3.2 Summary of literature
Around 36.4% of the total included articles applied to the strength of the providers (n = 425). About 25.2% of the included papers (n = 294) concerned substitutes for opioids. A total of 19.6% (n = 229) provided information on the customers in the industry, 15.7% (n = 183) focused on regulatory power in the opioid industry, 14% (n = 163) considered the industry itself, including evaluating new entrants into the industry and competitive rivalry between current players in the industry, and 11.7% (n = 137) of all 1166 included publications applied to all six categories (Fig. 3). Of the 1166 included papers, only 3 included papers with a central focus on orthopaedic trauma patients. These papers included a prospective cohort study, a systematic review, and a retrospective cohort study. There were no randomized-controlled trials concerning opioid misuse in the orthopaedic trauma population.
Of the 294 articles addressing the substitute theme, 133 were deemed “extremely relevant” (45.2%) by the reviewers. The sweeping majority of these papers focused on pharmaceutical opioid substitution therapies such as buprenorphine, naloxone, and methadone. A substantial proportion analyzed various procedures or treatments that reduced opioid requirements such as nerve blocks, acupuncture, and ankle aspiration. Some publications considered other pharmaceutical interventions that can be used in conjunction with opioids such as NSAIDs, benzodiazepines, and gabapentin. Few papers examined the role of complementary therapies for pain treatment.
The largest represented topic was opioid replacement therapies (ORTs). These interventions involve “replacing” an illegal or misused opioid (such as heroin or oxycodone) with a longer acting and less euphoria-producing opioid (Table 3). The most commonly prescribed ORTs in the United States are buprenorphine and methadone. In the context of the treatment of opioid use disorders, these medications are only prescribed and dispensed by certified physicians and, in the case of methadone, the patients are required to be under strict supervision. Collectively, these programs are described as Medication Assisted Therapies. Our examination of the literature produced 62 papers about buprenorphine. These papers focused on a wide and thorough range of topics such as regulation, implementation, effectiveness, education, access, prescribing practices, available formulations, safety concerns, and abuse. Methadone was another highly represented topic with 30 papers addressing the efficacy, stigma, outcomes, cost, retention, management, and safety concerns associated with methadone maintenance therapy. Authors also addressed gabapentin (3 papers) and benzodiazepines as co-prescribed interventions for the treatment of chronic pain and pain post-injury. Few publications (6 papers) discussed the use of NSAIDs as a complement or alternative to opioids. Ten papers considered the benefits of CAM, acupuncture, and talk therapy. A significant number of papers analyzed the effectiveness of using a specific procedure or analgesic such as a nerve block in order to reduce opioid use at discharge.
A total of 236 of the 425 provider-focused papers (55.5%) were considered “extremely relevant” by the reviewers. The vast majority of these papers focused on the role of the prescriber, typically physicians. Thirty-five papers focused on the role of pharmacists in the distribution and monitoring of opioid prescriptions. There were only 3 papers that focused directly on the role of pharmaceutical companies in the opioid industry.
Many papers that focused on the prescribers evaluated prescribing practices, especially those employed to treat postfracture pain in the emergency departments and chronic pain in ambulatory clinics. Additionally, there is a large focus in the literature on analyzing the efficacy of previously established physician guidelines for managing traumatic injury or chronic pain. This includes papers detailing successful trauma pain protocols and effective post-operative pain management protocols. Other prescriber-focused papers focused on physician education initiatives. The articles analyzing the power of pharmacists in the opioid industry focused on prescription drug monitoring programs, the role of pharmacists in dispensing buprenorphine, and collaboration between pharmacists and physicians. Two of the papers concerning pharmaceutical companies focused on the physician–pharma relationship, and the remaining paper examined the economics of substitution therapy from a pharmaceutical perspective.
Around 229 papers (19.6%) focused on the power of the buyer, 99 of these papers (43.2%) were considered “extremely relevant” by the reviewers. The majority of these papers focused on the patient. There were only five papers that focused on the role of insurance companies as “consumers” in the opioid industry.
