BACKGROUND: Critical limb ischemia (CLI) is increasing in prevalence, and remains a significant source of mortality and limb loss. The decision to recommend surgical or endovascular revascularization for patients who are candidates for both varies significantly among providers and is driven more by individual preference than scientific evidence. METHODS AND RESULTS: The Best Endovascular Versus Best Surgical Therapy for Patients With Critical Limb Ischemia (BEST‐CLI) Trial is a prospective, randomized, multidisciplinary, controlled, superiority trial designed to compare treatment efficacy, functional outcomes, quality of life, and cost in patients undergoing best endovascular or best open surgical revascularization. Approximately 140 clinical sites in the United States and Canada will enroll 2100 patients with CLI who are candidates for both treatment options. A pragmatic trial design requires consensus on patient eligibility by at least 2 investigators, but leaves the choice of specific procedural strategy within the assigned revascularization approach to the individual treating investigator. Patients with suitable single‐segment of saphenous vein available for potential bypass will be randomized within Cohort 1 (n=1620), while patients without will be randomized within Cohort 2 (n=480). The primary efficacy end point of the trial is Major Adverse Limb Event–Free Survival. Key secondary end points include Re‐intervention and Amputation‐Free‐Survival and Amputation Free‐Survival. CONCLUSIONS: The BEST‐CLI trial is the first randomized controlled trial comparing endovascular therapy to open surgical bypass in patients with CLI to be carried out in North America. This landmark comparative effectiveness trial aims to provide Level I data to clarify the appropriate role for both treatment strategies and help define an evidence‐based standard of care for this challenging patient population. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02060630.
OBJECTIVE: With more antiepileptic drugs (AED) becoming available in generic form, we estimated the risk of seizure-related events associated with refilling generic AEDs and the effect of switching between different manufacturers of the same generic drug. METHODS: We designed a population-based case-crossover study using the Medicaid Analytic eXtract and a US commercial health insurance database. We identified 83,001 generic AED users who experienced a seizure-related hospital admission or emergency room visit between 2000 and 2013 and assessed whether they received a refill of the same AED from the same manufacturer or a different manufacturer. Patients served as their own controls and conditional logistic regression was used to compare exposure to a refill during the hazard period, defined as days 2-36 preceding the seizure-related event, to exposure during the control period, defined as days 51-85 preceding the seizure-related event. RESULTS: Generic AED refilling was associated with an 8% increase in the odds of seizure-related events (odds ratio [OR] 1.08; 95% confidence interval [CI] 1.06-1.11). The OR following a switch to a different manufacturer of the same AED was 1.09 (95% CI 1.03-1.15); however, after adjusting for the process of refilling, there was no association between switching and seizure-related hospital visits (OR 1.00; 95% CI 0.94-1.07). CONCLUSIONS: Among patients on a generic AED, refilling the same AED was associated with an elevated risk of seizure-related event; however, there was no additional risk from switching during that refill to a different manufacturer. Generic AEDs available to US patients, with Food and Drug Administration-validated bioequivalence, appear to be safe clinical choices.
OBJECTIVE: The use of retail purchasing data may improve adherence prediction over approaches using healthcare insurance claims alone.
DESIGN: Retrospective. Setting and participants: A cohort of patients who received prescription medication benefits through CVS Caremark, used a CVS Pharmacy ExtraCare Health Care (ECHC) loyalty card, and initiated a statin medication in 2011.
OUTCOME: We evaluated associations between retail purchasing patterns and optimal adherence to statins in the 12 subsequent months.
RESULTS: Among 11 010 statin initiators, 43% were optimally adherent at 12 months of follow-up. Greater numbers of store visits per month and dollar amount per visit were positively associated with optimal adherence, as was making a purchase on the same day as filling a prescription ( p<0.0001 for all). Models to predict adherence using retail purchase variables had low discriminative ability (C-statistic: 0.563), while models with both clinical and retail purchase variables achieved a C-statistic of 0.617.
