[Federal Register Volume 85, Number 128 (Thursday, July 2, 2020)]
[Notices]
[Pages 39904-39909]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-14237]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality


Supplemental Evidence and Data Request on Breast Reconstruction 
After Mastectomy

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

ACTION: Request for supplemental evidence and data submissions.

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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 Breast 
Reconstruction after Mastectomy, 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published and unpublished pertinent scientific information will improve 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 30 days after the date of 
publication of this Notice.

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: Jenae Benns, Telephone: 301-427-1496 
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 Breast Reconstruction 
after Mastectomy. AHRQ is conducting this systematic review pursuant to 
Section 902(a) of the Public Health Service Act, 42 U.S.C. 299a(a).
    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 Breast Reconstruction after Mastectomy, including those 
that describe adverse events. The entire research protocol is available 
online at: https://effectivehealthcare.ahrq.gov/products/breast-reconstruction-mastectomy/protocol.
    This is to notify the public that the EPC Program would find the 
following information on Breast Reconstruction after Mastectomy 
helpful:
    [ssquf] A list of completed studies that your organization has 
sponsored for this indication. 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: 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 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 organization for 
this indication 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 
types not included in the review; or information on indications 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 four weeks. If 
you would like to be notified when the draft is posted, please sign up 
for the email list at: https://www.effectivehealthcare.ahrq.gov/email-updates.

[[Page 39905]]

    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.

Key Questions (KQ)

    KQ 1: For adult women who are undergoing (or have undergone) 
mastectomy for breast cancer, what are the comparative benefits and 
harms of implant-based (IBR) versus autologous (AR) breast 
reconstruction?
    KQ 2: For adult women undergoing IBR or AR after mastectomy for 
breast cancer that requires either chemotherapy or radiation therapy, 
what is the optimal time for IBR or AR with respect to
    (a) chemotherapy or
    (b) radiation therapy?
    KQ 3: For adult women undergoing IBR after mastectomy for breast 
cancer, what are the comparative benefits and harms of different types 
of implants (e.g., silicone, saline)?
    KQ 4: For adult women undergoing IBR after mastectomy for breast 
cancer, what are the comparative benefits and harms of different 
anatomic planes of implant placement (prepectoral, partial submuscular, 
and total submuscular)?
    KQ 5: For adult women undergoing IBR after mastectomy for breast 
cancer, what are the comparative benefits and harms of IBR with versus 
without the use of a human acellular dermal matrix (ADM) in the 
reconstruction procedure?
    KQ 6: For adult women undergoing AR after mastectomy for breast 
cancer, what are the comparative benefits and harms of different flap 
types for AR?

Contextual Questions

    Contextual Question 1:
    What patient preferences and values inform decisionmaking about 
breast reconstruction after mastectomy for breast cancer? This includes 
the initial choice to undergo reconstruction, as well as the type and 
timing of surgery.
    Contextual Question 2:
    What strategies or tools (including shared decisionmaking) are 
available to help women make informed choices about breast 
reconstruction after mastectomy for breast cancer?

Study Eligibility Criteria

    The specific eligibility criteria provided below have been refined 
based on discussions with a panel of Key Informants (KIs) and a 
Technical Expert Panel (TEP).

Key Question 1 (IBR Versus AR)

