[Federal Register Volume 81, Number 135 (Thursday, July 14, 2016)]
[Notices]
[Pages 45502-45504]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-16632]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality


Supplemental Evidence and Data for Systematic Reviews Request on 
Osteoarthritis of the Knee: An Update

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. 
Supplemental datasets are being solicited to inform the review of 
Osteoarthritis of the Knee: An Update, which is currently being 
conducted by AHRQ's Evidence-based Practice Centers (EPC) Programs. 
Obtaining access to published and unpublished pertinent scientific 
information will improve the quality of this review. AHRQ is conducting 
this systematic review pursuant to section 902(a) of the Public Health 
Service Act, 42 U.S.C. 299a(a).

DATES: Submission Deadline on or before August 15, 2016.

ADDRESSES: 
    Email submissions: src.org">SEADS@epc-src.org.
    Print submissions:
    Mailing Address: Portland VA Research Foundation, Scientific 
Resource Center, ATTN: SEADS Coordinator, P.O. Box 69539, Portland, OR 
97239.
    Shipping Address (FedEx, UPS, etc.): Portland VA Research 
Foundation, Scientific Resource Center, ATTN: SEADS Coordinator, 3710 
SW U.S. Veterans Hospital Road, Mail Code: R&D 71, Portland, OR 97239.

FOR FURTHER INFORMATION CONTACT: Ryan McKenna, Telephone: 503-220-8262 
ext. 51723 or Email: src.org">SEADS@epc-src.org.

SUPPLEMENTARY INFORMATION: The Agency for Healthcare Research and 
Quality has commissioned its Evidence-based Practice Centers (EPC) 
Programs to complete a review of the evidence a review that updates 
information on treatments for osteoarthritis of the knee. The review 
will be titled Osteoarthritis of the Knee: An Update.
    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, AHRQ is supplementing the usual manual and electronic 
database searches of the literature by requesting

[[Page 45503]]

information (e.g., details of studies conducted) from the public. We 
are looking for studies that report on treatments for osteoarthritis of 
the knee, including those that describe adverse events. The entire 
research protocol, including the key questions, is also available 
online at: https://www.effective healthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=2247.
    This notice is to notify the public that the EPC program would find 
the following information on treatments for osteoarthritis of the knee 
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 is very beneficial to the EPC Program. The 
contents of all submissions will be made available to the public upon 
request. Materials submitted must be publicly available or could 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 Web 
site 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/index.cfm/join-the-email-list1/.
    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 entire research 
protocol, is available online at: https://www.effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=2247

Key Questions

Key Question 1

I. What is the clinical effectiveness of oral glucosamine and/or 
chondroitin, physical treatments, weight loss, oral serotonin-
norepinephrine reuptake inhibitors (SNRIs), intraarticular 
corticosteroids and/or prolotherapy, topical or transdermal analgesics, 
acupuncture, or cell-based therapies in patients with primary or 
secondary OA of the knee, compared with appropriate placebo/sham 
controls or compared with other active interventions?
II. How do the outcomes of each intervention differ by the following 
population and study characteristics: Sex, disease subtype (lateral, 
patellofemoral), severity (stage/baseline pain and functional status), 
weight status (body mass index), baseline fitness (activity level), 
comorbidities, prior or concurrent treatments (including self-initiated 
therapies), and treatment duration or intensity?

Key Question 2

I. What harms are associated with each intervention in patients with 
primary or secondary OA of the knee?
II. How do the harms associated with each intervention differ by the 
following population or study characteristics: Sex, disease subtype 
(lateral tibiofemoral, patellofemoral), severity (stage/baseline pain 
and functional status), weight status (body mass index), baseline 
fitness (activity level), comorbidities, prior or concurrent treatments 
(including self-initiated therapies), and treatment duration or 
intensity?

PICOTS (Population, Intervention, Comparator, Outcome, Timing, Setting)

Population(s)

I. Adults (age 18 or over) with a diagnosis of primary (or secondary) 
OA of the knee, as defined by the American Academy of Orthopaedic 
Surgeons (AAOS, 2013), ACR clinical classification criteria, or 
Kellgren-Lawrence stage.
II. Subpopulations of interest include those defined by sex, disease 
subtype (e.g., patellofemoral, or medial tibiofemoral), disease 
severity (stage/pain or functional status), body mass index, fitness/
activity level, prior treatment, concurrent treatment(s), comorbidities
III. Exclusions:
    A. Studies of individuals under age 18; those with OA caused by a 
congenital condition; and those with OA concomitant with a meniscal or 
anterior cruciate ligament tear will be excluded because these 
participants have conditions that differ importantly from the vast 
majority of OA patients
    B. Studies that include those who have had knee replacement surgery 
on the affected limb or for whom outcomes will be measured after knee 
replacement surgery or who have concomitant joint disease such as 
rheumatoid arthritis or gout will be excluded because these conditions 
or procedures will confound assessment of the outcomes of 
interventions.
    C. If three or more RCTs of a particular intervention are included 
that enroll at least 50 participants per study arm, smaller studies of 
the same intervention will be excluded unless they report on a subgroup 
analysis of interest because studies on management of OA of the knee 
that enroll fewer than 50 participants per study arm have been shown to 
have high risk of bias and significantly larger effect sizes.

