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[Federal Register Volume 78, Number 157 (Wednesday, August 14, 2013)]
[Notices]
[Pages 49520-49523]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-19714]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality

Scientific Information Request on Imaging Techniques for the 
Surveillance, Diagnosis, and Staging of Hepatocellular Carcinoma

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

ACTION: Request for scientific information submissions.

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SUMMARY: The Agency for Healthcare Research and Quality (AHRQ) is 
seeking scientific information submissions from the public on imaging 
techniques for the surveillance, diagnosis, and staging of 
hepatocellular carcinoma. Scientific information is being solicited to 
inform our review of Imaging Techniques for the Surveillance, 
Diagnosis, and Staging of Hepatocellular Carcinoma, 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 Access to published and unpublished 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 on imaging techniques for the 
surveillance, diagnosis, and staging of hepatocellular carcinoma will 
improve the quality of this review. AHRQ is 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 September 13, 2013.

ADDRESSES: 
    Online submissions: http://effectivehealthcare.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: /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: Robin Paynter, Research Librarian, 
Telephone: 503-220-8262 ext. 58652 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 Imaging Techniques for the Surveillance, Diagnosis, and Staging of 
Hepatocellular Carcinoma.
    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 imaging techniques for the surveillance, diagnosis, and 
staging of hepatocellular carcinoma, including those that describe 
adverse events. 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=1600#7839
    This notice is to notify the public that the EHC program would find 
the following information on imaging techniques for the surveillance, 
diagnosis, and staging of hepatocellular carcinoma helpful:
    [ssquf] A list of completed studies your company has sponsored for 
this indication. In the list, 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: 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

[[Page 49521]]

to follow-up/withdrawn/analyzed, effectiveness/efficacy, and safety 
results.
    [ssquf] A list of ongoing studies your company 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 company for this 
indication and an index outlining the relevant information in each 
submitted file.
    Your contribution is very beneficial to the 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 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/.
    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://www.effectivehealthcare.AHRQ.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=1600#7839

Key Question 1

    What is the comparative effectiveness of available imaging-based 
surveillance strategies (listed below under interventions for KQ 1), 
used singly or in sequence for detecting hepatocellular carcinoma (HCC) 
among individuals undergoing surveillance for HCC (individuals at high 
risk for HCC and individuals who have undergone liver transplants for 
HCC)?
    a. What is the comparative test performance of imaging-based 
surveillance strategies for detecting HCC?
    i. How is a particular technique's test performance modified by use 
of various reference standards (e.g., explanted liver samples, 
histological diagnosis, or clinical and imaging followup)?
    ii. How is the comparative effectiveness modified by patient-level 
characteristics (e.g., body mass index, number of lesions, tumor 
diameter, or cause of liver disease) or other factors (e.g., technical 
aspects of imaging techniques, biomarker levels, test operator or 
interpreter skill, setting)?
    b. What is the comparative effectiveness of imaging-based 
surveillance strategies on intermediate outcomes like diagnostic 
thinking?
    c. What is the comparative effectiveness of imaging-based 
surveillance strategies on clinical and patient-centered outcomes?
    d. What are the adverse effects or harms associated with imaging-
based surveillance strategies?

Key Question 2

    What is the comparative effectiveness of imaging techniques (listed 
under the interventions for KQ 2), used singly, in combination, or in 
sequence in diagnosing HCC among individuals in whom an abnormal lesion 
has been detected while undergoing surveillance for HCC (individuals at 
high risk for HCC and individuals who have undergone liver transplants 
for HCC) or through the evolution of symptoms and abdominal imaging 
done for other indications?
    a. What is the comparative test performance of imaging techniques 
for diagnosing HCC?
    i. How is a particular technique's test performance modified by use 
of various reference standards (e.g., explanted liver samples, 
histological diagnosis, or clinical and imaging followup)?
    ii. How is the comparative effectiveness modified by patient-level 
characteristics (e.g., body mass index, number of lesions, tumor 
diameter, or cause of liver disease) or other factors (e.g., technical 
aspects of imaging techniques, biomarker levels, test operator or 
interpreter skill, setting)?
    b. What is the comparative effectiveness of the various imaging 
techniques on intermediate outcomes like diagnostic thinking and use of 
additional diagnostic procedures such as fine-needle or core biopsy?
    c. What is the comparative effectiveness of the various imaging 
techniques on clinical and patient-centered outcomes?
    d. What are the adverse effects or harms (related to testing or a 
test-associated diagnostic workup) associated with the various imaging 
techniques?

