Bronchoscopy is the safest procedure for lung cancer diagnosis when an invasive evaluation is required after imaging procedures. However its sensitivity is relatively low, especially for small and peripheral lesions. We assessed benefits and costs of introducing a bronchial gene-expression classifier (BGC) to improve the performance of bronchoscopy and the overall diagnostic process for early detection of lung cancer. We used discrete-event simulation to compare clinical and economic outcomes of two different strategies with the standard practice in former and current smokers with indeterminate nodules: (i) location-based strategy - integrated the BGC to the bronchoscopy indication; (ii) simplified strategy - extended use of bronchoscopy plus BGC also on small and peripheral lesions. Outcomes modeled were rate of invasive procedures, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios. Compared with the standard practice, the location-based strategy (i) reduced absolute rate of invasive procedures by 3.3% without increasing costs at the current BGC market price. It resulted in savings when the BGC price was less than $3,000. The simplified strategy (ii) reduced absolute rate of invasive procedures by 10% and improved quality-adjusted life expectancy, producing an incremental cost-effectiveness ratio of $10,109 per QALY. In patients with indeterminate nodules, both BGC strategies reduced unnecessary invasive procedures at high risk of adverse events. Moreover, compared with the standard practice, the simplified use of BGC for central and peripheral lesions resulted in larger QALYs gains at acceptable cost. The location-based is cost-saving if the price of classifier declines. This article is protected by copyright. All rights reserved.
Background Many factors contribute to suboptimal diabetes control including insufficiently-intensive treatment and non-adherence to medication and lifestyle. Determining which of these is most relevant for individual patients is challenging. Patient engagement techniques may help identify contributors to suboptimal adherence and address barriers (using motivational interviewing) and help facilitate choices among treatment augmentation options (using shared decision-making). These methods have not been used in combination to improve diabetes outcomes. Objective To evaluate the impact of a telephone-based patient-centered intervention on glycosylated hemoglobin (HbA1c) control for individuals with poorly-controlled diabetes. Design Two-arm pragmatic randomized control trial within an explanatory sequential mixed-methods design. Subjects 1,400 participants 18–64 years old with poorly-controlled type 2 diabetes. Intervention The intervention was delivered over the telephone by a clinical pharmacist and consisted of a 2-step process that integrated brief negotiated interviewing and shared decision-making to identify patient goals and options for enhancing diabetes management. Main measures The primary outcome was change in HbA1c. Secondary outcomes were medication adherence measures. Outcomes were evaluated using intention-to-treat principles; multiple imputation was used for missing values in the 12-month follow-up. We used information from pharmacist notes to elicit factors to potentially explain the intervention’s effectiveness. Key results Participants had a mean age of 54.7 years (SD:8.3) and baseline HbA1c of 9.4 (SD:1.6). Change in HbA1c from baseline was -0.79 (SD:2.01) in the control arm and -0.75 (SD:1.76) in the intervention arm (difference:+0.04, 95%CI: -0.22, 0.30). There were no significant differences in adherence. In as-treated analyses, the intervention significantly improved diabetes control (-0.48, 95%CI: -0.91, -0.05). Qualitative findings provided several potential explanations for the findings, including insufficiently addressing patient barriers. Conclusions A novel telephone-based patient-centered intervention did not improve HbA1c among individuals with poorly-controlled diabetes, though as-treated analyses suggest that the intervention was effective for those who received it. Trial registration ClinicalTrials.gov NCT02910089
Patient adherence to antidiabetic medications, especially insulin, remains poor, leading to adverse outcomes and increased costs. Most adherence interventions have only been modestly effective, partly because they are not targeted to patients who could benefit most.To evaluate whether delivering more intensive insulin-adherence interventions only to individuals with type 2 diabetes predicted to benefit most was more effective than delivering a lower-intensity intervention to a larger group of unselected individuals.This 3-arm pragmatic randomized clinical trial used data from Horizon, the largest health insurer in New Jersey, on 6000 participants 18 years or older with type 2 diabetes who were receiving basal insulin. Patients were excluded if they were insured by Medicaid or Medicare or had fewer than 3 months of continuous enrollment. The study was conducted from July 7, 2016, through October 5, 2017. Analyses were conducted from February 5 to September 24, 2018.Eligible patients were randomized to 3 arms in a 1:1:1 ratio. Randomization was stratified based on baseline availability of 1 or more glycated hemoglobin A1c (HbA1c) test values. All arms were designed to cost the same, and each cohort received a tailored