[Federal Register Volume 84, Number 53 (Tuesday, March 19, 2019)] [Notices] [Pages 10080-10083] From the Federal Register Online via the Government Publishing Office [www.gpo.gov] [FR Doc No: 2019-05145] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Agency for Healthcare Research and Quality Supplemental Evidence and Data Request on Opioid Treatments for Chronic Pain AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS. ACTION: Request for supplemental evidence and data submissions. ----------------------------------------------------------------------- SUMMARY: The Agency for Healthcare Research and Quality (AHRQ) is seeking scientific information submissions from the public. Scientific information is being solicited to inform our review on Opioid Treatments for Chronic Pain, which is currently being conducted by the AHRQ's Evidence-based Practice Centers (EPC) Program. Access to published and unpublished pertinent scientific information will improve the quality of this review. DATES: Submission Deadline on or before April 18, 2019. ADDRESSES: Email submissions: [email protected]. Print submissions: Mailing Address: Center for Evidence and Practice Improvement, Agency for Healthcare Research and Quality, ATTN: EPC SEADs Coordinator, 5600 Fishers Lane, Mail Stop 06E53A, Rockville, MD 20857. Shipping Address (FedEx, UPS, etc.): Center for Evidence and Practice Improvement, Agency for Healthcare Research and Quality, ATTN: EPC SEADs Coordinator, 5600 Fishers Lane, Mail Stop 06E77D, Rockville, MD 20857. FOR FURTHER INFORMATION CONTACT: Jenae Benns, Telephone: 301-427-1496 or Email: [email protected]. SUPPLEMENTARY INFORMATION: The Agency for Healthcare Research and Quality has commissioned the Evidence-based Practice Centers (EPC) Program to complete a review of the evidence for Opioid Treatments for Chronic Pain. AHRQ is conducting this systematic review pursuant to Section 902(a) of the Public Health Service Act, 42 U.S.C. 299a(a). The EPC Program is dedicated to identifying as many studies as possible that are relevant to the questions for each of its reviews. In order to do so, we are supplementing the usual manual and electronic database searches of the literature by requesting information from the public (e.g., details of studies conducted). We are looking for studies that report on Opioid Treatments for Chronic Pain, including those that describe adverse events. The entire research protocol is available online at: https://effectivehealthcare.ahrq.gov/topics/opioids-chronic-pain/protocol. This is to notify the public that the EPC Program would find the following information on Opioid Treatments for Chronic Pain helpful: [ssquf] A list of completed studies that your organization has sponsored for this indication. In the list, please indicate whether results are available on ClinicalTrials.gov along with the ClinicalTrials.gov trial number. [ssquf] For completed studies that do not have results on ClinicalTrials.gov, please provide a summary, including the following elements: Study number, study period, design, methodology, indication and diagnosis, proper use instructions, inclusion and exclusion criteria, primary and secondary outcomes, baseline characteristics, number of patients screened/eligible/enrolled/lost to follow-up/ withdrawn/analyzed, effectiveness/efficacy, and safety results. [ssquf] A list of ongoing studies that your organization has sponsored for this indication. In the list, please provide the ClinicalTrials.gov trial number or, if the trial is not registered, the protocol for the study including a study number, the study period, design, methodology, indication and diagnosis, proper use instructions, inclusion and exclusion criteria, and primary and secondary outcomes. [ssquf] Description of whether the above studies constitute ALL Phase II and above clinical trials sponsored by your organization for this indication and an index outlining the relevant information in each submitted file. Your contribution will be very beneficial to the EPC Program. Materials submitted must be publicly available or able to be made public. Materials that are considered confidential; marketing materials; study types not included in the review; or information on indications not included in the review cannot be used by the EPC Program. This is a voluntary request for information, and all costs for complying with this request must be borne by the submitter. The draft of this review will be posted on AHRQ's EPC Program website and available for public comment for a period of 4 weeks. If you would like to be notified when the draft is posted, please sign up for the email list at: https://www.effectivehealthcare.ahrq.gov/email-updates. The systematic review will answer the following questions. This information is provided as background. AHRQ is not requesting that the public provide answers to these questions. The Key Questions: Key Question 1. Effectiveness and Comparative Effectiveness a. In patients with chronic pain, what is the effectiveness of opioid therapy versus