CONCLUSIONS: While the use of retail purchases may improve the discriminative ability of claims-based approaches, these data alone appear inadequate for adherence prediction, even with the addition of more complex analytical approaches. Nevertheless, associations between retail purchasing behaviours and adherence could inform the development of quality improvement interventions.
OBJECTIVES: Medication discrepancies at the time of hospital discharge are common and can harm patients. Medication reconciliation by pharmacists has been shown to prevent such discrepancies and the adverse drug events (ADEs) that can result from them. Our objective was to estimate the economic value of nontargeted and targeted medication reconciliation conducted by pharmacists and pharmacy technicians at hospital discharge versus usual care. STUDY DESIGN: Discrete-event simulation model. METHODS: We developed a discrete-event simulation model to prospectively model the incidence of drug-related events from a hospital payer’s perspective. The model assumptions were based on data published in the peerreviewed literature. Incidences of medication discrepancies, preventable ADEs, emergency department visits, rehospitalizations, costs, and net benefit were estimated. RESULTS: The expected total cost of preventable ADEs was estimated to be $472 (95% credible interval [CI], $247-$778) per patient with usual care. Under the base-case assumption that medication reconciliation could reduce medication discrepancies by 52%, the cost of preventable ADEs could be reduced to $266 (95% CI, $150-$423), resulting in a net benefit of $206 (95% CI, $73-$373) per patient, after accounting for intervention costs. A medication reconciliation intervention that reduces medication discrepancies by at least 10% could cover the initial cost of intervention. Targeting medication reconciliation to high-risk individuals would achieve a higher net benefit than a nontargeted intervention only if the sensitivity and specificity of a screening tool were at least 90% and 70%, respectively. CONCLUSIONS: Our study suggests that implementing a pharmacist-led medication reconciliation intervention at hospital discharge could be cost saving compared with usual care.
BACKGROUND: The incidence of opioid-related death in women has increased 5-fold over the past decade. For many women, their initial opioid exposure will occur in the setting of routine medical care. Approximately 1 in 3 deliveries in the United States is by cesarean, and opioids are commonly prescribed for postsurgical pain management. OBJECTIVE: The objective of this study was to determine the risk that opioid-naive women prescribed opioids after cesarean delivery will subsequently become consistent prescription opioid users in the year following delivery and to identify predictors for this behavior. STUDY DESIGN: We identified women in a database of commercial insurance beneficiaries who underwent cesarean delivery and who were opioid naive in the year prior to delivery. To identify persistent users of opioids, we used trajectory models, which group together patients with similar patterns of medication filling during follow-up, based on patterns of opioid dispensing in the year following cesarean delivery. We then constructed a multivariable logistic regression model to identify independent risk factors for membership in the persistent user group. RESULTS: A total of 285 of 80,127 (0.36%, 95% confidence interval, 0.32-0.40), opioid-naive women became persistent opioid users (identified using trajectory models based on monthly patterns of opioid dispensing) following cesarean delivery. Demographics and baseline comorbidity predicted such use with moderate discrimination (c statistic = 0.73). Significant predictors included a history of cocaine abuse (risk, 7.41%; adjusted odds ratio, 6.11, 95% confidence interval, 1.03-36.31) and other illicit substance abuse (2.36%; adjusted odds ratio, 2.78, 95% confidence interval, 1.12-6.91), tobacco use (1.45%; adjusted odds ratio, 3.04, 95% confidence interval, 2.03-4.55), back pain (0.69%; adjusted odds ratio, 1.74, 95% confidence interval, 1.33-2.29), migraines (0.91%; adjusted odds ratio, 2.14, 95% confidence interval, 1.58-2.90), antidepressant use (1.34%; adjusted odds ratio, 3.19, 95% confidence interval, 2.41-4.23), and benzodiazepine use (1.99%; adjusted odds ratio, 3.72, 95% confidence interval, 2.64-5.26) in the year prior to the cesarean delivery. CONCLUSION: A very small proportion of opioid-naive women (approximately 1 in 300) become persistent prescription opioid users following cesarean delivery. Preexisting psychiatric comorbidity, certain pain conditions, and substance use/abuse conditions identifiable at the time of initial opioid prescribing were predictors of persistent use.
