Prenatal exposure to teratogenic medications in the era of Risk Evaluation and Mitigation Strategies.

BACKGROUND: Prevention of prenatal exposures to teratogenic drugs is a significant clinical and public health concern. With the enactment of the US Food and Drug Administration Amendments Act in 2007, the US Food and Drug Administration has begun to require manufacturers to implement Risk Evaluation and Mitigation Strategies to prevent prenatal exposures. Among 12 risk evaluation and mitigation strategy drugs, several had predecessor risk mitigation plans (eg, isotretinoin) and some were newly required (eg, mycophenolate). Only a small proportion of teratogenic drugs are currently subject to Risk Evaluation and Mitigation Strategies, and the extent of prenatal exposure to the universe of teratogenic drugs compared with drugs subject to Risk Evaluation and Mitigation Strategies is unknown. Moreover, the effectiveness of such advanced risk mitigation programs in preventing prenatal exposure is not clear. OBJECTIVE: This study aimed to characterize the epidemiology of prenatal exposures to definite and potential teratogens during the risk evaluation and mitigation strategy era. STUDY DESIGN: We constructed a time-series of pregnancies identified from a national private insurance claims database (IBM MarketScan) to estimate prenatal exposures to teratogenic drugs (2006-2017). Pregnancy outcomes, gestational age, and the onset of pregnancy were determined with previously validated algorithms. The Teratology Information Service and Clinical Pharmacology databases were used to identify drugs with definite (n=141) or potential (n=65) teratogenic effects, and drugs with debatable risks such as benzodiazepines, statins, tetracyclines, sex hormones, infertility treatments, and gonadotropin-releasing hormone analogs were excluded. We defined prenatal exposure as ≥1 prescription fill or medical encounter involving administration of drugs with a definite teratogenic risk (including 12 for which there is a "current or discontinued" risk evaluation and mitigation strategy) or a potential teratogenic risk. We evaluated secular trends and modeled the effects of age, preconception exposure, and state healthcare quality rankings on prenatal exposure, adjusting for demographic factors and clinical conditions. RESULTS: The cohort included 3,445,612 pregnancies (2,532,444 live deliveries). Prenatal exposures to definite teratogens decreased slightly during the study years from 1.86 to 1.24 per 100 pregnancies between 2006 and 2017, whereas exposure increased for potential teratogens from 3.40% to 5.33%. Prenatal exposure prevalences were higher during the first trimester and for pregnancies that ended in nonlive outcomes. Drugs subject to Risk Evaluation and Mitigation Strategies had low background utilization and contributed to a small proportion of prenatal exposures (15.1 per 100,000 pregnancies). We also observed fewer prenatal exposures to risk evaluation and mitigation strategy drugs among women of childbearing age who used these treatments (0.14% vs 0.36% for any definite teratogen). Age extremes and low state-level healthcare quality rankings were independent predictors of prenatal exposure. CONCLUSION: Fetuses in more than 1 in 16 pregnancies continued to be exposed to teratogenic drugs during the past decade. Drugs with Risk Evaluation and Mitigation Strategies imposed a small burden of prenatal exposure because of the low background utilization rates and lower pregnancy prevalence among women of childbearing age who used these drugs. Although the declining exposure rates to teratogenic drugs with definite risk are encouraging, the rising prenatal exposure to drugs with potential risk calls for more assessments. Future research is needed to elucidate the health outcomes of fetuses exposed to potential risk drugs, understand the effectiveness of risk evaluation and mitigation strategy programs, and prioritize teratogenic drugs for advanced risk mitigation.

Changes in Mortality Involving Extended-Release and Long-Acting Opioids After Implementation of a Risk Evaluation and Mitigation Strategy.

