Opioid Prescribing: A Systematic Review and Critical Appraisal of Guidelines for Chronic Pain

Across the United States, opioid-related overdoses have been implicated in increasing numbers of emergency department visits, hospitalizations, and deaths. Annual fatalities associated with prescription opioids increased from 4000 in 1999 to nearly 14000 by 2006 (1). Several factors may explain these trends. First, over the past several decades, the number of patients receiving opioids and the number of doses prescribed have increased dramatically (24). Treating chronic pain with opioids went from being largely discouraged to being included in standards of care (2, 5, 6), and titrating doses until patients self-report adequate control has become common practice (5, 7). Today, 8% to 30% of patients with chronic noncancer pain receive opioids, with average doses typically ranging from 13 to 128 mg of morphine equivalents daily; some receive much higher doses (8). Second, the public seems to consider prescription opioids safer to abuse than illicit drugs, influencing patterns of overdose deaths (9, 10). Third, common drugdrug and drugdisease interactions contribute to overdoses. Half of fatal opioid overdoses involve the concomitant use of sedative-hypnotics, particularly benzodiazepines (1). Given current rates of opioid overdose, policymakers are seeking solutions and standards of care are again evolving. The White House has issued action items, and an Institute of Medicine (IOM) report provides recommendations for policy audiences (11, 12). High-quality clinical practice guidelines would assist clinicians in making informed prescribing decisions and would mitigate the risks associated with using opioids. The objective of the current study was to systematically search for and evaluate the quality of guidelines addressing the use of opioids for chronic pain. A secondary objective was to compare guidelines recommendations related to mitigating the risk for accidental overdose and misuse, including considering the quality of the evidence that guidelines provide in support of their recommendations. Methods Study steps included searching for guidelines, applying selection criteria, assessing guideline quality, and extracting relevant content. Data Sources and Searches We searched for guidelines addressing the use of opioids in the treatment of chronic pain, which is generally defined as pain that persists beyond normal tissue healing time, assumed to be 3 months (13, 14). The long-term use of opioids has been variably defined as use for 3 to 6 months or longer (14, 15). Information sources included MEDLINE via PubMed, the National Guideline Clearinghouse, 12 Web sites of relevant specialty societies listed on the American Medical Association Web site (16), Web sites of selected state workers compensation agencies (1719), and 12 international search engines (2031) (Appendix Figure). The search was last updated in July 2013. Appendix Figure. Summary of evidence search and selection. AGREE II = Appraisal of Guidelines for Research and Evaluation II; AMSTAR = A Measurement Tool to Assess Systematic Reviews. * Includes the American Academy of Family Physicians, American Academy of Pain Medicine, American Academy of Physical Medicine and Rehabilitation, American College of Occupational and Environmental Medicine, American College of Physicians, American Geriatrics Society, American Society of Addiction Medicine, American Society of Anesthesiologists, American Society of Interventional Pain Physicians, Association of Military Surgeons of the United States, National Medical Association, and Society of Medical Consultants to the Armed Forces. The exact PubMed search terms were analgesics, opioid[MeSH], opioid[tiab], opioids[tiab], opioid analgesic[tiab], opioid analgesics[tiab], opiate[tiab], opiates[tiab], chronic pain[MeSH], chronic pain[tiab], pain management[MeSH], and pain management[tiab] combined with guideline[Publication Type], guideline*[tiab], position statement*[tiab], practice parameter*[tiab], position paper*[tiab], and consensus statement*[tiab] Includes the Guidelines International Network; National Institute for Health and Care Excellence; Canadian Medical Association Infobase: Clinical Practice Guidelines; Clinical Practice Guidelines Portal of the Australian Government; Scottish Intercollegiate Guidelines Network; New Zealand Guidelines Group; Biblioteca de Guas de Prctica Clnica del Sistema Nacional de Salud (Library of Clinical Practice Guidelines from the Spanish National Health System); German Agency for Quality in Medicine; German National Disease Management Guidelines Programme: German Disease Management Guidelines; British Columbia Ministry of Health; and Australian Government National Health and Medical Research Council: Guidelines and Publications. The American Geriatrics Society updated its guideline in 2009 and stated that the 2002 guideline, which covers slightly