pharmacist telephone consultation varying based on (1) proportion receiving the intervention and (2) intensity, including follow-up frequency and cointerventions. Arm 1 offered a low-intensity intervention to all patients. Arm 2 offered a moderate-intensity intervention to 60% of patients based on their predicted risk of insulin nonadherence. Arm 3 offered a high-intensity intervention to 40% of patients based on glycemic control and predicted risk of insulin nonadherence.The primary outcome was insulin persistence. Secondary outcomes were changes in HbA1c level and health care utilization. Outcomes were evaluated in arms 2 and 3 vs arm 1 using claims data, intention-to-treat principles, and multiple imputation for missing values in the 12-month follow-up.Among 6000 participants, mean (SD) age was 55.9 (11.0) years and 3344 (59.8%) were male. Compared with arm 1, insulin nonpersistence did not differ in arm 2 (relative risk, 0.88; 95% CI, 0.75-1.03) or arm 3 (relative risk, 0.91; 95% CI, 0.77-1.06). Glycemic control was similar in arm 2 and arm 1 (absolute HbA1c level difference, –0.15%; 95% CI, –0.34% to 0.05%) but was better in arm 3 (absolute HbA1c level difference, –0.25%; 95% CI, –0.43% to –0.06%). Total spending and office visits did not differ, but arm 2 (moderate intensity intervention) had more hospitalizations (odds ratio, 1.22; 95% CI, 1.06-1.41) and emergency department visits (odds ratio, 1.38; 95% CI, 1.24-1.53) than did arm 1 (low intensity intervention).Compared with an untargeted low-intensity intervention, delivering a highly targeted high-intensity intervention did not improve insulin persistence but modestly improved mean glycemic control. A partially targeted moderate-intensity intervention did not change insulin persistence or HbA1c level but was associated with a small increase in hospitalizations.ClinicalTrials.gov Identifier: NCT02846779
ABSTRACT BACKGROUND: The approval of new oral disease-modifying drugs (DMDs), such as fingolimod, dimethyl fumarate (DMF), and teriflunamide, has considerably expanded treatment options for relapsing forms of multiple sclerosis (MS). However, data describing the use of these agents in routine clinical practice are limited. OBJECTIVE: To describe time trends and identify factors associated with oral DMD treatment initiation and switching among individuals with MS. METHODS: Using data from a large sample of commercially insured patients, we evaluated changes over time in the proportion of MS patients who initiated treatment with an oral DMD and who switched from an injectable DMD to an oral DMD between 2009 and 2014 in the United States. We evaluated predictors of oral DMD use using conditional logistic regression in 2 groups matched on calendar time: oral DMD initiators matched to injectable DMDs initiators and oral DMD switchers matched to those who switched to a second injectable DMD. RESULTS: Our cohort included 7,576 individuals who initiated a DMD and 1,342 who switched DMDs, of which oral DMDs accounted for 6% and 39%, respectively. Oral DMD initiation and switching steadily increased from 5% to 16% and 35% to 84%, respectively, between 2011 and 2014, with DMF being the most commonly used agent. Of the potential predictors with clinical significance, a recent neurologist consultation (OR = 1.60; 95% CI = 1.20-2.15) and emergency department visit (OR = 1.43; 95% CI = 1.01-2.01) were significantly associated with oral DMD initiation. History of depression was noted to be a potential predictor of oral DMD initiation; however, the estimate for this predictor did not reach statistical significance (OR = 1.35; 95% CI = 0.99-1.84). No clinically relevant factors measured in our data were associated with switching to an oral DMD. CONCLUSIONS: Oral DMDs were found to be routinely used as second-line treatment. However, we identified few factors predictive of oral DMD initiation or switching, which implies that their selection is driven by patient and/or physician preferences. DISCLOSURES: This study was funded by CVS Caremark through an unrestricted research grant to Brigham and Women?s Hospital. Shrank and Matlin were employees of, and shareholders in, CVS Health at the time of the study; they report no financial interests in products or services that are related to the subject of this study. Spettell is an employee of, and shareholder in, Aetna. Chitnis serves on clinical trial advisory boards for Novartis and Genzyme-Sanofi; has consulted for Bayer, Biogen Idec, Celgene, Novartis, Merck-Serono, and Genentech-Roche; and has received research support from NIH, National Multiple Sclerosis Society, Peabody Foundation, Consortium for MS Centers, Guthy Jackson Charitable Foundation, EMD-Serono, Novartis Biogen, and Verily. Desai reports receiving a research grant from Merck for unrelated work. Gagne is principal investigator of a research grant from Novartis Pharmaceuticals Corporation to the Brigham and Women?s Hospital and has received grant support from Eli Lilly, all for unrelated work. He is also a consultant to Aetion and Optum. Minden reports grants from Biogen and other fees from Genentech, EMD Serano, Avanir, and Novartis, unrelated to this study. The other authors have no conflicts to report. This study was presented as a poster at the International Society for Pharmacoepidemiology 32nd Annual Meeting; August 25-28, 2016; Dublin, Ireland.
