[Federal Register Volume 85, Number 5 (Wednesday, January 8, 2020)]
[Notices]
[Pages 904-906]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-00104]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality


Supplemental Evidence and Data Request on Treatments for Acute 
Pain: A Systematic Review

AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS.

ACTION: Request for Supplemental Evidence and Data Submissions.

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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 Treatments for 
Acute Pain: A Systematic Review, 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published and unpublished pertinent scientific information will improve 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 30 days after date of 
publication of this Notice.

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 Treatments for Acute 
Pain: A Systematic Review. 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 Treatments for Acute Pain: A Systematic Review, 
including those that describe adverse events. The entire research 
protocol is available online at: https://effectivehealthcare.ahrq.gov/products/treatments-acute-pain/protocol.
    This is to notify the public that the EPC Program would find the 
following information on Treatments for Acute Pain: A Systematic Review 
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, 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 is very beneficial to the 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.

Key Questions (KQ)

    Each Key Question (KQ) focuses on a specific acute pain condition. 
The conditions and related subquestions are listed below:
    KQ1: Acute back pain (including back pain with radiculopathy)
    KQ2: Acute neck pain (including neck pain with radiculopathy)
    KQ3: Musculoskeletal pain not otherwise included in KQ1 or KQ2 
(including fractures)
    KQ4: Peripheral neuropathic pain (related to herpes zoster and 
trigeminal neuralgia)
    KQ5: Postoperative pain after discharge
    KQ6: Dental pain (surgical and nonsurgical after discharge)
    KQ7: Kidney stones
    KQ8: Sickle cell crisis (episodic pain)
    For each condition above, the following subquestions will be 
addressed:

Opioid Therapy

    a. What is the comparative effectiveness of opioid therapy versus: 
(1) Nonopioidpharmacologic therapy (e.g., acetaminophen, nonsteroidal 
anti-inflammatory drugs [NSAIDs], antidepressants, anticonvulsants) or 
(2) nonpharmacologic therapy (e.g., exercise, cognitive behavioral 
therapy, acupuncture) for outcomes related to pain, function, pain 
relief satisfaction, and quality of life and after followup at the 
following intervals: Less than 1 day; 1 day to less than 1 week; 1 week 
to less than 2 weeks; 2 weeks to less than 4 weeks; 4 weeks or longer?
    b. How does effectiveness of opioid therapy vary depending on: (1) 
Patient demographics (e.g. age, race, ethnicity, gender); (2) patient 
medical or psychiatric comorbidities; (3) dose of opioids; (4) duration 
of opioid therapy, including number of opioid prescription refills and 
quantity of pills used; (5) opioid use history; (6) substance use 
history; (7) use of concomitant therapies?
    c. What are the harms of opioid therapy versus nonopioid 
pharmacologic therapy, or nonpharmacologic therapy with respect to: (1) 
misuse, opioid use disorder, and related outcomes; (2) overdose; (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)?

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    d. How do harms vary depending on: (1) Patient demographics (e.g., 
age, gender); (2) patient medical or psychiatric comorbidities; (3) the 
dose of opioid used; (4) the duration of opioid therapy; (5) opioid use 
history; or (6) substance use history?
    e. What are the effects of prescribing opioid therapy versus not 
prescribing opioid therapy for acute pain on (1) short-term (<3 months) 
continued need for prescription pain relief, such as need for opioid 
refills, and (2) long-term opioid use (3 months or greater)?
    f. For patients with acute pain being considered for opioid 
therapy, what is the accuracy of instruments for predicting risk of 
opioid misuse, opioid use disorder, or overdose?
    g. For patients with acute pain being considered for opioid 
therapy, what is the effectiveness of instruments for predicting risk 
of opioid misuse, opioid use disorder, or overdose?
    h. For patients with acute pain being considered for opioid 
therapy, what is the effect of the following factors on the decision to 
prescribe opioids: (1) Existing opioid management plans; (2) patient 
education; (3) clinician and patient values and preferences related to 
opioids; (4) urine drug screening; (5) use of prescription drug 
monitoring program data; (6) availability of close followup?