Interventions

I. Pharmacologic treatments
    A. Oral agents
    i. Glucosamine and/or chondroitin
    ii. SNRIs (to be assessed for review in next update)
    B. Intra-articular injected agents (to be assessed for review in 
next update)
    i. Corticosteroids (to be assessed for review in next update)
    ii. Prolotherapeutic agents (e.g. dextrose) (to be reviewed in next 
update)

[[Page 45504]]

    iii. Hyaluronic acid (to be assessed for review in next update)
    C. Topical and transdermal agents (to be assessed for review in 
next update)
    i. Capsaicin (to be assessed for review in next update)
    ii. NSAIDs (to be assessed for review in next update)
II. Cell-based therapies
    A. Platelet-rich plasma
    B. Intraarticular or arthroscopic administration of mesenchymal 
stem-cells or chondrocytes or tissue
    C. Exclusions:
    i. Phase I or II trials will not be included for efficacy, as the 
interventions are generally not FDA-approved for use.
III. Physical treatments and/or weight loss
    A. Physical therapy and exercise programs
    i. Manual therapy
    ii. Land-based therapy and/or exercise
    iii. Exercise programs (aerobic, resistance)
    iv. Aquatherapy
    v. Balneotherapy, mud therapy
    vi. Heat or cold
    vii. Self-management programs
    B. Weight loss
    C. Braces or kinesiology taping
    D. Orthotic shoe inserts and/or wedges
    E. Vibrating platform
    F. Neuromuscular electrical stimulation (e.g., Transcutaneous 
electrical nerve stimulation)
IV. Acupuncture (to be assessed for review in next update)
    A. Needle acupuncture alone (to be assessed for review in next 
update)
    B. Moxibustion (to be assessed for review in next update)
V. Combination interventions (to be assessed for review in next update)
    A. Sequential treatment algorithms (to be assessed for review in 
next update)

Comparators

I. Pharmacologic treatments: Placebo-controlled or head-to-head non-
inferiority only
II. Cell-based therapies: Placebo- or sham-controlled only
III. Physical treatments and/or weight loss: Placebo-controlled, usual 
care-controlled, or wait list-controlled only except for weight loss
IV. Neuromuscular electrical stimulation: Sham stimulation without 
current
V. Wait list
VI. Treatment as usual
VII. Studies that use the untreated knee as a control will be excluded, 
based on evidence indicating that individuals with OA in one knee are 
likely to have some, but not necessarily identically, reduced function 
in the other knee and that treatment of one knee only may improve pain 
in that knee but may not markedly improve function
VIII. Studies that use participants as their own controls will be 
excluded, unless no randomized controlled trials are identified for a 
particular intervention of interest, as quasi-experimental designs 
provide weaker evidence.
IX. Exclusions:
    A. Studies that use an active control that has not been established 
to be effective will be excluded. Efficacy and effectiveness must be 
established before examining comparative effectiveness questions.

Outcomes

I. Short-term clinical outcomes
    A. Pain (e.g., VAS, WOMAC, KOOS,)
    B. Joint stiffness (WOMAC)
    C. Function (WOMAC, Lequesne, others)
    D. OARSI physical outcomes (e.g., timed up-and-go, 6-minute walk 
test)
    E. Patient Reported Outcome Measurement System (PROMIS[supreg]) and 
Osteoarthritis-Computer Adaptive Test (OA-CAT)
    F. Inflammation or effusion
    G. Medication use
II. Long-term clinical outcomes
    A. Any of the short-term clinical outcomes
    B. Instrumental activities of daily living (IADLs)
    C. Quality of life (e.g., SF-36, EuroQuol EQ-5D, Arthritis Self-
Efficacy scale, global assessment, patient satisfaction)
    D. Surgery (i.e., rate of undergoing knee replacement)
III. Adverse effects of intervention(s)
IV. Outcome reporting
    A. Only studies that report outcomes for knee OA alone
    B. Mean differences at followup or percent of responders at 
followup will be abstracted

Timing

Minimum 1 month follow-up from initiation of treatment

Settings

Any setting

Andrew B. Bindman,
AHRQ Director.
[FR Doc. 2016-16632 Filed 7-13-16; 8:45 am]
 BILLING CODE 4160-90-P