In the United States, the number of opioid overdoses has reached epidemic proportions [1-3]. In the past two decades (1999-2017), more than 700,000 people have died from drug overdose in the United States [1-3]. In 2017, more than 68 percent of the drug overdose deaths involved an opioid, and the opioid death rate was six times higher than in 1999 [1-3]. The top six states with the highest rates of opioid-related overdose death were West Virginia (WV) (57.8 per 100,000 people), followed by Ohio (OH) (46.3 per 100,000 people), Penn-sylvania (PA) (44.3 per 100,000 people), the District of Columbia (DC) (44.0 per 100,000 people), Kentucky (KY) (37.2 per 100,000 people), and Delaware (DE) (37.0 per 100,000 people). Three of these states (DE, PA, and WV) are within our Highmark Inc. service area [4].

People with Opioid Use Disorder (OUD) are seen with all educational and socioeconomic backgrounds [5,6]. Given that both epigenetics and related social determinants of health are associated with opioid addiction and fatal and non-fatal overdoses, other reported factors may have also played a role [7-12]. These include less-than-optimal legislation; drug industry supply/demand; health policy; safe prescribing practices; quality of data collection; multi-sector partnerships to address the opioid epidemic; monitoring and tracking of drug misuse, abuse, and fraud; provider-focused education and guidance for safe prescribing; and access to and availability of behavioral health services and treatment options, among others [7-12]. Evidence-based, data-driven models addressing these opioid-related factors remain sparse [7-12]. Individuals can become addicted to opioid in as little as five days of exposure [1, 9]. Furthermore, dose and duration of an opioid prescription is linked to the likelihood of a patient being diagnosed with OUD [1,9,13,14].

It is well documented that the rise in opioid overdose deaths involving any opioid is multifactorial [12-14]. Three distinct waves are commonly reported [1]: Wave 1 began in 1990, with a rise in prescription opioid overdose deaths [1,15]. Wave 2 began in 2010, with a rise in heroin overdose deaths. Wave 3 began in 2015, with a rise in synthetic opioid (illicitly-manufactured fentanyl) overdose deaths [1]. Opioids can be prescribed to patients by authorized healthcare practitioners to treat pain, but serious risks and side effects may result [1]. Non-medical use of prescription drugs exists [1,13,16,17], and typically involves a person taking more than the prescribed dose, taking a drug prescribed for another person, or taking a drug obtained illegally or without a legitimate prescription [1,13,17]. More than 12 million people report having misused these medications [12,17]. Health care costs for opioid abusers were eight times higher than for non-abusers [18]. Employees with substance abuse disorder have three times more in health care costs of the average worker, nearly $2,500 in absenteeism [19]. Strategies to prevent opioid misuse, abuse, and diversion may reduce the associated costs due to excessive healthcare utilization [20]. For insured members, the Blue Cross Blue Shield (BCBS) Health Index identifies OUD as the fifth-most impactful condition affecting the health of commercially insured members in America [6]. Given that OUD can be prevented [2], evidence-based strategies are needed to help reduce OUD risk; and to increase access to OUD treatment if the person has developed dependence.

As a public health crisis, it is important to consider a broad and comprehensive framework for intervening to mitigate harm and further spread of opioid addiction. Unlike other types of epidemics, this one was iatrogenic, due to a combination of social factors, pharmaceutical company marketing and some medical association support, leading to overprescribing of opioids in the late 1990's for acute and chronic pain [1,22]. With 11% of the U.S. population having some form of chronic pain, it is important to realize how this overprescribing created a large population of Americans conditioned to be or become addicted with escalating risk beyond just the addiction itself [23]. Generally, someone with chronic back pain would not seek street drugs for the relief of that pain. However, the prevailing medical practice of the late 1990's and early 2000's was to prescribe opioids more liberally for acute and chronic pain. This practice not only created persons with addiction, but also created a population of people who were conditioned now to seek opioids for pain relief that they would not otherwise had considered. If the legal source is cut off or insufficient, it is now a plausible alternative for this person to consider the cheaper and more potent street drugs. And that is exactly what we have seen. During the "second wave" of the opioid crisis, four in five (80%) of new heroin users started out misusing prescription painkillers [24]. This switch to street injectable drugs brings all of the additional issues of medical complications due to non-sterile injections, infectious diseases, criminal activity and unregulated drug compounds. The introduction of more deadly forms such as fentanyl has increased the stakes and the importance of interrupting this pathway as well as aggressive identification and rehabilitation for those with OUD.

