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The American Journal of Managed Care June 2017
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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.
The other clinical subgroup, ETDNC, was included to represent a potential subpopulation of B-MAT patients who may not require prolonged use of B-MAT to gain the benefits of treatment. These members were originally placed into the nonadherent group, as their 1-year MPR was less than 0.80 due to their short course of B-MAT. Despite their short period of B-MAT, they exhibited no negative consequences characteristic of active OUD following treatment discontinuation. These members more closely resembled adherent members, as evidenced by their service utilization and cost profiles, along with a high proportion of primary subscribers. Therefore, the ETDNC members were ultimately assigned to the enhanced adherent group on the basis of their short-term adherence to B-MAT and lack of relapse during the follow-up. To assess the potential implications of switching the ETDNC group from nonadherent to adherent, analyses comparing the original adherent and revised enhanced adherence groups were conducted. Findings demonstrated that, although the relapse rate is slightly decreased in the enhanced adherence group due to ETDNC members showing no relapses during their course of B-MAT treatment, the direction and significance of the remaining relationships between the adherent and the nonadherent groups remain unchanged, indicating that the ETDNC members may represent 1 subgroup of adherent B-MAT members. 

The findings of this study indicate great variability within the B-MAT population, calling into question whether a strict definition of adherence is fully appropriate for this population. Although an 80% cutoff has been widely accepted as an indicator of acceptable adherence in various therapeutic areas,24 the 0.60 to 0.79 MPR group exhibited a cost profile similar to the adherent group, suggesting that this level of nonadherence may be adequate for some OUD patients to avoid the consequences characteristic of active OUD. The authors are not suggesting that this lower tier of adherence should be the target for all cases; however, in some cases, there may be a therapeutic benefit to instituting an intermediate adherence goal of 0.60 or above. Further, it may be appropriate to consider interventions that effectively raise adherence to 0.60 or above as successful, even if the intervention is not able to move the patient to the optimal level of adherence of 0.80. 


Administrative claims are known to include administrative coding errors,28 and they lack the clinical data necessary to provide insight into treatment. For instance, it may be difficult to determine with certainty whether buprenorphine was prescribed to primarily treat OUD or pain, as buprenorphine is indicated for both conditions. Requiring an OUD diagnosis largely alleviated the issue in this study, although the possibility of pain being the reason for buprenorphine cannot be discounted. Also, claims-based proxies used to estimate relapse in this study returned slightly lower levels of relapse compared with a prior study that used clinically based endpoints for relapse.18 Alternative data sources, such as urine drug screen results, are needed to confirm the relapse proxies used here, and to define clinical indicators of success with treatment. Additionally, the small sample size of the IA and ETDNC groups prohibited statistical testing. Replication of this study in larger commercial or public sector data sets is warranted, as this study may not generalize to other populations. Additionally, although OUD is common within severely mentally ill populations, this study excluded these members, as the primary outcome was adherence. The final limitation is the potential endogeneity of B-MAT adherence, as factors unmeasured in the claims may drive these outcomes. 


This study confirms the burden of B-MAT nonadherence on the healthcare system through an analysis of service utilization and healthcare expenditure and extends these findings to relapse rates. Furthermore, specific patterns of adherence were examined through the construction of the adherence-based MPR subgroups and the clinically-focused ETDNC and IA subgroups. Although larger samples of OUD patients are needed to replicate and validate the findings of this study, the definition of various subgroups provides initial insight into patterns of B-MAT use. These groups could be essential to developing more effective methods for case finding in support of adherence-enhancing programs. Improved methods, such as those initiated here, to identify members in need of alternative interventions and to assess success with treatment are required to promote improved management of the OUD population, which stands to benefit both health plans and OUD patients by improving outcomes and containing healthcare costs.

Author Affiliations: Health Analytics, LLC (CR, JT, BLB), Columbia, MD; Indivior, Inc (VRN, NR), Richmond, VA; Aetna Behavioral Health (HU), Blue Bell, PA; Institute of Addiction Medicine (JV), Plymouth Meeting, PA.

Source of Funding: Indivior, Inc, funded this study.

Author Disclosures: Dr Ronquest is an employee of and Mr Nadipelli is an employee and stockholder of Individor Inc, which is engaged in addiction research and new product/pharmacotherapy development. Drs Ruetsch and Brady and Mr Tkacz are employed by Health Analytics, LLC, a CRO that was paid by Individor, Inc, to conduct the study. The remaining authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (BLB, VRN, CR, JT, HU, JV); acquisition of data (CR, JT, HU); analysis and interpretation of data (BLB, VRN, CR, NR, JT, JV); drafting of the manuscript (BLB, VRN, NR, JT, JV); critical revision of the manuscript for important intellectual content (BLB, VRN, CR, NR, JT, HU, JV); statistical analysis (JT); obtaining funding (VRN, CR); administrative, technical, or logistic support (VRN, CR); and supervision (BLB, VRN, CR).

Address Correspondence to: Joseph Tkacz, MS, Health Analytics, LLC, 9200 Rumsey Rd, Ste 215, Columbia, MD 21045. E-mail:

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