Population
 Adult (>=18 years old) women who are undergoing (or have 
undergone) mastectomy for any type of breast cancer (or carcinoma in 
situ) and have decided to undergo breast reconstruction
 Either therapeutic or prophylactic mastectomy
 Exclude: Studies where >=10% of women underwent breast 
reconstruction (combined across reasons):
    [cir] For solely cosmetic purposes (i.e., augmentation)
    [cir] for revision reconstruction (i.e., after a previous 
reconstruction for breast cancer)
Interventions
 IBR
    [cir] Either single- or multi-stage
    [cir] Any type of implant material, either smooth or textured, 
silicone or saline
    [cir] Any anatomic plane of implant placement
    [cir] With or without use of human ADM
    [cir] With or without mastectomy and reconstruction of the 
contralateral breast (i.e., unilateral or bilateral)
    [cir] With or without symmetry procedure (e.g., mastopexy) in the 
contralateral breast
Comparators
 AR using any flap (either free flap or pedicled), for example:
    [cir] Deep inferior epigastric perforator (DIEP)
    [cir] Latissimus dorsi (LD)
    [cir] Transverse rectus abdominis myocutaneous (TRAM)
    [cir] Superficial inferior epigastric artery perforator (SIEA)
    [cir] Gluteal artery perforator (GAP)
    [cir] Transverse musculocutaneous gracilis (TMG)
    [cir] Transverse upper gracilis (TUG)
    [cir] Profundal artery perforator (PAP)
 Combination of IBR and AR
 Exclude: Non-autologous flap transplants (i.e., cadaveric or 
xenotransplant)
 Exclude: Exclusive lipofilling/autologous fat reconstruction
Outcomes
 Quality of life
 Physical well-being (e.g., pain, discomfort)
 Psychosocial well-being (e.g., self-esteem, emotionality, 
normality)
 Sexual well-being
 Patient satisfaction with aesthetics (i.e., satisfaction with 
breast)
 Patient satisfaction with outcome (e.g., satisfaction with 
care)
 Planned staged surgeries for reconstruction
 Recurrence of breast cancer
 Harms
    [cir] Mortality
    [cir] Unplanned repeat hospitalization
    [cir] Duration of unplanned repeat hospitalization
    [cir] Unplanned repeat surgeries--for revision of reconstruction 
(e.g., for asymmetry)
    [cir] Unplanned repeat surgeries--for complications (e.g., for 
infection, bleeding)*
    [cir] Pain, including chronic pain
    [cir] Analgesic (e.g., opioid) use
    [cir] Necrosis, such as of the nipple or of the flap
    [cir] Animation deformity
    [cir] Complications that lead to delays in other cancer-related 
treatments (e.g., chemotherapy, radiation therapy)
    [cir] Thromboembolic events
    [cir] Infection
    [cir] Wound dehiscence
    [cir] Delayed healing
    [cir] Seroma
    [cir] Chronic conditions (e.g., rheumatologic diseases)
    [cir] Touch sensitivity
    [cir] Scarring
Potential Effect Modifiers
 Age
 Stage of breast cancer
 First occurrence versus recurrent breast cancer
 Immediate versus delayed reconstruction
 Single-stage (direct to reconstruction) versus multi-stage 
(with tissue expander) reconstruction
 Unilateral versus bilateral reconstruction
 Radiation therapy versus no radiation therapy
 Chemotherapy versus no chemotherapy
Timing
 Any
Setting
 Any, including single- and multicenter
Design
 Randomized controlled trials (RCTs), N>=10 per group
 Nonrandomized comparative studies (NRCSs), N>=30 per group
 Case-control studies, N>=100 per group
 Single group studies, N>=500
 Studies may be prospective or retrospective
 Exclude: case reports and series of individually-reported case 
reports

Key Question 2 (Optimal Time For IBR or AR)

Population(s)
 Adult (>=18 years old) women who are undergoing IBR or AR 
after a

[[Page 39906]]