Key Question 3

    What is the comparative effectiveness of imaging techniques (listed 
under the interventions for KQ 3), used singly, in combination, or in 
sequence in staging HCC among patients diagnosed with HCC?
    a. What is the comparative test performance of imaging techniques 
to predict HCC tumor stage?
    i. How is a particular technique's test performance modified by use 
of various reference standards (e.g., explanted liver samples, 
histological diagnosis, or clinical and imaging followup)?
    ii. How is the comparative effectiveness modified by patient-level 
characteristics (e.g., body mass index, number of lesions, tumor 
diameter, or cause of liver disease) or other factors (e.g., technical 
aspects of imaging techniques, biomarker levels, test operator or 
interpreter skill, setting)?
    b. What is the comparative test performance of imaging techniques 
on diagnostic thinking?
    c. What is the comparative effectiveness of imaging techniques on 
clinical and patient-centered outcomes?
    d. What are the adverse effects or harms associated with using 
imaging techniques related to testing or test-associated diagnostic 
workup?

PICOTS (Population(s), Interventions, Comparators, Outcomes, Timing, 
Settings) by Key Question

Population(s)
 Key Question 1.
     Patients at high risk for HCC undergoing surveillance. The 
population of high-risk patients is defined, as per the AASLD clinical 
guidelines, as composed of the following: Asian male HBV carriers over 
age 40, Asian female HBV carriers over age 50, HBV carriers with a 
family history of HCC, African/North American black HBV carriers, all 
individuals with cirrhosis (including alcoholic cirrhosis), HBV or HCV 
carriers with cirrhosis, and patients with stage 4 primary biliary 
cirrhosis.6 Other definitions of high-risk patients as defined by the 
primary studies will be accepted.
     Patients who have undergone liver transplants for HCC, 
either with or without HCC detected in the explanted liver.
     Both population groups will be considered separately.
 Key Question 2.
     Patients at high risk for HCC in

[[Page 49522]]