Nonopioid Pharmacologic Therapy

    i. What is the comparative effectiveness of nonopioid pharmacologic 
therapy (e.g., acetaminophen, nonsteroidal anti-inflammatory drugs 
[NSAIDs], antidepressants, anticonvulsants) versus: (1) Other nonopioid 
pharmacologic treatments, such as those in a different medication 
class; or (2) nonpharmacologic therapy for outcomes related to pain, 
function, pain relief satisfaction, and quality of life after followup 
at the following intervals: <1 day; 1 day to <1 week; 1 week to <2 
weeks; 2 weeks to less than 4 weeks; 4 weeks or longer?
    j. How does effectiveness of nonopioid pharmacologic therapy vary 
depending on: (1) Patient demographics (e.g. age, race, ethnicity, 
gender); (2) patient medical and psychiatric comorbidities; (3) the 
type of nonopioid medication; (4) dose of medication; (5) duration of 
treatment?
    k. What are the harms of nonopioid pharmacologic therapy versus 
other nonopioid pharmacologic therapy, or nonpharmacologic therapy with 
respect to: (1) Misuse, (2) overdose; (3) other harms including 
gastrointestinal-related harms, cardiovascular-related harms, kidney-
related harms, falls, fractures, motor vehicle accidents, 
endocrinological harms, infections, cognitive harms, and psychological 
harms (e.g., depression)?
    l. How do harms vary depending on: (1) Patient demographics (e.g. 
age, gender); (2) patient medical comorbidities; (3) the type of 
nonopioid medication; (4) dose of medication; (5) the duration of 
therapy?

Nonpharmacologic Therapy

    m. What is the comparative effectiveness of nonpharmacologic 
therapy versus sham treatment, waitlist, usual care, attention control, 
and no treatment after followup at the following intervals: Less than 1 
day; 1 day to less than 1 week; 1 week to less than 2 weeks; 2 weeks to 
less than 4 weeks; 4 weeks or longer?
    n. What is the comparative effectiveness of nonpharmacologic 
treatments (e.g. exercise, cognitive behavioral therapy, acupuncture) 
for outcomes related to pain, function, pain relief satisfaction, and 
quality of life after followup at the following intervals: Less than 1 
day; 1 day to less than 1 week; 1 week to less than 2 weeks; 2 weeks to 
less than 4 weeks; 4 weeks or longer?
    o. How does effectiveness of nonpharmacologic therapy vary 
depending on: (1) Patient demographics (e.g. age, gender); (2) patient 
medical and psychiatric comorbidities?
    p. How do harms vary depending on: (1) Patient demographics (e.g. 
age, gender); (2) patient medical and psychiatric comorbidities; (3) 
the type of treatment used; (4) the frequency of therapy; (5) the 
duration of therapy?

   PICOTS (Populations, Interventions, Comparators, Outcomes, Timing,
                                Settings)
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        Picots element                     Inclusion criteria
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Population...................  Adults with acute pain related to the
                                following conditions:
                               1. Acute back pain (including back pain
                                with radiculopathy).
                               2. Acute neck pain (including neck pain
                                with radiculopathy).
                               3. Other musculoskeletal pain.
                               4. Peripheral neuropathic pain (related
                                to herpes zoster and trigeminal
                                neuralgia).
                               5. Postoperative pain after discharge.
                               6. Dental pain.
                               7. Kidney stones.
                               8. Sickle cell crisis (episodic pain).
                               * Special populations:
                               [ssquf] General adult.
                               [ssquf] Older populations >65 years.
                               [ssquf] Patients with history of
                                substance use disorder.
                               [ssquf] Patients currently under
                                treatment for opioid use disorder with
                                opioid agonist therapy or naltrexone.
                               [ssquf] Patients with a history of
                                psychiatric illness.
                               [ssquf] Patients with history of
                                overdose.
                               [ssquf] Pregnant/breastfeeding women.
                               [ssquf] Patients with comorbidities
                                (e.g., kidney disease, sleep disordered
                                breathing).
Interventions................  Opioid therapy:
                               a-e. Any systemic opioid, including
                                agonists, partial agonists, and mixed
                                mechanism opioids.
                               f. Instruments, genetic/metabolic tests
                                for predicting risk of misuse, opioid
                                use disorder, and overdose.
                               g. Use of risk prediction instruments,
                                genetic/metabolic tests.
                               h. The following factors: (1) Existing
                                opioid management plans; (2) patient
                                education; (3) clinician and patient
                                values and preferences related to
                                opioids; (4) urine drug screening; (5)
                                use of prescription drug monitoring
                                program data; (6) availability of close
                                followup.
                               Nonopioid therapy: Oral, parenteral, or
                                topical nonopioid pharmacological
                                therapy used for acute pain
                                (acetaminophen, nonsteroidal anti-
                                inflammatory drugs, skeletal muscle
                                relaxants, benzodiazepines,
                                antidepressants, anticonvulsants,
                                cannabis).

