) patients were in EUS-FNA group. Patients with multiple comorbidities and more recent diagnosis were more likely to receive EUS-FNA. In multivariate analysis, after controlling for age, race, gender, tumour histology, tumour stage, tumour grade, tumour location, SEER site, year of diagnosis, undergoing percutaneous aspiration/biopsy, Charlson Comorbidity Index, radiation and chemotherapy, EUS-FNA was marginally associated with improved overall survival (HR 0.84, 95% CI 0.72 to 0.99), but did not affect cancer-specific survival (HR 0.87, 95% CI 0.74 to 1.03). CONCLUSIONS: Preoperative EUS-FNA was not associated with increased risk of mortality. These data suggest that EUS-FNA can be safely performed for the work-up of suspicious pancreatic lesions.

Follow up care for adults with diabetes treated for severe hypoglycemia by emergency medical Services, 2013-2019.

AIMS: To capture the types and content of healthcare encounters following severe hypoglycemia requiring emergency medical services (EMS) and to correlate their features with subsequent risk of severe hypoglycemia. METHODS: A retrospective cohort was obtained by linking data from a multi-state health system and an advanced life support ambulance service. This identified 1977 EMS calls by 1028 adults with diabetes experiencing hypoglycemia between 1/1/2013-12/31/2019. We evaluated the healthcare engagement over the following 7 days to identify rates of discussion of hypoglycemia, change of diabetes medications, glucagon prescribing, and referral for diabetes. RESULTS: Rates of hypoglycemia discussion increased with escalating levels of care, from 11.5 % after EMS calls without emergency department (ED) transport or outpatient clinical encounters to 98 % among hospitalized patients with outpatient follow-up. EMS transport and outpatient follow-up were associated with significantly higher odds of discussion of hypoglycemia (OR 60 and OR 22.1, respectively). Interventions were not impacted by previous severe hypoglycemia within 30 days. Prescription of glucagon was rare among all patients. CONCLUSIONS: Interventions to prevent recurrent hypoglycemia increase with escalating levels of care but remain inadequate and inconsistent with clinical guidelines. Greater attention is needed to ensure timely diabetes-related follow-up and treatment modification for patients experiencing severe hypoglycemia.

Association between primary care appointment lengths and subsequent ambulatory reassessment, emergency department care, and hospitalization: a cohort study.

BACKGROUND: To meet increasing demand, healthcare systems may leverage shorter appointment lengths to compensate for a limited supply of primary care providers (PCPs). Limiting the time spent with patients when evaluating acute health needs may adversely affect quality of care and increase subsequent healthcare utilization; however, the impact of brief duration appointments on healthcare utilization in the United States has not been examined. This study aimed to assess for potential inferiority of shorter (15-min) primary care appointments compare to longer (≥ 30-min appointments) with respect to downstream healthcare utilization within 7 days of the initial appointment. METHODS: We performed a retrospective cohort study using electronic health record (EHR), billing, and administrative scheduling data from five primary care practices in Midwest United States. Adult patients seen for acute Evaluation & Management visits between 10/1/2015 and 9/30/2017 were included. Patients scheduled for 15-min appointments were propensity score matched to those scheduled for ≥ 30-min. Multivariate regression models examined the effects of appointment length on repeat primary care visits, emergency department (ED) visits, hospitalizations, and diagnostic services within 7 days following the visit. Models were adjusted for baseline patient, visit, and provider characteristics. A non-inferiority approach was employed. RESULTS: We identified 173,758 total index visits (6.5% 15-min, 93.5% ≥ 30-min). 11,222 15-min appointments were matched to a comparable ≥ 30-min visit. Longer appointments were more frequent among trainee physicians, patients with limited English proficiency, and patients with more comorbidities. There was no significant effect of scheduled appointment length on the incidence of repeat primary care visits (OR = 0.983, CI: 0.873, 1.106) or ED visits (OR = 0.856, CI: 0.700, 1.047). Shorter appointments were associated with lower rates of subsequent hospitalizations (OR = 0.689, CI: 0.504, 0.941), laboratory services (OR = 0.682, CI: 0.643, 0.724), and diagnostic imaging services (OR = 0.499, CI: 0.466, 0.534). None of the non-inferiority thresholds were exceeded. CONCLUSIONS: For select indications and select low risk patients, shorter duration appointments may be a non-inferior option for scheduling of patient care that will not result in greater downstream healthcare utilization. These findings can help inform healthcare delivery models and triage processes as health systems and payers re-examine how to best deliver care to growing patient populations.

