Recommendation to Pharmacy Quality Alliance:

Stefan Kertesz, MD, MSc
8 min readOct 22, 2022

The Pharmacy Quality Alliance (PQA) regularly develops pharmacy-related quality measures, which are in turn adopted by more prominent quality metric agencies such as the National Committee for Quality Assurance. In 2022, PQA requested input on potential retirement of four quality measures related to opioid prescribing:

  1. Antipsychotic Use in Persons with Dementia: MDS (APD-MDS)
  2. Initial Opioid Prescribing at High Dosage (IOP-HD)
  3. Initial Opioid Prescribing for Long-Acting or Extended-Release Opioids (IOP-LA)
  4. Use of Opioids at High Dosage and from Multiple Providers in Persons without Cancer (OHDMP)

It’s important to note that one key measure not proposed for retirement is a measure that rates opioid prescribing quality based on the percentage of patients who receive doses greater than or equal to the equivalent of 90 morphine milligram equivalents (OHD). This latter measure has been the seedbed of insurance policy coverage decisions and law enforcement attention. It has played a substantial role in nonconsensual dose reductions among patients who receive prescribed opioids on a long-term basis

In response to the opportunity to comment, my colleagues and I focused on the value of retiring the fourth listed measure (Use of Opioids at High Dosage and from Multiple Providers in Persons without Cancer (OHDMP)). Our discussion also proposes that the OHD measure itself be considered for retirement as well. The letter submitted by myself, Juan Hincapie-Castillo, Kate Nicholson, and Adam J. Gordon is produced in full below:

We appreciate the opportunity to comment on the proposed retirement of the measure: “Use of Opioids at High Dosage and from Multiple Providers in Persons without Cancer (OHDMP)”. This measure assigns an adverse rating based on the combination of a dose received (greater than 90 morphine milligram equivalents) and reliance on ≥4 prescribers AND ≥4 pharmacies within ≤180 days. We urge the retirement of this measure. As part of this comment, we will urge retirement of an overlapping measure for which PQA has not sought public comment, but which overlaps in part with OHDMP, “Use of Opioids at High Dosage in Persons Without Cancer (OHD).”

This comment is offered by 4 individuals: two frontline primary care/addiction scholars (Kertesz & Gordon), a pharmacy scholar (Hincapie-Castillo), and a health rights attorney with lived experience of non-cancer pain (Nicholson).

The OHDMP measure has two components, both posing novel problems for patient safety when adopted as metrics of quality. One pertains to reliance on ≥4 prescribers AND ≥4 pharmacies within ≤180 days. The other concerns an opioid dose > 90 morphine milligram equivalents, which matches the existing “Use of Opioids at High Dosage in Persons Without Cancer (OHD)”. We discuss the two components in sequence.

At the outset, we note that reliance on the combination of four prescribers and four pharmacies drew PQA’s concern in 2015, for understandable reasons. In that era, redistribution of legal prescriptions and pill mills both played a significant role in the drug overdose crisis.

However, the US opioid prescribing environment has changed since 2015. Per capita opioid prescribing has fallen to levels last seen in 1993, according to the US Food and Drug Administration (1), and the illicit drug market has shifted definitively to illicitly sourced materials. Moreover, many additional prophylactic opioid-safety focused programs are operational. All states have enacted Prescription Drug Monitoring Programs, for example. At the same time, we have observed that many disabled patients with long-term opioid receipt actually require care from multiple clinicians and/or pharmacies in ways that should not be considered adverse either to them or their clinical caregivers.

For example, any patient who uses an integrated care system (including the Veterans Administration Medical Centers) may rely on a team of prescribing clinicians who cover for each other under a shared protocol. The four-prescriber threshold is easily exceeded. Separately, patients on long-term high-dose prescriptions have been forced to rely on multiple pharmacies, in our observation, because of a decisive clampdown by distributors and by commercial chain pharmacies worried about exceeding internal or federal thresholds. All clinicians should carefully review these situations, which they can do based on review of the mandatory prescription drug monitoring programs. However, the OHDMP metric promulgates a blanket understanding of all such situations as inappropriate. Inadvertently, it encourages an attitude of suspicion and mistrust toward a disabled patient population that is increasingly subject to abandonment.