mastectomy for breast cancer (or carcinoma in situ) that requires 
either chemotherapy or radiation therapy
 Either therapeutic or prophylactic mastectomy
 Exclude: Studies where >=10% of women underwent breast 
reconstruction (combined across reasons):
    [cir] For solely cosmetic purposes (i.e., augmentation)
    [cir] for solely prophylactic purposes (i.e., without diagnosed 
breast cancer)
    [cir] for revision reconstruction (i.e., after a previous 
reconstruction for breast cancer)
Interventions
(a) IBR or AR before chemotherapy
(b) IBR or AR before radiation therapy
    [cir] Either single- or multistage
    [cir] With or without mastectomy and reconstruction of the 
contralateral breast (i.e., unilateral or bilateral)
    [cir] With or without symmetry procedure (e.g., mastopexy) in the 
contralateral breast
    [cir] With or without use of human ADM
    [cir] For IBR--Any type of implant material, either smooth or 
textured
    [cir] For IBR--Any anatomic plane of implant placement
    [cir] For AR--Any flap type
Comparators
(a) IBR or AR after chemotherapy
(b) IBR or AR after radiation therapy
Outcomes
 Quality of life
 Physical well-being (e.g., pain, discomfort)
 Psychosocial well-being (e.g., self-esteem, emotionality, 
normality)
 Sexual well-being
 Patient satisfaction with aesthetics (i.e., satisfaction with 
breast)
 Patient satisfaction with outcome (e.g., satisfaction with 
care)
 Planned staged surgeries for reconstruction
 Recurrence of breast cancer
 Harms
    [cir] Mortality
    [cir] Unplanned repeat hospitalization
    [cir] Duration of unplanned repeat hospitalization
    [cir] Unplanned repeat surgeries--for revision of reconstruction 
(e.g., for asymmetry)
    [cir] Unplanned repeat surgeries--for complications (e.g., for 
infection, bleeding)*
    [cir] Pain, including chronic pain
    [cir] Analgesic (e.g., opioid) use
    [cir] Necrosis, such as of the nipple or of the flap
    [cir] Animation deformity
    [cir] Complications that cause delays in other cancer-related 
treatments (e.g., chemotherapy, radiation therapy)
    [cir] Thromboembolic events
    [cir] Infection
    [cir] Wound dehiscence
    [cir] Delayed healing
    [cir] Seroma
    [cir] Chronic conditions (e.g., rheumatologic diseases)
    [cir] Touch sensitivity
    [cir] Scarring
Potential Effect Modifiers:
 Age
 Stage of breast cancer
 First occurrence versus recurrent breast cancer
 Type of chemotherapy (for KQ 2a) or radiation therapy (for KQ 
2b)
 Immediate versus delayed reconstruction
 Single-stage (direct to reconstruction) versus multi-stage 
(with tissue expander) reconstruction
 Unilateral versus bilateral reconstruction
Timing
 Any
Setting
 Any, including single- and multicenter
Design
 RCTs, N>=10 per group
 NRCSs, N>=30 per group
 Case-control studies, N>=100 per group
 Single group studies, N>=500
 Studies may be prospective or retrospective
 Exclude: case reports and series of individually-reported case 
reports

Key Question 3 (Type of Implant Material)

Population(s)
 Adult (>=18 years old) women who are undergoing (or have 
undergone) mastectomy for any type of breast cancer (or carcinoma in 
situ) and have decided to undergo IBR
 Either therapeutic or prophylactic mastectomy
 Exclude: Studies where >=10% of women underwent breast 
reconstruction (combined across reasons):
    [cir] For solely cosmetic purposes (i.e., augmentation)
    [cir] for revision reconstruction (i.e., after a previous 
reconstruction for breast cancer)
Interventions
 IBR using one type of implant material
    [cir] Saline
    [cir] Silicone
    [cir] Other materials
    [cir] Either smooth or textured
    [cir] Either single- or multistage
    [cir] Any anatomic plane of implant placement
    [cir]
    With or without use of human ADM
    [cir] With or without mastectomy and reconstruction of the 
contralateral breast (i.e., unilateral or bilateral)
    [cir] With or without symmetry procedure (e.g., mastopexy) in the 
contralateral breast
Comparators
 IBR using another type of implant material
Outcomes
 Quality of life
 Physical well-being (e.g., pain, discomfort)
 Psychosocial well-being (e.g., self-esteem, emotionality, 
normality)
 Sexual well-being
 Patient satisfaction with aesthetics (i.e., satisfaction with 
breast)
 Patient satisfaction with outcome (e.g., satisfaction with 
care)
 Planned staged surgeries for reconstruction
 Recurrence of breast cancer
 Harms
    [cir] Mortality
    [cir] Unplanned repeat hospitalization
    [cir] Duration of unplanned repeat hospitalization
    [cir] Unplanned repeat surgeries--for revision of reconstruction 
(e.g., for asymmetry)
    [cir] Unplanned repeat surgeries--for complications (e.g., for 
infection, bleeding) *
    [cir] Pain, including chronic pain
    [cir] Analgesic (e.g., opioid) use
    [cir] Necrosis, such as of the nipple
    [cir] Animation deformity
    [cir] Implant-related infections
    [cir] Implant rupture, including asymptomatic rupture
    [cir] Implant deflation
    [cir] Implant malposition
    [cir] Need for explant surgery
    [cir] Capsular contracture
    [cir] New neoplasms (e.g., BIA-ALCL)
    [cir] Complications that cause delays in other cancer-related 
treatments (e.g., chemotherapy, radiation therapy)
    [cir] Thromboembolic events
    [cir] Wound dehiscence
    [cir] Delayed healing
    [cir] Seroma
    [cir] Chronic conditions (e.g., rheumatologic diseases)
    [cir] Touch sensitivity
    [cir] Scarring