BACKGROUND: The use of oral P2Y12 receptor inhibitors after acute myocardial infarction (MI) can reduce risks of subsequent major adverse cardiovascular events (composite of all-cause death, recurrent MI, and stroke), yet medication persistence is suboptimal. Although copayment cost has been implicated as a factor influencing medication persistence, it remains unclear whether reducing or eliminating these costs can improve medication persistence and/or downstream clinical outcomes. DESIGN: ARTEMIS is a multicenter, cluster-randomized clinical trial designed to examine whether eliminating patient copayment for P2Y12 receptor inhibitor therapy affects medication persistence and clinical outcomes. We will enroll approximately 11,000 patients hospitalized for acute ST-elevation and non-ST-elevation MI at 300 hospitals. Choice and duration of treatment with a P2Y12 receptor inhibitor will be determined by the treating physician. Hospitals randomized to the copayment intervention will provide vouchers to cover patients' copayments for their P2Y12 receptor inhibitor for up to 1 year after discharge. The coprimary end points are 1-year P2Y12 receptor inhibitor persistence and major adverse cardiovascular events. Secondary end points include choice of P2Y12 receptor inhibitor, patient-reported outcomes, and postdischarge cost of care. CONCLUSION: ARTEMIS will be the largest randomized assessment of a medication copayment reduction intervention on medication persistence, clinical outcomes, treatment selection, and cost of care after acute MI.
BACKGROUND: Variation in physician adoption of new medications is poorly understood. Traditional approaches (eg, measuring time to first prescription) may mask substantial heterogeneity in technology adoption. OBJECTIVE: Apply group-based trajectory models to examine the physician adoption of dabigratran, a novel anticoagulant. METHODS: A retrospective cohort study using prescribing data from IMS Xponent on all Pennsylvania physicians regularly prescribing anticoagulants (n=3911) and data on their characteristics from the American Medical Association Masterfile. We examined time to first dabigatran prescription and group-based trajectory models to identify adoption trajectories in the first 15 months. Factors associated with rapid adoption were examined using multivariate logistic regressions. OUTCOMES: Trajectories of monthly share of oral anticoagulant prescriptions for dabigatran. RESULTS: We identified 5 distinct adoption trajectories: 3.7% rapidly and extensively adopted dabigatran (adopting in 55 y). CONCLUSIONS: Trajectories of physician adoption of dabigatran were highly variable with significant differences across specialties. Heterogeneity in physician adoption has potential implications for the cost and effectiveness of treatment.
OBJECTIVE: Several trials suggest that triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) and biologic disease-modifying antirheumatic drugs (bDMARD) have similar efficacy in rheumatoid arthritis (RA). We investigated intensification to triple therapy after initial non-biologic (nbDMARD) prescription among patients with RA. METHODS: We used US insurance claims data to evaluate triple therapy use from 2009-2014. Patients with a visit for RA and initial nbDMARD prescription were included. Frequencies and rates to intensification to triple therapy or bDMARD were calculated. We evaluated whether sociodemographic, temporal, geographic, clinical, and healthcare utilization factors were associated with triple therapy intensification using Cox regression. Among those who intensified therapy, we investigated factors associated with triple therapy use by logistic regression. RESULTS: There were 24,576 patients initially with mean age of 50.3 (SD 12.3) years, and 78% were female. During the study period, 2,739 (11.1%) intensified treatment to bDMARD compared to 181 (0.7%) who intensified to triple therapy. There was no significant change in triple therapy use across calendar years. Patients who intensified to triple therapy were more likely to use glucocorticoids (HR 1.91, 95%CI 1.41-2.60) compared to no glucocorticoids and more likely to use nonsteroidal anti-inflammatory drugs (NSAID, HR 1.48, 95%CI 1.10-1.99) compared to no NSAID use within 180 days of initial nbDMARD prescription. Among those who intensified treatment to triple therapy or bDMARD, significant associations for triple therapy use included older age, US region (highest odds for triple therapy use in the West, lowest odds for triple therapy use in the Northeast), glucocorticoid use, and lower number of outpatient visits within 180 days of initial nbDMARD prescription. CONCLUSION: Despite reports published during the study period suggesting equivalent efficacy of triple therapy and bDMARDs for RA, the use of triple therapy was infrequent and did not increase over time in this large nationwide study. This article is protected by copyright. All rights reserved.
