```

[Federal Register Volume 79, Number 170 (Wednesday, September 3, 2014)]
[Notices]
[Pages 52339-52341]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-20690]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality

Scientific Information Request on Emerging Approaches To 
Diagnosis and Treatment of Non-Muscle-Invasive Bladder Cancer

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

ACTION: Request for Scientific Information 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 of Emerging 
Approaches to Diagnosis and Treatment of Non-Muscle-Invasive Bladder 
Cancer, which is currently being conducted by the Evidence-based 
Practice Centers for the AHRQ Effective Health Care Program. Access to 
published and unpublished pertinent scientific information will improve 
the quality of this review. AHRQ is conducting this systematic review 
pursuant to Section 1013 of the Medicare Prescription Drug, 
Improvement, and Modernization Act of 2003, Public Law 108-173, and 
Section 902(a) of the Public Health Service Act, 42 U.S.C. 299a(a).

DATES: Submission Deadline on or before October 3, 2014.

ADDRESSES: Online submissions: http://effectivehealthcare.AHRQ.gov/index.cfm/submitscientific-information-packets/. Please select the 
study for which you are submitting information from the list to upload 
your documents.
    Email submissions: /src.org">src.org">SIPS@epc-src.org.
    Print submissions:
    Mailing Address: Portland VA Research Foundation, Scientific 
Resource Center, ATTN: Scientific Information Packet Coordinator, PO 
Box 69539, Portland, OR 97239.
    Shipping Address (FedEx, UPS, etc.): Portland VA Research 
Foundation, Scientific Resource Center, ATTN: Scientific Information 
Packet 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. 58653 or Email: /src.org">src.org">SIPS@epc-src.org.

SUPPLEMENTARY INFORMATION: The Agency for Healthcare Research and 
Quality has commissioned the Effective Health Care (EHC) Program 
Evidence-based Practice Centers to complete a review of the evidence 
for Emerging Approaches to Diagnosis and Treatment of Non-Muscle-
Invasive Bladder Cancer.
    The EHC 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 Emerging Approaches to Diagnosis and Treatment of Non-
Muscle-Invasive Bladder Cancer, including those that describe adverse 
events. The entire research protocol, including the key questions, is 
also available online at: http://effectivehealthcare.AHRQ.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=1941.
    This notice is to notify the public that the EHC Program would find 
the following information on Emerging Approaches to Diagnosis and 
Treatment of Non-Muscle-Invasive Bladder Cancer helpful:
     A list of completed studies that your organization has 
sponsored for this indication. In the list, please indicate whether 
results are available on ClinicafTrials.gov along with the 
ClinicalTrials.gov trial number.
     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.
     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.
     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 EHC Program. The 
contents of all submissions will be made available to the public upon 
request. Materials submitted must be publicly available or can 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 EHC 
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 EHC 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: http://effectivehealthcare.AHRO.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 also available online at: http://effectivehealthcare.AHRO.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=1941.

The Key Questions

Key Question 1

    What is the diagnostic accuracy of various urinary biomarkers 
compared with other urinary biomarkers or standard diagnostic methods 
(cystoscopy, cytology, and imaging) in (1) persons with signs or 
symptoms warranting evaluation for possible bladder cancer or (2) 
persons undergoing surveillance for previously treated bladder cancer?
     Does the diagnostic accuracy differ according to patient 
characteristics (e.g., age, sex, ethnicity), or according to the nature 
of the presenting signs or symptoms?

Key Question 2

    For patients with non-muscle-invasive bladder cancer, does the use 
of a formal risk-adapted assessment approach to treatment decisions 
(e.g.,

[[Page 52340]]

Guidelines of the European Association of Urology or based on urinary 
biomarker tests) decrease mortality or improve other outcomes (e.g., 
recurrence, progression, need for cystectomy, quality of life) compared 
with treatment not guided by an assessed risk-adapted approach?

Key Question 3

    For patients with non-muscle-invasive bladder cancer treated with 
transurethral resection of bladder tumor (TURBT), what is the 
effectiveness of various intravesical chemotherapeutic or 
immunotherapeutic agents for decreasing mortality or improving other 
outcomes (e.g., recurrence, progression, need for cystectomy, quality 
of life) compared with other agents, TURBT alone, or cystectomy?
     What is the comparative effectiveness of various 
chemotherapeutic or imnnunotherapeutic agents, as monotherapy or in 
combination?
     Does the comparative effectiveness differ according to 
tumor characteristics, such as histology, stage, grade, size, or 
molecular/genetic markers?
     Does the comparative effectiveness of various 
chemotherapeutic or immunotherapeutic agents differ according to dosing 
frequency, duration of treatment, and/or the timing of administration 
relative to TURBT?
     Does the comparative effectiveness differ according to 
patient characteristics, such as age, sex, ethnicity, performance 
status, or medical comorbidities?

Key Question 4

    For patients with high risk non-muscle-invasive bladder cancer 
treated with TURBT, what is the effectiveness of external beam 
radiation therapy (either alone or with systemic chernotherapy/
immunotherapy) for decreasing mortality or improving other outcomes 
compared with intravesical chemotherapy/immunotherapy alone or 
cystectomy?

