Digital recruitment and enrollment in a remote nationwide trial of screening for undiagnosed atrial fibrillation: Lessons from the randomized, controlled mSToPS trial.

OBJECTIVES: The advent of large databases, wearable technology, and novel communications methods has the potential to expand the pool of candidate research participants and offer them the flexibility and convenience of participating in remote research. However, reports of their effectiveness are sparse. We assessed the use of various forms of outreach within a nationwide randomized clinical trial being conducted entirely by remote means. METHODS: Candidate participants at possibly higher risk for atrial fibrillation were identified by means of a large insurance claims database and invited to participate in the study by their insurance provider. Enrolled participants were randomly assigned to one of two groups testing a wearable sensor device for detection of the arrhythmia. RESULTS: Over 10 months, the various outreach methods used resulted in enrollment of 2659 participants meeting eligibility criteria. Starting with a baseline enrollment rate of 0.8% in response to an email invitation, the recruitment campaign was iteratively optimized to ultimately include website changes and the use of a five-step outreach process (three short, personalized emails and two direct mailers) that highlighted the appeal of new technology used in the study, resulting in an enrollment rate of 9.4%. Messaging that highlighted access to new technology outperformed both appeals to altruism and appeals that highlighted accessing personal health information. CONCLUSIONS: Targeted outreach, enrollment, and management of large remote clinical trials is feasible and can be improved with an iterative approach, although more work is needed to learn how to best recruit and retain potential research participants. TRIAL REGISTRATION: Clinicaltrials.govNCT02506244. Registered 23 July 2015.

Rationale and design of a home-based trial using wearable sensors to detect asymptomatic atrial fibrillation in a targeted population: The mHealth Screening To Prevent Strokes (mSToPS) trial.

Efficient methods for screening populations for undiagnosed atrial fibrillation (AF) are needed to reduce its associated mortality, morbidity, and costs. The use of digital technologies, including wearable sensors and large health record data sets allowing for targeted outreach toward individuals at increased risk for AF, might allow for unprecedented opportunities for effective, economical screening. The trial's primary objective is to determine, in a real-world setting, whether using wearable sensors in a risk-targeted screening population can diagnose asymptomatic AF more effectively than routine care. Additional key objectives include (1) exploring 2 rhythm-monitoring strategies-electrocardiogram-based and exploratory pulse wave-based-for detection of new AF, and (2) comparing long-term clinical and resource outcomes among groups. In all, 2,100 Aetna members will be randomized 1:1 to either immediate or delayed monitoring, in which a wearable patch will capture a single-lead electrocardiogram during the first and last 2 weeks of a 4-month period beginning immediately or 4 months after enrollment, respectively. An observational, risk factor-matched control group (n = 4,000) will be developed from members who did not receive an invitation to participate. The primary end point is the incidence of new AF in the immediate- vs delayed-monitoring arms at the end of the 4-month monitoring period. Additional efficacy and safety end points will be captured at 1 and 3 years. The results of this digital medicine trial might benefit a substantial proportion of the population by helping identify and refine screening methods for undiagnosed AF.

Patient-reported treatment satisfaction and choice of dosing frequency with biologic treatment for moderate to severe plaque psoriasis.