Management and Outcomes of Severe Hypoglycemia Treated by Emergency Medical Services in the U.S. Upper Midwest.

OBJECTIVE: To examine factors associated with emergency department (ED) transport after hypoglycemia treated by emergency medical services (EMS) and assess the impact of ED transport on severe hypoglycemia recurrence. RESEARCH DESIGN AND METHODS: We retrospectively analyzed electronic health records of a multistate advanced life support EMS provider and an integrated healthcare delivery system serving an overlapping geographic area in the upper Midwest. For adults with diabetes treated by EMS for hypoglycemia between 2013 and 2019, we examined rates of ED transport, factors associated with it, and its impact on rates of recurrent hypoglycemia requiring EMS, ED, or hospital care within 3, 7, and 30 days. RESULTS: We identified 1,977 hypoglycemia-related EMS encounters among 1,028 adults with diabetes (mean age 63.5 years [SD 17.7], 55.2% male, 87.4% non-Hispanic White, 42.4% rural residents, and 25.6% with type 1 diabetes), of which 46.4% resulted in ED transport (31.1% of calls by patients with type 1 diabetes and 58.0% of calls by patients with type 2 diabetes). Odds of ED transport were lower in patients with type 1 diabetes (odds ratio [OR] 0.44 [95% CI 0.31-0.62] vs. type 2 diabetes) and higher in patients with prior ED visits (OR 1.38 [95% CI 1.03-1.85]). Within 3, 7, and 30 days, transported patients experienced recurrent severe hypoglycemia 2.8, 5.2, and 10.6% of the time, respectively, compared with 7.4, 11.2, and 22.8% of the time among nontransported patients (all P < 0.001). This corresponds to OR 0.58 (95% CI 0.42-0.80) for recurrent severe hypoglycemia within 30 days for transported versus nontransported patients. When subset by diabetes type, odds of recurrent severe hypoglycemia among transported patients were 0.64 (95% CI 0.43-0.96) and 0.42 (95% CI 0.24-0.75) in type 1 and type 2 diabetes, respectively. CONCLUSIONS: Transported patients experienced recurrent hypoglycemia requiring medical attention approximately half as often as nontransported patients, reinforcing the importance of engaging patients in follow-up to prevent recurrent events.

Impact of the Registered Nurse Clinical Liaison Role in Ambulatory Care on Transitions of Care: A Retrospective Cohort Study.

PURPOSE OF STUDY: To determine the relationship between engagement with the novel register nurse care liaison (RNCL) and enrollment in care management compared with usual care in hospitalized patients. PRIMARY PRACTICE SETTING: Patients in the hospital from January 1, 2019, to September 30, 2019, who would be eligible for care management. METHODOLOGY AND SAMPLE: This was a retrospective cohort study. The authors compared a group of 419 patients who utilized the services of the RNCL at any time during their hospital stay with the RNCL to a propensity matched control group of 833 patients, which consisted of patients who were hospitalized during the same time as the RNCL intervention group. Our primary outcome was enrollment in care management programs. Our secondary outcome was 30-day readmissions, emergency department (ED) use, and office visits. The authors compared baseline characteristics and outcomes across groups using Wilcoxon-Mann-Whitney and χ2 tests and performed an adjusted analysis using conditional logistic regression models controlling for patient education and previous health care utilization. RESULTS: The authors matched 419 patients who had engaged an RNCL to 833 patients in the usual care group; this comprised the analytic cohort for this study. The authors found 67.1% of patients enrolled in a care management program with RNCL compared with only 15.3% in usual care (p < .0001). The authors found higher rates of enrollment in all programs of care management. After the full adjustment, the odds ratio for enrollment in any program was 13.7 (95% confidence interval: 9.3, 20.2) for RNCL compared with usual care. There was no difference between groups with 30-day hospitalization or ED visit. CONCLUSION: In this matched study of 419 patients with RNCL engagement, the authors found significantly higher enrollment in all care management programs. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: These findings encourage further study of this care model. This could help enhance enrollment in care management programs, increase relationships between inpatient practice and ambulatory practice, as well as increase communication across the continuum of care.