[[Page 39907]]

    [cir] Red breast syndrome
Potential Effect Modifiers
 Age
 Stage of breast cancer
 First occurrence versus recurrent breast cancer
 Immediate versus delayed reconstruction
 Single-stage (direct to reconstruction) versus multistage 
(with tissue expander) reconstruction
 Unilateral versus bilateral reconstruction
 Surface of implant (smooth versus textured)
 Shape of implant (round versus anatomic/teardrop)
 Size of implant (volume)
Timing
 Any
Setting
 Any, including single- and multicenter
Design
 RCTs, N>=10 per group
 NRCSs, N>=30 per group
 Case-control studies, N>=100 per group
 Single group studies, N>=500
 Studies may be prospective or retrospective
 Exclude: case reports and series of individually-reported case 
reports

Key Question 4 (Anatomic Plane of Implant Placement)

Population(s)
 Adult (>=18 years old) women who are undergoing (or have 
undergone) mastectomy for any type of breast cancer (or carcinoma in 
situ) and have decided to undergo IBR
 Either therapeutic or prophylactic mastectomy
 Exclude: Studies where >=10% of women underwent breast 
reconstruction (combined across reasons):
    [cir] for solely cosmetic purposes (i.e., augmentation)
    [cir] for revision reconstruction (i.e., after a previous 
reconstruction for breast cancer)
Interventions
 IBR with implant placement in one anatomic plane
    [cir] Prepectoral placement
    [cir] Partial submuscular placement
    [cir] Total submuscular placement
    [cir] Either single- or multi-stage
    [cir] Any type of implant material, either smooth or textured
    [cir] With or without use of human ADM
    [cir] With or without mastectomy and reconstruction of the 
contralateral breast (i.e., unilateral or bilateral)
    [cir] With or without symmetry procedure (e.g., mastopexy) in the 
contralateral breast
Comparators
 IBR with implant placement in a different anatomic plane
Outcomes
 Quality of life
 Physical well-being (e.g., pain, discomfort)
 Psychosocial well-being (e.g., self-esteem, emotionality, 
normality)
 Sexual well-being
 Patient satisfaction with aesthetics (i.e., satisfaction with 
breast)
 Patient satisfaction with outcome (e.g., satisfaction with 
care)
 Planned staged surgeries for reconstruction
 Recurrence of breast cancer
 Harms
    [cir] Mortality
    [cir] Unplanned repeat hospitalization
    [cir] Duration of unplanned repeat hospitalization
    [cir] Unplanned repeat surgeries--for revision of reconstruction 
(e.g., for asymmetry)
    [cir] Unplanned repeat surgeries--for complications (e.g., for 
infection, bleeding)*
    [cir] Pain, including chronic pain
    [cir] Analgesic (e.g., opioid) use
    [cir] Necrosis, such as of the nipple
    [cir] Animation deformity
    [cir] Implant-related infections
    [cir] Implant rupture, including asymptomatic rupture
    [cir] Implant deflation
    [cir] Implant malposition
    [cir] Need for explant surgery
    [cir] Capsular contracture
    [cir] New neoplasms (e.g., BIA-ALCL)
    [cir] Complications that cause delays in other cancer-related 
treatments (e.g., chemotherapy, radiation therapy)
    [cir] Thromboembolic events*
    [cir] Infection
    [cir] Wound dehiscence
    [cir] Delayed healing
    [cir] Seroma
    [cir] Chronic conditions (e.g., rheumatologic diseases)
    [cir] Touch sensitivity
    [cir] Scarring
    [cir] Red breast syndrome
Potential Effect Modifiers:
 Age
 Stage of breast cancer
 First occurrence versus recurrent breast cancer
 Immediate versus delayed reconstruction
 Single-stage (direct to reconstruction) versus multistage 
(with tissue expander) reconstruction
 Unilateral versus bilateral reconstruction
 Surface of implant (smooth versus textured)
 Shape of implant (round versus anatomic/teardrop)
 Size of implant (volume)
Timing
 Any
Setting
 Any, including single- and multicenter
Design
 RCTs, N>=10 per group
 NRCSs, N>=30 per group
 Case-control studies, N>=100 per group
 Single group studies, N>=500
 Studies may be prospective or retrospective
 Exclude: case reports and series of individually-reported case 
reports