placebo or no opioid therapy for outcomes related to pain, function, and quality of life, after short-term follow-up (up to 6 months), intermediate-term follow-up (6 to 12 months), and long- term follow-up (at least 1 year)? b. How does effectiveness vary depending on: (1) the specific type or cause of pain (e.g., neuropathic, musculoskeletal [including low back pain], visceral pain, fibromyalgia, sickle cell disease, inflammatory pain, headache disorders, and degree of nociplasticity); (2) patient demographics (e.g., age, race, ethnicity, gender, socioeconomic status); (3) patient comorbidities (including past or current alcohol or substance use disorders, mental health disorders, medical comorbidities and high risk for opioid use disorder); (4) the mechanism of action of opioids used (e.g., pure opioid agonists, partial opioid agonists such as buprenorphine or drugs with mixed opioid and nonopioid mechanisms of action such as tramadol or tapentadol)? c. In patients with chronic pain, what is the comparative effectiveness of opioids versus nonopioid therapies (pharmacologic or nonpharmacologic, including marijuana) on outcomes related to pain, function, and quality of life, after short-term follow-up (up to 6 months), intermediate-term follow-up (6 to 12 months), and long-term follow-up (at least 1 year)? d. In patients with chronic pain, what is the comparative effectiveness of opioids plus nonopioid interventions (pharmacologic or nonpharmacologic, including marijuana) versus opioids or nonopioid interventions alone on outcomes related to pain, function, quality of life, and doses of opioids [[Page 10081]] used, after short-term follow-up (up to 6 months), intermediate-term follow-up (6 to 12 months), and long-term follow-up (at least 1 year)? Key Question 2. Harms and Adverse Events a. In patients with chronic pain, what are the risks of opioids versus placebo or no opioid on: (1) substance misuse, substance use disorder, and related outcomes; (2) overdose (intentional and unintentional); (3) other harms, including gastrointestinal-related harms, falls, fractures, motor vehicle accidents, endocrinological harms, infections, cardiovascular events, cognitive harms, and psychological harms (e.g., depression)? b. How do harms vary depending on: (1) the specific type or cause of pain (e.g., neuropathic, musculoskeletal [including back pain], visceral pain, fibromyalgia, sickle cell disease, inflammatory pain, headache disorders, and degree of nociplasticity); (2) patient demographics; (3) patient comorbidities (including past or current substance use disorder or at high risk for opioid use disorder); (4) the dose of opioids used and duration of therapy; (5) the mechanism of action of opioids used (e.g., are there differences between pure opioid agonists and partial opioid agonists such as buprenorphine or drugs with opioid and nonopioid mechanisms of action such as tramadol and tapentadol); (6) use of sedative hypnotics; (7) use of gabapentinoids; (8) use of marijuana? Key Question 3. Dosing Strategies a. In patients with chronic pain, what is the comparative effectiveness of different methods for initiating and titrating opioids for outcomes related to pain, function, and quality of life; risk of misuse, opioid use disorder, and overdose; and doses of opioids used? b. In patients with chronic pain, what is the comparative effectiveness of short-acting versus long-acting opioids on outcomes related to pain, function, and quality of life; risk of misuse, opioid use disorder, and overdose; and doses of opioids used? c. In patients with chronic pain, what is the comparative effectiveness of different long-acting opioids on outcomes related to pain, function, and quality of life; and risk of misuse, opioid use disorder, and overdose? d. In patients with chronic pain, what is the comparative effectiveness of short- plus long-acting opioids versus long-acting opioids alone on outcomes related to pain, function, and quality of life; risk of misuse, opioid use disorder, and overdose; and doses of opioids used? e. In patients with chronic pain, what is the comparative effectiveness of scheduled, continuous versus as-needed dosing of opioids on outcomes related to pain, function, and quality of life; risk of misuse, opioid use disorder, and overdose; and doses of opioids used? f. In patients with chronic pain, what is the comparative effectiveness of opioid dose escalation versus dose maintenance or use of dose thresholds on outcomes related to pain, function, and quality of life? g. In patients with chronic pain, what is the comparative effectiveness of opioid rotation versus maintenance of current opioid therapy on outcomes related to pain, function, and quality of life; and doses of opioids used? h. In patients with chronic pain, what is the comparative effectiveness of different strategies for treating acute exacerbations of chronic pain on outcomes related to pain, function, and quality of life? i. In patients with chronic pain, what are the effects of decreasing opioid doses or of tapering