Safe Use of Opioids – Concurrent Prescribing

Strengths:

• Submission relies upon a CDC guideline finding a “dose-dependent association” between opioid use and risk for overdose events, including death, was found consistently across two studies in the clinical evidence review and several epidemiologic studies in the contextual evidence review.
• Co-prescription of opioids with benzodiazepines was also found to increase risk for potentially fatal overdose in three studies included in the contextual evidence review. The studies found evidence of concurrent benzodiazepine use in 31 to 61 percent of those deceased from overdose.
• The developer examined data across 11 hospitals based on the measure specifications. Individual hospital performance rates ranged from 14% to 23.92% with mean performance of 17%, indicating room for improvement.

Limitations:

• No empirical demonstration of an association between the measure focus and a material outcome.
• Submission does not mention potential adverse effects (e.g., insufficient pain management).
• No information on whether the target population finds the measure meaningful. However, evidence provided depict the safety concerns to patients due to risk of overdose.

Rationale:

Although there is no empirical demonstration of importance, further studies are highly unlikely to have a significant impact on domain rating.

The measure is based on guidelines. Concurrent prescriptions of opioids or opioids and benzodiazepines is identified in literature to place patients at a greater risk of unintentional overdose, tying measurement to improved patient outcomes. Allow lower scores equals better performance, mean performance of 17% still indicates less than optimal performance.

The developer did not provide sufficient information in the importance section of the submission to meet the criteria. 

• There is no evidence provided in the submission regarding why the measure is important.   Everyone knows that there is an opioid epidemic in this country, but no evidence is provided regarding this issue.   What is the business case for the measure/why is this measure important? Where’s the data showing that the opioid epidemic is an issue and that this measure will help to improve the outcome of overdose/death. 
• The submission includes this detail “A dose-dependent association” between opioid use and risk for overdose events, including death, was found consistently across two studies in the clinical evidence review and several epidemiologic studies in the contextual evidence review. However, the measure isn’t capturing the dosage the patient is discharged on.  The measure captures patients "prescribed, or continued on,        two or more opioids or an opioid and benzodiazepine concurrently at discharge." There are no empirical studies with data provided that support the first portion of the numerator (i.e., prescribed, or continued on, two or more opioids at discharge).  
• It is unclear if the evidence is reflective of the same measure population, as it is unclear from the  measure specifications what facilities (e.g., acute care hospitals, long-term acute care hospitals, cancer hospitals, psych hospitals) this measure is captured under. 
• There is a gap, but only 11 hospitals are analyzed.  The specifications say that the measure is not      based on a sample, so why is the gap data provided only for 11 hospitals and not all facilities captured in  the measure?   There is also no explanation of what types of hospitals are included in the analysis. Are   they acute care, rural, cancer hospitals, psych hospitals? 
• The information provided in the submission does not conclude that providers feel that this measure is meaningful.  The submission states, “We interviewed 12 providers for their feedback on the measure.    Some providers indicated that it will be useful to have data on sub-group prescribing practices to provide population-based evidence-based care to look for large discrepancies.”  Also in light of the opioid epidemic do patients/families find the measure meaningful? 

The intent of the measure to improve the safety of this population is appropriate. There is limited data to show any trends due to the measure being reported in 2023 to show any improvements. 

Evidence base exists to support the measure. The data from the first year of the measure indicates there is a gap with a mean performance of 17% across 11 hospitals. Additional data from a large sample of hospitals would be beneficial.

Provider feedback was not conclusive on support for the measure. 

Patient population wasn't surveyed but would be helpful to consider. 

The submission is based on CDC guidelines finding a “dose-dependent association” between opioid use and risk for overdose events, including death combination of opioids with benzodiazepines have been found to increase the risk for potentially fatal overdose. However, it would be helpful to know if this measure was meaningful and if there was any material outcome from implementing this measure. 

Significant post inpatient morbidity/mortality associated with being on multiple opioids as well as an opioid and a benzodiazepine.

The description provides a rational on measure importance. The opioid epidemic is well documented, but it does not provide a great link to the measure’s intention. Also, there was data from only 11 hospitals (out of 4,368 that reported) and only 12 providers were interviewed. Increasing the hospitals, especially a geographic mix, would provide greater insights.

Safe opioid prescribing is important issue. 

The importance of this measure is evident through the well documented nationwide opioid crisis. There is also extensive medical evidence reported by many reliable entities (CDC, CMS, AMA) affirms that patients who take opioids concurrently with central nervous system depressants such as benzodiazepines are at an increased risk of life threatening overdoses. 

In review of the importance section of the evaluation it appears to be lacking the appropriate information around trending to understand if we are seeing an increase in concurrent prescriptions. Adverse impact on patients with pain that do not currently have a diagnosis that is excluded, which can lead providers to prescribe less often due to provider level analysis. In showing the research and applying it and trending the data over time will show that the impact of improvement processes can lend to positive or desirable outcome. This is now implemented, and it would be useful to understand the ideal state and what measures/tactics can be taken to improve the overall measurement outcome. Additionally, the measure title states inpatient, but the measure logic definitions, data dictionary it states ED patients and observation unit patients. It is not clear if patients from these phases in care should or should not be included. Including a hospital's ED patients and Acute Inpatient Patients may have an impact on the denominator. it would be helpful to understand why we are seeing higher rates amongst elderly 65 and older or Medicare Population.

