Supplemental Evidence and Data Request on Opioid Treatments for Chronic Pain, 10080-10083 [2019-05145]

Download as PDF 10080 Federal Register / Vol. 84, No. 53 / Tuesday, March 19, 2019 / Notices date of delisting and revocation to complete the disposition of PSWP that is currently in the PSO’s possession. More information on PSOs can be obtained through AHRQ’s PSO website at http://www.pso.ahrq.gov. Gopal Khanna, Director. [FR Doc. 2019–05150 Filed 3–18–19; 8:45 am] BILLING CODE 4160–90–P DEPARTMENT OF HEALTH AND HUMAN SERVICES Agency for Healthcare Research and Quality Supplemental Evidence and Data Request on Opioid Treatments for Chronic Pain Agency for Healthcare Research and Quality (AHRQ), HHS. ACTION: Request for supplemental evidence and data submissions. AGENCY: 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 Access to published and unpublished pertinent scientific information will improve the quality of this review.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: epc@ ahrq.hhs.gov. 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. SUMMARY: FOR FURTHER INFORMATION CONTACT: Jenae Benns, Telephone: 301–427–1496 or Email: epc@ahrq.hhs.gov. 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 VerDate Sep<11>2014 17:54 Mar 18, 2019 Jkt 247001 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: D 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. D 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. D 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. D 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 PO 00000 Frm 00061 Fmt 4703 Sfmt 4703 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 longterm 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 E:\FR\FM\19MRN1.SGM 19MRN1 Federal Register / Vol. 84, No. 53 / Tuesday, March 19, 2019 / Notices used, after short-term follow-up (up to 6 months), intermediate-term follow-up (6 to 12 months), and long-term followup (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? VerDate Sep<11>2014 17:54 Mar 18, 2019 Jkt 247001 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 PO 00000 Frm 00062 Fmt 4703 Sfmt 4703 10081 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? E:\FR\FM\19MRN1.SGM 19MRN1 10082 Federal Register / Vol. 84, No. 53 / Tuesday, March 19, 2019 / Notices PICOTS (POPULATIONS, INTERVENTIONS, COMPARATORS, OUTCOMES, TIMING, SETTINGS) Key question Population Intervention Comparator 1a, b .................. Adults (age ≥18 years) with various types of chronic pain including pregnant/breast-feeding women and patients treated with opioids for opioid use disorder. 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). Adults (age ≥18 years) with various types of chronic pain. Long- or short-acting opioids (including partial agonists and dual mechanism agents). Exclude: Intravenous or intramuscular administration of opioids. Placebo or no opioid therapy ........ Pain, function, and quality of life). Long- or short-acting opioids (including partial agonists and dual action medications). Exclude: Intravenous or intramuscular administration of opioids. Pain, function, and quality of life; doses of opioids used. 1d ...................... Adults (age ≥18 years) with various types of chronic pain. 2a ...................... Adults (age ≥18 years) with various types of chronic pain. Key Question 2b: Subgroups (1) the specific type or cause of pain (e.g., neuropathic, musculoskeletal [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. Adults (age ≥18 years) with various types of chronic pain. Opioids plus nonopioid interventions (pharmacologic or nonpharmacologic). Exclude: Intravenous or intramuscular administration of opioids. Long- or short-acting opioids (including tapentadol, buprenorphine, and tramadol) opioids. Exclude: Intravenous or intramuscular administration of opioids. Nonopioid therapies (pharmacologic [antiepileptic drugs, benzodiazepines, nonsteroidal antiinflammatory drugs, skeletal muscle relaxants, serotonin norepinephrine reuptake inhibitors, topical lidocaine, topical capsaicin, topical diclofenac, tricyclica antidepressants, acetaminophen, memantine, and marijuana/cannabis] or nonpharmacologic [noninvasive]). Opioids or nonopioid interventions alone, including marijuana. Placebo or no opioid ..................... Substance misuse, substance use disorder and related outcomes, overdose, and other harms. 1c ....................... 3a ...................... Outcome Long- or short-acting opioids (including tapentadol, buprenorphine, and tramadol). Short-acting opioid ........................ Other opioids with different dose initiation and titration strategies. Pain, function, and quality of life; doses of opioids used. Long-acting opioid ......................... Pain, function, and quality of life; risk of misuse, opioid use disorder, overdose and other harms; doses of opioids used. Pain, function, and quality of life; risk of misuse, opioid use disorder, and overdose and other harms; doses of opioids used. Pain, function, and quality of life; risk of misuse, opioid use disorder, overdose and other harms; doses of opioids used. Pain, function, and quality of life; risk of misuse, opioid use disorder, overdose, and other harms; doses of opioids used. Pain, function, and quality of life. 3b ...................... Adults (age ≥18 years) with various types of chronic pain. 3c ....................... Adults (age ≥18 years) with various types of chronic pain. Long-acting opioid ......................... Other long-acting opioid ................ 3d ...................... Adults (age ≥18 years) with various types of chronic pain. Short and long acting opioid ......... Long-acting opioid ......................... 