whom a suspicious lesion(s) has been detected by surveillance or by 
other means.
     Patients who have undergone liver transplants for HCC, 
either with or without HCC detected in the explanted liver.
     Both population groups will be considered separately.
 Key Question 3
     Patients diagnosed with HCC who require staging before 
initial treatment.
 All Key Questions
     Patients with cholangiocarcinoma will be excluded.
Interventions
 Key Question 1
     US, spiral CT, multidetector CT (MDCT), dual energy CT, or 
MRI.
     Studies that included surveillance strategies of any other 
imaging test with or without additional biomarkers would also be 
included. The strategies could include the techniques being used singly 
or in a specific sequence.
 Key Question 2
     Imaging techniques, used singly, in combination, or in a 
specific sequence, including US, spiral CT, MDCT, dual energy CT, MRI 
(including contrast agents like Gd-EOB-DTPA and SPIO), or 
fluorodeoxyglucose positron emission tomography (FDG-PET) with 
different tracers (including 18F, fluorothymidine [FLT], 11C-choline, 
and 11C = methionine, or others).
 Key Question 3
     Imaging techniques, used singly, in combination, or in a 
specific sequence, including US, spiral CT, MDCT, dual energy CT, MRI 
with contrast (including contrast agents such as Gd-EOB-DTPA and SPIO), 
FDG-PET with different tracers (including 18F, FLT, 11C-choline, and 
11C-methionine, or others), or contrast CT.
     Test performance of imaging techniques will be stratified 
by the different staging systems used.
 All Key Questions
     Outdated imaging techniques (e.g., conventional, 
nonspiral/nonmultidetector CT, or imaging techniques used before 1995) 
will be excluded.
     Imaging techniques not available or in use in the United 
States (e.g., hepatic portography) will be excluded.
Comparators
     For studies of diagnostic accuracy (comparative test 
performance), the reference standard comparators will be histopathology 
(based on explanted liver specimens or biopsy) or clinical and imaging 
followup, and the imaging comparators will be alternative imaging tests 
or strategies.
     For studies of comparative effectiveness, the comparators 
will be no imaging or alternative imaging strategies.
Outcomes for Each Key Question
Key Question 1
 Diagnostic outcomes include:
     Detection rates of HCC lesions.
     Types of HCC lesions detected.
     Test performance (e.g., sensitivity and specificity, 
predictive values, likelihood ratios, area under the receiver operating 
curve, or others) for diagnosing HCC, including stage-specific 
accuracy.
     For all KQs, potential modifiers of measures of test 
performance will be evaluated, including the reference standards used 
(e.g., explanted liver samples, histological diagnosis, or clinical and 
imaging followup), patient and tumor-level characteristics (e.g., body 
mass index, number of lesions, tumor diameter, or cause of liver 
disease), or other factors (e.g., technical aspects of the imaging 
techniques, biomarker levels, test operator or interpreter skill, 
setting).
 Intermediate outcomes include:
     Effects on diagnostic thinking.
 Effects on clinical decisionmaking.
     Clinical and patient-centered outcomes include:
     Overall mortality or survival.
     Recurrence of HCC, including rates of seeding by fine-
needle aspiration.
     Quality of life as measured with scales such as the Short-
Form Health Survey (SF-36) or EuroQol 5D (EQ-5TM) or as 
defined by the primary studies.
     Psychosocial effects of diagnostic testing on patients, 
patients' caregivers, and other family members, as measured by self-
reported questionnaire instruments.
     Resource utilization and patient burden (e.g., costs 
associated with the imaging procedure, access to the imaging facility, 
the number of imaging procedures, and other procedures conducted).
Key Question 2
 Diagnostic outcomes include:
     Type of HCC lesions detected.
     Test performance (e.g., sensitivity and specificity, 
predictive values, likelihood ratios, area under the receiver operating 
curve, or others) for diagnosing HCC. As in KQ 1, potential modifiers 
of measures of test performance will be evaluated, including the 
reference standards used (e.g., explanted liver samples, histological 
diagnosis, or clinical and imaging followup), patient and tumor-level 
characteristics (e.g., body mass index, number of lesions, tumor 
diameter, or cause of liver disease), or other factors (e.g., technical 
aspects of the imaging techniques, biomarker levels, test operator or 
interpreter skill, setting).
 Intermediate outcomes include:
     Effects on diagnostic thinking.
 Effects on clinical decisionmaking.
     Clinical and patient centered outcomes include:
     Overall mortality or survival.
     Recurrence of HCC, including rates of seeding by fine-
needle aspiration
     Quality of life as measured with scales such as the Short-
Form Health Survey (SF-36) or EuroQol 5D (EQ-5TM) or as 
defined by the primary studies.
     Psychosocial effects of diagnostic testing on patients, 
patients' caregivers, and other family members, as measured by self-
reported questionnaire instruments.
     Resource utilization and patient burden (e.g., costs 
associated with the imaging procedure, access to the imaging facility, 
the number of imaging procedures and other procedures conducted).
Key Question 3
 Diagnostic outcomes include:
     Measures for stage-specific accuracy of imaging (e.g., 
Obuchowski method for calculating the area under the receiver operating 
curve, stage reclassification rates).
 Intermediate outcomes include:
     Effects on diagnostic thinking.
     Effects on clinical decisionmaking.
 Clinical and patient-centered outcomes include:
     Overall mortality or survival.
     Recurrence of HCC, including rates of seeding by fine-
needle aspiration
     Quality of life as measured with scales such as the Short-
Form Health Survey (SF-36) or EuroQol 5D (EQ-5TM) or as 
defined in the primary studies.
     Psychosocial effects of diagnostic testing on patients, 
patients' caregivers, and other family members as measured by self-
reported questionnaire instruments.
     Resource utilization and patient burden (e.g., costs 
associated with the imaging procedure, access to the imaging facility, 
the number of imaging procedures and additional procedures conducted).

[[Page 49523]]

Key Questions 1d, 2d, and 3d (Adverse Events or Harms)
 Adverse effects or harms associated with the imaging 
techniques (e.g., test-related anxiety, adverse events secondary to 
venipuncture, contrast allergy, exposure to radiation).
 Adverse effects or harms associated with test-associated 
diagnostic workup (e.g., harms of biopsy or harms associated with 
workup of other incidental tumors discovered on imaging).
Timing
     No restrictions will be placed on timing.
     For studies of comparative effectiveness, duration of 
followup, timing of interventions, and frequency of interventions will 
be recorded.
Settings
     All relevant care settings (e.g., primary and secondary 
care).

    Dated: August 6, 2013.
Carolyn M. Clancy,
AHRQ Director.
[FR Doc. 2013-19714 Filed 8-13-13; 8:45 am]
BILLING CODE 4160-90-P
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