[Federal Register Volume 89, Number 148 (Thursday, August 1, 2024)]
[Notices]
[Pages 62746-62748]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-16973]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality


Supplemental Evidence and Data Request on Blood-Based Tests for 
Multiple Cancer Screening: A Systematic Review

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

ACTION: Request for supplemental evidence and data submission.

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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 on Blood-based 
Tests for Multiple Cancer Screening: A Systematic Review, which is 
currently being conducted by the AHRQ's Evidence-based Practice Centers 
(EPC) Program. Access to published and unpublished pertinent scientific 
information will improve the quality of this review.

DATES: Submission Deadline on or before September 3, 2024.

ADDRESSES: 
    Email submissions: [email protected].
    Print submissions:
    Mailing Address: Center for Evidence and Practice Improvement, 
Agency for Healthcare Research and Quality, ATTN: EPC SEADs 
Coordinator, 5600 Fishers Lane, Mail Stop 06E53A, Rockville, MD 20857.
    Shipping Address (FedEx, UPS, etc.): Center for Evidence and 
Practice Improvement, Agency for Healthcare Research and Quality, ATTN: 
EPC SEADs Coordinator, 5600 Fishers Lane, Mail Stop 06E77D, Rockville, 
MD 20857.

FOR FURTHER INFORMATION CONTACT: Kelly Carper, Telephone: 301-427-1656 
or Email: [email protected].

SUPPLEMENTARY INFORMATION: The Agency for Healthcare Research and 
Quality has commissioned the Evidence-based Practice Centers (EPC) 
Program to complete a review of the evidence for Blood-based Tests for 
Multiple Cancer Screening: A Systematic Review. AHRQ is conducting this 
review pursuant to Section 902 of the Public Health Service Act, 42 
U.S.C. 299a.
    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, 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 Blood-based Tests for Multiple Cancer Screening: A 
Systematic Review. The entire research protocol is available online at: 
https://effectivehealthcare.ahrq.gov/products/cell-free-dna/protocol.
    This is to notify the public that the EPC Program would find the 
following information on Blood-based Tests for Multiple Cancer 
Screening: A Systematic Review helpful:
    [ssquf] A list of completed studies that your organization has 
sponsored for this topic. 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, a summary, including the following elements, if 
relevant: 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 topic. In the list, please provide the 
ClinicalTrials.gov trial number or, if the trial is not registered, the 
protocol for the study including, if relevant, 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 topic and an index outlining the relevant information in each 
submitted file.
    Your contribution is very beneficial to the Program. Materials 
submitted must be publicly available or able to be made public. 
Materials that are considered confidential; marketing materials; study

[[Page 62747]]

types not included in the review; or information on topics 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 
website 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/email-updates.
    The review will answer the following questions. This information is 
provided as background. AHRQ is not requesting that the public provide 
answers to these questions.

Key Questions (KQ)

    KQ 1: What is the effectiveness of screening with blood-based 
multicancer screening tests (MCST) on cancer-specific mortality and 
all-cause mortality?
    KQ 2a: What is the effectiveness of screening with MCSTs on the 
cumulative detection of cancer overall and by cancer type?
    KQ 2b: What is the effectiveness of screening with MCSTs on the 
cumulative detection of late-stage cancer (i.e., stage shift) overall 
and by cancer type?
    KQ 3: What is the accuracy of MCSTs for detection of cancer and 
does accuracy vary by cancer type or stage?
    KQ 4: What are the harms of screening with MCSTs?
    KQ 5: What are the harms of the evaluation and additional testing 
following a positive MCST or with surveillance following a negative 
evaluation after a positive MCST?

 PICOTS (Populations, Interventions, Comparators, Outcomes, Timing, and
                                Setting)
   [Detailed inclusion and exclusion criteria for systematic review on
            blood-based tests for multiple cancer screening]
------------------------------------------------------------------------
           Inclusion criteria                   Exclusion criteria
------------------------------------------------------------------------
                               Population
------------------------------------------------------------------------
KQs 1, 2, 4, 5.........................  All KQ: People younger than 18
Asymptomatic people 18 years of age or    years of age; other than human
 older.                                   populations (e.g., animal or
KQ 3: People 18 years of age or older     in vitro laboratory studies).
 with either (1) biopsy-confirmed        KQs 1, 2, 4, 5: Adults with
 cancer or (2) who are asymptomatic       active cancer; adults
 without suspicion for cancer (i.e.,      undergoing evaluation for
 ``healthy'' individuals).                suspected cancer or cancer
                                          recurrence; adults with a
                                          history of invasive or
                                          hematologic cancer (other than
                                          nonmelanoma skin cancer)
                                          within the previous 3 years or
                                          a history of untreated cancer.
                                         KQ 3: Adults undergoing
                                          diagnostic evaluation for
                                          possible cancer or cancer
                                          recurrence.
------------------------------------------------------------------------
                              Intervention
------------------------------------------------------------------------
KQs 1, 2, 3, 4.........................  KQs 1, 2, 3, 4: Tests that are
 Blood tests used for the         not blood based (e.g., tissue,
 screening of at least 2 different        saliva, urine, or other bodily
 types of cancer; tests using any         fluids).
 analytes with any technology are        KQ 5: Tests or interventions
 eligible.                                not performed as a result of a
 Tests that were designed for     positive MCST.
 cancer prognosis or surveillance in
 those with cancer or who have
 completed cancer treatment (i.e.,
 evaluation for minimal residual
 disease) are eligible as long as they
 are being evaluated in an eligible
 population as defined above.
 Blood tests used in
 combination with other tests such as
 imaging are eligible.
 MCSTs used instead of or in
 addition to usual care screening are
 eligible. We define usual care
 screening as follows: mammography
 (breast), direct visualization such as
 colonoscopy or stool-based tests
 (colorectal), low-dose computed
 tomography (lung), cytology, human
 papilloma virus testing (cervical),
 and prostate specific antigen
 (prostate).
KQ 5: Tests or procedures (imaging,
 tissue biopsy, blood, urine, or
 cerebrospinal fluid) to evaluate
 positive signal(s) resulting from an
 MCST or procedures used to surveil
 patients who have a negative
 evaluation after a positive MCST
 signal.
------------------------------------------------------------------------
                               Comparator
------------------------------------------------------------------------
KQs 1, 2, 4............................  KQs 1, 2, 4: No comparator
 No screening test.............   group.
 Usual care cancer screening as  KQ 3: No reference standard for
 defined above.                           comparison.
KQ 3: Tissue evaluation for              KQ 5: Studies without a
 confirmation of cancer; healthy          comparator group will not be
 asymptomatic status for controls.        excluded.
KQ 5: No comparator required...........
------------------------------------------------------------------------

