[Federal Register Volume 90, Number 8 (Tuesday, January 14, 2025)]
[Notices]
[Pages 3214-3218]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-00548]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality


Supplemental Evidence and Data Request on The Performance of 
Fusion Procedures for Degenerative Disease of the Lumbar Spine

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

ACTION: Request for Supplemental Evidence and Data Submission.

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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 The Performance 
of Fusion Procedures for Degenerative Disease of the Lumbar Spine, 
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 Access to published and unpublished 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 February 13, 2025.

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:  Kelly Carper, Telephone: 301-427-1656 
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 The Performance of 
Fusion Procedures for Degenerative Disease of the Lumbar Spine. AHRQ is 
conducting this review pursuant to Section 902 of the Public Health 
Service Act, 42 U.S.C. 299a.
    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 The Performance of Fusion Procedures for Degenerative 
Disease of the Lumbar Spine. The entire research protocol is available 
online at: https://effectivehealthcare.ahrq.gov/products/lumbar-spinal-fusion/protocol.
    This is to notify the public that the EPC Program would find the 
following information on The Performance of Fusion Procedures for 
Degenerative Disease of the Lumbar Spine helpful:
    [ssquf] A list of completed studies that your organization has 
sponsored for this topic. 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, if 
relevant: 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 topic. In the list, please provide the 
ClinicalTrials.gov trial number or, if the trial is not registered, the 
protocol for the study including, if relevant, 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 topic and an index outlining the relevant information in each 
submitted file.
    Your contribution is very beneficial to the Program. Materials 
submitted must

[[Page 3215]]

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 topics 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://effectivehealthcare.ahrq.gov/email-updates.
    The 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)

Questions on Surgery (KQ 1-4)

    In adults with symptomatic, stable degenerative lumbar 
spondylolisthesis (DLS) with or without radiculopathy or neurogenic 
claudication
     Key Question 1. What are the benefits and harms of surgery 
with instrumentation in addition to decompression compared with 
decompression alone?
    In symptomatic adults with unstable or stable DLS with or without 
radiculopathy or neurogenic claudication undergoing instrumented 
fusion:
     Key Question 2. What are the benefits and harms of the 
addition of an interbody cage to instrumentation (e.g., pedicle screws) 
compared to use of instrumentation alone (i.e., posterolateral fusion)?
     Key Question 3. What are the benefits and harms of the use 
of bone graft extenders and biologic substitutes compared to the use of 
autografts?
    In adults with symptomatic, degenerative lumbar spine disease 
undergoing instrumented fusion:
     Key Question 4. Does the use of intraoperative monitoring 
(IONM) decrease perioperative neurological injuries compared with not 
using IONM?

PICOTS (Populations, Interventions, Comparators, Outcomes, Timing, and 
Setting)

