From the perspective of the payer of direct medical costs, the cost-effectiveness ratio over the 1-year horizon was $1,376 per QALY and $308 per opioid-free year. While the point estimates of cost-effectiveness are well within the range of what would be considered cost effective, there is a considerable range of sampling uncertainty, particularly with respect to the results based on QALYs. For example, the acceptability curve shows that the cost-effectiveness ratio of BUP relative to DETOX has an 86% chance of being accepted as cost-effective for a threshold of $100,000 per QALY. 20
This finding means that at this threshold we cannot reject the null hypothesis of no difference with 95% confidence. However, the 95% confidence interval for the cost per opioid-free year suggests that for this endpoint the study result was positive so long as we are willing to pay $21,100 per opioid-free year. Putting these two results together, we conclude that the trial provides good, but not definitive, evidence that extended buprenorphine-naloxone treatment versus brief detoxification represents good value for this population of opioid-dependent youth.
A definitive declaration of cost-effectiveness would require that the cost-effectiveness ratio be below society’s willingness to pay for the unit of effectiveness 95% of the time. One problem with such a declaration is that the willingness to pay for a unit of effectiveness is unknown and can vary by setting. For example, in the U.S. the cited range is typically from $50,000 to $200,000 per QALY. 20
For effectiveness measures that are clinical in nature, such as an opioid-free year, even rules of thumb are unavailable. A second problem, specific to our study, is that the differences in QALYs are only marginally significant and lead to a cost-effectiveness ratio that is not statistically cost-effective. The clinical outcome is highly statistically significant, but there is no threshold from which to test the statistical significance of the cost-effectiveness ratio base on the clinical outcome. Thus, we are left with good, but not definitive evidence.
From the perspective of the outpatient treatment program initiating the intervention, the cost-effectiveness ratio over the 1-year horizon was $25,049 per QALY and $5,610 per opioid-free year. The lower ratio faced by payers of direct medical costs may suggest that they have a greater incentive for adoption of the intervention than do the treatment programs and that insurers would benefit from covering extended buprenorphine treatment.
Providing 12 weeks of buprenorphine-naloxone treatment compared to brief detoxification with buprenorphine-naloxone increased the outpatient program treatment cost by $1514 (P<.001). When all direct medical costs are considered, rather than only study-provided drug treatment, the 1-year incremental direct medical costs were only $83 (p=0.97). From a societal perspective, in which nonmedical costs are also included, there was a net social savings of $31,264 (p=0.20). These differing cost estimates reinforce the finding that the economic impact of BUP depends on the perspective from which it is evaluated. While the outpatient treatment program initiating the intervention would incur additional expenses, these expenses appear to be offset elsewhere in the healthcare system with additional savings generated in society largely from crime reduction. These offsets were considerable even in a population of youth with shorter addiction histories than are typical in outpatient treatment programs that serve older patients. They result largely because opioid dependent youth present to treatment with multiple co-existing conditions such as poor school attendance, criminal behaviors and juvenile justice system involvement and psychiatric disorders. 21
The favorable, though not statistically significant, net social costs of the intervention suggest that social benefits may result if treatment programs implement buprenorphine treatment for youth.
This is the first cost-effectiveness study of extended buprenorphine-naloxone treatment in opioid-dependent youth relative to detoxification. While in adults the comparison has usually been relative to methadone treatment22–24
, the limited use of agonist maintenance for youth makes comparison with detoxification the more relevant comparator. Methadone use for adolescents has been limited by stigma and regulations that require those under 18 to have two documented, unsuccessful drug-free treatments within a 12-month period, and that a legal guardian provide consent in writing before starting methadone maintenance.
The low follow-up rate is a limitation of this study. Because we did not find evidence of non-ignorable missingness, we addressed this issue with missing data methods that assume the data are missing at random. Lack of difference between our results and results observed when we employ an assumption of missing completely random means it is unlikely that the low follow-up rates negate our main findings. The low follow-up rate, however, does reduce the power of the 1-year result.
This study is also limited in its ability to inform policy related to the ideal duration of treatment. The economic impact of long-term maintenance with buprenorphine-naloxone may be very different than the 12-week extended-treatment protocol studied here, but this alternative would require further study. Substantial use of the treatment drug within the BUP group after the 12 week course of treatment was evident in our data, but those extending treatment did so beyond the treatment protocol and can not be reliably evaluated outside of the intent-to-treat approach taken in this analysis. Finally, the use of opioid-free urines for the calculation of cost-effectiveness ignores decreases in use of opioids which may have additional cost-benefits.
In conclusion, extended Buprenorphine-naloxone treatment for youth relative to detoxification may have social benefits and be cost-effective. It is of greater value to the insurer than to the outpatient treatment program because the effectiveness of treatment results in medical cost offsets that are not captured by the treatment program. This suggests that there is an incentive within health insurance plans to cover the provision of these services. Similarly, the apparent reduction in crime-related costs in the BUP group is a benefit to society that is not captured by the health care system. This finding suggests a role for public funding of effective treatment programs such as extended buprenorphine-naloxone treatment for opioid-dependent youth.