Importance Despite guideline recommendations, many patients discontinue P2Y12 inhibitor therapy earlier than the recommended 1 year after myocardial infarction (MI), and higher-potency P2Y12 inhibitors are underutilized. Cost is frequently cited as an explanation for both of these observations.Objective To determine whether removing co-payment barriers increases P2Y12 inhibitor persistence and lowers risk of major adverse cardiovascular events (MACE).Design, Setting, and Participants Cluster randomized clinical trial among 301 hospitals enrolling adult patients with acute MI (June 5, 2015, through September 30, 2016); patients were followed up for 1 year after discharge (final date of follow-up was October 23, 2017), with blinded adjudication of MACE; choice of P2Y12 inhibitor was per clinician discretion.Interventions Hospitals randomized to the intervention (n = 131 [6436 patients]) provided patients with co-payment vouchers for clopidogrel or ticagrelor for 1 year (median voucher value for a 30-day supply, $137 [25th-75th percentile, $20-$339]). Hospitals randomized to usual care (n = 156 [4565 patients]) did not provide study vouchers.Main Outcomes and Measures Independent coprimary outcomes were patient-reported persistence with P2Y12 inhibitor (defined as continued treatment without gap in use ≥30 days) and MACE (death, recurrent MI, or stroke) at 1 year among patients discharged with a prescription for clopidogrel or ticagrelor.Results Among 11 001 enrolled patients (median age, 62 years; 3459 [31%] women), 10 102 patients were discharged with prescriptions for clopidogrel or ticagrelor (clopidogrel prescribed to 2317 [36.0%] in the intervention group and 2497 [54.7%] in the usual care group), 4393 of 6135 patients (72%) in the intervention group used the voucher, and follow-up data at 1 year were available for 10 802 patients (98.2%). Patient-reported persistence with P2Y12 inhibitors at 1 year was higher in the intervention group than in the control group (unadjusted rates, 5340/6135 [87.0%] vs 3324/3967 [83.8%], respectively; P < .001; adjusted difference, 2.3% [95% CI, 0.4% to 4.1%]; adjusted odds ratio, 1.19 [95% CI, 1.02 to 1.40]). There was no significant difference in MACE at 1 year between intervention and usual care groups (unadjusted cumulative incidence, 10.2% vs 10.6%; P = .65; adjusted difference, 0.66% [95% CI, −0.73% to 2.06%]; adjusted hazard ratio, 1.07 [95% CI, 0.93 to 1.25]).Conclusions and Relevance Among patients with MI, provision of vouchers to offset medication co-payments for P2Y12 inhibitors, compared with no vouchers, resulted in a 3.3% absolute increase in patient-reported persistence with P2Y12 inhibitors and no significant reduction in 1-year MACE outcomes.Trial Registration ClinicalTrials.gov Identifier: NCT02406677
More than 50% of patients are non-adherent to medications, often without an easily identifiable reason to clinicians. No study has quantified the extent to which health behaviors like medication-taking are correlated within families using national or routinely collected data for a range of conditions.
To examine how an individual’s health behaviors are influenced by those of their family members, particularly in adherence to medications for chronic conditions.
Retrospective cohort study.
Using claims from a large nationwide insurer, we identified patients initiating medications for one of five chronic conditions with a family member who also recently filled one of these medications.
The primary exposure was whether family members were fully adherent (defined as a proportion of days covered ≥ 80%) before the patient’s date of initiation. The outcome of interest was whether patients were fully adherent in the 12 months after initiation. Baseline demographic and clinical characteristics were also measured before initiation. We used multivariable modified Poisson regression to examine the association between prior family adherence and subsequent patient adherence.
Among 254,144 patients, rates of full adherence among patients whose family members were and were not fully adherent were 37.3% and 26.9%, respectively (adjusted relative risk [aRR] 1.29, 95%CI 1.28–1.31). The association was stronger when both used cardiometabolic medications (aRR 1.35, 95%CI 1.32–1.37). Similarly, patients were also 38% more likely to be adherent if they and their family members used a medication for the same condition (aRR 1.38, 95%CI 1.35–1.40).
Adherence among family members appeared to be highly correlated, suggesting positive reinforcement by family or the sharing of unmeasured behaviors or characteristics associated with better adherence. Regardless, information about prior adherence among family members from routinely collected data could potentially inform adherence prediction or intervention efforts.
