[Federal Register Volume 76, Number 120 (Wednesday, June 22, 2011)]
[Notices]
[Pages 36539-36541]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-15580]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality


Scientific Information Request on Insulin Delivery and Glucose 
Monitoring Devices for Diabetes Mellitus

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 from medical device 
manufacturers of insulin pumps and continuous glucose monitors. 
Scientific information is being solicited to inform our Comparative 
Effectiveness and Safety of Insulin Delivery and Glucose Monitoring 
Methods for Diabetes Mellitus review, 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 Access to published and unpublished pertinent 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 this device 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.

DATES: Submission Deadline on or before July 22, 2011.

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 of current 
studies and complete the form to upload your documents.
    E-mail submissions: [email protected]. Print submissions: Robin 
Paynter, Oregon Health and Science University, Oregon Evidence-based 
Practice Center,

[[Page 36540]]

3181 SW Sam Jackson Park Road, Mail Code: BICC, Portland, OR 97239-
3098.

FOR FURTHER INFORMATION CONTACT: Robin Paynter, Research Librarian, 
Telephone: 503-494-0147 or E-mail: [email protected].

SUPPLEMENTARY INFORMATION: In accordance with Section 1013 of the 
Medicare Prescription Drug, Improvement, and Modernization Act of 2003, 
Public Law 108-173, the Agency for Healthcare Research and Quality has 
commissioned the Effective Health Care (EHC) Program Evidence-based 
Practice Centers to complete a comparative effectiveness review of the 
evidence for the Effectiveness and Safety of Insulin Delivery and 
Glucose Monitoring Methods for Diabetes Mellitus.
    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 the Comparative Effectiveness 
and Safety of Insulin Delivery and Glucose Monitoring Methods for 
Diabetes Mellitus, 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://effectivehealthcare.AHRQ.gov/index.cfm/search-for-guides-reviews-and-reports/?PAGEaction=displayproduct&productid=689.
    This notice is a request for industry stakeholders to submit the 
following:
     A current product label, if applicable (preferably an 
electronic PDF file).
     Information identifying published randomized controlled 
trials and observational studies relevant to the clinical outcomes. 
Please provide both a list of citations and reprints if possible.
     Information identifying unpublished randomized controlled 
trials and observational studies relevant to the clinical outcomes. If 
possible, please provide 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 withdrawn/follow-
up/analyzed, and effectiveness/efficacy and safety results. Registered 
ClinicalTrials.gov studies. Please provide a list including the 
ClinicalTrials.gov identifier, condition, and intervention.
    Your contribution is very beneficial to this program. AHRQ is not 
requesting and will not consider marketing material, health economics 
information, or information on other indications. This is a voluntary 
request for information, and all costs for complying with this request 
must be borne by the submitter.
    Please Note: The contents of all submissions, regardless of format, 
will be available to the public upon request unless prohibited by law.
    The draft of this review will be posted on AHRQ's EHC 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 e-mail list at: http://effectivehealthcare.AHRQ.gov/index.cfm/join-the-email-list1/.

Key Questions

    Our draft Key Questions (KQs) were posted for public comment in 
October 2010 (see Appendix 1). Based on the public comments, we made 
the following changes to the KQs:
    1. We will not include pregnant women with gestational diabetes in 
the review. There is a range of glucose abnormalities among women with 
gestational diabetes, and many women with gestational diabetes are not 
on intensive insulin therapy. Insulin pump therapy and CGM are more 
relevant to pregnant women with pre-existing diabetes. The population 
for this review will include patients with type 1 diabetes, patients 
with type 2 diabetes who are on insulin therapy, and pregnant women 
with pre-existing diabetes.
    2. We will see if there are any studies that focused on older 
adults (age >65 years). Currently, there is no upper age limit on our 
proposed study populations, so we should be able to examine this group 
if data are available. Therefore, the age categories considered for 
this review will be very young children, adolescents and adults, 
including older adults (age >65 years).
    3. KQ3 was made a subquestion of KQ 2.
    There were several other relevant comments about the KQs and the 
protocol. These comments and our responses are summarized below.
    1. We plan to abstract the following data to use in our analysis 
when available: measurement of adherence, MDI delivery method (pen vs. 
vial or syringe), study design, information about device use (e.g., 
analyses based on adherence to wearing the device, training of patient/
staff, generation/model of devices), study participant characteristics, 
adjustment to insulin therapy, definitions of hypoglycemia, definitions 
of diabetes, assessment of quality of life, rt-CGM alarm threshold, and 
study length and followup time.
    2. Because insulin regimens may change over time, it may be 
difficult to determine if the current delivery method is responsible 
for the long-term outcomes. Therefore, we will abstract data on the 
length of use of current technology, changes in the mode of insulin 
delivery over time, and changes in the type of insulin used over time 
if available.
    3. The list of process measures and intermediate outcomes will not 
change. Some of the suggested outcomes were either beyond the scope of 
the review (e.g., changes in carbohydrate counting, diet, and physical 
activity) or only applied to a particular insulin-delivery device or 
blood glucose-monitoring technique (e.g., time spent in the 
hypoglycemic range).
    The finalized KQs are:

KQ 1

    In patients receiving intensive insulin therapy, does mode of 
delivery (multiple daily injections [MDI] vs. continuous subcutaneous 
insulin infusion [CSII]) have a differential effect on process 
measures, intermediate outcomes, and clinical outcomes in patients with 
diabetes mellitus? (Process measures, intermediate outcomes, and 
clinical outcomes of interest are summarized below in Table 1.) Do 
these effects differ by:
    a. Type 1 or type 2 diabetes status?
    b. Age: Very young children, adolescents, and adults, including 
older adults (age >65 years)?
    c. Pregnancy status: Pre-existing type 1 or type 2 diabetes?