OBJECTIVE: To assess changes in mortality rates in extended-release and long-acting (ER/LA) opioid analgesics after the implementation of the Risk Evaluation and Mitigation Strategy (REMS). SETTING: All drug poisoning deaths in three states: Florida, Oregon, and Washington. Data were obtained through state vital records offices and the Researched Abuse, Diversion and Addiction-Related Surveillance System Medical Examiner Program. METHODS: Using cause-of-death literal text from death certificates, individual opioid active pharmaceutical ingredients (APIs) involved in each death were identified using rules-based natural language processing. Population-adjusted and prescriptions dispensed-adjusted mortality rates were calculated for all ER/LA opioid analgesic and individual opioid APIs. Rates before and after implementation of the REMS were compared. Rate changes were compared with rates from two APIs with little or no inclusion in the REMS: benzodiazepines and hydrocodone. RESULTS: The mean ER/LA opioid analgesic population-adjusted mortality rate significantly decreased in all three states (FL: P = 0.003; OR: P = 0.003; WA: P < 0.001). Mortality rates for benzodiazepines and hydrocodone also decreased and were not statistically different. Significant heterogeneity in mortality rates of individual opioids was observed between the three states. When adjusted for prescription volume, the ER/LA opioid analgesic mortality rate decreased in all three states, but was significant only for Washington (P < 0.001). CONCLUSIONS: The population-adjusted mortality rate of ER/LA opioid analgesics has decreased in three states. Notably, the contributions to mortality rates by individual opioid analgesics were not uniform across the three states in this study. However, these changes were not generally distinct from changes in mortality rates where comparator substances were involved.

Changes in misuse and abuse of prescription opioids following implementation of Extended-Release and Long-Acting Opioid Analgesic Risk Evaluation and Mitigation Strategy.

PURPOSE: An unintended consequence of extended-release (ER) and long-acting (LA) prescription opioids is that these formulations can be more attractive to abusers than immediate-release (IR) formulations. The US Food and Drug Administration recognized these risks and approved the ER/LA Opioid Analgesic Risk Evaluation and Mitigation Strategy (ER/LA REMS), which has a goal of reducing opioid misuse and abuse and their associated consequences. The primary objective of this analysis is to determine whether ER/LA REMS implementation was associated with decreased reports of misuse and abuse. METHODS: Data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS(R)) System Poison Center Program were utilized. Poison center cases are assigned a reason for exposure, a medical outcome, and a level of health care received. Rates adjusted for population and drug utilization were analyzed over time. RESULTS: RADARS System Poison Center Program data indicate a notable decrease in ER/LA opioid rates of intentional abuse and misuse as well as major medical outcomes or hospitalizations following implementation of the ER/LA REMS. CONCLUSIONS: While similar decreases were observed for the IR prescription opioid group, the decreasing rate for the ER/LA opioids exceeded the decreasing rates for the IR prescription opioids and was distinctly different than that for the prescription stimulants, indicating that the ER/LA REMS program may have had an additional effect on decreases in opioid abuse and intentional misuse beyond secular trends.

ER/LA Opioid Analgesics REMS: Overview of Ongoing Assessments of Its Progress and Its Impact on Health Outcomes.

Objective: Opioid abuse is a serious public health concern. In response, the Food and Drug Administration (FDA) determined that a risk evaluation and mitigation strategy (REMS) for extended-release and long-acting (ER/LA) opioids was necessary to ensure that the benefits of these analgesics continue to outweigh the risks. Key components of the REMS are training for prescribers through accredited continuing education (CE), and providing patient educational materials. Methods: The impact of this REMS has been assessed using diverse metrics including evaluation of prescriber and patient understanding of the risks associated with opioids; patient receipt and comprehension of the medication guide and patient counseling document; patient satisfaction with access to opioids; drug utilization and changes in prescribing patterns; and surveillance of ER/LA opioid misuse, abuse, overdose, addiction, and death. Results and Conclusions: The results of these assessments indicate that the increasing rates of opioid abuse, addiction, overdose, and death observed prior to implementation of the REMS have since leveled off or started to decline. However, these benefits cannot be attributed solely to the ER/LA opioid analgesics REMS since many other initiatives to prevent abuse occurred contemporaneously. These improvements occurred while preserving patient access to opioids as a large majority of patients surveyed expressed satisfaction with their access to opioids.

