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The American Journal of Managed Care June 2017
Comparative Effectiveness and Costs of Insulin Pump Therapy for Diabetes
Ronald T. Ackermann, MD, MPH; Amisha Wallia, MD, MS; Raymond Kang, MA; Andrew Cooper, MPH; Theodore A. Prospect, FSA, MAAA; Lewis G. Sandy, MD, MBA; and Deneen Vojta, MD
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Jeffrey J. Leow, MBBS, MPH; Joel S. Weissman, PhD; Linda Kimsey, PhD; Andrew Hoburg, PhD; Lorens A. Helmchen, PhD; Wei Jiang, MS; Nathanael Hevelone, MPH; Stuart R. Lipsitz, ScD; Louis L. Nguyen, MD, MPH, MBA; and Steven L. Chang, MD, MS
Patients' Views of a Behavioral Intervention Including Financial Incentives
Judy A. Shea, PhD; Aderinola Adejare, BA; Kevin G. Volpp, MD, PhD; Andrea B. Troxel, ScD; Darra Finnerty, MPH; Karen Hoffer, BS; Thomas Isaac, MD, MPH, MBA; Meredith Rosenthal, PhD; Thomas D. Sequist, MD, MPH; and David A. Asch, MD, MBA
How Do Medicare Advantage Beneficiary Payments Vary With Tenure?
Paul D. Jacobs, PhD, and Eamon Molloy, PhD
Patient Ratings of Veterans Affairs and Affiliated Hospitals
Paul A. Heidenreich, MD, MS; Aimee Zapata, MS; Lisa Shieh, MD, PhD; Nancy Oliva, PhD, RN; and Anju Sahay, PhD
Using "Roll-up" Measures in Healthcare Quality Reports: Perspectives of Report Sponsors and National Alliances
Jennifer L. Cerully, PhD; Steven C. Martino, PhD; Lise Rybowski, MBA; Melissa L. Finucane, PhD; Rachel Grob, PhD; Andrew M. Parker, PhD; Mark Schlesinger, PhD; Dale Shaller, MPA; and Grant Martsolf, PhD, MPH, RN
Does the Offer of Free Prescriptions Increase Generic Prescribing?
Bruce Stuart, PhD; Franklin Hendrick, PhD; J. Samantha Dougherty, PhD; and Jing Xu, PhD
Patients' Views on Price Shopping and Price Transparency
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Heterogeneity of Nonadherent Buprenorphine Patients: Subgroup Characteristics and Outcomes
Charles Ruetsch, PhD; Joseph Tkacz, MS; Vijay R. Nadipelli, MS, BPharm; Brenna L. Brady, PhD; Naoko Ronquest, PhD; Hyong Un, MD; and Joseph Volpicelli, MD, PhD

Heterogeneity of Nonadherent Buprenorphine Patients: Subgroup Characteristics and Outcomes

Charles Ruetsch, PhD; Joseph Tkacz, MS; Vijay R. Nadipelli, MS, BPharm; Brenna L. Brady, PhD; Naoko Ronquest, PhD; Hyong Un, MD; and Joseph Volpicelli, MD, PhD
Patient and treatment heterogeneity were characterized within a sample of nonadherent buprenorphine members; an improved understanding of these factors may optimize patient—treatment matching and intervention efforts.

Objectives: To examine patient characteristics and outcomes associated with nonadherence to buprenorphine and to identify specific patterns of nonadherent behavior.

Study Design: Cross-sectional, retrospective analysis of health claims data.

Methods: Aetna’s administrative claims data were used to categorize incident opioid use disorder (OUD) patients based on buprenorphine medication possession ratio (MPR) into adherent (n = 172) and nonadherent (n = 305) groups. Adherent groups were then divided into 5 subgroups based on level of MPR, as well as 2 a priori–defined groups: intermittent adherent (IA) and early treatment discontinuation—no consequences (ETDNC). Groups were compared on patient characteristics and outcomes.

Results: Nonadherent members incurred significantly greater healthcare costs and were more likely to relapse (P <.05). The use of high-cost healthcare services increased as a function of decreasing MPR (P <.05). Assessment of the a priori groups revealed IA members to have outcomes similar to nonadherent patients, while ETDNC members exhibited outcomes similar to adherent members.