High deductible health plans (HDHP) are associated with high levels of patient cost-sharing and are becoming increasingly used in the United Status as a means of reducing healthcare utilization and spending. Our objective is to determine whether HDHP enrollment is associated with a change in adherence to evidence-based medications to treat cardiovascular risk factors and whether such changes vary based on race/ethnicity or socioeconomic status.
Methods and Results:
We conducted a retrospective cohort study using an interrupted time series with concurrent control group design among beneficiaries of Aetna—a national commercial insurer. We included 14 866 patients who filled prescriptions for medications to treat hypertension, high cholesterol, or diabetes mellitus between 2009 and 2014 and who switched from a traditional plan into an HDHP and 14 866 controls who did not switch to an HDHP matched based on calendar time, medication class, race/ethnicity, socioeconomic status, and propensity score. We were specifically interested in evaluating 4 prespecified subgroups based on race/ethnicity (white versus nonwhite) and socioeconomic status (higher versus lower). The main outcome was medication adherence as measured by proportion of days covered. The overall cohort had an average age of 53 years, and 44% were women. Baseline adherence was the lowest in the nonwhite patient group. Switching to an HDHP was associated with a decrease in the level of adherence of 5 percentage points across all 4 subgroups (change in level, −5.0%; 95% CI, −5.9% to −4.0%; P<0.0001).
HDHP enrollment was associated with a reduction in adherence to medications to treat cardiovascular risk factors. The magnitude of this effect did not vary based on race/ethnicity or socioeconomic status. Because racial/ethnic minorities have lower rates of medication adherence, future studies should evaluate whether HDHP-associated changes in adherence have greater clinical consequences for these patients.
Background Data on primary nonadherence remains sparse, due to a lack of data resources that combine information on medication prescribing and dispensing. In addition, previous work on primary nonadherence has used follow-up periods ranging from 30 days up to 18 months, making results difficult to compare.
Objective To evaluate the prevalence and predictors of primary nonadherence by measuring time until filling in a cohort of elderly patients.
Design Retrospective cohort study of new prescription episodes.
Patients Data comes from a linked database of electronic health records and claims for patients aged ≥ 65 years enrolled in Medicare Parts A, B, and D during 2007–2014. We identified patients receiving a new prescription for a chronic disease medication with continuous Medicare enrollment for 180 days prior to the index prescription order and no fills or orders for the medication during this period.
Main Measures Time until filling of the index prescription for up to 1 year.
Key Results In 32,586 new medication orders, the majority (75%; 95% confidence interval [CI] 74–75%) of new prescriptions were filled within 7 days, 81% (81–82%) were filled within 30 days, and 91% (91–92%) were filled within 1 year. The rate and timing of dispensing were similar across therapeutic areas. Timing of initial filling within 7 days or within 30 days could be predicted with moderate accuracy (C-statistics = 0.70–0.74). Patients with > 5 current medications on hand at the time of the index prescription and average out-of-pocket medication costs < $5 filled 89% of prescriptions within 7 days. Patients with no current medications and out-of-pocket costs > $50 filled only 25% of prescriptions within 7 days.
Conclusions Nearly 20% of patients do not fill a new chronic disease prescription within 30 days. Patients with fewer recent fills and higher out-of-pocket costs are at higher risk of primary nonadherence.
