CDC Proposes Updating Practice Guideline for Prescribing Opioids, Warning Against Continued Misapplication

The Centers for Disease Control and Prevention (“CDC”) issued a voluntary practice guideline on opioid prescribing for clinicians treating chronic pain five years ago.  (We blogged on the final 2016 guideline here on March 17, 2016).  On February 10th, the agency published a comprehensive proposal to update the guideline.  Proposed 2022 CDC Clinical Practice Guideline for Prescribing Opioids, 87 Fed. Reg. 7,838 (Feb. 10, 2022); Dowell, Deborah, MD., et al, CDC Clinical Practice Guideline for Prescribing Opioids-United States, 2022, CDC.  As explained more fully below, CDC concedes that states, insurers, pharmacies and pharmacy benefit managers have implemented laws, regulations and policies that have misapplied the 2016 guideline.  Some have interpreted the 2016 guideline as requiring a hard, daily opioid dosage of 50-90 morphine milligram equivalent (“MMEs”) and opioid treatment duration of three to seven days.  CDC’s proposed 2022 practice guideline takes a more flexible, patient-specific approach relying on clinicians’ judgment rather than applying “inflexible standards of care across patient populations.”  Proposed 2022 CDC Practice Guideline, 7,839.

We believe the proposed 2022 guideline provides much needed clarification of CDC’s recommendations for both practitioners and regulators.  We remain concerned, however, that the “misapplication” of the 2016 guideline and the same risk for the 2022 proposed guideline, may continue to adversely affect patient care.

Purpose of the Proposed Guideline

CDC intends the proposed guideline to improve communication between clinicians and patients about the risks and benefits of pain treatment that includes opioid therapy; improve the safety and effectiveness of pain treatment with an eye towards improved function and patient quality of life; and reduce opioid use disorder, overdose and death associated with long-term opioid therapy.  Id.

2016 Guideline

As CDC notes in the 2022 proposed guideline, the 2016 guideline provided twelve recommendations for primary care clinicians who prescribe opioids for chronic pain in outpatient settings.  CDC Clinical Practice Guideline, 10.  The 2016 guideline recommendations were based on systematic review of the best available evidence with input from experts, the public and an advisory committee, noting that the goals were to ensure clinicians and patients consider safer, more effective pain treatment, improve patient outcomes with reduced pain and improved function and reduce opioid use disorder, overdose, or other adverse events.  Id. at 11.  The guideline impacted the continuing decline of total numbers of opioid prescriptions issued in the U.S., and although not an intention, also impacted laws, regulations and policies.  Id.  Over half the states enacted legislation limiting initial opioid prescriptions for acute pain to seven days or less while insurers, pharmacy benefit managers and pharmacies enacted similar policies.  Id.  CDC emphasizes that while some of the initiatives had positive results for some patients, guideline “recommendations are voluntary and intended to be flexible in support, not supplant, individualized, patient-centered care.”  Id. at 12.  CDC notes with “particular concern” that some policies purportedly from the 2016 guideline “have, in fact, been notably inconsistent” with the guideline “and have gone well beyond its clinical recommendations.”  Id.  CDC notes that misapplication of recommendations have even extended to cancer and palliative patients, opioid tapering and abrupt discontinuation without patient collaboration, rigid application of opioid dosage thresholds, duration limits, and patient dismissals.  Id.  Misapplication of the guideline has “contributed to patient harm, including untreated and undertreatment of pain, serious withdrawal symptoms, worsening pain outcomes, psychological distress, overdose, and suicidal ideation and behavior.”  Id.

The Proposed Guideline

From our perspective, given misapplication of the 2016 guideline, we begin with what the proposed guideline is not rather than what it is.  The proposed guideline is not “[a] replacement for clinical judgment or individualized, person-centered care” and its recommendations are not inflexible standards of patient care.  Id. at 2.  The guideline is neither law, regulation nor policy.  The guideline is not applicable to the treatment of pain related to sickle cell disease, or palliative or end-of-life care.  Id.