BACKGROUND: Moderate to severe plaque psoriasis has a serious effect on health-related quality of life. Patients treated with biologic medications place importance on satisfaction and treatment frequency options. We assessed patient-reported treatment satisfaction and dosing frequency choice with biologics. METHODS: We used a health care claims database to identify patients with moderate to severe plaque psoriasis. Participants completed the Treatment Satisfaction Questionnaire for Medication. Results were compared between patients experienced with biologics (adalimumab, etanercept, or ustekinumab) or not (cyclosporine or methotrexate). Participants were asked for their choices of dosing options of once every 1-2 weeks, 3-4 weeks, 1-2 months, or 2-3 months. Participants were also asked for their choices of dosing options of every 1, 2, 3, and so on up to every 12+ weeks. RESULTS: A total of 426 patients completed the survey (263 biologic-experienced and 163 biologic-naïve patients). Patient satisfaction with psoriasis treatment was significantly higher in the biologic-experienced cohort. The most frequently chosen option (38.8% of all participating patients) was every 2-3 months; 37.3% chose once every 1-2 weeks. Significant differences were found in the percentage of biologic-naïve patients choosing 2-3-month (49.7%) over 1-2-week (20.9%) dosing (P<0.001). Among biologic-experienced patients, the difference between the percentage of patients choosing the 2-3-month (35.7%) and 1-2-week (41.8%) options was not significant (P=0.264). The two most often week-specific intervals chosen by biologic-naïve patients were 12+ weeks (42.3%) and 4 weeks (15.6%). The biologic-experienced patients most often chose 12+ weeks (31.2%) and 1 week (25.9%). CONCLUSION: Patients using biologics reported satisfaction with their treatment, which may positively affect outcomes. Longer dosing intervals were chosen most frequently among all patients combined. Reports of patient satisfaction with prior treatments and choices regarding dosing frequency, among all other considerations, should be evaluated in determining an appropriate biologic medication for psoriasis.

Comparative multidatabase analysis of dosing patterns and infusion intervals for the first 12 infliximab infusions in patients with rheumatoid arthritis.

BACKGROUND: According to prescribing information for rheumatoid arthritis (RA) treatments in the United States, infliximab should be administered at weeks 1, 2, 6, and then every 8 weeks starting at a 3-mg/kg dose, with flexible dosing up to 10 mg/kg and/or every 4 weeks based on clinical response. OBJECTIVE: This study evaluated dosing and intervals of the first 12 infliximab infusions in patients with RA across multiple large administrative databases. METHODS: Data were obtained from 4 databases: HealthCore Integrated Research Database (HIRD), IMS LifeLink Health Plan Claims Database (IMS Lifelink), Premier Perspective Database (PPD), and Wolters Kluwer Pharma Solutions (WKPS). Patients were aged ≥18 years, diagnosed with RA, and naive to biologic therapy. Patients with other select inflammatory conditions were excluded. The induction period included infusions 1 through 3; the maintenance period included infusions 4 through 12. RESULTS: Observed dosing patterns from the HIRD, IMS LifeLink, PPD, and WKPS databases demonstrated minimal dose increases from the first infusion (93.5, 103.3, 58.8, and 73.2 mg, respectively) and from the first maintenance infusion (69.1, 64.3, 45.7, and 45.7 mg, respectively) to the highest dose during the first 12 infusions. The mean number of days between infusions in the maintenance period ranged from 53.3 to 63.5 in HIRD, 53.7 to 60.3 in IMS LifeLink, 53.4 to 59.4 in PPD, and 52.3 to 55.0 in the WKPS database. CONCLUSION: Data from multiple databases of patients with RA suggest that, in clinical practice, infliximab dosing and intervals are consistent with FDA prescribing information and remain relatively stable during the first 12 infusions.

Effect of a continuous measure of adherence with infliximab maintenance treatment on inpatient outcomes in Crohn's disease.