BACKGROUND: Medication nonadherence is a major public health problem. Identification of patients who are likely to be and not be adherent can guide targeted interventions and improve the design of comparative-effectiveness studies. OBJECTIVE: To evaluate multiple measures of patient previous medication adherence in light of predicting future statin adherence in a large U.S. administrative claims database. METHODS: We identified a cohort of patients newly initiating statins and measured their previous adherence to other chronic preventive medications during a 365-day baseline period, using metrics such as proportion of days covered (PDC), lack of second fills, and number of dispensations. We measured adherence to statins during the year after initiation, defining high adherence as PDC ≥ 80%. We built logistic regression models from different combinations of baseline variables and previous adherence measures to predict high adherence in a random 50% sample and tested their discrimination using concordance statistics (c-statistics) in the other 50%. We also assessed the association between previous adherence and subsequent statin high adherence by fitting a modified Poisson model from all relevant covariates plus previous mean PDC categorized as < 25%, 25%-79%, and ≥ 80%. RESULTS: Among 89,490 statin initiators identified, a prediction model including only demographic variables had a c-statistic of 0.578 (95% CI = 0.573-0.584). A model combining information on patient comorbidities, health care services utilization, and medication use resulted in a c-statistic of 0.665 (95% CI = 0.659-0.670). Models with each of the previous medication adherence measures as the only explanatory variable yielded c-statistics ranging between 0.533 (95% CI = 0.529-0.537) for lack of second fill and 0.666 (95% CI = 0.661-0.671) for maximum PDC. Adding mean PDC to the combined model yielded a c-statistic of 0.695 (95% CI = 0.690-0.700). Given a sensitivity of 75%, the predictor improved the specificity from 47.7% to 53.6%. Patients with previous mean PDC < 25% were half as likely to show high adherence to statins compared with those with previous mean PDC ≥ 80% (risk ratio = 0.49, 95% CI = 0.46-0.50). CONCLUSIONS: Including measures of previous medication adherence yields better prediction of future statin adherence than usual baseline clinical measures that are typically used in claims-based studies. DISCLOSURES: This study was funded by the Patient-Centered Outcomes Research Institute (ME-1309-06274). Kumamaru, Kohsaka, and Miyata are affiliated with the Department of Healthcare Quality Assessment at the University of Tokyo, which is a social collaboration department supported by National Clinical Database. The department was formerly supported by endowments from Johnson & Johnson K.K., Nipro, Teijin Pharma, Kaketsuken K.K., St. Jude Medical Japan, Novartis Pharma K.K., Taiho Pharmaceutical, W. L. Gore & Associates, Olympus Corporation, and Chugai Pharmaceutical. Gagne has received grants from Novartis Pharmaceuticals and Eli Lilly and Company to the Brigham and Women's Hospital for unrelated work. He is a consultant to Aetion, a software company, and to Optum. Choudhry has received grants from the National Heart, Lung, and Blood Institute, PhRMA Foundation, Merck, Sanofi, AstraZeneca, CVS, and MediSafe. Schneeweiss is consultant to WHISCON and Aetion, a software manufacturer of which he also owns equity. He is principal investigator of investigator-initiated grants to the Brigham and Women’s Hospital from Bayer, Genentech, and Boehringer Ingelheim unrelated to the topic of this study. He does not receive personal fees from biopharmaceutical companies. No potential conflict of interest was reported by the other authors.
BACKGROUND: Shortages of chronic medications are an increasingly common problem, yet little is known about their impact on drug utilization and clinical outcomes. We evaluated the population-level impact of metoprolol extended release shortage that occurred in the United States in 2009 to 2010.
METHODS AND RESULTS: We conducted a population-based, time series analysis of 38914 patients (mean age, 60 years; 69% men) discharged after hospitalization for myocardial infarction (MI) between January 2006 and November 2012 in a large commercial insurance database. The shortage period was defined as February 2009 to June 2010. Data before September 2008 was defined as preshortage period and data after June 2010 as postshortage period. Outcomes were proportion of patients who filled any long- or short-acting β-blocker within 30 days of discharge, adherence to β-blockers within the first year of therapy among patients who initiated β-blockers, and rates of 1-year rehospitalization for MI or unstable angina. Post-MI statin utilization and adherence were evaluated as control outcomes. During the preshortage period, 70% of patient filled a β-blocker, mean monthly adherence was 76%, and the average monthly rate of rehospitalization was 6.5 events per 100 person-years, as compared with β-blocker use of 62%, average adherence of 70%, and rehospitalization rate of 5.6 events per 100 person-years during the shortage. After accounting for the baseline (preshortage) trends, the shortage was associated with significant monthly reductions in postdischarge β-blocker use (−0.57% of patients [95% CI, −0.90 to −0.24] per month) and an immediate decrease in adherence (−4.58% days covered [95% CI, −6.12 to −3.04]). No negative impact on rates of rehospitalization, post-MI statin utilization, or statin adherence was observed. β-Blocker utilization began to increase after the resolution of the shortage.
CONCLUSIONS: The nationwide metoprolol extended release shortage in the United States was associated with fewer patients receiving any long- or short-acting β-blocker post-MI and lower adherence to β-blocker therapy for those who did receive it, but did not appear to appreciably affect clinical outcomes at the population level.
The influenza (‘flu’) vaccination is low cost1 and effective, typically reducing the likelihood of infection by 50–60%2 . It is recommended for nearly everyone older than 6 months of age3 ; yet, only 40% of Americans are immunized each year. Vaccination rates are higher among at-risk groups, such as those ≥65 years of age, but still only 6 in 10 receive it4. There have been numerous attempts to improve vaccination rates using strategies such as school-based programmes, financial incentives and reminders, but these have generally had limited success5–7 . Of the attempts that are successful, most are expensive—limiting scalability—and have not been evaluated in the elderly8. Conversely, lower-cost interventions, such as mailed information, hold promise for a scalable solution, but their limited effectiveness may result from how they have been designed. We randomly assigned 228,000 individuals ≥66 years of age to one of five versions of letters intended to motivate vaccination, including versions with an implementation intention prompt and an enhanced active choice implementation prompt. We found that a single mailed letter significantly increased influenza vaccination rates compared with no letter. However, there was no difference in vaccination rates across the four different letters tailored with behavioural science techniques.