Key Question 5 (Use of Human ADM)

Population(s)
 Adult (>=18 years old) women who are undergoing (or have 
undergone mastectomy) for any type of breast cancer (or carcinoma in 
situ) and have decided to undergo IBR
 Either therapeutic or prophylactic mastectomy
 Exclude: Studies where >=10% of women underwent breast 
reconstruction (combined across reasons):
    [cir] for solely cosmetic purposes (i.e., augmentation)
    [cir] for revision reconstruction (i.e., after a previous 
reconstruction for breast cancer)
Interventions
 IBR with use of human ADM
    [cir] Either single- or multistage
    [cir] Any anatomic plane of implant placement
    [cir] Any type of implant material, either smooth or textured
    [cir] With or without mastectomy and reconstruction of the 
contralateral breast (i.e., unilateral or bilateral)
    [cir] With or without symmetry procedure (e.g., mastopexy) in the 
contralateral breast
Comparators
 IBR without use of human or nonhuman ADM
Outcomes
 Quality of life
 Physical well-being (e.g., pain, discomfort)

[[Page 39908]]

 Psychosocial well-being (e.g., self-esteem, emotionality, 
normality)
 Sexual well-being
 Patient satisfaction with aesthetics (i.e., satisfaction with 
breast)
 Patient satisfaction with outcome (e.g., satisfaction with 
care)
 Planned staged surgeries for reconstruction
 Recurrence of breast cancer
 Harms
    [cir] Mortality
    [cir] Unplanned repeat hospitalization
    [cir] Duration of unplanned repeat hospitalization
    [cir] Unplanned repeat surgeries--for revision of reconstruction 
(e.g., for asymmetry)
    [cir] Unplanned repeat surgeries--for complications (e.g., for 
infection, bleeding)
    [cir] Pain, including chronic pain
    [cir] Analgesic (e.g., opioid) use
    [cir] Necrosis, such as of the nipple
    [cir] Animation deformity
    [cir] Implant-related infections
    [cir] Implant rupture, including asymptomatic rupture
    [cir] Implant deflation
    [cir] Implant malposition
    [cir] Need for explant surgery
    [cir] Capsular contracture
    [cir] New neoplasms (e.g., BIA-ALCL)
    [cir] Complications that cause delays in other cancer-related 
treatments (e.g., chemotherapy, radiation therapy)
    [cir] Thromboembolic events
    [cir] Infection
    [cir] Wound dehiscence
    [cir] Delayed healing
    [cir] Seroma
    [cir] Chronic conditions (e.g., rheumatologic diseases)
    [cir] Touch sensitivity
    [cir] Scarring
    [cir] Red breast syndrome
Potential Effect Modifiers
 Age
 Stage of breast cancer
 First occurrence versus recurrent breast cancer
 Immediate versus delayed reconstruction
 Single-stage (direct to reconstruction) versus multi-stage 
(with tissue expander) reconstruction
 Unilateral versus bilateral reconstruction
 Anatomic plane of implant placement (prepectoral versus 
partial submuscular versus total submusclar)
 Surface of implant (smooth versus textured)
 Shape of implant (round versus anatomic/teardrop)
 Size of implant (volume)
 Brand of human ADM (e.g., Alloderm[supreg], FlexHD[supreg], 
BellaDerm[supreg], AlloMax[supreg], Cortiva[supreg], DermACELL[supreg])
Timing
 Any
Setting
 Any, including single- and multicenter
Design
 RCTs, N>=10 per group
 NRCSs, N>=30 per group
 Case-control studies, N>=100 per group
 Single group studies, N>=500
 Studies may be prospective or retrospective
 Exclude: case reports and series of individually-reported case 
reports