Association of Fluoroquinolone Prescribing Rates With Black Box Warnings from the US Food and Drug Administration.

Importance: In 2013 and 2016, the US Food and Drug Administration (FDA) issued warnings and recommended limited use of fluoroquinolones for patients with certain acute conditions. It is not clear how prescribers have responded to these warnings. Objective: To analyze changes in prescribing of fluoroquinolones after the 2013 and 2016 FDA warnings and to examine the physician characteristics associated with these changes. Design, Setting, and Participants: This cross-sectional study used Medicare administrative claims data on Medicare fee-for-service beneficiaries and OneKey data on physicians and their organizations from January 1, 2011, to December 31, 2017. The sample was restricted to outpatient visits for sinusitis, bronchitis, and uncomplicated urinary tract infections. An interrupted time series approach was used to analyze the changes in the prescription rate after each FDA warning. Data analysis was performed between January 1, 2011, and December 31, 2017. Interventions: Two FDA black box warnings released in August 2013 and July 2016. Main Outcomes and Measures: The main outcome was an indicator for fluoroquinolone prescriptions in 3 periods: before the 2013 warning (baseline period), after the 2013 warning but before the 2016 warning (postwarning period 1), and after the 2016 warning (postwarning period 2). Results: The sample comprised 1 238 397 unique patients with a total of 2 720 071 outpatient acute care visits. Of this sample, 848 360 were women (68.5%), and the mean (SD) age was 69.7 (12.6) years. The immediate prescribing levels of fluoroquinolones in postwarning period 1 increased by 3.42 percentage points (95% CI, 3.23-3.62; P < .001) and declined by -0.77 percentage points (95% CI, -1.00 to -0.54; P < .001) in postwarning period 2. The prescribing trend increased by 0.08 percentage points per month (95% CI, 0.08-0.10; P < .001) in postwarning period 1 and 0.06 percentage points per month (95% CI, 0.04-0.08; P < .001) in postwarning period 2. In postwarning period 1, the prescribing levels for physicians who were affiliated with hospitals with a top 10th percentile case mix index vs those without such affiliation decreased by -1.13 percentage points (95% CI, -1.92 to -0.34; P = .005), whereas the levels for primary care physicians declined by -1.34 percentage points (95% CI, -1.78 to -0.88; P < .001) compared with non-primary care physicians in postwarning period 2. Physicians at teaching hospitals were the only ones who showed a decline in prescribing trend in postwarning period 1. Conclusions and Relevance: This cross-sectional study found an overall decline in prescribing of fluoroquinolones after the release of FDA warnings. Understanding the association of physician and organizational characteristics with fluoroquinolone prescribing behavior may ultimately help to identify mechanisms to improve de-adoption.

Outcomes of a Nursing Home-to-Community Care Transition Program.