The vast majority of consumer-focused papers concerned patients rather than insurance companies. A large number of these papers focused on how different patient characteristics such as race, gender, age, education status, injury, and self-reported pain intensity influenced opioid prescribing trends, typically in the emergency department after acute injuries. Another popular topic included patient risk factors for probable opioid misuse. There was a notable focus on patient satisfaction, pain as a medical condition (“the fifth vital sign”), and drug-seeking behaviors. There were very few publications considering patient education initiatives such as patient contracts. The limited publications concerning insurance companies compared patients on different insurance plans or analyzed the insurance status of patients. There was only 1 paper that focused on the insurance industry's role in the opioid crisis.
3.6 Regulations/restrictive policies
Around 86 of the 183 papers that focused on the power of regulations were considered “extremely relevant” (47%). The majority of these papers considered regulations and protocols that could affect physicians in order to make opioid prescribing a safer enterprise. There was also a notable focus on the restriction of opioid use through intervention at the pharmacy level. Our search produced no articles analyzing regulation of pharmaceutical companies or insurance companies.
Most of the regulation-focused papers assessed policies that would directly affect physicians. Fourteen of these papers analyzed the regulations placed on prescribing substitution therapies. Fourteen papers addressed physician education as a tool for reducing nontherapeutic opioid use. There was a large focus on implementing prescribing protocols and best practice guidelines for opioids at different levels of care, including in ambulatory clinics, emergency departments, and operating rooms. Seven papers discussed the implementation of opioid risk evaluation and mitigation strategies, including the FDA-approved risk evaluation and mitigation strategies for extended-release and long-acting opioids. Other topics included establishment of opioid review committees, standardization of multidimensional pain scales, creation of a pain care quality extraction tool, and patient-provider agreements. The role of regulation at the pharmacy level was also well represented in the literature; 12 papers examined the efficacy and importance of prescription monitoring programs.
The industry theme had the fewest number of papers (14%). About 83 of the 163 manuscripts were considered “extremely relevant” by the reviewers. The majority of these papers discussed differences in efficacy of FDA-approved opioid medications in trauma-related procedures and pain treatment. Other topics included: comparing extended versus controlled release medications, comparing time scheduled vs. pain contingent dosing, comparing methods of delivery (such as transdermal, intranasal, or buccal), and evaluating existing tamper-resistant or harm-reducing formulas. Surprisingly, only 2 papers analyzed the promotion and marketing of opioids. A small number of papers discussed the transition from prescription opioid use to the illicit use of heroin. Many papers focused on the implementation of new drugs such as nociception/orphanin FQ and ziconotide. A significant number of papers also examined the implementation of new medication and analyzed the efficacy as compared to the original. For example, 1 study compared the rate of abuse of a reformulated therapy to that of the original drug. Fourteen papers also considered the barriers to implementing new substitution therapies. Six papers discussed the efficacy of abuse deterrent technology at reducing opioid abuse. Only 1 paper considered novel off-label use of an opioid.
The findings of this study define areas of research attention and knowledge gaps in the literature relevant to opioid use and misuse among orthopaedic trauma patients (Fig. 4). Utilizing the novel scoping review technique allowed for the organization of the literature into five categories that directed the synthesis. More than 60% of the overall publications focused on either opioid providers (mainly physicians) or opioid substitutes (mainly ORTs). Very few of the identified publications studied the role of insurance providers or pharmaceutical firms and their involvement in opioid abuse and long-term nontherapeutic use. In line with the Centers for Disease Control and Prevention's (CDC) contention that, “long-term opioid use often begins with treatment of acute pain,” this study delineates previous academic investigation into possible drivers of the opioid epidemic emanating from an acute injury.
In Figure 4, the green upward arrows represent factors that increase opioid use and the red downward arrows represent factors that decrease, or have the potential to decrease, opioid use. The topics in gray font were not represented in the literature included in this scoping review.