  Table 1--EPC Proposed PICOTS and Corresponding Inclusion and Exclusion Criteria Key Questions 1,2,3 and 4 on
                                                     Surgery
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                                                  Inclusion                              Exclusion
----------------------------------------------------------------------------------------------------------------
Population.......................  Key Questions (1-3)                     ALL Key Questions
                                    Symptomatic adult patients      Patients <18 years old.
                                    with a radiographic diagnosis (based    Asymptomatic patients.
                                    on dynamic (flexion and extension       Other forms of
                                    radiographs) of degenerative lumbar     spondylolisthesis are excluded
                                    spondylolisthesis (any grade) who       (i.e., excluding dysplastic,
                                    remain symptomatic following            isthmic, traumatic, and pathologic
                                    conservative treatment                  causes/forms).
                                    Patients with or without        Patients with osteoporosis,
                                    evidence of nerve compression           vertebral compression fractures.
                                    (radiculopathy, neurogenic              Exclude pts undergoing
                                    claudication)                           revisions or repeat procedures.
                                   KQ 1                                     Patients having reoperation/
                                    Stable (non-mobile, static)     repeat procedures.
                                    DLS (<3 mm slip on extension/flexion   KQs 1-3
                                    radiographs)                            Patients without
                                   KQ 2, 3                                  degenerative spondylolisthesis.
                                    Patients with unstable or       Studies with <80% of
                                    stable DLS on radiographs               patients have spondylolisthesis.
                                   KQ 4                                    KQ 1
                                    Patients with symptomatic       Patients with unstable
                                    degenerative lumbar spine disease       (dynamic) DLS: (exclude study if
                                    undergoing fusion of 5 or fewer         stable is not specified, is
                                    levels (stratify by presence of DLS)    unclear).
Interventions....................  ALL Key Questions                       ALL Key Questions
                                    FDA approved devices or         Devices or materials that
                                    materials (or in Phase III trials) as   are not FDA approved or in Phase III
                                    applicable to the KQ                    trials (as applicable to the
                                    Open and minimally invasive     question) or not available in the
                                    (e.g., endoscopic) procedures           U.S.
                                   KQ 1                                     Mesenchymal stem cells
                                    Decompression (discectomy,      (MSCs)
                                    indirect and direct methods) with       Procedures that don't
                                    instrumented spinal fusion (e.g.,       include decompression
                                    with pedicle screws, interbody cages,   Non-instrumented fusions
                                    or other hardware)                      Coflex, interspinous
                                   KQ 2                                     fixation
                                    Surgical decompression and      Minimally invasive lumbar
                                    instrumented posterolateral fusion      decompression (MILD) procedure
                                    (e.g., using pedicle screws) with       Surgical procedures not
                                    addition of interbody cage              listed
                                    (expandable or static, ALIF, TLIF,     KQ 4
                                    LLIF)                                   Other monitoring formats
                                   KQ 3                                     (e.g., imaging, computer assisted
                                    Decompression and spinal        navigation systems, etc.)
                                    fusion using bone graft extenders or    Combinations of graft
                                    biologic substitutes (demineralized     materials (other than with
                                    bone matrix, cadaveric allograft,       autograft)
                                    cortical fibers, bone morphogenic       Comparison of graft
                                    protein, cellular allografts            materials with each other
                                   KQ 4
                                    IONM (Motor Evoked Potentials
                                    (MEP), Somatosensory Evoked
                                    Potentials (SSEP), Free Running EMG
                                    (electromyography) Direct Stimulation

[[Page 3216]]

 
Comparators......................  ALL Key Questions                       ALL Key Questions
                                    FDA approved devices or         Conservative care, non-
                                    materials (or in Phase III trials) as   operative care, usual care
                                    applicable to the KQ                    Devices or materials that
                                    Open and minimally invasive     are not FDA approved or in Phase III
                                    (e.g., endoscopic) procedures           trials (as applicable to the
                                   KQ 1                                     question) or not available in the
                                    Decompression alone             U.S.
                                   KQ 2                                     Mesenchymal stem cells
                                    Decompression and               (MSCs)