BACKGROUND: To assess the impact of a continuous measure of adherence with infliximab maintenance treatment in Crohn's disease (CD) during the first year of treatment on CD-related health care utilization, CD-related hospitalizations, inpatient costs, and length of hospital stay. PATIENTS AND METHODS: A retrospective claims analysis using the IMS LifeLink Health Plan Claims Database (September 1, 2004, to June 30, 2009) was conducted. Continuous enrollment for 12 months before and 12 months after the index date was required. Patients were required to have at least two claims with an International Classification of Diseases, 9th Revision, Clinical Modification diagnosis code for CD (555.xx) pre-index and be aged ≥ 18 years at index. Patients with three infusions during the first 56 days post-index and at least one infusion following day 56 post-index were considered to have maintenance therapy. Adherence and nonadherence were defined as a medication possession ratio of ≥ 80% and < 80%, respectively. RESULTS: Four hundred forty-eight patients were included in the analysis (mean age, 42.6 years; 56% female; mean ± standard deviation [SD] and median number of infliximab infusions, 7.35 ± 1.60 and 8). The number of patients who met the definition of adherence was 344 (77%). CD-related health care utilization was not significantly impacted by adherence except for ancillary services and radiology. Fewer adherent patients were hospitalized compared with nonadherent patients (9% versus 16%; P = 0.03). Adherent patients had fewer mean ± SD and median days in the hospital (5.5 ± 3.4 and 5 days) compared with nonadherent patients (13.1 ± 14.2 and 8 days; P = 0.01). Mean ± SD and median hospital costs were significantly greater for nonadherent patients ($40,822 ± $49,238 and $28,864) compared with adherent patients ($13,704 ± $10,816 and $9938; P = 0.002). CONCLUSION: Adherence with maintenance infliximab over 12 months was associated with lower rates of CD-related hospitalizations and inpatient costs and a shorter length of hospital stay.

Adalimumab, etanercept, and infliximab utilization patterns and drug costs among rheumatoid arthritis patients.

OBJECTIVES: To evaluate the utilization patterns of the anti-tumor necrosis factor (anti-TNF) agents Humira (adalimumab), Enbrel (etanercept), and Remicade (infliximab) in patients with rheumatoid arthritis (RA) and compare medication costs during the first year of treatment. (Humira is a registered trademark of Abbott Laboratories, IL; Enbrel is a registered trademark of Immunex Corporation, CA; and Remicade is a registered trademark of Janssen Biotech, Inc., PA). METHODS: This retrospective analysis of medical and pharmacy claims included patients who were aged ≥18 years, had ≥2 RA diagnosis codes, and had ≥365 days of persistence with the index anti-TNF. Patients excluded had claims for anti-TNF agents within 6 months before the index date. Refill patterns for adalimumab and etanercept, number of infliximab infusions, time between infusions, and dose per infusion were analyzed for 12 months. Direct anti-TNF medication costs were compared among anti-TNFs for the initial treatment year. RESULTS: Infliximab-treated patients (n = 457) were significantly older than adalimumab- (n = 337) or etanercept-treated patients (n = 902). Time between refills was longer than recommended for 28% and 30% of adalimumab and etanercept refill periods, respectively. Potential cumulative time without therapy was 33 days for adalimumab and 43 days for etanercept. Statistically significant differences in mean per-patient anti-TNF medication costs for the first year were reported for adalimumab, etanercept, and infliximab ($14,991, $13,361, and $18,139, respectively; p < 0.0001); however, a cost assessment using labeled dosing of the anti-TNF agents with optimal treatment compliance yielded comparable annual medication costs. LIMITATIONS: This analysis only evaluated utilization patterns for selected anti-TNF agents and was not inclusive of other medications that patients may have been using for RA. Absolute patient adherence could not be assessed due to lack of information on how patients were self-administering adalimumab and etanercept or if samples of the agents were made available. CONCLUSIONS: This study identified gaps in patients' refills compared with prescriber recommendations. The infliximab-treated group had infusion patterns consistent with prescribing information. Potential clinical and economic implications of dose attenuation with adalimumab and etanercept should be explored further.

Impact of infliximab adherence on Crohn's disease-related healthcare utilization and inpatient costs.