According to the CDC, the proposed guideline is a clinical tool meant “to improve communication between clinicians and patients, empowering them to make more informed, person-centered decisions related to pain care together.”  Id.  It is intended for clinicians (primary care, physicians, nurse practitioners, physician assistants, and oral health practitioners) who provide pain care to outpatients aged 18 years or older with acute pain (lasting less than a month), subacute pain (lasting 1-3 months) or chronic pain (lasting more than 3 months) in outpatient settings.  Recommendations do not apply to inpatient care during hospitalization, emergency department or other observed settings, but do apply to prescribing for pain management upon discharge.  Id. at 3.

Methodology

CDC developed the proposed practice guideline using Grading of Recommendations Assessment, Development, and Evaluation (“GRADE”) framework.  Id.  Recommendations are based on a review of available scientific evidence; benefits and harms; patients’, caregivers’, and clinicians’ values and preferences; and resource allocation (such as costs to patients or health systems, including clinician time).  CDC also obtained input from conversations with patients, caregivers, and clinicians, through Federal Register notices and comments from the public, peer reviewers, and an advisory committee.  Id.

Recommendations

The proposed guideline generally follows the organization of the 2016 guideline, listing recommendations within four general areas: (1) determining whether to initiate opioids for pain; (2) opioid selection and dosage; (3) opioid duration and follow-up; and (4) assessing risk and addressing potential harms of opioid use. Id. at 31.

Note:  Given nuances in language, we quote each recommendation verbatim in bold text below and include certain implementation considerations for each recommendation though not verbatim.  To fully understand and benefit from the proposed rationale and explanation of the guideline, clinicians and others should read the proposed recommendations and implementation considerations in their entirety.

 (a)  Determining Whether to Initiate Opioids for Pain

Recommendation 1.

Nonopioid therapies are effective for many common types of acute pain.  Clinicians should only consider opioid therapy for acute pain if benefits are anticipated to outweigh risks to the patient.  Id. at 64.

• Opioid therapy plays an important role in treating acute pain related to severe traumatic injuries such as crush injuries and burns, invasive surgeries with moderate to severe postoperative pain, and other severe acute pain when non-steroidal anti-inflammatory drugs (“NSAIDs”) and other therapies are contraindicated or ineffective. Opioids should not be first-line therapy for acute pain conditions, like low back and neck pain, pain related to musculoskeletal injuries including sprains, strains, tendonitis and bursitis, pain related to minor surgeries associated with minimal tissue injury and mild postoperative pain (for example, dental extraction), dental pain, kidney stones, and headaches including episodic migraines.
• Clinicians should maximize use of nonopioid pharmacologic therapies such as NSAIDs or acetaminophen and nonpharmacologic therapies that include ice, heat, elevation, rest, immobilization and exercise for specific conditions. They should continue such therapies as needed after opioid therapy is discontinued.
• Clinicians should prescribe opioids on an “as needed” basis rather than on a scheduled basis (e.g., “one tablet every 4 hours”) and encourage tapering if opioids are to be taken around the clock for more than a few days.

Recommendation 2.  

Nonopioid therapies are preferred for subacute and chronic pain.  Clinicians should only consider initiating opioid therapy if expected benefits for pain and function are anticipated to outweigh risks to the patient.  Before starting opioid therapy for subacute or chronic pain, clinicians should discuss with patients the known risks and realistic benefits of opioid therapy, should work with patients to establish treatment goals for pain and function, and should consider how opioid therapy will be discontinued if benefits do not outweigh risks.  Id. at 75.

• Clinicians should use noninvasive, nonpharmacologic approaches to help manage chronic pain.

(b)  Opioid Selection and Dosage

Recommendation 3.  

When starting opioid therapy for acute, subacute, or chronic pain, clinicians should prescribe immediate-release opioids instead of extended-release/long-acting (“ER/LA”) opioids.  Id. at 91.

• ER/LA opioids should be “reserved for severe, continuous pain.”

Recommendation 4.  