Conclusions: Administrative claims can be used to define subgroups of buprenorphine-medication assisted treatment (B-MAT) patients. Nonadherence was related to an increased likelihood of relapse, and there is an inverse relationship between MPR and cost. The heterogeneity observed within this sample indicates that treatment regimens effective for 1 subgroup may not be appropriate for all OUD patients. Increased understanding of B-MAT nonadherent subgroups may facilitate development of new interventions and medications specifically designed for nonadherent B-MAT patients, potentially leading to improved outcomes and reduced costs of care.
Takeaway Points
  • Using administrative claims data, patterns of buprenorphine nonadherence were assessed among individuals in treatment for opioid use disorder.
  • Nonadherence was related to increased service utilization, cost, and likelihood of relapse. Use of high-cost venue services increased as a function of decreasing adherence.
  • This study confirms previous reports of the relationship between buprenorphine-medication assisted treatment (B-MAT) adherence and costs and advances this line of research by exploring and delineating patterns associated with subgroups of nonadherent B-MAT patients, particularly intermittent adherent and assumed success cases.
The United States is experiencing an opioid abuse epidemic, characterized by increases in the use of illicit drugs and misuse of prescription opioid analgesics.1,2 Healthcare costs associated with opioid use disorder (OUD) have been estimated at $72 billion annually, with societal costs in excess of $50 billion.3 In response, the White House issued a mandate to improve access to OUD treatment,4-7 but significant challenges to the success of treatment remain, including initiation and persistence with treatment.

Medication-assisted treatment (MAT) for OUD includes methadone (M-MAT), naltrexone, and buprenorphine (B-MAT). Approval of B-MAT in 2002 addressed many of the barriers and stigmas associated with M-MAT.7-11 Yet, fewer than 50% of OUD patients receive MAT of any form,11-13 and between 40% and 60% of all substance abuse patients relapse within 1 year of discharge.7,14-16 Therefore, more effective outpatient OUD treatment models, including improved patient–treatment matching are needed. 

Nonadherence with buprenorphine and the associated elevated risk of relapse are pervasive challenges in the treatment of OUD. Although OUD is often characterized as a chronic relapsing disorder, treatment nonadherence is likely a contributing factor, as nonadherent patients incur significantly greater healthcare costs and have higher relapse rates than adherent patients.17,18 Although some patient and treatment characteristics are predictive of lower retention in therapy, treatment characteristics associated with buprenorphine nonadherence remain unclear, as does their possible relationship to relapse.19-22 

This study extends existing literature on B-MAT treatment failure and explores the factors associated with B-MAT medication nonadherence. An improved understanding of B-MAT adherence patterns could help providers identify early signs of nonadherence and lead to more effective patient–treatment matching. These analyses were designed to examine relationships among buprenorphine utilization, patient characteristics, and patient outcomes within administrative claims data to identify characteristics associated with nonadherent behavior in order to provide the insight necessary to more effectively manage OUD patient populations. 


Data Source

De-identified administrative commercial claims data (Q1 2012-Q1 2015) were supplied by Aetna, and the study was approved by Aetna’s human research protection safety committee. The following criteria were imposed (Table 1): 1) at least a 28 days’ supply of buprenorphine (single ingredient or combination with naloxone) during measurement year; 2) diagnosis of opioid dependence (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] procedure codes 304.0x; 304.7x), opioid abuse (305.5x), or opioid poisoning (965.0x); 3) 6-month buprenorphine-naïve period preceding earliest buprenorphine fill; 4) continuous eligibility with medical and pharmacy benefits for 6 months prior to (naïve period) and 12 months following (follow-up period) the earliest buprenorphine fill on record (index date); and 5) 18 years or older on the index date.

Patients with serious mental illnesses, neurological disorders, or at the end of life, were excluded from analyses. The following diagnoses (ICD-9-CM codes in parenthesis) were the basis for exclusion: adult failure to thrive (783.7); Alzheimer’s and other cerebral degenerations (331.x); chronic liver disease and cirrhosis (571.x); end-stage renal disease (585.6); dementias (290.x); debility, not otherwise specified (799.3); heart failure (428.x); Parkinson’s disease (332.x); schizophrenia (295.x); and senility without mention of psychosis (797.x).

Study Groups 

Members were divided into adherent and nonadherent groups based on their buprenorphine medication possession ratio (MPR). For the current study, adherence was calculated by dividing the total days’ supply of medication by the length of the study window (12 months) 23:  

MPR =  total days’ supply of buprenorphine
1 year post period (365 days)

An MPR cutoff of 0.80 was used to demarcate adherent from nonadherent members.24 

B-MAT Subgroups

MPR subgroups. B-MAT subgroups were identified by patterns of buprenorphine fills during the post period. Two methodologies were used to divide cases into subgroups. The first method stratified nonadherent members based on postperiod MPR. The nonadherent MPR subgroups were based on equal increments of 0.20: 1) 0.00-0.19, 2) 0.20-0.39, 3) 0.40-0.59, 4) 0.60-0.79.