OBJECTIVES: Most transitional care initiatives to reduce rehospitalization have focused on the transition that occurs between a patient's hospital discharge and return home. However, many patients are discharged from a skilled nursing facility (SNF) to their homes. The goal was to evaluate the effectiveness of the Mayo Clinic Care Transitions (MCCT) program (hereafter called program) among patients discharged from SNFs to their homes. DESIGN: Propensity-matched control-intervention trial. INTERVENTION: Patients in the intervention group received care management following nursing stay (a home visit and nursing phone calls). SETTING AND PARTICIPANTS: Patients enrolled after discharge from an SNF to home were matched to patients who did not receive intervention because of refusal, program capacity, or distance. Patients were aged ≥60 years, at high risk for hospitalization, and discharged from an SNF. METHODS: Program enrollees were matched through propensity score to nonenrollees on the basis of age, sex, comorbid health burden, and mortality risk score. Conditional logistic regression analysis examined 30-day hospitalization and emergency department (ED) use; Cox proportional hazards analyses examined 180-day hospital stay and ED use. RESULTS: Each group comprised 160 patients [mean (standard deviation) age, 85.4 (7.4) years]. Thirty-day hospitalization and ED rates were 4.4% and 10.0% in the program group and 3.8% and 10.0% in the group with usual care (P = .76 for hospitalization; P > .99 for ED). At 180 days, hospitalization and ED rates were 30.6% and 46.3% for program patients compared with 11.3% and 25.0% in the comparison group (P < .001). CONCLUSIONS AND IMPLICATIONS: We found no evidence of reduced hospitalization or ED visits by program patients vs the comparison group. Such findings are crucial because they illustrate how aggressive stabilization care within the SNF may mitigate the program role. Furthermore, we found higher ED and hospitalization rates at 180 days in program patients than the comparison group.

Comparing outcomes and costs among warfarin-sensitive patients versus warfarin-insensitive patients using The Right Drug, Right Dose, Right Time: Using genomic data to individualize treatment (RIGHT) 10K warfarin cohort.

Oral anticoagulant (OAC) therapy has been the main treatment approach for stroke prevention for decades. Warfarin is the most widely prescribed OAC in the United States, but is difficult to manage due to variability in dose requirements across individuals. Pharmacogenomics may mitigate risk concerns related to warfarin use by fostering the opportunity to facilitate individualized medicine approaches to warfarin treatment (e.g., genome-guided dosing). While various economic evaluations exist examining the cost-effectiveness of pharmacogenomics testing for warfarin, few observational studies exist to support these studies, with even fewer using genotype as the main exposure of interest. We examined a cohort of individuals initiating warfarin therapy between 2004 and 2017 and examined bleeding and cost outcomes for the year following initiation using Mayo Clinic's billing and administrative data, as well the Mayo Clinic Rochester Cost Data Warehouse. Analyses included descriptive summaries, comparison of characteristics across exposure groups, reporting of crude outcomes, and multivariate analyses. We included N = 1,143 patients for analyses. Just over a third of our study population (34.9%) carried a warfarin-sensitive phenotype. Sensitive individuals differed in their baseline characteristics by being of older age and having a higher number of comorbid conditions; myocardial infarction, diabetes, and cancer in particular. The occurrence of bleeding events was not significantly different across exposure groups. No significant differences across exposure groups existed in either the likelihood of incurring all-cause healthcare costs or in the magnitude of those costs. Warfarin-sensitive individuals were no more likely to utilize cardiovascular-related healthcare services; however, they had lower total and inpatient cardiovascular-related costs compared to warfarin-insensitive patients. No significant differences existed in any other categories of costs. We found limited evidence that warfarin-sensitive individuals have different healthcare spending than warfarin-insensitive individuals. Additional real-world studies are needed to support the traditional economic evaluations currently existing in the literature.

Identifying high-cost episodes in lower extremity joint replacement.