OBJECTIVE: To explore the association between unexpected potentially disruptive life events in a patient or family member that may challenge an individual's ability to take medications as prescribed and the discontinuation of evidence-based medications for common, chronic conditions. Understanding the relationship between medication adherence and life stressors, especially those that can be identified using administrative data, may help identify patients at risk of non-adherence. DESIGN: Observational self-controlled case-crossover design. SETTING: Individuals in a nationally representative US commercial health insurance database. PARTICIPANTS: Adult individuals who initiated an oral hypoglycaemic, antihypertensive and/or statin and subsequently stopped the medication for >/=90 days. MAIN OUTCOME MEASURE: Potentially disruptive life events among patients and their family members measured in the 30 days just before the medication was discontinued ('hazard period') compared with the 30 days before this period ('control period'). These events included personal injury, hospitalisation, emergency room visits, changes in insurance coverage, acute stress or acute anxiety. RESULTS: Among the 326 519 patients meeting study criteria who discontinued their chronic disease medications, 88 896 (27.2%) experienced at least one potentially disruptive life event. Newly experiencing an injury (OR: 1.26, 95% CI 1.12 to 1.42), an emergency room visit (OR: 1.19, 95% CI 1.13 to 1.26) and acute stress (OR: 1.19, 95% CI 1.08 to 1.31) were associated with discontinuation. Life events among patients' family members did not appear to be associated with medication discontinuation or occurred less frequently just prior to discontinuation. CONCLUSIONS: Potentially disruptive life events among individuals identified using routinely collected claims data are associated with discontinuation of chronic disease medications. Awareness of these events may help providers or payers identify patients at risk of non-adherence to maximise patient outcomes.
Background Approximately half of patients with chronic cardiometabolic conditions are nonadherent with their prescribed medications. Interventions to improve adherence have been only modestly effective because they often address single barriers to adherence, intervene at single points in time, or are imprecisely targeted to patients who may not need adherence assistance. Objective To evaluate the effect of a multicomponent, behaviorally tailored pharmacist-based intervention to improve adherence to medications for diabetes, hypertension, and hyperlipidemia. Trial design The STIC2IT trial is a cluster-randomized pragmatic trial testing the impact of a pharmacist-led multicomponent intervention that uses behavioral interviewing, text messaging, mailed progress reports, and video visits. Targeted patients are those who are nonadherent to glucose-lowering, antihypertensive, or statin medications and who also have evidence of poor disease control. The intervention is tailored to patients' individual health barriers and their level of health activation.We cluster-randomized 14 practice sites of a large multispecialty group practice to receive either the pharmacist-based intervention or usual care. STIC2IT has enrolled 4,076 patients who will be followed up for 12 months after randomization. The trial's primary outcome is medication adherence, assessed using pharmacy claims data. Secondary outcomes are disease control and health care resource utilization. Conclusion This trial will determine whether a technologically enabled, behaviorally targeted pharmacist-based intervention results in improved adherence and disease control. If effective, this strategy could be a scalable method of offering tailored adherence support to those with the greatest clinical need.
Prescription opioid misuse is a major public health issue in the United States. Since the late 1990s, sales of prescription opioids have risen 4-fold, and the rates of admissions for substance use treatment and of death from opioid overdose have grown proportionately.1 In response, training programs about the appropriate prescribing of opioid therapy have been developed, prescription monitoring programs implemented, and access to naloxone facilitated to reduce deaths among people who overdose. In general, these strategies focus on detecting and preventing harm in those who are already dependent on or misusing opioids. Although the impact of many of these programs is uncertain, the opioid epidemic continues to grow.