Key Question 5

    In surveillance of patients treated for non-muscle-invasive bladder 
cancer, what is the effectiveness of various urinary biomarkers to 
decrease mortality or improve other outcomes compared with other 
urinary biomarkers or standard diagnostic methods (cystoscopy, 
cytology, and imaging)?
     Does the comparative effectiveness differ according to 
tumor characteristics, such as histology, stage, grade, size, or 
molecular/genetic markers?
     Does the comparative effectiveness differ according to the 
treatment used (i.e., specific chemotherapeutic or immunotherapeutic 
agents and/or TURBT)?
     Does the comparative effectiveness differ according to the 
length of surveillance intervals?
     Does the comparative effectiveness differ according to 
patient characteristics, such as age, sex, or ethnicity?

Key Question 6

    For initial diagnosis or surveillance of patients treated for non-
muscle-invasive bladder cancer, what is the effectiveness of blue light 
or other methods of augmented cystoscopy compared with standard 
cystoscopy for recurrence rates, progression of bladder cancer, 
mortality, or other clinical outcomes?

Key Question 7

    What are the comparative adverse effects of various tests for 
diagnosis and post-treatment surveillance of bladder cancer, including 
urinary biomarkers, cytology, and cystoscopy?

Key Question 8

    What are the comparative adverse effects of various treatments for 
non-muscle-invasive bladder cancer, including intravesical 
chemotherapeutic or immunotherapeutic agents and TURBT?
     How do adverse effects of treatment vary by patient 
characteristics, such as age, sex, ethnicity, performance status, or 
medical connorbidities such as chronic kidney disease?

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

Population(s)

 For KQ 1, 6, and 7: Adults with signs or symptoms of possible 
bladder cancer (e.g., gross or microscopic hematurla, irritative 
voiding symptoms)
 For KQ 2: Adults with non-muscle-invasive bladder cancer 
(stages Ta, Tis, or Ti)
 For KQ 3 and 8: Adults with non-muscle invasive bladder cancer 
treated with TURBT
 For KQ 4 and 8: Adults with high-risk non-muscle invasive 
bladder cancer treated with TURBT
 For KQs 1 and 5 through 7: Adults undergoing surveillance 
following treatment for non-muscle invasive bladder cancer

Interventions

 For KQ 1, 5, and 7: Urinary biomarkers \a\
---------------------------------------------------------------------------

    \a\ Restricted to tests that are approved for diagnosis of 
bladder cancer by the U.S. Food and Drug Administration 
(BTAstat[supreg] [BTA], Alere NMP228, BladderChek[supreg] [NMP22], 
UroVysion[supreg] [FISH] and ImmunoCytrm [immunocytology]) or 
available in the U.S. and classified as a Laboratory Developed Test 
by the FDA (CxBladderrm).
---------------------------------------------------------------------------

 For KQ 2: Risk-adapted treatment approaches
 For KQ 3a, 3b, 3c, 3d, and 8: Intravesical chemotherapeutic or 
immunotherapeutic agents \b\
---------------------------------------------------------------------------

    \b\ Chemotherapeutic and immunotherapeutic agents of interest 
include: mitomycin; apaziquone; paclitaxel; gemcitabine; thiotepa; 
valrubicin; doxorubicin; bacillus Calnnette-Guerin (BCG); and 
interferon.
---------------------------------------------------------------------------

 For KQ 4: External beam radiation therapy, with or without 
systemic chemotherapy or immunotherapy
 For KQ 6: Blue light or other methods of augmented cystoscopy

Comparators

 For KQ 1, 5, and 7: Other urinary biomarkers or standard 
diagnostic methods (cystoscopy, cytology, and imaging)
 For KQ 2: Treatment not guided by risk-adapted approach
 For KQ 3a, 3b, 3c, 3d, and 8: Other intravesical 
chemotherapeutic or innmunotherapeutic agent, different dose or 
duration of intravesical chemotherapy or immunotherapy, or 
transurethral resection of bladder tumor (TURBT) alone
 For KQ 4: Intravesical chemotherapeutic or immunotherapeutic 
agents or cystectomy

Outcomes

 For KQ 1 and 5: Diagnostic accuracy, using cystoscopy with 
biopsy as the reference standard
 For KQ 2, KQ 3, KQ 4, KQ 5: Mortality, disease-specific and 
all-cause
 For KQ 2, KQ 3, KQ 4, KQ 5: Need for cystectomy
 For KQ 2, KQ 3, KQ 4, KQ 5, KQ 6: Recurrence of cancer
 For KQ 2, KQ 3, KQ 4, KQ 5: Progression of cancer
 For KQ 2, KQ 3, KQ 4, KQ 5: Quality of life
 For KQ 7: Adverse effects of diagnostic testing (e.g., false-
positives, labeling, anxiety, complications of cystoscopy)
 For KQ 8: Adverse effects of treatment (e.g., cystitis, 
urinary urgency, urinary frequency, incontinence, hematuria, pain, 
urosepsis, myelosuppression

Timing

Any duration of follow-up

Settings

 Inpatient settings
 Outpatient settings

[[Page 52341]]

    Dated: August 26, 2014.
Richard Kronick,
AHRQ Director.
[FR Doc. 2014-20690 Filed 9-2-14; 8:45 am]
BILLING CODE 4160-90-M
```