Key Question 6 (Different Flap Types For AR)

Population(s)
 Adult (>=18 years old) women who are undergoing (or have 
undergone mastectomy) for any type of breast cancer (or carcinoma in 
situ) and have decided to undergo AR
 Either therapeutic or prophylactic mastectomy
 Exclude: Studies where >=10% of women underwent breast 
reconstruction (combined across reasons):
    [cir] for solely cosmetic purposes (i.e., augmentation)
    [cir] for revision reconstruction (i.e., after a previous 
reconstruction for breast cancer)
Interventions
 AR using one flap (either free flap or pedicled), for example:
    [cir] Deep inferior epigastric perforator (DIEP)
    [cir] Latissimus dorsi (LD)
    [cir] Transverse rectus abdominis myocutaneous (TRAM)
    [cir] Superficial inferior epigastric artery perforator (SIEA)
    [cir] Gluteal artery perforator (GAP)
    [cir] Transverse musculocutaneous gracilis (TMG)
    [cir] Transverse upper gracilis (TUG)
    [cir] Profundal artery perforator (PAP)
    [cir] With or without mastectomy and reconstruction of the 
contralateral breast (i.e., unilateral or bilateral)
    [cir] With or without symmetry procedure (e.g., mastopexy) in the 
contralateral breast
    [cir] Exclude: Non-autologous flap transplants (i.e., cadaveric or 
xenotransplant)
    [cir] Exclude: Exclusive lipofilling/autologous fat reconstruction
Comparators
 AR using a different flap (either free flap or pedicled)
 Combination of IBR and AR
 Exclude: Non-autologous flap transplants (i.e., cadaveric or 
xenotransplant)
 Exclude: Exclusive lipofilling/autologous fat reconstruction
Outcomes
 Quality of life
 Physical well-being (e.g., pain, discomfort)
 Psychosocial well-being (e.g., self-esteem, emotionality, 
normality)
 Sexual well-being
 Patient satisfaction with aesthetics (i.e., satisfaction with 
breast)
 Patient satisfaction with outcome (e.g., satisfaction with 
care)
 Planned staged surgeries for reconstruction
 Duration of initial hospitalization
 Recurrence of breast cancer
 Harms
    [cir] Mortality
    [cir] Unplanned repeat hospitalization
    [cir] Duration of unplanned repeat hospitalization
    [cir] Unplanned repeat surgeries--for revision of reconstruction 
(e.g., for asymmetry)
    [cir] Unplanned repeat surgeries--for complications (e.g., for 
infection, bleeding)
    [cir] Pain, including chronic pain
    [cir] Analgesic (e.g., opioid) use
    [cir] Necrosis, such as of the nipple or of the flap
    [cir] Harms to area of flap harvest (e.g., hernia, bulge formation)
    [cir] Complications that lead to delays in other cancer-related 
treatments (e.g., chemotherapy, radiation therapy)
    [cir] Thromboembolic events
    [cir] Infection
    [cir] Wound dehiscence
    [cir] Delayed healing
    [cir] Seroma
    [cir] Touch sensitivity
    [cir] Scarring
Potential Effect Modifiers
 Age
 Stage of breast cancer
 First occurrence versus recurrent breast cancer
 Immediate versus delayed reconstruction
 Single-stage (direct to reconstruction) versus multi-stage 
(with tissue expander) reconstruction
 Unilateral versus bilateral reconstruction
Timing
 Any

[[Page 39909]]

Setting
 Any, including single- and multicenter
Design
 RCTs, N>=10 per group
 NRCSs, N>=30 per group
 Case-control studies, N>=100 per group
 Single group studies, N>=500
 Studies may be prospective or retrospective
 Exclude: case reports and series of individually-reported case 
reports

    Dated: June 26, 2020.
Virginia Mackay-Smith,
Associate Director.
[FR Doc. 2020-14237 Filed 7-1-20; 8:45 am]
BILLING CODE 4160-90-P