Unsure of how this measure will impact the intended outcome. There is no discussion of how to mitigate potential adverse effects of untreated pain. 

The information underscores the significance of the CDC guideline in guiding opioid prescribing practices, and the PQM data highlights variations in performance across hospitals. The feedback from providers suggests that further granularity in the data, focusing on subgroup prescribing practices, could enhance evidence-based care and address potential discrepancies.

A variety of studies show a relationship between prescription opioid dose (MEDD or Morphine Equivalent Daily Dose or MME or Morphine Milligram Equivalents) and risk for accidental poisoning. Boehnert et al and Dunn et. al were some of the earliest papers that reported on this phenomenon.  In both of these studies, hazard ratios for increased morbidity and mortality, increased exponentially above 50-90 MEDD/MME.  Most deaths have been observed to be associated with doses above 60 MEDD/MME.  

Park et. al and other authors have showed increased risk with the addition of benzodiazepines top opioids with risk increasing proportional to the base opioid MEDD/MME. Higher Opioid MEDD/MME when combined with a benzodiazepine drives roughly double the hazard ratio of accidental poisoning and death risk at each cut-point level. The Park et al paper showing this phenomenon associated with benzodiazepines appeared to be a class effect, however, temazepam did not appear to be associated with this phenomenon.  There is a lack of follow-up on temazepam in subsequent studies to see if this phenomena can be explained. 

It is less clear why two opioid prescriptions vs. one opioid prescription are thought to pose an increased risk to patients and often opioids prescriptions used in patients on chronic medications use a long acting and short acting opioid.  This criteria in the metric are therefore problematic as it not explained in the measure rationale.  In thinking about potential pitfalls associated with this, there is a possibility that providers, in order to meet the measure, might convert patients to a single opioid that might be less appropriate and result in a higher MEDD/MME. 

The challenge, physiologically to patients that causes mortality related harm is primarily the risk of Opioid Induced Respiratory Depression (OIRD), the primary mechanism thought to be responsible for causing the harms associated with high dose MEDD/MME and opioid and benzodiazepine concurrent use.  The relationship and concern with opioid and benzodiazepine co-prescribing as well as high dose opioid prescribing is more clearly defined and associated with OIRD in a dose dependent relationship and the latter portion of the metric is on more solid footing. Any dose of an opioid with a benzodiazepine is a concern for patient safety. 

Recently, Yale and other groups have published guidelines that advocate for chronic opioids to not be fully stopped prior to initiation of buprenorphine or buprenorphine-naloxone using a method known as overlap therapy which involves continuing the patient's opioid and titrating up the agonist/antagonist while titrating down the pure agonist.  Agonist/antagonist therapy is also being used to treat chronic pain and eliminate agonist therapy.  This transition takes time and may not be able to be completely accomplished during and inpatient stay.  

Benzodiazepines would be likely difficult to fully transition off of during the average hospitalization and thus an exclusion for patients transitioned to a longer-term care setting for benzodiazepine taper or who have been given a terminal script for benzodiazepine taper might be considered to incentivize this important intervention.   

Smaller patient populations seemed to fare worse than larger patient populations on performance on this metric.  Since most hospitals that are smaller are rural and less resourced, it might result in these hospitals not performing as well on this metric. 

Despite these shortcomings, which should be addressed, the metric adds considerable value with a focus on opioid and benzodiazepine concurrent prescribing being its strongest feature.  It would be advisable to consider modifying the first part of the measure to focus on MEDD/MME (as happened with the VA in the Opioid Safety Initiative) versus focusing on the number of opioid scripts written.  It would also be advised to allow exceptions for benzodiazepine tapers.  The addition of low dose buprenorphine or buprenorphine-naloxone concurrently prescribed at discharge might also be considered as an exclusion for this metric.  Lastly, expansion of the population and the number of sites evaluated should be expanded. 

The opioid crisis is a significant issue for US healthcare.  We need measures that can help recognize those that are at risk and perhaps should be treated differently.  This fills a gap in measurement that has been lacking for a long time.

As indicated, opioid overdoses are a major, and increasing, public health concern. Studies have demonstrated the impact of concurrent opioid or opioid and benzodiazepine use. 

Safety is an area of importance to patients.

The developer cites the 2022 CDC guideline, which states there is a dose-dependent association between opioid use and risk for overdose events. In addition, they cite three studies from the CDC guideline, which reported evidence of concurrent benzodiazepine use in 31 to 61 percent of those deceased from overdose. However, they do not present graded guidelines and they do not provide evidence indicating how much concurrent use of opioids or concurrent use of opioids and benzodiazepines leads to increased risk of negative outcomes (e.g., death, overdose, hospitalization). It would be helpful to see a more detailed summary of the evidence and empirical evidence linking the concurrent prescribing of opioids/benzodiazepines with health outcomes (if available). 

In addition, I did not see any information in the measure submission indicating that the developer had asked patients if the measure was meaningful to them. They could address this by asking patients for feedback on the measure (e.g., through focus groups or survey).

This measure is based on current guidelines for practice of limiting concurrent opioid or opioid/benzodiazepine medication prescribing.  There is limited data on this measure historically given initial measurement period was 2023 so limited trend data availability