OBJECTIVES: The burden of visiting pharmacies to fill medications is a central contributor to nonadherence to maintenance medications.Recently, pharmacies have begun offering services that align prescription fill dates to allow patients to pick up all medications on a single visit. We evaluated the prevalence and structure of synchronization programs and evidence of their impact on adherence and clinical outcomes.STUDY DESIGN: Mixed-methods approach consisting of semistructured interviews, data from surveillance activities, and a systematic literature review. METHODS: We conducted interviews with opinion leaders from nonprofit advocacy organizations and exemplary synchronization programs. Program prevalence was determined using data from regular surveillance efforts. A literature review included Medline,EMBASE, Google Scholar, and general Internet searches.RESULTS: Synchronization programs exist in approximately 10%of independent, 6% of stand-alone chain, and 11% of retail store pharmacies. The majority of programs include a monthly pharmacist appointment and reminder communication. Programs reported the importance of pharmacist buy-in, technology to track and recruit patients, links to other healthcare services, and flexible solutions for managing costs and communication preferences.Although existing peer-reviewed literature suggests that synchronization improves adherence, more evidence is needed to evaluate its impact on patient-centered outcomes.CONCLUSIONS: As medication synchronization programs shift directions and compete for patients and payer resources, it will be more important than ever to rigorously evaluate their ability to improve clinical outcomes while also providing the growing number of patients managing multiple chronic conditions with the highest level of patient engagement and consumer choice.
DESCRIPTION: The discrepancy between health care spending and achieved outcomes in the United States has fueled efforts to identify and address situations where unnecessarily expensive therapies are used when less costly, equally effective options are available. The underuse of generic medications is an important example. METHODS: A literature review was conducted to answer 5 questions about generic medications: 1) How commonly are brand-name medications used when a generic version is available? 2) How does the use of generic medications influence adherence? 3) What is the evidence that brand-name and generic medications have similar clinical effects? 4) What are the barriers to increasing the use of generic medications? 5) What strategies can be used to promote cost savings through greater generic medication use? This article was reviewed and approved by the American College of Physicians Clinical Guidelines Committee. BEST PRACTICE ADVICE: Clinicians should prescribe generic medications, if possible, rather than more expensive brand-name medications.
BACKGROUND: Medicaid programs face growing pressure to control spending. Despite evidence of clinical harms, states continue to impose policies limiting the number of reimbursable prescriptions (caps). We examined the recent use of prescription caps by Medicaid programs and the impact of policy implementation on prescription utilization. METHODS: We identified Medicaid cap policies from 2001-2010. We classified caps as applying to all prescriptions (overall caps) or only branded prescriptions (brand caps). Using state-level, aggregate prescription data, we developed interrupted time-series analyses to evaluate the impact of implementing overall caps and brand caps in a subset of states with data available before and after cap initiation. For overall caps, we examined the use of essential medications, which were classified as preventive or as providing symptomatic benefit. For brand caps, we examined the use of all branded drugs as well as branded and generic medications among classes with available generic replacements. RESULTS: The number of states with caps increased from 12 in 2001 to 20 in 2010. Overall cap implementation (n = 3) led to a 0.52 % (p < 0.001) annual decrease in the proportion of essential prescriptions but no change in cost. For preventive essential medications, overall caps led to a 1.12 % (p = 0.001) annual decrease in prescriptions (246,000 prescriptions annually) and a 1.20 % (p < 0.001) decrease in spending (-$12.2 million annually), but no decrease in symptomatic essential medication use. Brand cap implementation (n = 6) led to an immediate 2.29 % (p = 0.16) decrease in branded prescriptions and 1.26 % (p = 0.025) decrease in spending. For medication classes with generic replacements, the decrease in branded prescriptions (0.74 %, p = 0.003) approximately equaled the increase in generics (0.79 %, p = 0.009), with estimated savings of $17.4 million. CONCLUSIONS: An increasing number of states are using prescription caps, with mixed results. Overall caps decreased the use of preventive but not symptomatic essential medications, suggesting that patients assign higher priority to agents providing symptomatic benefit when faced with reimbursement limits. Among medications with generic replacements, brand caps shifted usage from branded drugs to generics, with considerable savings. Future research should analyze the patient-level impact of these policies to measure clinical outcomes associated with these changes.