OBJECTIVES: To evaluate the ability of claims-based risk adjustment and incremental components of clinical data to identify 90-day episode costs among lower extremity joint replacement (LEJR) patients according to the Centers for Medicare & Medicaid Services (CMS) Comprehensive Care for Joint Replacement (CJR) program provisions. DATA SOURCES: Medicare fee-for-service (FFS) data for qualifying CJR episodes in the United States, and FFS data linked with clinical data from CJR-qualifying LEJR episodes performed at High Value Healthcare Collaborative (HVHC) and Mayo Clinic in 2013. HVHC and Mayo Clinic populations are subsets of the total FFS population to assess the additive value of additional pieces of clinical data in correctly assigning patients to cost groups. STUDY DESIGN: Multivariable logistic models identified high-cost episodes. DATA COLLECTION/EXTRACTION METHODS: Clinical data from participating health care systems merged with Medicare FFS data. PRINCIPAL FINDINGS: Our three populations consisted of 363 621 patients in the CMS population, 4881 in the HVHC population, and 918 in the Mayo population. When modeling per CJR specifications, we observed low to moderate model performance (CMS C-Stat = 0.714; HVHC C-Stat = 0.628; Mayo C-Stat = 0.587). Adding CMS-HCC categories improved identification of patients in the top 20% of episode costs (CMS C-Stat = 0.758, HVHC C-Stat = 0.692, Mayo C-Stat = 0.677). Clinical variables, particularly functional status in the population for which this was available (Mayo C-Stat = 0.783), improved ability to identify patients within cost groups. CONCLUSIONS: Policy makers could use these findings to improve payment adjustments for bundled LEJR procedures and in consideration of new data elements for reimbursement.

Implementation of Bar-Code Medication Administration to Reduce Patient Harm.

OBJECTIVE: To assess the impact of implementing bar-code medication administration (BCMA) technology on the rate of medication administration errors in the inpatient setting, specifically those that affect the patient and result in harm. PATIENTS AND METHODS: Implementation of the new technology began in September 2008 in a staged rollout of 4 or 5 units at a time in 11 separate waves. All corresponding medication administrations and voluntarily reported medication-related adverse events from March 1, 2007, through September 30, 2013, were included for analyses. Adherence to the use of BCMA technology and the number of adverse events were tracked and compared across the preimplementation period through follow-up. Actual errors, not potential errors, were included in the analysis. RESULTS: After the BCMA technology was introduced, reported medication administration errors decreased by 43.5%. More importantly, the rate of harmful medication errors decreased from 0.65 per 100,000 medications preintervention to 0.29 per 100,000 medications postintervention. This resulted in a 55.4% decrease in actual patient harm events. None of the errors at category E or higher was caused by BCMA factors. CONCLUSION: Consistent use of BCMA technology improves patient safety by decreasing the number of patients harmed by medication administration errors.

Effect of integrated community neurology on utilization, diagnostic testing, and access.

BACKGROUND: The primary care medical home (PCMH) aims to promote delivery of high-value health care. However, growing demand for specialists due to increasingly older adults with complicated and chronic disease necessitates development of novel care models that efficiently incorporate specialty expertise while maintaining coordination and continuity with the PCMH. We describe the effect of a model of integrated community neurology (ICN) on health care utilization, diagnostic testing, and access. METHODS: This is a retrospective, matched case-control comparison of patients referred to ICN for a face-to-face consultation over a 12-month period. The control group consisted of propensity score-matched patients referred to a non-colocated neurology practice during the study period. Administrative data were used to assess for diagnostic testing, visit utilization, and patient time to appointment. RESULTS: From October 1, 2014, to September 30, 2015, we identified 459 patients evaluated by ICN for a face-to-face visit and 459 matched controls evaluated by the non-colocated neurology practice. The majority of patients were Caucasian and female. ICN patients had lower odds of EMGs ordered (adjusted odds ratio [OR] 0.64; 95% confidence interval [CI] 0.46-0.89; p = 0.009), MRI brain (adjusted OR 0.60; 95% CI 0.45-0.79; p = 0.0004), or subsequent referral to outpatient neurology (adjusted OR 0.62; 95% CI 0.47-0.83; p = 0.001). ICN was not associated with an increase in emergency department visits, hospitalizations, or appointment wait time. CONCLUSIONS: The ICN model in a PCMH has the potential to reduce diagnostic testing and utilization.