Candidate metrics for evaluating the impact of prescriber education on the safe use of extended-release/long-acting (ER/LA) opioid analgesics.

OBJECTIVE: The objective of this study was to develop metrics to assess opioid prescribing behavior as part of the evaluation of the Extended-Release/Long-Acting (ER/LA) Opioid Analgesic Risk Evaluation and Mitigation Strategies (REMS). DESIGN: Candidate metrics were selected using published guidelines, examined using sensitivity analyses, and applied to cross-sectional rolling cohorts of Medicare patients prescribed with extended-release oxycodone (ERO) between July 2, 2006 and July 1, 2011. Potential metrics included prescribing opioid-tolerant-only ER/LA opioid analgesics to non-opioid-tolerant patients, prescribing early fills to patients, and ordering drug screens. RESULTS: Proposed definitions for opioid tolerance were seven continuous days of opioid usage of at least 30 mg oxycodone equivalents, within the 7 days (primary) or 30 days (secondary) prior to first opioid-tolerant-only ERO prescription. Forty-four percent of opioid-tolerant-only ERO episodes met the primary opioid tolerance definition; 56% met the secondary definition. Fills were deemed "early" if a prescription was filled before 70% (primary) or 50% (secondary) of the prior prescription's days' supply was to be consumed. Five percent (primary) and 2% (secondary) of episodes had more than or equal to two early fills during treatment. At least one drug screen was billed in 14% of episodes. Stratified analyses indicated that older patients were less likely to be opioid tolerant at the time of the first opioid-tolerant-only ERO prescription. CONCLUSIONS: Investigators propose three metrics to monitor changes in prescribing behaviors for opioid analgesics that might be used to evaluate the ER/LA Opioid Analgesics REMS. Low frequencies of patients, particularly those >85 years, were likely to be opioid tolerant prior to receiving prescriptions for opioid-tolerant-only ERO.

The Importance of Gender-Neutral Terminology in Risk Evaluation and Mitigation Strategy Programs: A Call to Action.

The use of risk evaluation and mitigation strategy (REMS) programs is frequently required for prescriptions with potentially teratogenic effects, especially in the field of dermatology. Among these REMS programs, the most well-known example is isotretinoin, an oral retinoid that uses the iPLEDGE system. iPLEDGE has strict regulations and a lengthy approval process, and until recently, patients were grouped into 3 categories: male, female, or female of reproductive potential. This strict grouping has posed problems in the medical community, especially for gender-diverse individuals where their perceived gender conflates with their assigned grouping causing patient-specific distress. The distinction between gender-a multifactorial perception of identity-and biological sex is addressed under new iPLEDGE guidelines. Dermatologists now register patients under one of 2 categories: patients who can become pregnant and those who cannot become pregnant. This change simultaneously improves the accessibility to isotretinoin among gender-diverse individuals, while limiting prescription barriers. Despite initial success being limited due to lengthy system conversions, a registration process based on reproductive potential ultimately enhances iPLEDGE's goal to prevent potential birth defects. We propose that other REMS programs follow the standard set by the iPLEDGE system, including those for the medications thalidomide, acitretin, and mycophenolate mofetil, all of which currently have a similar taxonomy to that of the old iPLEDGE system. Implementing the standardization of gender-neutral terminology can maximize enrollment and minimize distress. Current and ongoing refinement of iPLEDGE and other REMS is needed to build protocols solely around the prevention of birth defects without regard to sex or gender.

Exploring the impact of mifepristone's risk evaluation and mitigation strategy (REMS) on the integration of medication abortion into US family medicine primary care clinics✰,✰✰.