                                    instrumented posterolateral spinal     KQ 1
                                    fusion (e.g., using pedicle screws      Other surgical procedures
                                    alone)                                 KQ 2, 3
                                   KQ 3                                     Non-instrumented fusion,
                                    Decompression and               Instrumentation prior to
                                    instrumented spinal fusion using        2000
                                    autograft                               Coflex, interspinous
                                   KQ 4                                     fixation
                                    No use of IONM                 KQ 3
                                                                            Combinations of graft
                                                                            materials with autograft
Outcomes.........................  ALL Key Questions                       ALL Key Questions
                                    Validated measures for pain     Measures of pain, function
                                    and symptoms                            that are not validated
                                   [cir] Pain (e.g., VAS)                   Measures/outcomes not listed
                                   [cir] Function (e.g., ODI)               Radiographic parameters
                                   [cir] Quality of Life (e.g., SF-36, SF-  (e.g., evidence of global spinal
                                    12)                                     alignment)
                                    Peri- and post-operative
                                    harms (including serious AEs/harms,
                                    persistent pain, sacro-iliac joint
                                    pain, instrument failure)
                                   Additional outcomes by KQ
                                   KQ 1: Reoperation rates
                                   KQ 2: Fusion (arthrodesis) rates
                                   KQ 3: Fusion (arthrodesis) rates
                                   KQ 4: Persistent neurological damage
                                    based on clinical exam (e.g., foot
                                    drop)
Timing...........................  Key Questions 1-3                       KQ 1
                                    Pain, function, reoperation:    Re-operation beyond 12
                                    3, 6 and >=12 months (up to 60          months
                                    months)                                KQs 1-3
                                    Reoperation-any time (KQ 2):    Outcomes measured less than
                                    Harms: any time                 3 months (except harms)
                                   KQ 4                                    KQ 4
                                    Any time during post-           Alerts and responses to
                                    operative followup                      alerts during surgery
Settings.........................  ALL Key Questions                       .....................................
                                    Inpatient care followed by
                                    care in specialty and primary care
                                    clinics
                                    Outpatient ambulatory surgery
                                    centers
Study designs....................  ALL Key Questions                       ALL Key Questions
                                    RCTs for effectiveness/         NRSI that do not control for
                                    efficacy outcomes                       confounding
                                    FDA SSED if there is            NRSI that include historical
                                    inadequate information from published   controls
                                    studies                                 NRSI of treatment with fewer
                                    Studies published in 2000 or    than 50 patients per treatment arm
                                    later                                   Case reports, case-series,
                                   KQ 1-3: NRSIs will be considered for     single-arm and pre-post studies
                                    harms only and must be specifically     Publication types:
                                    designed to evaluate/report on AE/      Conference abstracts or proceedings,
                                    harms and control for confounding and   editorials, letters, white papers,
                                    focused on rare or long-term harms.     citations that have not been peer-
                                   KQ 4: NRSIs on effectiveness and harms   reviewed, single site reports of
                                                                            multi-site studies
                                                                            Studies published prior to
                                                                            2000
                                                                            Studies not in English
                                                                           KQ 1-3
                                                                            Trials with fewer than 15
                                                                            patients per treatment arm
----------------------------------------------------------------------------------------------------------------
Serious adverse events are defined as events that are life-threatening or require additional medical attention.
  AE = adverse event; ALIF = anterior lumbar interbody fusion; DLS = degenerative lumbar spondylolisthesis; EQ-
  5D = EuroQol 5D scale; FDA = Food and Drug Administration; IONM = intraoperative neurological monitoring; KQ =
  Key Question; LLIF = lateral lumbar interbody fusion; MCID = minimum clinically important difference; NRSI =
  nonrandomized studies of intervention; ODI = Oswestry Disability Index; RCT = randomized controlled trial; RMD
  = Roland-Morris Disability Questionnaire; SSED = Summary of Safety and Effectiveness Data; SF-36/12 = Short
  Form 36 or 12 questionnaire; TLIF = transforaminal lumbar interbody fusion; U.S. = United States; VAS = visual
  analog scale.