As with other epidemics, a public health prevention framework seems particularly useful to address root causes and effects [5]. The recognition of "Deaths of Despair", in predominately middle-aged white males of which opioid addiction and overdoses are one of the manifestations which point to the underlying structural and social determinant factors that must be addressed over time to turn the tide on the crisis [7-35]. Reducing opioid prescriptions in the context of a comprehensive strategy would more likely result in sustainable improvement and reduction in the cost, disruption, morbidity and mortality of opioid addiction. With this approach in mind, Highmark developed, implemented and evaluated quality management-focused opioid interventions utilizing such a strategy (Fig. 1). The strategy focused on three preventive leverage points:

1. Primary Prevention: focused on the more appropriate management of pain to reduce the need to use opioids. This includes the application of evidence-based traditional and alternative treatments for pain.
2. Secondary Prevention: for those circumstances where opioids were indicated, the aim was to reduce overprescribing of opioids by putting in place tools and controls to encourage safe prescribing of opioids consistent with the CDC guidelines [8,9]. This also included de-escalating protocols for those on high doses.
3. Tertiary Prevention: for those with OUD the goal was to reduce morbidity, mortality and family/community disruption while proactively offering interventions to support a lasting recovery.

These were provider, member, and community-focused interventions in DE, PA, and WV, and executed over the time period. We examined medical and pharmacy claims for data (2013-2017) by age (18-65 years of age), product (commercial, diagnosis with OUD), total Opioid RX fills (per 1,000 members), opioid use by dose (dosage level by MME), opioid use by duration (number days of opioid use), rate per 1,000 members diagnosed with OUD, and region (DE, PA, and WV). We also discuss the integrated and coordinated strategies needed for the deployment of an integrated public health approach used to address the current opioid epidemic.

This opioid work was completed by Highmark Inc. for quality assurance, and now these collected data were used to conduct a retrospective review for research purposes. This retrospective review was approved by the Allegheny Singer Research Institute - WPAHS Institutional Review Board.

Total Opioid RX fills per 1,000 Members.

As shown in Fig. (2), between 2013 and 2017, there was a 19 percent decrease (starting point 589, ending point of 474) across the eligible Highmark membership of total opioid prescription fills normalized per 1,000 members. A 15% decrease was observed between 2016 and 2017, and this was a sharper decrease than observed in previous years between 2013 and 2016. In terms of RX fills by geography, the results varied by state between 2016 and 2017, with the biggest decreases in WV and PA at 16% each and 10% in DE. This trend was similar to the BCBSA^® national averages for commercial members. To also compare our averages with non-BCBSA^® national averages, we ran a secondary analysis and measured our results to Optum^® benchmarks, which included both commercial and Medicare Advantage members. A similar trend was also observed.

Opioid Use by Duration and Opioid Prescription average Dosage Level by MME.

As shown in Fig. (3), over the course of four years, significant positive changes were seen across the eligible Highmark member population. There was a shift in the duration of opioid prescriptions from being 4 or more days to being 3 days or fewer. The same trend was seen across BCBSA^® national trends for opioid use by duration. As shown in Fig. (4), when looking at average opioid prescription dosage in MME, Highmark exhibited significant shifts in decreasing the potency of the prescriptions to lower-dose and lower MME prescriptions. For those members who previously would have been prescribed higher doses, in particular in the 20-89 MME range, there was a significant shift to lower dose prescriptions, notably 0-19 MME. While trends were similar to BCBSA® national averages and Optum^® benchmarks (data not shown), Highmark exhibited superior results in lowering the average strength of opioid prescriptions compared to the BCBSA^®.