INTRODUCTION: Few published reports have described the impact of adherence with biologic agents on hospitalizations and inpatient costs in Crohn's disease (CD). METHODS: A retrospective claims analysis using the IMS LifeLink Health Plan Claims Database between September 1, 2004 and June 30, 2009 was conducted. Continuous enrollment for 12 months before and 12 months after the index date was required. Patients were required to have ≥2 claims with an International Classification of Diseases, 9th Edition, Clinical Modification diagnosis code for CD (555.xx) preindex, be ≥18 years of age at index, and have ≥4 infliximab infusions with a gap no greater than 12 weeks between each infusion. Patients with 7-9 infliximab infusions (12 months postindex) were considered adherent; patients with 4-6 infliximab infusions were considered nonadherent. RESULTS: In total, 638 patients were included in the analyses (mean age, 43 years; 58% female in the adherent group and 53% in the nonadherent group). The number of patients who met the definition of adherence was 466 (73%). A smaller proportion of adherent patients had a CD-related emergency room visit, compared with nonadherent patients (11% vs. 17%, P=0.029). A smaller proportion of adherent patients required CD-related hospitalization, compared with nonadherent patients (8% vs. 12%, P=0.117). Among those hospitalized, adherent patients had fewer mean [median] days in the hospital (5.9 [5] days), compared with nonadherent patients (12.8 [8] days, P=0.015). Mean [median] hospital costs were significantly lower for adherent patients ($13,427 [$9,352]), compared with nonadherent patients ($37,783 [$28,864], P=0.001). Multivariate analyses confirmed lower inpatient (P<0.001) costs for adherent versus nonadherent patients. CONCLUSION: Adherence with infliximab therapy during the first year of treatment in patients with CD was associated with a shorter hospital length of stay and lower inpatient costs compared with nonadherent patients. Strategies for increasing adherence rates to infliximab maintenance therapy may be valuable in reducing hospitalizations and inpatient costs in patients with CD.

Impact of persistence with infliximab on hospitalizations in ulcerative colitis.

OBJECTIVES: To assess infliximab infusion patterns in ulcerative colitis (UC) and assess the impact of persistence with infliximab maintenance therapy on UC-related hospitalizations, lengths of stay, and inpatient costs. STUDY DESIGN: Retrospective analysis of medical claims for UC patients newly initiating infliximab treatment. METHODS: Patients were aged >18 years and had 2 UC diagnosis codes, an infliximab index date between September 1, 2005, and January 31, 2008, and continuous enrollment for >12 months before and >14 months after the index date. Infliximab induction (first 56 days postindex) and maintenance (>56 days and <12 months postinduction) patterns were evaluated. Of patients with maintenance treatment, persistence was defined as a medication possession ratio (MPR) of >80%, and this group was compared with those without persistence (<80% MPR). RESULTS: Overall, 420 patients were included in the analysis; 84.3% (n = 354) continued to maintenance therapy. Maintenance infusion patterns were consistent with recommended prescribing information. A smaller proportion of patients with maintenance therapy persistence required hospitalization compared with patients without persistence (3.0% vs 20.4%; P <.001). Hospitalized patients with maintenance therapy persistence had significantly lower mean inpatient costs ($14,243 vs $32,745; P = .046), with a trend toward shorter mean lengths of stay (6.67 vs 9.71 days; P = .147) than patients without persistence. CONCLUSIONS: Infliximab maintenance therapy persistence in UC was associated with significantly fewer hospitalizations. Once hospitalized, patients with therapeutic persistence had significantly decreased inpatient costs.

The economic effect of oral linezolid versus intravenous vancomycin in the outpatient setting: the payer perspective.