OBJECTIVES: Preference weights derived from general population samples are often used for therapeutic decision making. In contrast, patients with cardiovascular disease may have different preferences concerning the benefits and risks of anticoagulant therapy. Using a discrete choice experiment, we compared preferences for anticoagulant treatment outcomes between the general population and patients with cardiovascular disease. METHODS: A sample of the general US population and a sample of patients with cardiovascular disease were selected from online panels. We used a discrete choice experiment questionnaire to elicit preferences in both populations concerning treatment benefits and risks. Seven attributes described hypothetical treatments: non-fatal stroke, non-fatal myocardial infarction, cardiovascular death, minor bleeding, major bleeding, fatal bleeding, and the need for monitoring. We measured preference weights and maximum acceptable risks in both populations. RESULTS: A total of 352 individuals from the general population and 341 patients completed the questionnaire. After propensity score matching, 284 from each group were included in the analysis. On average, the general population members valued a 1% increased risk of fatal bleeding as being the same as a 4.2% increase in a non-fatal myocardial infarction, a 2.8% increase in cardiovascular death, or a 14.1% increase in minor bleeding. Patients, in contrast, perceived a 1% increased risk of fatal bleeding as being the same as a 2.0% increase in a non-fatal myocardial infarction, a 3.2% increase in cardiovascular death, and a 16.7% increase in minor bleeding. CONCLUSIONS: The general population and patients with cardiovascular disease had slightly different preferences for treatment outcomes. The differences can potentially influence estimated benefits and risks and patient-centered treatment decisions.
Importance: Approximately half of patients with chronic conditions are nonadherent to prescribed medications, and interventions have been only modestly effective. Objective: To evaluate the effect of a remotely delivered multicomponent behaviorally tailored intervention on adherence to medications for hyperlipidemia, hypertension, and diabetes. Design, Setting, and Participants: Two-arm pragmatic cluster randomized controlled trial at a multispecialty group practice including participants 18 to 85 years old with suboptimal hyperlipidemia, hypertension, or diabetes disease control, and who were nonadherent to prescribed medications for these conditions. Interventions: Usual care or a multicomponent intervention using telephone-delivered behavioral interviewing by trained clinical pharmacists, text messaging, pillboxes, and mailed progress reports. The intervention was tailored to individual barriers and level of activation. Main Outcomes and Measures: The primary outcome was medication adherence from pharmacy claims data. Secondary outcomes were disease control based on achieved levels of low-density lipoprotein cholesterol, systolic blood pressure, and hemoglobin A1c from electronic health records, and health care resource use from claims data. Outcomes were evaluated using intention-to-treat principles and multiple imputation for missing values. Results: Fourteen practice sites with 4078 participants had a mean (SD) age of 59.8 (11.6) years; 45.1% were female. Seven sites were each randomized to intervention or usual care. The intervention resulted in a 4.7% (95% CI, 3.0%-6.4%) improvement in adherence vs usual care but no difference in the odds of achieving good disease control for at least 1 (odds ratio [OR], 1.10; 95% CI, 0.94-1.28) or all eligible conditions (OR, 1.05; 95% CI, 0.91-1.22), hospitalization (OR, 1.02; 95% CI, 0.78-1.34), or having a physician office visit (OR, 1.11; 95% CI, 0.91-1.36). However, intervention participants were significantly less likely to have an emergency department visit (OR, 0.62; 95% CI, 0.45-0.85). In as-treated analyses, the intervention was associated with a 10.4% (95% CI, 8.2%-12.5%) increase in adherence, a significant increase in patients achieving disease control for at least 1 eligible condition (OR, 1.24; 95% CI, 1.03-1.50), and nonsignificantly improved disease control for all eligible conditions (OR, 1.18; 95% CI, 0.99-1.41). Conclusions and Relevance: A remotely delivered multicomponent behaviorally tailored intervention resulted in a statistically significant increase in medication adherence but did not change clinical outcomes. Future work should focus on identifying which groups derive the most clinical benefit from adherence improvement efforts. Trial Registration: ClinicalTrials.gov identifier: NCT02512276.