off opioids versus continuation of opioids on outcomes related to pain, function, quality of life, and withdrawal? j. In patients with chronic pain, what is the comparative effectiveness of different tapering protocols and strategies on measures related to pain, function, quality of life, withdrawal symptoms, and likelihood of opioid cessation? k. In patients with chronic pain, what is the comparative effectiveness of different opioid dosages and durations of therapy for outcomes related to pain, function, and quality of life; risk of misuse, opioid use disorder, and overdose? Key Question 4. Risk Assessment and Risk Mitigation Strategies a. In patients with chronic pain being considered for opioid therapy, what is the accuracy of instruments and tests (including metabolic and/or genetic testing) for predicting risk of misuse, opioid use disorder, and overdose? b. In patients with chronic pain, what is the effectiveness of use of risk prediction instruments and tests (including metabolic and/or genetic testing) on outcomes related to misuse, opioid use disorder, and overdose? c. In patients with chronic pain who are prescribed opioid therapy, what is the effectiveness of risk mitigation strategies, including (1) opioid management plans, (2) patient education, (3) urine drug screening, (4) use of prescription drug monitoring program data, (5) use of monitoring instruments, (6) more frequent monitoring intervals, (7) pill counts, (8) use of abuse-deterrent formulations, (9) consultation with mental health providers when mental health conditions are present, (10) avoidance of co-prescribing of sedative hypnotics, and (11) co-prescribing of naloxone on outcomes related to misuse, opioid use disorder, and overdose? d. In patients with chronic pain, what is the comparative effectiveness of treatment strategies for managing patients with opioid use disorder related to prescription opioids on outcomes related to misuse, opioid use disorder, overdose, pain, function, and quality of life? [[Page 10082]] PICOTS (Populations, Interventions, Comparators, Outcomes, Timing, Settings) ---------------------------------------------------------------------------------------------------------------- Key question Population Intervention Comparator Outcome ---------------------------------------------------------------------------------------------------------------- 1a, b................... Adults (age >=18 Long- or short- Placebo or no opioid Pain, function, and years) with various acting opioids therapy. quality of life). types of chronic (including partial pain including agonists and dual pregnant/breast- mechanism agents). feeding women and Exclude: Intravenous patients treated or intramuscular with opioids for administration of opioid use disorder. opioids.. Key Question 1b: Subgroups: (1) The specific type or cause of pain (e.g., neuropathic, musculoskeletal [including low back pain], fibromyalgia, sickle cell disease, inflammatory pain, and headache disorders); (2) patient demographics (e.g., age, race, ethnicity, gender); (3) patient comorbidities (including past or current alcohol or substance use disorders, mental health disorders, medical comorbidities and high risk for opioid use disorder).. 1c...................... Adults (age >=18 Long- or short- Nonopioid therapies Pain, function, and years) with various acting opioids (pharmacologic quality of life; types of chronic (including partial [antiepileptic doses of opioids pain. agonists and dual drugs, used. action medications). benzodiazepines, Exclude: Intravenous nonsteroidal or intramuscular antiinflammatory administration of drugs, skeletal opioids.. muscle relaxants, serotonin norepinephrine reuptake inhibitors, topical lidocaine, topical capsaicin, topical diclofenac, tricyclica antidepressants, acetaminophen, memantine, and marijuana/cannabis] or nonpharmacologic [noninvasive]). 1d...................... Adults (age >=18 Opioids plus Opioids or nonopioid Pain, function, and years) with various nonopioid interventions quality of life, types of chronic interventions alone, including doses of opioids pain. (pharmacologic or marijuana. used. nonpharmacologic). Exclude: Intravenous or intramuscular administration of opioids.. 2a...................... Adults (age >=18 Long- or short- Placebo or no opioid Substance misuse, years) with various acting opioids substance use types of chronic (including disorder and pain. tapentadol, related outcomes, Key Question 2b: buprenorphine, and overdose, and other Subgroups (1) the tramadol) opioids. harms. specific type or Exclude: Intravenous cause of pain or intramuscular (e.g., neuropathic, administration of musculoskeletal opioids.. [including back pain], fibromyalgia, sickle cell disease, inflammatory pain, headache disorders); (2) patient demographics; (3) patient comorbidities (including past or current substance use disorder or at high risk for opioid use disorder); (4) the dose of opioids used; (5) the mechanisms of actions of the opioids; and (6) use of sedative hypnotics.. 