Oral antibiotic therapy can reduce complications and costs compared with intravenous (IV) therapy. The object of this study was to determine the health economic and resource utilization effects of outpatient treatment with oral linezolid relative to IV vancomycin. Longitudinal claims data from 80 health care plans were used. Patients 18 years and older, who did not have osteomyelitis, with a pharmacy claim for linezolid or vancomycin between January 1, 2002 and March 31, 2004 were eligible. Clinical and resource utilization data were collected for 12 months before and 35 days after treatment. Patients treated with linezolid were matched with controls treated with vancomycin, based on propensity scoring. Direct medical costs paid by health plans were compared. A total of 1,048 matched pairs were identified. Demographic and clinical characteristics were comparable between groups. Patients with linezolid claims had lower resource utilization versus those with vancomycin claims during follow-up, including fewer mean physician office visits (4.1+/-5.7 vs. 8.4+/-13.8 visits; P< .001); lab/diagnostic claims (6.3+/-18.0 vs. 10.4 +/-15.2 claims; P< .001); pharmacy claims (7.3+/-8.1 vs. 13.6+/-17.4 claims; P< .001); emergency room visits (9.7% vs. 13.9%; P= .003) and hospitalization (15.3% vs. 19.1%; P= .024). Patients receiving vancomycin were more likely to be hospitalized or have an emergency room visit than patients receiving linezolid. Mean total adjusted cost was 4,707 dollars less for linezolid compared with vancomycin (8,401dollars vs. 13,108 dollars; P< .001). Similar trends were observed for patients matched based on complicated skin and soft tissue infection diagnosis. Outpatient treatment with oral linezolid was associated with significantly lower resource utilization and total medical costs compared with IV vancomycin.

Burden of illness among commercially insured patients with Alzheimer's disease.

BACKGROUND: The purpose of this study was to examine the direct costs of care for patients newly diagnosed with Alzheimer's disease (AD) by using retrospective healthcare claims data. METHODS: Patients aged 65 years or older with >or=1 claims containing a listed diagnosis of AD between January 1999 and November 2003 were selected. The first observed AD claim was deemed the index date. Control patients with no evidence of AD or dementia also were identified. Patients had a 12-month pre-index period and minimum 30-day follow-up. AD patients were matched to control patients on the basis of age, gender, and follow-up duration. Annualized utilization and costs were calculated; generalized linear models (GLM) were undertaken, controlling for demographic and clinical characteristics. Analyses focused on differences in costs among AD patients and controls. RESULTS: The average age of AD and control patients was 82 years; 38% were men (n = 2,475 AD; 4,950 controls). Average total costs for AD patients were more than five-fold higher compared with controls ($28,263 vs $5,880; P < .001), driven primarily by inpatient costs. Total costs were significantly higher (P < .001) for AD patients in GLM modeling, with diagnosis group (AD vs control) as the most important predictor. Adjusted annual costs per patient were also five-fold higher ($21,150 vs $4,053 for AD vs control, respectively) during the follow-up period. CONCLUSIONS: The annual economic burden of AD to third-party payers is more substantial than previously estimated ($3,805 to $8,200).

Effect of initial ziprasidone dose on length of therapy in schizophrenia.

OBJECTIVE: To examine the effects of initial ziprasidone dose on discontinuation rates, using retrospective integrated medical and pharmacy claims data. METHODS: Patients > or = 18 years with a diagnosis of schizophrenia or schizoaffective disorder and a ziprasidone claim between March 2001 and February 2003 who were continuously enrolled for at least six months before and three months after initiation of ziprasidone were included. They were stratified by initial daily dose (> or = 40 and < 80 mg [low] vs. > or = 80 and < 120 mg [medium] vs. 120-160 mg [high]). The six-month risk of discontinuation was examined using Cox proportional hazards models controlling for gender, psychiatric comorbidities, and pre-ziprasidone utilization of antipsychotics (atypical, conventional, none). RESULTS: The mean age of the sample (n=1058) was 38 years; 42% were male. The six-month risk of discontinuation was significantly lower in patients in the high-dose group as compared to the low-dose group (HR=0.737 for high-dose vs. low-dose, 95% CI=0.581, 0.935; P=0.012) and trended towards significance when comparing high-dose and medium-dose groups (HR=0.857 for high-dose vs. medium-dose, 95% CI=0.694, 1.059; P=0.153). CONCLUSIONS: Patients initiating ziprasidone therapy with an initial dose of at least 120 mg/day had better medication adherence compared to those initiating at lower doses. These findings confirm results seen in clinical trials suggesting improved efficacy and tolerability at higher ziprasidone doses.