OBJECTIVES: In 2000, the United States' Food and Drug Administration (FDA) approved mifepristone for medication abortion. In this article, we explore how the Risk Evaluation and Mitigation Strategy (REMS) criteria for mifepristone specifically impede family physicians' ability to provide medication abortion in primary care settings. STUDY DESIGN: We conducted 56 qualitative interviews with a national sample of family physicians across the US who were not opposed to abortion. We examined how the REMS criteria for mifepristone impact family physicians' ability to provide medication abortion. RESULTS: Of the 56 interviews conducted, 23 participants (41%) raised the REMS criteria as a barrier to providing medication abortion in primary care. These participants reported the REMS added a layer of bureaucratic complexity that made it difficult for family physicians to navigate, even when trained, to provide abortion care. These family physicians described 2 predominant ways the REMS impede their ability to provide medication abortion: (1) The REMS require substantial involvement of clinic administration, who can be unsupportive; (2) The complexity of navigating the REMS results in physicians and clinic administration in primary care viewing medication abortion as not worth the effort, since it is only a small component of services offered in primary care. CONCLUSION: Removing the REMS could simplify integration of medication abortion into primary care, which could meet patient preferences, improve access, and reduce abortion stigma. The FDA's revised REMS criteria may ease administrative burden but will likely maintain key barriers to integrating medication abortion into family physicians' practice. IMPLICATIONS: Our study highlights that the REMS criteria are barriers to family physicians' ability to integrate medication abortion into their primary care practices. The FDA's removal of in person dispensing criteria may provide some impetus for trained family physicians to integrate medication abortion into their scope of practice but the revised REMS criteria maintain key barriers to broader adoption.

Obstetrician-gynecologist willingness to provide medication abortion with removal of the in-person dispensing requirement for mifepristone.

OBJECTIVE: To estimate obstetrician-gynecologists' (ob-gyns) willingness to provide medication abortion if the in-person dispensing requirement for mifepristone were removed. STUDY DESIGN: We analyzed a subsample (n = 868) from a 2016 to 2017 national survey of ob-gyns, focusing on questions related to provision of medication abortion. RESULTS: In the survey, 164 (19%) ob-gyns reported providing medication abortion in the prior year. When we asked those not providing medication abortion if they would offer the method to their patients if the in-person dispensing requirement for mifepristone were removed, 171 (24%) ob-gyns reported they would, suggesting a potential doubling of providers (+104%, 95% confidence interval (CI): 97%-112%). The largest theoretical increases were in the Midwest (+189%, 95% CI: 172%-207%) and South (+118%, 95% CI: 103%-134%). In multivariable regression analysis, female ob-gyns and those in university faculty practices had higher odds of reporting they would start providing medication abortion if the dispensing requirement were removed, while those in practice >10 years had lower odds. CONCLUSIONS: Removal of the in-person dispensing requirement could increase provision of medication abortion, including in regions with limited abortion access. IMPLICATIONS: In order to improve access to medication abortion, the mifepristone Risk Evaluation and Mitigation Strategy should be modified or removed to allow clinicians to prescribe the medication with dispensing by pharmacies, including mail-order pharmacies.

Optimization of REMS Program Compliance in a Large Academic Health System.

Ensuring compliance with all applicable Risk Evaluation and Mitigation Strategies (REMS) programs within a health system is challenging. These FDA-mandated programs are numerous, unique, and ever-changing. Actions require several stakeholders and moving parts. In addition, the effectiveness and impact of these programs has been challenged and is not always clear, which hampers buy-in and therefore compliance. F&MCW is a health network in southeastern Wisconsin that includes five hospitals and almost 40 clinics. Since 2014, several system-wide approaches to medication use, including formulary alignment and REMS program optimization, have taken place with an over-arching goal of providing efficient, safe, and consistent care for the patients and populations served. This manuscript describes the steps that took place over the past six years or so related to REMS program optimization. It also offers practical tips for other health systems based on lessons learned through this one institution's experiences.

Increase your Confidence in Opioid Prescribing: Marketing Messages in Continuing Medical Education Activities on ER/LA Opioids.