[[Page 62748]]

 
                                Outcomes
------------------------------------------------------------------------
KQ 1: Cancer mortality overall and by    Outcomes not specifically
 cancer type, all-cause mortality,        indicated as included.
 quality of life, functional status.     Composite measures composed of
KQ 2a: Cumulative detection of cancer     both included and excluded
 overall and by cancer type.              outcomes will be included but
KQ 2b: Cumulative detection of late-      considered only in sensitivity
 stage cancer overall and by cancer       analyses.
 type (i.e., Stage III or IV or organ-
 specific definition of late stage);
 distribution of cancer stage at
 diagnosis (i.e., stage shift).
KQ 3: Accuracy (sensitivity, false
 negatives, specificity, false
 positives, predictive value) by cancer
 type and by cancer stage.
KQ 4: Psychosocial and emotional
 distress including anxiety and worry,
 false reassurance resulting in
 decrease in receipt of usual care
 screening or change in health
 behaviors associated with cancer
 (alcohol, tobacco, drug use, diet,
 physical activity), overdiagnosis, out-
 of-pocket patient costs, patient
 financial toxicity, and impact on
 insurability.
KQ 5: Radiation exposure from imaging,
 harms from invasive procedures, other
 adverse effects from evaluation that
 occur after a positive MCST, or out-of-
 pocket patient costs, patient
 financial toxicity, and impact on
 insurability.
------------------------------------------------------------------------
                                 Timing
------------------------------------------------------------------------
KQ 1: At least 5 years of followup.....  KQ 1: Studies with less than 5
KQs 2, 4, 5: any timing................   years of followup.
KQ 3: At least 1 year of followup for
 prediagnostic performance designs.\a\
 For diagnostic performance designs,
 controls must be considered cancer
 free at the time of the sample.
------------------------------------------------------------------------
                                 Setting
------------------------------------------------------------------------
 Recruitment from outpatient      Acute care settings,
 clinical settings, including primary     inpatient care settings.
 care or specialty care, community-       Countries with a
 based or public health settings,         United Nations Human
 electoral rolls, or other population-    Development Index of less than
 based registries.                        high.
 Countries with a United
 Nations Human Development Index of
 high or very high (Appendix A).
------------------------------------------------------------------------
                              Study Design
------------------------------------------------------------------------
KQs 1, 2, 4, 5: Randomized controlled    For all KQ: Modeling studies,
 trials; controlled trials.               case series, case reports, in
KQs 1, 2: Registered NRSIs with 1 or      vitro lab studies, studies
 more eligible benefit outcomes listed    designed to assess analytic
 on study registration \b\.               validity, narrative reviews,
KQs 4, 5: Unregistered NRSIs are also     systematic reviews (reviews
 eligible.                                will not be included but will
KQ 3: Studies that provide data related   be manually reviewed to
 to test accuracy; both prediagnostic     identify primary research
 test performance and diagnostic test     studies that the search may
 performance designs are eligible.        have missed).
 However, only diagnostic performance    KQs 1, 2: Cohort studies that
 designs conducted in external            have not been registered or
 validation cohorts are eligible.         that report eligible outcomes
 Further, if results for multiple         that were not included in the
 variations of the test are reported by   study's registration \b\
 authors, only results from the test      studies designed with a sample
 version selected for future commercial   size that was not based on
 use or for evaluation in future          outcomes related to cancer
 intervention studies will be eligible.   detection or mortality.
                                         KQ 3: Accuracy results derived
                                          from discovery, development,
                                          internal validation, or split
                                          sample cohorts are not
                                          eligible because multiple
                                          analytes, technologies, or AI
                                          classifiers are being
                                          evaluated to develop the test
                                          and these results do not
                                          reflect the final state of the
                                          test that would be used in
                                          routine practice.
------------------------------------------------------------------------
                                Language
------------------------------------------------------------------------
English................................  Languages other than English.
------------------------------------------------------------------------
\a\ KQ 3 prediagnostic accuracy performance studies that use disease-
  free longitudinal followup as a reference standard should have a
  minimum of 1-year followup.
\b\ Refers to study registration in ClinicalTrials.gov database, or
  another study registry such as those included in the World Health
  Organization International Clinical Trials Registry Platform.
KQ = key question; MCST = multiple cancer screening test; NRSI = non-
  randomized study of interventions.


    Dated: July 25, 2024.
Marquita Cullom,
Associate Director.
[FR Doc. 2024-16973 Filed 7-31-24; 8:45 am]
BILLING CODE 4160-90-P