Clinical subgroups. The second methodology was based on buprenorphine fill patterns consistent with 2 hypothesized groups described during communication with Aetna medical and psychiatric leadership. The first group, intermittent adherence (IA), included members exhibiting a series of treatment initiations and discontinuations without moving toward sobriety, characteristic of drug holidays. The IA group was operationally defined as evidencing multiple episodes of B-MAT (1 episode includes 2 or more consecutive fills) separated by intermittent periods of medication discontinuation (gap in fills ≥30 days). Assignment to this group required at least 2 episodes of buprenorphine treatment separated by medication discontinuation. 

A small number of B-MAT patients completed treatment during a brief period of time (ie, less than 9 months) without evidencing any of the negative consequences normally associated with early discontinuation (ie, relapse). These members were placed in the early treatment discontinuation—no consequences (ETDNC) group, which was defined as demonstrating an MPR of at least 0.80 during their specific treatment period with B-MAT (minimum of 90 days) and showing an absence of relapse indicators following cessation of B-MAT. Given that the ETDNC subgroup exhibited characteristics of both the nonadherent group (briefer treatment window, <0.80 1-year MPR) and adherent group (short-term adherence ≥0.80, absence of relapse), exploratory analyses of this subgroup alone and with both adherent and nonadherent groups were performed. 


Demographics. Demographic variables of age, gender, region of residence, and member type were aggregated from the summary membership table. Health statuses during the pre- and post periods were estimated using the Charlson Comorbidity Index (CCI).25

Relapse indicators. Four relapse proxies based on procedure codes associated with relapse were identified during the post period26,27: 1) OUD status change: change in diagnosis code from opioid dependence in remission (ICD-9-CM codes: 304.03, 304.73) to continuous or episodic opioid dependence (304.01, 304.02, 304.71, 304.72); 2) OUD inpatient: presence of an inpatient admission with a primary diagnosis of OUD; 3) OUD emergency department (ED): presence of an ED visit with any OUD diagnosis; and 4) OUD detox: presence of a detoxification claim with any OUD diagnosis.

Healthcare service utilization and costs. Specific healthcare service utilization and costs were measured during both the pre- and post periods: physician office visits and costs, proportion of members with at least 1 inpatient admission, inpatient hospital costs, proportion of members with at least 1 ED visit, ED costs, total medical costs, total prescription fills and costs, and total healthcare costs (medical + pharmacy costs).


Overall adherence analysis. Overall adherence groups based on an MPR cutoff of 0.80 were compared on relapse, MPR subgrouping, and healthcare costs during the post period. Means and standard deviations were computed for continuous variables, and counts were presented as frequencies and percentages. Statistically significant differences among cost outcomes were assessed via Mann-Whitney U tests, as the distribution of cost data were skewed positive, while χ2 tests of equality of proportions were used for the relapse indicators. Linear trends between postperiod healthcare costs and B-MAT adherence were examined using the 5-way MPR grouping variable. Costs were log transformed to normalize the distributions and were entered into 1-way analyses of variance examining linear contrasts.

Clinical subgroup exploratory analysis. The ETDNC group was compared with both the adherent group and the balance of the nonadherent groups on demographics and cost. The distribution of MPR groupings within the IA group was also examined. Results of these analyses confirmed that the IA group was appropriately categorized as being nonadherent, while the ETDNC group more closely resembled the adherent cases. Therefore, the primary analyses were conducted with the ETDNC cases moved from the nonadherent group to the adherent group. This updated grouping made up the enhanced adherence analysis.

Enhanced adherence analysis. The adherent group, now including the ETDNC cases, was compared with the nonadherent group on all demographic, service use, cost, and relapse measures during the post period. Descriptive and bivariate analyses were conducted similar to the overall adherence analysis. In addition, multivariate models were also constructed for select cost measures. For pharmacy, total medical, and total healthcare costs variables, gamma models with a log-link were estimated, controlling for age, gender, member type, and preperiod CCI score. Only those cases with non-zero values were included in these models.

MPR-based analysis. MPR subgroups were compared on demographic and relapse indicators via χ2 tests of equality of proportions. Linear trends (contrasts) between postperiod healthcare costs and B-MAT adherence were examined using the 5-way MPR grouping scheme as the independent variable. Relationships between raw cost means at each of the 5 adherence levels were plotted. Costs were then log transformed to normalize the distributions and were entered into 1-way analyses of variance. 

Relapse group analysis. Relapse groups were compared on postperiod costs. Additionally, the associations between relapse status and adherence were calculated for the overall nonadherent, IA, and MPR groups. All data management and analyses were conducted in SPSS version 20 (SPSS Inc; Chicago, Illinois).


Overall Adherence Results

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