KQ 2

    In patients using intensive insulin therapy (MDI or CSII), does the 
type of glucose monitoring (real-time continuous glucose monitoring 
[rt-CGM] vs. self-monitoring of blood glucose [SMBG]) have a 
differential effect on process measures, intermediate outcomes, and 
clinical outcomes (see Table 1) in patients with diabetes mellitus 
(i.e., what is the incremental benefit of rt-CGM in patients already 
using intensive insulin therapy on process and outcome measures)? Do 
these effects differ by:
    a. Type 1 or type 2 diabetes status?

[[Page 36541]]

    b. Age: Very young children, adolescents, and adults, including 
older adults (age >65 years)?
    c. Pregnancy status: Pre-existing type 1 or type 2 diabetes?
    d. Intensive insulin delivery: MDI or CSII?

                   Table 1--Summary of Process Measures and Intermediate and Clinical Outcomes
----------------------------------------------------------------------------------------------------------------
           Process measures                    Intermediate outcomes                  Clinical outcomes
----------------------------------------------------------------------------------------------------------------
 Ratio of basal to bolus         Primary                      Microvascular*
 insulin.                                Hemoglobin A1c               Retinopathy
 Frequency of adjusting          Secondary                    Nephropathy
 insulin therapy.                        Hyperglycemia                Neuropathy
 Adherence to insulin therapy/   Weight gain                  Macrovascular*
 sensor use.                             Hypoglycemia frequency       Coronary heart disease
 Frequency of professional or                                         Cerebrovascular disease
 allied health visits.                                                        Peropheral arterial
                                                                              disease
                                                                              Severe hypoglycemia
                                                                              Quality of life
                                                                              Fetal outcomes [dagger]
                                                                              Maternal pregnancy
                                                                              outcomes
                                                                              C-section rates
----------------------------------------------------------------------------------------------------------------
* We will only include objective assessments of microvascular and macrovascular outcomes (i.e., we will be
  excluding patient self-reported microvascular and macrovascular outcomes).
[dagger] Fetal outcomes include gestational age, birth weight, frequency of neonatal hypoglycemia, birth trauma,
  major and minor anomalies, and admission to a neonatal intensive care unit.

    For each KQ we will identify:
    Population(s):
    Adults, adolescents, and children with type 1 or type 2 diabetes 
mellitus and pregnant women with pre-existing diabetes treated with 
insulin therapy.
    1. We will use age ranges prescribed by the Juvenile Diabetes 
Research Foundation (<8 years [very young children], 8-14 years 
[children], 14-25 years [adolescent], and >25 years [adults]); however, 
our final definitions will be guided by those used in the literature 
that is reviewed.
    2. If available, we will examine data among populations of older 
adult (>65 years).
    Interventions:
    The interventions of interest are CSII (see Appendix 2 for a list 
of insulin pumps and models) and rt-CGM (see Appendix 3 for a list of 
monitors).
    1. We will not be including the following devices because they are 
no longer used in the United States:

a. GlucoWatch continuous glucose meter
b. Insulin pumps with regular insulin

    Comparators:
    All studies must have a concurrent comparison group.
    1. CSII would be compared with MDI, which will be defined as at 
least three injections of basal and rapid-acting insulin per day.
    2. rt-CGM would be compared with SMBG, which will be defined as at 
least three fingersticks per day.
    Outcomes measures for each KQ:

1. Process measures
a. Ratio of basal to bolus insulin
b. Frequency of adjustments to insulin therapy
c. Adherence to insulin therapy/sensor use
d. Frequency of professional or allied health visits Intermediate 
outcomes

     HbA1c

a. Hyperglycemia
b. Weight gain
c. Hypoglycemia frequency
Clinical Outcomes
     Objective assessments of microvascular outcomes 
(retinopathy, nephropathy, and neuropathy)

a. Objective assessments of macrovascular outcomes (coronary heart 
disease, cerebrovascular disease, and peripheral arterial disease)
b. Severe hypoglycemia
c. Quality of life
d. Fetal outcomes (gestational age, birth weight, frequency of neonatal 
hypoglycemia, birth trauma, major and minor anomalies, and admission to 
a neonatal intensive care unit)
e. Maternal pregnancy outcomes (cesarean section rates)

    Timing: Usage of a device for at least 24 hours.
    Settings: Outpatient setting.

    Dated: June 10, 2011.
Carolyn M. Clancy,
AHRQ, Director.
[FR Doc. 2011-15580 Filed 6-21-11; 8:45 am]
BILLING CODE 4160-90-M