KQ 5 and 6: Questions on Non-Surgical Procedures for Chronic Low Back 
Pain Due To Degenerative Spine Disease

    Key Question 5. In adult patients with chronic low-back pain (>=3 
months) resulting from degenerative disease what are the benefits and 
harms of lumbar epidural steroid injections, intra-articular (facet) 
injection, medial branch blocks, or radio frequency ablation?
    Key Question 6. In adult patients with chronic low-back pain (>=3 
months) resulting from degenerative disease of the lumbar spine, does 
symptomatic improvement to therapeutic challenge with lumbar epidural 
steroid injections, intra-articular (facet) injection, medial branch 
blocks or radio frequency ablation predict positive outcomes after 
lumbar fusion surgery?
    Special populations and factors for Key Questions 5 and 6: Age, 
sex, BMI, presence of psychological comorbidities, presence of medical 
comorbidities, baseline pain severity, presence and type of concomitant 
degenerative lumbar spine disease, presence and severity of DLS.

[[Page 3217]]



    Table 2--EPC Proposed PICOTS and Corresponding Inclusion and Exclusion Criteria: Key Questions 5 and 6 on
          Specific Procedures in Patients With Chronic Low Back Pain Due To Degenerative Spine Disease
----------------------------------------------------------------------------------------------------------------
                                                  Inclusion                              Exclusion
----------------------------------------------------------------------------------------------------------------
Population.......................  KQ 5, 6                                 KQ 5, 6
                                    Adult patients with chronic     Patients with acute or
                                    low-back pain (>=3 months duration)     subacute LBP
                                    resulting from degenerative disease     Patients with disc
                                                                            herniation
                                                                            Patients with failed back
                                                                            surgery syndrome
                                                                            Sacroiliac pain
                                                                            Patients having reoperation
Interventions....................  KQ 5, 6                                 KQ 5, 6
                                    Epidural steroid injections     Discoblock, provocative
                                    (ESI)                                   discography
                                    Intra-articular (facet)         Neuromodulation (e.g.,
                                    injections                              spinal cord, dorsal column, dorsal
                                    Radiofrequency Ablation (RFA)   root stimulation, peripheral nerve
                                    Medial branch blocks            stimulation)
                                                                            Injections: exclude other
                                                                            biologics (e.g., PRP), intradiscal
                                                                            injections
                                                                            Minimally invasive lumbar
                                                                            decompression (MILD), percutaneous
                                                                            decompression
                                                                            Selective nerve root blocks
                                                                            Intraosseous basivertebral
                                                                            nerve ablation
                                                                            Combinations of procedures;
                                                                            Studies evaluating additive benefits
                                                                            of one procedure with another
Comparators......................  KQ 5                                    KQ 5, 6
                                    Other nonoperative treatment,   Combinations of procedures;
                                    no treatment, sham                      Studies evaluating additive benefits
                                   KQ 6                                     of one procedure to another
                                    No therapeutic challenge;      KQ 5
                                    (prognostic/predictive modeling         For ESI, exclude comparison
                                    study)                                  with disc procedures (e.g.,
                                                                            discography); comparisons of
                                                                            medications
                                                                            For RFA exclude comparisons
                                                                            of different types of neurotomy
                                                                            (conventional vs. pulsed [cooled]
                                                                            RF; RF vs. alcohol ablation)
Outcomes.........................  KQ 5 and 6: Harms (e.g., serious peri-  KQ 5, 6
                                    procedural and post-procedural harms)   Measures of pain, function
                                   KQ 5                                     that are not validated
                                    Validated measures for pain     Measures/outcomes not listed
                                    and symptoms
                                   [cir] Pain (e.g., VAS, NRS)
                                   [cir] Function (e.g., ODI)
                                   [cir] Quality of Life (e.g., SF-36,
                                    SF12)
                                   KQ 6
                                    Response to challenge:
                                    Improvement in symptoms vs. non-
                                    improvement; [stratify other outcomes
                                    by response]
                                    Validated measures for pain
                                    and symptoms following fusion surgery
                                   [cir] Pain (e.g., VAS, NRS)
                                   [cir] Function (e.g., ODI)
                                   [cir] Quality of Life (e.g., SF-36, SF-
                                    12)
                                   [cir] Symptoms associated with neural
                                    compression
                                    Successful arthrodesis [as
                                    radiographically determined via x-ray/
                                    computed tomography or by proxy
                                    (e.g., lack of revision, pedicle
                                    screw loosening)]
Timing...........................  KQ 5 and 6
                                    Serious harms--periprocedural
                                   KQ 5
                                    3-month and 6-month periods
                                    following the procedure
                                   KQ 6
                                    Outcomes measured at 3, 6 and
                                    >=12 months after surgical procedure
                                    (up to 24 months)
Settings.........................  KQ 5
                                    Outpatient
                                   KQ 6
                                    Outpatient care for
                                    therapeutic challenge. Inpatient care
                                    followed by care in specialty and
                                    primary care clinics for surgical
                                    procedure
                                    Outpatient ambulatory surgery
                                    centers for surgery

[[Page 3218]]

 
Study designs....................  KQ 5                                    KQ 5, 6
                                    RCTS for effectiveness/         NRSI that do not control for
                                    efficacy outcomes                       confounding
                                    Prospective NRSIs that          NRSI that include historical
                                    control for confounding will be         controls
                                    considered for effectiveness in the     NRSI with fewer than 50
                                    absence of RCTs                         patients per treatment arm
                                    NRSIs for harms must be         Case reports, case-series,
                                    specifically designed to evaluate/      single-arm and pre-post studies
                                    report on serious AE/harms and that     Publication types:
                                    control for confounding OR focused on   Conference abstracts or proceedings,
                                    rare or long-term harms                 editorials, letters, white papers,
                                   KQ 6                                     citations that have not been peer-
                                    Predictive/prognostic           reviewed, single site reports of
                                    modeling studies evaluating the         multi-site studies
                                    association of procedure response       Studies not in English
                                    impact on outcomes that control for
                                    confounding
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Serious adverse events are defined as events that are life-threatening or anything needing additional medical
  attention. AE = adverse event; DLS = degenerative lumbar spondylolisthesis; EQ-5D = EuroQol 5D scale; ESI =
  epidural steroid injection; FDA = Food and Drug Administration; IONM = intraoperative neuro monitoring; KQ =
  Key Question; LBP = low back pain; MCID = minimum clinically important difference; NRSI = nonrandomized
  studies of intervention; ODI = Oswestry Disability Index; RCT = randomized controlled trial; RF =
  radiofrequency ablation; RMD = Rolland-Morris Disability Questionnaire; SSED = Summary of Safety and
  Effectiveness Data; SF-36/12 = Short Form 36 or 12 questionnaire; VAS = visual analog scale.


    Dated: January 7, 2025.
Marquita Cullom,
Associate Director.
[FR Doc. 2025-00548 Filed 1-13-25; 8:45 am]
BILLING CODE 4160-90-P