Incorporating the Last Four Digits of Social Security Numbers Substantially Improves Linking Patient Data from De-identified Hospital Claims Databases.

OBJECTIVE: Assess algorithms for linking patients across de-identified databases without compromising confidentiality. DATA SOURCES/STUDY SETTING: Hospital discharges from 11 Mayo Clinic hospitals during January 2008-September 2012 (assessment and validation data). Minnesota death certificates and hospital discharges from 2009 to 2012 for entire state (application data). STUDY DESIGN: Cross-sectional assessment of sensitivity and positive predictive value (PPV) for four linking algorithms tested by identifying readmissions and posthospital mortality on the assessment data with application to statewide data. DATA COLLECTION/EXTRACTION METHODS: De-identified claims included patient gender, birthdate, and zip code. Assessment records were matched with institutional sources containing unique identifiers and the last four digits of Social Security number (SSNL4). PRINCIPAL FINDINGS: Gender, birthdate, and five-digit zip code identified readmissions with a sensitivity of 98.0 percent and a PPV of 97.7 percent and identified postdischarge mortality with 84.4 percent sensitivity and 98.9 percent PPV. Inclusion of SSNL4 produced nearly perfect identification of readmissions and deaths. When applied statewide, regions bordering states with unavailable hospital discharge data had lower rates. CONCLUSION: Addition of SSNL4 to administrative data, accompanied by appropriate data use and data release policies, can enable trusted repositories to link data with nearly perfect accuracy without compromising patient confidentiality. States maintaining centralized de-identified databases should add SSNL4 to data specifications.

Cervical cancer screening: a prospective cohort study of the effects of historical patient compliance and a population-based informatics prompted reminder on screening rates.

AIMS AND OBJECTIVES: The aim of this study was to assess the impact of historical screening compliance with the effectiveness of patient reminder letters on cervical cancer screening rates. METHOD: Using population-based informatics systems, women with no cervical cancer screening in the prior 3 years were identified in two primary care clinics, Mayo Family Clinic Northeast (NE; n = 1613) and Northwest (NW; n = 1088). Patients were divided into two compliance groups: overdue/unknown screening status at study start or previously compliant. The NE Clinic sent reminder letters over a 6 months window to patients eligible for screening at the study start or during the study that were also identified as employees/dependents (E/D). There were 795 intervention (NE Clinic E/D patients) and 1906 control subjects. Using an intent-to-treat analysis, differences in screening rates were assessed. RESULTS: A higher unadjusted screening rate was observed for the E/D group than the non-E/D group at both sites (32.7 versus 18.2% at NW, P < 0.001; 39.0 versus 14.7% at NE, P < 0.001). For the historically compliant group, unadjusted screening rates were higher for those who received letters (E/D subjects at NE) versus those who did not (E/D subjects at NW; 56.1 versus 44.5%, P = 0.01). No difference was observed between E/D subjects at NE (received letters) and NW (no letters) for the overdue/unknown group (27.4 versus 25.9%, P = 0.62). There was no difference in screening rates for non-E/D subjects at NE versus at NW (none of whom received letters) for both the compliant (24.2 versus 30.6%, P = 0.18) and the overdue/unknown groups (11.9 versus 13.0%, P = 0.59). Multivariate logistic regression models showed a significant overall effect of E/D status (P = 0.006), compliance group (P < 0.001), and the interaction between clinic site and E/D status (P = 0.04). CONCLUSION: Among insured women, reminder letters appear to improve cervical cancer screening rates for those with a history of screening compliance. Reminder letters appear insufficient to motivate women if screening is overdue. Further investigation of the cohort of women overdue for screening is needed to develop interventions to successfully target this group.