BACKGROUND: Continuation of antiplatelet therapy beyond 12 months after a drug-eluting stent procedure reduced the risk of a major adverse cardiovascular and cerebrovascular event (MACCE) in the DAPT trial (Dual Antiplatelet Therapy). Observational studies have evaluated outcomes related to different durations of therapy but are susceptible to bias. METHODS AND RESULTS: Using deidentified claims from commercially insured and Medicare populations in the United States, we compared how increasingly stringent definitions of exposure affect associations between antiplatelet continuation versus discontinuation and MACCE, myocardial infarction, and intracerebral hemorrhage or gastrointestinal bleeding in patients meeting DAPT trial inclusion criteria between 2004 and 2013. Therapy continuation at 12 months was defined as (1) having antiplatelet supply on hand versus not (landmark time); (2) refilling within 30 days versus not among individuals with antiplatelet supply; (3) criteria 2 plus continuous prior antiplatelet use; and (4) criteria 2 and 3 plus a cardiologist visit in months 10 to 12. Propensity score-adjusted hazard ratios were compared. Cohort sizes were 53 679, 27 524, 16 971, and 7948, respectively, of which 20% were discontinuers on average. Increasing restriction led to progressively larger associations with continued treatment: cohort 1 MACCE hazard ratio, 0.79 (0.73, 0.87); myocardial infarction, 0.74 (0.65, 0.83); bleed, 1.03 (0.96, 1.11) versus cohort 4 MACCE hazard ratio, 0.66 (0.48, 0.91); myocardial infarction, 0.56 (0.37, 0.86); bleed, 1.24 (0.95, 1.61). Estimates trended toward DAPT trial estimates and were associated with reduced levels of exposure misclassification. CONCLUSIONS: In an example of long-term antiplatelet use, increasing restrictions on the definition of therapy continuation yielded results consistent with trial estimates by reducing exposure misclassification.
The writing of a prescription has long been one of the most expected steps to occur at the end of a physician-patient encounter. The subsequent events are assumed to follow a natural order: patients fill their prescriptions at a pharmacy and then continue to use their medications as prescribed. Unfortunately, these assumptions often do not hold. The challenges of consistent medication use, often called secondary adherence or persistence, have been well characterized by decades of research estimating that, on average, fewer than half of patients use their medications as prescribed over the long-term and many stop using their medications within months of beginning.1 Much less well appreciated has been primary nonadherence, where patients do not fill the initial prescriptions they are given.
BACKGROUND: Efforts at predicting long-term adherence to medications have been focused on patients filling typical month-long supplies of medication. However, prediction remains difficult for patients filling longer initial supplies, a practice that is becoming increasingly common as a method to enhance medication adherence. OBJECTIVES: To (a) extend methods involving short-term filling behaviors and (b) develop novel variables to predict adherence in a cohort of patients receiving longer initial prescriptions. METHODS: In this retrospective cohort study, we used claims from a large national insurer to identify patients initiating a 90-day supply of oral medications for diabetes, hypertension, and hyperlipidemia (i.e., statins). Patients were included in the cohort if they had continuous database enrollment in the 180 days before and 365 days after medication initiation. Adherence was measured in the subsequent 12 months using the proportion of days covered metric. In total, 125 demographic, clinical, and medication characteristics at baseline and in the first 30-120 days after initiation were used to predict adherence using logistic regression models. We used 10-fold cross-validation to assess predictive accuracy by discrimination (c-statistic) measures. RESULTS: In total, 32,249 patients met the inclusion criteria, including 14,930 patients initiating statins, 12,887 patients initiating antihypertensives, and 4,432 patients initiating oral hypoglycemics. Prediction using only baseline variables was relatively poor (cross-validated c-statistic = 0.644). Including indicators of acute clinical conditions, health resource utilization, and short-term medication filling in the first 120 days greatly improved predictive ability (0.823). A model that incorporated all baseline characteristics and predictors within the first 120 days after medication initiation more accurately predicted future adherence (0.832). The best performing model that included all 125 baseline and postbaseline characteristics had strong predictive ability (0.837), suggesting the utility of measuring these novel postbaseline variables in this population. CONCLUSIONS: We demonstrate that long-term, 12-month adherence in patients filling longer supplies of medication can be strongly predicted using a combination of clinical, health resource utilization, and medication filling characteristics before and after treatment initiation. DISCLOSURES: This work was supported by an unrestricted grant from CVS Health to Brigham and Women's Hospital. Shrank and Matlin were employees and shareholders at CVS Health at the time of this study; they report no financial interests in products or services that are related to this subject. Spettell is an employee of, and shareholder in, Aetna. This research was previously presented at the 2016 Annual Conference of the International Society for Pharmacoepidemiology; August 25-28, 2016; Dublin, Ireland.