When opioids are initiated for opioid-naïve patients with acute, subacute, or chronic pain, clinicians should prescribe the lowest dosage to achieve expected effects.  If opioids are continued for subacute or chronic pain, clinicians should use caution when prescribing opioids at any dosage, should carefully evaluate individual benefits and risks when considering increasing dosage, and should avoid increasing dosage above levels likely to yield diminishing returns in benefits relative to risks to patients.  Id. at 95-96.

• “[B]efore increasing total opioid dosage to ≥ 50 MME/day, clinicians should pause and carefully reassess evidence of individual benefits and risks. If a decision is made to increase dosage, clinicians should use caution and increase dosage by the smallest practical amount.”
• “The recommendations related to opioid dosages are not intended to be used as an inflexible, rigid standard of care; rather, they are intended to be guideposts to help inform clinician-patient decision making. Further, these recommendations apply specifically to starting opioids or to increasing opioid dosages, and a different set of benefits and risks applies to reducing opioid dosages.”

Recommendation 5.

For patients already receiving higher opioid dosages, clinicians should carefully weigh benefits and risks and exercise care when reducing or continuing opioid dosage.  If risks outweigh benefits of continued opioid therapy, clinicians should optimize other therapies and work closely with patients to gradually taper to lower dosages or, if warranted based on the individual clinical circumstances of the patient, to appropriately taper and discontinue opioids.  Unless there are indications of a life-threatening issue, such as warning signs of impending overdose, e.g., confusion, sedation, or slurred speech, opioid therapy should not be discontinued abruptly, and clinicians should not abruptly or rapidly reduce opioid dosages from higher dosages.  Id. at 101. 

• When risks outweigh benefits of continued opioid therapy, clinicians should consider reducing opioid dosage, or tapering and discontinuing opioid therapy, collaborate with patients prior to initiating changes, how quickly tapering will occur and when tapering pauses may be warranted.
• Clinicians should follow up at least monthly with patients engaged in opioid tapering.
• Payers, health systems, and state medical boards should not set rigid standards related to opioid dose or opioid therapy duration, and should ensure that policies not result in rapid tapers or abrupt discontinuation of opioids and do not penalize clinicians for accepting chronic pain patients using prescribed opioids, including high doses. Id. at 103.

(c)  Opioid Duration and Follow-Up

Recommendation 6.

When opioids are needed for acute pain, clinicians should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids.  Id. at 115.

• Clinicians can often manage nontraumatic, nonsurgical acute pain without opioids.
• A few days or less are often sufficient when opioids are needed for nontraumatic, nonsurgical pain. “However, durations should be individualized based on the clinical circumstances of the specific patient.”
• Clinicians should evaluate patients continuing to receive opioids for acute pain at least every 2 weeks.
• Clinicians should refer to recommendations on subacute and chronic pain for follow-up (Recommendation 7) and tapering (Recommendation 5) for treating patients receiving opioids for a month or longer.

Recommendation 7.  

Clinicians should evaluate benefits and risks with patients within 1 to 4 weeks of starting opioid therapy for subacute or chronic pain or of dose escalation.  Clinicians should evaluate benefits and risks of continued therapy with patients every 3 months or more frequently.  Id. at 120.

(d)  Assessing Risk and Addressing Potential Harms of Opioid Use

Recommendation 8.  

Before starting and periodically during continuation of opioid therapy, clinicians should evaluate risk for opioid-related harms and discuss with patients.  Clinicians should work with patients to incorporate into the management plan strategies to mitigate risk, including offering naloxone when factors that increase risk for opioid overdose are present.  Id. at 125.

• Clinicians should offer naloxone when prescribing opioids to patients at increased risk for overdose including patients with a history of overdose, substance use disorder or sleep-disordered breathing. It also includes patients who take higher dosages of opioids, for example 50 MME/day or more, patients taking benzodiazepines with opioids and patients at risk for returning to a high dose who have lost tolerance.

Recommendation 9.  

When prescribing initial opioid therapy for acute, subacute, or chronic pain, and periodically during opioid therapy for chronic pain, clinicians should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving opioid dosages or combinations that put the patient at high risk for overdose.  Id. at 135.