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                               Noninvasive nonpharmacological therapy:
                                Noninvasive nonpharmacological therapies
                                used for acute pain (exercise [and
                                related therapies], cognitive behavioral
                                therapy, meditation, relaxation, music
                                therapy, virtual reality, acupuncture,
                                massage, manipulation/mobilization,
                                physical modalities [transcutaneous
                                electrical nerve stimulation,
                                ultrasound, braces, traction, heat,
                                cold]).
Comparators..................  Opioid therapy:
                               a-d. Usual care, another opioid,
                                nonopioid drug, or noninvasive,
                                nonpharmacological therapy.
                               e. Usual care, another opioid, nonopioid
                                drug, or noninvasive, nonpharmacological
                                therapy, no opioid/nothing prescribed.
                               f. Reference standard for misuse, opioid
                                use disorder, or overdose; or other
                                benchmarks.
                               g. Usual care.
                               h. Not utilizing the factors specified in
                                interventions (h) above.
                               Nonopioid pharmacological therapy:
                               Other nonopioid pharmacological therapy
                                or noninvasive nonpharmacological
                                therapy.
                               Noninvasive nonpharmacological therapy:
                               Sham treatment, waitlist, usual care,
                                attention control, and no treatment; or
                                other noninvasive nonpharmacological
                                therapy.
Outcomes.....................  Opioid therapy:
                               a-d, g, i. Pain, function, pain relief
                                satisfaction, and quality of life,
                                harms, adverse events (including
                                withdrawal, risk of misuse, opioid,
                                opioid use disorder, overdose).
                               e. Persistent opioid use.
                               f. Measures of diagnostic accuracy.
                               h. Opioid prescribing rates.
                               Nonopioid therapy: Pain, function, pain
                                relief satisfaction, quality of life and
                                quality of life, harms, adverse events,
                                opioid use.
                               Noninvasive nonpharmacological therapy:
                                Pain, function, pain relief
                                satisfaction, quality of life and
                                quality of life, harms, adverse events,
                                opioid use.
Time of followup.............  <1 day; 1 day to <1 week; 1 week to <2
                                weeks; 2 weeks to <4 weeks; >=4 weeks.
Setting......................  Emergency department (initiation of
                                therapy and following discharge),
                                physician's office, outpatient or
                                inpatient surgical center, dental clinic
                                or oral surgery center, inpatient
                                (sickle cell only).
Study design.................  All KQs: RCTs; in addition:
                               e. Cohort studies (for long-term opioid
                                use).
                               f. studies assessing diagnostic accuracy.
                               h. cohort studies and before-after
                                studies assessing effects on prescribing
                                rates.
------------------------------------------------------------------------
Abbreviations: RCT = randomized controlled trial.


    Dated: January 3, 2020.
Virginia Mackay-Smith,
Associate Director, Office of the Director, AHRQ.
[FR Doc. 2020-00104 Filed 1-7-20; 8:45 am]
BILLING CODE 4160-90-P