different material, was still up to date. When counting guidelines, we considered these to be components of 1 document. Search terms included opioid, opiate, narcotic, chronic pain, and pain management. For the National Guideline Clearinghouse, names of specific opioids were also used. For PubMed, narcotic was omitted (all results addressed substance abuse); this search was limited to documents published after 31 December 2006 because selection criteria included recent updating. Guideline Selection We selected English-language documents meeting the following definition: Clinical practice guidelines are statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options (32). Guidelines had to have been published after 2006 because half of guidelines can be outdated after 5 to 6 years (33). Because we sought to evaluate guidelines that address the use of opioids for chronic pain in adults in general, we excluded guidelines focusing on specific conditions (for example, low back pain or cancer), populations (for example, pediatric patients or homeless persons), types of pain (for example, neuropathic pain or postoperative pain), or settings (for example, long-term care). We excluded guidelines derived entirely from another guideline and those for which we could not identify detailed information on development. Two reviewers applied criteria independently and reached agreement; a third reviewer was available to resolve disputes. Guideline Quality Assessment We evaluated guideline quality by using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument (3436) and the systematic review supporting each guideline by using A Measurement Tool to Assess Systematic Reviews (AMSTAR) (37). AGREE II With AGREE II, appraisers rate 23 items across 6 domains (from 1 [strongly disagree] to 7 [strongly agree]), rate the overall quality of each guideline (1 to 7) and recommend for or against use. Scaled domain scores (0% to 100%) are based on the sum of ratings across all appraisers and the difference between the maximum and minimum possible scores (38). The guidelines were rated by 4 to 6 appraisers, including 5 clinician investigators (2 of whom had limited availability) and 1 trained graduate student. One author who was also the author of a guideline (13) provided general input on content and methods but played no role in appraisals. AMSTAR In the original version of AMSTAR, appraisers answer 6 domain questions (yes, no, can't answer, or not applicable). Each domain question typically addresses multiple concepts. For example, 1 question states that At least two electronic sources should be searched [concept 1]Key words and/or MeSH terms must be stated [concept 2] (37). Because including multiple concepts could lead to inconsistent scoring of yes or no responses, we modified AMSTAR by dividing the original domain questions into separate subquestions addressing single concepts (Supplement). Appraisers scored each subquestion (yes, no, can't answer, or not applicable), each of the 6 domains overall (poor, fair, good, excellent, or outstanding), and the overall quality of the review (same categories as for the domains). Four to 5 appraisers rated each review individually and then met to discuss ratings and reach agreement. Supplement. Modified AMSTAR Instrument Guideline Synthesis and Analysis Three appraisers abstracted recommendations from each guideline on dosing limits, medications and formulations, titration of dose, switching from one opioid to another, drugdrug interactions, drugdisease interactions, and risk mitigation strategies (opioid risk assessment tools, written treatment agreements, and urine drug testing). Role of the Funding Source The Commission on Health and Safety and Workers Compensation provided funding for this study. The funding source commissioned a synthesis of recent information on the risks and benefits of opioids for chronic pain but had no role in the design or execution of this evaluation. Results Search and Selection of Guidelines Of 1270 documents identified, 1132 unique records were eligible for screening, 19 full-text guidelines were considered for evaluation, and 13 were eligible (Appendix Figure). An online report includes a previous version of the search (39). Of 6 guidelines considered but found ineligible, 1 was derived from another guideline (18) and 5 lacked details on development methods (17, 4043). Selected Guidelines Appendix Table 1 lists the 13 eligible guidelines; all were published in 2009 or later. Systematic reviews were conducted in 2008 or later (among guidelines that reported this). Appendix Table 1. Guidelines Meeting All Selection Criteria and Included in Quality Appraisal Seven guidelines apply broadly to adults with chronic pain (13, 4450). Six have slightly narrower scopes: The American Geriatrics Society guideline addresses adults older than 65 years (51, 52); the American Society of Anesthesiologists guideline emphasizes procedures (53); a gui