The second component of the OHDMP measure concerns a dosage >90 MME. It is key to both OHDMP and to the OHD measure. This latter measure was taken up by the National Committee for Quality Assurance (NCQA) and in turn by federal agencies. It provided a convenient quality metric for payors, as well as a one-sized basis for scrutiny of prescribing by law enforcement agencies. Unfortunately the dose-focus of this measure was flawed in two regards, which we will review.

First, the high-dose metric conveyed an imprudent and aggressive simplification of the available science concerning predictors of overdose among persons who receive prescribed opioids (2). To be clear, prior retrospective observational studies lent credence to the idea that, on average, there is some increment in risk with a higher prescribed dose (2). However, enacting a binary quality metric based on prescription dose required assuming that limited retrospective findings reflected a simple cause-and-effect relationship, which proved to be untrue.

Large VA database analyses available in 2017 had, at the time, documented that non-prescription related risk factors conferred as much, or even greater risk increments, than prescribed dose itself (3).
Under such analyses a prescribed dose of 120 morphine milligram equivalents per day is associated with overdose/suicide similar to that in a person receiving <20 morphine milligram equivalents, if the latter patient also has Post-Traumatic Stress Disorder, for example. Second, among Veterans, the majority of overdose events happen at doses lower than 60 morphine milligram equivalents (4).

Together, such findings suggest that overdose death is not governed by prescribed dose in a simple, linear fashion. Rather, poisoning events are governed by a constellation of behavioral and medical risk factors. Some persons at high doses are safe, while others receiving low doses are at high risk. Using the dose threshold of 90 MME could, and in reality did, distract from safety-focused interventions that considered patients in a holistic way.

But perhaps most concerning is that the adoption of a 90-milligram threshold incentivized forced or abrupt opioid tapering practices that numerous studies now show increase patient risk. As of this writing, we are aware of 11 retrospective studies that report increased risk of suicidal events, illicit drug initiation, termination of care, or overdose events among persons receiving longterm prescribed opioids who undergo reduction or stoppage (5–15). Some such studies suggest that these practices elevate the risks of overdose and suicide by three to five fold. We would not assume that every retrospective study portrays a simple cause-and-effect relationship that operates similarly across all patients; not all patients are harmed by opioid reduction. But patients, on average, have been harmed by the way in which opioids have been terminated or reduced in connection with the quality metric.

Moreover, it bears underscoring that it was retrospective data, based on just 3 papers of modest methodologic quality, that led to the 90 morphine milligram equivalent quality metric in the first place. Even if that decision could have been defended at the time, it is no longer defensible.

For all of these reasons, we strongly urge PQA to withdraw its endorsement of any metric that enshrines the dose threshold of >90 morphine milligram equivalents. This would include the Use of Opioids at High Dosage and from Multiple Providers in Persons without Cancer (OHDMP), and the related OHD measure, and then to notify all partner agencies, including NCQA, that it has done so. We have personally witnessed grave harm to patients as a result of this measure and have labored for the last 5 years in the hope of returning safety to the care of such patients. We beg your support for this change.

Sincerely yours,

Stefan G. Kertesz, MD, MSc, Professor of Medicine, UAB Heersink School of Medicine

Kate Nicholson, JD Executive Director, National Pain Advocacy Center

Juan Hincapie-Castillo, PharmD, PhD, Assistant Professor, University of North Carolina School of Public Health and President, National Pain Advocacy Center

Adam J. Gordon, MD, MSc,
Elbert F. and Marie Christensen Endowed Research Professorship, Professor of Medicine and Psychiatry, University of Utah School of Medicine

We here note that we have no commercial payments or linkages to opioid litigations or firms involved in producing or selling these products.