Background Little is known about physicians’ approaches to adopting new cardiovascular drugs and how adoption varies between drugs of differing novelty. Methods Using data on dispensed prescriptions from IMS Health's Xponent™ database, we created a cohort of all primary care physicians (PCPs) and cardiologists in Pennsylvania who regularly prescribed anticoagulants, antihypertensives and statins from 2007 to 2011. We examined prescribing of three new cardiovascular drugs of differing novelty: dabigatran, aliskiren and pitavastatin. Outcomes were rapid adoption of each new drug, defined by early and sustained monthly prescribing detected by group-based trajectory models, by physicians within the first 15 months of marketplace introduction. Results 5953 physicians regularly prescribed each drug class. The majority of physicians (63.8%) adopted zero new drugs in the first 15 months, 35.0% rapidly adopted one or two, and 1.2% rapidly adopted all three. Physicians were more likely to rapidly adopt the most novel drug, dabigatran (27.3%), than aliskiren (10.5%) or pitavastatin (8.0%). Physician specialty and sex were the most consistent predictors of adoption. Compared to PCPs, cardiologists were more likely to rapidly adopt dabigatran (Adjusted Odds Ratio 8.90, 95% confidence interval 7.42–10.67; P<0.001) aliskerin (2.05, CI 1.56–2.69; P<0.001) and pitavastatin (3.44, CI 2.60–4.57; P<0.001). Female physicians were less likely to adopt dabigatran (0.71, CI 0.59–0.85; P <0.001) and aliskiren (0.64, CI 0.49–0.83; P <0.001). Conclusions Physicians vary in their prescribing of recently-introduced cardiovascular drugs. Though most physicians did not rapidly adopt any new cardiovascular drugs, drug novelty and cardiology training were associated with greater adoption.
Importance Medication nonadherence accounts for up to half of uncontrolled hypertension. Smartphone applications (apps) that aim to improve adherence are widely available but have not been rigorously evaluated.Objective To determine if the Medisafe smartphone app improves self-reported medication adherence and blood pressure control.Design, Setting, and Participants This was a 2-arm, randomized clinical trial (Medication Adherence Improvement Support App For Engagement—Blood Pressure [MedISAFE-BP]). Participants were recruited through an online platform and were mailed a home blood pressure cuff to confirm eligibility and to provide follow-up measurements. Of 5577 participants who were screened, 412 completed consent, met inclusion criteria (confirmed uncontrolled hypertension, taking 1 to 3 antihypertensive medications), and were randomized in a ratio of 1:1 to intervention or control.Interventions Intervention arm participants were instructed to download and use the Medisafe app, which includes reminder alerts, adherence reports, and optional peer support.Main Outcomes and Measures Co–primary outcomes were change from baseline to 12 weeks in self-reported medication adherence, measured by the Morisky medication adherence scale (MMAS) (range, 0-8, with lower scores indicating lower adherence), and change in systolic blood pressure.Results Participants (n = 411; 209 in the intervention group and 202 controls) had a mean age of 52.0 years and mean body mass index, calculated as weight in kilograms divided by height in meters squared, of 35.5; 247 (60%) were female, and 103 (25%) were black. After 12 weeks, the mean (SD) score on the MMAS improved by 0.4 (1.5) among intervention participants and remained unchanged among controls (between-group difference: 0.4; 95% CI, 0.1-0.7; P = .01). The mean (SD) systolic blood pressure at baseline was 151.4 (9.0) mm Hg and 151.3 (9.4) mm Hg, among intervention and control participants, respectively. After 12 weeks, the mean (SD) systolic blood pressure decreased by 10.6 (16.0) mm Hg among intervention participants and 10.1 (15.4) mm Hg among controls (between-group difference: −0.5; 95% CI, −3.7 to 2.7; P = .78).Conclusions and Relevance Among individuals with poorly controlled hypertension, patients randomized to use a smartphone app had a small improvement in self-reported medication adherence but no change in systolic blood pressure compared with controls.Trial Registration clinicaltrials.gov Identifier: NCT02727543
In the presence of heterogeneity of treatment effect (HTE), the average treatment effect from a randomized controlled trial (RCT) may not be applicable to different patients, such as those in observational settings. Our objective was to develop a novel approach that uses individual-level simulation to expand RCT results to target patient populations in the presence of HTE. For this purpose, we compared the results of the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, and two observational studies that compared benefits and risks of dabigatran to warfarin in patients with atrial fibrillation. We developed a simulation model that replicates the rates of ischemic stroke and major bleeding observed in RE-LY using published outcome risk models and participants' baseline characteristics. We used our validated simulation model to predict what the results of the RCT would have been had it been conducted in populations similar to those in the observational studies. This article is protected by copyright. All rights reserved.