Of the 1166 papers included in the study, 52% of these papers were marked as “extremely relevant” to our expanded research question. However, only 3 papers specifically focused on the orthopaedic trauma population. The majority of papers concerned either opioid providers (36.4%) or various substitutions for opioids (25.2%). There were few papers evaluating pharmacological or other therapeutic substitutes for trauma patients at the time of injury and a notable lack of papers concerning the involvement of pharmaceutical companies or insurance companies in opioid overuse relevant to trauma patients. The study has identified a knowledge gap pertaining to evaluating the transition from prescription opioid use to illicit heroin use among those patients with orthopaedic injury. Finally, we found limited investigation comparing the efficacy of various opioid medications in the treatment of acute post-traumatic pain.
Our use of the scoping review method allowed this study to address a broad topic with limited and unsystematic representation in scientific literature. The malleable nature of the scoping review method created the unique opportunity to seek resources in non-peer-reviewed journals, such as state guidelines, and allowed us to adjust our methods based on what was available. Despite this flexibility, we applied rigorous standards to our searches and screening, including verifying the strength of our search strategies, methodologies, and eligibility criteria with a health sciences research librarian. We also trained all 4 reviewers systematically and created an additional review system for papers whose relevance was not immediately apparent. Overall, the benefit of the scoping review is reflected in our ability to sort a large number of papers into digestible categories, which could then be evaluated in order to inform interested entities about the state of the field.
Our collaboration with experts on this topic allowed us to identify themes not represented in the literature, but prevalent in the field. We consulted a psychiatrist specializing in addiction, a doctor of social work specializing in opiates, and a healthcare business professor. Each of these individuals spoke of their experience treating patients with opioid addiction or studying opioid addiction and the surrounding industry. After being presented with the results of our searches, they identified key topics that seemed underrepresented in the literature but were highly pervasive in practice. Additionally, they each elaborated on the limitations of using a rigorous study design to examine a highly complex and fast-changing field, discussed in detail below.
We made several important observations about the content of the existing literature. The most widely discussed topic was ORTs within the category of “substitutions.” Generally considered as a viable therapeutic option for the treatment of severe opioid dependence, the safety and efficacy of ORTs remain unclear and requires more study. Another strongly represented topic was the control of physician involvement in opioid distribution, within the category of “provider-focused” papers. This was approached from various angles, such as physician education and implementation of prescribing guidelines. It is imperative to further investigate the willingness of physicians to engage in the types of programs implemented at select institutions in order to evaluate the potential impact of these programs.
The “regulations and restrictions” category, comprising 15.7% of the papers, represented perhaps the widest range of topics within a single category. Publications offered examples of regulation of every facet of the opioid industry, including physicians, pharmacists, and substitution therapies. Although most papers examined individual restrictions (e.g., a single prescription monitoring program or a particular physician education initiative), it would be interesting to evaluate the implementation of multiple regulatory interventions at an institution or within a medical system.
The papers sorted into the “consumer-focused” category focused mainly on various qualities of patients. This ranged from analyzing characteristics that predisposed patients to abuse (such as prior use of opioids) to analyzing characteristics that dictate how much and what types of medications are received (such as time of injury, gender, and race). There were also a number of papers evaluating patient satisfaction as a driver of opioid prescribing practices. This information exposes an opportunity for improvement within the industry: opioid prescriptions should reflect pain and extent of injury, rather than race, gender, or day of the week the injury occurred. Furthermore, the emphasis on pain and the evaluation of pain severity needs to be better standardized.
In contrast to those topics that were highly represented, there were many important facets of the opioid industry and various drivers of abuse that were absent from the literature. These topics had been identified by a separate narrative review and with the help of our expert collaborators (Table 4). To begin, there were only 3 papers that discussed the involvement of the pharmaceutical industry on the opioid epidemic. As evidenced by journalistic publications and various historical exposés on the opioid epidemic, the pharmaceutical industry has played an enormous role in establishing and maintaining opioids as a cornerstone of our pain treatment protocols. For instance, in a recent Washington Post article, the $10 billion industry is evaluated for its growth potential, specifically the emergence of a subindustry involving treatment of secondary effects. A physician interviewed for the article states, “The pharmaceutical industry literally created the problem [of opioid induced constipation]. They named it, and they started advertising what a serious issue it is. And now they’ve got the solution for it.” Despite the widely accepted role played by pharmaceuticals, little peer-reviewed research has been performed on the topics of marketing, questionable R&D methods, distribution, or dissemination of misinformation.