OBJECTIVE: Despite the proliferation of databases with increasingly rich patient data, prediction of medication adherence remains poor. We proposed and evaluated approaches for improved adherence prediction. DATA SOURCES: We identified Medicare beneficiaries who received prescription drug coverage through CVS Caremark and initiated a statin. STUDY DESIGN: A total of 643 variables were identified at baseline from prior claims and linked Census data. In addition, we identified three postbaseline predictors, indicators of adherence to statins during each of the first 3 months of follow-up. We estimated 10 models predicting subsequent adherence, using logistic regression and boosted logistic regression, a nonparametric data-mining technique. Models were also estimated within strata defined by the index days supply. RESULTS: In 77,703 statin initiators, prediction using baseline variables only was poor with maximum cross-validated C-statistics of 0.606 and 0.577 among patients with index supply 30 days, respectively. Using only indicators of initial statin adherence improved prediction accuracy substantially among patients with shorter initial dispensings (C = 0.827/0.518), and, when combined with investigator-specified variables, prediction accuracy was further improved (C = 0.842/0.596). CONCLUSIONS: Observed adherence immediately after initiation predicted future adherence for patients whose initial dispensings were relatively short.
BACKGROUND: Patient-physician communication often occurs outside the clinic setting; many institutions discourage electronic communication outside of established electronic health record systems. Little empirical data are available on patient interest in electronic communication and Web-based health tools that are technically feasible but not widely available. RESEARCH OBJECTIVE: To explore patient behavior and interest in using the Internet to contact physicians. DESIGN: National cross-sectional online survey. PARTICIPANTS: A sample of 4,510 CVS customers with at least one chronic condition in the household was used to target patients with chronic conditions and their caregivers. Subjects were identified from a national panel of over 100,000 retail pharmacy customers. Of those sampled, 2,252 responded (50.0 % response rate). MAIN MEASURES: Survey measures included demographic and health information, patient use of email and Facebook to contact physicians, and patient interest in and use of Web-based tools for health. KEY RESULTS: A total of 37 % of patients reported contacting their physicians via email within the last six months, and 18 % via Facebook. Older age was negatively associated with contacting physicians using email (OR 0.57 [95 % CI 0.41-0.78]) or Facebook (OR 0.28 [0.17-0.45]). Non-white race (OR 1.61 [1.18-2.18] and OR 1.82 [1.24-2.67]) and caregiver status (OR 1.58 [1.27-1.96] and OR 1.71 [1.31- 2.23]) were positively associated with using email and Facebook, respectively. Patients were interested in using Web-based tools to fill prescriptions, track their own health, and access health information (37-57 %), but few were currently doing so (4-8 %). CONCLUSIONS: In this population of retail pharmacy users, there is strong interest among patients in the use of email and Facebook to communicate with their physicians. The findings highlight the gap between patient interest for online communication and what physicians may currently provide. Improving and accelerating the adoption of secure Web messaging systems is a possible solution that addresses both institutional concerns and patient demand.
The potential of short message system (SMS) text messaging and other mobile-phone based methods (collectively often called "mHealth") to engage patients in their own health care has been met with great enthusiasm because of the relatively low cost, transportability, and widespread use of these technologies - more than six billion people worldwide have access to mobile phones.1 By providing reminders and enhancing communication and interaction with healthcare professionals, there is compelling evidence for patients with HIV/AIDS that mHealth can improve adherence to medications and suppress viral loads.2-4.