BACKGROUND: Overprescription of opioids has fueled an epidemic of addiction and overdose deaths. The FDA required manufacturers of extended-release/long-acting (ER/LA) opioids to fund continuing medical education (CME) on opioids as part of a Risk Evaluation and Mitigation Strategy (REMS). OBJECTIVES: We sought to determine whether industry-funded REMS on long-acting opioids were consistent with the FDA's goal to reduce serious, adverse outcomes resulting from inappropriate prescribing, misuse, and abuse. STUDY DESIGN: In 2018, we analyzed all internet-based REMS CME activities funded by the REMS Program Companies (RPC), a consortium of ER/LA opioid manufacturers. METHODS: We utilized systematic narrative thematic analysis, an inductive approach that allows for mapping of concepts and meanings across a body of data by identifying, recording, analyzing, and refining key narrative points, called "themes". Authors viewed all REMS activities multiple times. RESULTS: Ten themes were identified, all of which were at least somewhat incongruent with federal guidelines and their goals: 1. Chronic pain is a common, under-treated problem. 2.Chronic pain is a chronic disease.3.Opioids are an appropriate treatment for chronic pain. 4.LAs are more appropriate than immediate-release (IR) opioids for chronic pain. 5.Tolerance is normal, expected, and beneficial. 6. Opioid rotation" can maximize analgesia and minimize adverse effects.7. There is no population for whom opioids are absolutely contraindicated or inappropriate. 8. Screening and monitoring tools are effective for preventing opioid-related problems. 9. Opioid related adverse effects, such as respiratory depression and addiction, are due only to misuse and abuse. Addiction, overdose, and death are due to street drugs such as heroin and fentanyl, not prescription opioids.Themes and statements repeated in these activities were inconsistent with current medical knowledge, evidence-based federal guidelines, and FDA goals. LIMITATIONS: We evaluated only online, not live, CME. We also did not evaluate individual conflicts of interest of faculty. CONCLUSIONS: Industry-funded REMS-compliant CME on opioids contain messages that misrepresent scientific evidence and may foster overprescribing of opioids.

Pain Management and Opioid Therapy: Persistent Knowledge Gaps Among Primary Care Providers.

INTRODUCTION: Given the opioid epidemic in the US, it is vital that clinicians who prescribe opioids for pain management to do so in an evidence-based manner, eg considering all pharmacologic and non-pharmacologic options, assessing risk of opioid use disorder prior to initiating opioids. Continuing education regarding the evidence-based prescribing of opioids is now required for US healthcare providers who prescribe opioids. A "blueprint" of the content to be included in continuing education programs was developed by the US Food and Drug Administration and updated in 2018. METHODS: To understand the baseline knowledge and confidence of healthcare professionals in prescribing opioids for pain management, we posed 27 unique knowledge-based questions and 1 confidence question to clinician participants before or during 2 continuing educational programs that were based respectively on the 2016 and 2018 FDA Risk Evaluation and Mitigation Strategy (REMS) educational blueprints for pain management. RESULTS: Overall, 5571 clinicians completed these programs, including 1925 physicians (1516 [79%] identifying as primary care), 1181 physician assistants, 737 advanced practice nurses, 719 nurses, and 479 pharmacists. Responses to pretest questions in both programs indicated profound and persistent gaps in knowledge, particularly in definitions and mechanisms of pain, general principles of pharmacologic analgesic therapy, and specific aspects of opioid analgesic therapy and addiction. Participants in both programs also expressed limited confidence in their abilities to incorporate patient engagement techniques into pain management or develop a treatment plan for a patient with chronic pain. DISCUSSION: These data support an ongoing need for comprehensive clinician-based education as outlined in the FDA REMS educational blueprint, especially given recent data of escalating overdose deaths during the COVID-19 pandemic.

Sociodemographic, clinical and criminological characteristics of a sample of Italian Volterra REMS patients.

