42954 Federal Register / Vol. 78, No. 138 / Thursday, July 18, 2013 / Notices 

will be included 

• For bone health outcomes, only 

RCTs of greater than 1 year in 

duration will be included 

Comparators 

• As described for KQ 1. 

Outcomes 

• As specified in the original 2009 

report, unless otherwise noted: 

• CVD intermediate outcomes 

• Cancer intermediate outcomes 

(colorectal adenoma, aberrant crypt 

cells, and mammographic breast 

density) 

• Bone health intermediate outcomes 

(only bone mineral density/content) 

• Pregnancy-related intermediate 

outcomes 

• Pre-eclampsia 

• High blood pressure with or 

without proteinuria 

Timing 

• As described for KQ 1, except for 

intermediate bone health for which 

studies of less than 1 year in duration 

will be excluded. 

Settings 

• As described for KQ 1. 

Key Question 3 

What is the association between 

serum 25(OH)D concentrations and 

clinical outcomes?* 

Populations 

• As described for KQ 1. 

Interventions 

• Serum concentration of 25(OH)D or 

1,25 (OH)2D and the method used. 

Comparators 

• The serum concentration of 

25(OH)D or 1,25 (OH)2D and the 

method used for the placebo or other 

comparison group. 

Outcomes 

• As described for KQ 1. 

Timing 

• As described for KQ 1. 

Settings 

• As described for KQ 1. 

Key Question 4 

What is the effect of vitamin D or 

combined vitamin D and calcium intake 

on serum 25(OH)D concentrations? 

Populations 

• As described for KQ 1. 

Interventions 

• Randomized controlled trials 

(RCTs) identified to answer all other 

KQs. 

Comparators 

• Placebo or lower dose supplement. 

Outcomes 

• Dose-response relationship between 

intake levels and indices of exposure. 

Timing 

• As described for KQs 1 and 2. 

Settings 

• As described for KQs 1 and 2. 

Key Question 5 

What is the association between 

serum 25(OH)D concentration and 

surrogate or intermediate outcomes? 

Populations 

• As described for KQ 2. 

Interventions 

• As described for KQ 2. 

Comparators 

• As described for KQ 2. 

Outcomes 

• As described for KQ 2. 

Timing 

• As described for KQ 2. 

Settings 

• As described for KQ 2. 

Dated: July 11, 2013. 

Carolyn M. Clancy, 

AHRQ Director. 

[FR Doc. 2013–17177 Filed 7–17–13; 8:45 am] 

BILLING CODE 4160–90–P 

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). 

AHRQ is republishing this document 

due to errors found on our first 

publication of June 27, 2013 (http://

www.gpo.gov/fdsys/pkg/FR-2013-06-27/

pdf/2013-15288.pdf). Please disregard 

the June 27 publication. 

DATES: Submission Deadline by July 29, 

2013. 

ADDRESSES: Online submissions: http:// 

effectivehealthcare.AHRQ.gov/index.

cfm/submit-scientific-informationpackets/. 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, P.O. 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 


TKELLEY on DSK3SPTVN1PROD with NOTICES
Federal Register / Vol. 78, No. 138 / Thursday, July 18, 2013 / Notices 42955 

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/searchfor-guides-reviews-and-reports/

?pageaction=displayproduct&product

ID=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, pharmacokinetic 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) 

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. 


TKELLEY on DSK3SPTVN1PROD with NOTICES
42956 Federal Register / Vol. 78, No. 138 / Thursday, July 18, 2013 / Notices 

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: July 11, 2013. 

Carolyn M. Clancy, 

AHRQ Director. 

[FR Doc. 2013–17176 Filed 7–17–13; 8:45 am] 

BILLING CODE 4160–90–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Centers for Disease Control and 

Prevention 

[30Day–13–0307] 

Proposed Data Collections Submitted 

for Public Comment and 

Recommendations 

The Centers for Disease Control and 

Prevention (CDC) publishes a list of 

information collection requests under 

review by the Office of Management and 

Budget (OMB) in compliance with the 

Paperwork Reduction Act (44 U.S.C. 