3a...................... Adults (age >=18 Long- or short- Other opioids with Pain, function, and years) with various acting opioids different dose quality of life; types of chronic (including initiation and doses of opioids pain. tapentadol, titration used. buprenorphine, and strategies. tramadol). 3b...................... Adults (age >=18 Short-acting opioid. Long-acting opioid.. Pain, function, and years) with various quality of life; types of chronic risk of misuse, pain. opioid use disorder, overdose and other harms; doses of opioids used. 3c...................... Adults (age >=18 Long-acting opioid.. Other long-acting Pain, function, and years) with various opioid. quality of life; types of chronic risk of misuse, pain. opioid use disorder, and overdose and other harms; doses of opioids used. 3d...................... Adults (age >=18 Short and long Long-acting opioid.. Pain, function, and years) with various acting opioid. quality of life; types of chronic risk of misuse, pain. opioid use disorder, overdose and other harms; doses of opioids used. 3e...................... Adults (age >=18 Scheduled, As-needed dosing.... Pain, function, and years) with various continuous dosing. quality of life; types of chronic risk of misuse, pain. opioid use disorder, overdose, and other harms; doses of opioids used. 3f...................... Adults (age >=18 Opioid dose Dose maintenance or Pain, function, and years) with various escalation. use of dose quality of life. types of chronic thresholds. pain. 3g...................... Adults (age >=18 Opioid rotation..... Maintenance of Pain, function, and years) with various current opioid quality of life; types of chronic therapy. doses of opioids pain. used. 3h...................... Adults (age >=18 Treatments for acute Other treatments for Pain, function, and years) with various exacerbations of acute exacerbations quality of life. types of chronic chronic pain. of chronic pain. pain and an acute exacerbation. [[Page 10083]] 3i...................... Adults (age >=18 Decreasing opioid Continuation of Pain, function, and years) with various doses or of opioids. quality of life; types of chronic tapering off withdrawal and pain. opioids. other harms (including overdose, use of illicit opioids, suicidality, and anger/violence). 3j...................... Adults (age >=18 Tapering protocols Other tapering Pain, function, years) with various and strategies. protocols or quality of life, types of chronic strategies. likelihood of pain. opioid cessation, withdrawal symptoms and other harms (including overdose, use of illicit opioids, suicidality, and anger/violence). 3k...................... Adults (age >=18 Dosage of opioid.... Other dose of same Pain, function, and years) with various opioid. quality of life; types of chronic risk of misuse, pain. opioid use disorder, overdose and other harms. 4a...................... Adults (age >=18 Instruments, genetic/ Reference standard Measures of years) with various metabolic tests for for misuse, opioid diagnostic types of chronic predicting risk of use disorder, or accuracy. pain. misuse, opioid use overdose; or other disorder, and benchmarks. overdose. 4b...................... Adults (age >=18 Use of risk Usual care or other Misuse, opioid use years) with various prediction control. disorder, overdose types of chronic instruments, and other harms. pain. genetic/metabolic tests. 4c...................... Adults (age >=18 Risk mitigation Usual care.......... Pain, function, years) with various strategies, quality of life, types of chronic including (1) misuse, opioid use pain. opioid management disorder, overdose plans, (2) patient and other harms education, (3) (including use of urine drug illicit opioids, screening, (4) use suicidality, and of prescription anger/violence). drug monitoring program data, (5) use of monitoring instruments, (6) more frequent monitoring intervals, (7) pill counts, (8) use of abuse-deterrent formulations, (9) consultation with mental health providers when mental health conditions are present, (10) avoidance of benzodiazepine co- prescribing and (11) co-prescribing of naloxone. 4d...................... Adults (age >=18 Treatment strategies Other treatment Pain, function, years) with various strategies. quality of life, types of chronic misuse, opioid use pain and opioid use disorder, overdose, disorder. other harms, pain, function, and quality of life. ---------------------------------------------------------------------------------------------------------------- Additional Inclusion Criteria TimingFor all questions, studies with at least 1 month of followup will be included. Results will be stratified according to short-term (1 to 6 months), intermediate term (6 to 12 months), and long-term (>=1 year) followup. Setting Include: Outpatient settings (e.g., primary care, pain clinics, other specialty clinics, emergency rooms, urgent care clinics). Exclude: Addiction treatment settings, inpatient settings. Gopal Khanna, Director. [FR Doc. 2019-05145 Filed 3-18-19; 8:45 am] BILLING CODE 4160-90-P