BACKGROUND: In Italy the Law 9/2012 prescribed the total closure of forensic psychiatric hospitals (OPGs) and the conversion to a care model based on residential units in the community employing only clinical personnel (Residenze per l'Esecuzione delle Misure di Sicurezza - REMS) and fully integrated in public mental health services. The aim of this study is to report sociodemographic, clinical and criminological characteristics of patients admitted in Volterra REMS since it opened on 01/12/15 up to 31/12/17. METHODS: Sociodemographic and clinical information was collected from official documents (clinical files, ward reports) and from patients' personal health records. Psychiatric diagnoses were made by REMS psychiatrists according to the DSM-5 criteria. Criminological information was obtained from patients' criminal records. RESULTS: Volterra REMS patients' characteristics are similar to those of samples of OPGs patients (unmarried socially disadvantaged males with an average age of 40, no offsprings, low education, high rates of Schizophrenia Spectrum Disorders and medical comorbidity). However, the REMS model presents a very high turnover rate: during the study period 61 patients were admitted while 32 were discharged. Being assisted by public mental health services before committing the crime increased the probability of discharge. In non-EU patients long acting injectable antipsychotics were used more frequently than in community ones. Substance-Related Disorders are the main psychiatric comorbidity and resulted as being more frequent in bipolar patients than in other patients. CONCLUSIONS: Due to the high patients' turnover, we expect a progressive change in sociodemographic, clinical and criminological features of the REMS population. The REMS model provides a return for mentally disordered criminals to the care of local public mental health services which are recovering after many years some of their most challenging patients ensuring their deinstitutionalization and reintegration into society.

Management of treatment-related toxicities in advanced medullary thyroid cancer.

Progress in the treatment of advanced medullary thyroid cancer (MTC) has resulted from the approval of 2 drugs within the past 5 years, vandetanib and cabozantinib. These multikinase inhibitors (MKIs) possess overlapping specificities for multiple kinase targets implicated in the progression of MTC. Both drugs are associated with toxicities, including hypertension, hemorrhage/perforation, diarrhea and other gastrointestinal events, several dermatologic events, and hypothyroidism. In addition, vandetanib is uniquely associated with QTc prolongation through interaction with myocardial potassium channels, and cabozantinib is uniquely associated with hand-foot skin reaction. Treatment-related toxicities occur frequently and can be severe or life-threatening, and patients undergoing long-term treatment will likely experience adverse events (AEs). Here we offer specific practical recommendations for managing AEs commonly occurring with vandetanib and cabozantinib. The recommended approach relies on early recognition and palliation of symptoms, dose interruption, and dose reduction as necessary in order for the patient to maintain the highest tolerable dose for as long as possible and optimal quality of life. Treatment guidelines do not specify a recommended sequence for treating with vandetanib and cabozantinib; however, most patients will receive both drugs during their lifetime. The choice for first-line therapy is individualized after a risk-benefit assessment and depends on physician preference and patient-related factors, such as comorbid conditions. Because most generalist practices may not be familiar with the intricacies of agents such as vandetanib and cabozantinib, we commend that patients with advanced MTC be managed and treated by a thyroid cancer specialist with coordination of care within a multidisciplinary team.

Patient Access in Restrictive Risk Management Programs: The Case of iPLEDGE.

BACKGROUND: The isotretinoin risk management program iPLEDGE places requirements on patients and providers to ensure that the benefits of isotretinoin therapy outweigh the risks. Such burdens have the possibility of limiting patient access through mechanisms such as lowered physician participation. METHODS: In this study, we utilized prescription claims data to examine changes in patient and provider participation in isotretinoin therapy with iPLEDGE implementation. We examined the change in utilization among patients not targeted by iPLEDGE (male patients) to assess the program's impact on access. We also examined whether provider participation in isotretinoin therapy varies by specialty and isotretinoin prescribing history. RESULTS: Patient access to isotretinoin decreased in the period immediately following iPLEDGE implementation, but recovered to pre-iPLEDGE levels in the succeeding months. In addition, therapy completion rates increased with iPLEDGE implementation, suggesting that patients less committed to isotretinoin therapy may be self-selecting out of therapy. Lastly, iPLEDGE resulted in decreased participation by low-volume, general practitioners, while high-volume, specialists' participation was largely unchanged. CONCLUSION: We found that participants responded to iPLEDGE's burdens in predictable ways. Insufficient anticipation of potential iPLEDGE rollout issues initially disrupted patient treatment and resulted in far fewer patients starting therapy. Over a longer term, isotretinoin utilization and therapy completion increased and isotretinoin prescribing shifted toward high-volume, specialist providers. We argue that these changes are predictable based on the burdens iPLEDGE imposes on patients and prescribers and may not be inconsistent with the goals of the risk management program.

