[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]
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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.
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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 Access to published and unpublished pertinent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,
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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
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Process measures Intermediate outcomes Clinical outcomes
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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
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* 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