The insurance industry is also under-examined in peer-reviewed literature. The projected cost of opioids to United States insurance companies is $72.5 billion per year. In contrast to pharmaceutical firms, insurance providers are economically disadvantaged by the opioid industry and subindustries. Insurance providers also have the tools to establish ubiquitous prescription monitoring programs in order to monitor high risk patients. Furthermore, insurance agencies may have the ability to dictate which opioids or ORTs are covered by insurance, effectively manipulating prescribing practices. Despite the potential influence, there were no peer-reviewed publications on these topics.
There were also few papers discussing alternative medications. As mentioned, the majority of the “substitute-focused” papers concerned medication-assisted therapies to replace opioids after the transition to addiction has already occurred. There were minimal publications considering the use of alternate pharmaceuticals (such as NSAIDs) or interventions (such as physical therapy) for traumatic pain at time of injury. This was also the case for complementary medical techniques such as acupuncture. Research suggests that NSAIDs may offer the same pain relief at a lower cost for some patients. Finally, there was a gap in the literature concerning the optimum length of opioid prescription time post-injury. The CDC currently recommends 3 to 7 days of opioids for an acute injury. ER/LA opioids are not recommended to treat traumatic injury pain. Despite these short-term recommendations, 27% of patients prescribed an opioid on a short term basis ended up taking them considerably longer. This topic or the efficacy of these recommendations was not examined in the peer-reviewed literature.
Throughout the search and screening process, we identified various limitations of the methodology and the literature itself. We were advised on further limitations after consultation with experts in the field. To begin, our search was performed in late June 2016. Because of the rapid expansion of publications concerning opioids, the results do not reflect even more recent publications which may already fill some of the voids we have identified. Another limitation concerns the nature of government restrictive bodies. The CDC, FDA, DEA and other government organizations are not compelled to publish relevant information concerning controlled substances in the scientific literature, and as such, a literature search may miss information that is simply posted on agency websites or through non-peer-reviewed publications.
Additionally, the scientific community is limited by the nature of the opioid industry itself. It is difficult to quantify certain aspects of opioid use, for example, transition from therapeutic to nontherapeutic use, abuse of substitute therapies, prescription opioid diversion, length of use (as patients can seek the drugs elsewhere), and transition to use of illegal substances such as heroin. Lastly, a huge limitation was realized early during the searching process. The lack of publications concerning opioids and orthopaedic trauma (or trauma in general) required us to expand our search to include papers focused on the general population's use of opioid medications. While this enabled us to better describe the opioid industry's literature representation, it diluted the focus on post-injury opioid use.
The results of the current study provide a detailed summary of the available literature concerning opioid use relevant to orthopaedic trauma patients. The strengths and weaknesses identified provide plausible suggestions for future research projects. Using the results from this study, we will assess orthopaedic surgeons’ opinions and knowledge about the themes identified in the literature, such as physician education and various restrictive policies. Additionally, multiple opportunities to perform systematic reviews on topics that have been widely represented, such as ORTs, PMPs, or prescribing guidelines, have been identified. Finally, we have recognized multiple areas in which there is a blatant lack of peer-reviewed information, which can be addressed by the orthopaedic community (Table 5). The summaries from this paper will be used in future discussions between physicians, public health workers, and addiction specialists as we pursue interventions aimed at reducing long-term opioid misuse among orthopaedic injury patients.
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Keywords:© 2018 by Lippincott Williams & Wilkins, Inc.
literature review; musculoskeletal trauma; opioid epidemic; opioid misuse; opioids; orthopaedic Injury