• Clinicians ideally should review PDMP data before every opioid prescription for acute, subacute, or chronic pain in all jurisdictions where available and practicable.
• For long-term opioid therapy, clinicians should review PDMP data before an initial opioid prescription and at least every 3 months thereafter.
• Clinicians should not dismiss patients on the basis of PDMP information.

Recommendation 10.

When prescribing opioids for subacute or chronic pain, clinicians should consider toxicology testing to assess for prescribed medications as well as other prescribed and non-prescribed controlled substances.  Id. at 139.

• Clinicians should not dismiss patients based on toxicology test results.

Recommendation 11.

Clinicians should use extreme caution when prescribing opioid pain medication and benzodiazepines concurrently and consider whether benefits outweigh risks of concurrent prescribing of opioids and other central nervous system depressants.  Id. at 145.

• There are circumstances when it is appropriate to prescribe opioids to a patient who is prescribed benzodiazepines, for example a patient in acute pain who is taking long-term, low-dose benzodiazepines. Clinicians should consider whether benefits outweigh risks of concurrent use of opioids with other central nervous system depressants such as muscle relaxants, non-benzodiazepine sedative hypnotics and potentially sedating anticonvulsant medications like gabapentin and pregabalin.

Recommendation 12.

Clinicians should offer or arrange treatment with medication for patients with opioid use disorder.  Id. at 149. 

• Clinicians should not dismiss patients due to opioid use disorder.

CDC’s Conclusion

CDC observes that “[a] central tenet of the clinical practice guideline is that acute, subacute, and chronic pain needs to be appropriately and effectively treated independent of whether opioids are part of a treatment regimen.”  Id. at 162.  CDC notes that this is achieved by nonpharmacologic or pharmacologic treatments that “maximize patient safety and optimize outcomes in pain, function, and quality of life.”  Id.  CDC emphasizes the need for care “to be individualized and person-centered.”  Id.  CDC warns that the guideline not be misapplied beyond its intended use, and policies derived from it not result in unintended consequences for patients, warning that inflexibility on opioid dose and duration, discontinuing or dismissing patients, rapidly tapering patients who may be stable on higher doses without collaboration, and applying to cancer, sickle cell, or end receiving end-of-life patients.  Id. at 164.

HPM Comment

Clinicians face difficult decisions in deciding whether to prescribe opioids, the dosage to prescribe and duration of treatment for acute, subacute and chronic pain patients.  As we stated at the time, we found the 2016 guideline to be reasonable.  Its recommendations constituted sound medical practice applicable to prescribing opioids, and non-opioid controlled and non-controlled medication.  However, while the 2016 guideline helped clarify legitimate medical purpose standards for prescribing and dispensing controlled substances for clinicians, pharmacies and regulators, we cautioned that legitimate medical treatment may conflict with strict adherence opioid therapy of more than seven days or in excess of 50-90 MMEs daily.  We remain concerned.

CDC stressed that the 2016 guideline was “voluntary, rather than prescriptive” and advised clinicians to “consider the circumstances and unique needs of each patient when providing care.”  CDC Guideline for Prescribing Opioids for Chronic Pain-United States, 2016, 2.  CDC now  acknowledges that states, insurers, pharmacies and pharmacy benefit managers implemented laws, regulations and policies that have misapplied the 2016 guideline.  They misapplied the recommendations as inflexible CDC mandates to the chronic pain patient population and inappropriately applied them to cancer, palliative and end-of-life patients.

We questioned then as we question now whether the Drug Enforcement Administration and state regulators will similarly “misapply” the proposed guideline and pursue enforcement action against practitioners who do not strictly comply with the proposed guideline.  Clinicians and regulators must strive to apply the 2016 and proposed guideline in the manner in which CDC intended so that patients receive the appropriate opioid treatment their legitimate condition requires.  So both the regulators and the regulated industry must recognize the intent of the 2022 proposed  guideline and apply the recommendations appropriately.  Otherwise, legitimate patients will remain at risk for nontreatment or undertreatment of acute, subacute or chronic pain.

Public Comments

The public can comment on the proposed guideline and recommendations until April 11, 2022.  We urge all interested parties to weigh in.