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Searching for the lowest effective opioid dose: A framework for acute pain from the National Academies

Opioids should be used at the lowest effective dose for acute pain, but how clinicians should pursue that dose or know they have arrived is unclear. As literature regarding specific opioid dosing is sparse, most guidelines do not even hazard an Expert Opinion at specific opioid or dose recommendations. Given the relative lack of evidencebased guidance and indication-specific recommendations, high variability in opioid prescribing exists. To help guide appropriate opioid prescribing for acute pain, the Food and Drug Administration (FDA) charged the National Academies of Sciences, Engineering, and Medicine to, “develop a framework to evaluate existing clinical practice guidelines for prescribing opioids for acute pain indications, recommend indications for which new evidence-based guidelines should be developed, and recommend a future research agenda to inform and enable specialty organizations to develop and disseminate evidence-based clinical practice guidelines for prescribing opioids to treat acute pain indications.” While the opioid overdose crisis, efforts to mitigate it, and the National Academies report are multifaceted, this article addresses the Analytical Framework developed for and reported in National Academies report, Framing Opioid Prescribing Guidelines for Acute Pain. The Analytical Framework (Figure 1) is a core component developed to meet the request of FDA to help “right size” opioid prescribing and is intended to serve as a guide for researchers and clinical practice guideline developers. The Analytical Framework serves two main purposes, to (a) organize information for creating evidence-based recommendations for clinical practice guidelines and (b) highlight evidence gaps. Many clinical practice guidelines providing opioid prescribing recommendations only address the preliminary step of determining whether opioids are indicated, leaving out crucial details about opioid selection and treatment duration. One example are the American Academy of Orthopaedic Surgeons (AAOS) guidelines for surgical management of osteoarthritis of the knee which make several recommendations about strategies to reduce opioid consumption (eg, through use of anesthesia and nerve blocks), but do not make recommendations specific to the opioid therapy. Similarly, the American College of Physician's guideline for low back pain simply recommends, “[c]linicians should only consider opioids as an option in patients who have failed the aforementioned [non-opioid] treatments and only if the potential benefits outweigh the risk for individual patients.” While both guidelines met many criteria in the National Academies report regarding high-quality evidence-based guidelines, key aspects are absent, such as specific opioid medication(s), dose(s), regimen(s), and clarity on patients most likely to benefit. As would be expected when guidance is limited, the committee found evidence of variation in opioid prescribing following total knee arthroplasty, low back pain, and many other indications. In order to improve the management of acute pain, evidence is needed to support specific recommendations for opioid doses which have an established ability to improve health outcomes. Thus, the Analytical Framework highlights a research need given the frequency of opioid use. As research is completed, clinical practice guideline developers will be able to organize the developed evidence using the Analytical Framework to generate evidence-based recommendations for opioid dosing. In addition to direct evidence of improved outcomes, evidence assessing the link between current practices aimed at curbing opioid prescribing and important outcomes are greatly needed. For example, interventions which reduce the quantity of opioids prescribed are often assumed to be beneficial, yet have the potential to cause significant harm. And presently, there are no clinical trials which adequately demonstrate for acute pain that a reduced opioid “amount” (eg, day supply, quantity, dose, morphine milligram equivalent) in initial opioid prescription improves or maintains: (a) proportion of patients continuing to take opioids long-term, (b) proportion of patients progressing from acute to chronic pain, (c) proportion of patients that develop opioid use disorder, (d) proportion of patients diverting opioids, (e) pain control, (f) health disparities, (g) quality-of-life, (h) non-fatal or fatal overdose in patients, their family, and their community. Thus, research is needed to link key “intermediate outcomes” (eg, reduced opioid prescribing) to “health outcomes” (eg, pain control, opioid overdose). Pharmacists as part of a collaborative team of researchers are well positioned to complete research assessing this key evidence link given their role as medication expert across healthcare settings (eg, hospitals, community pharmacies, nursing facilities, clinics). As outcome data become available, the evidence-base will enable recommendations to meet the standards laid out in the National Academies report and the standards established in the 2011 Institute of Medicine report, Clinical Practice Guidelines We Can Trust. The utility of clinical practice guidelines will increase and we will be closer to knowing what is the lowest effective dose. However, dosing will need to be further refined in important sub-groups (eg, preexisting opioid use, extremes of age, renal dysfunction, genomic modifiers). Without short and long-term outcome data, guidance will continue to be absent, based on expert opinion, or come via government fiat. Completing the life cycle of the Analytical Framework, as guidelines are commissioned and published, they should be systematically Received: 13 July 2020 Accepted: 13 July 2020