References

1. United States Food and Drug Administration.FDA In Brief: FDA announces public
workshop to reconsider mandatory prescriber education for opioids. Accessible at: https://www.fda.gov/news-events/press-announcements/fda-brief-fda-announces-public-workshop-reconsider-mandatory-prescriber-education-opioids
2. Oliva EM, Bowe T, Tavakoli S, Martins S, Lewis ET, Paik M, et al. Development and applications of the Veterans Health Administration’s Stratification Tool for Opioid Risk Mitigation (STORM) to improve opioid safety and prevent overdose and suicide. Psychological Services. 2017;14(1):34–49.
3. Bohnert ASB, Valenstein M, Bair MJ, Ganoczy D, McCarthy JF, Ilgen MA, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011;305(13):1315–21.
4. Bohnert AS, Logan JE, Ganoczy D, Dowell D. A Detailed Exploration Into the Association of Prescribed Opioid Dosage and Overdose Deaths Among Patients With Chronic Pain. Med Care. 2016;54(5):435–41.
5. DiPrete BL, Ranapurwala SI, Maierhofer CN, Fulcher N, Chelminski PR, Ringwalt CL, et al. Association of Opioid Dose Reduction With Opioid Overdose and Opioid Use Disorder Among Patients Receiving High-Dose, Long-term Opioid Therapy in North Carolina. JAMA Network Open. 2022;5(4):e229191-e.
6. James JR, Scott JM, Klein JW, Jackson S, McKinney C, Novack M, et al. Mortality after discontinuation of primary care based chronic opioid therapy for pain: a retrospective cohort study (poster at Society of General Internal Medicine, 2018). Journal of General Internal Medicine. 2019;In Press.
7. Hallvik SE, El Ibrahimi S, Johnston K, Geddes J, Leichtling G, Korthuis PT, et al. Patient outcomes after opioid dose reduction among patients with chronic opioid therapy. Pain. 2022;163(1):83–90.
8. Larochelle MR, Lodi S, Yan S, Clothier BA, Goldsmith ES, Bohnert ASB. Comparative Effectiveness of Opioid Tapering or Abrupt Discontinuation vs No Dosage Change for Opioid Overdose or Suicide for Patients Receiving Stable Long-term Opioid Therapy. JAMA Netw Open. 2022;5(8):e2226523.
9. Oliva EM, Bowe T, Manhapra A, Kertesz S, Hah JM, Henderson P, et al. Associations between stopping prescriptions for opioids, length of opioid treatment, and overdose or suicide deaths in US veterans: observational evaluation. BMJ. 2020;368:m283.
10. Agnoli A, Xing G, Tancredi DJ, Magnan E, Jerant A, Fenton JJ. Association of Dose Tapering With Overdose or Mental Health Crisis Among Patients Prescribed Long-term Opioids. JAMA. 2021;326(5):411–9.
11. Fenton JJ, Magnan E, Tseregounis IE, Xing G, Agnoli AL, Tancredi DJ. Long-term Risk of Overdose or Mental Health Crisis After Opioid Dose Tapering. JAMA Netw Open. 2022;5(6):e2216726.
12. Perez HR, Buonora M, Cunningham CO, Heo M, Starrels JL. Opioid Taper Is Associated with Subsequent Termination of Care: a Retrospective Cohort Study. J Gen Intern Med. 2020;35(1):36–42.
13. Coffin PO, Rowe C, Oman N, Sinchek K, Santos GM, Faul M, et al. Illicit opioid use following changes in opioids prescribed for chronic non-cancer pain. PLoS One. 2020;15(5):e0232538.
14. Binswanger IA, Glanz JM, Faul M, Shoup JA, Quintana LM, Lyden J, et al. The Association between Opioid Discontinuation and Heroin Use: A Nested Case-Control Study. Drug and Alcohol Dependence. 2020;217:108248.
15. Glanz JM, Binswanger IA, Shetterly SM, Narwaney KJ, Xu S. Association Between Opioid Dose Variability and Opioid Overdose Among Adults Prescribed Long-term Opioid Therapy. JAMA Netw Open. 2019;2(4):e192613.

--

--

Stefan Kertesz, MD, MSc

I am a primary care doctor and researcher at University of Alabama at Birmingham who focuses on how to deliver high quality care for vulnerable populations.