3e ...................... Adults (age ≥18 years) with various types of chronic pain. Scheduled, continuous dosing ...... As-needed dosing ......................... 3f ....................... Adults (age ≥18 years) with various types of chronic pain. Adults (age ≥18 years) with various types of chronic pain. Adults (age ≥18 years) with various types of chronic pain and an acute exacerbation. Opioid dose escalation .................. Dose maintenance or use of dose thresholds. Maintenance of current opioid therapy. Other treatments for acute exacerbations of chronic pain. 3g ...................... 3h ...................... VerDate Sep<11>2014 17:54 Mar 18, 2019 Jkt 247001 Pain, function, and quality of life, doses of opioids used. Opioid rotation ............................... Treatments for acute exacerbations of chronic pain. PO 00000 Frm 00063 Fmt 4703 Sfmt 4703 E:\FR\FM\19MRN1.SGM 19MRN1 Pain, function, and quality of life; doses of opioids used. Pain, function, and quality of life. 10083 Federal Register / Vol. 84, No. 53 / Tuesday, March 19, 2019 / Notices PICOTS (POPULATIONS, INTERVENTIONS, COMPARATORS, OUTCOMES, TIMING, SETTINGS)—Continued Comparator Outcome 3i ........................ Key question Adults (age ≥18 years) with various types of chronic pain. Population Decreasing opioid doses or of tapering off opioids. Continuation of opioids .................. 3j ........................ Adults (age ≥18 years) with various types of chronic pain. Tapering protocols and strategies Other tapering protocols or strategies. 3k ....................... Adults (age ≥18 years) with various types of chronic pain. Dosage of opioid ........................... Other dose of same opioid ............ 4a ...................... Adults (age ≥18 years) with various types of chronic pain. Reference standard for misuse, opioid use disorder, or overdose; or other benchmarks. 4b ...................... Adults (age ≥18 years) with various types of chronic pain. Adults (age ≥18 years) with various types of chronic pain. Instruments, genetic/metabolic tests for predicting risk of misuse, opioid use disorder, and overdose. Use of risk prediction instruments, genetic/metabolic tests. 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 benzodiazepine co-prescribing and (11) co-prescribing of naloxone. Treatment strategies ..................... Pain, function, and quality of life; withdrawal and other harms (including overdose, use of illicit opioids, suicidality, and anger/violence). Pain, function, quality of life, likelihood of opioid cessation, withdrawal symptoms and other harms (including overdose, use of illicit opioids, suicidality, and anger/violence). Pain, function, and quality of life; risk of misuse, opioid use disorder, overdose and other harms. Measures of diagnostic accuracy. 4c ....................... Intervention Adults (age ≥18 years) with various types of chronic pain and opioid use disorder. 4d ...................... Additional Inclusion Criteria Usual care ..................................... Other treatment strategies ............ DEPARTMENT OF HEALTH AND HUMAN SERVICES Timing • For 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. Agency for Healthcare Research and Quality Agency Information Collection Activities: Proposed Collection; Comment Request Agency for Healthcare Research and Quality, HHS. ACTION: Notice. AGENCY: 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 VerDate Sep<11>2014 Usual care or other control ........... 17:54 Mar 18, 2019 Jkt 247001 This notice announces the intention of the Agency for Healthcare Research and Quality (AHRQ) to request that the Office of Management and Budget (OMB) approve the proposed information collection project: ‘‘Child Hospital Consumer Assessment of Healthcare Providers and Systems (Child HCAHPS) Survey Database.’’ This proposed information collection was previously published in the Federal Register on November 7th, 2018, and allowed 60 days for public comments. AHRQ received and responded to one substantive comment from a member of the public. The purpose of this notice is SUMMARY: PO 00000 Frm 00064 Fmt 4703 Sfmt 4703 Misuse, opioid use disorder, overdose and other harms. Pain, function, quality of life, misuse, opioid use disorder, overdose and other harms (including use of illicit opioids, suicidality, and anger/violence). Pain, function, quality of life, misuse, opioid use disorder, overdose, other harms, pain, function, and quality of life. to allow an additional 30 days for public comment. DATES: Comments on this notice must be received by April 18, 2019. ADDRESSES: Written comments should be submitted to: AHRQ’s OMB Desk Officer by fax at (202) 395–6974 (attention: AHRQ’s desk officer) or by email at OIRA_submission@ omb.eop.gov (attention: AHRQ’s desk officer). FOR FURTHER INFORMATION CONTACT: Doris Lefkowitz, AHRQ Reports Clearance Officer, (301) 427–1477, or by email at doris.lefkowitz@AHRQ.hhs.gov. SUPPLEMENTARY INFORMATION: Proposed Project Child Hospital Consumer Assessment of Healthcare Providers and Systems (Child HCAHPS) Survey Database In accordance with the Paperwork Reduction Act, 44 U.S.C. 3501–3521, AHRQ invites the public to comment on this proposed information collection. The Child Hospital CAHPS Survey (Child HCAHPS) assesses the experiences of pediatric patients (less E:\FR\FM\19MRN1.SGM 19MRN1

Agencies

[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: epc@ahrq.hhs.gov.
    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: epc@ahrq.hhs.gov.

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

Timing

     For 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