Chapter 35). To request a copy of these 

requests, call (404) 639–7570 or send an 

email to omb@cdc.gov. Send written 

comments to CDC Desk Officer, Office of 

Management and Budget, Washington, 

DC or by fax to (202) 395–5806. Written 

comments should be received within 30 

days of this notice. 

Proposed Project 

The Gonococcal Isolate Surveillance 

Project (GISP), OMB No. 0920–0307 

exp. 12/31/2013)—Revision—National 

Center for HIV/AIDS, Viral Hepatitis, 

STD, and TB Prevention (NCHHSTP), 

Centers for Disease Control and 

Prevention (CDC). 

Background and Brief Description 

The purpose of this request is to 

obtain Office of Budget and 

Management (OMB) approval to revise 

the data collection for the Gonococcal 

Isolate Surveillance Project (GISP) 

(OMB No. 0920–0307, expires 12/31/ 

2013). CDC seeks a three-year approval 

to conduct the GISP project. Revisions 

to this ICR consist of removing 4 

variables from Form 1: Demographic/ 

Clinical Data. The four variables to be 

removed are: (1) Total monthly number 

of gonococcal infections; (2) date of 

birth of the patient; (3) zip code of the 

patient; and (4) reason for visit. The 

variables to be removed have not proven 

useful at the federal level and removal 

of the variables will not increase or 

decrease the burden. The objectives of 

GISP are: (1) To monitor trends in 

antimicrobial susceptibility of strains of 

Neisseria gonorrhoeae in the United 

States and (2) to characterize resistant 

isolates. Surveillance of N. gonorrhoeae 

antimicrobial resistance is important 

because: (1) Nearly all gonococcal 

infections are treated empirically and 

susceptibility testing data are not 

routinely available in clinical practice; 

(2) N. gonorrhoeae has consistently 

demonstrated the ability to develop 

resistance to the antimicrobials used for 

treatment; (3) effective treatment of 

gonorrhea is a critical component of 

gonorrhea control and prevention, and 

(4) untreated or inadequately treated 

gonorrhea can cause serious 

reproductive health complications. GISP 

is the only source in the United States 

of critical national, regional, and sitespecific gonococcal antimicrobial 

resistance data. GISP provides 

information to support informed and 

scientifically-based treatment 

recommendations. 

GISP was established in 1986 as a 

voluntary surveillance project and now 

involves 5 regional laboratories and 30 

publicly funded sexually transmitted 

disease (STD) clinics around the 

country. The STD clinics submit up to 

25 gonococcal specimens (or isolates) 

per month to the regional laboratories, 

which measure susceptibility of the 

isolates to multiple antimicrobial drugs. 

Limited demographic and clinical 

information corresponding to the 

isolates (and that do not allow 

identification of the patient) are 

submitted directly by the clinics to CDC. 

During 1986–2012, GISP has 

demonstrated the ability to effectively 

achieve its objectives. The emergence of 

resistance in the United States to 

penicillin, tetracyclines, and 

fluoroquinolones among N. gonorrhoeae 

isolates was identified through GISP. 

Increased prevalence of 

fluoroquinolone-resistant N. 

gonorrhoeae (QRNG), as documented by 

GISP data, prompted CDC to update 

treatment recommendations for 

gonorrhea in CDC’s Sexually 

Transmitted Diseases Treatment 

Guidelines, 2006 and to release an 

MMWR article stating that CDC no 

longer recommended fluoroquinolones 

for treatment of gonococcal infections. 

Recently, GISP isolates demonstrated 

increasing minimum inhibitory 

concentrations of cefixime, which can 

be an early warning of impending 


TKELLEY on DSK3SPTVN1PROD with NOTICES