A Descriptive Evaluation of Prescriber Perceptions and Experience With Risk Evaluation and Mitigation Strategy (REMS) Programs in an Integrated Health Care System.

OBJECTIVE: To assess prescriber perceptions and experience with risk evaluation and mitigation strategy (REMS) programs in an integrated health care delivery system. METHODS: A cross-sectional online survey was e-mailed to eligible health care prescribers if they prescribed at least 1 selected REMS-related product within 6 months spanning January 1 to June 30, 2013; were an active employee of Kaiser Permanente Southern California; and had an active " kp.org " e-mail address. Descriptive analyses were conducted on the survey responses. RESULTS: Three hundred sixty-four respondents (34%) completed the online survey. The majority were primary care prescribers (65%) versus nonprimary prescribers. The majority of primary care, oncologist, and specialist prescribers responded that REMS was meaningful, improved patient safety, and made an impact on their patient interactions. The majority of surgeons and pain management prescribers responded that REMS was not meaningful, did not improve safety for the patients, or did not impact their interactions with their patients. Over 50% of prescribers counseled their patients or had another health care team member discuss the risks and benefits of these REMS-related medications; medication guides or other printed literature was not provided as much. CONCLUSION: The results from the survey suggest that prescriber specialty has an impact on the perceived value of the REMS program and the perceived need to counsel patients regarding medications with REMS programs.

Primary care physician attitudes and perceptions of the impact of FDA-proposed REMS policy on prescription of extended-release and long-acting opioids.

With increasing numbers of patients experiencing chronic pain, opioid therapy is becoming more common, leading to increases in concern about issues of abuse, diversion, and misuse. Further, the US Food and Drug Administration recently released a statement notifying sponsors and manufacturers of extended-release and long-acting opioids of the need to develop Risk Evaluation and Mitigation Strategies (REMS) programs in order to ensure that the benefits of this therapy choice outweigh the potential risks. There is little research on physician opinions concerning opioid-prescribing and education policies. To assess attitudes surrounding new opioid policies, a survey was designed and distributed to primary care physicians in October 2011. Data collected from 201 primary care physicians show that most are not familiar with the REMS requirements proposed by the Food and Drug Administration for extended-release and long-acting opioids; there is no consensus among primary care physicians on the impact of prescribing requirements on patient education and care; and increasing requirements for extended-release and long-acting opioid education may decrease opioid prescribing. Physician attitudes toward increased regulatory oversight of opioid therapy prescriptions should be taken into consideration by groups developing these interventions to ensure that they do not cause undue burden on already busy primary care physicians.

The changing landscape of opioid prescribing: long-acting and extended-release opioid class-wide Risk Evaluation and Mitigation Strategy.

Prescriptions for opioid analgesics to manage moderate-to-severe chronic noncancer pain have increased markedly over the last decade, as have postmarketing reports of adverse events associated with opioids. As an unintentional consequence of greater prescription opioid utilization, there has been the parallel increase in misuse, abuse, and overdose, which are serious risks associated with all opioid analgesics. In response to these concerns, the Food and Drug Administration announced the requirement for a class-wide Risk Evaluation and Mitigation Strategy (REMS) for long-acting and extended-release (ER) opioid analgesics in April 2011. An understanding of the details of this REMS will be of particular importance to primary care providers. The class-wide REMS is focused on educating health care providers and patients on appropriate prescribing and safe use of ER opioids. Support from primary care will be necessary for the success of this REMS, as these clinicians are the predominant providers of care and the main prescribers of opioid analgesics for patients with chronic pain. Although currently voluntary, future policy will likely dictate that providers undergo mandatory training to continue prescribing medications within this class. This article outlines the elements of the class-wide REMS for ER opioids and clarifies the impact on primary care providers with regard to training, patient education, and clinical practice.