38716 Federal Register / Vol. 78, No. 124 / Thursday, June 27, 2013 / Notices 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Agency for Healthcare Research and 

Quality 

Scientific Information Request on 

Imaging Tests for the Staging of 

Colorectal 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 on 

imaging tests for the staging of 

colorectal cancer (e.g., Chest x-ray, 

computed tomography, multidetector 

computed tomography (MD–CT), CT 

colonography, magnetic resonance 

imaging (MRI), transabdominal 

ultrasound (TUS), endoscopic 

ultrasound (EUS), transrectal ultrasound 

(TRUS), positron emission tomography 

(PET), positron emission tomography 

combined with computed tomography 

(PET/CT fusion), or positron emission 

tomography combined with magnetic 

resonance imaging (PET/MRI fusion)) 

from medical device manufacturers. 

Scientific information is being solicited 

to inform our Comparative Effectiveness 

Review of Imaging Tests for the Staging 

of Colorectal Cancer, which is currently 

being conducted by one of the Evidencebased Practice Centers for the AHRQ 

Effective Health Care Program. Access to 

published and unpublished pertinent 

scientific information on these devices 

will improve the quality of this 

comparative effectiveness review. 

AHRQ is requesting this scientific 

information and conducting this 

comparative effectiveness 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 July 29, 2013. 

ADDRESSES: 

Online submissions: http://effective

healthcare.AHRQ.gov/index.cfm/submit

scientific-information-packets/. Please 

select the study for which you are 

submitting information from the list to 

upload your documents. 

Email submissions: 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: 

Robin Paynter, Research Librarian, 

Telephone: 503–220–8262 ext. 58652 or 

Email: SIPS@EPC–SRC.ORG. 

SUPPLEMENTARY INFORMATION: The 

Agency for Healthcare Research and 

Quality has commissioned one of the 

Effective Health Care (EHC) Program 

Evidence-based Practice Centers to 

complete a comparative effectiveness 

review of the evidence for Imaging Tests 

for the Staging of Colorectal 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 systematically requesting 

information (e.g., details of studies 

conducted) from medical device 

industry stakeholders through public 

information requests, including via the 

Federal Register and direct postal and/ 

or online solicitations. We are looking 

for studies that report on Imaging Tests 

for the Staging of Colorectal Cancer, 

including those that describe adverse 

events, as specified in the key questions 

detailed below. The entire research 

protocol, including the key questions, is 

also available online at: http:// 

www.effectivehealthcare.AHRQ.gov/ 

search-for-GUIDES-reviews-and-reports/ 

?PAGEACTION=displayproduct&

productID=1510. 

This notice is a request for 

information about the following: 

• A list of all completed studies your 

company has sponsored for this 

indication, and if the results are 

available on ClinicalTrials.gov along 

with the CT.gov trial number. 

• For completed studies that do not 

have results on CT.gov, a summary that 

includes 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, and 

effectiveness/efficacy and safety results. 

• In addition, ongoing studies your 

company has sponsored for this 

indication. In the list, please provide the 

CT.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. 

Your contribution is very beneficial to 

this program. The contents of all 

submissions will be available to the 

public upon request. Materials 

submitted must be publicly available or 

materials that can be made public. 

Materials that are considered 

confidential; marketing materials; 

pharmacoeconomic, pharnnacokinetic 

or pharmacodynamic studies; study 

types not included in the review; or 

information on indications not included 

in the review cannot be used by the 

Effective Health Care 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.AHRQ.gov/ 

index.cfm/join-the-email-list1/. 

Key Question 1 

What is the comparative effectiveness 

of imaging techniques for pretreatment 

staging of patients with primary and 

recurrent colorectal cancer? 

a. What is the test performance of the 

imaging techniques used (singly, in 

combination, or in a specific sequence) 

to stage colorectal cancer when 

compared with a reference standard? 

b. What is the impact of alternative 

imaging techniques on intermediate 

outcomes, including stage 

reclassification and changes in 

therapeutic management? 

c. What is the impact of alternative 

imaging techniques on clinical 

outcomes? 

d. What are the adverse effects or 

harms associated with using imaging 

techniques, including harms of testdirected management? 

e. How is the comparative 

effectiveness of imaging techniques 

modified by the following factors: 

i. Patient-level characteristics (e.g., 

age, sex, body mass index) 

ii. Disease characteristics (e.g., tumor 

grade) 

iii. Imaging technique or protocol 

characteristics (e.g., use of different 

tracers or contrast agents, radiation dose 

of the imaging modality, slice thickness, 

timing of contrast) 

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Federal Register / Vol. 78, No. 124 / Thursday, June 27, 2013 / Notices 38717 

Key Question 2 

What is the comparative effectiveness 

of imaging techniques for restaging 

patients with primary and recurrent 

colorectal cancer after initial treatment? 

a. What is the test performance of the 

imaging techniques used (singly, in 

combination, or in a specific sequence) 

to restage colorectal cancer when 

compared with a reference standard? 

b. What is the impact of alternative 

imaging techniques on intermediate 

outcomes, including stage 

reclassification and changes in 

therapeutic management? 

c. What is the impact of alternative 

imaging techniques on clinical 

outcomes? 