Our results showed decreases in the total number of opioid RX fills; opioid use by duration; and opioid dosage in MME for our commercial members in DE, PA, and WV. Over these years, three major shifts in behavior resulted, which align with the CDC and NIDA prescribing guidelines [1, 10-23]. First, between 2013 and 2017, there was a decrease of 19% of total opioid prescription fills. A 15% decrease was observed in 2017, up from 5% in 2016, and with wide variation by state. Our 2017 initiatives included additional pharmacy policy changes like quantity limits for safe prescribing and to prevent abuse, misuse and diversions. We do not know whether individuals shifted from prescribed drugs to illicit injectable drugs because it was outside the scope of this study. However, our three-pronged strategy did include provider, member, and community focused education. As expected, additional studies examining OUD treatment and health policy options for the prevention of any unintended public health consequences which may result from illicit drug use are needed.Second, between 2013 and 2017, there was a shift for opioid prescription patterns to shorter durations, from being 4 or more days to being 3 days or fewer. The majority of these members switched to 7 days or less of opioid use. In 2017, 84% of the members took 7 days or less, which compared to 57% at that level in BCBSA^® data. Third, there was a shift for taking opioids at a much lower dosage. Results showed a reduction by 13 percentage points of the number of members on higher strength 20+ MMEs opioids.

Determining the pain management strategies used by members taking opioids at much lower levels and / or for a much shorter period of time was outside the scope of this study. However, our approach did include modifications of our opioid medical policies to reflect that alternative treatments are covered benefits for Highmark fully-insured members. Cognitive behavioral therapy through psychologists as adjunctive therapy for pain as well as a Complementary and Alternative Medicine network were also provided. Additional studies examining non-opioid prescribed therapy options and utilization of clinical and behavioral health services by age, sex, and regions are needed. In terms of OUD diagnosis, results showed that our members are getting diagnosed. However, additional studies are needed to determine whether these diagnosed patients received and / or completed treatment. Our findings did not rule out the possibility that other factors [1,33-35] like the increased prevalence of depression, environmental factors, epigenetics, and phenomena like "Death of Despair" [34-35], may also impact our results. If true, then we may yield more effective outcomes by refining our three-pronged strategy for particular populations.

Fig (1). Highmark Inc. three-pronged public health approach for addressing the opioid epidemic in delaware, pennsylvania, and west virginia, 2017-2018.

Fig (2). Highmark Inc. (HM) total opioid prescription (rx) fills per 1,000 commercial members compared to blue cross blue shield national averages, 2013-2017.

Fig (3). Highmark Inc. (HM) opioid use by duration (number of days) among commercial members, 2013 and 2017.

Fig (4). Highmark Inc. opioid prescription average dosage level by mme among commercial members, 2013 and 2017.

Our retrospective study had several limitations. First, our opioid results included only adult Highmark commercial members < 65 years of age in DE, PA, and WV and are not generalizable to all segments in society. Second, our data were reported by state-level only. Although we did follow the standard practice of state-level reporting used by others in the opioid space [1-3], other related reporting (e.g. by zip code or by race/ethnicity) was outside the scope of this study. Third, we did not examine the cause of pain or type of pain management therapy for which the member was issued the prescribed opioid. Thus, we cannot comment as to whether the member's pain could have been effectively managed without opioids and /or if the member received any complementary and alternative medicine options.

We enacted significant programs and policy changes designed to help members as they battle opioid abuse and addiction in our community-focused and partner-driven war on opioids. These were provider, member, and community focused interventions. Because no single entity can do this alone [1], we collaborated with local, state, and federal agencies; local school districts; businesses; law and drug enforcement; and community-and faith-based organizations.

Although our results showed improvements over a five-year period, it is unknown whether these results can be sustained in 2018 and beyond. Since our results were sustained in three of the top six states with the highest rates of opioid-related overdose death, we predict that these results could be sustained over time to some degree. Opioid prescribing is declining; diagnosis has increased, providing opportunity for evidence-based treatment. However, nationally, the opioid death rate has yet to peak [36-41]. We believe that continued comprehensive efforts, expansion of treatment access to MAT [42-43], risk reduction through availability of rescue medication [44-55], strategies around non-fatal overdose protocols and leveraging technologies such as telemedicine [46-47] will bend this curve.

The burden of opioid addiction and mortality in America is substantial and increasing, including in DE, PA, and WV. Utilizing a three-pronged strategy, coordinated approaches and CBPR frameworks, our study demonstrated improvements in total Opioid RX fills, opioid use by dose (MME), opioid use by duration, and number of members diagnosed with OUD. This innovative approach could also help alleviate the opioid epidemic by changing industry practices and building public awareness. No one organization alone can reverse this opioid epidemic. Other health systems, insurance plans, and policy makers in the opioid space should consider using these approaches when setting priorities, allocating their limited resources, designing programs to prevent OUD, improving access and options for proper management, and getting individuals into treatment.