d. What are the adverse effects or 

harms associated with using imaging 

techniques, including harms of testdirected management? 

e. How is the comparative 

effectiveness of imaging techniques 

modified by the following factors: 

i. Patient-level characteristics (e.g., 

age, sex, body mass index) 

ii. Disease characteristics (e.g., tumor 

grade) 

iii. Imaging technique or protocol 

characteristics (e.g., use of different 

tracers or contrast agents, radiation dose 

of the imaging modality, slice thickness, 

timing of contrast) 

PICOTS Criteria (Population, 

Intervention, Comparator, Outcomes, 

Timing, Setting) 

Populations 

• Adult patients with an established 

diagnosis of primary colorectal cancer 

• Adult patients with an established 

diagnosis of recurrent colorectal cancer 

Interventions 

Noninvasive imaging using the 

following tests (alone or in combination) 

to assess the stage of colorectal cancer: 

• CT 

• PET/CT 

• MRI 

• Endoscopic ultrasound 

Combinations of particular interest 

include endoscopic ultrasound to 

evaluate the T stage combined with 

PET/CT or CT to evaluate the N and M 

stages. 

Reference Standards To Assess Test 

Performance 

• Histopathological examination of 

tissue 

• Intraoperative findings 

• Clinical followup 

Histopathology of surgically resected 

specimens is the reference standard for 

pretherapy staging. In patients 

undergoing surgery, the nodal (N) stage 

and spread of the tumor to nearby 

regional structures and other organs is 

assessed intraoperatively, either by 

palpation or ultrasound. However, in 

patients with metastatic disease who 

undergo palliative care, a combination 

of initial biopsy results and clinical 

followup serves as the reference 

standard. 

Clinicians use the results from the 

imaging modality or modalities to arrive 

at a stage determination that is 

compared against the stage established 

by the reference standard. These 

comparisons tell us how many people 

were correctly classified in the various 

stages of the disease and allow us to 

calculate the test performance metrics of 

sensitivity, specificity, and accuracy. 

The selection of the reference standard 

is important in evaluating the true 

performance of an imaging modality for 

staging. 

Comparators 

• Any direct comparisons of the 

imaging tests of interest 

• Any direct comparisons of 

variations of any of the imaging tests of 

interest (e.g., diffusion-weighted MRI vs. 

T2-weighted MRI) 

Comparators thought to be of 

particular clinical interest are listed 

below: 

• For colon cancer: a contrastenhanced CT of the chest, abdomen, and 

pelvis versus whole-body PET/CT 

versus a contrast-enhanced MRI of the 

chest, abdomen, and pelvis 

• For rectal cancer: a contrastenhanced CT of the abdomen and pelvis 

versus an MRI of the abdomen and 

pelvis 

• For rectal cancer: endoscopic 

ultrasound versus MRI 

• For suspected liver metastasis: CT 

scan versus MRI or PET/CT of the 

abdomen 

• For suspected widespread 

metastasis, CT of the chest, abdomen, 

and pelvis versus whole-body PET/CT 

or contrast-enhanced MRI of the chest, 

abdomen, and pelvis 

We note that this list is based on a 

preliminary literature search and 

discussions with a limited number of 

clinicians and the Technical Expert 

Panel (TEP). Thus, we do not anticipate 

that the listed items cover all of the 

comparisons of interest. We expect that 

additional comparisons will be 

identified during the literature review. 

Outcomes 

• Test performance outcomes 

• Test performance (e.g., sensitivity, 

specificity, understaging, and 

overstaging) against a reference 

standard test (pathological 

examination, intraoperative 

findings, clinical followup) 

• Intermediate outcomes 

• Stage reclassification 

• Changes in therapeutic management 

• Clinical outcomes 

• Overall mortality 

• Colorectal cancer-specific mortality 

• Quality of life and anxiety 

• Need for additional staging tests, 

including invasive procedures 

• Need for additional treatment, 

including surgery, radiotherapy, or 

chemotherapy 

• Resource utilization related to 

testing and treatment (when 

reported in the included studies) 

• Adverse effects and harms 

• Harms of testing per se (e.g., 

radiation exposure) 

• Harms from test-directed treatments 

(e.g., overtreatment, 

undertreatment) 

Timing 

• Primary staging 

• Interim restaging 

• Duration of followup will vary by 

outcome (e.g., from no followup for test 

performance measurements to many 

years for mortality) 

Setting 

• Any setting will be considered 

Dated: June 13, 2013. 

Carolyn M. Clancy, 

AHRQ, Director. 

[FR Doc. 2013–15288 Filed 6–26–13; 8:45 am] 

BILLING CODE 4160–90–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2013–N–0001] 

Cardiovascular and Renal Drugs 

Advisory Committee; Notice of Meeting 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

This notice announces a forthcoming 

meeting of a public advisory committee 

of the Food and Drug Administration 

(FDA). The meeting will be open to the 

public. 

Name of Committee: Cardiovascular 

and Renal Drugs Advisory Committee. 

General Function of the Committee: 

To provide advice and 

recommendations to the Agency on 

FDA’s regulatory issues. 

Date and Time: The meeting will be 

held on August 6, 2013, from 8 a.m. to 

4 p.m. 

Location: FDA White Oak Campus, 

10903 New Hampshire Ave., Building 

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